JPS63159452A - Film composition - Google Patents
Film compositionInfo
- Publication number
- JPS63159452A JPS63159452A JP30700086A JP30700086A JPS63159452A JP S63159452 A JPS63159452 A JP S63159452A JP 30700086 A JP30700086 A JP 30700086A JP 30700086 A JP30700086 A JP 30700086A JP S63159452 A JPS63159452 A JP S63159452A
- Authority
- JP
- Japan
- Prior art keywords
- hyaluronic acid
- molecular weight
- film
- streptococcus
- membrane composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 45
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 83
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](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-DNGZLQJQSA-N 0.000 claims abstract description 82
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 82
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 14
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 241000194048 Streptococcus equi Species 0.000 claims abstract description 6
- 241000120569 Streptococcus equi subsp. zooepidemicus Species 0.000 claims abstract description 5
- 241000251468 Actinopterygii Species 0.000 claims abstract description 4
- 241000283153 Cetacea Species 0.000 claims abstract description 4
- 241000287828 Gallus gallus Species 0.000 claims abstract description 4
- 241000194017 Streptococcus Species 0.000 claims abstract description 4
- 241000283690 Bos taurus Species 0.000 claims abstract 2
- 241000282898 Sus scrofa Species 0.000 claims abstract 2
- 239000012528 membrane Substances 0.000 claims description 22
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 claims description 9
- 229920001287 Chondroitin sulfate Polymers 0.000 claims description 9
- 229940059329 chondroitin sulfate Drugs 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 7
- 244000005700 microbiome Species 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 abstract description 9
- 206010061218 Inflammation Diseases 0.000 abstract description 4
- 230000001580 bacterial effect Effects 0.000 abstract description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 4
- 210000000845 cartilage Anatomy 0.000 abstract description 3
- 238000012258 culturing Methods 0.000 abstract description 2
- 210000004127 vitreous body Anatomy 0.000 abstract description 2
- 235000015097 nutrients Nutrition 0.000 abstract 1
- 206010052428 Wound Diseases 0.000 description 24
- 208000027418 Wounds and injury Diseases 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 231100000419 toxicity Toxicity 0.000 description 10
- 230000001988 toxicity Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 210000002615 epidermis Anatomy 0.000 description 7
- 102000008186 Collagen Human genes 0.000 description 6
- 108010035532 Collagen Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229920001436 collagen Polymers 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229920001059 synthetic polymer Polymers 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 239000002657 fibrous material Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical class [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 108010003272 Hyaluronate lyase Proteins 0.000 description 3
- 102000001974 Hyaluronidases Human genes 0.000 description 3
- 239000001888 Peptone Substances 0.000 description 3
- 108010080698 Peptones Proteins 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229960002773 hyaluronidase Drugs 0.000 description 3
- 235000019319 peptone Nutrition 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000007602 hot air drying Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 229920000045 Dermatan sulfate Polymers 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 241000194042 Streptococcus dysgalactiae Species 0.000 description 1
- 241000264435 Streptococcus dysgalactiae subsp. equisimilis Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000001520 comb Anatomy 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- -1 polysiloxane Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940115920 streptococcus dysgalactiae Drugs 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Landscapes
- Compositions Of Macromolecular Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、分子量１万以上のヒアルロン酸またはその無
毒性塩、好ましくはヒアルロン酸産生微生物からの分子
量１万以上のヒアルロン酸を主成分としてなるヒアルロ
ン酸を有効成分とした膜組成物に関するもので、本発明
のヒアルロン酸を有効成分とした膜組成物は化粧用バッ
ク剤、炎症の治癒あるいは止血を目的として炎症部位や
傷口等の創面に貼付する医薬用貼付剤として、親和性の
優れた膜組成物である。 。Detailed Description of the Invention <Industrial Application Field> The present invention is directed to the use of hyaluronic acid with a molecular weight of 10,000 or more or a non-toxic salt thereof, preferably hyaluronic acid with a molecular weight of 10,000 or more from a hyaluronic acid-producing microorganism as a main component. The present invention relates to a film composition containing hyaluronic acid as an active ingredient.The film composition containing hyaluronic acid as an active ingredient of the present invention can be used as a cosmetic backing agent, or on wound surfaces such as inflamed areas and wounds for the purpose of healing inflammation or stopping bleeding. This film composition has excellent affinity for use as a pharmaceutical patch. .
〈従来の技術〉
従来ヒアルロン酸またはその無毒性塩は水性皮膚化粧料
の基剤中に混和配合され、感触官能効果、荒れ肌改善効
果、角質改善効果を奏する化粧料として利用されている
。<Prior Art> Conventionally, hyaluronic acid or its non-toxic salt has been mixed and blended into the base of aqueous skin cosmetics and used as cosmetics that have a tactile and sensory effect, an effect on improving rough skin, and an effect on improving keratin.
化粧用パック剤や医薬用貼付剤として有用な膜形成剤は
、表皮の形成能、抗原性、毒性、生分解性や創面への密
着性、創面からの剥離の容易性等の優れたものが好まし
く、従来よりの膜形成剤としては、ガム質、ゼラチン、
ペクチン、コラーゲン等の天然高分子、ポリビニルアル
コール、ポリビニルピロリドン、アセテートポリマー、
ヒドロキシアクリルポリマー、ポリアミノ酸等の合成高
分子が使用されている。さらに近年、ニワトリの８冠、
ウシの関節、クジラの軟骨等の動物細胞の結合組織内に
存在している天然のヒアルロン酸を抽出法にて回収し、
これをポリウレタン、ポリオレフィン、ビニルポリマー
、ポリアミド、ポリエステル、ポリシロキサン等のポリ
マー原料に包含させた膜組成物が知られている（特開昭
６０−１３０６２３号公報、特開昭６０−１３０６３８
号公報）。Film-forming agents useful as cosmetic packs and pharmaceutical patches are those with excellent epidermis-forming ability, antigenicity, toxicity, biodegradability, adhesion to wound surfaces, and ease of peeling from wound surfaces. Preferred conventional film forming agents include gums, gelatin,
Natural polymers such as pectin and collagen, polyvinyl alcohol, polyvinylpyrrolidone, acetate polymers,
Synthetic polymers such as hydroxyacrylic polymers and polyamino acids are used. Furthermore, in recent years, eight crowns of chickens,
Natural hyaluronic acid, which is present in the connective tissue of animal cells such as cow joints and whale cartilage, is recovered using an extraction method.
