KR20200048476A - Crosslinked hyaluronic acid compositions and method of producing the same - Google Patents
Crosslinked hyaluronic acid compositions and method of producing the same Download PDFInfo
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- KR20200048476A KR20200048476A KR1020180130623A KR20180130623A KR20200048476A KR 20200048476 A KR20200048476 A KR 20200048476A KR 1020180130623 A KR1020180130623 A KR 1020180130623A KR 20180130623 A KR20180130623 A KR 20180130623A KR 20200048476 A KR20200048476 A KR 20200048476A
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- hyaluronic acid
- acid composition
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- crosslinked
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- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 102
- 229960003160 hyaluronic acid Drugs 0.000 title claims abstract description 102
- 239000000203 mixture Substances 0.000 title claims abstract description 100
- 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 title claims abstract description 89
- 238000000034 method Methods 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 20
- 239000002537 cosmetic Substances 0.000 claims abstract description 19
- 150000002500 ions Chemical class 0.000 claims abstract description 7
- -1 hyaluronic acid ion Chemical class 0.000 claims description 35
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- 229910052782 aluminium Inorganic materials 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
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- 239000007788 liquid Substances 0.000 description 2
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- 239000002674 ointment Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
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- 239000003380 propellant Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
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- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- 239000004909 Moisturizer Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical compound OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
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- 150000001298 alcohols Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
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- 239000008346 aqueous phase Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
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- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical class C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 239000001023 inorganic pigment Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012035 limiting reagent Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
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- 239000003094 microcapsule Substances 0.000 description 1
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- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000012860 organic pigment Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
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- 230000007170 pathology Effects 0.000 description 1
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- 239000012071 phase Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229940071089 sarcosinate Drugs 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 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 compound [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 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
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- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/04—Dispersions; Emulsions
- A61K8/042—Gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/26—Aluminium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Abstract
Description
본 명세서에는 가교 히알루론산 조성물 및 이의 제조방법이 개시된다.Disclosed herein is a crosslinked hyaluronic acid composition and a method of making the same.
다당류는 당의 복합체로 글리코시드 결합에 의해 단당류가 결합된 형 태로써, 특히 다당류의 일종인 히알루론산은 화장품 및 의약분야에 광범위하게 사용되고 있다.Polysaccharides are complexes of sugars in which monosaccharides are bound by glycosidic bonds. In particular, hyaluronic acid, a type of polysaccharide, is widely used in cosmetics and medicine.
상기 히알루론산은 체액, 소의 안구, 닭 벼슬, 동물의 완층조직, 태반 등에서 발견되는 생체 구성 물질로 특히 결합 조직 및 피부에 고농도로 존재한다.The hyaluronic acid is a bio-constituent substance found in body fluids, bovine eyeballs, chicken crest, animal laminar tissue, placenta, etc., and is particularly present in high concentrations in connective tissue and skin.
또한, 히알루론산은 자기 무게의 1000 배 정도의 물을 함유할 수 있는 능력이 있기 때문에 피부의 건조를 방지시키는 화장품의 보습제로 널리 사용되어 왔으며, 피부 미용 분야에서는 특정부위에 삽입되어 연조직을 확장시킴으로써 주름개선이나 윤곽교정 등에 사용되는 피부 층전제 (dermal filler) 등으로 사용되고 있다. 또한, 히알루론산은 점탄성, 생체 적합성, 생분해성이 탁월하여 사용범위가 피부 미용뿐만 아니라 퇴행성 골관절염 치료제, 상처 치료제, 안구 수술보조제, 수술 후에 조직 간의 유착을 방지하기 위한 유착 방지제 등으로 널리 사용되고 있다.In addition, hyaluronic acid has been widely used as a moisturizing agent in cosmetics that prevents drying of the skin because it has the ability to contain about 1000 times its own weight of water. It is used as a dermal filler for wrinkle improvement and contour correction. In addition, hyaluronic acid is excellent in viscoelasticity, biocompatibility, and biodegradability, so its range of use is widely used not only for skin beauty, but also for degenerative osteoarthritis treatment, wound treatment, eye surgery aid, and adhesion prevention agent to prevent adhesion between tissues after surgery.
