US 2006O188465A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0188465 A1 Perrier et al. (43) Pub. Date: Aug. 24, 2006
(54) CROSS-LINKED POLYMER OF (30) Foreign Application Priority Data CARBOHYDRATE, NOTABLY BASED ON POLYSACCHARIDES, AND/OR ON Feb. 18, 2005 (FR)...... O5 O1674 OLGOSACCHARDES AND/OR ON POLYOLS Publication Classification (75) Inventors: Eric Perrier, Les Cotes D'Arey (FR): (51) Int. Cl. Nabil Abdul-Malak, Caluire (FR): A6IR 8/73 (2006.01) Julie Saget, Lyon (FR) A6II 3/765 (2006.01) C08G 63/9. (2006.01) Correspondence Address: (52) U.S. Cl...... 424/70.13; 424/78.37; 525/54.2 MERCHANT & GOULD PC P.O. BOX 2903 (57) ABSTRACT MINNEAPOLIS, MN 55402-0903 (US) (73) Assignee: Engelhard Lyon, Lyon (FR) The invention discloses a cross-linked polymer of at least one carbohydrate component comprising at least one pri (21) Appl. No.: 11/174,414 mary alcohol function in particular for the manufacture of a composition which is intended to be applied onto the skin to (22) Filed: Jul. 1, 2005 obtain a tensing and/or toning effect. US 2006/0188465 A1 Aug. 24, 2006
CROSS-LINKED POLYMER OF CARBOHYDRATE, which be capable of obtaining a tensing and/or toning effect NOTABLY BASED ON POLYSACCHARIDES, on the cutaneous Surface in a way which is perceptible by the AND/OR ON OLGOSACCHARDES AND/OR ON users, without inducing any identifiable allergic reaction. POLYOLS 0010. An aim of the present invention is to solve the 0001. The present invention relates to the preparation of technical problem consisting of providing a toning Solution an active principle having a tensing effect, based on various which is preferably based on a starting material of excellent protein or peptide Substances, so as to avoid problems of biocompatibility, of total biodegradability, of complete allergies encountered with these substances. The present assimilation, of total innocuousness, originating from a invention thus relates to the preparation of cross-linked renewable biological material, and being able to be present polymers of carbohydrates. not only in the animal kingdom, but also in the plant kingdom, and also being able to be produced by microbial STATE OF THE ART fermentation. 0002 Cosmetic formulations very often contain sub 0011. An aim of the present invention is also to solve the stances which enable characteristic tensing effects to be technical problem consisting of providing a novel method of induced. These effects in particular enable improving the manufacture of the compounds which enable solving the perception of effectiveness of a cosmetic formulation by technical problem mentioned above. sensory effects which are perceived significantly by con 0012. The whole of these technical problems is solved for SUCS. the first time in a manner which is satisfactory, inexpensive, 0003. Furthermore, these tensing effects enable on the which can be used on an industrial scale, notably cosmetic one hand an immediate but temporary reduction to be scale. brought about of the wrinkles and small wrinkles of the skin, and, on the other hand, a tension of the skin used for the DESCRIPTION OF THE INVENTION formulations of eye Surround, neck, neckline or hand type. 0013 Starting off from the prior art known to the inven 0004 Bovine serum albumin or collagen have been the tors, i.e. of polymerized proteins, the inventors have discov molecules which have been the most used in the past from ered in a Surprising way that cross-linked polymers of at amongst the Substances which are the best known for this least one type of carbohydrate or carbohydrate derivative property. More recently, the substances developed for this enabled a tensing and/or toning effect to be obtained of a activity are turned towards Substances of plant origin: plant proteins have in particular be widely used for this activity. cutaneous tissue, such as the skin of a human being. 0014 Thus, according to a first aspect, the invention 0005 Thus, for example, the plant albumin fraction of relates to a cross-linked polymer of at least one type of cereal grains or of leguminous plants has been the Subject of carbohydrate comprising at least one primary alcohol func a particularly interesting patent for its analogy with bovine tion, and in particular relates to a cross-linked polymer serum albumin (Coletica, FR 2,701,847, W094/18944). which is obtainable according to the method defined below. Similarly, the polymerization of plant proteins with the aid This polymer excludes polymers of at least one type of of bifunctional agents has been described for various cos carbohydrate comprising at least one primary alcohol func metic applications (Coletica, FR 2,766,090 (corresponding tion in the form of capsules or spheres; particularly in the to U.S. Pat. No. 5,912,016); FR 2,780,901, (corresponding form of microcapsules or of microspheres, or in the form of to U.S. Pat. No. 6,197.757). The substances prepared by nanocapsules or of nanospheres. polymerization of hydrolyzed fractions of plant proteins have also been described and used for tensing effects in 00.15 According to a second aspect, the invention relates cosmetics (FR 2,832,157, WO 03/040216 A1). to a cosmetic, and/or dermo-pharmaceutical, and/or phar maceutical composition, comprising a cross-linked polymer 0006. However, the use of proteins in cosmetics becomes problematic since they can induce more or less strong as defined above. immune reactions, even allergies which can lead to total 0016. Also, according to a third aspect, the invention intolerances. The proteins originating from wheat, nuts, relates to the use of a cross-linked polymeras defined above, hazelnuts, peanuts, milk, are a few examples of them which for the manufacture of a composition which is intended to be are well known to the person skilled in the art. applied onto a cutaneous tissue of a Subject to obtain a 0007. It is necessary to consider that in the future, com tensing and/or toning effect on this tissue. pounds of a character which is irritant for the skin, such as 0017. By the term <
