WO2018167622A1 - Process for the preparation of wound dressing sponge - Google Patents
Process for the preparation of wound dressing sponge Download PDFInfo
- Publication number
- WO2018167622A1 WO2018167622A1 PCT/IB2018/051585 IB2018051585W WO2018167622A1 WO 2018167622 A1 WO2018167622 A1 WO 2018167622A1 IB 2018051585 W IB2018051585 W IB 2018051585W WO 2018167622 A1 WO2018167622 A1 WO 2018167622A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chitosan
- sponge
- acid
- wound dressing
- drying
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 48
- 230000008569 process Effects 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000004108 freeze drying Methods 0.000 claims abstract description 30
- 229920001477 hydrophilic polymer Polymers 0.000 claims abstract description 22
- 238000000137 annealing Methods 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 13
- 229920001661 Chitosan Polymers 0.000 claims description 88
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 229960000583 acetic acid Drugs 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 12
- 229920001684 low density polyethylene Polymers 0.000 claims description 10
- 239000004702 low-density polyethylene Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000006185 dispersion Substances 0.000 claims description 9
- 238000004090 dissolution Methods 0.000 claims description 7
- 229920002101 Chitin Polymers 0.000 claims description 6
- 150000001398 aluminium Chemical class 0.000 claims description 6
- 239000000843 powder Substances 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000004815 dispersion polymer Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 230000001678 irradiating effect Effects 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 2
- 235000011054 acetic acid Nutrition 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 239000004220 glutamic acid Substances 0.000 claims description 2
- 235000013922 glutamic acid Nutrition 0.000 claims description 2
- 235000011167 hydrochloric acid Nutrition 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 230000001954 sterilising effect Effects 0.000 abstract description 16
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 16
- 238000004806 packaging method and process Methods 0.000 abstract description 8
- 239000008135 aqueous vehicle Substances 0.000 abstract description 3
- 206010052428 Wound Diseases 0.000 description 51
- 208000027418 Wounds and injury Diseases 0.000 description 51
- 239000000243 solution Substances 0.000 description 29
- 238000012360 testing method Methods 0.000 description 16
- 229920000642 polymer Polymers 0.000 description 11
- 238000001035 drying Methods 0.000 description 10
- 238000010521 absorption reaction Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000000845 anti-microbial effect Effects 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 230000023597 hemostasis Effects 0.000 description 5
- 239000004382 Amylase Substances 0.000 description 4
- 102000013142 Amylases Human genes 0.000 description 4
- 108010065511 Amylases Proteins 0.000 description 4
- 229920000945 Amylopectin Polymers 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- 235000019418 amylase Nutrition 0.000 description 4
- 229920001436 collagen Polymers 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- 239000000017 hydrogel Substances 0.000 description 4
- 230000036512 infertility Effects 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000006196 deacetylation Effects 0.000 description 3
- 238000003381 deacetylation reaction Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000002439 hemostatic effect Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000002522 swelling effect Effects 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 206010011985 Decubitus ulcer Diseases 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 206010056340 Diabetic ulcer Diseases 0.000 description 2
- -1 Elastic Bandages Substances 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 208000035874 Excoriation Diseases 0.000 description 2
- 229920001503 Glucan Polymers 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000034693 Laceration Diseases 0.000 description 2
- 208000005230 Leg Ulcer Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 208000004210 Pressure Ulcer Diseases 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 2
- 206010040943 Skin Ulcer Diseases 0.000 description 2
- 208000002847 Surgical Wound Diseases 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical group N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000012668 chain scission Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940059329 chondroitin sulfate Drugs 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 2
- 229940099552 hyaluronan Drugs 0.000 description 2
- 239000000416 hydrocolloid Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000058 polyacrylate Polymers 0.000 description 2
- 229920000768 polyamine Polymers 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 239000012602 primary packaging material Substances 0.000 description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 241001514662 Leptospermum Species 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229910021536 Zeolite Inorganic materials 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
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- 230000017531 blood circulation Effects 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
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- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000515 collagen sponge Substances 0.000 description 1
- 238000012505 colouration Methods 0.000 description 1
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- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
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- 230000005847 immunogenicity Effects 0.000 description 1
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- 230000003993 interaction Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F13/00—Bandages or dressings; Absorbent pads
- A61F13/00987—Apparatus or processes for manufacturing non-adhesive dressings or bandages
- A61F13/00991—Apparatus or processes for manufacturing non-adhesive dressings or bandages for treating webs, e.g. for moisturising, coating, impregnating or applying powder
-
- A61F13/01012—
-
- A61F13/01017—
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0036—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/08—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Definitions
- the present invention relates to a process for the preparation of wound dressing sponge comprising hydrophilic polymer, acid and aqueous vehicle.
- the present invention also relates to efficient process for the preparation of wound dressing sponge, wherein process comprising steps of freeze-drying, annealing, packaging and sterilization.
- wound dressing needs to provide some basic physical and biological function, such as avoiding fluid loss, human skin-like with flexibility, gas permeation, water vapour flux, absorbing wound exudate, mechanical strength, anti-bacterial or sterilization without causing wound aggravation, adherence to wound, non-toxicity, non-irritant and improvement of epithelization etc. Therefore, varieties of wound dressings have been developed to fulfil the aforementioned requirements in the form of non-woven, porous and membrane types are available for different wound conditions.
- Wounds are often treated by covering them with products such as alginates, composites, contract layers, foams, hydrocolloids, hydrogels, impregnated gauzes, specialty absorptive, and transparent films.
- products such as alginates, composites, contract layers, foams, hydrocolloids, hydrogels, impregnated gauzes, specialty absorptive, and transparent films.
- the theory behind the use of these products is that covering the wound decreases the risk of infection, keeps the wound from drying out, and decreases scarring.
- Hydrophilic polymers include but not limited to polyacrylate, an alginate, chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or combinations thereof.
- the starch may be of amylase, amylopectin and a combination of amylopectin and amylase.
- the hydrophilic polymer is chitosan.