Film compositions containing this in polymer raw materials such as polyurethane, polyolefin, vinyl polymer, polyamide, polyester, and polysiloxane are known (JP-A-60-130623, JP-A-60-130638).
Publication No.).
〈発明が解決しようとする問題点〉
しかしこれらの天然高分子や合成高分子の膜は、生体適
応生が悪く、また使用時において塗布した後に乾燥して
充分な膜となるまでに時間を要する膜形成性の欠点があ
った。また特に合成高分子の膜においては、抗原性、毒
性、生分解性の点において必ずしも適したものではなか
った。さらに天然のヒアルロン酸をポリマー原料に包含
させた膜組成物においても、天然のヒアルロン酸自体を
、合成ポリマーを使用しないで単独での膜形成は成し難
く、そのため成形加工された合成ポリマーに塗布する方
法しかないものであり、上記と同様の問題を含むもので
あった。<Problems to be solved by the invention> However, these natural polymer and synthetic polymer films have poor biocompatibility and require time to dry to form a sufficient film after being applied during use. There was a drawback in film formation. In addition, especially synthetic polymer membranes have not always been suitable in terms of antigenicity, toxicity, and biodegradability. Furthermore, even in film compositions containing natural hyaluronic acid in polymer raw materials, it is difficult to form a film by itself without using a synthetic polymer, so it is applied to a synthetic polymer that has been molded. This is the only way to do so, and it involves the same problems as above.
従って、生体適応性や膜形成性がよく、さらに表皮の形
成能、抗原性、毒性、生分解性や創面への密着性、創面
からの剥離の容易性等の優れた膜組成物が望まれている
。Therefore, there is a need for a membrane composition that has good biocompatibility and film-forming properties, as well as excellent epidermis-forming ability, antigenicity, toxicity, biodegradability, adhesion to the wound surface, and ease of peeling from the wound surface. ing.
く問題点を解決するための手段〉
本発明者らは、このような要望を充足すべき優れた膜組
成物について、鋭意研究した結果、意外にも、分子量１
万以上のヒアルロン酸またはその無毒性塩、好ましくは
ヒアルロン酸産生微生物、例えばストレプトコッカス属
に属するヒアルロン酸度生菌であるストレプトコッカス
・エクイまたはストレプトコッカス・ズーエピデミカス
からの分子量１万以上のヒアルロン酸を主成分としてな
るヒアルロン酸を有効成分とした用いることにより、簡
便に膜状物が得られ、かつこのようにして得られた膜組
成物は、生体適応性、膜形成性の点で優れ、さらに表皮
の形成能もよく、抗原性、毒性も見られず、生分解性や
創面への密着性、創面からの剥離の容易性等の優れた化
粧用パック剤、炎症の治癒あるいは止血を目的として炎
症部位や傷口等の創面に貼付する医薬用貼付剤として優
れ、さらに塗布面の組織に対しても親和性の優れた膜組
成物であることを見出した。さらにこのヒアルロン酸に
ムコ多糖体であるコンドロイチン硫酸を混合したものに
おいても、同様に優れた膜組成物が得られることを知っ
た。Means for Solving the Problems〉 As a result of intensive research into excellent membrane compositions that should satisfy such demands, the present inventors surprisingly found that the molecular weight 1.
10,000 or more hyaluronic acid or a non-toxic salt thereof, preferably hyaluronic acid with a molecular weight of 10,000 or more from hyaluronic acid-producing microorganisms, such as Streptococcus equi or Streptococcus zooepidemicus, which are hyaluronic bacteria belonging to the genus Streptococcus. By using hyaluronic acid as an active ingredient, a film-like material can be easily obtained, and the film composition thus obtained has excellent biocompatibility and film-forming properties, and further has the ability to form epidermis. It is a cosmetic pack that has excellent properties such as good hydration, no antigenicity or toxicity, biodegradability, adhesion to the wound surface, and ease of peeling from the wound surface. The present inventors have discovered that this membrane composition is excellent as a pharmaceutical patch for application to wound surfaces, and also has excellent affinity for the tissues on the applied surface. Furthermore, it has been found that a similarly excellent membrane composition can be obtained by mixing this hyaluronic acid with chondroitin sulfate, which is a mucopolysaccharide.
本発明は、上記の知見に基づいて完成されたもので、分
子量１万以上のヒアルロン酸またはその無毒性塩を主成
分としてなるヒアルロン酸を有効成分とした膜組成物で
ある。The present invention was completed based on the above findings, and is a membrane composition containing hyaluronic acid as an active ingredient, the main component being hyaluronic acid or a non-toxic salt thereof having a molecular weight of 10,000 or more.
まずヒアルロン酸としては、例えばニワトリの鶏冠、ブ
タの尾、ウシの関節、クジラの軟骨や魚類の眼球ガラス
体等の魚類を含む動物細胞、その他の動物組織からの抽
出、精製［ジャーナル・オブ・バイオロジカル・ケミス
トリー（Ｊ、Ｂｉ。First, hyaluronic acid can be extracted and purified from animal cells, including fish, such as chicken combs, pig tails, cow joints, whale cartilage, and fish ocular vitreous bodies, and other animal tissues [Journal of Biological Chemistry (J, Bi.