그러나, 특히 화장품의 제조시, 종래의 히알루론산은 미끌거림이 심하고 끈적임이 많아서 고농도로 사용하기 힘든 문제가 있으며, 이러한 미끌거림을 개선하기 위하여 화학적으로 가교된 히알루론산은 제조시간이 오래 걸리고, 자극도가 강하여 반드시 세척이 필요하며 세척이 충분치 않을 경우 인체 자극이 있을 수 있다는 문제가 지적되어 왔다. However, especially in the manufacture of cosmetics, the conventional hyaluronic acid has a lot of slippage and a lot of stickiness, which makes it difficult to use at a high concentration, and chemically cross-linked hyaluronic acid takes a long manufacturing time to improve the slippage and irritation. It has been pointed out that a strong degree of cleaning is necessary and that if there is insufficient cleaning, there may be human irritation.
일 측면에서, 본 발명의 목적은 2가 이상의 금속 양이온과 히알루론산 이온이 이온결합으로 가교된 가교 히알루론산을 포함하여, 끈적임과 미끌거림이 개선된 가교 히알루론산 조성물 및 이의 제조방법을 제공하는 것이다.In one aspect, the object of the present invention is to provide a crosslinked hyaluronic acid composition having improved stickiness and slipperiness, including a crosslinked hyaluronic acid in which bivalent or higher metal cations and hyaluronic acid ions are crosslinked by ion bonding, and a method for manufacturing the same. .
일 측면에서, 본 발명은, 2가 이상의 금속 양이온과 히알루론산 이온이 이온결합으로 가교된 가교 히알루론산을 포함하는, 가교 히알루론산 조성물을 제공한다.In one aspect, the present invention provides a crosslinked hyaluronic acid composition comprising a crosslinked hyaluronic acid in which a bivalent or higher metal cation and a hyaluronic acid ion are crosslinked by ion bonding.
다른 일 측면에서, 본 발명은 전술한 가교 히알루론산 조성물을 포함하는 화장료 조성물을 제공한다.In another aspect, the present invention provides a cosmetic composition comprising the aforementioned crosslinked hyaluronic acid composition.
다른 일 측면에서, 본 발명은 전술한 가교 히알루론산 조성물을 포함하는 피부 외용제 조성물을 제공한다.In another aspect, the present invention provides a composition for external application for skin comprising the aforementioned crosslinked hyaluronic acid composition.
다른 일 측면에서, 본 발명은 가교 히알루론산 조성물의 제조방법에 있어서, 2가 이상의 금속 양이온을 포함하는 산성 용액 및, 히알루론산 이온을 포함하는 염기성 용액을 준비하는 단계; 및 상기 산성 용액과 염기성 용액을 혼합하여 겔을 형성시키는 단계; 를 포함하는 가교 히알루론산 조성물 제조방법을 제공한다.In another aspect, the present invention provides a method for preparing a crosslinked hyaluronic acid composition, comprising: preparing an acidic solution containing a metal cation of divalent or higher and a basic solution containing a hyaluronic acid ion; And mixing the acidic solution with a basic solution to form a gel; It provides a method for producing a cross-linked hyaluronic acid composition comprising a.
일 측면에 있어서, 본 발명의 가교 히알루론산 조성물은 2가 이상의 금속 양이온과 히알루론산 이온이 이온결합으로 가교되어, 투명하면서도 끈적임이 거의 없고, 피부에 자극이 없어 화장료 조성물 또는 피부 외용제 조성물 제조에 적합하다. In one aspect, the crosslinked hyaluronic acid composition of the present invention is a crosslinked metal cation and a hyaluronic acid ion having a divalent value or more, and is transparent and hardly sticky, and has no irritation to the skin. Do.
다른 일 측면에 있어서, 본 발명의 가교 히알루론산 조성물 제조방법은 2가 이상의 금속 양이온과 히알루론산 이온의 가교를 위한 혼합 과정 외에 별도의 세척 과정이 불필요하여 간편하게 가교 히알루론산 조성물을 제조할 수 있다. In another aspect, the method for preparing a crosslinked hyaluronic acid composition of the present invention can easily produce a crosslinked hyaluronic acid composition because a separate washing process is unnecessary in addition to a mixing process for crosslinking a metal cation with a divalent or higher value and a hyaluronic acid ion.