- Chitin and its derivatives has gained great interest in biomedical application including tissue engineering, drug delivery, wound healing, obesity treatment because of their versatile features like natural source, antimicrobial property, low immunogenicity, biodegradability and biocompatibility. Furthermore, these can be molded easily into various forms and shapes including sponges, films, gels, beads and fibres.
- Chitin is a macromolecule commonly found in invertebrates, algae cell walls and yeast. Usually extracted from crab or shrimp shells. Deacetylated form of chitin is called as chitosan, it should contain at least 60% of D-glucosamine residues. Prudden et al. has developed and commercialized wound dressing as medical product named "bas-Chitin W", manufactured by UNITIKA, Japan, and its clinical manifestation was good.
- Chitosan is a linear, semi-crystalline polysaccharide composed of (l-4)-2- acetamido-2-deoxyb-D-glucan (N-acetyl D-glucosamine) and (l-4)-2-amino-2- deoxyb-D-glucan (D-glucosamine) units.
- Chitosan as wound dressing material is used in various types of conditions including haemostasis, pressure sores, diabetic ulcers, leg ulcer, donor sites and graft sites, surgical wounds, skin abrasions and lacerations, 1st and 2nd degree burns, trauma wounds.
- the superior physical and mechanical properties including high surface area, porosity and tensile strength of wound dressing sponge depends on chitosan concentration, manufacturing process and freeze-drying parameters, further depends on the physico-chemical properties chitosan including solubility, molecular weight, degree of deacetylation and viscosity.
- chitosan The antibacterial activity of chitosan is due to its cationic nature; hence, it can attach and penetrate the anionic bacterial cell wall, binds with DNA and inhibit transcription and protein synthesis. Further, chitosan can form impermeable layer and leads to bacterial cell death.
- US 4,532,134 disclose the medical properties of chitosan which include hemostasis, hindered of growth of fibroblast, and improving tissue regeneration.
- Japan Patent Publication Number 08-224293 mentions the medical properties of chitosan includes activating macrophage and leukocyte, anti-bacterial, and further preventing wound suppurated.
- CN 1387922 A discloses the composition of Chitosan and collagen sponge composition and process for the preparation thereof.
- the sponge of this invention is prepared by 1. Chitosan and collagen are weighed. 2. Chitosan solution with glacial acetic acid formulated as a concentration of 0.5% to 3% of the solution. 3. Collagen with glacial acetic acid formulated as a solution concentration of 1% to 4% solution. 4. Mixing the two solutions, and then the mixture by vacuum freeze-dried to give quick- setting hemostatic sponge. Collagen is extra here which is also polymer.
- US 2005/0147656 disclose the tissue dressing applied on a site of tissue injury to ameliorate bleeding, other forms of fluid loss and as protective covering. This patent discussed about the manufacture of tissue dressing pad assembly and tissue dressing sheet assembly. Further, indications and configurations for hydrophilic polymer sponge. The wound dressing sponge was prepared by freeze-drying technique and the duration to complete the process is about 42-48h.
- US 2005/0203058 disclose stable compositions comprising a- and ⁇ -chitosan and derivatives thereof for controlled absorption and/or coagulation of fluids from a wound or bleeding site. This invention further discloses methods for preparing these stable compositions and articles of manufacture comprising these compositions.
- the wound dressing pad was prepared by freeze-drying technique and the duration to complete the process is about 18h.
- US 2009/0130186 disclose wound dressing composition comprising chitosan and silver nanoparticles. It also discloses the process for the preparation of chitosan, silver nanoparticles composition, wherein chitosan/water solution is processed by the addition of an acid to the chitosan/water solution, then silver nanoparticle solution is prepared and both the solution are mixed, this solution is further poured and freeze dried. Freeze-drying process is well-established technique to fabricate porous materials for a wide range of applications. Freezing of solutions, emulsions or dispersions causes solute to be excluded by ice front into the interstitial spaces between ice crystals. Further sublimation leads to formation of porous structure (Jie Wu and J. Carson Meredith, 2014). Freeze-drying is a feasible strategy to improve physical, chemical and mechanical stability of the product.
- the objective of the present invention is to provide a process for preparing wound dressing sponge comprising hydrophilic polymer, acid and water. Another objective of the present invention is to provide an effective process for the preparation of wound dressing sponge, wherein process comprising freeze-drying, annealing, packaging and sterilization.
- Still another objective of the present invention is to provide a process for preparing wound dressing sponge comprising chitosan, acetic acid and water.
- Still another objective of the present invention is to provide an effective process for the preparation of chitosan wound dressing sponge, wherein process comprising freeze-drying, annealing, packaging and sterilization.
- Still another objective of the present invention is to provide an effective process for the preparing wound dressing sponge, wherein the processing time is reduced, there by increasing the productivity.
- Yet another objective of the present invention is to provide an effective process for preparing wound dressing sponge, where the process involves freeze-drying the product for 12-15 h, annealing at 60-80°C for 15-30 min, packaging in pouch, purged with nitrogen, heat sealed and sterilization by 60 Co source at the doses of 4 kGy to 25 kGy.
- One embodiment of the present invention provides a process for the preparation of wound dressing sponge comprising hydrophilic polymer, acid and water, wherein the processing time in freeze drying is reduced.
- Another embodiment of the present invention provides a process for preparing wound dressing sponge using freeze-drying technique for 12-15 h, annealing at 60- 80°C for 15-30 min, packaging in pouch, purged with nitrogen, heat sealed and sterilization by 60 Co source at the doses of 4 kGy to 25 kGy.
- Another embodiment of the present invention provides a process for preparing wound dressing sponge, the process comprising steps of: a) adding hydrophilic polymer to water and stirring at room temperature to obtain hydrophilic polymer dispersion,
- Yet another embodiment of the present invention provides a process for the preparation of wound dressing sponge comprising chitosan, acetic acid and water, wherein the processing time in freeze drying is reduced.
- Another embodiment of the present invention provides a process for preparing chitosan wound dressing sponge using freeze-drying technique for 12-15 h, annealing at 60-80°C for 15-30 min, packaging in pouch, purged with nitrogen, heat sealed and sterilization by 60 Co source at the doses of 4 kGy to 25 kGy.