１、Ｃｈｅｍ、）１８６．４９５〜５１１．（１９５０
） 、バイオケミ力・エト・バイオロジカル
ｃｔａ）１５８．１７〜３０．（１９６６）、特開昭５
２−１４５５９４号公報、特開昭５５−７４７９６号公
報］、ヒアルロン酸産生微生物からの醗酵、抽出、精製
により得られるもので、本発明においてはヒアルロン酸
産生微生物からのヒアルロン酸を用いることが目的とす
るヒアルロン酸の容易な精製、回収や再現性のある規格
化等の点で好ましい、ヒアルロン酸産生微生物としては
、例えばストレプトコッカス属に属するヒアルロン酸産
生菌株としてストレプトコッカス・エクイ（Ｓｔｏｒｅ
ｐｔｏｃｏｃｃｕｓ ｅｑｕｉ）、ストレプトコッカ
ス・ピオゲネス（Ｓｔｏｒｅｐｔｏｃｏｃｃｕｓ ｐ
ｙｏｇｅｎｅｓ）、ストレプトコッカス・エクイシミリ
ス（Ｓｔｏｒｅｐｔ。1, Chem,) 186.495-511. (1950
), biochemistry, etho, biological cta) 158.17-30. (1966), Japanese Patent Publication No. 5
2-145594, Japanese Patent Application Laid-open No. 55-74796], it is obtained by fermentation, extraction, and purification from hyaluronic acid-producing microorganisms, and the purpose of the present invention is to use hyaluronic acid from hyaluronic acid-producing microorganisms. For example, Streptococcus equi (Store
ptococcus equi), Streptococcus pyogenes (Storeptococcus p
yogenes), Streptococcus equisimilis (Storept.
ｃｏｃｃｕｓ ｅｑｕｉｓｉｍｉｌｉｓ）、ストレプ
トコッカス・ディスガラクチイエ（Ｓｔｏｒｅｐｔｏｃ
ｏｃｃｕｓ ｄｙｓｇａｌａｃｔｉａｅ）、ストレプ
トコッカス・ズーエピデミカス（Ｓｔｏｒｅｐｔｏｃｏ
ｃｃｕｓ ｚｏｏｅｐｉｄｅｍｉｃｕｓ）［キリパー
−ボルフ、エト・オール（Ｋｉｌｉｐｐｅｒ−Ｂａｌｚ
ｅｔ ａｌ）エフ・イー・エム・ニス・マイクロ
バイオロジー・レターズ（Ｆ、Ｅ、Ｍ、Ｓ、Ｍｉ ｃ
ｒｏｂ ｉ 。coccus equisimilis), Streptococcus dysgalactiae (Storeptocci)
occus dysgalactiae), Streptococcus zooepidemicus (Storeptococcus
ccus zooepidemicus) [Killipper-Balz, Et.
et al) FEM Niss Microbiology Letters (F, E, M, S, Mic
rob i.
１部ｇｙ Ｌｅｔｔｅｒｓ）、２４．３５５〜３６４
．１９８４．ファロウ・ジエー・ニー・イー、エト・オ
ール（Ｆａｒｒｏｗ Ｊ、Ａ、Ｅ、ｅｔ ａｌ）シ
ステマティック・アンド・アプライド・マイクロバイオ
ロジー（Ｓｙｓｔｅｍａｔｉｃ ａｎｄ Ａｐｐｌ
ｉｅｄ Ｍｉｃｒｏｂｉ。Part 1 gy Letters), 24.355-364
．． 1984. Farrow J, A, E, et al Systematic and Applied Microbiology
ied Microbi.
１部ｇｙ）、５．４８３〜４９３．１９８４．ブリデエ
ッグ・ビー・ディ、エト・オール（Ｂｒｉｄｅｇ Ｐ
、Ｄ、ｅｔ ａｌ）ジャーナル・オブ・ジェネラル・
マイクロバイオロジー（Ｊｕｏｒｎａｌ ｏｆ Ｇ
ｅｎｅｒａｌ Ｍｉｃｒｏｂｉｏｌｏｇｙ）、１２９
．５６５〜５９７．１９８３］が挙げられ、これらの醗
酵、抽出、精製法は、例えばアクタ・バンロジカエ・ミ
クロビオロジ力・スカンジナビ力・セクション・Ｂ（Ａ
ｃｔａ、Ｐａｔｈ、Ｍｉｃｒｏｂｉｏｌ、５ｃａｎｄ。1 part gy), 5.483-493.1984. Brideg P
, D. et al) Journal of General
Microbiology (Journal of G.
eneral Microbiology), 129
．． 565-597.1983], and these fermentation, extraction, and purification methods are described, for example, in Acta Vanlodicae, Microbiology, Scandinavia, Section B (A.
cta, Path, Microbiol, 5cand.
５ｅｃｔｉｏｎ Ｂ）８４．１６２〜１６４．（１９
７６）、特開昭５８−５６６９２号公報、特表昭６０−
５００５９７号公報、特開昭６１−１５６９８号公報等
を参照して得ればよい、特に、ストレプトコッカス・エ
クイまたはストレプトコッカス・ズーエピデミカスから
得られたヒアルロン酸（平均分子量が約１００万、８０
％の信頼限界で約１２万〜約３５０万）やこのヒアルロ
ン酸をヒアルロニダーゼで４０分間処理して得られるヒ
アルロン酸く平均分子量が約１０万、８０％の信頼限界
で約３万〜約２５万）が好ましく、このようなヒアルロ
ン酸またはこのヒアルロン酸をヒアルロニダーゼで６０
分間以内処理して得られるヒアルロン酸が使用できる。5ection B) 84.162-164. (19
76), Japanese Unexamined Patent Publication No. 58-56692, Special Publication No. 1988-
In particular, hyaluronic acid obtained from Streptococcus equi or Streptococcus zooepidemicus (with an average molecular weight of about 1 million, 80
The average molecular weight of hyaluronic acid obtained by treating this hyaluronic acid with hyaluronidase for 40 minutes is approximately 100,000, and the 80% confidence limit is approximately 30,000 to 250,000. ) is preferred, and such hyaluronic acid or this hyaluronic acid is treated with hyaluronidase for 60 min.