도 1은 본 발명에 따른 가교 히알루론산 조성물이 일 구현예로, 알루미늄 이온과 이온 결합으로 가교된 것을 나타내는 도면이다.
도 2은 본 발명의 실시예 1에 따른 가교 히알루론산 조성물의 투명도를 나타내기 위하여 촬영한 사진이다.
도 3은 본 발명의 따른 가교 히알루론산 조성물의 FTIR 분석 결과를 나타낸 것이다. 1 is a view showing that the crosslinked hyaluronic acid composition according to the present invention is crosslinked with an aluminum ion and an ionic bond in one embodiment.
2 is a photograph taken to show the transparency of the crosslinked hyaluronic acid composition according to Example 1 of the present invention.
Figure 3 shows the results of FTIR analysis of the crosslinked hyaluronic acid composition according to the present invention.
본 명세서에서, 어떤 부분이 어떤 구성 요소를 "포함"한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성 요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.In the present specification, when a part “includes” a certain component, it means that the component may further include other components, rather than excluding other components, unless otherwise specified.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
가교 히알루론산 조성물Cross-linked hyaluronic acid composition
본 발명의 예시적인 구현예들에서는, 2가 이상의 금속 양이온과 히알루론산 이온이 이온결합으로 가교된 가교 히알루론산을 포함하는, 가교 히알루론산 조성물을 제공한다. In exemplary embodiments of the present invention, there is provided a crosslinked hyaluronic acid composition, wherein the crosslinked hyaluronic acid is cross-linked by ion bonding with a divalent or higher metal cation and a hyaluronic acid ion.
종래 히알루론산은 보습에 효과가 좋은 성분이지만 미끌거림과 끈적임이 심해서 화장품 제형에서 고농도로 사용하기 힘들다는 단점이 있었다. 이를 극복하기 위하여 화학적 가교에 의한 히알루론산 겔을 만들 수 있는데, 일반적으로 히알루론산의 OH기와 에폭사이드(epoxide) 계열의 가교제 사이에서 에테르 결합이 일어나서 형성된다. 하지만 화학적 가교제를 사용한 경우, 반드시 세척이 필요하고, 세척이 충분치 않을 경우 인체자극이 있을 수 있으며, 제조시 오랜기간이 걸린다는 단점이 있었다.Conventional hyaluronic acid is a good moisturizing ingredient, but has a drawback that it is difficult to use in high concentrations in cosmetic formulations due to its great slipperiness and stickiness. In order to overcome this, a hyaluronic acid gel by chemical crosslinking can be made. In general, ether bonding occurs between the OH group of hyaluronic acid and an epoxide-based crosslinking agent. However, when a chemical cross-linking agent was used, washing must be carried out, and if washing is not sufficient, there may be a human irritation, and there is a disadvantage in that it takes a long time during manufacturing.
이를 극복하기 위하여, 본 발명자들은 히알루론산 이온의 COO- 부분과 2가 이상의 금속 양이온 사이의 이온결합에 의한 겔을 형성하도록 하여, 자극이 없으며 끈적임도 적은 가교 히알루론산 조성물을 발명하였다(도 1 참조). In order to overcome this problem, the inventors have found that hyaluronic acid ion COO - so as to form a gel by the ion coupling between the part and a bivalent or higher metal cation, there is no stimulation was invented stickiness even less cross-linked hyaluronic acid composition (see FIG. 1 ).
일 구현예에서, 상기 가교 히알루론산 조성물은 물을 더 포함할 수 있다. In one embodiment, the cross-linked hyaluronic acid composition may further include water.
일 구현예에서, 상기 이온은 아연 이온 또는 알루미늄 이온일 수 있고, 바람직하게는 안전성이 널리 알려진 알루미늄 이온일 수 있다. In one embodiment, the ions may be zinc ions or aluminum ions, preferably aluminum ions having well-known safety.
일 구현예에서, 상기 가교 히알루론산 조성물은 겔 형태일 수 있다. In one embodiment, the cross-linked hyaluronic acid composition may be in the form of a gel.
