THETWO TONTTITULUUS 20170319462A1 MUUTUNUMURTIN ( 19) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2017/ 0319462 A1 Marchant et al. (43 ) Pub . Date : Nov . 9 , 2017

(54 ) THERMOPLASTIC POLYURETHANE FILM Publication Classification FOR DELIVERY OF ACTIVE AGENTS TO (51 ) Int. Ci. SKIN SURFACES A61K 8 / 87 (2006 . 01 ) A610 19 /02 (2006 .01 ) (71 ) Applicant: Lubrizol Advanced Materials , Inc. , A61K 47 /34 ( 2006 .01 ) Cleveland , OH (US ) A61K 9 / 70 ( 2006 .01 ) A61K 9 / 00 ( 2006 . 01 ) (72 ) Inventors : Nancy S . Marchant, Medina , OH A61K 8 / 73 ( 2006 .01 ) (US ) ; Pallavi Kulkarni, Woburn , MA A61K 8 /64 (2006 .01 ) (US ) ; Anthony J . Walder, Essex , MA A61K 8 /42 ( 2006 .01 ) A61K 8 / 368 ( 2006 . 01 ) (US ) ; Paul M . Basone, Akron , OH A610 19 / 08 (2006 .01 ) (US ) ; Shawn Lankowski, Denvers, MA A61K 8 / 34 (2006 .01 ) (US ) ; Juan Cebrián Puche , Gava ( ES) ; ( 52 ) U . S . Cl. Sandra Mendez , Gava (ES ); Mireia CPC ...... A61K 8 / 87 ( 2013 .01 ); A610 19 / 08 Martin , Gava (ES ) ( 2013 .01 ) ; A610 19 / 02 (2013 .01 ) ; A61K 47/ 34 ( 2013 .01 ) ; A61K 9 / 7007 ( 2013 . 01 ) ; A61K 8 / 34 ( 21) Appl. No. : 15/ 520 , 661 ( 2013 . 01 ); A61K 8 / 735 (2013 .01 ) ; A61K 8 /64 ( 2013 .01 ) ; A61K 8 / 42 ( 2013 .01 ) ; A61K 8 / 368 (22 ) PCT Filed : Oct. 23, 2015 ( 2013 .01 ) ; A61K 9 /0014 ( 2013 .01 ) ( 86 ) PCT No. : PCT/ US2015 /057084 (57 ) ABSTRACT $ 371 (c )( 1 ), A polymer film suited to use as a face mask or transdermal ( 2 ) Date : patch includes at least 30 wt. % of a thermoplastic polyure Apr. 20 , 2017 thane polymer which is the reaction product of a first polyether polyol having a molecular weight of at least 3000 daltons, optionally , a second polyether polyol having a Related U . S . Application Data molecular weight of no more than 2500 daltons, at least one (60 ) Provisional application No . 62/ 220 ,552 , filed on Sep . of a third polyol having a molecular weight of up to 800 18 , 2015 , provisional application No . 62 /073 ,314 , daltons , and a chain extender , a diisocyanate , optionally, a filed on Oct. 31 , 2014 . catalyst. The film includes up to 5 wt. % water. 102

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THERMOPLASTIC POLYURETHANE FILM BRIEF DESCRIPTION FOR DELIVERY OF ACTIVE AGENTS TO [0007 ] In accordance with one aspect of the exemplary SKIN SURFACES embodiment, a polymer film includes at least 30 wt. % of a [0001 ] This application claims the priority of PCT/ thermoplastic polyurethane polymer which is the reaction US2015 /057084 (WO 2016 / 069396 ) , filed Oct . 23 , 2015 , product of a first polyether polyol having a molecular weight U . S . Provisional Application Ser . No. 62/ 073 , 314 , filed Oct. of at least 3000 daltons , optionally , a second polyether 31 , 2014 , and U . S . Provisional Application Ser. No . 62 / 220 , polyol having a molecular weight of no more than 2500 552 , filed Sep . 18 , 2015 , from which the PCT application daltons , at least one of a third polyol having a molecular claims priority , the disclosure of each of which is hereby weight of up to 800 daltons, and a chain extender, a incorporated by reference in its entirety . diisocyanate , optionally , a catalyst; and up to 5 wt. % water. [0008 ]. In accordance with another aspect of the exemplary embodiment, a method of forming a face mask or body patch BACKGROUND includes forming a thermoplastic polyurethane polymer [0002 ] The exemplary embodiment relates to the delivery from a first polyether polyol having a molecular weight of at of active agents to skin surfaces and finds particular appli least 3000 daltons, optionally , a second polyether polyol cation in connection with a thermoplastic polyurethane film having a molecular weight of no more than 2500 daltons , that serves as a vehicle for skin treatment active agents and and at least one of a third polyolhaving a molecular weight a face mask or body patch formed from the film . of up to 800 daltons and a chain extender . The method [0003 ] Face masks have been traditionally used for pro further includes casting the thermoplastic polyurethane viding active agents to the face and other skin surfaces. The polymer with an active agent in solution to form a cast film active agents may include vitamins , moisturizers , cleansers , which includes the active agent dispersed in the thermoplas anti - wrinkle agents , lightening agents , skin toning agents , tic polyurethane polymer . and others . [0009 ] In accordance with another aspect of the exemplary [0004 ] Conventional face masks include hydrocolloid lay embodiment, a face mask or body patch includes a hydrated ers containing the active agents and other nutrients . The film which includes at least 50 wt. % water , 5 to 30 wt. % hydrocolloid layers are often held together by fabric or a of a thermoplastic polyurethane polymer , and at least one synthetic mesh which provides a physical and mechanical active agent. support. Such multi - layered face masks tend to be time consuming and costly to manufacture . Hydrocolloid face BRIEF DESCRIPTION OF THE DRAWINGS masks are typically formed by hot solution casting of a [0010 ] FIG . 1 is a schematic top plan view of a face mask ; mixture of polysaccharide polymers such as carrageenan , [0011 ] FIG . 2 is a side sectional view of a hydrated face locust bean gum (galactomannans ) , agarose , agar , and xan mask on the skin of a wearer ; than gum . Generally the polysaccharide components are [ 0012 ]. FIG . 3 illustrates a body patch ; added to a mixture of water , glycerin , and polypropylene [0013 ]. FIG . 4 illustrates rate of swell for an exemplary glycol and heated to approximately 80 to 90° C . to dissolve polyurethane film ; the polymer and obtain a molten state . The colloid solution [ 0014 ] FIG . 5 illustrates buffer uptake for different poly is cooled to about 60° C . and the cosmetic additives are urethane films at different thicknesses ; added . This intermediate cooling step is to avoid harming [0015 ]. FIG . 6 illustrates percutaneous absorption by pig temperature -sensitive active agents . The thickened solution skin of 1. 8 % caffeine solution loaded on an exemplary is cast as a film with a knife at a set thickness . A rayon polymer film ; reinforcing material may be added . The solution is then [ 0016 ] FIG . 7 shows percutaneous absorption by pig skin cooled to 25° C . and kept between release films until the film of a 1 . 8 % caffeine solution loaded on an exemplary polymer sets to a firm gel before cutting to shape . The final gel film film and on biocellulose (microbial cellulose ) ; thickness is between 0 . 7 and 0 . 8 mm for hydrocolloid masks [0017 ]. FIG . 8 shows percutaneous absorption by pig skin that are not reinforced and about 0 . 5 mm for reinforced of 2 % dimethylmethoxychromanyl palmitate solution masks . loaded on an exemplary polymer film ; [ 0005 ] Hydrocolloid face masks are also often opaque and [0018 ] FIG . 9 shows salicylic acid penetration in skin slippery . This requires the subject being treated to lie down from polymer films; and while the face mask is being applied and remain in this [0019 ] FIG . 10 shows lidocaine hydrochloride penetration position for a treatment period of typically 30 -60 minutes . in skin from polymer films. Even if the subject is able to sit or stand , the face mask is very noticeable . DETAILED DESCRIPTION [ 0006 ] There remains a need for a face mask material with [0020 ] Aspects of the exemplary embodiment relate to a transparency , flexibility , strength and ability to adhere to the polymer film which includes a thermoplastic polyurethane skin while the subject is in an upright position , which is able polymer , suited to use as a face mask or body patch , which to deliver active agents to the skin and that would enable the may include one or more actives and / or excipients . The subject to walk around and perform other activities while polymer film is able to absorb a considerable quantity of still continuing with the facial treatment. Additionally , the water that may include the one or more actives and /or face mask material should not leave behind a residue the excipients . skin once it is removed so that there is no need to wash the [0021 ] With reference to FIG . 1 , a cosmetic sheet facial face unless the skin treatment is to be removed . It would also mask ( face mask ) 10 suited to delivering an active agent 12 be advantageous to be able to use cold processing techniques to a surface 14 of the skin of a person , such as the face , is to form the face mask . shown . The illustrated face mask is contoured to fit the US 2017 /0319462 A1 Nov. 9 , 2017 user ' s face , for example is generally oval in shape , or to 60 wt. % , or up to 50 wt. % , or up to 40 wt. % , or up to otherwise shaped to cover at least a part of a face of a wearer, 20 wt. % , or up to 10 wt. % of the dry film . and has apertures 16 appropriately positioned to align with (0030 ) One or more active agents may be present in the the eyes , nose , and / or mouth of the person . dry film /face mask in a pharmaceutically effective amount, [0022 ] In one embodiment, shown in FIG . 2 (not to scale ) , i . e ., an amount sufficient to have a beneficial effect on the the face mask 10 includes only a single water - insoluble film skin . The amount of each active agent may thus vary , or layer 18 of a polyurethane material, having a first surface depending on the active agent being used . The one or more 20 and a second surface 22 . In use , the first surface 20 active agents may be present in the dry film / face mask at a contacts the surface 14 of the wearer ' s face while the second total concentration of at least 0 . 00001 wt. % , or at least surface 22 is exposed to the atmosphere . 0 . 0001 wt. % , or at least 0 . 001 wt. % , or at least 0 .01 wt. % , 10023 ] FIG . 3 shows another embodiment, which suited to or at least 0 . 1 wt. % , or at least 0 . 2 wt. % , or at least 0 . 4 wt. use as a body patch 30 . In this embodiment, the film 18 may % , or at least 1 wt. % , or about 2 wt. % , and in some be at least partially covered , on the outer surface 22 , by a embodiments , up to 20 wt. % , or up to 18 wt. % , or up to 16 second layer 32 . The layer 32 may serve as one or more of: wt. % , or up to 10 wt. % , or up to 5 wt. % . an adhesive for assisting in adhering the layer 18 to the skin ; [0031 ] In one embodiment, the active agent includes at a moisture barrier to resist drying out of the hydrated film ; least one of a skin whitening or depigmenting agent and an and a sterile layer to avoid contamination of the film with anti- acne agent, or combinations thereof, which may be dirt, microorganisms, or the like . In this embodiment, the present at a concentration of at least 0 . 00001 wt. % , or at adhesive layer 32 and film 18 may be stored separately until least 0 .0001 wt . % , or at least 0 .001 wt . % , or at least 0 .01 use , e . g . , in separate sterile packages, or may be stored as a wt. % , or at least 0 . 1 wt. % , or at least 0 . 5 wt. % , or at least combination of film and adhesive layer. The layer 32 , prior 1 wt. % of the dry film , and in some embodiments , up to 10 to use , may be covered by a removable liner material ( not wt. % , or up to 5 wt. % , or about 2 wt. % . The one or more shown ) . active agents may be homogeneously incorporated /dis 10024 ] As will be appreciated , while the illustrated face persed in the film /face mask , for example , by casting the film mask / patch is formed as a single piece of film , a face mask from a dispersion containing the TPU and active agent or by may be formed from two or more pieces of the film , such as soaking the TPU in a hydrating solution containing the one piece covering an upper part of the wearer ' s face and desired active agents and /or excipients . one piece for covering a lower part, with a respective [0032 ] One or more excipients may be present in the dry aperture or apertures in each part . film / facemask at a total concentration of at least 0 . 01 wt. % , [0025 ] The polyurethane material of the film 18 includes or at least 0 . 2 wt. % , or at least 0 . 4 wt. % , or at least 1 wt. a soft, flexible , clear thermoplastic polyurethane ( TPU ) or a % , and in some embodiments , up to 10 wt. % . The one or blend of TPUs, which is extruded or solvent cast to form a more excipients may be homogeneously dispersed in the thin film 18 . The exemplary thin film 18 is water- swellable film / face mask , for example, by casting the film from a but is not soluble in water. dispersion containing the TPU and active agent and /or [ 0026 ] The dry polyurethane film 18 may have a thick excipient. ness, prior to hydration , of at least 0 .08 mm , or at least 0 . 1 [0033 ] The hydrated film 18 (or face mask 10 formed mm , or at least 0 . 2 mm and can be up to 1 mm in thickness , therefrom ) after swelling in an aqueous formulation for at or up to 0 .6 mm , or up to 0 .4 mm , or up to 0 .35 mm . least 10 minutes , or 30 minutes , at room temperature , may [0027 ] A water content of the dry polyurethane film 18 be at least 0 . 2 or at least 0 . 5 mm in thickness and in some (prior to hydration ) may be less than 5 wt. % , or less than 2 embodiments, is up to 1 . 5 mm , or up to 1 . 2 mm , or up to 1 . 0 wt. % , or less than 1 wt. % . The thin polyurethane film 18 mm , or up to 0 . 8 mm in thickness . The hydrated film / face has a high water pickup . For example, when soaked in an mask may include at least 5 wt. % of thermoplastic poly aqueous formulation ( at least 50 wt. % water ) at room urethane polymer , or at least 10 wt. % thereof , and in some temperature (defined herein as 22 -26° C . ) for a period of 30 embodiments up to 25 wt. % , or up to 20 wt. % , or up to 18 minutes , the film may swell by at least 300 wt. % ( 2 g wt. % , or up to 10 wt. % of the thermoplastic polyurethane water/ 1 g polymer ), or at least 500 wt. % (4 g water / 1 g polymer at room temperature . Polymers other than thermo polymer ), and in some embodiments , up to 2000 wt. % (19 plastic polyurethane which have a molecular weight of over g water / 1 g polymer ) , or up to 1500 wt. % (14 g water / 1 g 500 daltons may be present at up to 10 wt. % , or up to 5 wt. polymer ) , or up to 1200 wt. % ( 10 g water / 1 g polymer ) , or % , or up to 1 wt. % , or as little as 0 % of the hydrated up to 1000 wt. % ( 9 g water/ 1 g polymer ) , while maintaining film / face mask . The hydrated film / face mask may include at its integrity as a film . least 30 wt. % water , or at least 50 wt. % water. [0028 ] While particular reference is made in the following [0034 ] One or more of the active agents may be present in to use of the film in a face mask , it is to be appreciated that the hydrated film / face mask in a pharmaceutically effective a body patch is also contemplated . amount. For example, the active agents may be present at a [0029 ] The dry film 18 (or dry face mask 10 formed total concentration of at least 0 . 00001 wt. % , or at least therefrom ) may include at least 20 wt. % of thermoplastic 0 .001 wt. % , or at least 0 . 01 wt. % , or at least 0 . 1 wt. % , or polyurethane polymer as disclosed herein , or at least 30 wt. at least 0 .2 wt. % , or at least 0 .5 wt. % , or at least 1 wt. % . % , or at least 40 wt. % , or at least 50 wt. % , or at least 60 [0035 ] In one embodiment, the active agent includes a wt. % , or at least 70 wt. % of the thermoplastic polyurethane skin whitening or depigmenting agent, e . g . , at a concentra polymer, and in some embodiments up to 99. 9 wt. % , or up tion of at least 0 .00001 wt. % , or at least 0 . 1 wt. % , or at least to 99 wt. % of the thermoplastic polyurethane polymer, at 0 . 2 wt. % of the hydrated film / face mask . In one embodi room temperature . Polymers other than the thermoplastic ment, the active agent includes an anti - acne agent, e .g . , at a polyurethane polymer disclosed herein which have a concentration of at least 0 . 1 wt. % or at least 0 . 2 wt. % of molecular weight of over 500 daltons may be present at up the hydrated film / face mask . US 2017 /0319462 A1 Nov. 9 , 2017

10036 ] One or more excipients may be present in the example , by punching out the cavities 16 for the eyes , nose , hydrated film / face mask at a total concentration of at least and mouth . The hydrated face mask , containing the selected 0 .01 wt. % , or at least 0 . 1 wt. % , or at least 0 . 5 wt. % , or at active agents and excipients , may be packaged in a foil least 1 wt. % , and in some embodiments , up to 50 wt. % . pouch . These steps may be performed at different locations , [0037 ] A ratio by weight of the total amount of active for example , the dry film may be shipped to a facial mask agents to the exemplary thermoplastic polyurethane polymer manufacturer who may select and add the hydrating solu in the dry film , hydrated film , and / or face mask may be at tion . This method eliminates the need for reinforcing the least 1 : 100 ,000 , or at least 1 : 10 ,000 or at least 1 : 1000 , or at face mask using a mesh , fabric , or other substrate . least 1 : 200 , or at least 1 : 100 , or at least 1 : 50 and may be up [0044 ] While the thin film finds particular use in facial to 1 : 5 . masks, it may be used for applying an active agent to any [ 0038 ] As an example , the hydrated film / face mask part of the body, for example to apply an active agent to a includes at least 5 wt. % , and / or up to 30 wt. % , or up to 20 wound . wt. % of (what was ) the dry film , at least one active agent at a total concentration of at least 0 . 0001 wt. % , or at least The Thermoplastic Polyurethane 0 . 001 wt. % , or at least 0 . 001 wt. % , or at least 0 .01 wt. % , [0045 ] The unhydrated polyurethane film 18 includes, as a or at least 0 . 2 wt. % , optionally at least one excipient, and significant component ( at least 30 wt . % , or at least 50 wt. at least 30 wt. % , or at least 50 wt. % , or at least 60 wt. % , % , or at least 80 wt. % ) , a thermoplastic polyurethane which or at least 70 wt. % , or at least 80 wt. % water, and in some includes a hard segment and a soft segment and optionally embodiments , up to 95 % water or up to 90 % water. an intermediate segment. [0039 ] The hydrated film 18 and contoured face mask 10 [0046 ] In one embodiment, the thermoplastic polyure formed therefrom are clear and flexible and have the ability thane ( denoted TPU1) includes a soft segment which is to conform and adhere to the contours of the face and body. derived from a first high molecular weight polyether polyol The hydrated film also has " drape ” or “ cling ” type charac ( Polyol A ) and a second high molecular weight polyether teristics that enable them to hold on to the skin even when polyol ( Polyol B ) of lower molecular weight than the first the face is in an upright position . The film is capable of polyol. Polyols A and B may be of the general form maintaining film integrity over time, such as for at least 30 HO ( R ' (R2 ) O )n - H , where : minutes or at least 1 hour, and in some cases , for days , [0047 ] RP is selected from C2 C4 alkylene groups and weeks, or months under standard storage conditions. mixtures thereof, such as CH CH and [0040 ] The hydrated film may have high clarity when wet. CH , CH , CH?, The hydrated film is generally stronger than hydrocolloid [0048 ] R2 is a side group and is selected from H and films of the same thickness and thus can be free of all C - C , alkyl groups and mixtures thereof, and reinforcing materials , such as woven or non -woven fabric or [0049 ] n is an integer which represents the average num mesh . Thinner sheets can also be used than for hydrocolloid ber of ether units by weight in each polyol , and where n is films. The exemplary face mask 10 is free of reinforcing at least 20 . materials . 10050 ] A ratio of the value of n for the first polyol to the [0041 ] The hydrated TPU film when tested for wet burst value of n for the second polyol may be at least 1 . 5 : 1 or at strength may have higher absolute peak force at break and least 2 : 1 , or at least 3 : 1, or at least 4 : 1 , and may be up to 20 : 1 greater % elongation than hydrocolloid films of the same or up to 10 : 1 . The value of n for Polyol A may be at least 60 thickness. This facilitates stretching of the film around facial or at least 100 or at least 150 and may be up to 500 or up to or other body features without ripping and allows it to be 240 . The value of n for Polyol B may be at least 25 , or at handled easily . least 30 , and may be up to 50 or up to 45 . 0042] The film may be solvent cast or extruded . In one [0051 ] All molecular weights mentioned herein are weight embodiment, the film is solvent cast with or without the average molecular weights and are expressed in daltons , active agent 12 . For example , the exemplary thermoplastic unless otherwise noted . Polyol A may have an average polyurethanes can be formed into granules which can be molecular weight of at least 3000 , or at least 4000 , or at least easily solubilized in alcohol/ water mixtures and cast to form 6000 daltons , and in some embodiments , up to 15 , 000 , or up monolithic thin films 18 . As an alcohol, ethanol and isopro to 12, 000 , or up to 10 , 000 daltons. Polyol B may have an panol may be used . As an alternative to alcohol, tetrahydro average molecular weight of no more than 2500 , or no more furan , dimethylacetamide , dimethylformamide, or other than 2000 , or no more than 1600 daltons, and in some water -miscible non -aqueous solvents can be used . The gran embodiments , at least 800 daltons or at least 1000 daltons . ules can also be extruded to form thin films 18 . The films A ratio of the molecular weight of Polyol A to polyol B may may be cast or extruded onto a release layer. be at least 1 . 4 : 1 or at least 2 : 1 and may be up to 15 : 1 or up [ 0043 ] Being formed of a single layer 18 of material to 10 : 1 , or up to 8 : 1 . The soft segment thus has a bimodal renders the face mask relatively inexpensive to produce . The distribution of average length of the polyether segments . active agent may be incorporated into the film prior to [0052 ] A molar ratio of Polyol B to Polyol A in the hydration ( e . g . during solvent casting , during the hydration reaction mixture for forming the thermoplastic urethane may process , or after partial hydration , allowing customers to be at least 5 : 1 or at least 8 : 1 such as up to 20 : 1 . tailor the active agents to their particular treatments . For [0053 ] A weight ratio of Polyol B to Polyol A in forming example , a cosmetic solution includes water , optionally a the thermoplastic urethane may be from 1 : 1 to 5 : 1 , such as moisturizer/ humectant , such as glycerin , and one or more at least 1 . 5 : 1 , or at least 1 : 1 . (additional ) active agents . Dry films of the TPU , on the f0054 ] The hard segment may be derived from a diiso release layer, may be soaked in a selected hydrating solution cyanate , and at least one of a diisocyanate and a chain containing the selected active agents and excipients . The extender . The chain extender may also be a polyol, such as hydrated film may be shaped to form the face 10 mask , for a C1 - C20 or C , C12 , or C2 C10 alkyl and/ or aryl polyol. US 2017 /0319462 A1 Nov . 9 , 2017

A molecular weight of the chain extender may be up to 300 [0065 ] Wt. isocyanate in hard segment= [moles isocyanate daltons, or up to 250 daltons , or up to 200 daltons. moles polyols having a molecular weight of at least 250 [0055 ] An optional intermediate segment may be derived daltons ]xMw isocyanate . from a third polyol ( Polyol C ) and a diisocyanate ( in general, 10066 ] In one embodiment, the hard segment content the same as is used for generating the hard segment) . Polyol (calculated as above ) in the TPU is at least 4 wt. % , or at C may be a polyether polyol as for Polyols A and B , but least 4 . 3 wt. % . The hard segment content in the TPU may where n is at least 3 or at least 5 , or at least 7 , and may be be up to 12 wt. % , or up to 10 wt. % , or up to 9 wt. % . up to 20 or up to 12 . A molecular weight of Polyol C may [0067 ] In one embodiment, the soft segment content (cal be at least 200 , or at least 250 , or at least 300 daltons and culated as above ) in the TPU is at least 75 wt. % , or at least may be up to 800 or up to 500 , or up to 400 daltons. 80 wt. % . The soft segment content in the TPU may be up [ 0056 ] An example thermoplastic polyurethane is the to 94 wt. % , or up to 92 wt. % . In one embodiment, the TPU reaction product of: 20 - 30 wt . % Polyol A , 40 - 70 wt. % is 9 - 11 wt. % hard segment, 84 - 88 wt. % soft segment, and Polyol B , 5 - 20 wt. % polyisocyanate , 0 - 5 wt. % Polyol C , the balance ( e . g . , 3 - 4 wt. % ) intermediate segment. In one 0 . 2 - 5 wt. % chain extender, optionally , one or more addi embodiment, the TPU is 4 . 5 - 11 wt. % hard segment, 84 - 91 tional polymer forming components , and optionally up to 2 wt. % soft segment, and the balance ( e . g ., 2 . 5 - 4 wt. % ) is wt. % of a catalyst ( totaling 100 wt. % . In combination , intermediate segment. Polyols A and B may comprise at least 50 wt. % , or at least 70 wt. % of the total weight of polymer forming components Polyols A , B , and C in the reaction mixture . [0068 ] Suitable hydroxyl terminated polyether polyols [0057 ] The thermoplastic polyurethane may have a weight which are useful as Polyols A and B , and optionally Polyol average molecular weight of from about 50 ,000 to about C are derived from a diol or polyol having a total of, for 1 ,000 ,000 daltons , or from about 75 ,000 to about 500 , 000 , example , from 2 to 15 carbon atoms, such as an alkyl diol or from about 100 ,000 to about 300 , 000 daltons . or glycol, which is reacted with an ether comprising an [0058 ] In another embodiment a thermoplastic polyure alkylene oxide of, for example , from 2 to 6 carbon atoms, thane composition ( TPU2) is as described for TPU1 but such as ethylene oxide, propylene oxide or a mixture includes Polyol A but not Polyol B . In another embodiment thereof . For example , polyether polyols can be produced by a thermoplastic polyurethane composition ( TPU3 ) is as first reacting propylene glycol with propylene oxide fol described for TPU1 but includes Polyol B but not Polyol A . lowed by subsequent reaction with ethylene oxide . Primary Blends of two or more of the thermoplastic polyurethanes hydroxyl groups resulting from ethylene oxide are more TPU1, TPU2 , and TPU3 are also contemplated . A weight reactive than secondary hydroxyl groups and thus are often ratio of TPU1: TPU2 and / or TPU3 may be at least 1 : 2 . In one more suitable . embodiment, the ratio is at least 1 : 1 . 5 , or at least 1 : 1 , or at [0069 ] Example polyether polyols include poly ( ethylene least 2 : 1 , and may be up to 100 : 1, or higher , such as up to glycol) formed by reaction of ethylene oxide with ethylene 20 : 1 , or up to 10 : 1 . glycol , poly (propylene glycol) formed by reaction of pro [0059 ] The exemplary thermoplastic polyurethane is pylene oxide with propylene glycol, a copolymer of ethylene optionally blended in the dry film with one or more addi oxide and a Cz to C15 alkylene oxide, in particular, a Cz to tional polymers . Additional polymers suitable for use herein Co alkylene oxide, such as poly ( propylene glycol) , e . g ., a include thermoplastic polyurethanes and crosslinked poly copolymer polyol comprising poly (propylene glycol) and ( acrylic acid ) polymers . poly ( ethylene oxide ) segments , poly ( tetramethylene ether [0060 ] Example crosslinked poly (acrylic acid ) polymers glycol) formed by reaction of water with tetrahydrofuran , include those that are crosslinked with an alkyl ether of which can also be described as polymerized tetrahydrofuran , pentaerythritol or an alkyl ether of sucrose . Suitable cross and which is commonly referred to as PTMEG . Suitable linked poly ( acrylic acid ) polymers are available under the polyether polyols also include polyamide adducts of an trade name Carbopol® from Lubrizol Advanced Materials , alkylene oxide and can include, for example , ethylenedi Inc . Examples include Carbopol® 934 , Carbopol® 940 , amine adduct formed by reaction of ethylenediamine with Carbopol® 941, Carbopol® 980 , and Carbopol® 981, Car propylene oxide , diethylenetriamine formed by reaction of bopol® 981F and Carbopol® ETD 2020 polymers . A weight diethylenetriamine with propylene oxide , and similar poly ratio of TPU : cross - linked poly (acrylic acid ) polymer ( s ) amide type polyether polyols . may be at least 5 : 1 , or at least 10 : 1 , or at least 20 : 1, or at least [0070 ] Copolyethers can also be utilized in the described 40 :1 , or at least 50 : 1 and may be up to 1000 : 1 or up to 100 :1 , compositions . Typical copolyethers include the reaction such as about 60 : 1, where the TPU can include one or more product of THF and ethylene oxide ; THF and propylene of TPUs 1 , 2 , and 3 . oxide ; or ethylene oxide and propylene oxide . The first two [0061 ] The proportions of hard segment, soft segment, and are available from BASF as PolyTHFTM B , a block copo intermediate segment in the TPU may be calculated as lymer , and PolyTHFTM R , a random copolymer. The third is follows : available as PolyGTM 55 - 56 from Lonza . [ 0062 ] Wt. % soft segment = wt. % polyols having a molecular weight of at least 250 daltons. Chain Extender [ 0063] Wt. % hard segment= wt. % isocyanate in hard [0071 ] The exemplary TPU composition is made using a segment + wt. % chain extender: low molecular weight diol chain extender ( chain lengthening agent ). Chain extenders ( less than 200 daltons ) or other chain extender . include diols , diamines, and combinations thereof. The [ 0064 ] Wt. % intermediate segment = 100 wt. % soft seg chain extender may have a molecular weight of up to 500 ment wt. % hard segment. daltons or up to 300 daltons, such as at least 46 daltons . US 2017 /0319462 A1 Nov. 9 , 2017

10072 ] One or more short chain polyols having from 2 to lized . In one embodiment, one or more diisocyanates are 20 , or 2 to 12 , or 2 to 10 or 2 - 8 carbon atomsmay be used utilized . The polyisocyanates useful herein generally have a as chain extenders in the polyurethane forming composition formula R (NCO )n , where n is at least 2 . R can be an to increase the molecular weight of the polyurethane . aromatic , a cycloaliphatic , an aliphatic , or combinations Examples of chain extenders include lower aliphatic polyols thereof having from 2 to about 20 carbon atoms. and short chain aromatic glycols having molecular weights [0080 ) Examples of aromatic diisocyanates include 4 , 4 ' of less than 500 or less than 300 . Suitable chain extenders diphenylmethane diisocyanate (MDI ) , m -xylene diisocya include organic diols ( including glycols ) having a total of nate (XDI ) , phenylene - 1 , 4 - diisocyanate , naphthalene - 1 , 5 from 2 to about 20 carbon atoms such as alkane diols , diisocyanate , 2 , 4 - toluene diisocyanate ( 2 , 4 - TDI) , 2 , 6 cycloaliphatic diols , alkylaryl diols, and the like . Exemplary toluene diisocyanate (2 ,6 - TDI) , 1 ,4 -phenylene diisocyanate , alkane diols include ethylene glycol, diethylene glycol, 1 , 3 -phenylene diisocyanate , 3 , 3 '- dimethoxy - 4 , 4 - biphe 1 ,3propanediol , 1 , 3butanediol, 1 ,4butanediol , (BDO ) , nylene diisocyanate , 3 , 3 - dimethyl - 4 , 4 ' -biphenylene diiso 1 ,3butanediol , 1, 5pentanediol , 2 ,2dimethyl - 1, 3propanediol, cyanate ( TODI) , 4 ,4 -diisocyanate - diphenyl ether , 2 ,4 -naph propylene glycol, dipropylene glycol, 1 ,6hexanediol , thalene diisocyanate , 1 , 5 - naphthalene diisocyanate , 1 , 3 1 ,7heptanediol , 1, 9nonanediol , 1 , 10decanediol, 1, 12dode xylene diisocyanate , 1 , 4 -xylene diisocyanate . canediol, tripropylene glycol, triethylene glycol, and [0081 ] Examples of aliphatic diisocyanates include iso 3methyl- 1 ,5pentanediol . Examples of suitable cycloali phorone diisocyanate ( IPDI) , 1 , 4 -butane diisocyanate phatic diols include 1 ,2cyclopentanediol , and 1 , 4cyclo ( BDI) , tetramethylene diisocyanate , hexamethylene diiso hexanedimethanol (CHDM ). Examples of suitable aryl and cyanate (HDI ) , 1 , 4 - cyclohexyl diisocyanate (CHDI ) , alkylaryl diols include hydroquinone di( 13hydroxyethyl ) decane- 1 , 10 -diisocyanate , lysine diisocyanate (LDI ) , iso ether (HQEE ) , 1 ,2dihydroxybenzene , 1, 3dihydroxybenzene , phorone diisocyanate (PDI ) , 1 , 5 -naphthalene diisocyanate 1 ,4dihydroxybenzene , 1 , 2 , 3trihydroxybenzene , 1 ,2di ( hy (ND ! ) , 4 , 4 '- diisocyanato dicyclohexylmethane (H12MDI ) , droxymethyl) benzene , 1, 4di ( hydroxymethyl ) benzene , 1, 3di 1 ,3 -diisocyanate methylcyclohexane , 1 ,4 -diisocyanate ( 2hydroxyethyl) benzene , 1, 2d i ( 2hydroxyethoxy )benzene , methylcyclohexane , 4 , 4 - diisocyanate dicyclohexane , 4 , 4 1 ,4di ( 2hydroxyethoxy )benzene , bisethoxy biphenol, 2 , 2di diisocyanato dicyclohexylmethane , and isomers , dimers , ( 4hydroxyphenyl) propane ( i. e ., bisphenol A ), bisphenol A trimers and mixtures thereof. ethoxylates, bisphenol F ethoxylates, 4 ,4 - isopropylidenedi [0082 ] In one embodiment, the isocyanate is selected from phenol, 2, 2 - di [ 4 -( 2- hydroxyethoxy )phenyl ] propane cycloaliphatic and aromatic diisocyanates . In one specific (HEPP ) , and mixtures thereof and the like. embodiment, the isocyanate is selected from MDI and [0073 ] Mixtures of one or more of the above chain extend H12MDI. ers can also be utilized . [0083 ] Suitable polyisocyanates are commercially avail [0074 ] Chain extenders with functionality greater than 2 able from companies such as Bayer Corporation of Pitts may be used so long as the resulting TPU retains its burgh , Pa ., The BASF Corporation of Parsippany , N . J ., The thermoplasticity. Examples of such chain extenders include Dow Chemical Company ofMidland , Mich ., and Huntsman trimethylolpropane ( TMP ), glycerin and pentaerythritol. Chemical of Utah . Generally , the addition of such chain extenders should not 10084 ] The molecular weight of the polymers described exceed 10 % relative to the weight of the difunctional chain herein are determined by gel permeation chromatography extenders . (GPC ) calibrated with a poly (methyl methacrylate ) [0075 ] In one embodiment, the chain extender is selected ( PMMA ) standard . Number average molecular weights are from 1 , 4 - butanediol, and 1 , 10 -decanediol . measured by GPC using a PL -GPC 220 high temperature [ 00761 Chain extenders can also be based on diamines. GPC instrument manufactured by Polymer Laboratories Exemplary diamines may have molecular weights of less ( Varian , Inc. ). Approximately 0 . 02 g polymer sample is than 500 , and include , for example , as ethylenediamine, dissolved in 5 ml of dimethyl acetamide (DMAC ), contain diethylenediamine , tetramethylenediamine , hexamethylene ing 250 ppm of butylated hydroxytoluene (BHT ) and 0 . 05 diamine, diethylenetriamine triethylenetetramine , tetraethyl molar NaNO3. The test sample solution is gently shaken for enepentamine , pentaethylenehexamine , piperazine ,morpho about two hours and filtered by passing the sample solution line, substituted morpholine , piperidine , substituted through a 0 . 45 um PTFE disposable disc filter. The chro piperidine, 2 - amino - 1 - ethylpiperazine hydrazine , 1 , 4 - cyclo matographic conditions are : Mobile phase : DMAC, with 250 hexanediamine , and mixtures thereof. Alkanolamines , such ppm BHT and 0 . 05 M NaNO2, 70° C . , 1 . 0 ml/min . Sample as ethanolamine , diethanolamine , and triethanolamine, may size: 100 ul Column set : PLgel (Guard + 2x Mixed - A ) , all 10 also be used . Further examples of chain lengthening agents um , in series . Waters Empower Pro LC /GPC software is include aniline , and the like . used to analyze the results and to calculate Mn. The weight 100771. The molar amount or ratio of the total hydroxyl average and number weight average molecular weights of groups of the one or more chain extenders utilized to the the polymers described herein are obtained by integrating total hydroxyl groups of Polyols A , B , and C may be from the area under the peak corresponding to the polymer, which about 0 . 1 to about 5 . 0 , or from about 0 . 2 to about 4 . 0 , or is normally the major high molecular weight peak , exclud from about 0 . 4 to about 2 . 5 . ing peaks associated with diluents , impurities, and other Polyisocyanate additives. [0078 ] The polyisocyanate includes one or more polyiso Catalyst cyanates . Suitable polyisocyanates include aromatic diiso [0085 ] One or more polymerization catalysts may be pres cyanates , aliphatic diisocyanates , and mixtures thereof. ent during the polymerization reaction . Generally , any con [0079 ] In order to form relatively long linear polyurethane ventional catalyst can be utilized to react the diisocyanate chains, di- functional or polyfunctional isocyanates are uti with the polyol intermediates and /or the chain extender. US 2017 /0319462 A1 Nov. 9 , 2017