- Yet another embodiment of the present invention provides a process for preparing chitosan wound dressing sponge, the process comprising steps of: a) adding chitosan powder or flakes to water and stirring at room temperature to obtain chitosan dispersion,
- a dressing is a sterile sponge or compress applied to a wound to promote healing and protect the wound from further harm.
- a dressing is designed to be in direct contact with the wound, as distinguished from a bandage, which is most often used to hold a dressing in place. Many modern dressings are self-adhesive.
- Wound Dressing is categorised as follows: Absorptives, Alginates, Antimicrobial Dressings, Biophysical agents, Collagens, Composites, Contact layers, Elastic Bandages, Foams, Gauzes & Non-wovens, Honey (Active Leptospermum), Hydrocolloids, Hydrogels: Amorphous, Hydrogels: Impregnated, Hydrogels: Sheets, Impregnated Dressings, Silicone Gel Sheets, Transparent Films and Wound fillers. Sponges come under the categories of Antimicrobial Dressings.
- Wound dressing may comprise a hemostatic sponge and a backing. Sponge may be placed in contact with a bleeding wound to accelerate and/or promote clotting of blood around the wound. Sponge may be used to promote clotting for blood flows that arise from trauma, medical procedures, nose bleeds, dental procedures, and/or other causes. Wound dressing may be made at least in part by freeze-drying a hemostatic solution to form. Sponge used in the present invention is based on the fact that sponge 1) should not be reactive with the product 2) should be stable to gamma irradiation dose 3) should not show leaching property 4) should maintain its physical property after gamma irradiation 5) should maintain its integrity.
- Hydrophilic polymers include but not limited to polyacrylate, an alginate, chitosan, chitin, salts of chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or combinations thereof.
- the starch may be of amylase, amylopectin and a combination of amylopectin and amylase.
- the hydrophilic polymer is chitosan.
- Hydrophilic polymer used in the present invention is a medium molecular weight ranging from about 1,90,000 to about 3,10,000 g/mol.
- the concentration of hydrophilic polymer used in the present invention is 0.5% - 3.0%, preferably 1.0% to 2.0% and most preferably 1.75%.
- Acids includes but not limited to acetic acid, glutamic acid, lactic acid, formic acid, hydrochloric acid, glycolic acid, succinic acid.
- the acid used is acetic acid.
- the concentration of the acid used in the present invention is about 0.5% to 2%, preferably 1% w/w to 2% w/w, most preferably 1.5%.
- the acetic acid is added and mixed through the dispersion to cause dissolution of the chitosan solid in order to get homogeneous viscous solution. The rate of dissolution will depend on the temperature of the solution, the molecular weight of the chitosan.
- the chitosan solution percentage is greater than 0.5% chitosan and less than 3.0% chitosan, preferably 1.0% to 2.0% and most preferably 1.75%.
- the acetic acid is added to the solution to provide for an acetic acid solution percentage (w/w) at more than 0.5% and less than 2%, preferably 1% w/w to 2% w/w, most preferably 1.5%.
- aqueous vehicle is water percentage (w/w) is greater than 95% and less than 99%.
- the chitosan used to prepare the chitosan solution preferably has a degree of deacetylation in the range of 75-85%.
- the chitosan solution preferably prepared at room temperature by addition of chitosan powder or flakes to water under stirring.
- acetic acid is added under stirring to facilitate dissolution of chitosan solid.
- the concentration of chitosan should be in the range of 0.5- 3% (w/w) hydrophilic polymer.
- the acid should be acetic acid in the range of 1-2% (w/w) and the balance (about 95% - 97% w/w) being milli-q- water.
- Chitosan Freeze-drying of aqueous chitosan solution Chitosan has greater affinity to form hydrogen bond with water.
- the water absorption depends on the initial moisture present and storage conditions, like temperature and humidity.
- the presence of water plays an important role especially in chitosan based solid formulations, affect flow properties, compressibility of powders and tensile strength.
- at higher amounts of water in chitosan structure leads to faster and significant damage or deterioration to the polymer by hydrolysis.
- the prepared chitosan solution is subjected for freeze-drying step.
- the chitosan solution is transferred into tray or mold should have good thermal conductivity and made of iron, aluminium, silver.
- the mold may also be coated with thin inert metallic coating including nickel, gold, platinum or polytetrafluoroethylene (Teflon) or fluorinated ethylene polymer (FEP). Freezing of the chitosan, solution in this way improves the quality of product.
- the time taken to complete freezing and drying steps is within 12 - 15 h, which significantly reduces the process time and cost to fabricate chitosan sponge with superior physical and mechanical properties.
- the freezing temperature is preferably in the range of -10°C to -40°C, most preferably at -20°C.
- -10°C When frozen at -30°C and -40°C sponge is more closed and intact with smaller pore size, at -10°C the formed sponge is very porous in structure with bigger pore size.
- the formed sponge is microporous, intact and with optimum mechanical properties.
- the frozen chitosan sample undergoes water removal, in drying step without damaging chitosan structure and integrity.
- primary drying temperature is preferably in the range of 15°C to 30°C, most preferably 25°C with ramp rate of 0.05°C/min to 0.1°C/min, most preferably 0.08°C/min and preferable vacuum of 200 mTorr for a preferable holding period of 12 h to 15 h, most preferably, for a period of 12.5 h.
- temperature is preferably in the range of 25°C to 50°C, most preferably 35°C with ramp rate of 0.2°C/min to 0.8°C/min, most preferably 0.5°C/min and preferable vacuum of 150 mTorr for a preferable holding period of 2h to 5h, most preferably, for a period of 3h.
- the prepared sponge After freeze-drying, the prepared sponge is exposed to 60-80°C in an oven for 15 - 30 min for annealing to remove free water and residual acetic acid. Annealing at optimal or moderate temperatures can enhance tensile strength without affecting water absorption, swelling and other physical properties of sponge. Samples without annealing showed excess amounts of loose water, residual acetic acid and poor tensile properties. Exposure to elevated temperature may change several polymer properties, including aqueous solubility, viscosity and appearance. Decomposition of chitosan increases as increase in temperature and duration of exposure. Exposure to higher temperature causes significant loss of moisture (dehydration), which results poor physical and mechanical properties. Dark brown colouration of sponge with poor tensile strength and no swelling properties.