일 구현예에서, 상기 가교 히알루론산 조성물의 점도는 0.75 내지 1 Pa·s일 수 있고, 예컨대 0.8 내지 0.95 Pa·s 또는 0.85 내지 0.9 Pa·s일 수 있다. 상기 점도가 0.75 Pa·s 미만인 경우 조성물의 제어가 어렵고, 상기 점도가 1 Pa·s 초과인 경우 끈적임이 너무 심하고, 이를 피부에 적용시 이물감이 느껴질 수 있다. In one embodiment, the viscosity of the cross-linked hyaluronic acid composition may be 0.75 to 1 Pa · s, for example, 0.8 to 0.95 Pa · s or 0.85 to 0.9 Pa · s. When the viscosity is less than 0.75 Pa · s, it is difficult to control the composition, and when the viscosity is more than 1 Pa · s, the stickiness is too great, and when applied to the skin, a foreign feeling may be felt.
일 구현예에서, 상기 가교 히알루론산 조성물의 끈적임은 0.15N 이하, 0.1 이하 또는 0.09N 이하일 수 있다. In one embodiment, the stickiness of the crosslinked hyaluronic acid composition may be 0.15 N or less, 0.1 or less, or 0.09 N or less.
일 구현예에서, 상기 가교 히알루론산 조성물은 반투명할 수 있고, 예컨대 660nm에서 흡광도가 0.5 내지 1.5일 수 있고, 예컨대 1.0일 수 있다. 따라서 화장료 조성물 또는 피부 외용제 조성물 제조시, 예를 들어 철 이온을 가교제로 사용한 경우와 달리 색깔을 띄지 않아 적합하다. In one embodiment, the cross-linked hyaluronic acid composition may be translucent, for example, absorbance at 660 nm may be 0.5 to 1.5, for example 1.0. Therefore, when preparing a cosmetic composition or a composition for external application for skin, it is suitable because it does not have a color unlike the case where, for example, iron ions are used as a crosslinking agent.
일 구현예에서, 상기 이온의 농도는 상기 가교 히알루론산 조성물 총 중량 기준으로 0.01 내지 0.1 중량%일 수 있고, 예컨대 0.02 내지 0.09 중량%, 0.3 내지 0.08 중량% 또는 0.04 내지 0.07 중량% 일 수 있다. 상기 농도가 0.01 중량% 미만인 경우 가교가 충분히 이루어지지 않아 끈적임이 심해질 수 있고, 상기 농도가 0.1 중량% 초과인 경우 알루미늄 이온이 석출될 수 있다. In one embodiment, the concentration of the ions may be 0.01 to 0.1% by weight based on the total weight of the cross-linked hyaluronic acid composition, for example, 0.02 to 0.09% by weight, 0.3 to 0.08% by weight, or 0.04 to 0.07% by weight. When the concentration is less than 0.01% by weight, cross-linking is not sufficiently performed, so that stickiness may become severe, and when the concentration is more than 0.1% by weight, aluminum ions may be precipitated.
일 구현예에서, 상기 히알루론산의 농도는 상기 가교 히알루론산 조성물 총 중량을 기준으로, 0.1 내지 1 중량%일 수 있고, 예컨대 0.2 내지 0.9 중량%, 0.3 내지 0.8 중량%, 또는 0.4 내지 0.7 중량%일 수 있다. 상기 농도가 0.1 중량% 미만인 경우 히알루론산의 보습 효과가 충분하게 나타나지 않을 수 있고, 상기 농도가 1 중량% 초과인 경우 끈적임이 심해서 화장료 조성물 또는 피부 외용제 조성물 제조시 제형 구형이 어려울 수 있다. In one embodiment, the concentration of the hyaluronic acid may be 0.1 to 1% by weight, for example, 0.2 to 0.9% by weight, 0.3 to 0.8% by weight, or 0.4 to 0.7% by weight based on the total weight of the cross-linked hyaluronic acid composition. Can be When the concentration is less than 0.1% by weight, the moisturizing effect of hyaluronic acid may not be sufficiently exhibited, and when the concentration is more than 1% by weight, stickiness is severe, and thus the formulation spherical shape may be difficult when preparing a cosmetic composition or a composition for external application for skin.