Examples of suitable catalysts which in particular accelerate solution and cast together to form a polyurethane polymer the reaction between the NCO groups of the diisocyanates film , which may be then dried to form the dry polyurethane and the hydroxy groups of the polyols and chain extenders film . include organic tin compounds such as dibutyltin diacetate , [0090 ] Active agents useful herein may be categorized or dibutyltin dilaurate (DBTL ) , dioctyltin dilaurate ( DOTDL ) , described herein by their therapeutic and /or cosmetic benefit and dibutyltin bis (ethoxybutyl 3 -mercaptopropionate ) ; or their postulated mode of action or function . However, it titanic acid ; organic titanium compounds such as tetraiso is to be understood that the active and other ingredients propyl titanate , tetra - n - butyl titanate, polyhydroxytitanium useful herein can , in some instances, provide more than one stearate and titanium acetylacetonate ; tertiary amines such cosmetic and / or therapeutic benefit or function or operate as triethylene diamine, triethylamine N -methylmorpholine , via more than one mode of action . Therefore , classifications N , N , N ', N ' -tetramethylethylenediamine , N , N , N ', N ' -tetram herein are made for the sake of convenience and are not ethylhexamethylene diamine , triethylamine, N , N -dimethyl intended to limit an ingredient to the particularly stated piperazine , N , N -dimethylaminoethanol , dimethylcyclohex application or applications listed . ylamine , and diazabicyclo [ 2 . 2 . 2 ] octane ; and mixtures of two [0091 ] Active agents useful herein may be delivered to the or more thereof. surface of the skin , known as the stratum corneum , may be [ 0086 ] The total amount of the catalyst used may be from delivered to the underlying portions of the skin known as the 0 . 0001 to 0 . 1 part by weight per 100 parts by weight of the dermis and epidermis . Active agents may also be medicinal polyols A , B , and C . drug substances which penetrate through the initial layers of the skin to the underlying tissue , in this respect the active agents may have local effect and are not systemic . Active Other Additives agents may also have percutaneous absorption and have a [0087 ] Various types of optional components can be pres systemic effect where the active agent is considered a ent during the polymerization reaction , and /or incorporated medicinal drug substance and after absorption is transported into the TPU described above to improve processing and via the blood to the body systemically . other properties . These additives include antioxidants , such [0092 ] The active agents may be selected from skin whit as phenolic types, organic phosphites, phosphines and phos ening or depigmenting agents , anti -acne agents , anti -wrinkle phonites , hindered amines, organic amines, organosulfur and / or anti - aging agents , pain management agents , agents compounds , lactones and hydroxylamine compounds, bio stimulating healing , emollients , AQP - 3 modulating agents , cides, fungicides, antimicrobial agents , compatibilizers, aquaporin modulating agents , proteins from the aquaporin electro -dissipative or anti -static additives , fillers and rein family, collagen synthesis stimulating agents , agents modu forcing agents , such as titanium dioxide , alumina , clay and lating PGC - 1 - a synthesis , agents modulating the activity of carbon black , flame retardants, such as phosphates , haloge PPARy, agents which increase or reduce the triglyceride nated materials , and metal salts of alkyl benzenesulfonates , content of adipocytes, agents stimulating or delaying adi impact modifiers , such as methacrylate -butadiene -styrene pocyte differentiation , lipolytic agents or agents stimulating ( “MBS ” ) and methyl methacrylate /butyl acrylate (“ MBA ” ) , lipolysis , anti - cellulite agents , adipogenic agents , inhibitors mold release agents such as waxes , fats and oils , pigments of acetylcholine -receptor aggregation , agents inhibiting and colorants, plasticizers , polymers, rheology modifiers muscle contraction , anticholinergic agents , elastase inhibit such as monoamines, polyamide waxes , silicones , and poly ing agents , matrix metalloproteinase inhibiting agents ,mela siloxanes , slip additives , such as paraffinic waxes, hydro nin synthesis stimulating or inhibiting agents , propigment carbon polyolefins and /or fluorinated polyolefins , and UV ing agents , self - tanning agents , NO -synthase inhibiting stabilizers , which may be of the hindered amine light agents , 5a - reductase inhibiting agents, lysyl- and / or prolyl stabilizers (HALS ) and /or UV light absorber (UVA ) types. hydroxylase inhibiting agents , antioxidants , free radical Other additives may be used to enhance the performance of scavengers and / or agents against atmospheric pollution , the TPU composition or blended product. All of the addi reactive carbonyl species scavengers , anti - glycation agents , tives described above may be used in an effective amount antihistamine agents , antiviral agents , antiparasitic agents , customary for these substances . skin conditioners, humectants , substances which retain moisture, alpha hydroxy acids, beta hydroxy acids, mois [0088 ] These additional additives can be incorporated into turizers , hydrolytic epidermal enzymes, vitamins, amino the components of, or into the reaction mixture for, the acids , proteins, biopolymers , gelling polymers , agents able preparation of the TPU resin , or after making the TPU resin . to reduce or treat the bags under the eyes , exfoliating agents , In another process , all the materials can be mixed with the desquamating agents , keratolytic agents, antimicrobial TPU resin and then melted or they can be incorporated agents , antifungal agents , fungistatic agents , bactericidal directly into the melt of the TPU resin . agents , bacteriostatic agents , agents stimulating the synthe sis of dermal or epidermal macromolecules and /or capable Active Agents of inhibiting or preventing their degradation , elastin synthe sis - stimulation agents , decorin synthesis -stimulation agents , [0089 ] The hydrated polyurethane film includes one or laminin synthesis - stimulation agents , defensin synthesis more active agents . One or more excipients may also be stimulating agents , chaperone synthesis - stimulating agents , present. One or more of the active agents and/ or excipients CAMP synthesis - stimulating agents , heat shock proteins , may be introduced to the preformed dry film in a hydrating HSP70 synthesis stimulators , heat shock protein synthesis composition , such as water , an alcohol or other organic stimulating agents, hyaluronic acid synthesis -stimulating solvent, combination thereof, or the like . In another embodi agents , fibronectin synthesis - stimulating agents , sirtuin syn ment, one or more of the active agents and / or excipients is thesis - stimulating agents , agents stimulating the synthesis of combined with the polyurethane polymer to form a casting lipids and components of the stratum corneum (ceramides , US 2017 /0319462 A1 Nov. 9 , 2017 fatty acids ), agents that inhibit collagen degradation , agents EtiolineTM [ INCI: glycerin , butylene glycol, Arctostaphylos that inhibit elastin degradation , agents that inhibit serine uva ursi leaf extract, Mitracarpus scaber extract ] marketed proteases , agents stimulating fibroblast proliferation , agents by Sederma, SepiwhiteTM MSH [INCI : undecylenoyl phe stimulating keratinocyte proliferation , agents stimulating nylalanine ] marketed by Seppic , AchromaxylTM [ INCI: adipocyte proliferation , agents stimulating melanocyte pro water, Brassica napus extract ] marketed by Vincience , liferation , agents stimulating keratinocyte differentiation , GigawhiteTM [ INCI: water, glycerin , Malva sylvestris (mal agents that inhibit acetylcholinesterase , skin relaxant agents , low ) extract, Mentha piperita leaf extract, Primula veris glycosaminoglycan synthesis -stimulating agents , antihyper extract, Alchemilla vulgaris extract, Veronica officinalis keratosis agents , comedolytic agents , anti -psoriasis agents , extract , Melissa officinalis leaf extract , Achillea millefolium anti- dermatitis agents , anti - eczema agents , DNA repair extract ), Melawhite® [INCI : leukocyte extract, AHA ] or agents , DNA protecting agents , stabilizers , anti - itching Melfade® - J [ INCI: water, Arctostaphylos uva -ursi leaf agents , agents for the treatment and /or care of sensitive skin , extract, glycerin , magnesium ascorbyl phosphate ] marketed firming agents , redensifying agents , restructuring agents , by Pentapharm , Albatin® [ INCI: laminoethylphosphinic anti- stretch mark agents, binding agents , agents regulating acid , butylene glycol, water ] marketed by Exsymol, Tyro sebum production , antiperspirant agents, coadjuvant healing statTM - 11 [ INCI: water, glycerin , Rumex occidentalis agents , agents stimulating reepithelialization , coadjuvant extract ] and Melanostatine® - 5 [ INCI: dextran , nonapeptide reepithelialization agents , cytokine growth factors, cytokine 1 ] marketed by Atrium Innovations, arbutin and its isomers , growth factors , agents which act on capillary circulation kojic acid and derivatives thereof, ascorbic acid and deriva and / or microcirculation , calming agents , anti - inflammatory tives thereof such as 6 - O - palmitoylascorbic acid , ascorbyl agents , anesthetic agents , agents acting on capillary circu glucoside, dipalmitoyl ascorbic acid , sodium ascorbyl phos lation and / or microcirculation , agents stimulating angiogen phate (NAP ), magnesium ascorbyl phosphate (MAP ) , esis , agents that inhibit vascular permeability , venotonic aminopropyl ascorbyl phosphate , ascorbyl glucoside or agents , agents acting on cell metabolism , agents to improve ascorbyl tetraisopalmitate ( VCIP ) ; retinol and derivatives dermal- epidermal junction , agents inducing hair growth , thereof including tretinoin and isotretinoin , idebenone , hair growth inhibiting or retardant agents , chelating agents , hydroxybenzoic acid and derivatives thereof , niacinamide , plant extracts , essential oils , marine extracts , agents liquiritin , resorcinol and derivatives thereof, hydroquinone , obtained from a biofermentation process , mineral salts , cell a - tocopherol, y -tocopherol , azelaic acid , potassium azeloyl extracts , sunscreens and organic or mineral photoprotective diglycinate , resveratrol, linoleic acid , a - lipoic acid , dihy agents active against ultraviolet A and / or B rays , and mix drolipoic acid , a -hydroxy acids, B -hydroxy acids, ellagic tures thereof. acid , ferulic acid , cinnamic acid , oleanolic acid , aloesin and [ 0093] Skin Whitening and Depigmenting Agents its derivatives , serine protease inhibitors , for example [0094 ] Exemplary skin -whitening or depigmenting agents tryptase, trypsin and PAR - 2 inhibitors , and mixtures thereof. include hydrogen peroxide , pyridine - 3 - carboxamide ( nico [0095 ] Anti -Acne Agents tinamide ), kojic acid , hydroquinine , mulberry root extract, [0096 ] Exemplary anti- acne agents include salicylic acid , liquorice root extract , Scutellaria baicalensis extract , grape glycolic acid , lactobionic acid , azelaic acid , benzoyl perox extract, ferulic acid , hinokitiol, arbutin , a -arbutin ( bearberry ide , antibiotics such as Clindamycin , sodium sulfacetamide extract ), and mixtures thereof. extracts of Achillea millefo and erythromycin , retinoids such as adapalene, tazarotene, lium , Aloe vera , Azadirachta indica , Osmunda japonica , and tretinoin , which may be sold under trade names such as Artocarpus incisus , Bidens pilosa , Broussonetia papyrifera , Retin - A , DifferinTM , RenovaTM , and TazoracTM , and mix Chlorella vulgaris , Cimicifuga racemosa , Emblica officina tures thereof. lis, Glycyrrhiza glabra, Glycyrrhiza uralensis, Ilex purpu [0097 ] Anti- Wrinkle and /or Anti- Aging Agents rea , Ligusticum lucidum , Ligusticum wallichii , Mitracarpus [0098 ] Exemplary anti -wrinkle agents and / or anti -aging scaber , Morinda citrifolia , Morus alba , Morus bombycis , agents include extracts or hydrolyzed extracts of Vitis Naringi crenulata , Prunus domestica , Pseudostellaria het vinifera , Rosa canina , Curcuma longa , Iris pallida , Theo erophylla , Rumex crispus, Rumex occidentalis , Sapindus broma cacao , Ginkgo biloba , Leontopodium alpinum , mukorossi , Saxifraga sarmentosa , Scutellaria galericulata , Dunaliella salina , synthetic compounds or products , such as Sedum sarmentosum Bunge , Stellaria medica , Triticum Vul Matrixyl® [INCI : palmitoyl pentapeptide -4 ], Matrixyl® gare , Arctostaphylos uva ursi or Withania somnifera , fla 3000 [ INCI: palmitoyl tetrapeptide -7 , palmitoyl oligopep vonoids, soy extract, lemon extract , orange extract , ginkgo tide ], EssenskinTM [INCI : calcium hydroxymethionine ], extract , cucumber extract , geranium extract , bearberry RenovageTM [ INCI: teprenone ] or DermaxylTM [ INCI: (gayuba ) extract, carob extract, cinnamon extract, marjoram palmitoyl oligopeptide ] marketed by Sederma/ Croda , Via extract, rosemary extract , clove extract , soluble liquorice loxTM [ INCI: pentapeptide 3 ], Syn® - Ake [INCI : dipeptide extract, blackberry leaf extract, Lipochroman -6TM [INCI : diaminobutyroyl benzylamide diacetate ] , Syn®Coll [ INCI: dimethylmethoxy chromanol] and ChromabrightTM [INCI : palmitoyl tripeptide - 5 ] , PhytaluronateTM [INCI : locust bean dimethylmethoxy chromanyl palmitate ) marketed by Lipo (Ceratonia siliqua ) gum ] or PreregenTM [INCI : Glycine soja tec , ActiwhiteTM LS 9808 [ INCI: water, glycerin , sucrose ( soybean ) protein , oxidoreductases ] marketed by Pentap dilaurate , polysorbate 20 , Pisum sativum (pea ) extract] and harm /DSM , MyoxinolTM [ INCI: hydrolyzed Hibiscus escu Dermawhite® NF LS 9410 [ INCI: mannitol, arginine HC1, lentus extract] , SyniorageTM [ INCI: acetyl tetrapeptide - 11] , phenylalanine , disodium EDTA , sodium citrate , kojic acid , DermicanTM [ INCI: acetyl tetrapeptide - 9 ] or DN AGETM LS citric acid , yeast extract] marketed by Laboratoires Serobi [ INCI: Cassia alata leaf extract ] marketed by Laboratoires ologiques/ Cognis , LumiskinTM [ INCI: caprylic / capric tri Serobiologiques / Cognis , Algisium CTM [ INCI: methylsila glyceride, diacetyl- boldine ) , MelaclearTM [ INCI: glycerin , nol mannuronate ] or Hydroxyprolisilane CNTM [INCI : water , dithiaoctanediol, gluconic acid , sutilains, beta - caro methylsilanol hydroxyproline aspartate ) marketed by Exsy tene ], O .D .A .whiteTM [ INCI: octadecenedioic acid ] and mol, ArgirelineTM [ INCI: acetyl hexapeptide - 8 ], SNAP - 7 US 2017 /0319462 A1 Nov. 9 , 2017

[ INCI: acetyl heptapeptide- 4 ] , SNAP - 8 [ INCI: acetyl octa (6substituted 7methoxy - 2 ,2dimethylchromanes ), and cos peptide - 3 ] , Leuphasyl® [ INCI: pentapeptide - 18 ] , InylineTM metically or pharmaceutically acceptable salts , wherein R is [ INCI: acetyl hexapeptide - 30 ] , Aldenine® [ INCI: hydro a linear or branched , saturated or unsaturated aliphatic group lyzed wheat protein , hydrolyzed soy protein , tripeptide 1 ], containing 2 to 23 carbon atoms, or a cyclic group , and Preventhelia® [ INCI: diaminopropionoyl tripeptide - 33 ], which can contain substituents selected from hydroxy , Decoriny1TM [INCI : tripeptide - 10 citrulline ], Trylagen® alkoxy , amino , carboxyl, cyano , nitro , alkylsulfonyl or halo [ INCI: Pseudoalteromonas ferment extract , hydrolyzed wheat protein , hydrolyzed soy protein , tripeptide 10 citrul gen atoms; and X is selected from O and S . line , Tripeptide 1 ] , Eyeseryl® [ INCI: acetyl tetrapeptide - 5 ) , [0100 ] Moisturizing Agents , Humectants , Substances that Peptide AC29 [ INCI; acetyl tripeptide - 30 citrulline ] , Retain Moisture, and Emollients RelistaseTM [INCI : acetylarginyltriptophyl diphenylgly [0101 ] Exemplary moisturizing agents , humectants and cine ], ThermostressineTM [ INCI: acetyl tetrapeptide - 22 ] , emollients include sodium pyrrolidone carboxylate ; Lipochroman 6 [ INCI: dimethylmethoxy chromanol] , betaines, such as N , N , N - trimethylglycine ; yeast extract ; ChromabrightTM [ INCI: dimethylmethoxy chromanyl palmi polyols and polyethers such as glycerin , ethylhexylglycerin , tate ) , Antarcticine® [ INCI: Pseudoalteromonas ferment extract ], dGlyageTM [ INCI: lysine HC1, lecithin , tripeptide - 9 caprylyl glycol, pentylene glycol, butylene glycol, propyl citrulline ] , VilasteneTM [ INCI: lysine HC1, lecithin , tripep ene glycol and their derivatives, triethylene glycol, polyeth tide - 10 citrulline ] or HyadisineTM [ INCI: Pseudoalteromo ylene glycol, Glycereth -26 , Sorbeth - 30 ; panthenol; pyroglu nas ferment extract ] marketed by Lipotec , KollarenTM tamic acid and its salts and derivatives ; amino acids , such as [ INCI: tripeptide 1 , dextran ] marketed by Institut Europeen serine, proline , alanine , glutamate or arginine ; ectoine and de Biologie Cellulaire , CollaxylTM IS [ INCI: hexapeptide its derivatives ; N ( 2hydroxyethyl) acetamide ; N -lauroyl - pyr 9 ], Laminixyl ISTM TINCI: heptapeptide ) , OrsirtineTM GL rolidone carboxylic acid ; N - lauroyl- L - lysine ; N -alphaben [ INCI: Oryza sativa (rice ) extract ], D 'OrientineTM IS [INCI : zoyl- L - arginine ; urea ; creatine ; a - and B -hydroxy acids such Phoenix dactylifera (Date ) seed extract ) , Phytoquintes as lactic acid , glycolic acid , malic acid , citric acid or cineTM [ INCI: Einkorn ( Triticum monococcum ) extract ) or salicylic acid , and their salts , such as sodium lactate and QuintescineTM IS [ INCI: dipeptide - 4 ] marketed by Vin lactic acid bacteria fermented solution ; polyglyceryl acry cience /ISP , BONTLPeptide [ INCI: palmitoyl hexapeptide late ; sugars and polysaccharides, such as glucose , saccharide 19 ] marketed by Infinitec Activos, DeepalineTM PVB [ INCI: isomerate, sorbitol, pentaerythritol, inositol, xylitol, treha palmitoyl hydrolyzed wheat protein ] or SepiliftTM DPHP lose and derivatives thereof , sodium glucuronate , carragh [ INCI: dipalmitoyl hydroxyproline ) marketed by Seppic , enates ( Chondrus crispus ) and chitosan ; glycosaminogly GatulineTM Expression [ INCI: Acmella oleracea extract ] , cans such as hyaluronic acid and derivatives thereof such as GatulineTM In - TenseTM [ INCI: Spilanthes acmella flower sodium hyaluronate ; aloe vera in any of its forms; honey ; extract ) and GatulineTM Age Defense 2 [ INCI: Juglans regia soluble collagen ; lecithin and phosphatidylcholine; cer (walnut ) seed extract] marketed by Gattefosse , ThalassineTM amides ; cholesterol and its esters ; tocopherol and its esters , [ INCI: algae extract ] marketed by Biotechmarine , ChroNO such as tocopheryl acetate or tocopheryl linoleate ; long lineTM [INCI : caprooyl tetrapeptide - 3 ] and Thymulen -4TM chain alcohols such as cetearyl alcohol, stearyl alcohol, cetyl [ INCI: acetyl tetrapeptide - 2 ] marketed by Atrium Innova alcohol, oleyl alcohol, isocetyl alcohol or octadecan - 2 -ol ; tions/ Unipex Group , EquiStatTM CINCI: Pyrus malus fruit long -chain alcohol esters such as lauryl lactate , myristyl extract, glycine soja seed extract ] or Juvenesce [ INCI: lactate or C12 - C15 alkyl benzoates; fatty acids such as octyldodecanol, caprylic / capric triglyceride , Retinol, ursolic stearic acid , isostearic acid or palmitic acid ; polyunsaturated acid , BHT, butylene glycol, ilomastat ] marketed by fatty acids (PUFAs ) ; sorbitans such as sorbitan distearate ; Coletica /Engelhard /BASF , AmelioxTM [INCI : carnosine , glycerides such as glyceryl monoricinoleate , glyceryl tocopherol, Silybum marianum fruit extract) and Phyto monostearate , glyceryl stearate citrate or caprylic and capric CellTecTM Malus domestica [ INCI: Malus domestica fruit acid triglyceride ; saccharose esters such as saccharose cell culture ) marketed by Mibelle Biochemistry , BioxiliftTM palmitate or saccharose oleate ; butylene glycol esters , such [INCI : Pimpinella anisum extract ] and SMS Anti WrinkleTM as dicaprylate and dicaprate ; fatty acid esters such as iso [ INCI: Annona squamosa seed extract ] marketed by Silab , propyl isostearate , isobutyl palmitate , isocetyl stearate , iso antagonists of the Ca2 + channel , such as alverine , manga propyl laurate , hexyl laurate , decyl Oleate , cetyl palmitate , nese or magnesium salts , certain secondary or tertiary di- n -butyl sebacate , isopropyl myristate , isopropyl palmi amines , retinol and its derivatives , idebenone and its deriva tate , isopropyl stearate , butyl stearate , butyl myristate , iso tives, Coenzyme Q10 and its derivatives , boswellic acid and propyl linoleate , 2 - ethylhexyl palmitate, 2ethylhexyl its derivatives , GHK and its derivatives and / or salts , car cocoate , decyl Oleate ,myristyl myristate ; squalene; mink oil ; nosine and its derivatives, chloride channel agonists , and lanolin and its derivatives ; acetylated lanolin alcohols ; sili mixtures thereof. cone derivatives such as cyclomethicone, dimethicone or [ 0099 ] For example , U . S . Pat. No . 8 , 110 , 207 describes dimethylpolysiloxane ; Antarcticine® [ INCI: Pseudoaltero compound of general formula (I ) monas Ferment extract ] or acetyl- glutamyl- methionyl - ala nyl- isoleucine , acetyl- arginyl - phenylglycyl - phenylglycine or acetyl- arginyl - 6aminohexanoyl - alanine marketed by Lipotec , petrolatum ; mineral oil; mineral and synthetic waxes ; beeswax (Cera alba ); paraffin ; or waxes and oils with vegetable origins such as candelilla wax (Euphorbia cerifera ), carnauba wax ( Copernicia cerifera ) , shea butter ( Butirospermum Parkii ) , cocoa butter ( Theobroma cacao ) , castor oil (Ricinus communis ), sunflower oil (Helianthus annuus ) , olive oil (Olea europaea ) , coconut oil ( Cocos nucifera ), palm oil (Elaeis guineensis ) , wheat germ oil US 2017 /0319462 A1 Nov. 9 , 2017

( Triticum vulgare ) , sweet almond oil (Prunus amygdalus (0106 ] Skin Lipid Barrier Repair Agents dulcis) , musk rose oil ( Rosa moschata ), soya bean oil [0107 ] Exemplary skin lipid barrier repair agents include (Glycine soja ), grape seed oil ( Vitis vinifera ) , calendula oil phytosphingosine , linoleic acid , cholesterol , and mixtures (Calendula officinalis ), jojoba oil ( Simmondsia chinensis) , thereof mango oil (Mangifera indica ) , avocado oil (Persea gratis f0108 ] Anti - Cellulite Agents (0109 ] Exemplary anti -cellulite agents include Coleus for sima ), and mixtures thereof. skohlii root extract, Magnolia grandiflora bark extract, [0102 ] Anti- Inflammatory Agents Nelumbo nucifera leaf extract, and mixtures thereof. [0103 ] Exemplary anti - inflammatory agents include seal [ 0110 ] Wound Healing Agents whip extract, Polygonum cuspidatum root extract, allantoin , [0111 ] Exemplary wound -healing agents , coadjuvant heal madecassoside extract , echinacea extract, amaranth seed oil, ing agents , agents stimulating re - epithelialization and / or sandal wood oil , peach tree leaf extract, extract of Aloe vera , coadjuvant re -epithelialization agents include extracts of Arnica montana , Artemisia vulgaris , Asarum maximum , Aristolochia clematis , Centella asiatica , Rosa moschata , Calendula officinalis , Capsicum , Centipeda cunninghamii, Echinacea angustifolia , Symphytum officinale , Equisetum Chamomilla recutita , Crinum asiaticum , Hamamelis virgini arvense , Hypericum perforaturn , Mimosa tenuiflora , Persea ana , Harpagophytum procumbens, Hypericum perforaturn , gratissima , Prunus africana , Tormentilla erecta , Aloe vera , Lilium candidum , Malva sylvestris , Melaleuca alternifolia , soybean protein , Polyplant® Epithelizing [ INCI: Calendula Origanum majorana , Origanum vulgare , Prunus laurocera officinalis , Hypericum perforatum , Chamomilla recutita , sus , Rosmarinus officinalis , Salix alba , Silybum marianum , Rosmarinus officinalis ] marketed by Provital, Cytokinol® Tanacetum parthenium , Thymus vulgaris, Uncaria guianen LS 9028 [ INCI: hydrolyzed casein , hydrolyzed yeast pro sis or Vaccinium myrtillus , spike moss extract, lysozyme tein , lysine HCl] marketed by Laboratories Serobiologiques/ chloride, mometasone furoate , prednisolone , nonsteroidal Cognis or Definer® [ INCI: Zea May (Corn ) Kernel extract ) anti - inflammatories including loxoprofen sodium , flurbipro marketed by Coletica / Engelhard /BASF , allantoin , cadher fen , diclofenac sodium , tiaramide hydrochloride, cyclooxy ins, integrins , selectins , hyaluronic acid receptors, immuno genase or lipoxygenase inhibitors , benzydamine , acetylsali globulins, fibroblast growth factor, connective tissue growth cylic acid , rosmarinic acid , ursolic acid , glycyrrhizic acid factor, platelet - derived growth factor, vascular endothelial and sodium , potassium and ammonium salts thereof, a -bis growth factor , epidermal growth factor, insulin - like growth abolol , azulene and analogues , sericoside, ruscogenin , escin , factor, keratinocyte growth factors , colony - stimulating fac scoline , rutin and analogues , hydrocortisone , clobetasol, tors , transforming growth factor beta, tumor necrosis factor dexamethasone , prednisone , paracetamol, amoxiprin , beno alpha , interferons, interleukins, matrix metalloproteinases , rilate , choline salicylate , faislamine, methyl salicylate , mag cytokines , extra cellular matrices such as collagen I, II , and nesium salicylate , salsalate , diclofenac, aceclofenac , acem III, receptor protein tyrosine phosphatases, Antarcticine® etacin , bromfenac , etodolac , indomethacin , oxametacin , [ INCI: Pseudoalteromonas ferment extract ], Decorinyl® proglumetacin , sulindac , tolmetin , ibuprofen , dexibuprofen , [ INCI: Tripeptide- 10 citrulline ], Trylagen® [ INCI: Pseudo carprofen , fenbufen , fenoprofen , flurbiprofen , ketoprofen , alteromonas ferment extract , hydrolyzed wheat protein , dexketoprofen , ketorolac , loxoprofen , naproxen , miropro hydrolyzed soy protein , tripeptide - 10 citrulline , Tripeptide fen , oxaprozin , pranoprofen , tiaprofenic acid , suprofen , 1 ] , BodyfensineTM [ INCI: acetyl dipeptide - 3 aminohexano mefenamic acid , meclofenamate , meclofenamic acid , flufe ate ), marketed by Lipotec, and mixtures thereof. namic acid , tolfenamic acid , nabumetone , phenylbutazone , [0112 ] Muscle Relaxants , Aagents Inhibiting Muscle Con azapropazone , clofezone , kebuzone , metamizole , mofebuta traction , Agents Inhibiting Acetylcholine Receptor Cluster zone, oxyphenbutazone , phenazone , sulfinpyrazone , piroxi ing and Anticholinergic Agents cam , lornoxicam , meloxicam , tenoxicam , celecoxib , etori [0113 ] Exemplary muscle relaxants , agents inhibiting coxib , lumiracoxib , parecoxib , rofecoxib , valdecoxib , muscle contraction , agents inhibiting acetylcholine receptor nimesulide, naproxcinod , fluproquazone or licofelone , clustering and anticholinergic agents include extracts of omega - 3 and omega - 6 fatty acids, morphine , codeine, oxy Atropa belladonna , Hyoscyamus niger , Mandragora offici codone, hydrocodone , diamorphine , pethidine , tramadol, narum , Chondrodendron tomentosum , plants of the Brug buprenorphine , benzocaine, lidocaine , chloroprocaine , tet mansia genus , or the Datura genus , Clostridium botulinum racaine, procaine , amitriptyline , carbamazepine , gabapentin , toxin , peptides derived from the protein SNAP- 25 or pregabalin , bisabolol, NeutrazenTM INCI: water, butylene InylineTM [ INCI: acetyl hexapeptide- 30 ) marketed by Lipo glycol, dextran , palmitoyl tripeptide - 8 ] marketed by Atrium tec, baclofen , carbidopa, levodopa , bromocriptine , chlorphe Innovations /Unipex Group , Meliprene® [ INCI: dextran , nesin , chlorzoxazone, donepezil , mephenoxalone, reserpine , Acetyl Heptapeptide - 1 ] marketed by Institut Europeen de tetrabenazine, dantrolene , thiocolchicoside, tizanidine , clo Biologie Cellulaire/ Unipex Group , SkinasensylTM [ INCI: nidine, procyclidine, glycopyrrolate , atropine ,hyoscyamine , acetyl tetrapeptide- 15 ] or Anasensy?TM [INCI : mannitol, benztropine , scopolamine, promethazine, diphenhydramine , ammonium glycyrrhizate , caffeine , Hippocastanum (Horse dimenhydrinate , dicyclomine , cyclobenzaprine , Chestnut) extract] marketed by Laboratoires Serobi orphenadrine, flavoxate , cyclopentolate , ipratropium , oxy ologiques /Cognis , CalmosensineTM [INCI : acetyl dipeptide butynin , pirenzepine , tiotropium , trihexyphenidyl, tolt 1 ] marketed by Sederma, coenzyme Q10 or alkylglyceryl erodine , tropicamide, solifenacin , darifenacin , mebeverine , ethers , and mixtures thereof. trimethaphan , atracurium (besylate ) , cisatracurium , doxacu rium , fazadinium , metocurine, mivacurium , pancuronium , [0104 ] DNA Repair Agents pipecuronium , rapacuronium , tubocurarine , dimethyl tubo [0105 ] Exemplary DNA repair agents include C1 - C8 curarine , rocuronium , vecuronium , suxamethonium , alkyl tetrahydroxycyclohexanoate , micrococcus lysate , 18 -methoxycoronaridine , carisoprodol , febarbamate , mep bifida ferment lysate , DNA repair enzymes such as pho robamate , metocarbamol, phenprobamate , tibamate, anti tolyase and T4 endonuclease V , and mixtures thereof. convulsant agents such as levetiracetam , stiripentol, pheno US 2017 /0319462 A1 Nov. 9 , 2017 10 barbital, methylphenobarbital, pentobarbital, metharbital, 5 ,015 ,470 ; tyrosine kinase inhibitors , for example lamido barbexaclone, primidone, carbamazepine, oxcarbazepine , 1 - cyano( 3 , 4 -dihydroxyphenyl ) ethylene and those described benzodiazepines, for example clonazepam , cloxazolam , clo - in document EP 0403238 and corresponding U . S . Pat. No. razepate , diazepam , flutoprazepam , lorazepam , midazolam , 5 , 124 , 354 , diazoxides, for example 7 - ( acetylthio ) - 4 , 5 - di nitrazepam , nimetazepam , phenazepam , temazepam , tet hydrospiro [ androst- 4 - ene - 17 , 2 '- (3H ) furan ] - 3 - one, 1 , 1 - diox razepam , clobazam , hydrochloric acid epihydrochloride, tal ide of 3 -methyl - 7 - chloro [ 2H ]- 1 ,2 , 4 -benzothiadiazine and ipexole hydrochloride , tolperisone hydrochloride , and mix spirooxazine ; phospholipids, for example lecithin ; salicylic tures thereof. acid and derivatives thereof, hydroxycarboxylic and keto [0114 ] Pain Management Agents carboxylic acids and esters thereof, lactones and their salts ; [0115 ] Exemplary pain management agents and local anthralin , eicosa - 5 , 8 , 11- trienoic acids and esters thereof and anesthetics include lidocaine and salts such as lidocaine amides among others , minoxidil and derivatives, acetyl hydrochloride , bupivacaine and bupivacaine hydrochloride , glucosamine , and mixtures thereof. mepivacaine and mepivacaine hydrochloride , etidocaine , [0119 ] Agents for Reducing Bags Under the Eyes prilocaine and prilocaine hydrochloride , tetracaine , pro 10120 ] Exemplary agents for reducing bags under the eye caine , chloroprocaine , benzocaine , and their salts; counter and dark circles include hesperidin methyl chalcone , dipep irritant agents that mask pain such as menthol, camphor, tide - 2 , Passiflora incarnate flower extract , linoleic acid , methylsalicylate , cinnamaldehyde, capsaicin and mixtures isolinoleic acid , peptides as described in U . S . 20100098769 , thereof, acetylsalicylic acid ( aspirin ) and other salicylic acid and mixtures thereof. esters , diclofenac and salts thereof such as sodium , diethyl [0121 ] Collagen Synthesis or Blood Circulation Enhanc amine, ibuprofen , ketoprofen , acetaminophen and other non ing Agents steroidal anti - inflammatory drugs, analgesic drugs such as [0122 ] Exemplary collagen synthesis or blood circulation morphine hydrochloride, fentanyl citrate , buprenorphine enhancing agents include arginine, Ascophyllum nodosum hydrochloride , and the like , and mixtures thereof. extract, Asparagopsis armata extract, and mixtures thereof. [ 0116 ] Hair Growth Retardation and Stimulation Agents [0123 ] Antioxidants [0117 ] Exemplary hair growth retardation agents include (0124 Exemplary antioxidants include nordihydrogua ursolic acid , Boswellia serrata extract, activin and activin iaretic acid , butylhydroxyanisole (BHA ), butylhydroxytolu agonists , flavonoids such as quercetin , curcumin , galangin , ene (BHT ), propyl gallate , erythorbic acid , sodium erythor fisetin , myricetin , apigenin ; propyl gallate , nordihydrogua bate , para -hydroxyanisole , tert -butylhydroquinone ( TBHQ ) , iaretic acid , caffeic acid , tyrosine kinase inhibitors such as 2 ,6 , - di- tert -butyl - 4methylphenol, gallic acid esters such as lavendustin , erbstatin , tyrphostins , benzoquinone - ansamy propyl gallate and octyl gallate , probucol, polyphenols , cin herbimycin A , thiazolidinediones, phenazocine , 2 , 3 ascorbic acid and its salts , enzymes such as catalase , super dihydro - 2thioxo - 1Hindo1 - 3alkanoic acids, phenothiazine oxide dismutase and peroxidases ; citric acid , citrates, mono derivatives such as thioridazine ; sphingosine and derivatives glyceride esters , calcium metabisulfite , lactic acid , malic thereof such as phytosphingosine ; staurosporine and deriva acid , succinic acid , tartaric acid , vitamin A or ß -carotene , tives thereof, glycyrrhetinic acid , lauryl isoquinolinium bro vitamins E and C , tocopherols such as vitamin E acetate , mide , DecelerineTM INCI : lauryl isoquinolinium bromide , ascorbic acid esters such as ascorbylpalmitate and ascorbyl Pseudoalteromonas ferment extract ] marketed by Lipotec , acetate , zinc , copper , mannitol , reduced glutathione, caro serine protease inhibitors, trypsin , and mixtures thereof. tenoids such as cryptoxanthin , astaxanthin and lycopene ; [0118 ] Exemplary hair growth stimulating agents include cysteine , uric acid , carnitine , taurine, tyrosine, lutein , zeax Serenoa serrulata fruit extract, licorice extract, Tussilago anthin , N - acetyl- cysteine , carnosine , y - glutamylcysteine , farfara or Achillea millefolium , nicotinic acid esters such as quercetin , lactoferrin , dihydrolipoic acid , tea catechins , reti CzCoalkyl nicotinates such as methyl or hexyl nicotinate , nyl palmitate and derivatives thereof, bisulfate , metabisulfite benzyl nicotinate , or tocopheryl nicotinate ; biotin , 5a - re and sodium sulfite , chromans , chromenes and their ana ductase - inhibiting agents , anti- inflammatory agents , ret logues, Lipochroman - 6 [ INCI: Dimethylmethoxy Chroma inoids , for example all -trans - retinoic acid or tretinoin , isot nol ] , chelating agents of metals such as EDTA , sorbitol , retinoin , retinol or vitamin A , and derivatives thereof, such phosphoric acid or dGlyageTM [ INCI: Lysine HC1, Lecithin , as zinc salt of acetate , palmitate , propionate , motretinide , Tripeptide - 9 Citrulline ]; extract of Ginkgo Biloba , plant etretinate and trans - retinoate ; anti -bacterial agents , calcium extracts such as sage , pomegranate , rosemary , oregano , channel blockers , for example cinnarizine and diltiazem ; ginger, marjoram , cranberry , grape seed , tomato , green leaf hormones , for example estriol and its analogues and thy tea and black leaf tea ; oleoresin extract, extract of plants roxine and its analogues and /or salts ; antiandrogenic agents , which contain phenols such as vanillin , ellagic acid and for example oxendolone , spironolactone and diethylstilbe resveratrol ; tertiary butylhydroquinone or mixtures thereof, strol ; anti- radical agents , esterified oligosaccharides , for metal salts with a valence of 2 such as selenium , cadmium , example those described in documents EP 0211610 and vanadium or zinc ; a - lipoic acid , coenzyme Q , idebenone corresponding U . S . Pat. No . 4, 761 , 401 and EP 0064012 and and derivatives thereof, and mixtures thereof . corresponding U . S . Pat. No . 4 ,607 ,025 ; derivatives of [0125 ] Antihistamine Agents hexosaccharic acids , for example glucosaccharic acid or [0126 ] Exemplary antihistamine agents include chlorphe those described in EP 0375388 and corresponding U . S . Pat. niramine maleate , promethazine hydrochloride, cetirizine No . 5 ,081 , 151 ; glucosidase inhibitors, for example D - glu hydrochloride , and mixtures thereof. caro - 1 ,5lactam and those described in document EP [0127 ] UV Absorbers 0334586 and corresponding U . S . Pat . No. 4 , 975 , 441; gly [0128 ] Exemplary ultraviolet ray absorbers and agents cosaminoglycanase and proteoglycanase inhibitors , for capable of filtering UV rays include benzophenone deriva example L - galactono - 1 , 4 - lactone and those described in tives such as 2 , 4 - dihydroxybenzophenone , organic and min document EP 0277428 and corresponding U .S . Pat. No . eral photoprotective agents active against A and /or B ultra US 2017 /0319462 A1 Nov. 9 , 2017