ous tissue of a subject to obtain a reduction of wrinkles the oligosaccharide, with respect to the cross-linking agent, and/or small wrinkles of this tissue. is greater than 0.1, and preferably greater than or equal to 1. 0020. According to another variant, the invention relates 0032. In a second embodiment, the carbohydrate, par to the use of the cross-linked polymer, for the manufacture ticularly the polysaccharide, has a molecular weight of of a composition which is intended to be applied onto a greater than or equal to 50,000 Da, preferably greater than cutaneous tissue of a Subject to improve the biomechanical or equal to 100,000 Da, more preferably greater than or properties of this tissue. equal to 300,000 Da. In this case, a hydrolysis can be carried out before the cross-linking reaction, so that the polymer 0021 Advantageously, the composition is a cosmetic, ization reaction can lead to polymers mainly soluble. Meth dermo-pharmaceutical or pharmaceutical composition, ods of hydrolyzing carbohydrates are known to the person which is intended to be applied onto at least one part of the skilled in the art. face, particularly onto the contour of the eye, and/or of the neck, and/or of the hands, and/or of the neckline, and/or the 0033 Advantageously, in this second embodiment the bust. molar ratio of the carbohydrate, particularly of the polysac charide, with respect to the cross-linking agent, is less than 0022. The products originating from this invention pos sess a toning effect upon applying a composition containing 0.1, and preferably less than 0.01. them onto the skin. The products originating from this 0034 Advantageously, the polysaccharide comprises 0.5 invention do not have any identifiable allergy forming effect to 4 primary alcohol functions per diosidic moiety. upon applying Such a composition on the skin. 0035 Advantageously, the carbohydrate before reaction 0023 The products of the invention adsorbent onto the is in a mixture with an excipient which is acceptable via the surface of the skin and form an elastic film which is smooth topical route, particularly a cosmetically or dermatologically and continuous. The filmogenic, tensing and plastifying acceptable excipient. properties of the carbohydrates, notably of the polysaccha 0036). According to another particular embodiment vari rides, and/or of the oligosaccharides, and/or of the polyols, ant, the concentration of carbohydrate having a primary thus polymerized, are thus particularly interesting. alcohol function, notably of polysaccharide and/or of oli 0024 Advantageously, the products of the invention thus gosaccharide, and/or of polyols, is between 0.001% and possess filmogenic and/or plastifying properties. 50% by weight of the aqueous phase, and more particularly between 0.1 and 10% by weight. 0025 Preferably, the carbohydrate is selected from a polysaccharide, an oligosaccharide, a polyol, and any one of 0037 Advantageously, the cross-linking agent is a poly their mixtures. functional cross-linking agent, i.e. comprising at least two reactive functions which can react mainly with the primary 0026. According to a fourth aspect, the invention relates alcohol function of the carbohydrate, and is advantageously to a method of cosmetic care comprising topically applying selected from polycarboxylic acid chlorides, carboxylic acid a composition as defined above. anhydrides, polyisocyanates, polythioisocyanates, polyalde 0027. The Applicant knows of a method of polymeriza hydes, and any one of their mixtures. tion of polysaccharides or of oligosaccharides (COLETICA 0038. When the carbohydrate has between high molecu FR 2.688,422, U.S. Pat. No. 5,562.924). However, this lar, it is preferable that it undergo a hydrolysis prior to the method is a method of interfacial polymerization in an reaction in homogeneous aqueous phase, before being emulsion for the manufacture of microcapsules and of placed in contact with the cross-linking agent. microspheres. Therefore, this method does not enable obtaining a high molecular weight polymer of carbohy 0039 Advantageously, the method comprises, after the drates, other than in the form of spheres and/or capsules, cross-linking reaction, a removal of the compounds which particularly in the form of microcapsules or of microspheres. are insoluble in the aqueous phase, when insoluble com pounds are present at the end of the reaction. 