상기 2가 이상의 금속 양이온과 히알루론산 이온의 당량비는 1: 1 내지 1: 3일 수 있고, 바람직하게는 1:3 일 수 있다. The equivalent ratio of the metal cation of the divalent or higher and the hyaluronic acid ion may be 1: 1 to 1: 3, and preferably 1: 3.
일 구현예에서, 상기 가교 히알루론산 조성물의 FTIR(fourier tranformation infra red) 분석시, 1615 cm-1 에서 COO- 피크가 나타날 수 있다. 구체적으로, 히알루론산의 FTIR 분석 시 1649cm-1에서 관찰되던 COO- 피크가, 알루미늄 이온과 가교시(이온결합) 1615cm-1 에서 관찰된다.In one embodiment, when analyzing the FTIR (fourier tranformation infra red) of the cross-linked hyaluronic acid composition, a COO- peak may appear at 1615 cm -1 . Specifically, COO release observed during FTIR analysis of hyaluronic acid, 1649cm -1 - a peak, when the aluminum ion and crosslinked (ionic bonding) is observed at 1615cm -1.
본 발명의 예시적인 구현예들에서는, 전술한 가교 히알루론산 조성물을 포함하는 화장료 조성물을 제공한다. In exemplary embodiments of the present invention, a cosmetic composition comprising the aforementioned cross-linked hyaluronic acid composition is provided.
일 구현예에서, 상기 화장료 조성물의 외형은 화장품학 또는 피부과학적으로 허용 가능한 매질 또는 기제를 함유한다. 이는 국소적용에 적합한 모든 제형으로, 예를 들면, 용액, 겔, 고체, 반죽 무수 생성물, 수상에 유상을 분산시켜 얻은 에멀젼, 현탁액, 마이 크로에멀젼, 마이크로캡슐, 미세과립구 또는, 이온형(리포좀) 및 비이온형의 소낭 분산제의 형태로, 또는 크림, 스킨, 로션, 파우더, 연고, 스프레이 또는 콘실 스틱의 형태로 제공될 수 있다. 이들 조성물은 당해 분야의 통상적인 방법에 따라 제조될 수 있다. 본 발명에 따른 조성물은 또한 포말(foam)의 형태로 또는 압축된 추진제를 더 함유한 에어로졸 조성물의 형태로도 사용될 수 있다.In one embodiment, the appearance of the cosmetic composition contains a cosmetic or dermatologically acceptable medium or base. These are all formulations suitable for topical application, e.g. solutions, gels, solids, dough anhydrous products, emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic forms (liposomes) obtained by dispersing the oil phase in an aqueous phase. And non-ionic vesicle dispersants, or in the form of creams, skins, lotions, powders, ointments, sprays or conceal sticks. These compositions can be prepared according to conventional methods in the art. The composition according to the invention can also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.
본 발명의 일 실시예에 따른 상기 화장료 조성물은 그 제형에 있어서 특별히 한정되는 바가 없으며, 예를 들면, 앰플, 크림, 유연화장수, 수렴화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 아이크림, 아이에센스, 클렌징크림, 클렌징폼, 클렌징워터, 상기 화장료 조성물을 포함하는 클렌징 티슈, 팩, 파우더, 바디로션, 바디크림, 바디오일 및 바디에센스 등의 화장품으로 제형화될 수 있다.The cosmetic composition according to an embodiment of the present invention is not particularly limited in its formulation, for example, ampoule, cream, softening lotion, converging makeup, nutritional makeup, nutritional cream, massage cream, essence, eye cream, It can be formulated into cosmetics such as eye essence, cleansing cream, cleansing foam, cleansing water, cleansing tissue containing the cosmetic composition, pack, powder, body lotion, body cream, body oil, and body essence.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물섬유, 식물섬유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal fibers, plant fibers, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. Can be.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / Propellant such as butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액의 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or sorbitan.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, suspensions such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide as a carrier component Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linoline derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
본 발명의 일 실시예에 따른 화장료 조성물에는 상기 가교 히알루론산 조성물 이외에 기능성 첨가물 및 일반적인 화장료 조성물에 포함되는 성분이 추가로 포함될 수 있다. 상기 기능성 첨가물로는 수용성 비타민, 유용성 비타민, 고분자 펩티드, 고분자 다당, 스핑고 지질 및 해초 엑기스로 이루어진 군에서 선택된 성분을 포함할 수 있다.The cosmetic composition according to an embodiment of the present invention may further include a functional additive and a component included in a general cosmetic composition in addition to the cross-linked hyaluronic acid composition. The functional additive may include a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingo lipids, and seaweed extract.