violet rays such as substituted benzotriazoles, substituted cyl- valyl - phenylglycine , diaminopropionyl- alanyl- asparagi diphenylacrylates , organic nickel complexes , umbelliferone, nyl- histidine , acetyl- arginyl - asparaginyl -histidyl - citrulline urocanic acid , biphenyl derivatives , stilbene , 3 -benzylidene amide, Aldenine® [ INCI: hydrolyzed wheat protein , camphor, and derivatives thereof such as 3 -( 4 -methylben hydrolyzed soy protein , tripeptide - 1 ] , Decorinyl® [ INCI: zylidene ) camphor; 4 - aminobenzoic acid and derivatives tripeptide - 10 citrulline ], Serilesine® [ INCI: hexapeptide thereof, 2 - ethylhexyl 4 - ( dimethylamino ) benzoate , 2 - octyl 10 ] , Peptide AC29 [INCI : acetyl tripeptide - 30 citrulline ], 4 - ( dimethylamino ) benzoate and amyl 4 - (dimethylamino ) benzoate ; cinnamic acid derivatives such as benzyl cinna VilasteneTM [ INCI: lysine HCI, lecithin , tripeptide - 10 citrul mate , cinnamic acid esters , such as 2 - ethylhexyl 4 -methoxy line ], dGlyageTM [ INCI: Lysine HCl, Lecithin , Tripeptide- 9 cinnamate and diethylamino hydroxybenzoyl hexyl Citrulline ], Eyeseryl® [ INCI: acetyl tetrapeptide - 5 ] , Preven benzoate , propyl 4methoxycinnamate , isoamyl 4 -methoxy thelia® [ INCI: diaminopropionoyl tripeptide -33 ], Argire cinnamate , 2 - ethylhexyl- 2 -cyano - 3 , 3 - diphenyl cinnamate line® [INCI : acetyl hexapeptide - 8 ], SNAP - 7 [ INCI: acetyl (octocrylene ); salicylic acid derivatives such as benzyl heptapeptide - 4 ], SNAP - 8 [INCI : acetyl octapeptide- 3 ], Leu salicylate and salicylic acid esters , such as 2 - ethylhexyl phasyl® [ INCI: pentapeptide - 18 ], Trylagen® [ INCI: Pseu salicylate , 4 - isopropylbenzyl salicylate , homonienthyl doalteromonas ferment extract, hydrolyzed wheat protein , salicylate ; benzophenone derivatives , such as 2 -hydroxy -4 hydrolyzed soy protein , tripeptide- 10 citrulline, tripeptide methoxybenzophenone, 2 -hydroxy - 4 -methoxy - 4 ' -methyl 1 ] , InylineTM [ INCI: acetyl hexapeptide - 30 ] , MelatimeTM benzophenone, and 2 , 2 -dihydroxy - 4 -methoxybenzophe [INCI : acetyl tripeptide -40 ], ThermostressineTM [INCI : none ; benzalmalonic acid esters, such as di - 2 - ethylhexyl acetyl tetrapeptide -22 ] and Liporeductyl® [ INCI: caffeine , 4methoxybenzalmalonate ; triazine derivatives, such as 2 , 4 , Butcher' s broom ( Ruscus Aculeatus) root extract , triethano 6 - trianilino - ( p - carbo - 2 ' ethyl- 1 ' -hexyloxy ) - 1 , 3 , 5 - triazine , laminehydroiodide, carnitine, Ivy (Hedera helix ) extract, octyl triazone or diethylhexyl butamido triazone ; propane escin , tripeptide - 1 ] marketed by Lipotec , Matrixyl® [ INCI: 1 ,3 -diones , such as 1- ( 4 -tert -butylphenyl ) - 3 - (4 '- methoxy Palmitoyl Pentapeptide -4 ], Matrixyl® 3000 [ INCI: palmi phenyl) propane - 1 , 3dione ; ketotricyclo ( 5 . 2 . 1 . 0 )decane toyl tetrapeptide - 7 , palmitoyl oligopeptide ], Dermaxyl® derivatives ; 2 - phenylbenzimidazole- 5sulfonic acid ; benzo [ INCI: palmitoyl oligopeptide) , CalmosensineTM [ INCI: phenone sulfonic acid derivatives, such as 2hydroxy - 4 acetyl dipeptide - 1 ], Biopeptide CLTM [ INCI: glyceryl methoxybenzophenone - 5 - sulfonic acid and its salts ; 4 ( 2oxo polymethacrylate , propylene glycol, palmitoyl oligopeptide ] 3 -bornylidenemethyl ) benzenesulfonic acid , benzoyl and Biopeptide ELTM [ INCI: palmitoyl oligopeptide ) mar methane derivatives, such as benzoyl methane 2methyl - 5 keted by Sederma, pseudodipeptides, IP 2000 [ INCI: dex ( 2 - oxo - 3 -bornylidene ) sulfonic acid , such as 1 ( 4 '- tert - butyl tran , trifluoroacetyl tripeptide - 2 ] marketed by IEB and phenyl) - 3 - ( 4 '- methoxyphenyl ) propane - 1 , 3 - dione , 4 - tertbu Atrium , Pepha®TIMP [ INCI: Human Oligopeptide -20 ] , tyl -4 -methoxydibenzoylmethane , 1 -phenyl - 3 - (4 ' ECMProtect® [ INCI: Water (water ) , dextran , Tripeptide- 2 ] isopropylphenyl) - propane - 1 , 3 -dione , enamine compounds, and Melanostatine® -5 [INCI : dextran , nonapeptide - 1 ] mar anthranilates , silicons , benzimidazole derivatives, imidazo keted by Atrium Innovations, TIMP - PeptideTM [proposed lines , benzoyl derivatives, ChromabrightTM [ INCI: dimeth INCI: acetyl hexapeptide ], Bronzing S . F . [proposed INCI: ylmethoxy chromanyl palmitate ) and Preventhelia® [INCI : butyryl pentapeptide ] , BONTL Peptide [INCI : Palmitoyl diaminopropionoyl tripeptide -33 ] both marketed by Lipotec , Hexapeptide - 19 ] and ECM Moduline [ proposed INCI: metal oxides such as zinc oxide , titanium , iron , zirconium , Palmitoyl tripeptide - 28 ] marketed by Infinitec Activos , silicon , manganese , aluminum and cerium ; silicates, talc , IP2000TM [ INCI: dextran , Trifluoroacetyl tripeptide -2 ] mar barium sulfate , zinc stearate , carbon nanotubes , and mix keted by Institut Européen de Biologie Cellulaire , Syn®Coll tures thereof. [ INCI: Palmitoyl Tripeptide- 5 ] marketed by Pentapharm , [ 0129 ] Amino Acids and Their Salts NeutrazenTM TINCI: Water, butylene Glycol, dextran , Palmi [0130 ] Exemplary amino acids include glycine , alanine , toyl Tripeptide - 8 ], ChroNOlineTM [ INCI: Caprooyl Tetra valine, leucine , isoleucine , serine , threonine , phenylalanine , peptide - 3 ] and Thymulen - 4 [ INCI: Acetyl Tetrapeptide - 2 ] tyrosine , tryptophan , cystine , cysteine , methionine, citrul marketed by Atrium Innovations/ Unipex Group , Melip line, proline , hydroxyproline , aspartic acid , asparagine , glu rene® [ INCI: dextran , Acetyl Heptapeptide - 1 ] and Meli tamic acid , glutamine , arginine, histidine , lysine , y - amin tane® [ INCI: Acetyl Hexapeptide- 1 ] marketed by Institut obutyric acid , salts thereof and mixtures thereof. Example Européen de Biologie Cellulaire /Unipex Group, Skinasen salts include glutamate , trisodium methylglycine diacetate sylTM [ INCI: Acetyl Tetrapeptide - 15 ] marketed by Labora ( e . g . , Trilon® M marketed by BASF ) , derivatives of amino toires Serobiologiques /Cognis , Vialox® [ INCI: Pentapep acids which contain cysteine , in particular N -acetyl cysteine , tide - 3 ] , Syn® - Ake® [ INCI: Dipeptide Diaminobutyroyl ergothioneine or S - carboxymethylcysteine, and/ or mixtures Benzylamide Diacetate ] , Syn® - Coll [ INCI: Palmitoyl Trip thereof. eptide - 5 ] , SyniorageTM [ INCI: Acetyl Tetrapeptide - 11 ], Der [ 0131] Peptides and Commercial Formulations Contain micanTM [INCI : Acetyl Tetrapeptide - 9 ] marketed by Labo ing Them ratoires Serobiologiques /Cognis , Kollaren® [INCI : [0132 ] Exemplary peptides and commercial mixtures Tripeptide - 1 , dextran ] marketed by Institut Européen de which contain them some of which are mentioned elsewhere Biologie Cellulaire , Collaxyl® IS CINCI: Hexapeptide - 91 , herein for particular effects, and may include wheat pep Laminixyl ISTM [INCI : Heptapeptide ] , QuintescineTM IS tides , soybean peptide, copper peptideGHKCu [ INCI: Trip TINCI: Dipeptide - 4 ) , UCPeptideTM V JINCI: Pentapeptidel eptide - 1 ] , acetyl- glutamyl- methionyl - alanyl- isoleucine , and AT PeptideTM IS [ INCI: Tripeptide - 3 ] marketed by acetyl- arginyl - phenylglycyl- phenylglycine , BodyfensineTM Vincience / ISP , glutathione, carnosine and / or mixtures [ INCI: acetyl dipeptide - 3 aminohexanoate ], RelistaseTM thereof; and peptides of pharmaceutical use , such as gluca [ INCI: acetylarginyltriptophyl diphenylglycine ) , acetyl- ar gon , leuprolide , goserelin , triptorelin , buserelin , nafarelin , ginyl- phenylglycyl - valyl - glycine , acetyl- arginyl - phenylgly deslorelin , histrelin , avorelin , abarelix , cetrorelix , ganirelix , US 2017 /0319462 A1 Nov. 9 , 2017 degarelix , desmopressin , somatostatin and analogues of No .: 9 selected from SEQ ID NO . : 10 (MAEDADMRNEL somatostatin such as octreotide , vapreotide and lanreotide , EEMQRRADQL ) , SEQ ID NO .: 11 ( ADESLESTRRM among others . LOLVEESKDAGI) , SEQ ID NO . : 12 ( ELEEMQR [0133 ] Specific examples of peptides include those RADQLA ) , SEQ ID NO . : 13 ( ELEEMQRRADQL ), SEQ described in the following U . S . Publications, patents , and ID NO .: 14 ( ELEEMORRADQ ) , SEQ ID NO . : 15 (EL international applications, where in each case, R , and R , are EEMQRRAD ), SEQ ID NO .: 16 (ELEEMQRRA ), SEQ ID respective N and C peptide terminating groups which are NO .: 17 ( ELEEMORR ) , SEQ ID NO . : 18 (LEEMOR generally not aamino acids, examples of which are given in RADQL ), SEQ ID No. : 19 (LEEMQRRADQ ), SEQ ID the respective patent documents : NO .: 20 (LEEMQRRAD ,) , SEQ ID No. : 21 [0134 ] U . S . Pat. No. 6 , 169, 074 , which describes an iso (LEEMORRA , ), SEQ ID NO . : 22 (LEEMORR ) , SEO ID lated excitationsecretory uncoupling peptide (ESUP ) for NO .: 23 ( EEMQRRADQL ) , SEQ ID NO . : 24 ( EEMQR inhibiting neurotransmitter secretion from neuronal cells , RADO ) , SEO ID NO . : 25 ( EEMORRAD ) , SEO ID NO . : 26 consisting of the amino acid sequence of SEQ ID NO . : 1 (EEMORRA ) , SEO ID NO . : 27 (EEMORR ) , SEO ID NO . : ( 170 - EIDTQNRQIDRIMEKADSNKTRIDEANQRATKM 28 ( LESTRRMLQLVEE ) , SEQ ID NO . : 29 (NKDMKE LGSG - 206 , which is the amino acid sequence of the sub AEKNLT ) , SEQ ID NO : 30 (KNLTDL ) , SEQ ID NO .: 31 strate binding domain of SNAP -25 ) , SEQ ID NO . : 2 ( 170 (IMEKADSNKTRIDEANQRATKMLGSG ), SEQ ID NO .: EIDTONRQIDRIMEKADSNK - 189 , which is the amino 32 (SNKTRIDEANORATKMLGSG ) , SEQ ID NO . : 33 acid sequence of ESUP /E20h ) , SEQ ID NO . : 3 ( 181IME ( TRIDEANORATKMLGSG ) , SEO ID NO . : 34 (DEAN KADSNKTRIDEANQRATKMLGSG - 206 , which is the QRATKMLGSG ) , SEQ ID NO . : 35 (NQRATKMLGSG ) amino acid sequence of ESUP / E26h ), SEQ ID NO .: 4 and SEQ ID NO .: 36 (QRATKMLGSG ) , SEQ ID NO . : 9 ( 187SNKTRIDEANQRATKMLGSG - 206 , the amino acid being Met Ala Glu Asp Ala Asp Met Arg Asn Glu Leu Glu sequence of ESUP / A20h ) , and SEQ . ID . NO . : 5 (Gln -Asn Glu Met Gin Arg Ala Asp Gin Leu Ala Asp Glu Ser Leu Glu Arg -Gln - lle - Asp - Arg - Ile -Met - Glu - Lys - Ala -Asp -Ser - Asn Ser Thr Arg Arg Met Leu Gln Leu Val Glu Glu Ser Lys Asp Lys, the amino acid sequence of an ESUP derived from Ala Gly Ile Arg Thr Leu Val Met Leu Asp Glu Gln Gly Glu SNAP - 25 ) . All residues correspond to substrate binding Gln Leu Glu Arg Ile Glu Glu Gly Met Asp Gln Ile Asn Lys domain residues. Asp Met Lys Glu Ala Glu Lys Asn Leu ThrAsp Leu Gly Lys [ 0135 ] U . S . Pat . Nos. 7 ,015 , 192 and 7 ,473 ,679 , which Phe Cys Gly Leu Cys Val Cys Pro Cys Asn Lys Leu Lys Ser describe peptides having a sequence at least 3 and no more Ser Asp Ala Tyr Lys Lys Ala Trp Gly Asn Asn Gln Asp Gly than 30 adjacent amino acids from the amino end of protein Val Val Ala Ser Gin Pro Ala Arg Val Val Asp Glu Arg Glu SNAP - 25 and which is useful as neuronal exocytosis inhibi Gln Met Ala Ile Ser Gly Gly Phe Ile Arg Arg Val Thr Asn tor, in particular, the synthetic peptide whose complete Asp Ala Arg Glu Asn Glu Met Asp Glu Asn Leu Glu Gin Val amino acid sequence is selected from the amino acid Ser Gly Ile Ile Gly Asn Leu Arg His Met Ala Leu Asp Met sequence of SEQ ID NO : 6 (Glu Glu Met Gln Arg Arg ) and Gly Asn Glu Ile Asp Thr Gln Asn Arg Gln Ile Asp Arg Ile the amino acid sequence of SEQ ID NO : 7 (Glu Leu Glu Glu MetGlu Lys Ala Asp Ser Asn Lys Thr Arg Ile Asp Glu Ala Met Gln Arg Arg Ala Asp Gln Leu Ala ). The Nterminus of Asn Gln Arg Ala Thr Lys Met Leu Gly Ser Gly . the peptide may be acetylated and the amino acid at the C [0139 ] U . S . 20100098769, which describes a peptide terminus of the peptide may be amidated . capable of reducing or removing bags formed under the eyes [ 0136 ] U . S . Pat. No . 7 ,943 ,156 , which describes peptides of general formula ( V ) : capable of increasing firmness of skin and delaying aging of skin . These XIKVAV peptides of general formula ( III ): X SEQ ID NO . 8Y : HN

O O O =O

= = =0 X H - CH - C - CH - C H - CHH - C - C - Y . N Z N CH - CH3 - CH - CH, CH , CH - CH3 CH2 CHZ CH3 NANHNH N CH3 its stereoisomers, mixtures thereof, and its cosmetically and dermopharmaceutically acceptable salts , where X is selected from cysteinyl, seryl, threonyl and aminobutyryl. [0137 ] wherein X is selected from the group consisting of [0140 ] U . S . 20110002969, which describes a peptide hydrogen , an amino acid and an acyl group and Y is selected which includes only four amino acids and which is capable from the group consisting of amino , hydroxyl and thiol . The of inhibiting the activity of matrix metalloproteinases , of XIKVAV peptides of general formula XSEQ ID NO . 8 - Y general formula (VI ) : R1 - AA - AA , - AAz- AAL - R , ( R , stimulate bioadhesion of cutaneous cells by increasing (SEQ ID NO .: 37 ) -R2 ) , stereoisomers thereof, mixtures expression of bioadhesion peptides . thereof and cosmetically or pharmaceutically acceptable [0138 ] U . S . 20100021510 , which describes a peptide salts thereof, wherein : AA , is - Arg - ; AA , is selected from capable of regulating neuronal exocytosis , of the general - His - and - Asn -; AAz is selected from -His - and - Arg -; AA4 formula ( IV ) : R - AA - R , its stereoisomers , mixtures thereof, is - Cit -, Specific examples include R - Arg -His - His - Cit- R2 and its cosmetically and pharmaceutically acceptable salts , (R1 - ( SEQ ID NO .: 38 )- R2 ) , R , - Arg - Asn - Arg - Cit -R2 (R1 wherein AA is a sequence of a least 3 and up to 40 adjacent (SEQ ID NO . : 39 ) - R , ) , and stereoisomers , mixtures thereof amino acids contained in the amino acid sequence SEQ ID and /or cosmetic or pharmaceutical acceptable salts thereof. US 2017 /0319462 A1 Nov. 9 , 2017 13

[0141 ] U .S . 20090155317 , which describes a peptide cosmetic or pharmaceutical acceptable salts , wherein : AA , which includes only four amino acids and which is capable and AA , are independently selected from - Tyr - and -Phe - ; of reducing facial wrinkles, of general formula ( VII ) : and AAz is selected from - Nle - and -Met - . Specific examples include R L - Tyr- L - Tyr- L -Met -R2 , R - L - Tyr- L -Phe - L -Met R2, and R - L - Tyr- L - Tyr- L -Nle - R2 , and stereoisomers , mix tures thereof and / or cosmetic or pharmaceutical acceptable salts thereof. [0146 ] U . S . 20120121675 , which describes a peptide of general formula (XI ) : R - W ,, - Xm - AA7- AA2- AA3 - AA4 N AA3- AAG- Y , - Z R2 (R1 - (SEQ ID No .: 49 ) -R2 ) , its stereoi IZ somers , mixtures thereof and /or its cosmetic or pharmaceu tical acceptable salts , wherein AA , is selected from Asp , Glu and Pro ; AA , is Asp ; AAz is selected from Tyr and Arg ; AAA is selected from Phe and Tyr ; AA , is selected from Arg and Lys ; AAG is selected from Leu and Met; W , X , Y and Z are OH independently selected from coded amino acids and non coded amino acids ; n , m , p and s independently have a value [0142 ] and cosmetically ordermopharmaceutically of between 0 and 1 . Specific examples include 131 - L -Glu acceptable salts thereof, wherein : X and Y are selected from L - Asp - L - Tyr- L - Tyr- L - Arg - L -Leu -R , (R -( SEQ ID No .: natural amino acids in their L - or D - form and non - encoded 50 ) -R2 ) , Ri- L -Pro - L - Asp - L - Tyr- L - Tyr- L - Lys - L -Leu - Rz amino acids. Specific examples include peptides where X is (R - (SEQ ID No .: 51 ) - R2) , R - L -Glu - L - Asp - L - Arg - L - Phe glycyl, D -alanyl or D - seryl, and /or where Y is L -methionyl L - Arg - L -Met -R2 ( R , - (SEQ ID No. : 52 ) - R2 ) , R , - L -Glu - L or L - leucyl. Asp - L - Tyr - L - Tyr - L - Arg - L -Met -R2 (R1 - ( SEQ ID No .: 53 ) [0143 ] U . S . 20110195102 , which describes a peptide of R ) , and R - L -Pro - L - Asp - L - Tyr- L - Tyr - L - Arg - L -Met - R , only four amino acids, which is capable of inhibiting the ( R , -( SEQ ID No. : 54 ) - R2) , and corresponding peptides activity of Reactive Carbonyl Species ( RCS ) with general wherein at least one of W , X , Y and Z is present, and formula (VIII ) : R -AA7 - AA2- AA3- AA4- R2 ( R - SEQ ID stereoisomers, mixtures thereof and /or cosmetic or pharma NO .: 40 ) - R2 ), its stereoisomers, mixtures thereof, and its ceutical acceptable salts thereof. cosmetically or pharmaceutically acceptable salts , wherein [0147 ] U . S . 20130101662 , which describes a peptide of AA , is selected from - Lys -, -Orn -, -Dab - , - Dpr- , -Agl - , general formula (XII ): R -Wn - Xm -AA , -AA2 - AA3 -AA4 - Y , - 3 , 4 -dehydrolysine and - 4 , 5 - dehydrolysine ; AA , is - Ala - ; Z - R , ( R , -( SEQ ID No. : 55 ) - R , ), its stereoisomers, mixtures AAz is selected from -Asp -, - Ala -, - Asn - , -Glu - and -Pro -; thereof and /or its cosmetically or pharmaceutically accept and AA , is -His - . Specific examples include R , - L -Dpr - D able salts , wherein : AA , is -His - ; AA , is selected from the Ala -L -Ala - L -His -R , (R7 -( SEQ ID NO .: 41) -R2 ) , R , L -Dpr group consisting of -His -, - Leu - and -Pro - ; AAz is - Leu -; D - Ala -L -Pro - L -His -R , ( R -( SEQ ID NO .: 42 )- R2) , R , L AA , is selected from the group consisting of - Arg - and Dpr- L - Ala - L - Pro - L - HisR , ( R - (SEQ ID NO . : 43 )- R2) , and -Asn -; W , X , Y and Z are independently selected from stereoisomers , mixtures thereof and /or cosmetic or pharma amongst themselves from the group consisting of the codi ceutical acceptable salts thereof. fied amino acids and uncodified amino acids; n , m , p and a [0144 ] U . S . 20110300199, which describes a peptide hav are independently selected from amongst themselves and ing a maximum of seven amino acids which is capable of have a value between 0 and 1 ; n + m + p + q is less or equal to inhibiting elastase activity and /or stimulating collagen syn 2 . Specific examples include R - L -His - L - Leu - L -Leu - L thesis in the skin of general formula ( IX ): R . - W . - X , - AA Arg - R , ( R - (SEQ ID No .: 56 ) - R , ) and R , - L -His - L - Pro - L AA2- AA3 -AA4 - Ym - R2 ( R - ( SEQ ID NO . : 44 ) - R2) , its ste Leu - L - Arg -R2 (R /- (SEQ ID No. : 57) -R2 ) . reoisomers , mixtures thereof, and /or its cosmetically or [0148 ] U . S . 20130309281 , which describes a peptide of pharmaceutically acceptable salts , wherein at least one of the general formula ( XIII ) : amino acids AA , , AA , and AA , is uncoded ; AA , is selected from - Arg - , - Phg - and - Nle - or is absent; AA , is selected from - Ala - , - Phg - , -Cit - and -Nle - ; AA , is selected from H?N . - Trp - , - Val- and - Tyr - ; AA4 is selected from - Phg - and -Gly - ; W , X and Y are independently selected from the group consisting of coded and uncoded amino acids , and p , n and R - 44 m each range between 0 and 1 . Specific examples include - N R1- L - Arg - L -Nle - L - ( or D - ) -Phg - L - Tyr - L - ( or D ) - PhgR , ( R , ! ( SEO ID No . : 45 ) - R , ) , R - L - Arg - or L - Nle or absent ) - L - or COOH D )- Phg - L - Tyr -L - (or D )- Phg -R2 ( R , -( SEQ ID No .: 46 ) -R2 ), Ri- L - Arg - L -( or D -) -Phg - L - Val - L -( or D -) -Phg (or - L -Gly -) NH R , ( R , - (SEQ ID No . : 47 ) - R , ) , and R , - L - ( or D - ) - Phg - L - ( or D - ) -Phg - L - Trp - L - ( or D - ) -Phg -R2 ( R - (SEQ ID No. : 48 ) R2) , and corresponding peptides wherein at least one of W , 0 NH2 X , and Y is present, and stereoisomers, mixtures thereof and / or cosmetic or pharmaceutical acceptable salts thereof. stereoisomers thereof, mixtures thereof, and cosmetically [0145 ] U . S . 20120021029 , which describes a peptide hav and dermopharmaceutically acceptable salts thereof, ing only three amino acids of general formula (X ): R1- AA , wherein : Z is selected from the group consisting of alanyl, AA2- AA3 - R2 , its stereoisomers , mixtures thereof and /or its alto - isoleucyl, glycyl, isoleucyl, isoseryl, isovalyl, leucyl , US 2017 /0319462 A1 Nov. 9 , 2017 14 norleucyl, norvalyl, prolyl, seryl, threonyl, allo - threonyl or valyl; n and m range independently from one another between 1 and 5 ; AA is selected from the group consisting of natural encoded amino acids in their L - or D - form and R1 - AA - AA2 - NH - CH — C — AA3 - R2, non - encoded amino acids; x and y range independently from (CH2 ) one another between 0 and 2 . Specific examples include those where wherein Z is L - isoleucyl, L - threonyl or L -valyl NHR3 and wherein x and y are 0 , and stereoisomers , mixtures thereof and / or cosmetic or pharmaceutical acceptable salts [0154 ] its stereoisomers , mixtures thereof and / or its cos thereof. metic or pharmaceutical acceptable salts , wherein AA , is selected from - Asp -, -Glu -, - Asn - , -Gln - , - Lys - and -Gly - , [0149 ] U . S . 20140120141 , which describes a peptide of AA , is selected from - Val -, - Leu - , - Ile - , -Met - , -Cit - , -His - , general formula ( XIV ) : R - W -Xm - AA1 -AA2 - AA3- AA4 - Thr- and -Gln - ; AAz is selected from - Tyr- , - Trp - and AA3- AAG - Y , - Z , -R2 (R1 - ( SEQ ID No .: 58 )- R2 ) its stereoi 4 - Abz; n is selected from 1 , 2 , 3 and 4 , Rz is selected from somers ,mixtures thereof and / or its cosmetic or pharmaceu H and - AA , - AA , - R , R , is selected from H , a polymer tical acceptable salts , wherein : AA , is selected from the derived from polyethylene glycol, substituted or unsubsti group consisting of - Ser - , - Thr- and - Tyr - ; AA , is selected tuted non - cyclic aliphatic groups , substituted or unsubsti from the group consisting of - Pro - and - Val- ; AAz is - Ala -; tuted alicyclyl groups, substituted or unsubstituted hetero AA4 is selected from the group consisting of -Glu - , -Gly cyclyl groups, substituted or unsubstituted heteroarylalkyl and - Val- ; AA , is -Gly -; AA , is selected from the group groups, substituted or unsubstituted aryl groups, substituted consisting of -Gln - , -Gly -, -His - and -Pro - ; W , X , Y , Z are or unsubstituted aralkyl groups and RGCO - , wherein Ro is amino acids and are independently selected from amongst selected from H , substituted or unsubstituted non -cyclic themselves ; n , m , p and q are independently selected from aliphatic groups, substituted or unsubstituted alicyclyl amongst themselves and have a value of 0 or 1 ; n + m + p + q is groups , substituted or unsubstituted aryl groups, substituted lower than or equal to 2 . Specific examples include R - L or unsubstituted aralkyl groups, substituted or unsubstituted heterocyclyl groups and substituted or unsubstituted het Tyr- L -Pro - L - Ala - L -Glu - L -Gly - L -Gln - R2, ( R - (SEQ ID No. : eroarylalkyl groups; R2 is selected from — NR4R5, — ORA 59) -R2 ) R - L -Ser - L - Val - L - Ala - L - Val- L -Gly - L -Gln - R2 (R1 and — SR4, wherein R4 and R , are independently selected (SEQ ID No. : 60 ) -R2 ) , and R , L - Ser - L - Pro - L - Ala - L -Gly - L from H , a polymer derived from polyethylene glycol, sub Gly - L -Pro -R2 (R / -( SEQ ID No .: 61 ) - R2) , and stereoisomers , stituted or unsubstituted non - cyclic aliphatic group , substi mixtures thereof and / or cosmetic or pharmaceutical accept tuted or unsubstituted alicyclyl, substituted or unsubstituted able salts thereof. heterocyclyl , substituted or unsubstituted heteroarylalkyl, [0150 ] U .S . 20150183823 , which describes peptides of substituted or unsubstituted aryl, and substituted or unsub general formula (XV ) : R / -AAL - AA2- AA3- R2 , where AA , is stituted aralkyl ; and R , and / or R2 are not a - amino acids. selected from - Tyr - and - Phe -, AA , is - Tyr -, and AAz is [0155 ] Vitamins selected from - Nle - and -Met -, its stereoisomers , mixtures 10156 ] Example vitamins and factors acting like a vitamin thereof and / or their cosmetically or pharmaceutically include vitamin A and analogues thereof such as retinol and retinoic acid , carotenoids such as a - carotene and ( 3 -caro acceptable salts , which is suited to the treatment and /or care tene , vitamin B , and analogues thereof such as thiamines , of conditions, disorders and /or diseases of the skin and /or vitamin B2 and analogues thereof such as riboflavin , vitamin hair by stimulating cyclic adenosine monophosphate syn Bo and analogues thereof such as pyridoxine, vitamin B12 thesis ( CAMP ) . Specific examples include R - L - Tyr- L - Tyr and analogues thereof such as cyanocobalamin , folic acid , L -Met - R2 , R , L - Tyr - L -Phe - L -Met -R2 , and R L - Tyr- L - Tyr nicotinic acid , pantothenic acid , vitamin C and analogues L - Nle -R2 , and stereoisomers , mixtures thereof and / or thereof such as L - ascorbic acid , vitamin D and analogues cosmetic or pharmaceutical acceptable salts thereof. thereof such as ergocalciferol and cholecalciferol, vitamin E [0151 ] WO2014 /086785 (and U .S . Ser . No . 14 /649 , 747 ; and analogues thereof such as d - a - tocopherol and y - tocoph Filed Jun . 4 , 2015 ), which describes compounds capable of erol, Coenzyme Q10 , vitamin K and analogues thereof , accelerating the DNA protection and repair processes of carnitine, ferulic acid , a - lipoic acid , orotic acid , and mix general formula (XVII ): tures thereof. [0157 ] In one specific embodiment, the vitamins are [0152 ] R / - W , - Xm -AA , - AA2- AA3 - AA4- AA5 - AA . - Y . Z , selected from hydrosoluble vitamins , such as vitamin C , R , ( R , - ( SEQ ID No. : 62 ) - R , ) , its stereoisomers , mixtures vitamin B1 , vitamin B2 , vitamin B3 , vitamin B5 , vitamin thereof and /or its cosmetically or pharmaceutically accept B6 , vitamin B7, vitamin B9, vitamin B12 , carnitine and /or able salts , wherein AA , is - Tyr- ; AA , is selected from - Asn - , mixtures thereof. - His -, - Tyr- and -Glu - ; AAz is selected from -Lys -, -Ser - and [0158 ] Free Radical Scavengers , Anti - Atmospheric Pollu - Pro - ; AA4 is selected from -Gly - , - Leu -, -Lys - and - His - ; tion Agents , and Reactive Carbonyl Species Scavengers AA , is selected from -Gln - and - Asn - ; AA , is - Val - ; W , X , [0159 ] Exemplary free radical scavengers and /or anti Y , Z are independently selected from amino acids. n , m , p atmospheric pollution agents, and /or reactive carbonyl spe and q independently have a value of 0 or 1 ; n + m + p + q is cies scavengers include tea extract , olive leaf extract , extract of Rosmarinus officinalis or extract of Eichhornia crassipes , smaller than or equal to 2 . benzopyrenes , vitamin C and derivatives thereof , vitamin E [0153 ] WO2014 / 170347 (and U .S . application Ser . No . and derivatives thereof, in particular tocopheryl acetate , 14 /783 ,689 , filed Oct . 9 , 2015 ), which describes a com ascorbyl glycoside , phenols and polyphenols , in particular pound of general formula (XVI ) : tannins, tannic acid and ellagic acid , gallocatechol, antho US 2017 /0319462 A1 Nov. 9 , 2017 15

cyanins , chlorogenic acid , stilbenes, indoles , cysteine- con [0164 ] Exemplary vegetable extracts include hydrosoluble taining amino acid derivatives , in particular N - acetylcyste vegetable extracts , for example hydrosoluble extracts of ine , ergothioneine, S - carboxymethylcysteine , chelating chamomile , ivy, lemon , ginseng , raspberry , Roast amaranth , agents , in particular ethylene diamine tetraacetic acid Rehmanniae radix , gardenia , carrot, orange , peach , pine ( EDTA ) trisodium ethylenediamine hydroxyethyl triacetate , apple, gentian , hibiscus flower , walnut leaf, pumpkin , peony, sodium citrate , gluconic acid , phytic acid , sodium polyphos quinoa, boldo , rough bindweed , salvia , pomegranate , phate , sodium metaphosphate and ethylenediamines, caro oregano , ginger, marjoram , cranberry , grape , tomato , green tenoids , bioflavonoids , ubiquinone , idebenone, catalase , superoxide dismutase , lactoperoxidase , glutathione peroxi tea , black tea , aloe vera ( Aloe Barbadensis ), Sophora dase , glutathione, benzylidene camphor, pidolates, lignans , japonica , papaya , pineapple , pumpkin , sweet potato , melatonin , oryzanol, carnosine and derivatives thereof, Bupleurum chinensis , Cecropia obtusifolia , Celosia cristata , GHK [ INCI: tripeptide - 1 ] and its salts and / or derivatives, Centella asiatica , Chenopodium quinoa , Chrysanthellum Aldenine® [INCI : hydrolyzed wheat protein , hydrolyzed indicum , Citrus aurantium amara , Coffea arabica , Coleus soy protein , tripeptide - 1 ] , Preventhelia® [ INCI: diamino Forskohlii , Commiphora myrrha , Crithmum maritimum , propionoyl tripeptide -33 ], diaminopropionyl- alanyl- aspar Eugenia caryophyllus, Ginkgo biloba , Hedera helix ( ivy ), Hibiscus sabdariffa , Ilex paraguariensis , Laminaria digi aginyl -histidine , and LipochromanTM -6 [INCI : dimethyl tata , Nelumbium speciosum , Paullinia cupana , Peumus bol methoxy chromanol] marketed by Lipotec, and mixtures dus , Phyllacantha fibrosa , Prunella vulgaris , Prunus thereof. amygdalus dulcis , Ruscus aculeatus (Butcher ' s broom [0160 ] Hydrophilic Cosmetic , Pharmaceutical and Ali extract ) , Sambucus nigra , Spirulina platensis Algae , mentary Active Agents Uncaria tomentosa , Verbena Officinalis , Opuntia ficus - in [0161 ] Examples of hydrophilic cosmetic , pharmaceutical dica , Salix alba , Lupinus spp ., Secale cereale , Tussilago and / or alimentary active agents include amino acids , pep farfara , Achillea millefolium , Azadirachta indica , Osmunda tides , proteins, hydrolyzed proteins , enzymes , hormones , japonica , Artocarpus incisus, Bidens pilosa , Broussonetia vitamins, mineral salts , sugars , nucleotides , nucleic acids, papyrifera , Chlorella vulgaris , Cimicifuga racemosa , molecules and extracts of biological and biotechnological Emblica officinalis , Glycyrrhiza glabra, Glycyrrhiza ural origin , vaccines , synthetic or partially synthetic hydrophilic ensis , Ilex purpurea , Ligusticum lucidum , Ligusticum wal molecules and /or mixtures thereof. lichii , Mitracarpus scaber, Morinda citrifolia , Morus alba , [ 0162] Exemplary proteins , hydrolyzed protein , enzymes Morus bombycis , Naringi crenulata , Prunus domestica , and hormones, as well as the commercial mixtures which Radix pseudostellaria , Rumex crispus, Rumex occidentalis, contain them , include Elhibin® [ INCI: glycine soja ( soy Sapindus mukorossi, Saxifraga sarmentosa , Scutellaria Gal bean ) protein ) , Preregen® [INCI : glycine soja ( soybean ) ericulata , Sedum sarmentosum Bunge, Stellaria medica , protein , oxidoreductases ] and Regu® -Age [INCI : hydro Triticum Vulgare , Uva ursi , Withania somnifera , Aristolo lyzed rice bran protein , glycine soja ( soybean ) protein , chia clematis , Rosa moschata , Echinacea angustifolia , Sym oxidoreductases ] marketed by Pentapharm / DSM , cadherins , phytum officinale , Equisetum arvense , Hypericum perfora integrins, selectins , hyaluronic acid receptors , immuno turn , Mimosa tenuiflora , Persea gratissima, Prunus globulins, fibroblast growth factor, connective tissue growth africana , Tormentilla erecta , Solanum tuberosum , Rosmari factor, platelet- derived growth factor, vascular endothelial nus officinalis , Vaccinium angustifolium , Macrocystis pyrif growth factor, epidermal growth factor, insulin - like growth era algae , Padina pavonica , Malpighia puniciftolia , Cynara factor, keratinocyte growth factors , colony - stimulating scolymus, Gossypium herbaceum , Panicum miliaceum , growth factors, transforming growth factor- beta , tumor Morus nigra , Sesamum indicum , Glycine soja , Triticum necrosis factor -alpha , interferons, interleukins, matrix met vulgare, Glycine Max ( soy ) , malt , flax , red clover, kakkon alloproteinases , receptor protein tyrosine phosphatases , to , white lupine , hazelnut , maize , beech tree shoots , Trifo hydrolyzed vegetable proteins such as hydrolyzed wheat lium pratense ( red clover ) , Phormium tenax (New Zealand protein , hydrolyzed soy protein or hydrolyzed whey protein , flax ), Cinnamomum verum , Laminaria saccharina , Spiraea hydrolyzed vegetable protein , Collalift® [ INCI: hydrolyzed ulmaria , Nettle Root, Pygeum africanum , Avena sativa , malt extract] marketed by Coletica / Engelhard , Colhibin Arnica montana , Cinchona succirubra , Eugenia caryophyl PF® [ INCI: hydrolyzed rice protein ) marketed by Pentap lata , Humulus lupulus , Hypericum perforatum , Mentha pip harm , Cytokinol® LS CINCI: hydrolyzed casein , hydrolyzed erita , Rosmarinus officinalis , Thymus vulgaris , plant extract yeast protein , lysine HCL ] marketed by Laboratoires Sero of the genus Silybum , extract of legume seeds , extracts of red biologiques/ Cognis , Liftline® [INCI : hydrolyzed wheat pro algae from the genus Porphyra , Phytovity1 C® [ INCI: water, tein ] and Ridulisse C® [hydrolyzed soy protein ] marketed Zea Mays extract ] marketed by Solabia , MicromerolTM by Silab , catalase , superoxide dismutase , lactoperoxidase , INCI: Pyrus Malus extract ] and heather extract [ INCI: glutathione peroxidase , lactoprotein , casein , lactoperoxi Calluna vulgaris extract] marketed by Coletica /Engelhard / dase , lysozyme, glycosidases, stratum corneum chymotryp BASF , Proteasyl® TP LS8657 [ INCI: Pisum sativum tic enzyme (SCCE ) ; proteases such as trypsin , chy extract] marketed by Laboratoires Serobiologiques/ Cognis , motrypsin , sutilain , papain and bromelain ; DNA repair RadicaptolTM [INCI : propylene glycol, water, Passiflora enzymes such as photolyase or T4 endonuclease V , lipase , incarnata Flower extract , Ribes nigrum (blackcurrant ) leaf luteinizing hormone (LH ) , follicle -stimulating hormone extract , Vitis vinifera ( grape ) leaf extract ] marketed by ( FSH ) , growth hormone, insulin , and mixtures thereof. Solabia and ViaPureTM Boswellia [ INCI: olibanum (Bo [0163 ] Exemplary extracts of biological or biotechnologi swellia serrata ) extract ] marketed by Soliance, EquiStatTM cal origin , which can be chemically modified , as well as the [ INCI Pyrus malus fruit extract, glycine soja seed extract ] commercial mixtures which contain them , include vegetable marketed by Coletica /Engelhard , LitchidermTM TINCI: extracts , marine extracts , cell extracts and extracts produced Litchi chinensis pericarp extract) and ArganylTM [ INCI: by microorganisms. Argania spinosa leaf extract] marketed by Laboratories US 2017 /0319462 A1 Nov. 9 , 2017

