US010143755B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 143, 755 B2 Borja et al. ( 45 ) Date of Patent: * Dec . 4 , 2018 ( 54 ) ANHYDROUS HYDROGEL COMPOSITION ( 52 ) U . S . CI. AND DELIVERY SYSTEM CPC .. .. .. A61K 47 / 38 ( 2013 . 01 ) ; A23L 29 / 20 ( 2016 .08 ) ; A61K 8 /0216 ( 2013 .01 ) ; A61K (71 ) Applicant : Acupac Packaging , Inc ., Mahwah , NJ 8 /042 ( 2013 .01 ) ; A61K 8 /345 (2013 . 01 ) ; A61K (US ) 8 /355 ( 2013 .01 ) ; A61K 8 / 731 (2013 .01 ) ; A61K 9 / 006 (2013 .01 ) ; A61K 9 /06 ( 2013 .01 ) ; A61K (72 ) Inventors : John Borja , Keyport , NJ (US ) ; 31/ 05 ( 2013 .01 ) ; A61K 31/ 122 ( 2013 .01 ) ; Stephanie Sharon Hayano , Millerton , A61K 31/ 785 ( 2013 . 01 ) ; A61K 33 / 18 NY (US ) (2013 .01 ) ; A61K 33 / 38 ( 2013 .01 ) ; A61K 38 / 1793 (2013 . 01 ) ; A61K 38 / 18 ( 2013 .01 ) ; ( 73 ) Assignee : Acupac Packaging Inc ., Mahwah , NJ A61K 38 / 1858 ( 2013 . 01 ) ; A61K 38 / 40 ( 2013 .01 ) ; A61K 39 / 3955 ( 2013 .01 ) ; A61K (US ) 47 / 10 ( 2013 .01 ) ; A61Q 11 /00 ( 2013 .01 ) ; A610 ( * ) Notice : Subject to any disclaimer , the term of this 19 /00 ( 2013 .01 ) ; CO7K 14 / 7151 (2013 .01 ) ; patent is extended or adjusted under 35 CO7K 16 / 241 ( 2013 . 01 ) ; A23V 2002 / 00 ( 2013 .01 ) ; A61K 2039 /505 (2013 .01 ) ; A61K U . S . C . 154 ( b ) by 0 days. 2800 / 10 ( 2013 .01 ) ; A61K 2800 / 31 ( 2013 . 01 ) ; This patent is subject to a terminal dis A61K 2800 / 591 ( 2013 .01 ) ; A6IK 2800 / 805 claimer . ( 2013 .01 ) ; A61K 2800 / 81 ( 2013 . 01 ) ; A61K 2800 /92 ( 2013 .01 ) ; COZK 2317 / 21 ( 2013 .01 ) ; ( 21 ) Appl. No .: 15 /835 ,517 CO7K 2317 /76 ( 2013 . 01) ; COZK 2317 / 94 ( 2013 .01 ) ; CO7K 2319 / 035 (2013 . 01 ) ; CO7K ( 22 ) Filed : Dec . 8 , 2017 2319 / 32 (2013 .01 ) (58 ) Field of Classification Search (65 ) Prior Publication Data CPC .. A61K 31/ 4427 ; A61K 38/ 40 ; A61K 47 / 38 US 2018 /0099052 A1 Apr . 12 , 2018 USPC .. .. .. .. .. 514 / 332 ; 424 /468 See application file for complete search history . Related U . S . Application Data ( 56 ) References Cited (63 ) Continuation of application No. 15 /454 , 244 , filed on Mar . 9 , 2017 , now Pat. No . 9 , 839 ,693 , which is a U . S . PATENT DOCUMENTS continuation of application No. 14 /280 ,220 , filed on 2008/ 0226715 Al * 9 / 2008 Cha .. .. .. .. .. .. .. .. A61K 9 / 2009 May 16 , 2014 , now Pat. No . 9 ,603 ,934 . 424 /468 (60 ) Provisional application No .61 / 824 ,893 , filed on May 17 , 2013 . OTHER PUBLICATIONS (51 ) Int. CI. Verma et al. “ Drug Delivery Technologies and Future Directions. " A61K 4738 ( 2006 .01 ) Pharmaceutical Technology On -Line , 25 ( 2 ) , 1 - 14 , ( 2001) Pharma ceutical Technology, Feb . 2001, www .pharmaportal .com , 14 pages . A61K 8 / 02 ( 2006 . 01 ) Slomkowski et al. Terminolgoy of polymers and polymerization A61K 8 / 04 ( 2006 .01 ) processes in dispersed systems ( IUPAC Recommendations 2011 , A61K 8 / 34 ( 2006 .01 ) Pure Appl. Chem ., vol. 83 , No . 12 , pp . 2229 - 2259, 2011, doi : A61K 8 / 35 ( 2006 . 01 ) 10 . 1351 /PAC -REC - 10 -06 -03 , copyright 2011 IUPAC , Publication A61K 9 / 06 ( 2006 .01 ) date (Web _ : Sep . 10 , 2011 , 31 pages . A61K 31/ 05 ( 2006 .01 ) Finnin et al. “ Transdermal Penetration Enhancers : Applications, A61K 38 / 17 ( 2006 . 