이외에 포함되는 배합 성분으로서는 유지 성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, 식물 추출물, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한(制汗)제, 정제수 등을 들 수 있다.Other ingredients included include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavors, blood circulation Accelerators, cooling agents, limiting agents, purified water, and the like.
본 발명의 예시적인 구현예들에서는, 전술한 가교 히알루론산 조성물을 포함하는 피부 외용제 조성물을 제공한다. 상기 피부 외용제는 피부 외부에서 도포되는 어떠한 것이라도 포함될 수 있는 총칭으로서 다양한 제형의 화장품, 의약품이 여기에 포함될 수 있다.In exemplary embodiments of the present invention, there is provided a composition for external application for skin comprising the aforementioned cross-linked hyaluronic acid composition. The external preparation for skin is a generic term that may include anything applied from outside the skin, and various types of cosmetics and pharmaceuticals may be included therein.
본 발명의 예시적인 구현예들에서는, 전술한 가교 히알루론산 조성물을 포함하는 약학 조성물을 제공한다. 본 발명에 따른 조성물을 의약품에 적용할 경우에는, 본 발명에서 사용되는 유효성분에 상용되는 무기 또는 유기의 담체를 가하여 반고체 또는 액상의 형태로 비경구 투여제로 제형화할 수 있으며, 본 발명에 따른 상기 약학 조성물은 비경구, 직장, 국소, 경피, 정맥 내, 근육 내, 복강 내, 피하 등으로 투여될 수 있다. In exemplary embodiments of the present invention, there is provided a pharmaceutical composition comprising the aforementioned cross-linked hyaluronic acid composition. When the composition according to the present invention is applied to a pharmaceutical product, an inorganic or organic carrier compatible with the active ingredient used in the present invention may be added to form a semi-solid or liquid parenteral dosage form, and according to the present invention, Pharmaceutical compositions can be administered parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.
상기 비경구 투여를 위한 제형으로는 주사제, 필러, 점적제, 연고, 로션, 스프레이, 현탁제, 유제, 좌제 등을 들 수 있다. 본 발명에 따른 조성물은 당업계에 널리 알려진 통상적인 방법에 따라 실시함으로써, 유효성분을 용이하게 제형화할 수 있으며, 이 때 계면활성제, 부형제, 착색료, 향신료, 보존료, 안정제, 완충제, 현탁제, 기타 상용하는 보조제를 적당히 사용할 수 있다.Formulations for parenteral administration include injections, fillers, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, and the like. The composition according to the present invention can be easily formulated into an active ingredient by carrying out according to a conventional method well known in the art. At this time, surfactants, excipients, colorants, spices, preservatives, stabilizers, buffers, suspensions, etc. Commercially available adjuvants can be used as appropriate.
특히, 본 발명의 조성물이 주사제, 필러 등의 형태로 제형화될 경우, 프리필드 시린지(prefilled syringe), 바이알(vial) 등으로 제형화될 수 있다. In particular, when the composition of the present invention is formulated in the form of an injection, a filler, etc., it may be formulated as a prefilled syringe, a vial, or the like.
본 발명의 약학 조성물의 유효 성분의 투여 용량은 투여받을 대상의 연령, 성별, 체중, 병리 상태 및 그 심각도, 투여 경로 또는 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 적당한 용량의 결정은 당업자의 수준 내에 있으며, 이의 1일 투여 용량은 예를 들어 0.1mg/kg/일 내지 100mg/kg/일, 보다 구체적으로는 5mg/kg/일 내지 50mg/kg/일이 될 수 있으나, 이에 제한되는 것은 아니다.The dosage of the active ingredient of the pharmaceutical composition of the present invention will vary depending on the age, gender, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber. Determination of a suitable dose based on these factors is within the level of those skilled in the art, and the daily dose administered is, for example, 0.1 mg / kg / day to 100 mg / kg / day, more specifically 5 mg / kg / day to 50 mg / kg. / Can be, but is not limited to.