- the sponge is placed in a pouch and evacuated, then it is desirably purged with inert gas such as argon or nitrogen gas and heat-sealed.
- the pouch is usually made of triple laminated aluminium pouch (TLAP) or low-density polyethylene (LDPE) pouch.
- TLAP triple laminated aluminium pouch
- LDPE low-density polyethylene
- the pouch should act as barrier to air and moisture to extend the shelf life of the product.
- PP polypropylene
- Selection of primary packaging material for sponge is based on 1) should not be reactive with the product 2) should be stable to gamma irradiation dose 3) should not show leaching property 4) should maintain its physical property after gamma irradiation 5) should maintain its integrity.
- Chitosan based formulations especially applicable for wounds have to be sterilized.
- Commonly used sterilization methods include steam sterilization, exposure to dry heat and ethylene oxide or gamma irradiation. All these methods may cause irreversible alteration of physical, chemical and functional properties of chitosan.
- Sterilization by saturated steam may cause chain scission of the polymer results in reduced viscosity.
- sterilization by autoclave is not suitable for chitosan films and sponges results in reduced tensile strength.
- chitosan heated at 160°C for 2 h showed poor or no swelling and become insoluble in acidic solutions, which may be related to inter chain crosslinking of polymer functional groups.
- Sterilization by ethylene oxide has to be quarantined prior to use in order to remove gas residue.
- Gamma irradiation is a potential sterilization technique for chitosan-based formulations.
- Gamma irradiation also may cause chain scission, significant decrease in molecular weight and increase degree of deacetylation in a dose dependent manner.
- sponges showed lower water sorption capacity and higher tensile strength due to polymer chain rearrangements.
- Irradiation conditions are very important determinants in extent of radiation induced reactions in chitosan polymer network structure. Radiation induced scission of chitosan chains results in lower glass transition temperature. Irradiation in presence of air can alter its physical and mechanical properties of chitosan sponge including loss of water sorption capability, swelling and improved tensile strength, probably due to changes in chain interaction and rearrangement, Irradiation in anoxia showed poor water absorption and swelling properties. Sponge packaged in presence of inert gas like nitrogen did not affect sponge physical and mechanical properties.
- Packaged pouch is sterilized by gamma irradiation at the dose in the range of 4kGy to 25 kGy.
- Chitosan is obtained from purer sources compared to other chitosan from exoskeletons that competition use. Formulations were developed using different concentrations of chitosan and various freeze-drying conditions. Further, the final product is sterilized by gamma irradiation at different doses. The formulations prepared with different variations were evaluated for their description, thickness, moisture content, acetic acid content, water absorption capacity, disintegration test, tensile strength, bacterial endotoxin test and sterility.
- the obtained homogenous solution was transferred into trays and trays were subjected for freeze-drying process for 12 - 15 h. After freeze-drying, obtained sponge was subjected for annealing in hot air oven at 80°C/20 min. Sponges were cut into predetermined sizes and placed in triple laminated aluminium pouch, purged with nitrogen and heat- sealed.
- Thickness of the sponge was measured using digital Vernier calliper
- Acetic acid content Acetic acid content was measured using HPLC.
- Tensile strength Tensile strength of sponge was measured using universal testing machine. Sterility test: Sterility testing was performed according to USP general chapter ⁇ 71>.
- Antimicrobial effectiveness testing was performed according to USP General Chapter (51).
- Bacterial Endotoxin Test Bacterial Endotoxin Test was performed for optimized formulation. The testing was performed according to USP General Chapter ⁇ 85 >.
Abstract
The present invention relates to a process for the preparation of wound dressing sponge comprising hydrophilic polymer, acid and aqueous vehicle. The present invention also relates to efficient process for the preparation of wound dressing sponge, wherein process comprising steps of freeze-drying, annealing, packaging and sterilization.
Description
PROCESS FOR THE PREPARATION OF WOUND DRESSING
SPONGE
FIELD OF THE INVENTION
The present invention relates to a process for the preparation of wound dressing sponge comprising hydrophilic polymer, acid and aqueous vehicle.
The present invention also relates to efficient process for the preparation of wound dressing sponge, wherein process comprising steps of freeze-drying, annealing, packaging and sterilization.
BACKGROUND OF THE INVENTION Ideally, wound dressing needs to provide some basic physical and biological function, such as avoiding fluid loss, human skin-like with flexibility, gas permeation, water vapour flux, absorbing wound exudate, mechanical strength, anti-bacterial or sterilization without causing wound aggravation, adherence to wound, non-toxicity, non-irritant and improvement of epithelization etc. Therefore, varieties of wound dressings have been developed to fulfil the aforementioned requirements in the form of non-woven, porous and membrane types are available for different wound conditions.
Wounds are often treated by covering them with products such as alginates, composites, contract layers, foams, hydrocolloids, hydrogels, impregnated gauzes, specialty absorptive, and transparent films. The theory behind the use of these products is that covering the wound decreases the risk of infection, keeps the wound from drying out, and decreases scarring.
Hydrophilic polymers include but not limited to polyacrylate, an alginate, chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or combinations thereof.
The starch may be of amylase, amylopectin and a combination of amylopectin and amylase. Preferably, the hydrophilic polymer is chitosan.
Chitin and its derivatives has gained great interest in biomedical application including tissue engineering, drug delivery, wound healing, obesity treatment because of their versatile features like natural source, antimicrobial property, low immunogenicity, biodegradability and biocompatibility. Furthermore, these can be molded easily into various forms and shapes including sponges, films, gels, beads and fibres.
Chitin is a macromolecule commonly found in invertebrates, algae cell walls and yeast. Mostly extracted from crab or shrimp shells. Deacetylated form of chitin is called as chitosan, it should contain at least 60% of D-glucosamine residues. Prudden et al. has developed and commercialized wound dressing as medical product named "bas-Chitin W", manufactured by UNITIKA, Japan, and its clinical manifestation was good. Chitosan is a linear, semi-crystalline polysaccharide composed of (l-4)-2- acetamido-2-deoxyb-D-glucan (N-acetyl D-glucosamine) and (l-4)-2-amino-2- deoxyb-D-glucan (D-glucosamine) units.