0028. Thus, according to a fifth aspect, the present inven tion describes a method of manufacturing a cross-linked 0040. In a particular embodiment, the method comprises polymer, said method comprising a cross-linking reaction in dissolving the carbohydrate in aqueous phase, and then homogeneous aqueous phase between the primary alcohol placing in contact with a phase containing the cross-linking agent, which can be dissolved or not in an alcohol Such as function of the carbohydrate and a reactive function of a ethanol and/or butylene glycol, for a period of time which is cross-linking agent, to obtain a cross-linked polymer of at sufficient to obtain the cross-linking of said carbohydrate least one type of carbohydrate. and to thus form a cross-linked polymer of carbohydrate, 0029 Preferably, the carbohydrate is selected from a notably of high molecular weight. polysaccharide, an oligosaccharide, a polyol, and any one of 0041 As is illustrated in the paragraphs above, the inven their mixtures. tors have obtained polymers of carbohydrate of high 0030. In a first embodiment, the carbohydrate, particu molecular weight by polymerization in homogeneous aque larly the polyol and/or the oligosaccharide, has a molecular ous phase. This method is entirely advantageous from the weight of greater than or equal to 150 grams per mole (noted point of view of industrial production, since it limits the as g/mol or Dalton or Da in the rest of the text), preferably number of reaction steps, the cost of starting materials, and of greater than or equal to 2,000 Da. also maintains the safety of the personnel. 0031 Advantageously, in this first embodiment the molar 0042. It was not imaginable that the polymers obtained ratio of the carbohydrate, particularly of the polyol and/or of would have properties known as “tensing effect” properties. US 2006/0188465 A1 Aug. 24, 2006
DETAILED DESCRIPTION OF THE The Following Polysaccharides: INVENTION 0052 Galactomannans, for example galactomannans 0043. The present invention relates in particular to the originating from guar Such as Viscogum R (SANOFI). use of cross-linked carbohydrates, such as polysaccharides, or from carob Such as those available commercially and/or oligosaccharides, and/or polyols, which are cross under the name of LygommeR (SANOFI) or Meypro linked, notably via their primary alcohol functions, prefer Fleur R, or Meyprodyn R. (MEYHALL); ably with the aid of a multifunctional agent known to the person skilled in the art. 0053 Carrageenans, such as those extracted from red alga Such as those available commercially under the 0044) The present invention relates to a method of pre name of Satiagel(R) or Satiagum(R) (DEGUSSA) or paring carbohydrates comprising a primary alcohol function, notably Such as polysaccharides and/or oligosaccharides Genuvisco(R) (HERCULES); and/or polyols, which are polymerized (or cross-linked), of 0054 Glucomannans, such as those originating from high molecular weight, said method comprising the follow konjac gum, Such as those available commercially ing consecutive steps consisting in: under the name of Nutricol R (FMC Corporation) or of 1) Dissolving, in aqueous phase, a material which is rich in Propol R (FMC SCHIITZU): carbohydrates, notably in polysaccharides, and/or in oli 0055 Polysaccharides having a primary alcohol func gosaccharides, and/or in polyols; tion originating from fermentation, Such as Xanthane 2) Polymerizing the carbohydrates by adding a multifunc (KELKO), Gellane.R. (KELKO), Curdlane(R) tional agent (cross-linking agent) selected as described (TAKEDA) or hyaluronic acid; above; 0056 Celluloses, such as Natrosol R 250HHX(AQUA 3) Optionally removing the reaction products having LON), Klucel EF(R) (AQUALON), Vivapur R. (Instel become insoluble (non-soluble) in the reaction medium. Chimos). 0045. The method of the present invention enables pre 0057 Cellulose derivatives, such as hydroxypropyl paring carbohydrates, notably polysaccharides, and/or oli methyl cellulose (Aqualon), methyl ethyl cellulose gosaccharides, and/or polyols, which are polymerized (Aqualon), methylhydroxy methyl cellulose (Aqualon) (cross-linked) and which are of interest, notably of interest or Blanose(R) (Aqualon); in cosmetics. The polymerized carbohydrates thus obtained have a high molecular weight and Surprisingly provide a 0.058 Polyholosides, such as Dextran?R), Dextran T70, T500 or T2000, dextran sulfate (Pharmacia Fine perfect skin tolerance. Chemicals); 0046) One of the advantages of the method of the present invention is to enable, from a material which is rich in 0059 Agars, such as Food grade Agar (Sigma), Bac carbohydrates, in polysaccharides and/or in oligosaccha teriological Agar (Setexam), Monogar M540 Agar (Set rides and/or in polyols, creating a molecular architecture of exam) or Agar QSN5 (Setexam) high molar mass which enables a three-dimensional network 0060 Alginates, such as sodium salts of alginic acid to be created which is capable of inducing an improvement A2158 (Sigma), Satialgine(R) (Degussa) or Sodium algi of the biomechanical properties of the skin. nate FD 125(Danisco); 0047. It is not easy to provide in a clear manner to define the cross-linked polymer according to the present invention, 0061 Starches, such as amylopectin (Fluka), amylose since the degrees of cross-linking are not identifiable. As an (Fluka), Nastar R (Cosucra), Waxy Maize starch illustration, by the term <