Serobiologiques/ Cognis , DakalineTM [INCI : Prunus amygd repair agents and / or DNA protecting agents , for example alus dulcis, Anogeissus leiocarpus bark extract ]marketed by extracts of Centella asiatica , Saccharomyces cerevisiae , Soliance , Actimp 1 . 9 . 3® [INCI : hydrolyzed lupine protein ] Solanum tuberosum , Rosmarinus officinalis , Vaccinium marketed by Expanscience® Laboratoires, Pronalen® Firm angustifolium , extract of the algae Macrocystis pyrifera , ing HSC [INCI : Triticum vulgare , Silybum marianum , gly Padina pavonica , extract of the plants soy, malt, flax , sage , cine soy , Equisetum arvense , Alchemilla vulgaris , Medicago red clover , kakkon - to , white lupine , hazelnut extract, corn sativa , Raphanus sativus] and Polyplant® Firming [ INCI: extract, yeast extract, extract of beech tree shoots , extract of coneflower , Centella asiatica , fucus , fenugreek ] marketed leguminosae seeds , extract of plant hormones such as gib by Provital, Lanablue® [ INCI: sorbitol, algae extract ] mar berellins, auxins or cytokinins among others , or extract of keted by Atrium Innovations, Firmiderm® LS 9120 [ INCI: zooplankton Salina , the product of milk fermentation with Terminalia catappa leaf extract, Sambucus nigra flower Lactobacillus Bulgaricus, asiaticosides and derivatives extract, PVP , tannic acid ] marketed by Laboratoires Sero thereof, vitamin C and derivatives thereof, cinnamic acid biologiques / Cognis , among others . and derivatives thereof, Matrixyl® [ INCI: palmitoyl penta 10165 ] The amount of hydrophilic active ingredient con peptide - 3 ] ,Matrixyl® 3000 [ INCI: palmitoyl tetrapeptide - 3 , tained in the face mask or body patch may be from 0 . 00001 palmitoyl oligopeptide ] or Biopeptide CLTM [ INCI: glyceryl to 50 wt. % of the total weight of the mask ( on an unhydrated polymethacrylate , propylene glycol, palmitoyl oligopeptide ] basis ) , such as at least 0 . 0001 wt. % , or at least 0 . 001 wt. % , marketed by Sederma, Antarcticine® [ INCI: Pseudoaltero or at least 0 .01 wt. % , and may be up to 40 wt. % , or up to monas ferment extract ], Decorinyl® [ INCI: tripeptide- 10 30 wt. % , or up to 10 wt. % . citrulline ], Serilesine® [ INCI: hexapeptide - 10 ], Lipeptide [0166 ] Agents Inhibiting Elastin Degradation [ INCI: hydrolyzed vegetable protein ) , Aldenine® [ INCI: [0167 ] Exemplary agents inhibiting elastin degradation hydrolyzed wheat protein , hydrolyzed soy protein , tripep include Elhibin® [ INCI: glycine soja (Soybean ) protein ) , tide - 1 ] , Peptide AC29TM [ INCI: acetyl tripeptide -30 citrul Preregen® [ INCI: glycine soja ( soybean ) protein , oxi line ] , acetyl- arginyl - phenylglycyl - tryptophyl- phenylgly doreductases ) or Regu® - Age [ INCI: hydrolyzed rice bran cine , acetyl- arginyl - phenylglycyl - valyl- glycine , or acetyl protein , glycine soja (Soybean ) protein , oxidoreductases ] arginyl- phenylglycyl - valyl- phenylglycine , marketed by marketed by Pentapharm /DSM , Juvenesce [ INCI: ethoxy Lipotec , Drieline® PF [ INCI: yeast betaglucan ]marketed by diglicol and caprylic triglyceride , retinol, ursolic acid , phy Alban Muller, Phytovityl Co [INCI : water, Zea Mays tonadione , ilomastat] , MicromerolTM [ INCI: Pyrus Malus extract ] marketed by Solabia , Collalift® [ INCI: hydrolyzed extract) , heather extract [INCI : Calluna vulgaris extract) , malt extract] marketed by Coletica /Engelhard , Phytoco Extracellium® [ INCI: hydrolyzed potato protein ] or Fla hesine® PSP [proposed INCI: sodium beta - sitosteryl sul vagrumTM PEG [ INCI: PEG - 6 isostearate, hesperetin lau fate ) marketed by Seporga , minerals such as calcium among rate ) marketed by Coletica/ Engelhard /BASF , Proteasyl® TP others , retinoids and derivatives thereof, isoflavonoids, caro LS 8657 [ INCI: Pisum sativum extract] marketed by Labo tenoids , in particular lycopene , pseudodipeptides , retinoids ratoires Sérobiologiques/ Cognis , RelistaseTM [ INCI: acety and derivatives thereof such as retinol and retinyl palmitate , larginyltriptophyl diphenylglycine ) marketed by Lipotec , heparinoids , and mixtures thereof. SepiliftTM DPHP [INCI : dipalmitoyl hydroxyproline ) mar [0169 ] Matrix Metalloproteinase - Inhibiting Agents keted by Seppic , Vitaderm® [INCI : alcohol , water , glycerin , [0170 ] Exemplary matrix metalloproteinase - inhibiting hydrolyzed rice protein , Ilex aquifolium extract, sodium agents include ursolic acid , isoflavones such as genistein , ursolate , sodium oleanolate ) marketed by Rahn , Gatuline® quercetin , carotenoids , lycopene , soy extract, cranberry Age Defense 2 [INCI : Juglans regia (walnut ) seed extract ] extract , rosemary extract, Trifolium pratense (red clover ) marketed by Gattefossé , IP 2000 [ INCI: dextran , trifluoro extract , Phormium tenax (New Zealand flax ) extract, kak acetyl tripeptide - 2 ] marketed by IEB and Atrium , Radicap kon - to extract, sage extract , retinol and derivatives thereof, tolTM [ INCI: propylene glycol, water , Passiflora incarnata retinoic acid and derivatives thereof, sapogenins such as flower extract, Ribes nigrum (blackcurrant ) leaf extract , Vitis diosgenin , hecogenin , smilagenin , sarsapogenin , tigogenin , vinifera ( grape ) leaf extract] marketed by Solabia or yamogenin and yuccagenin , Collalift® [ INCI: hydrolyzed ViaPureTM Boswellia [INCI : olibanum ( Boswellia serrata ) malt extract] , Juvenesce [ INCI: ethoxydiglicol and caprylic extract] marketed by Soliance , and mixtures thereof. triglyceride, retinol, ursolic acid , phytonadione , ilomastat] and EquiStatTM INCI Pyrus malus fruit extract, glycine soja Agents Stimulating Dermal or Epidermal Macromolecular seed extract] marketed by Coletica / Engelhard , Pepha® Synthesis TIMP [INCI : human oligopeptide- 20 ], Regu®Age [ INCI: [ 0168 ] Exemplary agents stimulating dermal or epidermal hydrolyzed rice bran protein , glycine soja protein , oxi macromolecular synthesis include agents stimulating colla doreductases ) and ColhibinTM [ INCI: hydrolyzed rice pro gen synthesis , agents stimulating elastin synthesis , agents tein )marketed by Pentapharm , Lipeptide [ INCI: hydrolyzed stimulating decorin synthesis , agents stimulating laminin vegetable protein ), Peptide AC29 [ INCI: acetyl tripeptide - 30 synthesis, agents stimulating chaperone synthesis , agents citrulline ], and acetyl- arginyl- asparaginyl - histidyl - citrul stimulating sirtuin synthesis , agents stimulating hyaluronic line - amide marketed by Lipotec , LitchidermTM [ INCI: Litchi acid synthesis , agents stimulating aquaporin synthesis , chinensis pericarp extract ] and ArganylTM [ INCI: Argania agents stimulating fibronectin synthesis , agents inhibiting spinosa leaf extract ] marketed by Laboratories Serobi collagen degradation , agents inhibiting elastin degradation , ologiques / Cognis , MDI Complex® [ INCI: glycosaminogly agents inhibiting serine proteases such as leukocyte elastase cans ] and ECM -Protect® [ INCI: water , dextran , tripeptide or cathepsin G , agents stimulating fibroblast proliferation , 2 ] marketed by Atrium Innovations, DakalineTM [ INCI: agents stimulating adipocyte proliferation , agents stimulat Prunus amygdalus dulcis , Anogeissus leiocarpus bark ing adipocyte differentiation , agents stimulating angiogen extract ] marketed by Soliance , HomeostatineTM [ INCI: esis, agents stimulating glycosaminoglycan synthesis , DNA Enteromorpha compressa , Caesalpinia spinosa ] marketed US 2017 /0319462 A1 Nov. 9 , 2017 17 by Provital, TIMP- PeptideTM ( proposed INCI: acetyl hexa [ 0172 ] Anti -Glycation Agents peptide ) and ECM ModulineTM [proposed INCI: palmitoyl (0173 ] Exemplary anti - glycation agents include Vac tripeptide ) marketed by Infinitec Activos, IP2000 [INCI : cinium angustifolium extracts , ergothioneine and derivatives dextran , trifluoroacetyl tripeptide - 2 ] marketed by Institut thereof, lysine, Aldenine® [ INCI: hydrolyzed wheat protein , Européen de Biologie Cellulaire , Actimp 1. 9 .3® [INC ! : hydrolyzed soy protein , tripeptide - 1 ], VilasteneTM [INCI : hydrolyzed lupine protein ) marketed by Expanscience Labo lysine HCI, lecithin , tripeptide - 10 citrulline ] , dGlyageTM ratories , Vitaderm® [ INCI: alcohol, water , glycerin , hydro [INCI : lysine HC1, lecithin , tripeptide - 9 citrulline ] and Eye lyzed rice protein , ilex aquifolium extract, sodium ursolate , seryl® [ INCI: acetyl tetrapeptide - 5 ] marketed by Lipotec , sodium oleanolate ) marketed by Rahn , adapalene , tetracy hydroxystilbenes and derivatives thereof, resveratrol, 3 ,3 ', 5 , clines and derivatives thereof such as minocycline , rolitet 5 '- tetrahydroxystilbene, and mixtures thereof. racycline , chlortetracycline, metacycline , oxytetracycline , 10174 ] 5a -Reductase Inhibiting Agents doxycycline , demeclocycline and their salts , Batimastat [0175 ] Exemplary 5a -reductase inhibiting agents include [ BB94 ; [4 - (N -hydroxyamino )- 2R - isobutyl -3S -( thiophene extracts of Cinnamomum verum , Laminaria saccharina , 2 - ylthiomethyl) succinyl ] - L - phenylalanine - N -methylam Spiraea ulmaria , Nettle Root, Pygeum africanum , Avena ide ), MarimastatTM [BB2516 ; [2S -[ N4 (R * ), 2R * ,3S ] ]- N4 [ 2 , Sativa , Serenoa repens, extracts of the plants Arnica mon 2 -dimethyl - 1 - [methylaminocarbonyl ] propyl ]- N1, 2 tana , Cinchona succirubra , Eugenia caryophyllata , Humu dihydroxy - 3 - ( 2 -methylpropyl )butanediamide ), and mixtures lus lupulus, Hypericum perforatum , Mentha piperita , Ros thereof. marinus officinalis, Salvia officinalis, and Thymus vulgaris , extract of plants of the genus Silybum , extracts of plants Firming , Redensifying, and Restructuring Agents which contain sapogenins and in particular extract of plants [0171 ] Exemplary firming and /or redensifying and / or of the genus Dioscorea , phytosterols , retinoids and in par restructuring agents include extracts of Malpighia punicif ticular retinol, sulfur and derivatives thereof, zinc salts and tolia , Cynara scolymus, Gossypium herbaceum , Aloe Bar in particular zinc lactate , zinc gluconate , zinc pidolate , zinc badensis , Panicum miliaceum , Morus nigra , Sesamum indi carboxylate , zinc salicylate and zinc cysteate, selenium cum , Glycine soja , Triticum vulgare , Pronalen® Firming chloride , vitamin B6 , pyridoxine , capryloyl glycine , sar HSC [ INCI: Triticum vulgare , Silybum marianum , glycine cosine , finasteride , dutasteride , izonsteride , turosteride and soy, Equisetum arvense , Alchemilla vulgaris , Medicago their salts , and mixtures thereof. sativa , Raphanus sativus ) and Polyplant® Firming [INCI : [0176 ] Lysyl - and / or Prolyl- Hydroxylase - Inhibiting Coneflower, Centella Asiatica , Fucus, Fenugreek ] marketed Agents by Provital, Lanablue® [ INCI: sorbitol, algae extract] mar [0177 ] Exemplary lysyl- and /or prolyl- hydroxylase - inhib keted by Atrium Innovations , Pepha® - Nutrix [ INCI: natural iting agents include 2 , 4 - diaminopyrimidine 3 -oxide , 2 , 4 nutrition factor ]marketed by Pentapharm , vegetable extracts diamino - 6 -piperidinopyrimidine 3 - oxide, and mixtures which contain isoflavones , Biopeptide ELTM [ INCI: palmi thereof. toyl oligopeptide ), Biopeptide CLTM [ INCI: palmitoyl oli gopeptide ], Vexel® [ INCI: water, propylene glycol, lecithin , Defensin Synthesis -Stimulating Agents caffeine, palmitoyl carnitine ] , Matrixyl® [ INCI: palmitoyl [0178 ] Exemplary defensin synthesis - stimulating agents pentapeptide -3 ], Matrixyl® 3000 [INCI : palmitoyl tetrapep include extracts of or hydrolyzed Aloe Vera , Roast ama tide - 3 , palmitoyl oligopeptide ] and Bio - Busty ]TM [INCI : ranth , Rehmanniae radix , arnica , gardenia , carrot , orange , glyceryl polymethacrylate , Rahnella soy protein ferment, peach , pineapple , mint, gentian , hibiscus flower, walnut tree water, propylene glycol, glycerin , PEG -8 , palmitoyl oligo leaf, calabaza , peony , quinoa , boldo , rough bindweed , sun peptide ] marketed by Sederma, Dermosaccharides® HC flower, elderberry, seaweed , hydrolyzed corn , hydrolyzed [ INCI: glycerin , water , glycosaminoglycans, glycogen ) , soy, hydrolyzed rice , valine and its isomers and derivatives , Aglycal® [ INCI: mannitol, cyclodextrin , glycogen , Arcto calcium and its salts , a -MSH and fragments contained in the staphylos uva ursi leaf extract ] , Cytokinol® LS [INCI : amino acid sequence of a -MSH , vitamin A and its deriva hydrolyzed casein , hydrolyzed yeast protein , lysine HCl ] tives and precursors , vitamin D3 and its derivatives, jas and Firmiderm® LS 9120 [ INCI: Terminalia catappa leaf monic acid , fumaric acid , malic acid , citric acid , ascorbic extract, Sambucus Nigra Flower extract , PVP, tannic acid ] acid , lactic acid , acetic acid , adipic acid , tartaric acid , marketed by Laboratoires Serobiologiques/ Cognis , Lift cinnamic acid , glutamic acid , succinic acid , inulin , alkyl liner [ INCI: hydrolyzed wheat protein ) , Raffermine glucosides, poly -D - glutamic acid , glycine , L -methionine , [ INCI: hydrolyzed soy flour ] and Ridulisse C® [hydrolyzed L - alanine, L - citrulline , lactoprotein , casein , lactoperoxidase , soy protein ] marketed by Silab , Serilesine® [ INCI: hexa lysozyme, polyphenol , alkyl glucosides , Lactobacillus peptide - 10 ] , DecorinyiTM [ INCI: tripeptide - 10 citrulline ] , extract, fusobacteria extracts , non -photosynthetic and non Trylagen® [ INCI: Pseudoalteromonas ferment extract , fruiting filamentous bacteria , BodyfensineTM [ INCI: acetyl hydrolyzed wheat protein , hydrolyzed soy protein , tripep dipeptide - 3 aminohexanoate ) marketed by Lipotec , and mix tide - 10 citrulline , tripeptide - 1 ] , marketed by Lipotec , Ursoli some® [INCI : lecithin , ursolic acid , atelocollagen , xanthan tures thereof. gum , sodium chondroitin sulfate ) and Collalift® [ INCI: Antiseptic Agents and Disinfectants hydrolyzed malt extract] marketed by Coletica /Engelhard , Syn® - Coll [ INCI: palmitoyl tripeptide - 5 ] marketed by Pen [0179 ] Exemplary antiseptic agents and disinfectants tapharm , Hydriame® [ INCI: water , glycosaminoglycans, include those serving as bactericidal, bacteriostatic , antimi sclerotium gum ) marketed by Atrium Innovations , IP2000 crobial, germicidal, fungicidal, fungistatic and /or germ [ INCI: dextran , trifluoroacetyl tripeptide - 2 ] marketed by inhibiting agents . Institut Europeen de Biologie Cellulaire , and mixtures [0180 ] Examples of such agents include , macrolides , pyra thereof. nosides , calcium channel blockers , for example cinnarizine US 2017 /0319462 A1 Nov. 9 , 2017 and diltiazem ; hormones, for example estril and analogues Chamomilla recutita , Echinacea purpurea, Hyssopus offici thereof, thyroxine and / or its salts , caprylyl glycol, imidazo nalis , Melaleuca alternifolia or tea tree oil, carnation lidinyl urea , sodium 4 -oxybenzoate methyl, methyl 4 -hy essence , menthol and mint essence , light sensitive dye No. droxybenzoate [ INCI: methylparaben ), ethyl 4 - oxybenzo 101 , light sensitive dye No . 201 and light sensitive dye No . ate , ethyl 4 - hydroxybenzoate [ INCI: ethylparaben ], propyl 401 , and mixtures thereof. 4 -oxybenzoate , isopropyl 4oxybenzoate , propyl 4hydroxy benzoate [INCI : propylparaben ], butyl 4oxybenzoate , butyl NO -Synthase - Inhibiting Agents 4hydroxybenzoate [ INCI: butylparaben ) , isobutyl [0181 ] Exemplary NO - synthase - inhibiting agents include 4hydroxybenzoate [INCI : isobutylparaben ], 1, 3bis (hy extracts of the plants Vitis vinifera , Olea europaea , Gingko droxymethyl) - 5 ,5dimethylimidazolidine - 2 ,4dione [INCI : biloba , and mixtures thereof. DMDM hydantoin ) , benzyl 4oxybenzoate , benzyl 4hydroxybenzoate [ INCI: benzylparaben ) , benzyl alcohol, Desquamating Agents and Keratolytic Agents dehydroacetic acid , benzoic acid , sodium benzoate , potas sium sorbate , dehydroacetic acid , sodium dehydroacetate [0182 ] Exemplary desquamating agents and / or keratolytic sorbic acid , salicylic acid , formic acid , propionic acid , agents and / or exfoliating agents include hydroxy acids and 2 -bromo - 2 - nitropropane - 1 , 3 - diol, 3 - p -chlorophenoxy - 1 , 2 derivatives thereof, B - hydroxyacids, in particular salicylic propanediol [INCI : chlorphenesin ) , dichlorobenzyl alcohol, acid and derivatives thereof, and gentisic acid ; a -hydroxy iodopropynyl butylcarbamate , benzalkonium chloride , odor acids and its salts , such as glycolic acid , ammonium glyco absorbing fungicides such as zinc ricinoleate , cyclodextrins, late , lactic acid , 2 - hydroxyoctanoic acid , a - hydroxycaprylic benzethonium chloride , chlorhexidine , ethanol, propanol, acid , mandelic acid , citric acid , malic acid and tartaric acid ; 1 , 3 -butanediol , 1 , 2 - propylene glycol, undecylenic acid , a - and B -hydroxybutyric acids ; polyhydroxy acids such as dehydroacetic acid , N -methylmorpholine acetonitrile gluconic acid , glucuronic acid and saccharic acid ; keto acids (MMA ) , isopropanol, methanol, 1 , 2 -hexanediol , 1 , 2 -octane such as pyruvic acid , and glyoxylic acid ; pyrrolidinecarbox diol, pentylene glycol, glycerin laurate , glycerin caprylate , ylic acid ; cysteic acid and derivatives thereof; aldobionic glyceryl caprate , benzoyl peroxide , chlorhexidine gluconate , acids ; azelaic acid and derivatives thereof such as azeloyl triclosan and derivatives thereof, phenoxyethanol, terpinen diglycinate ; ascorbic acid and derivatives thereof such as 4 - ol, a - terpineol, resorcinol, stiemycin , erythromycin , neo 6 -Opalmitoylascorbic acid , ascorbyl glucoside , dipalmitoyl mycin , clindamycin and its esters , tetracyclines , metronida ascorbic acid , magnesium salt of ascorbic acid - 2phosphate zole , azelaic acid , tolnaftate , nystatin , clotrimazole , (MAP ) , sodium salt of ascorbic acid - 2phosphate (NAP ) , ketoconazole , derivatives of zinc such as zinc pyrithionate or ascorbyl tetraisopalmitate (VCIP ) ; nicotinic acid , its esters trithionate , zinc oxide and zinc undecylenate , piroctone and nicotinamide (also called vitamin B3 or vitamin PP ) ; olamine, isothiazolinones, selenium sulfur , benzyl hemifor nordihydroguaiaretic acid ; urea ; oligofucoses ; cinnamic mal, boric acid , sodium borate , 6 , 6 - dibromo - 4 , 4 - dichloro acid ; derivatives of jasmonic acid ; hydroxy stilbenes such as 2 , 2 ' -methylenediphenol [ INCI: bromochlorophene ], resveratrol; Saccharum officinarum extract; enzymes 5bromo- 5 -nitro - 1 ,3 - dioxane , tosylchloramide sodium involved in desquamation or degradation of the corneodes INCI: chloramine T ] , chloroacetamide , pchloromcresol, mosomes , such as glycosidases, stratum corneum chy 2benzyl- 4 -chlorophenol [INCI : chlorophene ), dimethyl motryptic enzyme (SCCE ) and other proteases such as oxazolidine , dodecyl dimethyl- 2 - phenoxyethyl ammonium trypsin , chymotrypsin , sutilain , papain and bromelain ; bromide [ INCI: domiphen bromide ) , Tethyl bicyclooxazo chelating agents such as ethylenediaminetetraacetic acid lidine, hexetidine , glutaraldehyde , N -( 4 - chlorophenyl) - N (EDTA ) and salts thereof, aminosulfonic compounds such as [4chloro - 3 ( trifluoromethyl) phenyl] urea [ INCI: cloflucar 4 - ( 2 - hydroxyethyl) piperazine - 1 - ethanesulfonic acid ban ] , 2 -hydroxy - 4isopropyl- 2 , 4 ,6cycloheptatriene - lone (HEPES ) and sodium methyiglycine diacetate ( TRILON® [ INCI: Hinokitiol] , isopropylmethylphenol, mercury salts , M marketed by BASF ); derivatives of 2 -oxothiazolidine aluminum salts , nisin , phenoxyisopropanol, o phenylphenol , 4carboxylic acid (procysteine ) ; derivatives of sugars such as 3 -heptyl -2 - [( 3 -heptyl - 4 -methyl - 3H -thiazole - 2 -ylidene ) O -octanoyl - 6 - D -maltose and N - acetylglucosamine; chestnut methyl) - 4 -methylthiazole iodide [ INCI: Quaternium - 73 ], extract (Castanea sativa ) such as that marketed by SILAB silver chloride , sodium iodide , thymol, undecylenic acid , under the name Recoverine® [ INCI: water, Castanea sativa diethylenetriaminepentaacetic acid , ethylenediaminetet seed extract ] ; opuntia extract (Opuntia ficus - indica ) such as raacetic acid and ethylenediaminetetraacetates, lactoperoxi that marketed by SILAB as Exfolactive® [ INCI: hydrolyzed dase , glucose oxidase , lactoferrin , alkylaryl sulfonates , halo Opuntia ficus Indica flower extract] ; Phytosphingosine genated phenols , phenol mercury acetate and /or mixtures SLC® [ INCI: salicyloyl phytosphingosine ) marketed by thereof, benzamidines, isothiazolines , derivatives of phthal Degussa / Evonik , Peel- MoistTM [INCI : glycerin , papain , cal imide , derivatives ofpyridine , guanidines, quinolines, 1 ,2di cium pantothenate , Xanthan gum , caprylyl glycol, urea , bromo - 2 ,4dicyanobutane , iodine - 2 - propylbutyl carbamate , magnesium lactate , ethylhexylglycerin , potassium lactate , iodine , tamed iodines , peroxo compounds , 4chloro - 3 , 5 - di serine, alanine , proline , magnesium chloride , sodium cit methylphenol, 2 , 2 -methylene - bis ( 6 - bromo - 4 -chlorophe rate ) ; extract or combination of extracts of Sophora nol) , 3methyl- 4 ( 1 -methylethyl )phenol , 3 - ( 4 - chlorophe japonica , papaya , pineapple , pumpkin or sweet potato , and noxy ) - 1 , 2 - propanediol , 3 , 4 , 4 '- trichlorocarbanilide ( TTC ) , mixtures thereof. betalactams, thiamine essence , eugenol, farnesol, glycerol [0183 ] Melanin Stimulating , Propigmenting, Self - Tanning monolaurate , diglycerin monocaprinate , N -alkyl salicylic and / or Melanocyte Proliferation Stimulating Agents acid amides such as n - octyl salicylic acid amide or n - decyl [0184 ] Example agents which stimulate the synthesis of salicylic acid amide, derivatives of halogenated xylene and melanin , the propigmenting agent, the self - tanning agent cresol, such as p -chloro -meta - cresol or p - chloro -meta - xy - and / or the melanocyte proliferation stimulating agent lene, extracts of Allium sativum , Calendula officinalis , include extracts of Citrus Aurantium Dulcis Fruit, Coleus US 2017 /0319462 A1 Nov. 9 , 2017 forskohlii, Coleus esquirolii, Coleus scutellarioides, Coleus [0187 ] Heat Shock Protein Synthesis Stimulating Agents xanthanthus, Ballota nigra , Ballota lanata , Ballota suaveo [0188 ] Exemplary heat shock protein synthesis stimulat lens, Marrubium cylleneum , Cistus creticus , Amphiachyris ing agents include extracts of Opuntia ficus indica , Salix amoena , Aster oharai, Otostegia fruticosa , Plectranthus alba , Lupinus spp ., Secale cereale , extracts of red algae from barbatus, Halimium viscosum and Larix laricina , dihydroxy the genus Porphyra , extracts of crustaceans from the genus acetone and derivatives thereof , sugars , for example eryth Artemia , jojoba seed oil, grape seed extracts , green tea rulose , melanin and derivatives thereof including melanin extracts , geranylgeranylacetone , celastrol, zinc and its salts , polymers and derivatives of melanin with a low molecular 2 - cyclopenten - 1 - one, proteasome inhibitors , for example weight which are soluble in water , forskolin and derivatives bortezomib ; prostaglandins and derivatives thereof, hydrox thereof including deacetylforskolin and isoforskolin , tyro ylamine and derivatives thereof, for example bimoclomol; sine and derivatives thereof including acetyl tyrosine , oleoyl chalcone and derivatives thereof, hyperosmotic agents , for tyrosine , 3 - amino tyrosine and 3 - nitrotyrosine , copper salts example sorbitol and derivatives thereof, mannitol and such as CuCl2 , carotenoids , canthaxanthins , polymers of derivatives thereof or glycerol and derivatives thereof, dihydroxyindole carboxylic acid , 3 ,4 -dihydroxybenzoic isosorbide ( dianhydro - D - glucitol) urea or salicylic acid and acid , 3 -amino -4 -hydroxybenzoic acid , aloin , emodin , aliza derivatives thereof among others , ThermostressineTM TINCI : rin , dihydroxyphenylalanine , 4 , 5 - dihydroxynaphthalene - 2 acetyl tetrapeptide - 22 ] , and mixtures thereof. sulfonic acid , 3 - dimethylaminophenol and p - aminobenzoic [0189 ] Agents Inhibiting Sweat - Degrading Enzymes acid , MelatimeTM INCI: acetyl tripeptide - 40 ] marketed by [0190 ] Exemplary agents for inhibiting sweat- degrading Lipotec , Heliostatine ISRTM [ INCI: water , glycerin , Pisum enzymes include trialkyl citrates such as trimethyl citrate , sativum extract ] marketed by Vincience / ISP , Vegetan® tripropyl citrate , triisopropyl citrate , tributyl citrate or tri [ INCI: dihydroxyacetone ] or Vegetan® Premium [ INCI: ethyl citrate ; lanosterine sulfate and lanosterine phosphate , dihydroxyacetone , melanin ) marketed by Soliance , Melano cholesterol, campesterol, stigmasterol and sitosterol; dicar BronzeTM [ INCI: Vitex agnus - castus extract , acetyl tyrosine ] boxylic acids and their esters , such as glutaric acid , mono marketed by Mibelle Biochemistry , Melitane® [ INCI: acetyl ethyl glutarate , diethyl glutarate, adipic acid , monoethyl hexapeptide - 1 ] marketed by Institut Européen de Biologie adipate , diethyl adipate ; malonic acid and diethylmalonate , Cellulaire /Unipex Innovations, Actibronze® [ INCI: hydro hydroxycarboxylic acids and their esters such as malic acid , lyzed wheat protein , acetyl tyrosine , copper gluconate ) and tartaric acid and diethyl tartrate , zinc glycinate, and mixtures Instabronze? [ INCI: dihydroxyacetone , tyrosine) marketed thereof. by Alban Muller , ThalitanTM [ INCI: hydrolyzed algin , mag [0191 ] Agents Stimulating or Regulating Keratinocyte nesium sulfate , manganese sulfate ) marketed by CODIF , Differentiation Tyrosilane® [ INCI: methylsilanol acetyl tyrosine ) marketed [0192 ] Exemplary agents for stimulating or regulating by Exsymol, TyrExcelTM [ INCI: oleoyl tyrosine , Luffa Cylin keratinocyte differentiation include minerals such as cal drica seed oil , oleic acid ] or Tyr- OITM [ INCI: oleoyl tyro cium , retinoids such as retinol and tretinoin , analogues of sine , butylene glycol, oleic acid ] marketed by Sedermal vitamin D3 such as calcitriol, calcipotriol and tacalcitol, Croda , Bronzing S . F . (proposed INCI: butyryl lupine (Lupinus albus ) extract such as that marketed by pentapeptide ] marketed by Infinitec Activos or Biotanning® SILAB under the name Structurin® [ INCI: hydrolyzed [ INCI: hydrolyzed Citrus aurantium dulcis fruit extract] lupine protein ), B - sitosterol sulfate , such as that marketed by marketed by Silab , and mixtures thereof. Vincience/ ISP under the name Phytocohesine PSP® [ INCI: [0185 ] Lipolytic Agents , Agents Stimulating Lipolysis , sodium beta - sitosterol sulfate ), maize (Zea Mays) extract Venotonic Agents and Anti - Cellulite Agents such as that marketed by Solabia under the name Phytovityl [0186 ] Exemplary lipolytic agents, agents stimulating C® [ INCI: water , Zea Mays extract ] , Helix aspersa Müller lipolysis , venotonic agents and / or anticellulite agents glycoconjugates, and mixtures thereof . include extracts of Bupleurum chinensis , Cecropia obtusi [0193 ] Exopolysaccharides folia , Celosia cristata , Centella asiatica , Chenopodium qui [0194 ] Exemplary exopolysaccharides, such as those of noa , Chrysanthellum indicum , Citrus aurantium amara , bacterial origin , include those secreted by a strain of the Coffea arabica , Coleus forskohlii , Commiphora myrrha , Halomonas anticariensis species , which reduce lipid accu Crithmum maritimum , Eugenia caryophyllus, Ginkgo mulation , as described in WO 2015 /063240 , and an exopo biloba , Hedera helix ( ivy extract ), Hibiscus sabdariffa , Ilex lysaccharide which inhibits neuronal exocytosis and stimu paraguariensis , Laminaria digitata , Nelumbium speciosum , lates the fibroblast proliferation which is excreted by the Pauffinia cupana , Peumus boldus, Phyllacantha fibrosa , strain of the Vibrio sp . species with deposit number CNCM Prunella vulgaris , Prunus amygdalus dulcis, Ruscus acu 1 -4239 according to the Budapest Treaty on Sep . 4 , 2009 , in leatus ( Butcher' s broom extract) , Sambucus nigra , Spirulina the “ Collection Nationale de Culture de Microorganismes ” platensis algae , Uncaria tomentosa and Verbena officinalis , [National Microorganism Culture Collection ] (CNCM ) , Pas dihydromyricetin , coenzyme A , lipase , glaucine, visnadine , teur Institute , 28 rue du Docteur Roux , 75724 Paris, France , Regu®Shape [ INCI: isomerized linoleic acid , lecithin , glyc as described in WO 2014147255 and U . S . Ser. No. 14 /778 , erin , polysorbate 80 ] marketed by Pentapharm / DSM , 874 , filed Sep . 21, 2015 . UCPeptideTM V TINCI: pentapeptide ) and AT PeptideTM IS [0195 ] Exemplary cell extracts and extracts produced by [ INCI: tripeptide - 3 ] marketed by Vincience/ ISP , Liporeduc microorganisms, or commercial mixtures which contain tyl® [ INCI: caffeine , Butcher ' s broom (Ruscus aculeatus ) them include hydrosoluble cell extracts and hydrosoluble root extract , TEA -hydroiodide , carnitine, ivy (Hedera helix ) extracts produced by microorganisms, for example Antarc extract , escin , tripeptide -1 ] marketed by Lipotec , Adi ticine® [INCI : Pseudoalteromonas ferment extract) and poslimTM [INCI : sorbitan laurate , lauroyl praline ) marketed Trylagen® [INCI : Pseudoalteromonas ferment extract , by SEPPIC , caffeine , carnitine , escin , triethanolamine hydrolyzed wheat protein , hydrolyzed soy protein , Tripep iodide , and mixtures thereof. tide - 10 citrulline, Tripeptide - 1 ] marketed by Lipotec , yeast US 2017 /0319462 A1 Nov. 9 , 2017 extract, extract of Saccharomyces cerevisiae and the product tate , isostearyl palmitate , 2 -ethylhexyl stearate , isocetyl of milk fermentation with Lactobacillus Bulgaricus, among stearate , isodecyl Oleate , octyldodecyl Oleate, octyldodecyl others . ricinoleate , ethyl isostearate , isopropyl isostearate , cetyl [0196 ] Excipients 2 - ethylhexanoate , cetostearyl 2 - ethylhexanoate , stearyl [ 0197 ] Excipients which may be present include emulsi 2 -ethylhexanoate , hexyl isostearate , ethylene glycol dioc fiers, organic solvents , surfactants , liquid propellants , bind tanoate , ethylene glycol dioleate , propylene glycol dicapry ers and thickeners , fillers , lubricants , glidants , pigments , late , propylene glycol dicaprylate /dicaprate , lauryl lactate , dyes , perfumes, flavoring agents , preservatives , and combi myristyl lactate , cetyl lactate , trioctyl citrate , diisostearyl nations thereof. malate , 2 -ethylhexyl hydroxystearate , diisopropyl adipate , [ 0198 ] Components serving as lubricants , solvents , pro diisopropyl sebacate , dioctyl sebacate , cholesteryl stearate , pellants , binders and thickeners and emulsifiers may include cholesteryl isostearate , cholesteryl hydroxystearate , choles one or more of liquid hydrocarbons, waxes , natural fats and teryl oleate , dihydrocholesteryl oleate , phytosteryl isostear fatty oils , alcohols , ethers , esters, silicone oils , monosaccha ate , phytosteryl oleate , isocetyl 12stearoyl hydroxystearate , rides, polymers , and the like . stearyl 12stearoyl hydroxystearate , isostearyl 12 - stearoyl [0199 ] Exemplary liquid hydrocarbons include a -olefins , hydroxystearate , octyl isononanoate . C10 _ Can alkanes, C10C40 alkenes, and mixtures thereof, [0206 ] Exemplary silicone oils include polysiloxanes , such as squalene, ceresin , mineral oils , and petroleum jelly . polyether modified silicones , alcohol modified silicones , [ 0200 ] Exemplary waxes include microcrystalline wax , alkyl modified silicones, and amino modified silicones. natural waxes such as jojoba oil, carnauba wax , candelilla [ 0207 ] Exemplary saccharides include mannitol , sorbitol, wax , rice bran wax , shellac , lanolin , mink sebaceous wax , xylitol, maltitol, erythritol, pentaerythritol, glucose , sucrose , spermaceti wax , sugarcane wax , sperm whale oil, beeswax fructose , lactose , maltose, xylose and trehalose . and montan wax . [0208 ] Exemplary polymers include sodium alginate , car [0201 ] Exemplary natural fats and fatty oils include avo rageenan , agar , guar gums, tamarind gum , dextrin , starch , cado oil , almond oil , olive oil , extra virgin olive oil, sesame locust bean gum , gum arabic , pectin , quince , chitosan , seed oil, rice bran oil , rice oil, rice germ oil , corn oil, starch , curdlan , xanthan gum , dextran , pullulan , microcrys safflower oil , soybean oil , maize oil, rape seed oil, persic oil , talline cellulose , methyl cellulose , ethyl cellulose , hydroxy palm kernel oil , palm oil , castor oil, sunflower oil , high oleic ethyl cellulose , hydroxypropyl cellulose , hydroxypropyl sunflower oil, grape seed oil, cottonseed oil, coconut oil , methylcellulose , carboxymethyl cellulose , carboxy starch , hydrogenated coconut oil, beef tallow , hydrogenated oil , cationized cellulose , starch phosphate ester , albumin , casein , horse oil , mink oil , yolk oil , yolk fat oil , rose hip oil , kukui gelatin , sodium polyacrylate , polyacrylamides, carboxyvi nut oil , evening primrose oil, wheat germ oil , peanut oil , nyl polymers , polyethylene imines , polyethylene glycol, Camellia japonica oil , Camellia kissi oil, cacao butter, Japan polyvinyl alcohol, polyvinyl pyrrolidone , polyvinyl ether , wax , beef bone tallow , nest’ s -foot oil , swine tallow , equine polyacrylamides , acrylic acid copolymers, methacrylic acid tallow , ovine tallow , shea butter, macadamia nut oil and copolymers , maleic acid copolymers, vinylpyridine copoly meadow foam seed oil. mers, ethylene /acrylic acid copolymers , vinyl pyrrolidone [ 0202 ] Exemplary fatty acids include lauric acid , myristic based polymers , vinyl alcohol/ vinyl pyrrolidone copoly acid , palmitic acid , stearic acid , behenic acid , oleic acid , mers , N - substituted acrylamide based polymers , amino linoleic acid , linolenic acid , y - linolenic acid , isostearic acid , modified silicones, dimethylacrylic acid based polymers , 12 - hydroxystearic acid , undecenoic acid and coconut oil acrylic acid based anionic polymers , methacrylic acid based fatty acid . anionic polymers, modified silicone , acrylate /methacrylate [0203 ] Exemplary lower alcohols include ethanol, 1 -pro C10 - C30 alkyl copolymers , and polyoxyethylene /polyoxy panol, 2 -propanol , 1 -butanol , 2 - butanol and benzyl alcohol. propylene copolymers . Exemplary higher alcohols include isostearyl alcohol, 2 -oc [0209 ] Exemplary anionic surfactants include potassium tyldodecan - 1 - ol, 2 -hexyldecan - 1 -ol , cholesterol, phytoster coconut oil fatty acid , sodium coconut oil fatty acid , trietha ols , lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl nolamine coconut oil fatty acid , potassium laurate , sodium alcohol, oleyl alcohol, behenyl alcohol and cetostearyl alco laurate , triethanolamine laurate , potassium myristate , hol. Exemplary polyhydric alcohols include ethylene glycol, sodium myristate , isopropanolamine myristate , potassium diethylene glycol, triethylene glycol, polyethylene glycol, palmitate , sodium palmitate , isopropanolamine palmitate , propylene glycol, dipropylene glycol, polypropylene glycol, potassium stearate , sodium stearate , triethanolamine stear pentanediol, glycerin , diglycerin , polyglycerin , isoprene ate , potassium oleate , sodium oleate , castor oil fatty acid glycol, 1 , 3 -butylene glycol, 3 -methyl - 1 , 3 -butanediol , 1 ,3 sodium , zinc undecylate , zinc laurate , zinc myristate , mag butanediol, 1, 2 -pentanediol and 1 ,2 -hexanediol . nesium myristate , zinc palmitate , zinc stearate , calcium [0204 ] Exemplary alkyl glyceryl ethers include stearyl stearate , magnesium stearate , aluminum stearate , calcium monoglyceride , 3 -hexadecoxypropane - 1 , 2 - diol, 3 - [ ( Z ) - octa myristate , magnesium myristate , aluminum dimyristate , alu dec - 9 - enoxy ] propane - 1 , 2 - diol and isostearyl glyceryl ether . minum isostearate , polyoxyethylene lauryl ether acetate , [ 0205 ] Exemplary esters include isopropyl myristate , sodium polyoxyethylene lauryl ether acetate , polyoxyethyl butyl myristate , isopropyl palmitate , ethyl stearate, butyl ene tridecyl ether acetate , sodium polyoxyethylene tridecyl stearate , ethyl oleate , ethyl linoleate , isopropyl linoleate , ether acetate , sodium stearoyl lactate , sodium isostearoyl cetyl caprylate , hexyl laurate , isooctyl myristate , decyl lactate , sodium lauroyl sarcosinate , coconut oil fatty acid myristate , myristyl myristate , cetyl myristate , octadecyl sarcosinate , sodium coconut oil fatty acid sarcosinate , coco myristate , cetyl palmitate , stearyl stearate , decyl oleate , nut oil fatty acid sarcosine triethanolamine , lauroyl sar oleyl oleate , cetyl ricinoleate , isostearyl laurate , isotridecyl cosine , potassium lauroyl sarcosinate , lauroyl sarcosine tri myristate , isocetyl myristate , isostearyl myristate, 2 -octyl ethanolamine, oleoyl Sarcosine , sodium myristoyl dodecyl myristate , 2 - ethylhexyl palmitate , isocetyl palmi sarcosinate , sodium stearoyl glutamate , coconut oil fatty US 2017 /0319462 A1 Nov. 9 , 2017