01) Limitations, and Potential ” Journal of Pharmaceutical Sciences vol . A61K 47 / 10 ( 2017 .01 ) 88, No . 10 , Oct . 1999, 4 pages . A610 11 /00 ( 2006 . 01 ) A23L 29 / 20 ( 2016 .01 ) * cited by examiner A61K 9 / 00 ( 2006 .01 ) A61K 31 / 122 ( 2006 .01 ) Primary Examiner — Walter E Webb A61K 31 / 785 ( 2006 .01 ) (74 ) Attorney , Agent, or Firm - Ziegler IP Law Group , A61K 33 / 18 ( 2006 .01 ) LLC A61K 33 /38 ( 2006 .01 ) A61K 8 / 73 ( 2006 .01 ) ( 57 ) ABSTRACT A61K 39 / 395 ( 2006 .01 ) The present disclosure relates to anhydrous hydrogels useful COZK 14 /715 ( 2006 .01 ) as mucoadhesive (oral compositions ) or as topical agents COZK 16 /24 ( 2006 . 01 ) and may be used to deliver an active agent such as active A61Q 19 / 00 ( 2006 .01 ) pharmaceutical agents ( API' s ) , coagulants , fragrances , fla A61K 38 / 18 ( 2006 .01 ) vors , and other actives and excipients . A61K 38 / 40 ( 2006 .01 ) A61K 39 /00 (2006 .01 ) 20 Claims, No Drawings US 10 , 143 ,755 B2 ANHYDROUS HYDROGEL COMPOSITION present disclosure do not dry out or change shape upon AND DELIVERY SYSTEM standing . They are also resistant to so called " cold creep " upon standing . CROSS -REFERENCE TO RELATED Suitable biocompatible polymers include sodium car APPLICATIONS 5 boxymethylcellulose , pectin , sodium alginate , sodium / cal cium alginate , polylactic acid , chitosan , carageenan , xan This application is a continuation of U . S . patent applica than , gellan , polyaspartic acid , polyglutamic acid , tion Ser. No . 15 / 454 . 244 . filed on Mar . 9 . 2017 . which is a hyaluronic acid or salts or derivatives thereof. Most pre continuation of U . S . Pat . No . 9 ,603 , 934 , issued on Mar . 28 , ferred is sodium carboxymethylcellulose . 2017 which claims benefit to U . S . provisional 61/ 824 . 893 10 Polyalcohols include alcohols containing 2 to 10 carbon filed May 17 , 2013 , which are incorporated herein by atoms and 2 to 7 hydroxyl groups including ethylene glycol, reference . 1 , 2 -propylene glycol, 1 , 4 -butylene glycol , glycerine , eryth rit (meso - 1 , 2 , 3 , 4 - Butantetrol) , sorbit , mannit , methylgluco FIELD side, diglycerine , triglycerine and /or pentaerythrit . Particu 15 larly , the polyol is glycerin . The aspects of the present disclosure relates to anhydrous Active agents include pharmaceutical agents such as hydrogels useful as mucoadhesive ( oral compositions ) or as analgesics, decongestants , bronchodilators and other antia topical agents and may be used to deliver an active agent sthmatic agents , cardiovascular agents such as beta -block such as active pharmaceutical agents (API ' s ) , coagulants , ers , ACE inhibitors , diuretics , antithrombics , etc ., diabetic fragrances , flavors , and other actives and excipients . 20 agents , antihistamines , anesthetics , antifungals, antinause ants , antiemetics, antibacterial agents , antifungal agents , BACKGROUND corticosteroids, neurological agents , anti - inflammatories, vaccines , biological agents ( such as Humera , Enbrel and Hydrogels refer to a network of hydrophilic polymer Remicade ), wound healing agents and anticonvulsants . Vita chains that are generally found as a colloidal gel in which 25 mins (particularly A , C , D and E ) are a particular embodi water is the dispersion medium . Hydrogels are highly absor - ment of an active agent. The concentration of the active bent ( they can contain over 99. 