Hyaluronic acid obtained by processing within minutes can be used.
なおこのヒアルロン酸を９０ないし１５０分間またはそ
れ以上の時間でのヒアルロニダーゼ処理して得られるヒ
アルロン酸は、１万以下のヒアルロン酸成分が多くなり
使用に適さなくなるため、少なくとも分子量が１万以上
のヒアルロン酸を主成分として含有するヒアルロン酸で
あればよい、またヒアルロン酸の無毒性塩としては、そ
のナトリウム、カリウム塩が挙げられる。さらにこのよ
うなヒアルロン酸に。The hyaluronic acid obtained by treating this hyaluronic acid with hyaluronidase for 90 to 150 minutes or longer contains a large amount of hyaluronic acid components with a molecular weight of 10,000 or less, making it unsuitable for use. Any hyaluronic acid containing acid as a main component may be used, and non-toxic salts of hyaluronic acid include its sodium and potassium salts. Furthermore, this kind of hyaluronic acid.
ヒアルロン酸以外のムコ多糖体、例えばコンドロイチン
硫酸、デルマタン硫酸、グラタン硫酸、ヘパラン硫酸等
を、ヒアルロン酸１部当たり０．１〜１０部を混合して
用いてもよく、特にコンドロイチン硫酸が好ましい。Mucopolysaccharides other than hyaluronic acid, such as chondroitin sulfate, dermatan sulfate, gratan sulfate, heparan sulfate, etc., may be used in a mixture of 0.1 to 10 parts per part of hyaluronic acid, and chondroitin sulfate is particularly preferred.
次いで本発明の膜組成物を得るに当たり、例えばヒアル
ロン酸の０．５％以上、好ましくは１〜１０部程度の水
溶液を調製し、これを任意の形状の膜形成用トレイに適
宜の厚さ、好ましくは１ｍｍ以上、好ましくは１〜１５
ｍｍ程度になるように注入し、その後水分を除去すれば
よく、簡便には常温、加温条件での通風乾燥、温風乾燥
、熱風乾燥するかまたは凍結条件下で凍結乾燥して水分
を除去して所望の膜組成物を得ればよい、さらにトレイ
の代わりにガーゼやろ紙等の布紙類、コラーゲン等の皮
膚類似物等の膜支持体の上で、同様の方法にて膜形成し
てもよい。Next, in order to obtain the film composition of the present invention, for example, an aqueous solution of 0.5% or more of hyaluronic acid, preferably about 1 to 10 parts, is prepared, and this is placed on a film forming tray of any shape to an appropriate thickness. Preferably 1 mm or more, preferably 1 to 15
It is sufficient to inject the material to a thickness of about 1.0 mm, and then remove the moisture.Easy methods include ventilation drying, hot air drying, hot air drying at room temperature, heated conditions, or freeze drying to remove moisture. Furthermore, instead of a tray, a membrane can be formed on a membrane support such as cloth paper such as gauze or filter paper, or a skin analogue such as collagen, in the same manner. It's okay.
さらに本発明の膜組成物を得るに当たり水溶性ビタミン
類、脂溶性ビタミン類、レシチン、γ−リルン酸、ホル
モン類、酵素、酵素阻害剤、殺菌剤その他の生理活性物
質、紫外線吸収剤、紫外線除去剤、角質軟化剤、保湿剤
等化粧用、医薬用貼付剤に使用し得る添加物を予め添加
するか、または膜成形後に塗布または含浸せしめてもよ
い。Furthermore, in order to obtain the film composition of the present invention, water-soluble vitamins, fat-soluble vitamins, lecithin, γ-lylunic acid, hormones, enzymes, enzyme inhibitors, bactericides and other physiologically active substances, ultraviolet absorbers, ultraviolet ray removers, etc. Additives that can be used in cosmetic and pharmaceutical patches, such as emollients, keratin softeners, and moisturizers, may be added in advance, or may be applied or impregnated after film formation.
さらに、ヒアルロン酸を希釈して使用するに当たり、必
要に応じて、ポリビニルアルコール、ポリビニルピロリ
ドン等の無毒性高分子水溶性ポリマーを用いてもよい。Furthermore, when using diluted hyaluronic acid, a non-toxic water-soluble polymer such as polyvinyl alcohol or polyvinylpyrrolidone may be used as necessary.
このようにして得られたヒアルロン酸を有効成分として
なる膜組成物は、生体適応性、膜形成性の点で優れ、さ
らに表皮の形成能もよく、抗原性、毒性も見られず、生
分解性や創面への密着性、創面からの剥離の容易性等の
優れた化粧用パック剤、炎症の治癒あるいは止血を目的
として炎症部位や傷口等の創面に貼付する医薬用貼付剤
として優れ、さらに塗布面の組織に対しても親和性の優
れたものである。The membrane composition containing hyaluronic acid as an active ingredient obtained in this way has excellent biocompatibility and membrane-forming properties, has good epidermis-forming ability, is neither antigenic nor toxic, and is biodegradable. It is excellent as a cosmetic pack with excellent adhesiveness, adhesion to the wound surface, and ease of removal from the wound surface, and as a pharmaceutical patch to be applied to the wound surface such as an inflamed area or wound for the purpose of curing inflammation or stopping bleeding. It also has excellent affinity for the structure of the applied surface.