acid acyl glutamic acid , potassium coconut oil fatty acid acyl ( e . g . , amine oxides ), as well as alkyl amine oxides. Other glutamate , sodium coconut oil fatty acid acyl glutamate , suitable nonionics include mono - or di- alkyl alkanolamides lauroyl glutamic acid , potassium lauroyl glutamate , sodium and alkyl polysaccharides , sorbitan fatty acid esters, poly lauroyl glutamate , myristoyl glutamic acid , potassium oxyethylene sorbitan fatty acid esters , polyoxyethylene sor myristoyl glutamate , sodium myristoyl glutamate , stearoyl bitol esters , polyoxyethylene acids , and polyoxyethylene glutamic acid , potassium stearoyl glutamate , disodium alcohols . Examples of nonionic surfactants include alkyl stearoyl glutamate , sodium hydrogenated beef tallow fatty polyglucoside, cocamidopropyl and lauramine oxide , poly acid acyl glutamate , sodium coconut oil fatty acid /hydroge sorbate 20 , ethoxylated linear alcohols , cetearyl alcohol, nated beef tallow fatty acid acyl glutamate , lauroyl methyl lanolin alcohol, stearic acid , glyceryl stearate , polyoxyeth alanine, sodium lauroyl methyl alanine , sodium myristoyl ylene lauryl ether , polyoxyethylene oleyl ether, PEG - 100 methyl alanine , sodium lauroyl methyl taurate , sodium stearate , sorbitan monooleate , sorbitan isostearate , and oleoyl methyl taurate , sodium alkane sulfonate , sodium oleth - 20 , and mixtures thereof. tetradecene sulfonate , sodium dioctyl sulfosuccinate , diso [0213 ] Exemplary powdered fillers include kaolin , silicic dium lauryl sulfosuccinate , sodium coconut oil fatty acid anhydride, magnesium aluminum silicate , sericite , talc , ethyl ester sulfonate , sodium lauryl sulfate , triethanolamine lauryl sulfate , sodium cetyl sulfate , triethanolamine alkyl boron nitride, mica , montmorillonite, cellulose powder, sulfates, sodium alkyl sulfates , triethanolamine alkyl sul wheat starch , silk powder, maize starch , and mixtures fates , alkyl ammonium sulfates , diethanolamine alkyl sul thereof. fates , triethanolamine alkyl sulfates , triethanolamine alkyl [ 0214 ] Exemplary dyes and pigments include nitro dyes, sulfates , lauryl ammonium sulfate , potassium lauryl sulfate , azo dyes, nitroso dyes , xanthene dyes , quinoline dyes , magnesium lauryl sulfate , monoethanolamine lauryl sulfate , anthraquinone dyes, indigo dyes , sepia powder, caramel , diethanolamine lauryl sulfate , sodium myristyl sulfate , cochineal, carbon black , yellow iron oxide , black iron oxide , sodium stearyl sulfate , sodium oleyl sulfate , triethanolamine red iron oxide , titanium oxide, titanium dioxide , and mix oleyl sulfate , sodium polyoxyethylenes lauryl ether sulfates, tures thereof. triethanolamine polyoxyethylene lauryl ether sulfate , [0215 ] Exemplary pH adjusting agents include sodium sodium polyoxyethylene alkyl ether sulfates , trietha hydroxide, potassium hydroxide , triethanolamine, and mix nolamine polyoxyethylene alkyl ether sulfates , sodium poly oxyethylene myristyl ether sulfates, sodium higher fatty acid tures thereof. alkanolamide sulfate esters, lauryl phosphate , sodium lauryl [ 0216 ] Exemplary salts include sodium chloride , potas phosphate , potassium cetyl phosphate , diethanolamine cetyl sium chloride, magnesium chloride, sodium sulfate , and phosphate , polyoxyethylene oleyl ether phosphate , polyoxy mixtures thereof. ethylene lauryl ether phosphate , sodium polyoxyethylene [0217 ] Exemplary ahydroxy acids include citric acid , gly lauryl ether phosphate , polyoxyethylene cetyl ether phos phate , sodium polyoxyethylene cetyl ether phosphate , poly colic acid , tartaric acid and lactic acid , and mixtures thereof. oxyethylene stearyl ether phosphate , polyoxyethylene oleyl [ 0218 ] Exemplary cosmetic and / or absorbent and / or body ether phosphate, sodium polyoxyethylene oleyl ether phos odor masking deodorant and /or antiperspirant agent, per phate , polyoxyethylene alkylphenyl ether phosphates, fuming substance and /or perfumed oils include the complex sodium polyoxyethylene alkylphenyl ether phosphates , tri zinc salt of ricinoleic acid , Styrax , derivatives of abiotic ethanolamine polyoxyethylene alkylphenyl ether phos acid , sage essence , chamomile essence , carnation essence , phates, polyoxyethylene octyl ether phosphate , polyoxyeth lemon balm essence , mint essence , cinnamon leaf essence , ylene alkyl ether phosphate , triethanolamine lime flower essence , juniper berry essence, vetiver essence , polyoxyethylene lauryl ether phosphate, and diethanolamine olibanum essence , galbanum essence , labdanum essence , lavender essence , peppermint essence , bergamot orange, polyoxyethylene oleyl ether phosphate . dihydromyrcenol, lilial, lyral , citronellol, lemon essence , [0210 ] Exemplary cationic surfactants include alkyl mandarin essence , orange essence , lavender essence , mus amines, alkyl imidazolines, ethoxylated amides, quaternary cat, geranium bourbon essence , aniseed , cilantro , cumin , compounds, quaternized esters , and alkyl amine oxides. juniper , extracts of fleur - de - lis , lilac , roses, jasmine , bitter Examples include lauramine oxide , dicetyldimonium chlo orange blossom ; benzyl acetate , p - tert - butylcyclohexyl ride, and cetrimonium chloride . acetate , linalyl acetate , phenylethyl acetate , ethylmethylphe [ 0211 ] Exemplary amphoteric and zwitterionic surfactants nyl glycinate , linalyl benzoate , benzyl formate , allyl cyclo include betaines , alkyl amidopropyl betaines, alkyl sulfo hexyl propionate , styrallyl propionate , benzyl salicylate , betaines, alkyl glycinates , alkyl carboxyglycinates , alkyl benzyl ethyl ether , linear alkanes with from 8 to 18 carbon amphopropionates, alkyl amidopropyl hydroxysultaines , atoms, citral, ricinoleic acid , citronellal , citronellyl oxyac acyl taurates and acyl glutamates wherein the alkyl and acyl etaldehyde, cyclamen aldehyde, hydroxycitronellal, bour groups have from 8 to 18 carbon atoms. Examples include geonal, ionones, methyl cedryl ketone , anethole , eugenol, cocoamidopropyl betaine , sodium cocoamphoacetate , isoeugenol, geraniol, linalool, terpineol, phenylethyl alco cocoamidopropyl hydroxysultaine , and sodium cocoampho hol, a -hexylcinnamaldehyde , geraniol, benzylacetone , propionate. cyclamen aldehyde , hydroxycitronellal , ambroxan , indole, [ 0212 ] Exemplary nonionic surfactants include aliphatic hedione, sandelice, cyclovertal, B - damascone , allyl amyl (Co - C ) primary or secondary linear or branched chain glycolate, dihydromyrcenol, phenoxyethyl isobutyrate , acids, alcohols or phenols , alkyl ethoxylates , alkyl phenol cyclohexyl salicylate , phenylacetic acid , geranyl acetate , alkoxylates (especially ethoxylates and mixed ethoxy / irotyl, floramate , active astringent products such as alumi propoxy ), block alkylene oxide condensate of alkyl phenols , num chloride, aluminum chlorohydrate , aluminum dichlo alkylene oxide condensates of alkanols , ethylene oxide/ rohydrate, aluminum sesquichlorohydrate , aluminum dihy propylene oxide block copolymers , semipolar nonionics droxyallantoinate , aluminum chlorotartrate , aluminum and US 2017 /0319462 A1 Nov. 9 , 2017

zirconium trichlorohydrate, aluminum and zirconium tetra costeroids ; products for gynecological use ( e . g ., oxytocics , chlorohydrate , aluminum and zirconium pentachlorohydrate contraceptives, androgen , estrogen , progestogen , ovulation and / or mixtures thereof. stimulants , gonadotropins , antiandrogens) ; products for uro [ 0219] Exemplary essential oils include Archangelica offi logical use ; antispasmodics , drugs used in benign prostatic cinalis (angelica ) oil , Canangium odoratum (ylang ylang ) hypertrophy; hormones; hormone antagonists ; antibiotics ; oil, Canarium luzonicum ( elemi) oil, orange oil , Chamo tetracyclines ; amphenicols ; penicillin ; sulfonamides ; milla recutita (matricaria ) oil, Anthemis nobilis oil, Elettaria trimethoprim ; macrolides ; lincosamides ; streptogramins ; cardamomum ( cardamom ) oil, Acorus calamus ( calamus ) antibacterial aminoglycosides ; antibacterial quinolones ; oil, Ferula galbaniflua ( galbanum ) oil , Cinnamomum cam antivirals ; immune serum ; immunoglobulins ; antineoplastic phora (camphor ) oil, Daucus carota ( carrot ) seed oil, Salvia agents ; immunomodulatory agents ; alkylation agents ; anti sclarea ( clary sage ) oil , Citrus paradisi (grapefruit ) oil, metabolites ; plant alkaloids and other natural products ; Eugenia caryophyllus ( clove ) oil, Cinnamon bark oil , Cori cytotoxic antibiotics ; immunosuppressive agents ; drugs for andrum sativum ( coriander ) oil, Cupressus sempervirens disorders of the musculoskeletal system ; antirheumatics ; ( cypress ) oil , Santalum album ( sandalwood ) oil , Juniperus agents which affect bone structure and mineralization ; drugs virginiana ( cedar wood ) oil, Cymbopogon nardus ( citro which act on the nervous system ; general anesthetics ; local nella ) oil, Cinnamomum verum (Cinnamon ) leaf oil , Jasmine anesthetics ; opioids ; antimigraine agents ; anticonvulsants ; officinale ( jasmine ) absolute oil, Juniperus communis ( juni dopaminergic agents ; antipsychotics ( e . g . , chlorpromazine per Berry ) oil, Zingiber officinale ( ginger ) extract , Mentha hydrochloride , levomepromazine hydrochloride , clo spicata ( spearmint) oil , Salvia officinalis ( sage ) oil , cedar oil, capramine hydrochloride ); anxiolytics ; hypnotics; sedatives ; Pelargonium graveolens ( geranium ) oil, Thymus vulgaris antidepressants ( e .g ., imipramine hydrochloride , trazodone ( thyme) oil, Melaleuca altemifolia ( tea tree ) oil, Myristica hydrochloride , fluvoxamine maleate ); psychostimulants ; fragrans (nutmeg ) oil , Melaleuca viridiflora (niaouli ) oil, anti - dementia drugs ( e . g . , donepezil, rivastigmine , galanth Citrus aurantium ( neroli ) oil , pine oil , Ocimum basilicum amide hydrobromide, memantine hydrochloride ) ; antianxi (basil ) oil , Mentha arvensis oil , Pogostemon cablin (pa ety drugs ( e . g ., diazepam , alprazolam , tandospirone citrate ) ; tchouli ) oil, Cymbopogon martinii ( palmarosa ) oil, Foen tranquilizers (hydroxyzine hydrochloride ); brain function iculum vulgare ( fennel) oil , Citrus bigaradia (petitgrain ) oil, stimulant/ activators ( e . g ., tiapride hydrochloride , protirelin Piper nigrum (black pepper) oil, Boswellia carteri ( frank tartrate ) ; cerebral circulation improving drugs ( isosorbide incense ) oil , Chrysopogon zizanioides ( vetiver ) oil, Mentha mononitrate or dinitrate , pentoxifylline , fasudil hydrochlo piperita (peppermint ) oil, Citrus bergamia (bergamot ) oil , ride ) ; Parkinson ' s disease therapeutic agents (hydrochloric benzoin oil, Aniba rosaeodora (rosewood ) oil, Origanum acid benserazide, amantadine hydrochloride, talipexole majorana ( marjoram ) oil, mandarin oil, Commiphora myr hydrochloride ) ; chemical - transmitter release - inhibition rha (myrrh ) oil , Melissa officinalis (balm mint ) oil , Euca drugs ( emedastine fumarate , suplatast tosilate , epinastine lyptus globulus oil, Citrus junos oil , Citrus aurantiifolia hydrochloride ) ; cardiac disease therapeutic - agents ( e . g . , ( lime) oil , Ravensara aromatica (clove ) oil , Lavandula aminophylline, diltiazem hydrochloride , nicorandil , propra latifolia ( lavandin ) oil, Lavandula angustifolia (lavender ) nolol hydrochloride, isoprenaline hydrochloride, disopyra oil , Tilia vulgaris ( linden ) oil, lemon oil, lemon grass oil , mide phosphate , procainamide hydrochloride ) ; antihyper rose oil , Aniba rosaeodora ( rosewood ) oil , Rosmarinus tensive drugs ( e. g. , captopril, enalapril maleate , amosulalol officinalis ( rosemary ) oil and Levisticum officinale ( lovage ) hydrochloride , prazosin hydrochloride , urapidil , clonidine oil, and mixtures thereof . hydrochloride ) ; vasodilators ( e . g . , tolazoline hydrochlo [ 0220 ] In one embodiment, the active agent includes at ride ) ; vasoconstrictors ( e . g . , amezinium metilsulfate , etile least one active agent which is selected from skin whitening frine hydrochloride , phenylephrine hydrochloride , mido or depigmentation agents , anti- acne agents , and mixtures drine hydrochloride ); antihyperlipidemic drugs ( pravastatin thereof. sodium , fluvastatin sodium , cerivastatin sodium ) ; parasym [ 0221 ] Other pharmaceutical active ingredients and / or pathomimetics; drugs used in addictive disorders ; anti adjuvants useful herein include antacids; agents against vertigo agents ; antiparasitic agents ; insecticides; insect peptic ulcers ( e . g . , butylscopolamine bromide , pirenzepine repellants; nasal decongestants ; antitussives and expecto hydrochloride , timepidium bromide ) and gastroesophageal rants (dextromethorphan hydrobromide , fominoben hydro reflux disease ; antispasmodics; analgesics ; anticholinergic chloride , acetylcysteine ) ; asthma preparations ( clenbuterol drugs ; propulsive drugs; antiemetics ; anti- nausea drugs ; hydrochloride , fenoterol hydrobromide , procaterol hydro agents for biliary therapy ; agents for hepatic therapy ; lipo chloride ); mucolytic agents ; cough suppressants ; ophthalmic tropics; laxatives ; antidiarrhetics; intestinal adsorbents ; anti active ingredients; otological active ingredients ; antiglau propulsives ; anti- inflammatory drugs; active ingredients coma drugs ;miotics ; mydriatics; cycloplegics; anti -dandruff against obesity ; enzymes; hypoglycemic drugs ; insulin and agents ; muscle contraction inhibitory agents ; H2 blockers analogues ; vitamins, proteins ; minerals ; anabolic steroids ; ( e . g ., ranitidine hydrochloride , roxatidine -hydrochloride antithrombotic agents ; antifibrinolytics ; hemostatic agents ; acetate ) ; proton pump inhibitors ( e . g . , omeprazole , lanso antiarrhythmic agents ; cardiac stimulants ; cardiac glyco prazole , rabeprazole ), antiemetic ( e . g . , granisetron hydro sides ; vasodilators ; antiadrenergic agents ; antihypertensive chloride , azasetron hydrochloride , ondansetron hydrochlo drugs ; diuretics; potassium - saving agents ; antihemorrhoid ride , ramosetron hydrochloride ) , anti - rheumatism agents als ; antivaricose therapy agents ; capillary stabilizing agents ; ( e . g ., bucillamine , penicillamine ) ; urological- diseases drugs agents which act on the reninangiotensin system ; beta ( e . g . , oxybutynin hydrochloride , tamsulosin hydrochloride , blockers ; selective calcium -channel blockers ; non -selective propiverine hydrochloride ) ; (beta ) -blockers ( e . g ., bisoprolol calcium -channel blockers; ACE inhibitors ; angiotensin II fumarate , betaxolol hydrochloride) ; and mixtures thereof . inhibitors ; agents modifying lipids; antifungals; antiprurit [0222 ] The nature of these active ingredients excipients ics ; anesthetics; antipsoriatics , chemotherapy drugs; corti can be synthetic or natural, such as vegetable extracts , or US 2017 /0319462 A1 Nov. 9 , 2017 come from a biotechnological process or from a combina multiple feed ports between its feed end and its die end . The tion of a synthetic process and a biotechnological process . ingredients may be added at one or more of the feed ports Additional examples can be found in the Personal Care and the resulting TPU composition that exits the die end of Product Council (PCPC ) International Cosmetic Ingredient the extruder may be pelletized , granulated , or used directly Dictionary & Handbook , 15th Edition ( 2014 ) . A biotechno for forming into the film . logical process is understood to be any process which [0229 ] 3 . Continuous Process produces the active ingredient, or part of it, in an organism , [0230 ] The “ pre- polymer ” process and the " one shot" or in a part of it . process can be performed in either a batch or continuous [ 0223] In some embodiments , one or more of the active manner. That is , in some embodiments the TPU may be agents and /or excipients may be present in the exemplary made by reacting the components together in a " one shot " film or on a surface thereof in the form of liposomes , mixed polymerization process wherein all of the components , liposomes , oleosomes , niosomes, millicapsules , microcap including reactants are added together simultaneously or sules, nanocapsules , nanostructured lipid carriers , cyclodex substantially simultaneously to a heated extruder and reacted trins , vesicles , micelles, mixed micelles of surfactants , sur to form the TPU . In other embodiments the TPU may be factant- phospholipid mixed micelles, millispheres , made by first reacting the polyisocyanate component with microspheres , nanospheres , lipospheres, microemulsions, someportion of the polyols forming a pre -polymer , and then nanoemulsions, miniparticles, milliparticles, microparticles, completing the reaction by reacting the pre - polymer with the nanoparticles and solid lipid nanoparticles . remaining reactants , resulting in the TPU . After exiting the extruder, the composition may be pelletized , granulated , or Processes to Make the TPU and Face Mask directly formed into the film . [ 0224 ] 1 . " One - Shot ” Process [ 0231 ] To form the film , the polyurethane polymer may be [0225 ] The reactants ( the polyols , the diisocyanate , and solvent cast or extruded onto a release layer . the chain extender ), and optionally a catalyst , may be [0232 ] Solvent casting may include combining the TPU reacted together to form the TPU . Any known processes to with a casting liquid to form a casting solution . The casting react these reactants may be used to make the TPU . In one liquid may be a mixture of water and a water -miscible embodiment, the process is a so - called " one - shot” process organic solvent, such as one or more of a C2 - Ci alcohol, where all the reactants are added to an extruder reactor and tetrahydrofuran , dimethylacetamide , dimethylformamide , reacted . The equivalentweight amount of the diisocyanate to and the like . A ratio of solvent to water in the casting the total equivalent weight amount of the hydroxyl contain liquid / solution may be from 20 : 1 to 1 : 10 . As an example , a ing components , that is , the polyols and the chain extender , mixture of ethanol and water is used for casting . The casting can be from 0 . 95 to 1 . 10 , or from 0 . 96 to 1 . 02 , and even from solution may optionally include one or more of the active 0 . 97 to 1 . 005. Reaction temperatures utilizing a urethane agents and / or excipients . The casting solution may be catalyst can be from 175 to 245° C . , and in another embodi applied to a release layer , such as a sheet of high density ment from 180 to 220° C . The resulting composition may be polyethylene (HDPE ) , TeflonTM , or low density polyethyl pelletized , granulated , or directly formed into the film . ene (LDPE ) , to provide a cast film . The cast film may be [ 0226 ] 2 . Pre -Polymer Process dried to form the dry polymer film , e .g . , in air or another [ 0227 ] The TPU can also be prepared utilizing a pre atmosphere , at room temperature or slightly above . polymer process . In the pre - polymer route , the polyols are [0233 ] The resulting dry film may be shaped to form the first reacted with generally an equivalent excess of one or face mask , e. g . , by cutting the film to the desired shape . The more diisocyanates to form a pre - polymer solution having face mask may be hydrated , prior to use, with an aqueous free or unreacted diisocyanate therein . The reaction is gen solution . The aqueous hydration solution may contain one or erally carried out at temperatures of from 80 to 220° C ., or more of the active agents and /or excipients . The hydration from 150 to 200° C . in the presence of a suitable urethane may be performed before or after cutting the film to the catalyst . Subsequently , a chain extender, as noted above , is desired shape. added in an equivalent amount generally equal to the iso [0234 ] In one embodiment , the active agent is present in cyanate end groups as well as to any free or unreacted the film prior to shaping and hydration . For example , the diisocyanate compounds . The overall equivalent ratio of the active agent is incorporated during solvent casting of the total diisocyanate to the total equivalent of the polyol film . The active agent- containing film may be hydrated intermediate and the chain extender is thus from 0 . 95 to before or after cutting the film in to the shape of the face 1 . 10 , or from 0 . 96 to 1 . 02 and even from 0 .97 to 1 . 05 . The mask . chain extension reaction temperature is generally from 180 [0235 ) The release layer is removed before or after apply to 250° C . or from 200 to 240° C . Typically , the pre - polymer ing the face mask to the skin of the user. route can be carried out in any conventional device includ [0236 ] One advantage of the exemplary TPU film is that it ing an extruder . In such embodiments , the polyol interme can be cold processed (e . g. , solvent cast , e .g ., at a tempera diates are reacted with an equivalent excess of a diisocya ture of less than 40° C ., or less than 30° C .) , allowing nate in a first portion of the extruder to form a pre - polymer customized formulations by salons and in office preparations solution and subsequently the chain extender is added at a by dermatologists . For conventional hydrocolloid films, cold downstream portion and reacted with the pre - polymer solu processing is not available , which limits the active agents tion . Any conventional extruder can be utilized , including and the use of hydrocolloid films to larger manufacturers . extruders equipped with barrier screws having a length to [ 0237 ] The hydrated TPU films when tested for wet burst diameter ratio of at least 20 and in some embodiments at strength may have higher absolute peak force at break and least 25 . a greater % elongation than hydrocolloid films of the same ( 0228 ] In one embodiment, the ingredients are mixed on a thickness so that the films may be stretched around facial or single or twin screw extruder with multiple heat zones and other body features without ripping and handled easily . US 2017 /0319462 A1 Nov. 9 , 2017 24

[0238 ] The exemplary TPU substrate does not support [0242 ] Different polyisocyanates are evaluated : 4 , 4 -diiso bacterial growth and can be stored for extended periods cyanato dicyclohexylmethane (H12MDI ) , available from without the need for preservatives . A preservative may be Bayer as DesmodurTM W ; and hexamethylene diisocyanate included in the aqueous hydration formulation . (HDI ) . [ 0239 ) Without intending to limit the scope of the exem [0243 ] Different chain extenders are evaluated : 1 , 4 - bu plary embodiment, the following examples illustrate poly tanediol (bdo ) and 1 , 10 -decanediol (ddo ) . urethane films and face mask compositions . [0244 ]. As the catalyst for Examples A - H , an organotin catalyst , Cotin® 430 , is used , which is a dioctyltin carboxy EXAMPLES late , available from Vertellus Specialties Inc . Example 1 [0245 ] The proportions of hard , soft and intermediate segment are calculated as described above , therefore : Preparation of Polyurethane Films [0246 ] Wt. % soft segment= wt. % PEG - 8000 + wt. % [ 0240 ) Polyurethane films are formed using the reactants PEG - 1450 + wt. % PEG -300 ( or PolyGTM 55 - 56 ) . shown in TABLE 1. Examples A - H are formed using a [0247 ] Wt. % hard segment= wt. % isocyanate in hard mixture of Polyols A and B while examples J and K use only segment + wt. % chain extender. one of the two polyols . In all the examples , Polyol A = PEG 102481. Wt. isocyanate in hard segment = [moles isocya 8000 ( a poly( ethylene glycol) with an average molecular nate -moles (PEG - 8000 + PEG - 1450 + PEG - 300 ( or PolyGTM weight of 8000 daltons ) and Polyol C = PEG 300 ( a poly 55 - 56 ) ]xMw isocyanate ( ethylene glycol) with an average molecular weight of 300 [0249 ] Wt. % intermediate segment= 100 wt. % soft seg daltons) . ment wt. % hard segment. [ 0241] As polyol B , PEG 1450 , “ 1450 ” ( a poly ( ethylene 10250 ). The ratings in TABLE 1 are based on the overall glycol) with an average molecular weight of 1450 daltons ) performance of the compositions as a thin face mask , where is employed . Alternatively , a polyether copolymer diol with 1 indicates the TPU performed poorly and 5 indicates the polypropylene glycol and polyethylene oxide segments and TPU performed exceptionally well . It is to be appreciated an average molecular weight of 2000 daltons, available as that the compositions may be useful in thicker face mask or Poly -GTM 55 - 56 (“ PolyG ” ) from Lonza , is used . for other purposes even when the rating is low . TABLE 1 TPU Compositions Polyol A Polyol C Chain (PEG8000 ) (PEG300 ) extender TPU wt. % Polyol B wt. % Diisocyanate wt. % wt. % wt. % Ex . A 24 . 7 57. 7 (1450 ) 15. 0 H12MDI 0 . 99 0 . 99 bdo Ex . B 24 . 73 57. 82 (1450 ) 15 .03 H12MDI 0 . 75 1 . 12 bdo Ex . C 24 . 73 57 . 82 ( 1 15 . 11 H12MDI 0 . 60 1 . 19 bdo Ex . D 26 . 29 61. 25 ( 1450 ) 10 . 13 HDI 0 . 6 1 . 21 bdo Ex. E 26 . 29 61. 25 ( Poly - G ) 9 . 47 HDI 0 .82 1 . 64 bdo Ex . F 24 . 73 57. 82 14 . 39 H12MDI 1 .68 0 . 84 bdo Ex . G 24 . 49 57. 07 ( 1450 ) 14. 98 H12MDI 0 .65 2 . 27 ddo Ex . H 24 . 49 57 . 07 (Poly - G ) 14 H12MDI 0 .87 3 . 03 ddo Ex . J 82 . 5 13. 3 H12MDI 3 . 6 bdo Ex . K 90 . 5 7 . 4 H12MDI 1 . 5 bdo Ex . L 89 . 52 — 7 . 12 H12MDI 2 .83 ddo Ex . M 87 .04 8 . 8 H12MDI 3 . 84 ddo Ex . N 86 . 6 — 10 .41 H12MDI 2 .52 bdo TPU Wt. % hard Wt. % Soft Wt. % Intermediate Rating Ex . A 3 . 87 83 . 4 12 . 74 2 (weak ) Ex . B 4. 21 83 . 15 12 .64 Ex . C 4 . 43 83 12 . 57 Ex . D 3 . 35 88 . 14 8 .51 Ex . E 4 .95 88 . 36 6 .69 Ex . F 5 . 37 84 . 23 10 . 40 Ex. FAQIJG 5 . 55 82 . 21 12 . 24 Ex . H 7 . 98 82. 43 9 . 59 Ex . J 14 . 19 82. 5 3 . 31 1 ( hard ) Ex . K 5 . 93 90 . 5 3 . 57N Ex . L 7 .01 89 .52 3 . 47N uAuuw Ex . M 9 . 59 87. 04 3 . 37 Ex . N 10 .09 86 . 6 3 . 36 US 2017 /0319462 A1 Nov. 9 , 2017 25

[ 0251 ] Ex A - H vary compositionally but generally exhibit Viscosity similar water uptake, flexibility and other physical proper [0254 ] Brookfield rotating spindle method (all viscosity ties . Examples J- N include no Polyol B or C . measurements reported herein are conducted by the Brook field method ): The viscosity measurements are calculated in [0252 ] Formulations are also prepared which include a centipoise (Cps ), employing a Brookfield rotating spindle mixture of one of Examples A - H with one of Examples J and viscometer , Model RVT ( Brookfield Engineering Laborato K . Additionally, formulations are prepared which include a ries, Inc. ), at about 20 revolutions per minute ( rpm ), at mixture of one of examples A - K with a Carbomer homopo ambient room temperature of about 20 to 25° C . (hereafter lymer type A (Carbopol® 981F polymer , obtainable from referred to as viscosity ). Spindle sizes are selected in accor Lubrizol Advanced Materials , Inc . ) dance with the standard operating recommendations from the manufacturer. Generally , spindle sizes are selected as Example 2 follows:

Solubility Study Spindle Size No. Viscosity Range ( Cps) [0253 ] Some of the polymers formed in Example 1, in 1 - 50 500 - 1 ,000 granular form , are heated to between 40 and 60° C . in 1 ,000 - 5 ,000 various solvents to test solubility . If the polymer remained in 5 ,000 - 10 , 000 10 , 000 - 20 ,000 solution upon cooling to room temperature, it is deemed vauAWNA 20 ,000 -50 ,000 soluble. TABLE 2 below shows the 24 hour granule swell > 50 , 000 data in water. TABLE 3 shows the amountof solvent uptake if the polymer is soluble or swollen . If swollen , then TABLE [0255 ] The spindle size recommendations are for illustra 3 shows the gm solvent/ gm polymer uptake. TABLES 4 and tive purposes only . The artisan of ordinary skill in the art will 5 show the viscosity at various concentrations in EtOH :H2O select a spindle size appropriate for the system to be mea mixtures, as measured by Brookfield viscosity at 20 rpm . sured . TABLE 2 24 hr. Granule Swell data of 3 wt. % granule form of polymer in water