9 % water ) natural or syn ingredient in the gel base is , of course, dependent on the thetic polymers . Hydrogels also possess a degree of flex - identity of the active agent, the condition and patient being ibility very similar to natural tissue , due to their significant treated and the potency desired . water content (“ Terminology of polymers and polymeriza - 30 One group of particularly interesting active agents include tion processes in dispersed systems ( IUPAC Recommenda - pharmaceutical agents that are moisture sensitive such as tions 2011) ” . Pure and Applied Chemistry 83 ( 12) : 2229 - biologicals , enzymes, proteins (and fragments thereof) . 2259 . 2011) . Common uses for hydrogels include : tissue Other moisture sensitive pharmaceutical agents include engineering , sustained - release drug delivery systems, sen - Adderall , alprazolam , gemifloxacin , hydromorphone and sors ( including biosensors ) , disposable diapers or sanitary 35 zolmitriptan . napkins, contact lenses, and dressings for healing of burn or Another embodiment relates to antifungal active agents other wounds . such as Amphotericin B , Candicidin , Filipin , Hamycin , Hydrogels are characterized by the inclusion of water Natamycin , Nystatin , Rimocidin , Bifonazole , Butoconazole , which acts to disperse the polymer into a colloidal mass . Clotrimazole , Econazole , Fenticonazole , Isoconazole , Keto Unfortunately , the presence of water limits the utility of 40 conazole , Luliconazole, Miconazole , Omoconazole , Oxi these products to water sensitive materials or environments conazole , Sertaconazole , Sulconazole , Tioconazole , Alba where moisture is contraindicated . The physical properties conazole , Fluconazole , Isavuconazole , Itraconazole , of water also dictate the physical properties of the hydrogel, Posaconazole , Ravuconazole , Terconazole , Voriconazole , such as reactivity to acids and bases . Thus there is a need to Abafungin , Amorolfin , Butenafine , Naftifine , Terbinafine , identify new hydrogels without the aqueous limitations. 45 Anidulafungin , Caspofungin , and Micafungin . Another embodiment of the present disclosure relates to SUMMARY wart removal compounds such as salicylic acids. Such treatments are of specific interest due to heightened response The aspects of the present disclosure relate to an anhy - to the anhydrous medium of the hydrogel. drous hydrogel for the delivery of an active agent( s ). Par - 50 One specific embodiment relates to wound healing agents ticularly important active agents are those that are moisture and products ( such as gauze , bandage, and synthetic skin ) . sensitive . The aspects of the present disclosure also relate to Such agents include aloe, benzyl alcohol, coagulants ( such processes for the preparation of, intermediates used in the as styptic , chitosan , vitamin K , phytomenadione , menadi preparation of , compositions