The Following Oligosaccharides, Monosaccharides or glycerol (for example 10%, w/w) and of xanthan (for Disaccharides: example 2%, w/w) which is cross-linked with terephthalic acid dichloride, a mixture of mannitol (for example 10%, 0073 (marketed by the company Sigma, unless speci w/w) and of inulin (for example 5%, w/w) which is cross fied otherwise) given as examples: linked with terephthalic acid dichloride, and any one of their 0074 Cyclodextrins (particularly O, B, or Y cyclodex mixtures. trins or their derivatives), 0086 According to an advantageous embodiment, the 0075) Dextrins (Glucidex 40R or Glucidex 47(R), method of manufacture is characterized in that a carbohy Roquette); drate, notably a polysaccharide, and/or an oligosaccharide, and/or a polyol, having primary alcohol functions, is dis 0076 Raffinose, cellobiose, sucrose, maltose, lactose, Solved in aqueous phase, and then this aqueous phase trehalose, dihydroxyacetone (DHA), fructose, Sorbose, containing the carbohydrate is placed in contact with a phase ribose, deoxyribose, Xylose, arabinose, glucose, man containing a cross-linking agent, which can be dissolved or nose, galactose, erythrose, threose, allose, atrose, not in an alcohol, notably Such as ethanol and/or butylene gulose, idose, talose, erythrulose, Xylulose, psicose, glycol, having functions which are capable of preferentially tagatose, Sedoheptulose, Xylobiose, chitobiose, reacting with the primary alcohol functions of the carbohy nigerose, aminaribiose, kojibiose, Sophorose, gen drate, to carry out a polymerization between the primary tianose, gentiobiose, melibiose, melezitose, turanose, alcohol functions of the carbohydrate and the reactive func stachyose, Verbascose; tions of the cross-linking agent, for a period of time which 0077. Gluconic acid, gluconolactone, glucosamine, is sufficient to obtain a polymerized carbohydrate of high galactosamine, galactosamine Sulfate, glucosamine Sul molecular weight. fate; 0087. According to an embodiment variant of the method 0078 Saponins, such as saponins from the bark of according to the invention, the cross-linking agent is quillaya; selected from the group consisting of a poly(acid chloride), a poly(acid anhydride), a polyisocyanate, a polythioisocy 0079 Guanosine, uridine: anate, a polyaldehyde, and any one of their mixtures. A 0080 Streptomycin sulfate: cross-linking agent will advantageously be selected the non-reactive part of which is acceptable for the skin, so as 0081 Riboflavin; and to enable, after neutralization of the reaction, to not carry out The Following Polyols: separation operations. 0088. The poly(acid chloride) is for example selected 0082 (marketed by the company Roquette, unless from an acid trichloride or an acid dichloride to thus form specified otherwise) given as examples; ester bonds. 0083) glycerol, sorbitol, erythritol (Sigma), maltitol, Sorbitol, mannitol, lactitol (Sigma), galactitol (Sigma), 0089 Advantageously, the proportion by weight of cross ribitol (Sigma), glycerol (Sigma), Xylitol, myro-inosi linking agent dissolved in the alcohol varies in general tol, polyethylene glycol or PEG having a molecular between 5 and 30%, but is preferably situated between 10 mass, therefore varied polymerisation level, etc. . . . and 20%. 0090 According to a preferred feature, the cross-linking 0084. According to a particular embodiment, the polysac agent is selected from phthalic acid trichlorides, phthalic charides and/or the oligosaccharides and/or the polyols acid dichlorides, sebacic acid dichlorides, azelaic acid having primary functions mentioned above are preferably dichlorides, succinic acid dichlorides, dichlorides or trichlo selected from the group consisting of a polysaccharide of rides of a tricarboxylic acid, such as citric acid. The poly Xanthan, a cellulose, a gum from carob, xylitol, maltose, a (acid anhydride) is for example an acid dianhydride, such as, carrageenan, raffinose, an acacia gum, a mixture of glycerol for example, Succinic dianhydride or maleic dianhydride. (for example 10%, w/w) and of xanthan (for example 2%, w/w), a mixture of mannitol (for example 10%, wifw) and of 0091. According to another particularly advantageous inulin (for example 5%, w/w), and any one of their mixtures, embodiment variant of the method according to the inven which are preferably cross-linked with sebacic acid dichlo tion, the aqueous phase is an aqueous alkaline phase, i.e. the ride or by terephthalic acid dichloride. pH of which is alkaline, therefore greater than 7. A preferred 0085. According to a particular embodiment, the polysac pH range is a pH range between about 7.1 and about 10. A charides and/or the oligosaccharides and/or the polyols more preferred pH is between 8 and 10, and preferably having primary functions mentioned above are preferably between 8 and 9. A strong base, such as KOH or NaOH, or selected from the group consisting of a polysaccharide of a weak base such as ammonia Solution, borate, phosphate or Xanthan which is cross-linked with sebacic acid dichloride, carbonate, can be used as base for bringing the aqueous a cellulose which is cross-linked with sebacic acid dichlo phase to a basic pH. ride, a gum from carob which is cross-linked with sebacic 0092. The cross-linked polymers of carbohydrates acid dichloride, xylitol which is cross-linked with sebacic according to the present invention are prepared in the form acid dichloride, maltose which is cross-linked with sebacic of topical compositions, notably cosmetic, dermo-pharma acid dichloride, a carrageenan which is cross-linked with ceutical, or pharmaceutical compositions. From this, for terephthalic acid dichloride, raffinose which is cross-linked these compositions, the excipient contains for example at with terephthalic acid dichloride, an acacia gum which is least one compound selected from the group consisting of cross-linked with terephthalic acid dichloride, a mixture of preservatives, emollients, emulsifiers, Surfactants, moistur US 2006/0188465 A1 Aug. 24, 2006