Polymer Ex . A Ex . B Ex .CEx . D Ex . E Ex. F Ex . G Ex . H Ex . J Ex . K Ex . M Ex . N

Water 8 .56 12 . 38 14 .07 High 6 . 18 4 .84 6 .78 6 .12 3 . 6 9 . 2 7 .69 7 . 8 gm / gm

TABLE 3 Solubility of 3 wt. % granule form of polymer in various solvents

Polymer Ex . A ExEx . B CEx Ex . C E Exx . F ExEx . KK

Water gm / gm 8 . 56 12 . 38 14 . 07 4 . 84 9 . 2 50 :50 Hazy, soluble Hazy , soluble Hazy, soluble 22 .67 gm /gm EtOH :H2O & thin & thin & thin 95 : 5 Clear , soluble Clear , soluble Clear , soluble Insoluble EtOH :H2O & thin & thin & thin 50 :50 EtOH : ethyl Clear, soluble Clear, soluble Clear , soluble acetate & thin & thin & thin 50 :50 ETOH : THF Clear , soluble Clear , soluble Clear, soluble Insoluble & thin & thin & thin 90 : 10 Clear, soluble Clear , soluble Clear, soluble THF :H2O & thin & thin & thin US 2017 /0319462 A1 Nov. 9 , 2017

TABLE 4 [ 0259 ] The square is placed in approximately 50 gm of soaking solution and suspended for 30 minutes in the Brookfield Viscosity of Polymers in 50 : 50 EtOH : H , O at 20 rpm solution , unless noted otherwise. The square is checked to Wt. % Polymer Ex . A Ex . B ExC . Ex . D Ex . E Ex . F ensure it does not stick to the container or have surfaces exposed out of the solution . 4 . 91 thin thin thin 10 360 342342 274 120 110 [0260 ] At the end of soaking time, the square is removed 13. 4 1392 1364 1110 15 1280 1730 1160 350 350 and placed on HDPE ( with no additives ) and measured for 18. 6 4930 3600 3880 2500 X , Y and Z growth . If strong enough , it is patted dry and 20 4950 , 6640 740 720 3160 weighed . The wet film is then covered with another sheet of release film and placed in a sealed plastic bag for further testing . Measurements are as follows: TABLE 5 [0261 ] Area growth with time: 5x5 cm film samples are cut and the corners are marked with a black , water insoluble , Brookfield Viscosity of Polymers in 80 : 20 EtOH :H20 at 20 rpm ink to show the edges . The film is placed in a zippered Wt. % polymer Ex. J Ex. K Ex. L Ex . M polyethylene bag with 100 gm of pH 6 .8 USP phosphate buffer solution and the bag with film is placed on a grid 4 . 91 148 10 Not soluble 650 210 graph paper. The size is taken at a set time and recorded . 15 Not soluble 6000 635 20 Not soluble 30, 400 1450 1555 [0262 ] Hydrating Solutions : [ 0263 ] Solution uptake studies on the films are conducted in order to understand how ingredients in formulations will influence the properties of the film . The following soaking Example 3 (hydrating ) formulations are evaluated : Soaking Solution and Uptake Studies [0264 ] 1. De- ionized water. 10256 ] The films are cast from an ethanol /water solution [0265 ] 2 . glycerin : 10 wt. % USP grade glycerin in DI either with a 2 inch draw down square of set thickness or an water. 8 inch draw down bar with adjustable thicknesses using an [ 0266 ] 3 . Buffer : USP pH = 6 . 8 phosphate buffer , formed by automatic film applicator with vacuum plate (Byko - driveTM dissolving 6 . 805 g potassium phosphate monobasic and with vacuum plate , Material # 2121 ; BYK Gardner, Md . , 0 .896 g sodium hydroxide in water q . s . , adding 1 liter of USA ) , at a drawdown speed of 1 in / sec . All casting solutions water, and adjusting the pH , if necessary , with 2N HCl or 2N are centrifuged before use to remove bubbles for 30 minutes NaOH . The pH is checked for 1 L solution and the volume at 1500 rpm using a Thermo Electron Corporation , IEC of acid / base necessary for adjustment is recorded . Centra GP8 Centrifuge . The film is allowed to dry in a hood at room temperature , in air overnight. The Ex . A - C polymers [0267 ] 4 . Aloe Vera Formulation : The formulation give good pliable films . The Example J polymer is an included Aloe vera concentrate , available as ActiveraTM 10X extrusion grade and does not dissolve in a water / ethanol (Clear ) , supplied by Active Organics . ( INCI Name Aloe mixture and therefore could not be formed into films by Barbadensis leaf Juice ) . 2 wt. % of the Aloe vera concentrate casting . Ex . K dissolution is molecular weight dependent is combined with 10 wt. % glycerin and water to give a final and the melt index is recommended to be above 5 to 6 if it concentration of 20 wt % aloe vera in the formulation . is to be solution cast. Good solvent cast films are obtained [0268 ] The formulation is preserved with a mixture of from the highest water content: solvent combinations (50 :50 phenoxyethanol and ethylhexylglycerin supplied as EtOH :H2O ) . The addition of a low level of Carbopol® Euxy TM -PE9010 by Schülke Inc. The resulting aloe formu polymer ( 1 :60 Carbopol: polymer K ) provides a good cast lation is as follows: film . A casting solution for this film is formed from 0 . 2 wt. % Carbopol® ETD 2020 , 12 wt. % Ex . K , in Ethanol: water [0269 ] Aloe Clear Formulation : at a weight ratio of 80 / 20 . Studies with Ex . C and Ex . F polymers suggest that the small amount of Carbopol® ETD 2020 does not influence the film solution uptake . Wt.. % 50 g DI Water 87 . 48 43. 74 [ 0257 ] Degassed blends are used to solvent cast films on glycerin (excipient ) 10 5 .00 polyethylene substrates ( 5 mil natural high density polyeth Activera TM 10 x 10 : 1 1 . 00 ylene sheets from Griff Paper and Films, PA , USA ) and High Na , EDTA 0 .02 0 . 01 density polyethylene roll from Griff Paper. Euxyl TM - PE9010 0 . 5 0 . 25 [ 0258 ) Film samples are cut into either 5x5 cm squares or Total 100 3x3 cm squares . The squares are weighed to 4 decimal places . The solvent cast squares show more variability in thickness than the extruded films. The squares are marked [ 0270 ] 5 . Salicylic Acid Gel Formulation : The salicylic for the starting point and the thickness measured at four acid gel formulation includes 5 wt. % CurcylicTM 40 ( a 40 corners and averaged . The extruded film data in the tables wt. % solution of salicylic acid in a proprietary stabilizer at below are measured with the X Direction being perpendicu 60 wt. % ) , 10 wt. % glycerin , with a final concentration of lar to the extruded film and Y Direction being parallel to the salicylic acid of 2 wt. % . The formulation is preserved with extruded film . Euxyl®PE9010 . US 2017 /0319462 A1 Nov. 9 , 2017 27

[0271 ] Salicylic Acid Gel Formulation TABLE 7 Release of active agent from films Ingredient name Wt. % 50 g Example Release media % release at 30 mins DI Water 84 . 50 42. 25 glycerin 5 .00 Ex . 4 Deionized water 87 . 0 % Curcylic ?40 2 .50 Ex . 5 Deionized water 87 . 9 % ( actual amount of salicylic acid ) u? Ex . 4 Buffer 80 . 8 % Euxyl ® -PE9010 0 . 5 0. 25 Ex . 5 Buffer 84 . 3 % Total 100 [0275 ] Uptake Rate [0272 ] 6 . Niacinamide Formulation : Niacinamide is a 0276 ] In detailed studies with the Ex . J and K TPUs, it is Bgroup vitamin , sometimes referred to as Vitamin PP. It is observed that the films show different rate of uptake depend incorporated into formulations for whitening . Niacinamide ing upon the thickness of the film and that thicker films are is used at 2 wt. % with 10 wt. % glycerin for moisturizing . found to have slower uptake. Solvent cast Ex . Fis studied at The formulation is preserved with EuxylTM PE9010 . 0 . 254 mm ( 10 mil ) dry thickness at room temperature in the 10273 ] Niacinamide Formulation buffer . [ 02771 TABLE 8 shows the rate of growth of solvent cast Ex . F at 23° C . in the buffer. FIG . 4 illustrates the results . Ingredient name % w / w 50 g Niacinamide 1 .00 TABLE 8 glycerin 10 5 .00 Euxyl ® -PE9010 0 . 5 0 . 25 Rate of growth of solvent cast Ex. F at 23° C . in buffer DI Water 87 . 5 43 . 75 Dry Film Thickness Time volume growth area growth Total 100 (mm ) (mins ) gm /gm cm / cm3 cm + /cm² 0 . 000 0 . 298 ????? 1 . 983 2 . 141 0 . 988 Example 4 0 . 275 2 .618 3 . 524 1 .592 0 . 280 30 5 . 025 4 . 355 1 . 856 0 . 313 40 4 . 791 4 . 251 1 . 957 Solvent Casting of films with Actives 0 . 293 60 5 .018 4 . 222 1 .855 0 . 275 40 4 . 860 4 . 556 1 . 924 [0274 ] TABLE 6 shows solvent cast films with an example 0 . 270 5 . 108 4 .505 1 . 958 active agent ( salicylic acid or a commercial salicylic acid 40 % gel, CurcylicTM 40 ) . For some of the films, a blend of TPU and Carbopol® 981NF polymer ( a cross -linked poly [0278 ] FIG . 5 shows results for Example F films where the (acrylic acid ) , abbreviated as “ 981 polymer ” ), is used . soaking solution is buffer and the soak is stopped at 30 TABLE 7 shows the release of the active agent upon minutes and conducted at room temperature . It can be seen soaking . Salicylic acid content was determined by HPLC . that the Ex . A , B , and C films are all similar in their TABLE 6 Solvent Cast Films with Active Agents

981 Wt. % Wt. % polymer, Salicylic Salicylic Example TPU Polymer wt. % Active agent Acid Cast Acid found Ex . 1 Ex . C ( 98 wt. % ) salicylic acid 2 1 .65 40 % gel Ex . 2 Ex . F ( 98 wt. % ) salicylic acid 2 1 . 741 40 % gel Ex . 3 Ex . C ( 96 .4 wt. % ) 1 .61 salicylic acid 1 . 776 Ex . 4 Ex . K ( 96 . 4 wt. % ) 1 .61 salicylic acid 1 .821 Ex . a5 Ex . K ( 96 . 4 wt. % ) 1 .61 salicylic acid 1 . 699 40 % gel Ex . 6 Ex . F (99 .5 wt. % ) salicylic acid 0 . 5 0 . 43 Ex . 6 Ex . F (97 wt. % ) salicylic acid 3 . 0 2 . 76 Ex . 8 Ex . F ( 96 wt. % ) salicylic acid 4 . 0 3 . 70 Ex. 9 Ex . K (97 . 88 wt. % ) 1. 63 salicylic acid 0 .5 0 .47 Ex. 10 Ex . K (97 . 4 wt. % ) 1. 62 salicylic acid 1. 0 0 .83 US 2017 /0319462 A1 Nov. 9 , 2017 28 properties . Ex . F had somewhat lower uptake . The results TABLE 10 are shown in greater detail in TABLES 9 - 12 . Growth of EX . B solvent cast films in buffer at 23° C . after 30 minutes ( gm wet - gm (gm wetgm –dry gm dry) Thick - Wt dry wet Vol. Z XY ness gain vol . vol. growth growth growth (mm ) gm / gm cm3 cm3 cm3/ cm3 mm /mm cm²/ cm² [ 0279] Gm / gm growth is calculated as : 0 . 182 8 .113 0 .456 3 .498 6 . 668 1 . 534 2 .026 0 .2007 .674 0 .500 3. 1416 5 . 283 1 . 2 1. 856 ( Vol wet – Vol dr 0 . 2636 . 847 0 .656 4 . 459 5 .796 1 .467 1 .755 (Vol wetVol cm dry– Volcm dry cm 0. 347 6. 299 0. 868 . 5. 297 5. 097 1. 324 1. 624 [ 0280 ] Volume growth is calculated as: TABLE 11 (Area wet cm ? – Area dry cm ?) Growth of EX . C solvent cast films in buffer at 23° C . after 30 minutes Area dry cm2 ThickThick - Wt dry wet VolVol. Z x y ness gain vol. vol. growth growth growth (mm ) gm / gm cm3 cm3 cm3/ cm3 mm /mm cm -/ cm² 0 . 117 9 .151 0 .294 2 .008 5 .835 1 .064 2 .312 [0281 ] Area growth (XY growth ) is calculated as : 0 . 173 7 . 716 0 .425 1 . 694 2 . 987 1 .739 2 . 133 0 . 195 7 . 177 0 . 488 4 .045 7 .298 1 .590 2 . 204 0 .285 6 . 234 0 . 700 3 . 342 3 .775 1 . 465 2 . 062 ( Thickness wet mm - thickness dry mm ) thickness dry mm 0 . 290 6 . 438 0 . 725 5 . 141 6 . 091 1 . 483 1 . 856 0 . 367 5 . 105 0 .8504 .712 4 .544 1 . 388 1 . 755

TABLE 12 Growth of blend of EX . C and EX . K solvent cast films in buffer at 23° C . after 30 minutes Thickness Wt gain dry vol. wet vol. Vol. growth z growth xy growth (mm ) gm / gm cm cm3 cm²/ cm3 mm /mmcm / cm² 0 . 170 8 . 107 0 . 425 3 .710 7 .731 1 . 471 2 . 534 0 . 223 7 . 708 0 .556 4 .659 7 . 377 1 . 449 2 . 42 0 . 273 6 .948 0 .681 5 .042 6 . 401 1 . 284 2 . 24

[ 0282] Z growth is calculated as: TABLE 13 TABLE 9 Growth of EX F solvent cast films in buffer at 23° C . after 30 minutes Thick Wt dry wet Vol . Z Growth of Example A solvent cast ness gain vol. vol . growth g rowth growth films in buffer at 23° C . after 30 minutes (mm ) gm /gm cm3 cm3 cm3/ cm3 mm /mm cm²/ cm² 0 . 130 6 . 175 0 . 325 2 .497 Thick Wt dry wet Vol. Z xy?? 0 . 310 4 . 531 0 . 775 4 . 463 4 . 759 0 . 83871 2 . 132 ness gain vol. vol. growth growth growth 0 . 310 4 . 757 0 . 775 4 . 277 4 .519 0 . 741935 2 . 168 (mm ) gm /gm cm3 cm3 cm3/ cm3 mm /mm cm²/ cm² 0 . 368 4 . 043 0 . 919 1 . 822 0 . 300 4 .495 0 . 75 4 . 163 4 . 551 0 . 966667 1 . 822 0 . 145 9 . 292 0 . 300 2. 743 8 . 146 1 . 310 2 . 276 0 . 213 8 . 223 0 . 375 3 . 292 7 .779 1 .024 2 . 062 [0283 ] TABLE 14 shows data for the 30 ( or 90 minute 0 . 247 7 . 790 0 .600 3 .994 5 .657 1 . 061 2 . 133 solution uptake for films cast from 50 /50 ethanol water in 0 . 297 7 . 233 0 . 850 4 .550 4 . 354 1 . 143 1 . 855 buffer, deionized water, and in formulations as described 0 . 320 6 . 360 0 . 900 4 . 760 4 . 289 1 . 188 1 .72 above containing various active agents : Aloe vera formula 0 . 323 6 .612 0 .750 5 .411 6 .215 1 .217 2 .027 tion with Activera? , niacinamide formulation , and salicylic acid gel formulation with CurcylicTM gel. Data for some extruded films is also shown, denoted by † . US 2017 /0319462 A1 Nov. 9 , 2017 29

TABLE 14 Growth of solvent cast and extruded films in buffer and in hydrating formulations containing active agents 23° C . after 30 or 90 minutes Salicylic 2 Deionized Aloe vera acid gel Niacinamide Buffer water Formulation Formulation Formulation Up Up Up Up Up Thick take Thick - take Thick - take Thick take Thick take TPU ness gm / 11ness gm / ness gm ness gm ness gm / (mm ) gm (mm ) gm (mm ) gm (mm ) gm 010(mm ) gm 0 .32 6 .61 0 . 28 6 . 93 0 .27 5 . 67 0 . 26 6 .85 0 . 26 637 0 . 27 603 0 .29 8 . 99 0 . 25 653 0 .25 687 MOA 0 . 21 fell 0 . 21 fell apart apart I 0 .31 fell apart 0 . 28 5 .02 0 . 31 5 . 34 0 . 31 4 .60 0 . 25 4 .57 0 . 25 4 . 49 0 . 29 4 .67 0 . 24 4 . 76 0 . 25 5 . 07 0 . 255 4 .72 0 . 25 5 . 68 LLLLLLLLS 0 . 27 4 .67 0 . 32 4 . 67 If 0 . 38 4 . 14 0 . 37 4 . 35 0 . 37 4 .27 0 . 38 4 .02 0 . 38 4 . 44 0 . 13 3 .53 0 . 13 3 .77 0 . 13 4 .04 0 . 12 4 .97 0 . 13 4 . 44 0 . 38 3 . 80 0 . 37 3 . 94 0 . 41 3 . 83 0 . 38 4 . 19 0 . 37 4 . 10 +- 0 . 27 9 .06 0 . 27 9 . 27 30595955830 . 15 14 . 0 0 . 14 . 17 . 12 0 . 31 8 . 82 0 . 30 8 . 98 0 . 38 8 . 15 0 . 42 7 . 47 t 0 . 39 8 . 01 0 . 36 8 . 09 0 . 27 11 . 1 0 . 28 11. 50 HE 0 . 15 9 . 05 0 . 16 9 . 77 0 . 46 6 . 72 0 . 49 5 . 5 0 .49 6 . 6 0 . 18 8 . 50 0 . 22 8 . 49 0 . 33 7 . 57 0 . 29 8 . 20 0 . 29 9 . 04 N† 0 . 26 5 .67 0 . 3 * 9 . 79 * N† 0 . 43 5 . 36 0 . 38 * 8 . 01* 50 /50 0 .27 5 .8 0 .2786 . 12 0 .278 6 .52 0. 27 7. 24 0 .26 7 .04 J/ K † * 90 minute hydration data .

[ 0284 ] Several of the concept filmswere also extruded and TABLE 15 hydrated in a similar manner as described above. The extruded films showed similar hydration as the solution cast Salicylic Acid remaining in films after soaking 1 films. The Curcylic soaking solution shows the highest swell Average Average Theoretical Actual progressing in the following order : Curcylic TM Salicylic Average Salicylic Salicylic Curcylic > Niacinamide > Aloe > glycerin > DI water > Buffer . 40 in Acid in Solution acid in acid in Films formed from Ex . K take up between 1750 and 1200 % Example Solution , solution , uptake , film , film , of the initial weight in solution in the same order. The films Polymer Wt. % Wt. % gm /gmW t. % Wt. % are clear when swollen . A film formed from a 50 / 50 melt EX . F 1 .25 0 . 426 3. 98 0 . 34 1 . 42 EX . F 2. 5 0 . 849 3 . 84 0 .67 2 . 08 mixture of Ex . J and Ex . K also takes up solution in similar EX . F 5 1 . 843 3 .79 1 .45 2 . 82 order. The films are clear when swollen . EX . F 7 . 5 2 . 758 3 . 64 2 . 16 3 . 29 EX . F 10 3 .663 3 . 90 2 . 91 3 . 99 [ 0285 ] Comparison of the uptake show that the films Ex . K 1 . 25 0 . 426 10 .68 0 . 426 0 . 46 Ex. K 2. 5 0 . 849 10 . 42 0 . 849 0 . 89 formed from Ex . J , the 50 / 50 melt blend , and Ex . K swell at Ex . K 1 . 843 10 . 37 1 . 843 1 . 85 different rates , with Ex . J being consistently about 30 % of Ex . K 7 .5 2 .758 9 . 12 2 . 758 2 . 81 Ex . Kand approximately 60 % of the 50 / 50 melt blend across Ex. K 10 3 . 663 8 . 19 3 . 26 3 . 87 all solutions. The Ex. K films tend to take longer to reach equilibrium than the Ex . J films of the same thickness . [0288 ] It can be seen that both example polymers quickly [ 0286 ] The active agent remaining in films after soaking is absorb salicylic acid from the solution into the hydrated shown in TABLES 15 and 16 for salicylic acid and niaci polymer film . Ex F absorbs more salicylic acid from the namide . solution , selectively concentrating the active into the film . [ 0287] For the salicylic acid tests , extruded 0 . 24 to 0 . 28 [0289 ] For the niacinamide tests , extruded 0 .24 to 0 .28 mm films are hydrated in a solution containing CurcylicTM mm films are hydrated in a solution containing niacinamide / 40 ( 40 wt. % salicylic acid )/ 10 wt. % glycerin at room 10 wt. % glycerin at room temperature for 30 minutes. The temperature for 30 minutes . The theoretical wt. % of sali theoretical wt. % of niacinamide in the hydrated polymer cylic acid in the hydrated polymer film is calculated by the film is calculated by the gm / gm uptake of the solution and gm / gm uptake of the solution and the concentration of the the concentration of the niacinamide found in the hydrating salicylic acid found in the hydrating solution . solution . US 2017 /0319462 A1 Nov. 9 , 2017 30

TABLE 16 TABLE 17 Niacinamide remaining in films after soaking Soaking solution containing caffeine Average Average Average Ingredients (INCI ) % ( w / w ) Niacinamide Solution Theoretical Actual Example in solution , uptake , Niacinamide in Niacinamide in water 97 .60 Polymer Wt. % gm / gm film , Wt. % film , Wt. % caffeine 2 disodium EDTA 0 . 2 EX . F 1 . 08 % 4 . 59 0 . 89 % 1 . 15 % potassium sorbate 0 . 1 EX . F 3 . 13 % 4 . 96 2 .61 % 2 . 93 % sodium benzoate 0 . 1 EX . F 5 .93 % 5 . 28 4 . 98 % 4 .75 % citric acid cs to pH 4 EX . F 7 .67 % 5 . 76 6 . 54 % 5 . 47 % Ex . K 1 .08 % 10 . 53 0 .99 % 1. 03 % Ex . K 3 . 13 % 11. 11 2 . 87 % 2 .66 % Ex . K 5 .93 % 11 . 72 5 .46 % 4 .28 % [0295 ] The concentration of caffeine in the wet polymer Ex. K 7 .67 % 12. 03 7 .08 % 5 .15 % sample is measured by HPLC and is shown in TABLE 18 (HPLC : Shimadzu Scientific Prominence System ; Column: [ 0290 ] It is shown that both example polymers quickly Macherey -Nagel NucleosilTM 120 -5 C18 , LxI. D .: 250x4 .6 absorb niacinamide from the solution into the hydrated mm ; Carrier Phase : A : Water, B : Methanol (65 : 35 v / v ) ; polymer film . Oven Temperature : Room Temperature (approx . 22° C .) ; [ 0291] The results indicate that in Examples B and C , the Flow Rate : 1 mL /min . ; UV detection : 254 nm ). about 83 % PEG which is highly hydrophilic , gives the TPU greater water uptake characteristics . The hard segment TABLE 18 formed by H12MDI (DesmodurTM W ) and 1 ,4butanediol Final concentration of caffeine after 30 min soaking period provides the necessary processing and physical properties to Dry weight Wet weight the TPU . The TPU is soluble in 50 : 50 water: ethanol mixture Sample % caffeine ( w / w ) , at up to 15 wt. % solids. Thin films of 0 . 125 to 0 . 4 mm can (mg ) (mg ) vs . wet polymer be solvent cast on polyethylene substrates using this solution 20 . 0 259 . 5 2 . 59 17 . 0 217 . 4 2 .64 using a drawdown bar . The films dry in 8 - 12 hrs . and can be 18 .0 240 . 9 2 .63 easily peeled off from the substrate . The films when cut in 20 . 0 252 . 9 2 .63 precise dimensions and soaked in excess water pick up 19 . 0 235 . 9 2 .60 almost 100 % of water capacity within 15 - 30 mins , depend 24 . 0 319 . 0 2 . 57 ing on film thickness . The fully hydrated films are shown to retain physical strength and flexibility and are completely transparent. [0296 ] b ) Preparation of a Film Containing Dimethyl [0292 ] Example F is a blend of PEG - 8000 and PolyG methoxy Chromanyl Palmitate 55 - 56 in the soft segment. Poly G 55 - 56 enhances the [0297 ] Round samples ( 0 . 8 cm in diameter and 0 .305 mm “ cling " characteristics of the hydrated film on the skin as it thick ) weighing approximately 25 - 31 mg are prepared from loses water over time. Also , increased film flexibility is a film of Polymer K . The sample is immersed in a vessel obtained with the addition of PolyG 55 -56 . The amount of containing approximately 4 mL of a dimethylmethoxy chro PolyG 55 -56 decreases the amount of water absorbed by the manyl palmitate soaking solution ( TABLE 19 , all weight polymer and balances the hydrophobic hydrophilic proper percents on an undiluted basis ) for 30 minutes . The sample ties . As seen in TABLES 15 and 16 , the absorption of active is periodically checked to ensure that it remains totally is also related to the character of polyol B . Blends of immersed in the soaking solution and does not adhere to the polyurethanes ( Ex . B or Ex . F with Ex . K ) in a 50 : 50 ratio vessel surface . At the conclusion of the 30 min . soaking with are also found to have desirable characteristics. Adding period the sample is removed from the dimethylmethoxy a Carbopol® polymer in small quantities to the TPU solution chromanyl palmitate solution and re- weighed ( TABLE 20 ). is found to increase film strength while maintaining flex ibility and water uptake properties . The final sample diameter is about 2 . 0 cm . TABLE 19 Example 5 Soaking solution containing Liposomes of Dimethylmethoxy Chromanyl Palmitate Preparation of Simulated Face Masks and Transdermal Patches Ingredients (INCI ) % ( w / w ) water 62 . 2 [0293 ] a ) Preparation of a Film Containing Caffeine propanediol lecithin [0294 ] Simulated face masks are prepared from round ethylhexyl methoxycinnamate samples of about 0 . 8 cm diameter weighing approximately phenoxyethanol 2 . 6 15 - 25 mg from a film of polymer K . The sample is placed dimethylmethoxy chromanyl palmitate in approximately 5 mL of soaking solution ( TABLE 17 ) and inulin lauryl carbamate , water , ethyl pyrrolidone 0 . 2 suspended for 30 minutes in the solution . The sample is periodically checked to ensure it remains totally immersed in the solution . At the end of soaking time, the sample is [ 0298 ] The concentration of dimethylmethoxy chromanyl removed and reweighed ( final sample diameter, about 2 . 1 palmitate in the wet polymer is measured by HPLC ( TABLE cm ) . 20 ) . US 2017 /0319462 A1 Nov. 9 , 2017 31

TABLE 20 vessel surface . At the conclusion of the 90 min . soaking period the sample is removed from the acetyl hexapeptide Final concentration of dimethylmethoxy chromanyl palmitate in % versus wet polymer and weight change after soaking with a solution 37 solution and re -weighed . The final sample diameter is containing Liposomes of dimethylmethoxy chromanyl palmitate about 2 . 2 cm . Dry weight Wet weight % Dimethylmethoxy chromanyl TABLE 23 Sample (mg ) (mg ) palmitate ( w / w ) , vs. wet polymer Acetyl Hexapeptide - 37 Soaking solution 28 . 7 426 . 0 0 . 994 28 . 7 382 . 3 0 . 888 Ingredients ( INCI) % ( w / w ) 27. 2 358 . 7 1 .074 25 . 3 355 . 8 0 . 964 water 49 . 95 UAWNE 31. 0 446 . 6 1 . 009 butylene glycol 50 acetyl hexapeptide- 37 0 .05 [0299 ] c ) Preparation of a Film Containing Arbutin [0300 ] Simulated face masks are prepared from round [ 0304 ] The concentration of acetyl hexapeptide - 37 in the samples of a film of polymer K of about 0 . 8 cm diameter wet polymer is measured by HPLC ( TABLE 24 ) . with a total weight of about 25 -35 mg. The film is placed in approximately 4 mL of soaking solution containing arbutin TABLE 24 [ (2R , 3S ,4S , 5R ,6S ) - 2Hydroxymethyl- 6 ( 4hydroxyphenoxy ) Final concentration of Acetyl Hexapeptide -37 in % oxane - 3 , 4 ,5triol ] ( TABLE 21 ) and suspended for 30 minutes versus wet polymer and weight change after soaking in the solution . The sample is periodically checked to ensure with a solution containing Acetyl Hexapeptide - 37 that it remains totally immersed in the soaking solution and does not adhere to the vessel surface . At the conclusion of Dry weight Wet weight % Acetyl Hexapeptide - 37 ( w / w ), the 30 min . soaking period the sample is removed from the Sample (mg ) (mg ) vs . wet polymer arbutin solution and re- weighed . The final sample diameter 27 . 2 352 . 2 0 . 0401 25 . 9 344 . 1 0 . 0379 is about 2 . 2 cm . 26 . 2 341 . 0 0 .0365 26 . 3 350 . 6 0 .0367 TABLE 21 anmt Arbutin Soaking Solution [0305 ] e ) Preparation of a Film Containing Acetyl Hexa peptide - 8 Ingredients ( INCI) % (w / w ) [0306 ] A simulated face mask is prepared from a round water 95 . 6 piece of polymer K of about 0 . 8 cm diameter with a total arbutin 4 . weight of about 20 - 30 mg. The film is placed in approxi disodium EDTA 0 . 2 mately 5 mL of soaking solution containing acetyl hexapep potassium sorbate 0 . 1 tide - 8 obtained from Lipotec , S . A . ( TABLE 25 ) and sus sodium benzoate 0 . 1 pended for 90 minutes in the acetyl hexapeptide - 8 solution . sodium hydroxide cs to pH 5 . 5 The sample is checked to ensure it does not stick to the container or have surfaces exposed out of the solution . At the [0301 ] The concentration of Arbutin in the wet polymer is end of the 90 minute soaking time, the square is removed measured by HPLC (as described above ) ( TABLE 22 ) . and weighed again ( final piece diameter : 2 . 2 cm ). TABLE 22 TABLE 25 Acetyl Hexapeptide - 8 Soaking Solution Final concentration of Arbutin in % versus wet polymer and weight change after soaking with a solution containing Arbutin Ingredients ( INCI) % ( w / w ) Dry weight Wet weight % Arbutin ( w / w ) , water 99 . 65 Sample (mg ) (mg ) vs . wet polymer Phenonip TM (phenoxyethanol , methylparaben , butylparaben , ethylparaben, isobutylparaben , propylparaben ) 0 . 3 34 . 1 491. 7 1 .61 acetyl hexapeptide- 8 29 . 1 437 . 0 6142 0 .05 30 . 9 453 . 9 1 . 78 25 . 7 400 . 0 1 . 42 [ 0307 ] The concentration of acetyl hexapeptide - 8 in the auAWN 32 . 6 497 . 5 1 .61 33. 2 490 . 6 1 .45 wet polymer is measured by HPLC , as described above ( TABLE 26 ) . [0302 ] d ) Preparation of a Film Containing Acetyl Hexa peptide -37 TABLE 26 Final concentration of Acetyl Hexapeptide - 8 in % [0303 ] A simulated face mask is prepared from a round versus wet polymer and weight change after soaking piece of polymer K of about 0 . 8 cm diameter with a total with a solution containing Acetyl Hexapeptide - 8 weight of about 25 - 30 mg . The film is placed in approxi mately 5 mL of soaking solution containing acetyl hexapep Dry weight Wet weight % Acetyl Hexapeptide - 8 ( w / w ) , tide - 37 obtained from Lipotec , S . A . ( TABLE 23 ) and sus Sample (mg ) (mg ) vs . wet polymer pended for 90 minutes in the solution . The sample is 27 . 2 402 . 8 0 .0418 periodically checked to ensure that it remains totally NA 28 . 9 428 . 5 0 .0434 immersed in the soaking solution and does not adhere to the US 2017 /0319462 A1 Nov. 9 , 2017 32

TABLE 26 - continued TABLE 28 -continued Final concentration of Acetyl Hexapeptide - 8 in % Soaking Solution Containing a Dimethylmethoxy versus wet polymer and weight change after soaking Chromanyl Palmitate Emulsion with a solution containing Acetyl Hexapeptide - 8 Ingredients ( INCI) % (w /w ) Dry weight Wet weight % Acetyl Hexapeptide - 8 ( w / w ) , Sample (mg ) (mg ) vs . wet polymer dimethylmethoxy chromanyl palmitate phenoxyethanol 0 . 5 28 .0 407. 1 0 .0425 mt 23 . 4 338 . 1 0 .0420 [0312 ] g ) Preparation of a Film Containing Hyaluronic Acid 10308 ]. The same study is performed with a lower concen [0313 ] A square of polymer K of about 3x3 cm with a total tration of peptide , as follows. A round piece of the same weight of about 358 mg is placed in approximately 200 mL polymer of about 0 . 8 cm diameter with a total weight of of soaking solution containing hyaluronic acid ( TABLE 29 ) about 20 - 30 mg is placed in approximately 5 mL of soaking and suspended for 60 minutes in the solution . The piece is solution formed by a 1/ 5000 dilution with water of the checked to ensure it does not stick to the container or have soaking solution described in TABLE 25 and suspended for surfaces exposed out of the solution . At the end of soaking 90 minutes in the solution . The piece is checked to ensure it time, the square is removed and weighed again ( final size : does not stick to the container or have surfaces exposed out 12 . 3x12 . 3 cm , final weight: 4 . 164 g ) . of the solution . At the end of the soaking time, the square is removed from the low concentration acetyl hexapeptide - 8 TABLE 29 solution and weighed again ( final piece diameter : 2 .2 cm ). [ 0309 ] The concentration of acetyl hexapeptide -8 in the Hvaluronic Acid Soaking Solution wet polymer is measured by HPLC ( TABLE 27 ) . Ingredients (INCI ) % ( w / w ) water csp 100 TABLE 27 sodium benzoate 0 . 1 disodium EDTA 0 . 2 Final concentration of Acetyl Hexapeptide - 8 in % versus wet potassium sorbate 0 . 1 polymer and weight change after soaking with a dilution 1/ 5000 sodium hyaluronate in water of a solution containing Acetyl Hexapeptide - 8 Dry weight Wet weight % Acetyl Hexapeptide- 8 ( w / w ), [0314 ] h ) Preparation of Films Containing Diclofenac Sample (mg ) (mg ) vs . wet polymer Sodium 27. 3 355 . 8 0 . 0017 [ 0315 ] 3x3 cm squares are cut from extruded films of 3 23 . 6 320 . 2 0 . 0019 polymers F , K and N . The weight of each square is measured by a Mettler Toledo AE100 Balance . Thickness at 4 corners is measured using a Mitutoyo Digital Thickness Gauge , and [0310 ] f) Preparation of a Film Containing a Dimethyl the thickness of the square is expressed as the average of the methoxy Chromanyl Palmitate Fluid Emulsion four corners . The X and Y dimensions of each square are [ 0311 ] A square of polymer K of about 3x3 cm with a total recorded . A soaking solution is prepared according to weight about 444 mg is placed in approximately 200 mL of TABLE 30 . First , 10 % glycerin and 0 . 25 % Euxyl® PE9010 soaking emulsion containing dimethylmethoxy chromanyl ( a preservative ) obtained from Schulke & Mayr GmbH are palmitate (obtained from Lipotec, S .A .) ( TABLE 28 ) and added to deionized water, and the solution is stirred for 15 suspended for 60 minutes in the solution . The sample is minutes. Then , 0 . 84 % of Diclofenac Sodium [ 2 - ( 2 , 6 -dichlo periodically checked to ensure that it remains totally ranilino ) phenylacetic acid ) , obtained from Spectrum Chemi immersed in the soaking solution and does not adhere to the cal Mfg . Corp . is added and stirred for 1 hour or until clear. vessel surface . At the conclusion of the 60 minute soaking Diclofenac sodium is a nonsteroidal antiinflammatory drug time, the square is removed from the dimethylmethoxy (NSAID ) taken or applied to reduce inflammation and as an chromanyl palmitate soaking emulsion and re -weighed (fi analgesic reducing pain . The film squares are placed into the nal size: 9 . 27x9 . 27 cm , final weight: 3 . 909 g ) . soaking solution , and saturated for 30 minutes. The sample squares are then removed from the solution and blotted dry TABLE 28 with a paper towel. The samples are measured for weight, thickness and the X and Y dimensions. Uptake and dimen Soaking Solution Containing a Dimethylmethoxy Chromanyl Palmitate Emulsion sion change are calculated based on the measurement above . Ingredients ( INCI) % ( w / w ) TABLE 30 water csp 100 Soaking solution containing Diclofenac Sodium sodium hydroxide cs to pH 6 .94 disodium EDTA 0 . 2 INGREDIENT % IN WEIGHT potassium sorbate 0 . 1 acetyl hexapeptide - 8 0 .05 deionized water 88 .91 acrylates copolymer glycerin 10 acrylates /beheneth - 25 methacrylate copolymer 0 . 25 diclofenac sodium 0 .84 caprylic / capric triglyceride 33 Euxyl ® PE9010 0 . 25 methyl glucose dioleate 2 . 5 US 2017 /0319462 A1 Nov. 9 , 2017 33