〈実施例〉
次いで本発明の実施例を挙げるが、本発明は何らこれに
よって限定されるものではない。<Example> Next, examples of the present invention will be given, but the present invention is not limited thereto in any way.
実施例１
−１２０℃、２０分間加熱殺菌したグルコース２％、ペ
プトン１．５％、コーンスチープリ力−２％含有培地２
０Ｌ （ｐＨ７，２）を有する３０Ｌ用ジャーファーメ
ンタ−に、予めグルコース１％、イーストエキス０．５
％、ペプトン１．５％含有培地Ｉして培養したストレプ
トコッカス・エクイ（ＡＴＣＣ９５２７）の培養物全量
を移植した、培養は、窒素ガスを吹き込むことにより撹
拌しなからＩＯＮ水酸化ナトリウムを用いてｐＨ６゜８
〜７．５に調製しながら３７℃、１日間行った、培養終
了後、培養液を１００℃、３０分間加熱処理後、遠心分
離にて菌体およびその他の夾雑物を除去し、得られた上
清液に４ＯＬのエタノールを撹拌下加えて繊維状物質を
沈澱せしめた。これをろ取後、エタノールで充分洗浄後
、再び水に溶解し、セチルピリジウムクロライドを加え
、生じた沈澱物質をろ取し、水および０．１Ｍ塩化ナト
リウム水溶液にて十分洗浄後、５Ｌの０．５Ｍ塩化すｌ
・リウム水溶液にてヒアルロン酸を抽出し、その溶液に
エタノールＩＯＬを加え、生じた繊維状物質をろ取し、
この繊維状物質を７５％エタノール水、次いでエタノー
ルで十分洗浄後、真空乾燥して培養液ＩＬ当たり３９の
ヒアルロン酸（本島の高速液体クロマトグラフィーによ
る分子量分４Ｉは第１図に示す、なお高速液体クロマト
グラフィーは溶出液として０．１Ｍリン酸カリウム水溶
液を用い、流量０．３ｍｌ／分で２０８ｎｍで検出した
。また第１図における保持時間５８分のピークは塩化ナ
トリウムピークである。この結果、木晶は極めて均質な
平均分子量約１００万のヒアルロン酸を主成分としたも
のである。）を得た。Example 1 Medium 2 containing 2% glucose, 1.5% peptone, and 2% corn steeple strength heat sterilized at -120°C for 20 minutes
0L (pH 7.2) in a 30L jar fermenter, add 1% glucose and 0.5 yeast extract in advance.
A total culture of Streptococcus equi (ATCC 9527) cultured in medium I containing 1.5% peptone and 1.5% peptone was transplanted. 8
After culturing, the culture solution was heated at 100°C for 30 minutes, and the bacterial cells and other impurities were removed by centrifugation. 4OL of ethanol was added to the supernatant under stirring to precipitate fibrous substances. After filtering this, after thoroughly washing with ethanol, it was dissolved in water again, cetylpyridium chloride was added, the resulting precipitate was collected by filtration, and after thoroughly washing with water and 0.1M sodium chloride aqueous solution, 5L of 0.5M sulfur chloride
・Extract hyaluronic acid with an aqueous solution of hyaluronic acid, add ethanol IOL to the solution, filter the resulting fibrous material,
After thoroughly washing this fibrous substance with 75% ethanol water and then ethanol, it was dried under vacuum to yield 39 hyaluronic acids per IL of the culture solution (the molecular weight of 4I as determined by Honjima's high performance liquid chromatography is shown in Figure 1). Chromatography was performed using a 0.1 M aqueous potassium phosphate solution as an eluent, and detection was performed at 208 nm at a flow rate of 0.3 ml/min.The peak at a retention time of 58 minutes in Fig. 1 is a sodium chloride peak. An extremely homogeneous crystal containing hyaluronic acid as a main component with an average molecular weight of about 1 million was obtained.
さらに本島を水酸化ナトリウム水溶液に加えて、常法に
より、ヒアルロン酸ナトリウム塩を得た。Further, Honjima was added to an aqueous sodium hydroxide solution to obtain sodium hyaluronate salt by a conventional method.
次いでこのヒアルロン酸ナトリウム塩ｌ＆を１００ｍ１
の水溶液に添加して溶解し、これを１０×１００ｍ２の
トレイに厚さ５ ｍ ｍになるよう注入した。さらにこ
れを、通風乾燥して厚さ約０゜５ ｒｏ ｍの膜を得た
。このようにして得られた膜は、膜形成性や生体組織へ
の親和適応性、表皮の形成能、抗原性、毒性、生分解性
や創面への密着性、創面からの剥離の容易性等の優れた
膜組成物であった。Next, 100ml of this hyaluronate sodium salt l&
The mixture was added to an aqueous solution of 1, dissolved, and poured into a 10 x 100 m2 tray to a thickness of 5 mm. Further, this was dried through ventilation to obtain a film having a thickness of about 0°5 rom. The membrane thus obtained has properties such as film-forming properties, affinity for living tissues, ability to form epidermis, antigenicity, toxicity, biodegradability, adhesion to wound surfaces, ease of peeling from wound surfaces, etc. It was an excellent film composition.