izers, thickeners, conditioners, matifying agents, stabilizers, EXAMPLES antioxidants, texture agents, brightening agents, filmogenic agents, solubilizers, pigments, dyes, perfumes and Solar Example 1 filters. These excipients are preferably selected from the Cross-Linking a 2% Aqueous Solution of Xanthan, demon group consisting of amino acids and their derivatives, polyg stration of the tensing effect on the human skin. lycerols, esters, polymers and derivatives of cellulose, lano lin derivatives, phospholipids, lactoferrins, lactoperoxi 0098 1. A preparation of polysaccharide of Xanthan dases, sucrose-based stabilizers, E vitamins and its (5,000,000 Da) is prepared as follows: 2.10 g of xanthan (KELTROL, SPCI) are dissolved in 93.1 g of cold, derivatives, natural and synthetic waxes, plant oils, triglyc demineralized water. 4.8g of NaHCOs are then added to erides, insaponifiables, phytosterols, plant esters, silicones the preparation under strong agitation. After complete and its derivatives, protein hydrolyzates, jojoba oil and its dissolution, the pH stabilizes at a value of between 8 and derivatives, lipofhydroSoluble esters, betaines, aminoxides, 8.4. plant extracts, esters of Sucrose, titanium dioxides, glycines, and parabens, and more preferably from the group consist 0099 2. Preparation of the cross-linking agent: 0.75 g. ing of butylene glycol, Steareth-2, Steareth-21, glycol-15 of sebacic acid dichloride are dissolved in 4.25 g of Stearyl ether, cetearyl alcohol, phenoxyethanol, methyl para butylene glycol. ben, ethyl paraben, propylparaben, butylparaben, butylene 0.100 3. Cross-linking of the aqueous solution of Xan glycol, natural tocopherols, glycerol, Sodium dihydrox than: the solution prepared in 27 is added, under agita ycetyl, isopropyl hydroxycetyl ether, glycol Stearate, tri tion, to the solution prepared in 1/. The whole is left isononaoine, octyl cocoate, polyacrylamide, isoparaffin, lau under agitation for 60 minutes, so as to cause a poly reth-7, a carbomer, propylene glycol, glycerol, bisabolol. merization between the activated diacid on the one dimethicone, sodium hydroxide, PEG 30-dipolyhydroxys hand and the alcohol functions of the polysaccharides terate, capric/caprylic triglycerides, cetearyl octanoate, on the other hand. This reaction is promoted in basic dibutyl adipate, grape seed oil, jojoba oil, magnesium Sul medium. After reaction, the Solution of cross-linked phate, EDTA, cyclomethicone, Xanthan gum, citric acid, Xanthan can be used as Such but has insoluble Sub Sodium lauryl Sulphate, mineral waxes and oils, isostearyl stances. The product can be filtered by filtration carried isostearate, propylene glycol dipelargonate, propylene gly out for example on a device having a cut-off threshold col isostearate, PEG 8 Beeswax, hydrogenated palm tree of 0.22 um to remove the insolubles. heart oil glycerides, hydrogenated palm oil glycerides, lano lin oil, sesame oil, cetyl lactate, lanolin alcohol, castor oil, 0101 4. Principle of a measurement of tensing effect: in titanium dioxide, lactose, Sucrose, low density polyethylene, order to characterize the cosmetic effectiveness of the poly and an isotonic saline solution. merized polysaccharides produced by the present invention on the biomechanical properties of the skin, the tensing 0093 Advantageously, the compositions mentioned effect is measured mainly with the aid of a device sold under above are formulated in a form selected from the group the commercial designation <
Example 2 Cross-Linking a 2% Aqueous Solution of Xanthan. Sensory evaluation on the human skin 0102 During step 1 of Example 1, 1% of trisodium citrate is added to the 2% Xanthan solution. All the other Solution of non-cross-linked Solution of cross-linked steps are identical. Natrosol (R) 25OHHX. Natrosol (R) 25OHHX. ------0103) The tensing effect is close to the effect obtained in Example 1. +: tensing effect perceived non-significantly: +++: tensing effect perceived very significantly. Example 3 It is demonstrated by this test that the products of the Cross-Linking a 2% Aqueous Solution of Xanthan. invention enable a significant tensing effect to be obtained on skins of healthy volunteers, that it is possible to detect by 0104. During step 1 of Example 1, 0.4% of (trishy sensory evaluation. droxymethylaminomethane) is added to the 2% xanthan solution. All the other steps are identical. Example 6 0105 The tensing effect is close to the effect obtained in Cross-Linking an Aqueous Solution of Gum from Carob Example 1. (300,000 Da). 0.112. During step 1 of Example 5, a 5% solution of Example 4 carob, and preferably a 2% solution of carob, is pre Cross-Linking a 2% Aqueous Solution of Xanthan. pared. All the other steps are identical. 0113. The tensing effect is close to the effect obtained in 0106 During step 1 of Example 1, 0.5% of disodium Example 5. phosphate is added to the 2% xanthan solution. All the other steps are identical. Example 7 0107 The tensing effect is close to the effect obtained in Cross-Linking an Aqueous Solution of Xylitol (152 Da). Example 1. 0114. During step 1 of Example 5, a 5% solution of xylitol is prepared. All the other steps are identical. Example 5 0115 The tensing effect is close to the effect obtained in Cross-Linking an Aqueous Solution of Cellulose and Sen Example 5. sory Evaluation. Example 8 0.108 1. Preparation of an aqueous solution of cellulose (1,000,000 Da) as follows: 0.56 g of Natrosol (R) Cross-Linking an Aqueous Solution of Maltose (342 Da). 