[0316 ] The active agent remaining in films after soaking is [ 0323 ] Another Soaking Solution is prepared at pH 4 . 6 shown in TABLE 31 . ( TABLE 33 ). [ 0317] For the diclofenac sodium hydration , extruded 0 . 33 to 0 .37 mm films are hydrated in a solution containing 0 .84 [0324 ] The active agent remaining in films after soaking in wt. % diclofenac sodium /10 wt. % glycerin at room tem Lidocaine HCl solution is shown in TABLE 33 . perature for 30 minutes . The theoretical wt. % of diclofenac sodium in the hydrated polymer film is calculated by the TABLE 33 gm /gm uptake of the solution and the concentration of the diclofenac sodium found in the hydrating solution . Lidocaine Hydrochloride remaining in films after soaking Average Average Lidocaine Solution Theoretical Average Actual TABLE 31 Example HCl in uptake , Lidocaine HCl in Lidocaine HCI Diclofenac Sodium remaining in films after soaking Polymer solution , Wt. % gm / gm film , Wt. % in film , Wt. % 13 . 12 4 . 98 4 . 921 Diclofenac Average Average Average 4 . 29 4 . 98 4 . 947 Sodium Solution Theoretical Actual Diclofenac ALLZ Example Solution , uptake, Diclofenac Sodium Sodium in film , uuu 7 . 32 4 . 50 4 .600 Polymer Wt. % gm / gm in film , Wt. % Wt. % Ex . K 0 . 84 10 . 70 0 . 81 1 . 174 Ex . N 0 . 64 6 . 12 0 . 59 1 . 095 [0325 ] For the lidocaine hydrochloride hydration , films of 0 . 54 6 . 05 0 .46 Ex . K and F are extruded at 0 .28 to 0 .31 mm and are Ex . F 0 . 901 hydrated in a solution containing 5 wt. % lidocaine hydro [ 0318 ] It can be seen that all example polymers quickly chloride /10 wt. % glycerin (pH 6 . 4 ) at room temperature for absorb diclofenac sodium from the solutions into the 90 minutes. Films of Ex . N are extruded at 0 . 28 to 0 .31 mm hydrated polymer films. Films of K , N and F all absorb more and are hydrated in a solution containing 5 wt. % lidocaine diclofenac sodium from the hydrating solution , selectively hydrochloride / 10 wt. % glycerin (pH 4 .6 ) at room tempera concentrating the active into the film . Film K has a higher ture for 90 minutes . The theoretical wt. % of lidocaine gm / gm solution uptake than N and F , while lower ratio of hydrochloride in the hydrated polymer film is calculated by actual active amount to theoretical active amount. the gm / gm uptake of the solution and the concentration of [ 03191 i ) Preparation of Films Containing Lidocaine HC1 the lidocaine hydrochloride found in the hydrating solution . [0320 ] Lidocaine HCl stabilizes the neuronal membrane 103261. The results suggest that within 90 -minute hydra by inhibiting the ionic fluxes required for the initiation and tion , three example polymers absorb from the solution to conduction of impulses , thereby effecting local anesthetic form hydrated films and have different solution uptake action . It is incorporated into this formulation for pain relief. [ 0321 ] 3x3 cm squares are cut from extruded films of ability . Average solution uptake rank in an increasing order polymers of Ex . F , K and N and weighed and thickness is F < N < K . For all three example polymers , average actual measured as for Example 5h . A soaking solution is prepared active in film is equivalent to average theoretical active in according to TABLE 32 . First , a phosphate buffer is pre film , indicating they are not selectively concentrating the pared by adding monopotassium phosphate and sodium active into the film . hydroxide to deionized water, and the pH is measured ( 6 . 8 ) . Into the phosphate buffer , 10 % glycerin and 0 . 25 % Euxyl® [0327 ] j) Release of Actives from Films PE9010 are added . The solution is stirred for 15 minutes. [0328 ] Release of diclofenac sodium from example films Then 5 % Lidocaine HCl obtained from Spectrum Chemical is studied as follows. Six pieces of 3x3 cm diclofenac Mfg . Corp . is added and stirred for 15 minutes. The solution sodium - containing hydrated films of each kind are cut from is stirred for 30 minutes at room temperature before use . example films prepared in Example 5h . Each piece is placed [ 0322 ] The pH is measured ( 6 . 43 ) . The film squares are against a glass disc and retained with a 17 mesh Teflon placed into the soaking solution and saturated in the solution screen . Four Teflon clip /feet retain the assembly and position for 90 minutes . Then , the sample squares are removed from the assembly in a dissolution vessel . The transdermal patch the solution and blotted dry with a paper towel. The samples retainer is USP 724 compliant and purchased from Quality are measured for weight, thickness and the X and Y dimen Lab Accessories. USP dissolution apparatus 5 (paddle over sions. Uptake and dimension change are calculated based on disk ) is applied to test active release from the example films. the measurement above . VK7010 with 1000 ml vessels and stainless steel paddles ( obtained from Agilent ) are used to perform the release test TABLE 32 of diclofenac sodium loaded films. The dissolution vessels Soaking solution containing Lidocaine HCl (pH 6 . 4 ) are loaded with 800 ml of release medium (degassed phos phate buffered saline pH = 7 . 4 ) . The temperature of release INGREDIENT Wt. % medium is kept at 32 . 0 - 0 .5° C . throughout the test ( the Phosphate Buffer (pH 6 . 8 ) in 83 . 9799 temperature of the release medium is selected to reflect the Deionized Water physiological skin conditions ) . The paddle height is set to Monopotassium Phosphate 0 .6805 2 . 5 cm from the bottom of the vessel to the disc . The paddle Sodium Hydroxide 0 .0896 rotation speed is 50 rpm . The samples ( 10 ml) are withdrawn glycerin 10 Lidocaine HCl automatically by Varian VK 810 sampling station at time Euxyl ® PE9010 0 . 25 points 2 , 5 , 9 , 12 , 15 , 20 , 30 , 45 , 60 , 90 , and 120 min , and analyzed by Cary® 50 UV - Vis (Agilent , USA ) . TABLE 34 shows release of diclofenac sodium from the films. US 2017 /0319462 A1 Nov. 9 , 2017 34

TABLE 34 TABLE 37 -continued Release of diclofenac sodium from films Sample Example Release media % release at 120 mins 37 . 1 37. 2 37 . 3 37. 4 37 .5 Ex . K Phosphate buffered saline 72. 7 Theoretical wt. % 1 .0 % 2 . 5 % 5 . 0 % 7 . 0 % 8 .0 % Ex . N Phosphate buffered saline 77 . 4 menthol in dry film Ex . F Phosphate buffered saline 77. 3 Dry film Thickness (mm ) 0 .23 0 . 20 0 . 31 0 .27 0 . 30 [0329 ] Release of lidocaine HC1 from example films is [0334 ] c ) Menthol and Methyl Salicylate - Containing Cast studied as described above for the diclofenac sodium using ing Mixtures six pieces of 5x5 cm hydrated lidocaine HCl- containing [0335 ) Casting mixtures of solution B and a 20 wt. % films of each kind which are cut from example films menthol and 10 wt. % methyl salicylate stock solution prepared in Example 5i . TABLE 35 shows release of (Solution E ) are prepared as shown in TABLE 38 and stirred diclofenac sodium from the films. until homogeneous. Films are cast using a 2 in ( 5 .08 cm ) 125 mil ( 3 . 175 mm ) draw down bar on LLDPE sheets to give TABLE 35 clear, soft pliable films. The films are dried overnightand the Release of lidocaine HCl from films thickness measured . Example Release media % release at 30 mins TABLE 38 K Phosphate buffered saline 87. 3 F Phosphate buffered saline 79 . 5 Sample 38 .1 38. 2 38 .3 38 .4 38. 5 Solution B (polymer ) 64 62 60 59 58 Example 5 ( gm ) Solution E ( 20 wt. % 1 . 52 3 .03 6 . 17 7 . 85 Preparation of Simulated Face masks and menthol and 10 wt. % Transdermal Patches from Solvent Cast Films methyl salicylate ) ( gm ) polymer in casting 14 .72 14 . 26 13 .8 13. 57 13. 34 solution ( gm ) [0330 ] a ) Stock Solutions menthol in casting 0. 304 0 .606 0. 91 1. 234 1. 57 [ 0331 ] Polymer stock solutions (Solutions A , B , C ) are solution ( gm ) prepared using Ex . F and K polymers and stirred at room methyl salicylate in 0 . 152 0 . 303 0 .617 0 .785 temperature until all ingredients dissolved , according to casting solution ( gm ) Theoretical wt. % TABLE 36 below . menthol 2 % 4 % 6 % 8% 10 % Theoretical wt. % methyl 1 % 2 % 3 % 4 % 5 % TABLE 36 salicylate Dried film thickness 0 . 41 0 . 38 0 . 34 0 . 4 0 .31 Solution A Solution B Solution C ( mm ) Ingredients (Ex . F ) (Ex . F ) (Ex . K ) Polymer ( gm ) 135 288 .75 150 Ethanol ( gm ) 307 . 5 288 . 75 480 [ 0336 ] A stock solution containing Carbopol® 981 (Solu Water ( gm ) 307 . 5 172 . 5 123 tion F ) is prepared according to TABLE 39 . Wt. % polymer in Solution 18 23 19 . 92 TABLE 39 [ 0332] b ) Menthol- Containing Casting Mixtures Ingredient Solution F 103331 Casting mixtures of solution A and a 20 wt. % menthol stock solution ( Solution D ) are prepared as shown Polymer (Carbopol ® 981) ( gm ) Ethanol (gm ) 197 in TABLE 37 and stirred until homogeneous . Films are cast Water ( gm ) 197 using a 2 in ( 5 . 08 cm ) 100 mil ( 2 .54 mm ) draw down bar on Tris ( 30 % ) (gm ) 11 . 5 LLDPE sheets to give clear , soft pliable films. The films are Wt. % polymer 1 . 46 dried overnight and the thickness measured . [0337 ] Polymer Solution C ( 470 gm ) is mixed with Car TABLE 37 bopol® solution F ( 104 . 4 ) to give a Stock Solution G Sample containing 0 . 26 wt. % Carbopol® 981. 37. 1 37. 2 37. 3 37. 4 37 .5 [0338 ] d ) Menthol/ Carbopol - Containing Casting Mix tures Solution A 110 110 110 110 110 (18 wt. % polymer ) ( gm ) [0339 ] Casting mixtures of the Stock solution G ( contain Solution D ing polymer with Carbopol® 981 ) and the stock Solution D (20 wt. % menthol) ( gm ) 1 2. 5 5. 21 7. 45 8 .61 polymer in casting 19 . 8 19 . 8 19 . 8 19 . 8 19 . 8 (menthol ) at the indicated concentrations shown in TABLE solution (gm ) 40 are combined and stirred until homogeneous. Films are menthol in casting 0 .2 0. 5 1. 042 1. 49 1. 722 cast using a 2 in ( 5 .08 cm ) 125 mil ( 3 . 175 mm ) draw down solution ( gm ) bar on HDPE and dried overnight to give white films of the indicated thickness . US 2017 /0319462 A1 Nov. 9 , 2017 35

TABLE 40 TABLE 42 Sample Capsaicin Films 40 . 1 40. 2 40 .3 40 . 4 40 . 5 Sample Solution G ( 14 . 1 wt. % 110 110 110 110 110 143 . 43. 2 43 .3 Ex . K ) polymer (gm ) Solution A (18 wt. % polymer Ex . F ) 90 90 90 Solution D 0 .91 2 .45 5 .02 6 .46 7 .33 (ml ) (20 wt. % menthol ) ( gm ) Capsaicin stock solution H (ml ) 2 . 7 5 . 4 13. 5 polymer in casting Polymer in casting solution ( gm ) 16 . 2 16 . 2 16 . 2 solution (gm ) 15. 51 15. 51 15. 51 15. 51 15. 51 Capsaicin in casting solution ( gm ) 0 .00823 0 .016459 0 .041148 0 . 182 0 .49 1 .004 1 . 292 1 . 466 Theoretical wt. % capsaicin in film 0 .05 % 0 . 10 % 0 .25 % menthol in casting Dried film thickness (mm ) 0 . 23 0 . 24 0 . 25 solution (gm ) Measured Capsaicin in Film (wt . % ) 0 .0476 % 0 .0946 % 0 . 248 % Theoretical wt. % 1. 2 3 .1 6 .1 7. 7 8 .6 menthol in film Dried film thickness 0 . 40 0 .40 0 .55 0 . 24 0 . 34 [0346 ] g ) Wet Patch with Cover (mm ) [0347 ] A 12 mil ( 0 . 3 mm ) thick extruded film of Ex . K produced from Stock Solution C ( 19 . 92 wt. % polymer ) is hydrated in the Aloe Vera Clear formulation of Example 3 [ 0340 ] e ) Menthol and Methyl Salicylate/ Carbopol- Con for 30 minutes to produce a 2x5 cm hydrated patch . The taining Casting Mixtures patch is placed on the forearm and covered to hold it in place by an adhesive transparent film dressing TegadermTM ( 3M [ 0341] Casting mixtures of the Stock solution G (contain Company ) . The adhesive dressing is 4 in ( 10 . 16 cm ) by 4 .75 ing polymer with Carbopol® 981) and the stock Solution E in ( 12 . 065 cm ). The hydrated patch is held in place for 0 .5 (menthol and methyl salicylate ) at the indicated concentra hours and then removed demonstrating the utility of the tions shown in TABLE 41 are combined and stirred until hydrated patch as a dermal delivery system under a barrier homogeneous. Films are cast using a 2 in (5 .08 cm ) 125 mil film . ( 3 .175 mm ) draw down bar on HDPE and dried overnight to give white films. Example 6 TABLE 41 Skin Studies Sample [0348 ] a ) Skin Study with Caffeine [0349 ] A percutaneous absorption study is performed on 41. 1 42. 2 42 .3 42. 3 42. 3 pig skin test samples obtained from the back of domestic Solution G 110 110 110 110 110 pigs ( Sus domesticus ) weighing about 30 kg . The pig skin is ( 14 . 1 wt. Ex. K ) ( gm ) Solution E ( 20 wt. % 1. 86 3 . 72 5. 66 7. 66 9. 72 dermatomed to a thickness of about 500 microns and then menthol and 10 wt. % test discs having a diameter of 2 . 5 cm are sectioned from the methyl salicylate ) (gm ) dermatomed skin . An extruded polymer film of polymer K polymer in casting 15. 51 15 .51 15 .51 15. 51 15 .51 is loaded is with 1 . 8 % caffeine ( as described for Example solution (gm ) menthol in casting 0 . 372 0 .744 1 . 132 1 .532 1. 944 5A ). The loaded films are applied to the sample discs (in solution ( gm ) contact with the stratum corneum ) for 30 minutes. Different methyl salicylate in 0 . 186 0 . 372 0 .566 0. 766 0 .972 layers of the film treated skin ( stratum corneum , epidermis casting solution ( gm ) and dermis ) are separated , assayed and analyzed for the Theoretical wt. % 2 % 4 % 7 % 9 % 11 % quantity of caffeine and permeation into the respective menthol in film Theoretical wt. % 1 %% 2 %% 33 % 44 % 55 % layers of the skin . The quantitative analysis for caffeine and methyl salicylate in film is conducted by HPLC utilizing the instrumentation identi fied above . [0350 ) Additionally , the same solutions utilized to load the [ 0342 ] f ) Capsaicin - Containing Casting Mixtures polymer films are topically applied across the entire surface of the stratum corneum of comparative pig skin disc samples [ 0343] A stock solution ( Solution H ) is prepared from prepared as above . The topically treated discs are allowed to 0 .0762 gm Capsaicin in 25 ml ethanol (0 .003104 mg/ ul stand for 30 mins. before being assayed . The topically Capsaicin ). coated discs are used to compare the impact of the applica [ 0344 ] Stock Solution A (18 wt. % polymer ) is prepared tion of the active ingredient loaded polymer film with topical using the same weight percent of ingredients as used in application of active ingredients on dermal absorption . The TABLE 35 . OECD 428 methodology (OECD Guideline for the testing of chemicals : Skin absorption : in vitro Method , Paris , adopted [ 0345 ) Stock Solution A and stock Solution H are com 13 Apr. 2004 ) is followed for the experimental design . bined in the amounts shown in TABLE 42 and are blended [ 0351 ] The treated skin discs are placed between the upper until homogeneous. Films are cast using a 2 in ( 5 .08 cm ) 100 and the lower chambers of a Franz diffusion cell (Per mil ( 2 . 54 mm ) 2 draw down bar on LDPE sheets to give meGear, Inc . , Hellertown , Pa . ) with a contact area of 1 . 77 clear soft pliable films. The films are dried overnight and the cm². The lower chamber contained the receptor fluid ( PBS dried thickness measured . Capsaicin content was measured solution , Sigma- Aldrich Co . LLC ) . The integrity of the skin by HPLC . is evaluated by measuring the transepidermal water loss US 2017 /0319462 A1 Nov. 9 , 2017 36

( TEWL ) . Only the sample discs with a TEWL value lower [0362 ] The results of the Franz cell studies suggest that the than 15 g /m²hr . are used in the experiment. A value higher exemplary polymer hydrogel increases , by more than 3 than 15 g / m hr. could indicate the presence of a hole in the times , the amount of caffeine found in the skin layers as biopsied skin sample . The receptor fluid is collected, and the compared to the same caffeine amount applied in a single bottom of the skin is washed with distilled water and added lotion after only 30 minutes of application ( see FIG . 6 ) . to the receptor fluid to a final volume of 10 mL with [0363 ] Additionally , another hydrogel polymer film which extraction solution (H20 , pH 3 . 0 ) . The collected receptor one (with a different thickness ) is tested against a typical fluid is analyzed by HPLC as described above. No caffeine benchmark mask made of Biocellulose in order to compare was present in the analyzed fluids indicating that the active caffeine permeation . Results comparing the exemplary poly remained in the skin samples . mer film versus Biocellulose suggest that the polymer 10352 ] The quantities of caffeine that permeated into each hydrogel increases by more than 2 times the amount of of the three different layers of the skin samples ( stratum caffeine found in the skin layers compared to the same corneum , epidermis and dermis) are collected separately as caffeine amount applied in Biocellulose after only 30 min follows. To remove residual formulation remaining on the utes of application (FIG . 7 ) . surface of the stratum corneum of the skin samples, the skin [0364 ] Results relating to microbiological risk , using surface is washed once with a surfactant solution ( 0 . 5 wt. % analysis by water activity measurements are shown in sodium dodecyl sulfate in water ) and twice with pure water. TABLE 43 . The stratum corneum of the treated skin samples is adhe sively separated from the underlying layers by applying 10 TABLE 44 adhesive strips on the skin surface at a constant pressure ( 100 g / cm²) for 5 seconds. In order to minimize the damage Comparison of microbiological analysis of the exemplary experimental on the dermoepidermal junction , the strips are applied and polymer film vs Biocellulose removed in different directions (rotations of) 90° . All of the Exp . Polymer Biocellulose strips ( containing the adhered stratum corneum cells ) are placed in 2 mL of extraction solution . Temperature (° C .) 24 23 . 5 Relative Humidity ( % ) 51 . 8 54 . 5 [ 0353] The epidermis is separated from the dermis by Water activity 0 . 48 0 . 55 heating the remaining skin samples at 80° C . for approxi mately 5 seconds. The remaining separated epidermis layer also is placed in 1 mL of extraction solution . The remaining [0365 ] According to ISO 11930 “ Evaluation of antimicro dermis layer is cut into small pieces and placed in 1 mL of bial protection of a cosmetic product" , when a cosmetic extraction solution . The exacted actives for each of the skin product is a formulation intrinsically hostile to microbial layers are assayed by HPLC described above to determine growth and it needs specific manufacturing conditions, the quantity of active that permeated into each layer of the packaging type and /or condition for use , the ISO 29621 pig skin test sample . “ Guidelines for the risk assessment and identification of [0354 ] Additionally , a caffeine solution with the same microbiologically low - risk products ” are applied . According concentration of caffeine is used to compare the impact of to these guidelines, if the water activity (WA ) is below 0 . 5 , the polymer on dermal absorption . the product is hostile to microbial growth . In this case , there [ 0355 ] Additionally , the water activity of the dried poly is no need of preservatives in the dried polymer to avoid mer is studied in order to analyze possible microbiological microbiological contamination . risks . The water activity is the partial vapor pressure of water [0366 ] During the sensory evaluation , the panel noticed in a substance divided by the standard state partial vapor face masks made from polymer hydrogel offered a more pressure of water. When the value is lower there is less risk pleasing experience than the classic face mask sheets due to of microbiological contamination . better handling resistance , better aesthetics and softness , [0356 ] In parallel , a sensory evaluation was conducted by higher transparency , and absence of residue upon removal. a panel of Asian participants on several key cosmetic [0367 ] b ) Skin Study with Dimethylmethoxy Chromanyl attributes to assess the robustness and in - use sensory expe Palmitate rience offered by the polymer hydrogel film compared to [0368 ] The same experiment is performed as in Example classic facial mask sheets . 6a , but in this case using a lipophilic whitening ingredient [ 03571. The polymer loaded with caffeine allows applying (dimethylmethoxy chromanyl palmitate ) . In this case , two a very high concentration of caffeine , much more than that different experiments are performed with the same concen specified in the OECD 428 guideline . For that reason , four tration of dimethylmethoxy chromanyl palmitate . different experiments are done with the same concentration [0369 ] 1 . 2 % Dimethylmethoxy chromanyl palmitate in of caffeine . the polymer hydrogel, applied for 30 minutes ( 387 mg [0358 ] 1. 1. 8 % caffeine in the experimental polymer total applied ). film , applied for 30 minutes (50 mg total caffeine [ 0370 ] 2 . 2 % Dimethylmethoxy chromanyl palmitate applied ) . encapsulated in liposomes , applied for 30 minutes ( 387 [0359 ] 2 . 1 . 8 % caffeine in water solution , applied for 30 mg total applied ) . minutes (50 mg total caffeine applied ) . [0371 ] In this study, dimethylmethoxy chromanyl palmi [0360 ] 3 . 1 . 8 % caffeine in water solution , applied for 30 tate penetrates much more from the film polymer than from minutes under OECD 428 amounts (0 . 3 mg total caf the liposomes (FIG . 8 ) . Results are even better than for the feine applied ) . hydrophilic active ( caffeine ) , obtaining around ten times [0361 ] 4 . 1 . 8 % caffeine in water solution , applied for 24 more skin permeation than the active inside the liposome, hours under OECD 428 amounts (0 . 3 mg total caffeine which is a conventional delivery system to increase skin applied ) . permeation . US 2017 /0319462 A1 Nov. 9 , 2017 37

[0372 ] c ) Skin Study with Salicylic Acid [0384 ] 2 % salicylic acid in hydroalcoholic solution , [0373 ] A skin permeation study is performed on der applied for 30 minutes . matomed human cadaver skin , thickness ranging 400 - 1500 [0385 ) The results of the skin permeation study suggest um , surface area of 0 .25 ft ? ( 0 .093 m²) obtained from The that the exemplary polymer K improves salicylic acid per New York Firefighters Skin Bank . Skin is cut into about 2 meation in the stratum corneum , compared to hydroalco cmº pieces with sterilized scissors , and soaked in filtered pH holic solution which contains 10 % ethanol to increase skin 7 .4 phosphate buffered saline (PBS ) at room temperature for permeation ( see FIG . 9 ) . 15 - 30 minutes to allow thawing. Then , a Franz diffusion cell [0386 ) d ) Skin Study with Lidocaine HCl is assembled with thawed skin , connected to a circulating [0387 ] Skin preparation and assembling of the Franz dif water bath system , and equilibrated to 37° C . for at least fusion cell was performed as for the skin study with salicylic 15 - 30 minutes . acid . [0374 ] A circular area of a drug loaded film is cut using a [0388 ] The loaded films or commercial patch are applied biopsy punch that fits 0 .64 cm2 area of skin . The drug loaded to the skin ( in contact with the stratum corneum ) for 24 film is prepared as described in TABLE 15 . The circular hours . 300 ul of the receptor compartment media is with pieces are applied as the donor on the skin with aid of a glass drawn at 0 . 5 , 1 , 2 , 4 , 8 and 24 hours for HPLC analysis , and rod . After preparation , the donor compartment is left non replaced with 300 ul of fresh PBS . At 24 hours , the donor occluded exposing to air . In addition , 3 to 5 pieces of these compartment ( film or patch sample ) is removed and col circular films are analyzed for salicylic acid content by lected in a centrifuge tube . A Q - tip soaked with PBS is used HPLC . to gently wipe the skin to remove excess formulation and is collected along with the sample film or patch . Samples are [0375 ] For the solution samples , a certain volume of the lyophilized and dispersed in 10 mlmethanol and stored at 4° solution that contains a similar salicylic acid content to the C . until HPLC analysis. circular film pieces is applied on the skin using pipet . Five [0389 ] The area of the skin is that has been in contact with replicates per sample are performed . the formulation is further cut into small pieces with sterile [ 0376 ] The loaded films or solutions are applied to the skin scissors . The small pieces of skin are collected in micro ( in contact with the stratum corneum ) for 30 minutes . Then homogenizer tubes and 1 mlof methanol added to each tube . film or sample is removed and collected in centrifuge tube . Samples are stored in the fridge until being subjected to A Q -tip soaked with PBS is used to gently wipe the skin to homogenization using the micro tube homogenizer . Then , remove excess formulation and is collected along with the the samples are centrifuged and the supernatant is collected film . Sample will further be storage at 4° C . in HPLC vials . The samples are stored at 4° C . until HPLC [0377 ] To collect stratum corneum , 3M Scotch Book Tape analysis. 845 is cut into 1 . 5 cm² pieces for tape stripping . The [0390 ] Polymer K and D loaded with lidocaine HCl are PBS -washed skin is mounted on aluminum foil plus a tested in a skin permeation study , and one commercial patch support using 4 pins ( one on each corner) . The skin sample is tested to compare to the experimental films: is sandwiched between a pre - cut plastic sheet with circular [0391 ] 5 % lidocaine HCl in polymer film K area of 0 .64 cm - and aluminum foil. The skin is stripped 20 [0392 ] 5 % lidocaine HCl in polymer film D times with 1 .5 cm² 3M Scotch Book Tape 845 by pressing [0393 ] 5 % lidocaine base in the commercial patch gently with a spatula to the area that was exposed to the [0394 ] The results of the skin permeation study suggest formulation . The 20 tapes are pooled into one sample and that the exemplary polymer K increases lidocaine HC1 extracted with 10 ml of methanol in a 37° C . water bath penetration in skin , 2 times higher than that from commer overnight. Then the samples are stored at 4° C . until HPLC cial patch in the first 8 hours (see FIG . 10 ) . Film D also analysis . induces higher drug penetration than commercial patch [0378 ] After tape stripping , the area of the viable epider within 24 hour application , and shows higher penetration mis and dermis that has been in contact with the formulation percentage than Film Kin the long term ( 16 - 24 hours ) . is further cut into small pieces with sterile scissors . The [0395 ] e ) Skin Study with Diclofenac Sodium small pieces of skin are collected in micro - homogenizer [0396 ] Skin preparation and assembling of the Franz dif tubes. Samples are incubated in a 37° C . water bath over fusion cell was performed as for the skin study with salicylic night. The samples are then subjected to homogenization acid . using a micro tube homogenizer. The samples are then [0397 ] Study time and sampling time points follow the centrifuged and the supernatant is collected in HPLC vials . details in skin study with lidocaine HCl. The samples are stored at 4° C . until HPLC analysis . [0398 ] Sample preparation for HPLC analysis is per [ 0379 ] All of the 5 mL of receptor compartment is col formed as for the skin study with lidocaine HC1. lected into a 15 mL polypropylene tube , lyophilized and [0399 ] Polymer K and L loaded with diclofenac sodium stored at 4° C . until HPLC analysis . are tested in skin permeation study , and 1 commercial patch [0380 ] Polymer K , D and L loaded with salicylic acid are is tested to compare to the experimental films: tested in the skin permeation study , and a hydroalcoholic [ 0400 ] 1 % diclofenac sodium in the experimental polymer solution with 10 % ethanol is tested as a reference to deter film K mine any improved permeation effect by the films: [ 0401 ] 1 % diclofenac sodium in the experimental polymer [0381 ] 2 % salicylic acid in the experimental polymer film L film K , applied for 30 minutes . [0402 ] 1 . 3 % diclofenac epolamine in the commercial [0382 ] 4 % salicylic acid in the experimental polymer patch film D , applied for 30 minutes . [ 0403 ] The results of the skin permeation study suggest [0383 ] 2 % salicylic acid in the experimental polymer that the exemplary polymers K and L dramatically increase film L , applied for 30 minutes. diclofenac sodium penetration in skin , which compared to US 2017 /0319462 A1 Nov. 9 , 2017 38 commercial patch , allow for earlier drug detection in skin composition referred to herein should be interpreted as being and four times higher drug permeation percentage at 24 hour a commercial grade materialwhich may contain the isomers , ( see FIG . 11 ) . by -products , derivatives , and other such materials which are normally understood to be present in the commercial grade . [0404 ] These studies demonstrate facial masks made from However, the amount of each chemical component is pre the exemplary polymer hydrogels improve skin penetration sented exclusive of any solvent or diluent oil , which may be of active ingredients for better performance or formulation customarily present in the commercial material, unless oth cost optimization . Due to the strong mechanical properties , erwise indicated . It is to be understood that the upper and high clarity , better sensory perception , and being not con lower amount, range , and ratio limits set forth herein may be ducive to microbial growth of bacteria , the results suggest independently combined . Similarly , the ranges and amounts that the exemplary film is highly suited to facial masks . for each element of the invention may be used together with [0405 ] Each of the documents referred to above is incor ranges or amounts for any of the other elements . porated herein by reference in its entirety , as is the priority [ 0406 It will be appreciated that variants of the above document and all related applications, if any, of which this disclosed and other features and functions , or alternatives application claims the benefit . Except in the Examples , or thereof, may be combined into many other different systems where otherwise explicitly indicated , all numerical quanti or applications . Various presently unforeseen or unantici ties in this description specifying amounts of materials , pated alternatives , modifications, variations or improve reaction conditions, molecular weights , number of carbon ments therein may be subsequently made by those skilled in atoms, and the like , are to be understood as modified by the the art which are also intended to be encompassed by the word " about. ” Unless otherwise indicated , each chemical or following claims.

SEQUENCE LISTING

< 160 > NUMBER OF SEQ ID NOS : 62 < 210 > SEQ ID NO 1 < 211 > LENGTH : 37 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 1 Glu Ile Asp Thr Gin Asn Arg Gin Ile Asp Arg Ile Met Glu Lys Ala 10 15 Asp Ser Asn Lys Thr Arg Ile Asp Glu Ala Asn Gln Arg Ala Thr Lys 20 25 Asn Gin Arg 30Ala Thr Lys Met Leu Gly Ser Ser 35

< 210 > SEQ ID NO 2 < 211 > LENGTH : 20 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 2 Glu Ile Asp Thr Gin Asn Arg Gin Ile Asp Arg Ile Met Glu Lys Ala 10 15 Asp Ser Asn Lys 20

< 210 > SEQ ID NO 3 A< 211 > LENGTH : 26 A< 212 > TYPE : PRT A< 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 3 Ile Met Glu Lys Ala Asp Ser Asn Lys Thr Arg Ile Asp Glu Ala Asn 1 10 15 Gin Arg Ala Thr Lys Met Leu Gly Ser Gly 20 25

< 210 > SEQ ID NO 4 < 211 > LENGTH : 20 US 2017 /0319462 A1 Nov. 9 , 2017 39

- continued < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 4 Ser Asn Lys Thr Arg Ile Asp Glu Ala Asn Gin Arg Ala Thr Lys Met 10 15 Leu Gly Ser Gly 20

< 210 > SEQ ID NO 5 < 211 > LENGTH : 16 < 212 > TYPE : PRT AAN 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 5 Gin Asn Arg Gin Ile Asp Arg Ile Met Glu Lys Ala Asp Ser Asn Lys 55 10 15

< 210 > SEQ ID NO 6 < 211 > LENGTH : 6 < 212 > TYPE : PRT ? 13 > ORGANISM : Artificial Sequence

? 20 > FEATURE : ?< NNN223 > OTHER INFORMATION : Synthesized peptide < 400 > SEQUENCE : 6 Glu Glu Met Gin Arg Arg 1

< 210 > SEQ ID NO 7 ?.< 211 > LENGTH : 13

? < .212 > TYPE : PRT

? ?< 213ME??? > ORGANISM : Artificial Sequence ? ? 20 > FEATURE : ?< ?223NNEPE > OTHER INFORMATION : Synthetic peptide < 400 > SEQUENCE : 7 Glu Leu Glu Glu Met Gln Ara Ara Ala Asp Gin Leu Ala 5 10

< 210 > SEQ ID NO 8 < 211 > LENGTH : 6 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : 21 > NAME / KEY : X 22 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is any amino acid or absent < 400 > SEQUENCE : 8 Xaa Ile Lys Val Ala Val

< 210 > SEQ ID NO 9 < 211 > LENGTH : 205 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 9 Met Ala Glu Asp Ala Asp Met Arg Asn Glu Leu Glu Glu Met Gln Arg 10 15 US 2017/ 03 19462 Al Nov . 9 , 2017 40

- continued | TEAla Asp Gin Leu Ala 1Asp Glu Ser Leu Glu Ser Thr |Arg Arg Met Leu 20 25 &J Gin Leu Val Glu Glu Ser Lys Asp Ala Gly Ile Arg Thr Leu Val Met 35 40

Leu Asp Glu Gin Gly Glu Gin Leu Glu Arg Ile JGlu Glu Gly Met Asp

32 SGin Ile Asn Lys Asp Met Lys Glu Ala Glu Lys Asn Leu 3?Thr Asp Leu ???p? Gly Lys Phe Cys Gly Leu Cys Val Cys &Pro Cys Asn Leu Leu Lys Ser |SEEA 95 Ser Asp Ala Tyr Lys Lys Ala Trp Gly Asn Asn Gin Asp Gly Val Val 100 105 Ala Ser Gln Pro TJ°Ala Ara Val Val Asp Glu Arq Glu Gln Met Ala Ile 115 120 Ser Gly Gly Phe Ile RArg Arg Val Thr Asn Asp Ala Arg Glu mmmmAsn Glu Met Asp Glu Asn Leu Glu Gin Val Ser Gly ??????Ile °Ile Gly Asn Leu Arg mmm 155 His Met Ala Leu Asp Met Gly Asn Glu Ile Asp ?Thr Gln Asn Arg Gln 175 Ile Asp Arg Ile Met Glu Lys Ala Asp Ser Asn Lys Thr Arg Ile Asp 180 185

Glu Ala Asn Gin Arg Ala Thr Lys Met Leug Gly Ser Gly 195 mmmmmm200 < 210 > SEQ ID NO 10 < 211 > LENGTH : 21 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 10 Met Ala Glu Asp Ala Asp Met Arg Asn Glu Leu Glu Glu Met Gln Arg 10 15 Arg Ala Asp Gin Leu 20

< 210 > SEQ ID No 11 11 > LENGTH : 23 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 11 Ala Asp Glu Ser Leu Glu Ser Thr Arg Arg Met Leu Gin Leu Val Glu 10 15 Glu Ser Lys Asp Ala Gly Ile 20

< 210 > SEQ ID NO 12 < 211 > LENGTH : 13 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 12 Glu Leu Glu Glu Met Gln Arg Arq Ala Asp Gln Leu Ala N 0 10 US 2017 /0319462 A1 Nov. 9 , 2017

- continued < 210 > SEQ ID NO 13 < 211 > LENGTH : 12 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 13 Glu Leu Glu Glu Met Gin Arg Arg Ala Asp Gin Leu 10

< 210 > SEQ ID NO 14 < 211 > LENGTH : 11 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens

< 400 > SEQUENCE : 14 Glu Leu Glu Glu Met Gin Arg Arg Ala Asp Gin 1 10

< 210 > SEQ ID NO 15 < 211 > LENGTH : 10 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 15 Glu Leu Glu Glu Met Gin Arg Arg Ala Asp 1 5 10

< 210 > SEQ ID NO 16 < 211 > LENGTH : 9 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 16 Glu Leu Glu Glu Met Gin Arg Arg Ala

< 210 > SEQ ID NO 17 < 211 > LENGTH : 8 ?M 12 > TYPE : PRT ?M 13 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 17 Glu Leu Glu Glu Met Gin Arg Arg

< 210 > SEQ ID NO 18 < 211 > LENGTH : 11 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 18 Leu Glu Glu Met Gin Arg Arg Ala Asp Gin Leu 10

< 210 > SEQ ID NO 19 < 211 > LENGTH : 10 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 19 Leu Glu Glu Met Gin Arg Arg Ala Asp Gln 1 10 US 2017 /0319462 A1 Nov. 9 , 2017

- continued

< 210 > SEQ ID NO 20 < 211 > LENGTH : 9 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 20 Leu Glu Glu Met Gln Arg Arg Ala Asp

< 210 > SEQ ID NO 21 < 211 > LENGTH : 8 < 212 > TYPE : PRT V 2132 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 21 Leu Glu Glu Met Gln Arg Arg Ala 1 5

< 210 > SEQ ID NO 22 < 211 > LENGTH : 7 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 22 Leu Glu Glu Met Gin Arg Arg

< 210 > SEQ ID NO 23 < 211 > LENGTH : 10 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 23 Glu Glu Met Gin Arg Arg Ala Asp Gin Leu 10

< 210 > SEQ ID NO 24 < 211 > LENGTH : 9 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 24 Glu Glu Met Gin Arg Arg Ala Asp Gin

< 210 > SEQ ID NO 25 < 211 > LENGTH : 8 < 212 > TYPE : PRT VVV 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 25 Glu Glu Met Gin Arg Arg Ala Asp

< 210 > SEQ ID NO 26 < 211 > LENGTH : 7 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 26 Glu Glu Met Gin Arg Arg Ala US 2017 /0319462 A1 Nov. 9 , 2017 43

- continued

< 210 > SEQ ID NO 27 < 211 > LENGTH : 6 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 27 Glu Glu Met Gln Arg Arg

?< 210 > SEQ ID NO 28 < 211 > LENGTH : 13 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 28 Leu Glu Ser Thr Arg Arg Met Leu Gin Leu Val Glu Glu 10

< 210 > SEQ ID NO 29 < 211 > LENGTH : 12 < 212 > TYPE : PRT V 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 29 Asn Lys Asp Met Lys Glu Ala Glu Lys Asn Leu Thr 10

< 210 > SEQ ID NO 30 < 211 > LENGTH : 6 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 30 Lys Asn Leu Thr Asp Leu

< 210 > SEQ ID NO 31 < 211 > LENGTH : 26 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 31 Ile Met Glu Lys Ala Asp Ser Thr Arg Ile Asp Glu Ala Asp 10 15 Gin Arg Ala Thr Lys Met Leu Gly Ser Gly 20 25

< 210 > SEQ ID NO 32 < 211 > LENGTH : 20 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 32 Ser Asn Lys Thr Arg Ile Asp Glu Ala Asn Gin Arg Ala Thr Lys Met 10 15 Leu Gly Ser Gly 20

< 210 > SEQ ID NO 33 < 211 > LENGTH : 17 US 2017 /0319462 A1 Nov. 9 , 2017 44

- continued < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 33 Thr Arg Ile Asp Glu Ala Asn Gin Arg Ala Thr Lys Met Leu Gly Ser 10 15 Gly

< 210 > SEQ ID NO 34 < 211 > LENGTH : 14 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens

< 400 > SEQUENCE : 34 Asp Glu Ala Asn Gin Arg Ala Thr Lys Met Leu Gly Ser Gly 10

< 210 > SEQ ID NO 35 < 211 > LENGTH : 11 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 35 Asn Gin Arg Ala Thr Lys Met Leu Gly Ser Gly 10

< 210 > SEQ ID NO 36 < 211 > LENGTH : 10 < 212 > TYPE : PRT < 213 > ORGANISM : Homo sapiens < 400 > SEQUENCE : 36 Gln Arg Ala Thr Lys Met Leu Gly Ser Gly 10

< 210 > SEQ ID NO 37 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : synthetic peptide A 20 > FEATURE : < 221 > NAME / KEY : misc _ feature A LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is His or Asn < 220 > FEATURE : A 221 > NAME / KEY : misc _ feature A 22 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X at 3 is His or Arg < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature A 22 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X at 4 is Cit < 400 > SEQUENCE : 37 Arg Xaa Xaa Xaa

< 210 > SEQ ID NO 38 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic Peptide < 20 > FEATURE : US 2017 /0319462 A1 Nov. 9 , 2017 45

- continued < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) A 223 > OTHER INFORMATION : X at 4 is Cit < 400 > SEQUENCE : 38 Arg His His Xaa

< 210 > SEO ID NO 39 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : 21 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is Cit < 400 > SEQUENCE : 39 Arg Asn Arg Xaa

< 210 > SEQ ID NO 40 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X at 1 is Lys , Orn , Dab , Dpr , Agl , 3 , 4 - dehydrolysine , or 4 , 5 - dehydrolysine < 220 > FEATURE : A 21 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is Ala A FEATURE : A 21 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) A 3 > OTHER INFORMATION : X at 3 is Asp , Ala , Asn , Glu , or Pro < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223N > OTHER INFORMATION : X at 4 is His < 400 > SEQUENCE : 40 Xaa Xaa Xaa Xaa

< 210 > SEQ ID NO 41 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : A< 223 > OTHER INFORMATION : Synthetic peptide A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 1 ) . . ( 1 ) A< 223 > OTHER INFORMATION : X at 1 is L - Dpr A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 2 ) . . ( 2 ) A< 223 > OTHER INFORMATION : X at 2 is D - Ala A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : 13 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X at 3 is L - Ala A 20 > FEATURE : US 2017 /0319462 A1 Nov. 9 , 2017 46

- continued < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) A 223 > OTHER INFORMATION : X at 4 is L - His

< 400 > SEQUENCE : 41 Xaa Xaa Xaa Xaa y

< 210 > SEQ ID NO 42 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : A 21 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X at 1 is L - Dpr < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature A 2 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is D - Ala A 20 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X at 3 is L - Pro < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X at 4 is L -His < 400 > SEQUENCE : 42 ??? ??? ??? ???