実施例２
上記実施例１と同様にして得た、菌体および夾雑物を除
去した上清液を、限外ろ過（分子量排除限界１３０００
：旭化成社製）して分子量１万以下の培養上滑液に含
有されている成分を除去し、濃縮した０次いで、この濃
縮液５Ｌに、エタノールＩＯＬを加え、生じた繊維状物
質をろ取し、さらにエタノールで十分洗浄後、再び水に
溶解し、セチルピリジウムクロライドを加え、生じた沈
澱物質をろ取し、水およびＯ，１Ｍ塩化ナトリウム水溶
液にて十分洗浄後、１０Ｌの０．５Ｍ塩化ナトリウム水
溶液にてヒアルロン酸を抽出し、再び限外ろ過（分子量
排除限界６０００）して水、セチルピリジウムクロライ
ドを除去し、濃縮した。Example 2 A supernatant liquid obtained in the same manner as in Example 1 above, from which bacterial cells and impurities had been removed, was subjected to ultrafiltration (molecular weight exclusion limit: 13,000
: manufactured by Asahi Kasei Co., Ltd.) to remove components contained in the cultured synovial fluid with a molecular weight of 10,000 or less, and concentrate the fluid.Next, ethanol IOL was added to 5 L of this concentrated solution, and the resulting fibrous material was collected by filtration. Then, after thoroughly washing with ethanol, dissolve in water again, add cetylpyridium chloride, collect the resulting precipitate by filtration, wash thoroughly with water and O, 1M aqueous sodium chloride solution, and dissolve in 10L of 0.5M sodium chloride. Hyaluronic acid was extracted with an aqueous sodium chloride solution, ultrafiltered again (molecular weight exclusion limit 6000) to remove water and cetylpyridium chloride, and concentrated.
濃縮液５ＬにエタノールＩＯＬを加え、生じた繊維状物
質をろ取し、この繊維状物質を７５％エタノール水、次
いでエタノールで十分洗浄後、真空乾燥して培養液ＩＬ
当たり２．５ｇのヒアルロン酸（本島の高速液体クロマ
トグラフィーによる分子及分布は第２図に示すもので、
第１図に比較し分子ｆｆｉ １０００前後の物質が完全
に除去されたもので、かつ水晶は極めて均質な平均分子
量約１００万のヒアルロン酸を主成分としたものである
。Ethanol IOL was added to 5 L of the concentrated solution, the resulting fibrous material was collected by filtration, and the fibrous material was thoroughly washed with 75% ethanol water and then ethanol, and then vacuum dried to obtain the culture solution IL.
2.5g of hyaluronic acid (the molecular structure and distribution determined by Motojima's high-performance liquid chromatography are shown in Figure 2).
Compared to FIG. 1, substances with a molecular ffi of around 1000 have been completely removed, and the crystals are extremely homogeneous and are mainly composed of hyaluronic acid with an average molecular weight of about 1 million.
なお高速液体クロマトグラフィーは実施例１の場合と同
一条件である。）を得た。さらに氷晶を水酸化ナトリウ
ム水溶液に加えて、常法により、ヒアルロン酸ナトリウ
ム塩を得た。Note that the high performance liquid chromatography was performed under the same conditions as in Example 1. ) was obtained. Furthermore, ice crystals were added to an aqueous sodium hydroxide solution to obtain sodium hyaluronate salt by a conventional method.
次いでこのヒアルロン酸ナトリウム塩１ｇを１００ｍ１
の水溶液に添加して溶解し、これを１０Ｘ１０ｃｒｎ２
のトレイに厚さ５ｍｍになるよう注入した。さらにこれ
を、温風乾燥して厚さ約０゜５ ｒｎ ｍの膜を得た。Next, add 1 g of this sodium hyaluronate salt to 100 ml.
and dissolve it in an aqueous solution of 10X10crn2.
The mixture was poured into a tray to a thickness of 5 mm. Further, this was dried with hot air to obtain a film having a thickness of about 0.5 nm.
このようにして得られた膜は、上記実施例１で得られた
膜組成物に比較して、若干膜形成性や創面への密着性が
よく、さらに生体組織への親和適応性、表皮の形成能、
抗原性、毒性、生分解性や創面からの剥離の容易性等の
優れた膜組成物であった。The membrane thus obtained has slightly better film-forming properties and adhesion to the wound surface than the membrane composition obtained in Example 1 above, and also has better affinity and adaptability to living tissues and better adhesion to the epidermis. formability,
The membrane composition had excellent antigenicity, toxicity, biodegradability, and ease of peeling from the wound surface.
実施例３
実施例】と同様にして得られたヒアルロンｅ１５％水溶
液を調製し、これを実施例１と同様にしてｌ・レイに厚
さ４ ＋ｎ ｍになるよう注入した。さらにこれを、温
風乾燥して厚さ約０．９ｍｍの膜形成性や生体組織への
親和適応性、表皮の形成能、抗原性、毒性、生分解性や
創面への密着性、創面からの剥離の容易性等の優れた膜
組成物かえられた実施例４
実施例１と同様にして得られたヒアルロン酸１部とコン
ドロイチン硫酸１部との混合物の５％水溶液を、実施例
１と同様のトレイに注入し、乾燥して膜強度が良好で、
かつ膜形成性や生体組織への親和適応性、表皮の形成能
、抗原性、毒性、生分解性や創面への密着性、創面から
の１．す離の容易性等の優れた膜組成物を得た。Example 3 A 15% aqueous solution of hyaluronic e was prepared in the same manner as in Example 1, and injected into L-ray in the same manner as in Example 1 to a thickness of 4 + nm. Furthermore, it is dried with hot air to form a film with a thickness of about 0.9 mm, affinity for biological tissues, ability to form epidermis, antigenicity, toxicity, biodegradability, adhesion to wound surfaces, and Example 4: A 5% aqueous solution of a mixture of 1 part of hyaluronic acid and 1 part of chondroitin sulfate obtained in the same manner as in Example 1 was used in Example 1 and in Example 4. Injected into a similar tray and dried to ensure good film strength.