250HHX are dissolved in 94.64 g of cold, demineral 0116. During step 1 of Example 5, a 20% solution of ized water, 4.8 g of NaHCO, are then added to the preparation under strong agitation. After complete dis maltose is prepared. All the other steps are identical. solution, the pH stabilizes at a value of between 8 and 0.117) The tensing effect is close to the effect obtained in 8.4. Example 5. 0.109 2. Preparation of the cross-linking agent: 1.5g of Example 9a sebacic acid dichloride are dissolved in 8.5 g of buty lene glycol. Cross-Linking an Aqueous Solution of Carrageenans: Modi fication of the Rheology. 0.110) 3.Cross-linking of the aqueous solution of cel lulose: the solution prepared in 27 is added, under 0118 1. Preparation of an aqueous solution of carrag agitation, to the solution prepared in 1/. The whole is eenans (500,000 Da) (Genuvisco R, HERCULES) as left under agitation for 60 minutes, so as to cause a follows: 0.55 g of Genuvisco R. (HERCULES) are polymerization between the activated diacid on the one placed in 94.65 g of cold, demineralized water, 4.8g of hand and the alcohol functions of the polysaccharides NaHCOs are then added to the preparation under strong on the other hand. This reaction is promoted in basic agitation. After complete dissolution, the pH stabilizes medium. After reaction, the Solution of cross-linked at a value of between 8 and 8.4. Natrosol (R) 25OHHX can be used as such. 0119 2. Preparation of the cross-linking agent: 0.1 g of terephthalic acid dichloride are dissolved in 0.9 g of 0111 4.Principle of a measurement of tensing effect: two ethanol. areas of measurement are determined on the forearm (2cmx 2cm), and 50 mg of the solution of cross-linked Natrosol (R) 0120 3. Cross-linking of the aqueous solution of car 250HHX are applied onto the first area. 50 mg of the rageenans: the solution prepared in 27 is added, under solution of non-cross-linked Natrosol R 250HHX are agitation, to the aqueous solution prepared in 1/. The applied onto the second area. After having been left to dry whole is left under agitation for 60 minutes, so as to for one minute, the toning sensation is noted by sensory cause a polymerization between the activated diacid on evaluation by a panel of Volunteers. the one hand and the alcohol functions of the polysac US 2006/0188465 A1 Aug. 24, 2006
charide on the other hand. This reaction is promoted in Example 10 basic medium. After reaction, the Solution of cross Cross-Linking an Aqueous Solution of Raffinose Pentahy linked carrageenans can be used as Such or can be filtered so as to remove the compounds which are drate (594. Da): insoluble. 0127. During step 1 of Example 9, a 10% solution of raffinose is prepared. All the other steps are identical. 0121 The tensing effect is close to the effect obtained in Example 5. 0128. The tensing effect is close to the effect obtained in Example 5, but a very clear emollient effect is detected by Principle of a measurement of the viscosity: the measure the panelists. ment of the viscosity is carried out on the aqueous Solution of cross-linked polysaccharides versus the aque Example 11 ous solution of non-cross-linked polysaccharides. The Cross-Linking an Aqueous Solution of Acacia Gum. viscosimeter used is a rotation apparatus of Brookfield RVTDV-II type which is used a speed 50 and with needle 0129. During step 1 of Example 9, a 5% solution of 04. acacia gum (250,000 Da) is prepared. All the other steps are identical. 0122 Furthermore, the polymerization of the carbohy 0.130. The tensing effect is greater than the effect obtained drates induces an increase in their molecular mass, and this in Example 5. induces an increase in the Viscosity in a dissolution medium. The survey of the increase of this viscosity enables the Example 12 intensity of this polymerization to be measured. Cross-Linking an Aqueous Solution of a Polysaccharide/ Polyol Mixture. Measurement of the viscosity O131. Duriuring step 1l of EExample le 9,9 a solutionlution of glglycero 1 (92 Da) (10%, w/w) and of xanthan (2%, w/w) is pre Solution of non-cross-linked Solution of cross-linked pared. All the other steps are identical. carrageenans carrageenans 0.132. The tensing effect is close to the effect obtained in 588 cps 2632 cps Example 5, but a very clear emollient effect is detected by the panelists. Example 9b Example 13 Cross-Linking an Aqueous Solution of Prior-Hydrolyzed Cross-Linking an Aqueous Solution of an Oligosaccharide/ Carrageenans. Polyol Mixture. 0133. During step 1 of Example 9, a solution of mannitol 0123 1. Preparation of a hydrolyzed aqueous solution (182 Da) (10%, w/w) and of inulin (ca. 5000 Da) (5%, of carrageenans (Genuvisco(R), HERCULES) as fol w/w) is prepared. All the other steps are identical. lows: 10 g of Genuvisco R. (HERCULES) are placed in 90 g of 0.1M HCl solution (0.1 mole/liter). The 0.134. The tensing effect is close to the effect obtained in hydrolysis is carried out at 60° C. for 5 hours, under Example 5, but a very clear emollient effect is detected by moderate agitation, and is then stopped by neutraliza the panelists. tion with the aid of 1M NaOH up to a pH of between 8 and 9. Example 14 0.135 Use of the products of the invention in cosmetic or 0.124 2. Preparation of the cross-linking agent: 0.1 g of pharmaceutical formulations of oil-in-water emulsion type. terephthalic acid dichloride are dissolved in 0.9 g of ethanol.