Chitosan as wound dressing material is used in various types of conditions including haemostasis, pressure sores, diabetic ulcers, leg ulcer, donor sites and graft sites, surgical wounds, skin abrasions and lacerations, 1st and 2nd degree burns, trauma wounds.
The superior physical and mechanical properties including high surface area, porosity and tensile strength of wound dressing sponge depends on chitosan
concentration, manufacturing process and freeze-drying parameters, further depends on the physico-chemical properties chitosan including solubility, molecular weight, degree of deacetylation and viscosity.
The antibacterial activity of chitosan is due to its cationic nature; hence, it can attach and penetrate the anionic bacterial cell wall, binds with DNA and inhibit transcription and protein synthesis. Further, chitosan can form impermeable layer and leads to bacterial cell death.
US 4,532,134 disclose the medical properties of chitosan which include hemostasis, hindered of growth of fibroblast, and improving tissue regeneration. Japan Patent Publication Number 08-224293 mentions the medical properties of chitosan includes activating macrophage and leukocyte, anti-bacterial, and further preventing wound suppurated.
CN 1387922 A discloses the composition of Chitosan and collagen sponge composition and process for the preparation thereof. The sponge of this invention is prepared by 1. Chitosan and collagen are weighed. 2. Chitosan solution with glacial acetic acid formulated as a concentration of 0.5% to 3% of the solution. 3. Collagen with glacial acetic acid formulated as a solution concentration of 1% to 4% solution. 4. Mixing the two solutions, and then the mixture by vacuum freeze-dried to give quick- setting hemostatic sponge. Collagen is extra here which is also polymer. US 2005/0147656 disclose the tissue dressing applied on a site of tissue injury to ameliorate bleeding, other forms of fluid loss and as protective covering. This patent discussed about the manufacture of tissue dressing pad assembly and tissue dressing sheet assembly. Further, indications and configurations for hydrophilic polymer sponge. The wound dressing sponge was prepared by freeze-drying technique and the duration to complete the process is about 42-48h.
US 2005/0203058 disclose stable compositions comprising a- and β-chitosan and derivatives thereof for controlled absorption and/or coagulation of fluids from a wound or bleeding site. This invention further discloses methods for preparing these
stable compositions and articles of manufacture comprising these compositions. The wound dressing pad was prepared by freeze-drying technique and the duration to complete the process is about 18h.
US 2009/0130186 disclose wound dressing composition comprising chitosan and silver nanoparticles. It also discloses the process for the preparation of chitosan, silver nanoparticles composition, wherein chitosan/water solution is processed by the addition of an acid to the chitosan/water solution, then silver nanoparticle solution is prepared and both the solution are mixed, this solution is further poured and freeze dried. Freeze-drying process is well-established technique to fabricate porous materials for a wide range of applications. Freezing of solutions, emulsions or dispersions causes solute to be excluded by ice front into the interstitial spaces between ice crystals. Further sublimation leads to formation of porous structure (Jie Wu and J. Carson Meredith, 2014). Freeze-drying is a feasible strategy to improve physical, chemical and mechanical stability of the product.
All the prior art references shows use of hydrophilic polymers as wound dressing material in haemostasis, pressure sores, diabetic ulcers, leg ulcer, donor sites and graft sites, surgical wounds, skin abrasions and lacerations, 1st and 2nd degree burns, trauma wounds and process for preparing wound dressing sponges comprising hydrophilic polymers. However, the inventors of present invention provide the process for the preparation of wound dressing sponge by freeze-drying technique. The total duration to complete the process is about 12-15 hours, which is more time saving and cost effective.
OBJECTIVE OF INVENTION The objective of the present invention is to provide a process for preparing wound dressing sponge comprising hydrophilic polymer, acid and water.
Another objective of the present invention is to provide an effective process for the preparation of wound dressing sponge, wherein process comprising freeze-drying, annealing, packaging and sterilization.
Still another objective of the present invention is to provide a process for preparing wound dressing sponge comprising chitosan, acetic acid and water.
Still another objective of the present invention is to provide an effective process for the preparation of chitosan wound dressing sponge, wherein process comprising freeze-drying, annealing, packaging and sterilization.
Still another objective of the present invention is to provide an effective process for the preparing wound dressing sponge, wherein the processing time is reduced, there by increasing the productivity.
Yet another objective of the present invention is to provide an effective process for preparing wound dressing sponge, where the process involves freeze-drying the product for 12-15 h, annealing at 60-80°C for 15-30 min, packaging in pouch, purged with nitrogen, heat sealed and sterilization by 60 Co source at the doses of 4 kGy to 25 kGy.
SUMMARY OF INVENTION
One embodiment of the present invention provides a process for the preparation of wound dressing sponge comprising hydrophilic polymer, acid and water, wherein the processing time in freeze drying is reduced.
Another embodiment of the present invention provides a process for preparing wound dressing sponge using freeze-drying technique for 12-15 h, annealing at 60- 80°C for 15-30 min, packaging in pouch, purged with nitrogen, heat sealed and sterilization by 60 Co source at the doses of 4 kGy to 25 kGy.
Another embodiment of the present invention provides a process for preparing wound dressing sponge, the process comprising steps of: a) adding hydrophilic polymer to water and stirring at room temperature to obtain hydrophilic polymer dispersion,
b) adding acid to the above polymer dispersion under stirring to cause dissolution of hydrophilic polymer,
c) transferring above homogeneous viscous solution into trays,
d) subjecting trays for freeze-drying process for about 12-15 h,
e) heating the formed sponge at 60 - 80°C for 20 min in an oven for annealing, f) placing the obtained Sponge in pouch which is made up of triple laminated aluminium pouch (TLAP) or low-density polyethylene (LDPE), purged with nitrogen and heat sealed and
g) irradiating the packaged sponge by using gamma irradiation 60 Co source at the doses of 4 kGy to 25 kGy.