In addition, film-forming properties, affinity for living tissues, ability to form epidermis, antigenicity, toxicity, biodegradability, adhesion to wound surfaces, and 1. A film composition with excellent ease of removal was obtained.
実施例５
実施Ｍｌと同様にして得られたヒアルロン酸１部とコン
ドロイチン硫酸４部との混合物の５％水溶液を、実施例
１と同様のトレイに注入し、乾燥して膜強度が良好で、
かつ膜形成性や生体組織への親和適応性、表皮の形成能
、抗原性、毒性、生分解性や創面への密着性、創面から
の剥離の容易性等の優れた膜組成物を得た。Example 5 A 5% aqueous solution of a mixture of 1 part of hyaluronic acid and 4 parts of chondroitin sulfate obtained in the same manner as in Example M1 was injected into the same tray as in Example 1, and dried to give a good film strength.
In addition, a membrane composition with excellent membrane-forming properties, affinity for living tissues, ability to form epidermis, antigenicity, toxicity, biodegradability, adhesion to wound surfaces, and ease of peeling from wound surfaces was obtained. .
実施例６
実施例１と同様にして得られたヒアルロン酸１部とコン
ドロイチン硫１’！！１部との混合物の５％水溶液を、
コラーゲン４Ｊｌ維の上に流し込み、次いでこれを凍結
乾燥し°ζ水分を除去して、コラーゲン繊維上にヒアル
ロン酸膜を形成せしめた。Example 6 1 part of hyaluronic acid and 1 part of chondroitin sulfate obtained in the same manner as in Example 1! ! A 5% aqueous solution of the mixture with 1 part
The mixture was poured onto collagen 4Jl fibers, and then freeze-dried to remove water to form a hyaluronic acid film on the collagen fibers.
実施例７
実施例１と同様にして得られたヒアルロン酸１部とコン
ドロイチン硫酸４部との混合物の５％水溶液を、ガーゼ
上に流し込み、次いでこれを凍結乾燥して水分を除去し
て、カーゼ上にヒアルロン酸膜を形成せしめた。Example 7 A 5% aqueous solution of a mixture of 1 part of hyaluronic acid and 4 parts of chondroitin sulfate obtained in the same manner as in Example 1 was poured onto gauze, and then it was freeze-dried to remove water and made into a case. A hyaluronic acid film was formed on top.
実施例８
実施ＰＡｌと同様にして得られたヒアルロン酸１部とポ
リビニルアルコール２部との混合物の１５％水溶液を、
ガーゼの上に流し込み、次いでこれ凍結乾燥して水分を
除去して、ガーゼ上にヒアルロン酸膜を形成せしめた。Example 8 A 15% aqueous solution of a mixture of 1 part of hyaluronic acid and 2 parts of polyvinyl alcohol obtained in the same manner as in Example PAl was
The mixture was poured onto gauze and then freeze-dried to remove moisture, forming a hyaluronic acid film on the gauze.
実施例９
実施例１と同様にして得られたヒアルロン酸１部とポリ
ビニルピロリドン１部、コンドロイチン硫酸１部との混
合物の７％水溶液を、コラーゲン繊維の１に流し込み、
次いでこれを凍結乾燥して水分を除去して、コラーゲン
繊維上にヒアルロン酸膜ご形成せしめた。Example 9 A 7% aqueous solution of a mixture of 1 part of hyaluronic acid, 1 part of polyvinylpyrrolidone, and 1 part of chondroitin sulfate obtained in the same manner as in Example 1 was poured into collagen fiber 1,
This was then freeze-dried to remove water and form a hyaluronic acid film on the collagen fibers.
実施例１０
実施例１と同様にして得られたヒアルロン酸１部とポリ
ビニルピロリドン４部との混合物の２０％水溶液を、実
施例１と同様のトレイに注入し、乾燥してヒアルロン酸
膜を形成せしめた。Example 10 A 20% aqueous solution of a mixture of 1 part of hyaluronic acid and 4 parts of polyvinylpyrrolidone obtained in the same manner as in Example 1 was poured into the same tray as in Example 1 and dried to form a hyaluronic acid film. I forced it.
〈発明の効果〉
本発明は、分子量１万以上のヒアルロン酸またはその無
毒性塩を主成分としてなるヒアルロン酸を有効成分とす
る膜組成物であって、従来の膜形成剤に比較して膜形成
性の点で優れ、さらに表皮の形成能もよく、抗原性、毒
性も見られず、生分解性や創面への密着性、０１面から
の剥離の容易性等の優れた化粧用パック剤、炎症の治癒
あるいは止血を目的として炎症部位や傷口等の創面に貼
付する医薬用貼付剤として優れ、さらに塗布面の組織に
対しても親和性の優れた生体適応性の良好な膜組成物で
ある。<Effects of the Invention> The present invention provides a film composition containing hyaluronic acid as an active ingredient, the main component of which is hyaluronic acid with a molecular weight of 10,000 or more or a non-toxic salt thereof, which has a lower film formation rate than conventional film forming agents. A cosmetic pack with excellent formability, good ability to form the epidermis, no antigenicity or toxicity, and excellent biodegradability, adhesion to wound surfaces, and ease of peeling from the 01 surface. It is an excellent medicinal patch to be applied to the wound surface such as an inflamed site or wound for the purpose of curing inflammation or stopping bleeding, and it is also a film composition with excellent biocompatibility and excellent affinity for the tissues on which it is applied. be.