H < 210 > SEQ ID NO 43 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence 20 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : 1 > NAME / KEY : misc feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X at 1 is L - Dpr < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) OTHER INFORMATION : X at 2 is L - Ala < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X at 3 is L - Pro < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature 2 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X at 4 is L -His < 400 > SEQUENCE : 43 ??? ??? ??? ??? 1

< 210 > SEQ ID NO 44 < 211 > LENGTH : 7 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : 2 21 > NAME / KEY : misc _ feature US 2017 /0319462 A1 Nov. 9 , 2017 47

- continued < 222 > LOCATION : ( 1 ) . . ( 1 ) A 3 > OTHER INFORMATION : X at 1 is any amino acid or is absent < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is any amino acid or is absent A 20 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) A 3 > OTHER INFORMATION : X at 3 is Ara , Pha , Nle , or absent < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) A 223 > OTHER INFORMATION : X at 4 is Ala , Phg , Cit , or Nle < 220 > FEATURE : A 1 > NAME / KEY : misc feature < 222 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X at 5 is Trp , Val , or Tyr < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X at 6 is Phg or Gly < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 7 ) . . ( 7 ) < 223 > OTHER INFORMATION : X at 7 is any amino acid or absent < 400 > SEQUENCE : 44 ??? ??? ??? ??? ??? ??? ???

< 210 > SEQ ID NO 45 < 211 > LENGTH : 5 < 212 > TYPE : PRT A 13 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic Peptide A 0 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X at 1 is L - Arg < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is L - Nle < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X at 3 is L - Phg or D - Phg < 220 > FEATURE : A 1 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X at 4 is L - Tyr < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature A 22 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X at 5 is L - Phg or D - Phg < 400 > SEQUENCE : 45 Xaa Xaa Xaa Xaa Xaa

< 210 > SEQ ID NO 46 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220N > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X at 1 is L - Arg , L -Nle , or absent US 2017 /0319462 A1 Nov. 9 , 2017 48

- continued < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is L - Phg or D - Phg < 220 > FEATURE : 1 > NAME / KEY : misc _ feature 22 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X at 3 is L - Tyr < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X at 4 is L - Phg or D - Phg < 400 > SEQUENCE : 46 Xaa Xaa Xaa Xaa

< 210 > SEO ID NO 47 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X at 1 is L - Arg < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) A 23 > OTHER INFORMATION : X at 2 is L - Phg or D - Phg < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X at 3 is L - Val < 220 > FEATURE : A NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) A 23 > OTHER INFORMATION : X at 4 is L - Phg , D - Phg , or L -Gly < 400 > SEQUENCE : 47 ??? ??? ??? ??? 2

< 210 > SEQ ID NO 48 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) 3 > OTHER INFORMATION : X at 1 is L - Phg or D - Phg < 220 > FEATURE : < 221 > NAME / KEY : misc feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X at 2 is L - Phg or D - Phg < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) A 23 > OTHER INFORMATION : X at 3 is L - Trp < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X at 4 is L - Phg or D - Phg < 400 > SEQUENCE : 48 Xaa Xaa Xaa Xaa 1 US 2017 /0319462 A1 Nov. 9 , 2017 49

- continued

H

A< 210 > SEQ ID NO 49 A< 211 > LENGTH : 10 A< 212 > TYPE : PRT A< 213 > ORGANISM : Artificial Sequence A< 220 > FEATURE : A< 223 > OTHER INFORMATION : Synthetic Peptide A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) A< 223 > OTHER INFORMATION : X at 1 is any amino acid or absent A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 2 ) . . ( 2 ) A OTHER INFORMATION : X at 2 is any amino acid or absent A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 3 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X at 3 is Asp , Glu , or Pro A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A A LOCATION : ( 4 ) . . ( 4 ) A > OTHER INFORMATION : X at 4 is Asp A< 220 > FEATURE : A 1 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 5 ) . . ( 5 ) A< 223 > OTHER INFORMATION : X at 5 is Tyr or Arg A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 6 ) . . ( 6 ) A 3 > OTHER INFORMATION : X at 6 is Phe or Tyr A 20 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 7 ) . . ( 7 ) A< 223 > OTHER INFORMATION : X at 7 is Arg or Lys A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 8 ) . . ( 8 ) A< 223 > OTHER INFORMATION : X at 8 is Leu or Met A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 9 ) . . ( 9 ) A< 223 > OTHER INFORMATION : X at 9 is any amino acid or absent A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 10 ) . . ( 10 ) A< 223 > OTHER INFORMATION : X at 10 is any amino acid or absent < 400 > SEQUENCE : 49 Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa 10

< 210 > SEQ ID NO 50 < 211 > LENGTH : 6 A< 212 > TYPE : PRT A< 213 > ORGANISM : Artificial Sequence A< 220 > FEATURE : A< 223 > OTHER INFORMATION : Synthetic Peptide A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 ?> LOCATION : ( 1 ) . . ( 1 ) A< 223 > OTHER INFORMATION : X is L -Glu A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 ?> LOCATION : ( 2 ) . . ( 2 ) A< 223 > OTHER INFORMATION : X is L - Asp A 220 > FEATURE :

N A< N221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 3 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X is L - Tyr A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 4 ) . . ( 4 ) A< 223 > OTHER INFORMATION : X is L - Tyr US 2017 /0319462 A1 Nov. 9 , 2017 50

- continued < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X is L - Arg < 220 > FEATURE : A 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is L - Leu < 400 > SEQUENCE : 50 ??? ??? ??? ??? ??? ???

< 210 > SEQ ID NO 51 < 211 > LENGTH : 6 < 212 > TYPE : PRT A< 213 > ORGANISM : Artificial Sequence A< 220 > FEATURE : A< 223 > OTHER INFORMATION : Synthetic peptide A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 1 ) . . ( 1 ) A< 223 > OTHER INFORMATION : X is L - Pro A< 220 > FEATURE : A 1 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 2 ) . . ( 2 ) A< 223 > OTHER INFORMATION : X is L - Asp A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 3 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X is L - Tyr A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 4 ) . . ( 4 ) A< 223 > OTHER INFORMATION : X is L - Tyr A< 220 > FEATURE : A NAME / KEY : misc _ feature A< 222 > LOCATION : ( 5 ) . . ( 5 ) A< 223 > OTHER INFORMATION : X is L - Lys < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is L - Leu < 400 > SEQUENCE : 51 ??? ??? ??? ??? ??? ???

< 210 > SEQ ID NO 52 < 211 > LENGTH : 6 < 212 > TYPE : PRT A< 213 > ORGANISM : Artificial Sequence A< 220 > FEATURE : A< 223 > OTHER INFORMATION : Synthetic peptide A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 1 ) . . ( 1 )

N A< 223 > OTHER INFORMATION : X is L -Glu A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 2 ) . . ( 2 ) A< 223 > OTHER INFORMATION : X is L -Asp A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 3 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X is L - Arg A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 ?> LOCATION : ( 4 ) . . ( 4 ) A< 223? > OTHER INFORMATION : X is L - Phe A< 220 > FEATURE : 21 > NAME / KEY : misc _ feature US 2017 /0319462 A1 Nov. 9 , 2017 51

- continued < 222 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X is L - Arg < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is L - Met < 400 > SEQUENCE : 52 ??? ??? ??? ??? ??? ??? 1

< 210 > SEQ ID NO 53 < 211 > LENGTH : 6 N TYPE : PRT < 213 > ORGANISM : Artificial Sequence o FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is L -Glu < 220 > FEATURE : A 1 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is L - Asp < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X is L - Tyr A 20 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) A 23 > OTHER INFORMATION : X is L - Tyr < 220 > FEATURE : A 1 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X is L - Arg < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is L - Met < 400 > SEQUENCE : 53 ??? ??? ??? ??? ??? ???

H

A< 210 > SEQ ID NO 54 A< 211 > LENGTH : 6 A< 212 > TYPE : PRT A< 213 > ORGANISM : Artificial Sequence A FEATURE : A< 223 > OTHER INFORMATION : Synthetic peptide A 20 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 1 ) . . ( 1 ) A< 223 > OTHER INFORMATION : X is L - Pro A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 2 ) . . ( 2 ) A< 223 > OTHER INFORMATION : X is L - Asp A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : 13 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X is L - Tyr A 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A 22 > LOCATION : ( 4 ) . . ( 4 ) A< 223 > OTHER INFORMATION : X is L - Tyr A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature A< 222 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X is L - Arg US 2017 /0319462 A1 Nov. 9 , 2017

- continued < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is L - Met < 400 > SEQUENCE : 54 ??? ??? ??? ??? ??? ???

< 210 > SEQ ID NO 55 < 211 > LENGTH : 8 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence FEATURE : < 223 > OTHER INFORMATION : Synthetic pepride < 220 > FEATURE : 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) 3 > OTHER INFORMATION : X is any amino acid or absent < 220 > FEATURE : < 221 > NAME / KEY : misc feature 2 2 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is any amino acid or absent < 220 > FEATURE : 1 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is His , Leu , or Pro < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) 23 > OTHER INFORMATION : X is Arq or Asn < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 7 ) . . ( 7 ) 23 > OTHER INFORMATION : X is any amino acid or absent < 220 > FEATURE : NAME / KEY : misc _ feature < 222 > LOCATION : ( 8 ) . . ( 8 ) < 223 > OTHER INFORMATION : X is any amino acid or absent < 400 > SEQUENCE : 55 ??? ??? His Xaa Leu ??? ??? ??? 2 5

< 210 > SEQ ID NO 56 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is L - His < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is L - Leu < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) A 23 > OTHER INFORMATION : X is L - Leu < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is L - Arg < 400 > SEQUENCE : 56 Xaa Xaa Xaa Xaa 1 US 2017 /0319462 A1 Nov. 9 , 2017 53

- continued H < 210 > SEQ ID NO 57 < 211 > LENGTH : 4 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is L - His < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is L - Pro < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X is L - Leu < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature A 2 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is L - Arg < 400 > SEQUENCE : 57 ??? ??? ??? ???

< 210 > SEQ ID NO 58 < 211 > LENGTH : 10 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is any amino acid or absent < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is any amino acid or absent A 20 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) A 3 > OTHER INFORMATION : X is Ser , Thr , or Tyr < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is Pro or Val < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is Glu , Gly , or Val A 20 > FEATURE : < 221 > NAME /KEY : misc _ feature A > LOCATION : ( 8 ) . . ( 8 ) < 223 > OTHER INFORMATION : X is Gin , Gly , His , or Pro < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 9 ) . . ( 9 ) < 223 > OTHER INFORMATION : X any amino acid or absent < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 10 ) . . ( 10 ) < 223 > OTHER INFORMATION : X any amino acid or absent < 400 > SEQUENCE : 58 Xaa Xaa Xaa Xaa Ala Xaa Gly Xaa Xaa Xaa 10

< 210 > SEQ ID NO 59 US 2017 /0319462 A1 Nov. 9 , 2017 54

- continued < 211 > LENGTH : 6 < 212 > TYPE : PRT ORGANISM : Artificial Sequence < 220 > FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is L - Tyr < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is L - Pro 20 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X is L - Ala < 220 > FEATURE : 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is L - Glu < 220 > FEATURE : < 221 > NAME / KEY : misc feature < 222 > LOCATION : ( 5 ) . . ( 5 ) < 223 > OTHER INFORMATION : X is L -Gly < 220 > FEATURE : NAME / KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) < 223 > OTHER INFORMATION : X is L - Gln < 400 > SEQUENCE : 59 ??? ??? ??? ??? ??? ???

< 210 > SEQ ID NO 60 < 211 > LENGTH : 6 TYPE : PRT < 213 > ORGANISM : Artificial Sequence FEATURE : < 223 > OTHER INFORMATION : Synthetic peptide FEATURE : 21 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 1 ) . . ( 1 ) < 223 > OTHER INFORMATION : X is L - Ser < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 2 ) . . ( 2 ) < 223 > OTHER INFORMATION : X is L - Val < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature LOCATION : ( 3 ) . . ( 3 ) < 223 > OTHER INFORMATION : X is L - Ala < 220 > FEATURE : 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 4 ) . . ( 4 ) < 223 > OTHER INFORMATION : X is L - Val < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 5 ) . . ( 5 ) 23 > OTHER INFORMATION : X is L - Gly < 220 > FEATURE : < 221 > NAME / KEY : misc _ feature < 222 > LOCATION : ( 6 ) . . ( 6 ) 3 > OTHER INFORMATION : X is L - Gln < 400 > SEQUENCE : 60 ??? ??? ??? ??? ??? ??? 2 5

< 210 > SEQ ID NO 61 < 211 > LENGTH : 6 < 212 > TYPE : PRT US 2017 /0319462 A1 Nov. 9 , 2017 55

- continued

A< 213 > ORGANISM : Artificial Sequence A< 220 ?> FEATURE : A< 223 > OTHER INFORMATION : Synthetic peptide ? A< 220 > FEATURE :

A MOMO < 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 1 ) . . ( 1 )

? A< N223 > OTHER INFORMATION : X is L - Ser A< 220 > FEATURE : N A< 221 > NAME / KEY : misc _ feature

N A< 222 A> LOCATION : ( 2 ) . . ( 2 ) A< N223 A> OTHER INFORMATION : X is L - Pro

N A< 220 A> FEATURE : A< 221MOMO > NAME /KEY : misc _ feature A< 222 ?> LOCATION : 13 ) . . ( 3 ) A< 223 > OTHER INFORMATION : X is L - Ala A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 4 ) . . ( 4 ) A< 223 > OTHER INFORMATION : X is L - Gly A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 5 ) . . ( 5 ) A< 223 > OTHER INFORMATION : X is L -Gly A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 6 ) . . ( 6 ) A< 223 > OTHER INFORMATION : X is L - Pro

< 400 > SEQUENCE : 61

??? ??? ??? ??? ??? ??? 5

< 210 > SEQ ID NO 62 < 211 > LENGTH : 10 < 212 > TYPE : PRT < 213 > ORGANISM : Artificial Sequence A< 220 > FEATURE : A< 223 > OTHER INFORMATION : Synthetic peptide A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature

~ A< 222 ?> LOCATION : ( 1 ) . . ( 1 )

~ A 23NMO ?> OTHER INFORMATION : X is any amino acid or absent

~ A< 220 ?> FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 2 ) . . ( 2 ) A< 223 > OTHER INFORMATION : X is any amino acid or absent A< 220 > FEATURE : A< 221 > NAME /KEY : misc _ feature

A< 222 > LOCATION : ( 4 ) . . ( 4 )

A< 223 > OTHER INFORMATION : X is Asn , His , Tyr , or Glu A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222? > LOCATION : ( 5 ) . . ( 5 ) A< 223 > OTHER INFORMATION : X is Lys , Ser , or Pro A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 6 ) . . ( 6 ) A< 223 > OTHER INFORMATION : X is Gly , Leu , Lys , or His A< 220 > FEATURE : A< 221 > NAME / KEY : misc _ feature A< 222 > LOCATION : ( 7 ) . . ( 7 )

A< 223 > OTHER INFORMATION : X is Gin or Asn < 220 > FEATURE : < 221 > NAME /KEY : misc _ feature < 222 > LOCATION : ( 9 ) . . ( 9 ) US 2017 /0319462 A1 Nov. 9 , 2017 56

- continued < 223 > OTHER INFORMATION : X is any amino acid or absent < 220 > FEATURE : ? 1 > NAME / KEY : misc _ feature ? 2 > LOCATION : ( 10 ) . . ( 10 ) < 223 > OTHER INFORMATION : X is any amino acid or absent < 400 > SEQUENCE : 62 ??? Xaa Tyr ??? ??? ??? ??? v?l Xaa ??? 1 10

What is claimed is : R2 is selected from H and C1 C2 alkyl groups and 1 . A polymer film comprising : mixtures thereof , and a ) at least 30 wt. % of a thermoplastic polyurethane n is an integer which represents the average number of polymer which is the reaction product of: ether units by weight in each polyol, and where n is at a first polyether polyolhaving a molecular weight of at least 20 . least 3000 daltons ; 21. The polymer film of claim 20 , wherein a ratio of the optionally , a second polyether polyol having a molecu value of n for the first polyether polyol to the value of n for lar weight of no more than 2500 daltons; the second polyether polyol is at least one of: at least one of: at least 1. 5 : 1 , and a third polyol having a molecular weight of up to 800 up to 10 : 1. daltons , and 22 . (canceled ) a chain extender; 23 . (canceled ) a diisocyanate ; and 24 . ( canceled ) optionally , a catalyst ; and 25 . ( canceled ) b ) up to 5 wt. % water . 26 . ( canceled ) 2 . The polymer film of claim 1 , wherein the thermoplastic 27 . ( canceled ) polyurethane polymer has a hard segment content of at least 28 . (canceled ) 29 . ( canceled ) 4 wt. % . 30 . (canceled ) 3 . (canceled ) 31 . (canceled ) 4 . (canceled ) 32 . ( canceled ) 5 . The polymer film of claim 1 - 4 , wherein the thermo 33 . ( canceled ) plastic polyurethane polymer has a soft segment content of 34 . The polymer film of claim 1 , wherein the thermoplas at least 80 wt. % . tic polyurethane polymer is 5 - 11 wt. % hard segment, 84 - 91 6 . The polymer film of claim 1 , wherein the film includes wt. % soft segment, and 2 . 5 - 4 wt. % intermediate segment . at least 50 wt. % of the thermoplastic polyurethane . 35 . (canceled ) 7 . ( canceled ) 36 . The polymer film of claim 1 , wherein the film further 8 . The polymer film of claim 1 , wherein the first polyether includes at least one cross - linked poly (acrylic acid ) polymer. polyol has a molecular weight of at least 4000 daltons . 37 . The polymer film of claim 36 , wherein a ratio by 9 . (canceled ) weight of the thermoplastic polyurethane polymer to cross 10 . ( canceled ) linked poly ( acrylic acid ) polymer is at least 5 : 1 . 11 . ( canceled ) 38 . ( canceled ) 12 . ( canceled ) 39. (canceled ) 13 . The polymer film of claim 1 , wherein the thermoplas 40 . The polymer film of claim 1 , wherein the film further tic polyurethane polymer includes the second polyether includes at least one other thermoplastic polyurethane which polyol, the second polyether polyol having a molecular is different from the thermoplastic polyurethane polymer a ) , weight of no more than 2000 daltons. and optionally , wherein a ratio by weight of the thermoplas 14 . (canceled ) tic polyurethane polymer a ) to the total amount of the at least 15 . ( canceled ) one other thermoplastic polyurethane is at least 1 : 2 . 16 . ( canceled ) 41 . ( canceled ) 17 . ( canceled ) 42 . ( canceled ) 18 . The polymer film of claim 13, wherein a ratio of the 43. (canceled ) molecular weight of the first polyether polyol to the second 44 . The polymer film of claim 1 , wherein the film has a polyether polyol is at least 1. 4 :1 . thickness of up to 1 mm . 19 . (canceled ) 45 . ( canceled ) 20 . The polymer film of claim 1 , wherein at least one of 46 . ( canceled ) the first polyether polyol and the second polyether polyol is 47 . (canceled ) of the general form : 48 . ( canceled ) 49 . (canceled ) HO — (R '( R2) 0 )n — H , where : 50 . The polymer film of claim 1 , wherein the film includes Rl is selected from C2 - C4 alkyl groups and mixtures at least one active agent. thereof, such as CH CH , 51. ( canceled ) US 2017 /0319462 A1 Nov. 9 , 2017 57

52 . ( canceled ) a ) a peptide comprising a sequence of at least 3 and no 53 . The polymer film of claim 50 , wherein the at least one more than 30 adjacent amino acids from the amino end active agent includes at least one of the group consisting of of protein SNAP - 25 ; a skin whitening or depigmentation agent, an anti -acne b ) a peptide of general formula : XSEQ ID NO . 8Y: agent , and an anti -wrinkle or anti- aging agent.

O O O =O OE= = 54 . (canceled ) =0 =0 H - CH - C H - CH - O7C CH - C H - CH 0 H - CH - C - Y , N N Lu- l - HN - CH - C - Y, 55. ( canceled ) CH - CH2 CH2 N CH - CH , CH , CH - CH, 56 . The polymer film of claim 53, wherein the anti - acne CH2 CH2 CH3 CH3 agent is selected from the group consisting of salicylic acid , CH3 CH2 glycolic acid , lactobionic acid , azelaic acid , benzoyl perox CH2 ide, antibiotics , retinoids, and mixtures thereof. NH2 57 . (canceled ) 58 . The polymer film of claim 53, wherein the anti wherein X is selected from the group consisting of wrinkle agent is selected from the group consisting of hydrogen , an amino acid and an acyl group and Y is dipeptide - 4 , tripeptide- 1 , acetyl tetrapeptide- 2 , palmitoyl selected from the group consisting of amino , tetrapeptide - 7 , caprooyl tetrapeptide - 3 , pentapeptide - 3 , pen hydroxyl and thiol; tapeptide- 18 , dipeptide diaminobutyroyl benzylamide diac c ) a peptide of the general formula R - AA - R , its stereoi etate , palmitoyl tripeptide - 5 , acetyl tetrapeptide -5 , acetyl somers , mixtures thereof, and its cosmetically and tetrapeptide - 9 , acetyl tetrapeptide - 11, acetyl tetrapeptide - 22 , pharmaceutically acceptable salts , wherein AA is a hexapeptide - 9 , acetyl heptapeptide - 4 , palmitoyl pentapep sequence of a least 3 and up to 40 adjacent amino acids tide- 4 , acetyl hexapeptide -8 , acetyl hexapeptide - 30 , acetyl contained in the amino acid sequence SEQ ID No . : 9 octapeptide - 3 , palmitoyl hexapeptide - 19, diaminopropi selected from : onoyl tripeptide -33 , methylsilanol mannuronate , methylsi lanol hydroxyproline aspartate , tripeptide -9 citrulline , trip eptide - 10 citrulline , acetyl tripeptide - 30 citrulline , calcium ( SEO ID No . : 10 ) hydroxymethionine , teprenone , palmitoyl oligopeptide , MAEDADMRNELEEMORRADQL , acetylarginyltriptophyl diphenylglycine, dimethylmethoxy ( SEQ ID No . : 11 ) chromanol, dimethylmethoxy chromanyl palmitate , ADESLESTRRMLQLVESSKDAGI, dipalmitoyl hydroxyproline, Pseudoalteromonas ferment ( SEO ID No . : 12 ) extract, and mixtures thereof. ELEEMQRRADQLA , 59 . The polymer film of claim 53, wherein the anti wrinkle agent comprises a compound selected from the ( SEO ID No . : 13 ) compound of general ELEEMORRADQL , ( SEO ID No . : 14 ) ELEEMORRADO , Formula ( I ) (SEQ ID NO . : b15 ) ELEEMORRAD , ( SEO ID No . : 16 ) ELEEMORRA , ( SEQ ID No . : 17 ) ELEEMORR , ( SEQ ID No . : 18 ) LEEMORRADOL , ( SEQ ID No . : able19 ) formula (I ) and cosmetically or pharmaceutically acceptable LEEMORRADO , salts thereof, wherein R is a linear or branched , saturated or ( SEQ ID No . : 20 ) unsaturated substituted or unsubstituted aliphatic group con LEEMORRAD , taining 2 to 23 carbon atoms, or a cyclic group , and wherein ( SEQ ID NO . : 21 ) when R is an unsubstituted aliphatic group , its substituents LEEMORRA , are selected from hydroxy, alkoxy, amino , carboxyl, cyano , nitro , alkylsulfonyl or halogen atoms; and X is selected from ( SEQ ID No . : 22 ) O and S . LEEMQRR , 60 . The polymer film of claim 50 , wherein the at least one ( SEQ ID NO . : 23 ) active agent includes a peptide comprising no more than 30 EEMQRRADQL , amino acids . ( SEQ ID No . : 24 ) EEMQRRADO , 61. The polymer film of claim 60 , wherein the peptide is selected from the group consisting of: mmmmmmmmmmm US 2017 /0319462 A1 Nov . 9 , 2017 58

- continued ( SEO ID No . : 25 ) EEMQRRAD ,

( SEO ID No . : 26 ) EEMQRRA , ZE - R2 ( SEQ ID NO . : 27 ) EEMORR ,

( SEO ID No . : 28 ) LESTRRMLQLVEE , OH ( SEQ ID No . : 29 ) NKDMKEAEKNLT ,

( SEO ID No . : 30 ) and cosmetically or dermopharmaceutically acceptable KNLTDL , salts thereof, wherein : X and Y are selected from natural amino acids in their L - or D - form and non ( SEQ ID NO . : 31 ) encoded amino acids; IMEKADSNKTRIDEANQRATKMLGSG , g ) a peptide of only four amino acids of general formula R2 - AA , - AA2- AA3- AA4 - R2( R , - (SEQ ID NO .: 40 ) -R2 ) , ( SEQ ID No . : 32 ) wherein AA , is selected from - Lys- , -Orn -, -Dab -, SNKTRIDEANORATKLMGSG , -Dpr - , - Agl -, -3 , 4 -dehydrolysine and -4 , 5 -dehydroly sine ; AA , is - Ala- ; AAz is selected from - Asp - , - Ala - , ( SEQ ID NO . : 33 ) - Asn - , -Glu - and -Pro - ; and AA , is -His - ; TRIDEANORAT KMLGSG , h ) a peptide having a maximum of seven amino acids of ( SEO ID No . : 34 ) general formula R2- W , - X , - AA - AA2- AA3- AA4 - Ym R2 (R /- ( SEQ ID NO .: 44 )- R2 ) , wherein at least one of DEANORATKMLGSG , the amino acids AA , AA , and AA , is uncoded ; AA , is selected from - Arg -, - Phg - and -Nle - or is absent ; AA , ( SEQ ID NO . : ö35 ) is selected from - Ala - , -Phg -, -Cit - and - Nle -; AAz is NORTKMLGSG , selected from - Trp -, - Val- and - Tyr - ; AA4 is selected and from -Phg - and -Gly -; W , X and Y are independently selected from the group consisting of coded and ( SEQ ID No . : e36 ) uncoded amino acids; and p , n and m each range QRATKMLGSG ; between 0 and 1 ; i ) a peptide having only three amino acids of general d ) a peptide of general formula : formula R4- AA1- AA2- AA3 -R2 , wherein : AA , and AA2 are independently selected from - Tyr- and - Phe - ; and AAz is selected from -Nle - and -Met - ; j ) a peptide of general formula R - W ,, - Xm - AA - AA2 H N AA3- AA4- AA3- AAG- Y , - Z - R2 IR ,- (SEQ ID No .: 49) Ri R2) , wherein AA , is selected from - Asp - , -Glu - and - Pro ; AA , is - Asp - ; AA , is selected from - Tyr - and - Arg -; AA4 is selected from - Phe - and - Tyr- ; AA , is selected from - Arg - and - Lys - ; AA , is selected from N NH N . -Leu - and -Met - ; W , X , Y and Z are independently selected from coded amino acids and non -coded amino acids ; and n , m , p and s independently have a value of where X is selected from cysteinyl, seryl, threonyl and between 0 and 1 ; aminobutyryl; k ) a peptide of general formula R - W ., , - Xm -AA -AA2 e ) a peptide which includes only four amino acids of AA3 - AA4 - Yr- Z -R2 (R1 - (SEQ ID No .: 55 ) -R2 ) , general formula R2- AA ,- AA2 - AA3- AA4- R2 (R1 - ( SEQ wherein : AA , is -His - ; AA , is selected from the group consisting of - His -, -Leu - and - Pro - ; AAz is -Leu - ; AA4 ID NO . : 37 ) -R2 ) , wherein : AA , is - Arg -; AA , is is selected from the group consisting of - Arg - and selected from -His - and - Asn - ; AAz is selected from - Asn - ; W , X , Y and Z are independently selected from - His - and - Arg -; and AA4 is - Cit - ; the group consisting of codified amino acids and f ) a peptide which includes only four amino acids of uncodified amino acids ; n , m , p and q each have a value general formula , between 0 and 1; n + m + p + q is less than or equal to 2 ; US 2017 /0319462 A1 Nov. 9 , 2017 59

I ) a peptide of general formula : lalkyl groups ; R2 is selected from — NR R5, OR4 and — SR4 , wherein R4 and R , are independently selected from H , a polymer derived from polyethylene glycol , H2P T substituted or unsubstituted non -cyclic aliphatic group , In substituted or unsubstituted alicyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted R , IZ A4, heteroarylalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted aralkyl; and R , and / or R , are not a - amino acids; VECOOHCOOH p ) a compound of general formula : NH R2- W „ Xm -AA1 - AA2 - AA3 - AA4 - AA5 - AA - YA -Z -R2 (R1 - (SEQ ID No .: 62 )- R2) , wherein AA , is - Tyr -; AA , is selected from - Asn - , 0 NH2 - His -, - Tyr - and -Glu - ; AA , is selected from -Lys -, - Ser - and -Pro - ; AA4 is selected from -Gly - , - Leu - , wherein : Z is selected from the group consisting of - Lys - and -His - ; AA , is selected from -Gln - and alanyl , allo - isoleucyl, glycyl, isoleucyl, isoseryl, - Asn - ; AA , is - Val -; W , X , Y , Z are independently isovalyl, leucyl, norleucyl, norvalyl, prolyl, seryl , selected from amino acids. n , m , p and q indepen threonyl, allo - threonyl and valyl; n and m are inde dently have a value of 0 or 1 ; and n + m + p + q is pendently from 1 to 5 ; AA is selected from the group smaller than or equal to 2 ; and consisting of natural encoded amino acids in their L stereoisomers , mixtures thereof, and cosmetically and or D - form and non -encoded amino acids; x and y are dermopharmaceutically acceptable salts thereof, independently from 0 to 2 ; wherein R , and R , are peptide terminating groups . m ) a peptide of general formula : 62 . (canceled ) R , W „ Xm -AA1 - AA2- AA3 -AA4 - AA5- AA - Y , - 2 ,- R2 (R1 63 . (canceled ) (SEQ ID Na : 58 ) - R2) , wherein : AA , is selected from 64 . ( canceled ) -Ser -, - Thr - and - Tyr - ; AA , is selected from -Pro - and 65 . ( canceled ) -Val - ; AAz is Ala ; AAA is selected from -Glu -, -Gly - and 66 . ( canceled ) - Val- ; AA , is -Gly - ; AA , is selected from -Gln - , -Gly -, 67 . A hydrated film formed from the polymer film of -His - and -Pro -; W , X , Y , Z are independently amino claim 1 , wherein the hydrated film comprises at least 30 wt. acids ; n , m , p and q are independently selected from 0 % water . and 1 ; n + m + p + q is less than or equal to 2 ; 68 . The hydrated film of claim 67, further comprising at n ) a peptide of general formula : R1- AA7- AA2- AA3- R2 , least one excipient selected from the group consisting of where AA , is selected from - Tyr- and -Phe -, AA , is emulsifiers, organic solvents, surfactants, liquid propellants , - Tyr -, and AAz is selected from - Nle - and -Met -; binders and thickeners , fillers , lubricants , glidants , pigments , o ) a compound of general formula : dyes , perfumes , flavoring agents , preservatives, and combi nations thereof. 69 . ( canceled ) 70 . A face mask comprising the polymer film of claim 1 . R - AA - AA2 - NH - CH = C - AA3 - R , , , 71 . The face mask of claim 70 , wherein the film is supported on a release layer. (CH2 ) 72 . (canceled ) NHR3 73 . A face mask of comprising : up to 20 wt. % of the polymer film of claim 1 ; wherein AA , is selected from - Asp -, -Glu - , - Asn -, -Gln - , at least one active agent at a total concentration of at least - Lys - and -Gly - , AA , is selected from - Val- , - Leu - , 0 .00001 wt. % , and - Ile - , -Met - , -Cit -, -His -, - Thr - and -Gln -; AAz is at least 30 wt. % water . selected from - Tyr- , - Trp - and 4 - Abz - ; n is selected 74 . (canceled ) from 1 , 2 , 3 and 4 , Rz is selected from H and -AA 75 . A method of forming a face mask or transdermal patch AA , R1, R , is selected from H , a polymer derived from comprising: polyethylene glycol, substituted or unsubstituted non cyclic aliphatic groups, substituted or unsubstituted forming a thermoplastic polyurethane polymer from : alicyclyl groups , substituted or unsubstituted heterocy a first polyether polyol having a molecular weight of at clyl groups, substituted or unsubstituted heteroarylal least 3000 daltons , kyl groups, substituted or unsubstituted aryl groups , optionally , a second polyether polyol having a molecu substituted or unsubstituted aralkyl groups and lar weight of no more than 2500 daltons, and R - CO — , wherein R , is selected from H , substituted at least one of a third polyol having a molecular weight or unsubstituted non -cyclic aliphatic groups, substi of up to 800 daltons and a chain extender ; tuted or unsubstituted alicyclyl groups , substituted or casting the thermoplastic polyurethane polymer with an unsubstituted aryl groups, substituted or unsubstituted active agent in solution to form a cast film which aralkyl groups, substituted or unsubstituted heterocy includes the active agent dispersed in the thermoplastic clyl groups and substituted or unsubstituted heteroary polyurethane polymer . US 2017 /0319462 A1 Nov. 9 , 2017 60

76 . A face mask or transdermal patch comprising : a hydrated film comprising at least 50 wt. % water, 5 to 30 wt. % of a thermoplastic polyurethane polymer, and at least one active agent . * * * * *