Yet another embodiment of the present invention provides a process for the preparation of wound dressing sponge comprising chitosan, acetic acid and water, wherein the processing time in freeze drying is reduced.
Another embodiment of the present invention provides a process for preparing chitosan wound dressing sponge using freeze-drying technique for 12-15 h, annealing at 60-80°C for 15-30 min, packaging in pouch, purged with nitrogen, heat sealed and sterilization by 60 Co source at the doses of 4 kGy to 25 kGy.
Yet another embodiment of the present invention provides a process for preparing chitosan wound dressing sponge, the process comprising steps of: a) adding chitosan powder or flakes to water and stirring at room temperature to obtain chitosan dispersion,
b) adding acetic acid to the above chitosan dispersion under stirring to cause dissolution of chitosan powder or flakes,
c) transferring above homogeneous viscous solution into trays,
d) subjecting trays for freeze-drying process for about 12-15 h,
e) heating the formed sponge at 60 - 80°C for 20 min in an oven for annealing, f) placing the obtained Sponge in pouch which is made up of triple laminated aluminium pouch (TLAP) or low-density polyethylene (LDPE), purged with nitrogen and heat sealed and
g) irradiating the packaged sponge by using gamma irradiation 60 Co source at the doses of 4 kGy to 25 kGy.
DETAILED DESCRIPTION OF THE INVENTION
A dressing is a sterile sponge or compress applied to a wound to promote healing and protect the wound from further harm. A dressing is designed to be in direct contact with the wound, as distinguished from a bandage, which is most often used to hold a dressing in place. Many modern dressings are self-adhesive.
Wound Dressing is categorised as follows: Absorptives, Alginates, Antimicrobial Dressings, Biophysical agents, Collagens, Composites, Contact layers, Elastic Bandages, Foams, Gauzes & Non-wovens, Honey (Active Leptospermum), Hydrocolloids, Hydrogels: Amorphous, Hydrogels: Impregnated, Hydrogels: Sheets, Impregnated Dressings, Silicone Gel Sheets, Transparent Films and Wound fillers. Sponges come under the categories of Antimicrobial Dressings.
Wound dressing may comprise a hemostatic sponge and a backing. Sponge may be placed in contact with a bleeding wound to accelerate and/or promote clotting of blood around the wound. Sponge may be used to promote clotting for blood flows that arise from trauma, medical procedures, nose bleeds, dental procedures, and/or other causes. Wound dressing may be made at least in part by freeze-drying a hemostatic solution to form. Sponge used in the present invention is based on the fact that sponge 1) should not be reactive with the product 2) should be stable to gamma irradiation dose 3) should not show leaching property 4) should maintain its physical property after gamma irradiation 5) should maintain its integrity.
Hydrophilic polymers include but not limited to polyacrylate, an alginate, chitosan, chitin, salts of chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan or combinations thereof. The starch may be of amylase, amylopectin and a combination of amylopectin and amylase. Preferably, the hydrophilic polymer is chitosan. Hydrophilic polymer used in the present invention is a medium molecular weight ranging from about 1,90,000 to about 3,10,000 g/mol.
The concentration of hydrophilic polymer used in the present invention is 0.5% - 3.0%, preferably 1.0% to 2.0% and most preferably 1.75%.
Acids includes but not limited to acetic acid, glutamic acid, lactic acid, formic acid, hydrochloric acid, glycolic acid, succinic acid. Preferably the acid used is acetic acid. The concentration of the acid used in the present invention is about 0.5% to 2%, preferably 1% w/w to 2% w/w, most preferably 1.5%. The acetic acid is added and mixed through the dispersion to cause dissolution of the chitosan solid in order to get homogeneous viscous solution. The rate of dissolution will depend on the temperature of the solution, the molecular weight of the chitosan. Preferably the chitosan solution percentage (w/w) is greater than 0.5% chitosan and less than 3.0% chitosan, preferably 1.0% to 2.0% and most preferably 1.75%.. Preferably the acetic acid is added to the solution to provide for an acetic acid solution percentage (w/w) at more than 0.5% and less than 2%, preferably 1% w/w to 2% w/w, most preferably 1.5%.
Most preferably used aqueous vehicle is water percentage (w/w) is greater than 95% and less than 99%.
Manufacturing process for the preparation of chitosan wound dressing sponge which involves the following steps
Preparation of chitosan solution
The chitosan used to prepare the chitosan solution preferably has a degree of deacetylation in the range of 75-85%. The chitosan solution preferably prepared at room temperature by addition of chitosan powder or flakes to water under stirring. To the chitosan dispersion, acetic acid is added under stirring to facilitate dissolution of chitosan solid. Preferably, the concentration of chitosan should be in the range of 0.5- 3% (w/w) hydrophilic polymer. Preferably, the acid should be acetic acid in the range of 1-2% (w/w) and the balance (about 95% - 97% w/w) being milli-q- water.
Freeze-drying of aqueous chitosan solution Chitosan has greater affinity to form hydrogen bond with water. The water absorption depends on the initial moisture present and storage conditions, like temperature and humidity. The presence of water plays an important role especially in chitosan based solid formulations, affect flow properties, compressibility of powders and tensile strength. In addition, at higher amounts of water in chitosan structure leads to faster and significant damage or deterioration to the polymer by hydrolysis.
The prepared chitosan solution is subjected for freeze-drying step. The chitosan solution is transferred into tray or mold should have good thermal conductivity and made of iron, aluminium, silver. The mold may also be coated with thin inert metallic coating including nickel, gold, platinum or polytetrafluoroethylene (Teflon) or fluorinated ethylene polymer (FEP). Freezing of the chitosan, solution in this way improves the quality of product.
In the present invention, the time taken to complete freezing and drying steps is within 12 - 15 h, which significantly reduces the process time and cost to fabricate chitosan sponge with superior physical and mechanical properties. The freezing temperature is preferably in the range of -10°C to -40°C, most preferably at -20°C. When frozen at -30°C and -40°C sponge is more closed and intact with smaller pore size, at -10°C the formed sponge is very porous in structure with
bigger pore size. At -20°C the formed sponge is microporous, intact and with optimum mechanical properties.