0.125 3. Cross-linking of the aqueous solution of car Formulation 14a: rageenans: the solution prepared in 27 is added, under A. Water Qsp 100 agitation, to the aqueous solution prepared in 1/. The Butylene Glycol 2 whole is left under agitation for 60 minutes, so as to Glycerin cause a polymerization between the activated diacid on Sodium Dihydroxycetyl : Phosphate, the one hand and the alcohol functions of the polysac Isopropyl Hydroxycetyl ether charide on the other hand. This reaction is promoted in B Glycol Stearate SE 1 basic medium. After reaction, the Solution of cross Trisononacoin linked carrageenans can be diafiltered so as to remove Octyl Cocoate C Butylene Glycol, the salts, and then filtered so as to remove the com Methylparaben, pounds which are insoluble, or can be used as such. Ethylparaben, Propylparaben, pH adjusted to 5.5 0126 The tensing effect is greater than that observed in D Products of the invention O.O1-10% the preceding Examples (and particularly the effect obtained for the product of Example 5). US 2006/0188465 A1 Aug. 24, 2006
0136 Example 16 of the Invention 0139)
Formulation 14b: Water qsp 100 Butylene Glycol 2 Use of the products of the invention in a formulation Glycerin 3 of shampoo or shower gel type. Polyacrylamide, Isoparaffin, 2.8 A. Xantham Gum O.8 Laureth-7 Butylene Glycol, 2 Water qsp 100 Methylparaben, B Butylene Glycol, O.S Ethylparaben, Propylparaben; Methylparaben, Phenoxyethanol, 2 Ethylparaben, Propylparaben Methylparaben, Phenoxyethanol, O.S Propylparaben, Butylparaben, Methylparaben, ethylparaben Propylparaben, Butylparaben, Butylene Glycol O.S ethylparaben Products of the invention O.O1-10% C Citric acid O.8 D Sodium Laureth Sulfate 40.O E Product of the invention O.O1-10% 0137) Example 17 of the Invention Formulation 14c: 0140 Carbomer O.SO Propylene Glycol 3 Glycerol 5 Water qsp 100 Use of the products of the invention in a formulation Octyl Cocoate 5 of lipstick type and other anhydrous products. Bisabolol O.30 Dimethicone O.30 A. Mineral Wax 17.0 Sodium Hydroxide 160 Isostearyl IsoStearate 31.5 s Phenoxyethanol, O.SO Propylene Glycol Dipelargonate 2.6 Methylparaben, Propylene Glycol Isostearate 1.7 Propylparaben, Butylparaben, PEG 8 Beeswax 3.0 ethylparaben Hydrogenated Palm Kernel Oil 3.4 Perfume O.30 Glycerides, Products of the invention O.O1-10% Hydrogenated Palm Glycerides Lanolin Oil 3.4 Sesame Oil 1.7 Cetyl Lactate 1.7 Example 15 of the Invention Mineral Oil, Lanolin Alcohol 3.0 B Castor Oil qsp 100 Titanium Dioxide 3.9 0138) CI 1.5850:1 O.616 CI4S410:1 O.256 CI 1914.0:1 O.048 CI 77491 2.048 Use of the products of the invention in a formulation of water-in-oil type. C Products of the invention O.O1-5% A. PEG 30 -3 dipolyhydroxyStearate Capric Triglycerides 3 Cetearyl Octanoate 4 Example 18 of the Invention Dibutyl Adipate 3 Grape Seed Oil 1.5 0141) ojoba Oil 1.5 Phenoxyethanol, O.S Methylparaben, Propylparaben, Butylparaben, ethylparaben Use of the products of the invention in a formulation of Glycerin 3 aqueous gels (eye surrounds, slimmers, etc . . . ) Butylene Glycol 3 A. Water Qsp 100 Magnesium Sulfate O.S Carbomer O.S EDTA O.OS Butylene Glycol 15 Water qsp 100 Phenoxyethanol, Methylparaben, O.S Cyclomethicone 1 Propylparaben, Butylparaben, Dimethicone 1 Ethylparaben Perfume O.3 B Products of the invention O.O1-10% P Products of the invention O.O1-10% US 2006/0188465 A1 Aug. 24, 2006
Example 19 What is claimed is: 1. A method for manufacturing a cross-linked polymer of Evaluation of the Cosmetic Acceptance of a Preparation at least one carbohydrate component comprising at least one Containing the Subject of the Invention primary alcohol function, said method comprising cross 0142 Toxicology tests were carried out on the compound linking in an aqueous phase at least one primary alcohol obtained according to Example 2 incorporated at 10% in function of the carbohydrate component with at least one a 0.5% xanthan gel, by an ocular evaluation in the rabbit, reactive function of a cross-linking agent to obtain the by the study of the absence of abnormal toxicity by single cross-linked polymer of said carbohydrate component. oral administration in the rat and by the study of the 2. The method of claim 1, wherein the carbohydrate sensitizing power in the guinea