第１図および第２図は、ヒアルロン酸産生菌株であるス
トレプト；１ツカス・エクイによるヒアルロン酸の高速
液体クロマトグラフィーのチャートを示す。
、特許出題人 東洋醸造株式会社
第１図
第２図FIGS. 1 and 2 show charts of high performance liquid chromatography of hyaluronic acid using the hyaluronic acid-producing bacterial strain Streptochus equi. , Patent issuer: Toyo Jozo Co., Ltd. Figure 1 Figure 2
Claims (8)
塩を主成分としてなるヒアルロン酸を有効成分とした膜
組成物。(1) A membrane composition containing hyaluronic acid as an active ingredient, the main component being hyaluronic acid or a non-toxic salt thereof having a molecular weight of 10,000 or more.
塩を主成分としてなるヒアルロン酸が、ヒアルロン酸産
生微生物からのヒアルロン酸である特許請求の範囲第１
項記載の膜組成物。(2) Claim 1, wherein the hyaluronic acid whose main component is hyaluronic acid with a molecular weight of 10,000 or more or a non-toxic salt thereof is hyaluronic acid from a hyaluronic acid-producing microorganism.
The film composition described in .
属に属するヒアルロン酸産生菌である特許請求の範囲第
２項記載の膜組成物。(3) The membrane composition according to claim 2, wherein the hyaluronic acid-producing microorganism is a hyaluronic acid-producing microorganism belonging to the genus Streptococcus.
菌が、ストレプトコッカス・エクイまたはストレプトコ
ッカス・ズーエピデミカスである特許請求の範囲第３項
記載の膜組成物。(4) The membrane composition according to claim 3, wherein the hyaluronic acid-producing bacteria belonging to the genus Streptococcus are Streptococcus equi or Streptococcus zooepidemicus.
塩を主成分としてなるヒアルロン酸が、動物組織からの
ヒアルロン酸である特許請求の範囲第１項記載の膜組成
物。(5) The membrane composition according to claim 1, wherein the hyaluronic acid whose main component is hyaluronic acid or a non-toxic salt thereof having a molecular weight of 10,000 or more is hyaluronic acid from animal tissue.
、ウシ、クジラまたは魚類からのヒアルロン酸である特
許請求の範囲第５項記載の膜組成物。(6) The membrane composition according to claim 5, wherein the hyaluronic acid from animal tissue is hyaluronic acid from chicken, pig, cow, whale, or fish.
万〜約３５０万である特許請求の範囲第１項記載の膜組
成物。(7) Hyaluronic acid with a molecular weight of 10,000 or more has a molecular weight of about 12
2. The membrane composition of claim 1, wherein the membrane composition is from 1,000,000 to about 3,500,000.
ヒアルロン酸またはその無毒性塩を主成分としてなるヒ
アルロン酸を用いてなる特許請求の範囲第１項記載の膜
組成物。(8) The membrane composition according to claim 1, which uses hyaluronic acid whose main component is hyaluronic acid with a molecular weight of 10,000 or more mixed with chondroitin sulfate, or a non-toxic salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30700086A JPS63159452A (en) | 1986-12-23 | 1986-12-23 | Film composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30700086A JPS63159452A (en) | 1986-12-23 | 1986-12-23 | Film composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63159452A true JPS63159452A (en) | 1988-07-02 |
Family
ID=17963807
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP30700086A Pending JPS63159452A (en) | 1986-12-23 | 1986-12-23 | Film composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63159452A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002017853A3 (en) * | 2000-08-31 | 2007-10-25 | Genzyme Biosurgery Corp | Hyaluronan-based antiadhesion compositions, their preparation and use |
| JP2014024828A (en) * | 2012-06-17 | 2014-02-06 | Kosumedei Seiyaku Kk | Hyaluronic acid gel and producing method thereof |
| JP2014114355A (en) * | 2012-12-07 | 2014-06-26 | Dainichiseika Color & Chem Mfg Co Ltd | Method for manufacturing hyaluronic acid film, and hyaluronic acid film |
| CN104411296A (en) * | 2012-05-16 | 2015-03-11 | 考希德芭以奧帕有限公司 | Cosmetics, pharmaceuticals, and food composition containing pieces or extract from fish eyes |
| WO2019082922A1 (en) | 2017-10-27 | 2019-05-02 | 大日精化工業株式会社 | Cosmetic molded article and method for manufacturing same |
-
1986
- 1986-12-23 JP JP30700086A patent/JPS63159452A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002017853A3 (en) * | 2000-08-31 | 2007-10-25 | Genzyme Biosurgery Corp | Hyaluronan-based antiadhesion compositions, their preparation and use |
| CN104411296A (en) * | 2012-05-16 | 2015-03-11 | 考希德芭以奧帕有限公司 | Cosmetics, pharmaceuticals, and food composition containing pieces or extract from fish eyes |
| JP2014024828A (en) * | 2012-06-17 | 2014-02-06 | Kosumedei Seiyaku Kk | Hyaluronic acid gel and producing method thereof |
| WO2014061332A1 (en) * | 2012-10-17 | 2014-04-24 | コスメディ製薬株式会社 | Hyaluronic acid gel and method for producing same |
| US9855206B2 (en) | 2012-10-17 | 2018-01-02 | Cosmed Pharmaceutical Co., Ltd. | Hyaluronic acid gel and manufacturing method thereof |
| JP2014114355A (en) * | 2012-12-07 | 2014-06-26 | Dainichiseika Color & Chem Mfg Co Ltd | Method for manufacturing hyaluronic acid film, and hyaluronic acid film |
| WO2019082922A1 (en) | 2017-10-27 | 2019-05-02 | 大日精化工業株式会社 | Cosmetic molded article and method for manufacturing same |
| KR20200052353A (en) | 2017-10-27 | 2020-05-14 | 다이니치 세이카 고교 가부시키가이샤 | Cosmetic molding and manufacturing method |
| US11458088B2 (en) | 2017-10-27 | 2022-10-04 | Dainichiseika Color & Chemicals Mfg. Co., Ltd. | Cosmetic molded article and method for manufacturing same |
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