A freezing temperature of about -20°C with preferably ramp rate of -0.2°C /min to -0.6°C /min, most preferably -0.4°C /min for a preferable holding period of about 2h to 6h, most preferably for a period of 3h to forms a chitosan sponge with superior quality.
The frozen chitosan sample undergoes water removal, in drying step without damaging chitosan structure and integrity. In drying process, primary drying temperature is preferably in the range of 15°C to 30°C, most preferably 25°C with ramp rate of 0.05°C/min to 0.1°C/min, most preferably 0.08°C/min and preferable vacuum of 200 mTorr for a preferable holding period of 12 h to 15 h, most preferably, for a period of 12.5 h.
In secondary drying process, temperature is preferably in the range of 25°C to 50°C, most preferably 35°C with ramp rate of 0.2°C/min to 0.8°C/min, most preferably 0.5°C/min and preferable vacuum of 150 mTorr for a preferable holding period of 2h to 5h, most preferably, for a period of 3h.
Primary and secondary drying steps were carried out in presence of air. If nitrogen is used for primary and secondary drying, the formed sponge lost its water absorption capacity and swelling properties. Water content at the end of lyophilisation is NMT 25%, preferably NMT 20% .
Annealing
After freeze-drying, the prepared sponge is exposed to 60-80°C in an oven for 15 - 30 min for annealing to remove free water and residual acetic acid. Annealing at optimal or moderate temperatures can enhance tensile strength without affecting water absorption, swelling and other physical properties of sponge. Samples without annealing showed excess amounts of loose water, residual acetic acid and poor tensile properties.
Exposure to elevated temperature may change several polymer properties, including aqueous solubility, viscosity and appearance. Decomposition of chitosan increases as increase in temperature and duration of exposure. Exposure to higher temperature causes significant loss of moisture (dehydration), which results poor physical and mechanical properties. Dark brown colouration of sponge with poor tensile strength and no swelling properties.
Packaging in pouch
Finally, the sponge is placed in a pouch and evacuated, then it is desirably purged with inert gas such as argon or nitrogen gas and heat-sealed. The pouch is usually made of triple laminated aluminium pouch (TLAP) or low-density polyethylene (LDPE) pouch. The pouch should act as barrier to air and moisture to extend the shelf life of the product. When polypropylene (PP) was used as primary packaging material, lost its integrity and become brittle.
Selection of primary packaging material for sponge is based on 1) should not be reactive with the product 2) should be stable to gamma irradiation dose 3) should not show leaching property 4) should maintain its physical property after gamma irradiation 5) should maintain its integrity.
Sterilization
Chitosan based formulations especially applicable for wounds have to be sterilized. Commonly used sterilization methods include steam sterilization, exposure to dry heat and ethylene oxide or gamma irradiation. All these methods may cause irreversible alteration of physical, chemical and functional properties of chitosan.
Sterilization by saturated steam may cause chain scission of the polymer results in reduced viscosity. Similarly, sterilization by autoclave is not suitable for chitosan films and sponges results in reduced tensile strength. In addition, chitosan heated at 160°C for 2 h showed poor or no swelling and become insoluble in acidic solutions, which may be related to inter chain crosslinking of polymer functional groups.
Sterilization by ethylene oxide has to be quarantined prior to use in order to remove gas residue.
Gamma irradiation is a potential sterilization technique for chitosan-based formulations. Gamma irradiation also may cause chain scission, significant decrease in molecular weight and increase degree of deacetylation in a dose dependent manner. At higher gamma doses, sponges showed lower water sorption capacity and higher tensile strength due to polymer chain rearrangements.
Irradiation conditions are very important determinants in extent of radiation induced reactions in chitosan polymer network structure. Radiation induced scission of chitosan chains results in lower glass transition temperature. Irradiation in presence of air can alter its physical and mechanical properties of chitosan sponge including loss of water sorption capability, swelling and improved tensile strength, probably due to changes in chain interaction and rearrangement, Irradiation in anoxia showed poor water absorption and swelling properties. Sponge packaged in presence of inert gas like nitrogen did not affect sponge physical and mechanical properties.
Packaged pouch is sterilized by gamma irradiation at the dose in the range of 4kGy to 25 kGy.
Advantages
> Better water and blood absorbency & adhesion.
> Quicker hemostasis than zeolite/kaolin-based dressings due to inherent cationic charge of reengineered chitosan
Quicker hemostasis than chitosan impregnated gauze (celox) due to higher porosity, blood absorbency and adhesion.
Chitosan is obtained from purer sources compared to other chitosan from exoskeletons that competition use.
Formulations were developed using different concentrations of chitosan and various freeze-drying conditions. Further, the final product is sterilized by gamma irradiation at different doses. The formulations prepared with different variations were evaluated for their description, thickness, moisture content, acetic acid content, water absorption capacity, disintegration test, tensile strength, bacterial endotoxin test and sterility.
The following examples describes the nature of the invention and are given only for the purpose of illustrating the present invention in more detail and are not limitative and relate to solutions which have been particularly effective on a bench scale.
Example 1
Manufacturing Process
Required quantity of chitosan was added to batch quantity of purified water under stirring at room temperature to obtain homogenous dispersion.
Required quantity of acetic acid, glacial was added to chitosan dispersion under stirring at room temperature to obtain homogenous viscous solution.
The obtained homogenous solution was transferred into trays and trays were subjected for freeze-drying process for 12 - 15 h. After freeze-drying, obtained sponge was subjected for annealing in hot air oven at 80°C/20 min.
Sponges were cut into predetermined sizes and placed in triple laminated aluminium pouch, purged with nitrogen and heat- sealed.
Such packaged sponge was irradiated with gamma irradiation by 60Co source at the doses of 4 kGy for sterilization. Evaluation tests for wound dressing sponge:
Description: Description of the product was evaluated by visual observation.
Size : Size of the sponge was measured using digital Vernier calliper
Thickness: Thickness of the sponge was measured using digital Vernier calliper
Loss on drying: Weigh the LOD bottle (Wl). Weigh the sample in grams along with bottle and note the reading as W2. Dry the sample at 105°C for 2 hours and place in a desiccator to cool. Weigh the sample after drying (W3). Record the observations.