pig. component is selected from a polysaccharide, an oligosac charide, a polyol, and any mixture thereof. Evaluation of the Primary Irritation of the Skin in the Rabbit: 3. The method of claim 1, wherein the cross-linking agent The preparations described above are applied without dilu is selected from a polycarboxylic acid chloride, a carboxylic tion at the dose of 0.5 ml on the skin of 3 rabbits according acid anhydride, a polyisocyanate, a polythioisocyanate, a to the method recommended by the OECD Directive in polyaldehyde, and any mixture thereof. relation to the study of < chitosan; group consisting of a polysaccharide of Xanthan which is cross-linked with sebacic acid dichloride, a cellulose which curdlan; is cross-linked with sebacic acid dichloride, a gum from gum adragante or gum tragacanth; carob which is cross-linked with sebacic acid dichloride, gum arabic or acacia gum, xylitol which is cross-linked with sebacic acid dichloride, maltose which is cross-linked with sebacic acid dichloride, Chia gum; a carrageenan which is cross-linked with terephthalic acid Gum elemi; dichloride, raffinose which is cross-linked with terephthalic acid dichloride, an acacia gum which is cross-linked with Gellan gum, terephthalic acid dichloride, a mixture of glycerol and of Gum ghatti or Indian gum, xanthan which is cross-linked with terephthalic acid dichlo gum karaya; ride, a mixture of mannitol and of inulin which is cross linked with terephthalic acid dichloride, and any mixture Shellac; and thereof. Manilla gum, 11. A composition selected from a cosmetic composition, a dermo-pharmaceutical composition, and a pharmaceutical b) a saccharide component selected from an oligosaccha ride, a monosaccharide and a disaccharide selected composition, comprising a polymer as defined in claim 7. from the group consisting of: 12. A composition selected from a cosmetic composition, a dermo-pharmaceutical composition, and a pharmaceutical a cyclodextrin, a C. cyclodextrin, a B cyclodextrin, or a composition, comprising a polymer as defined in claim 10. Y cyclodextrin and any mixture thereof; 13. A method of cosmetic care selected from the group a dextrin; consisting of tensing skin, toning skin, obtaining a reduction raffinose, cellobiose, Sucrose, maltose, lactose, treha of wrinkles, obtaining Small wrinkles, and improving the lose, dihydroxyacetone (DHA), fructose, Sorbose, biomechanical properties of the skin, comprising applying ribose, deoxyribose, Xylose, arabinose, glucose, onto the skin a crosslinked polymer as defined in claim 7. mannose, galactose, erythrose, threose, allose, 14. The method according to claim 13, wherein the atrose, gulose, idose, talose, erythrulose, Xylulose, cosmetic care is performed on at least one part selected from psicose, tagatose, Sedoheptulose, Xylobiose, chito the group consisting of the face, the neck, the hands and the biose, nigerose, aminaribiose, kojibiose, Sophorose, neckline. gentianose, gentiobiose, melibiose, melezitose, tura 15. A method of cosmetic care selected from the group nose, stachyose, verbascose, consisting of tensing skin, toning skin, obtaining a reduction gluconic acid, gluconolactone, glucosamine, galac of wrinkles, obtaining Small wrinkles, and improving the tosamine, galactosamine Sulfate, glucosamine Sul biomechanical properties of the skin, comprising applying fate; onto the skin a crosslinked polymer as defined in claim 10. 16. The method according to claim 15, wherein the a saponin, a Saponin from the bark of quillaya; cosmetic care is performed on at least one part selected from guanosine, uridine, the group consisting of the face, the neck, the hands and the streptomycin Sulfate; and neckline. 17. A method of cosmetic care comprising topically riboflavin; and applying a cosmetic composition comprising a polymer as c) a polyol selected from the group consisting of glycerol, defined in claim 7. sorbitol, erythritol, maltitol, sorbitol, mannitol, lactitol, 18. A method of cosmetic care comprising topically galactitol, ribitol, glycerol. Xylitol, myro-inositol, and a applying a cosmetic composition comprising a polymer as polyethylene glycol. defined in claim 10. 10. The cross-linked polymer according to claim 7. wherein the carbohydrate component is selected from the