W2 - W3
LOD = X 100
W2 - W1 Water uptake capacity: Water absorption capacity of sponge was measured by taking known weight of sponge sample was immersed in excessive distilled water at room temperature for 10 minutes. Then the swollen samples were collected carefully and blotted with tissue until no free water remained. The water absorption of the sponge was derived from the mass change before and after swelling. Water absorption = Weight after immersion / Initial weight of sponge
Acetic acid content: Acetic acid content was measured using HPLC.
Tensile strength: Tensile strength of sponge was measured using universal testing machine.
Sterility test: Sterility testing was performed according to USP general chapter < 71>.
Antimicrobial effectiveness testing: Antimicrobial effectiveness testing was performed according to USP General Chapter (51).
Bacterial Endotoxin Test: Bacterial Endotoxin Test was performed for optimized formulation. The testing was performed according to USP General Chapter < 85 >.
Table 1. Specifications for wound dressing sponge:
10 Bacterial endotoxins NMT 300 IU/g of chitosan
The wound dressing sponge prepared as per Example 1 of the present invention is evaluated for the above characters at different stability conditions and the data is given below tables; Table 2
Sterility To pass the test as per Pass -
Anti-microbial To pass the test as per
Pass - performance USP
Bacterial NMT 300 IU/g of
Complies - Endotoxin test chitosan
Table 3
Acetic acid content NMT 5000 ppm 156 ppm -
Tensile strength NLT l.O kgf/cm2 2.089 kgf/cm2 1.893 kgf/cm2
To pass the test as
Sterility Pass - per USP
Anti-microbial To pass the test as
Pass - performance per USP
Bacterial Endotoxin NMT 300 IU/g of
Complies - test chitosan
Claims
1. A process for the preparation of wound dressing sponge comprising hydrophilic polymer, acid and water, wherein the processing time in freeze drying is reduced.
2. A process for preparing wound dressing sponge, the process comprising steps of:
a) adding hydrophilic polymer to water and stirring at room temperature to obtain hydrophilic polymer dispersion,
b) adding acid to the above polymer dispersion under stirring to cause dissolution of hydrophilic polymer,
c) transferring above homogeneous viscous solution into trays,
d) subjecting trays for freeze-drying process for about 12-15 h,
e) heating the formed sponge at 60 - 80°C for 20 min in an oven for annealing, f) placing the obtained Sponge in pouch which is made up of triple laminated aluminium pouch (TLAP) or low-density polyethylene (LDPE), purged with nitrogen and heat sealed and
g) irradiating the packaged sponge by using gamma irradiation 60 Co source at the doses of 4 kGy to 25 kGy.
3. The process of claim 1, wherein the hydrophilic polymer is selected from the group of chitosan derivatives consisting of chitosan, chitin and salts of chitosan.
4. The process of claim 1, wherein the acid is selected from acetic acid, glutamic acid, lactic acid, formic acid, hydrochloric acid, glycolic acid, succinic acid, preferably acetic acid.
5. A process for the preparation of wound dressing sponge comprising chitosan, acetic acid and water, wherein the processing time in freeze drying is reduced.
6. A process for preparing chitosan wound dressing sponge, the process comprising steps of:
a) adding chitosan powder or flakes to water and stirring at room temperature to obtain chitosan dispersion,
b) adding acetic acid to the above chitosan dispersion under stirring to cause dissolution of chitosan powder or flakes,
c) transferring above homogeneous viscous solution into trays,
d) subjecting trays for freeze-drying process for about 12-15 h,
e) heating the formed sponge at 60 - 80°C for 20 min in an oven for annealing,
f) placing the obtained Sponge in pouch which is made up of triple laminated aluminium pouch (TLAP) or low-density polyethylene (LDPE), purged with nitrogen and heat sealed and
g) irradiating the packaged sponge by using gamma irradiation 60 Co source at the doses of 4 kGy to 25 kGy.
7. The process of claim 4, where the composition comprises about 0.5 % to about 3% w/w of the chitosan, wherein said chitosan is deacetylated in the range of 75 - 85 %.
8. The process of claim 4, wherein the water concentration is ranges from 95 - 99% w/w.
9. The process of claim 4, wherein the composition comprises about 0.5 % to about 2% w/w of the glacial acetic acid.
10. The process of claim 4, wherein the composition is subjected to freeze-drying about 12 - 15 hrs, preferably 12.5 hours.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN201741008594 | 2017-03-11 | ||
| IN201741008594 | 2017-03-11 |
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| WO2018167622A1 true WO2018167622A1 (en) | 2018-09-20 |
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| PCT/IB2018/051585 WO2018167622A1 (en) | 2017-03-11 | 2018-03-10 | Process for the preparation of wound dressing sponge |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925554A (en) * | 2020-08-28 | 2020-11-13 | 盐城工学院 | Polytetrafluoroethylene sponge and preparation method thereof |
| RU2804241C1 (en) * | 2022-05-27 | 2023-09-26 | Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук (ИНЭОС РАН) | Method for producing antimicrobial porous material containing silver nanoparticles |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7482503B2 (en) * | 2001-06-14 | 2009-01-27 | Providence Health System-Oregon | Wound dressing and method for controlling severe, life-threatening bleeding |
-
2018
- 2018-03-10 WO PCT/IB2018/051585 patent/WO2018167622A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7482503B2 (en) * | 2001-06-14 | 2009-01-27 | Providence Health System-Oregon | Wound dressing and method for controlling severe, life-threatening bleeding |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925554A (en) * | 2020-08-28 | 2020-11-13 | 盐城工学院 | Polytetrafluoroethylene sponge and preparation method thereof |
| CN111925554B (en) * | 2020-08-28 | 2023-01-31 | 盐城工学院 | Polytetrafluoroethylene sponge and preparation method thereof |
| RU2804241C1 (en) * | 2022-05-27 | 2023-09-26 | Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук (ИНЭОС РАН) | Method for producing antimicrobial porous material containing silver nanoparticles |
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