가교 히알루론산 조성물 제조방법Method for preparing crosslinked hyaluronic acid composition
본 발명의 예시적인 구현예들에서는, 전술한 가교 히알루론산 조성물의 제조방법에 있어서, 2가 이상의 금속 양이온을 포함하는 산성 용액 및, 히알루론산 이온을 포함하는 염기성 용액을 준비하는 단계; 및 상기 산성 용액과 염기성 용액을 혼합하여 겔을 형성시키는 단계; 를 포함하는 가교 히알루론산 조성물 제조방법을 제공한다. In exemplary embodiments of the present invention, the method for preparing a crosslinked hyaluronic acid composition described above includes: preparing an acidic solution containing a metal cation of a divalent or higher value, and a basic solution comprising a hyaluronic acid ion; And mixing the acidic solution with a basic solution to form a gel; It provides a method for producing a cross-linked hyaluronic acid composition comprising a.
종래 히알루론산에 화학적 가교제를 첨가하는 경우, 제조 시간이 최소 하루에서 3일 이상 소요되었으나, 본 발명의 제조방법에 따르면, 예컨대 2가 이상의 금속 양이온이 포함된 HCl 용액과 히알루론산 이온이 포함된 NaOH 용액을 혼합하는 것만으로도 이온 결합에 의한 겔이 형성되어, 빠른 시간 내에 간편하게 가교 히알루론산 조성물을 제조할 수 있다. In the case of adding a chemical cross-linking agent to the conventional hyaluronic acid, the production time was at least 3 days or more, but according to the manufacturing method of the present invention, for example, HCl solution containing a metal cation of divalent or higher and NaOH containing hyaluronic acid ion By mixing the solution, a gel formed by ion bonding is formed, and a crosslinked hyaluronic acid composition can be easily prepared in a short time.
또한, 일반적인 화학적 가교제를 포함하는 가교 히알루론산 조성물 제조시 히알루론산의 OH기와 에폭사이드(epoxide) 계열의 가교제 사이에서 에테르 결합으로 연결되므로, 인체에 자극이 있을 수 있어 반드시 세척이 필요한 것과 달리, 본원 발명의 제조방법에 따르면 겔 형성 후에는 Na+나 Cl-와 같이 유해하지 않은 이온만 남게되어, 유해성으로 인한 별도의 세척과정도 불필요하다. In addition, when preparing a cross-linked hyaluronic acid composition containing a general chemical cross-linking agent, since it is connected by an ether bond between the OH group of hyaluronic acid and an epoxide-based cross-linking agent, there may be irritation to the human body, and unlike washing is necessary, the present application According to the manufacturing method of the present invention, after the gel formation, only non-toxic ions such as Na + and Cl - remain, and a separate washing process due to harmfulness is also unnecessary.
일 구현예에서, 상기 겔을 형성시키는 단계는 1시간 이내일 수 있고, 예컨대, 50분 이내, 40분 이내 또는 30분 이내일 수 있다. In one embodiment, the step of forming the gel may be within 1 hour, for example, within 50 minutes, within 40 minutes or within 30 minutes.
일 구현예에서, 상기 혼합하는 단계에서, pH는 5 내지 7일 수 있다. 상기 pH가 5 미만인 경우 히알루론산이 일부 분해되어 제대로된 가교가 일어나지 않으며, pH가 7 초과인 경우 겔의 안정도가 떨어진다. In one embodiment, in the mixing step, the pH may be 5 to 7. When the pH is less than 5, hyaluronic acid is partially decomposed to prevent proper crosslinking, and when the pH is greater than 7, the stability of the gel is deteriorated.
이하, 하기의 실시예를 통하여 본 발명을 보다 구체적으로 설명한다. 그러나 하기의 실시에는 본 발명에 대한 이해를 돕기 위해 예시의 목적으로만 제공된 것일 뿐, 본 발명의 범주 및 범위가 이에 한정되지 않는다.Hereinafter, the present invention will be described in more detail through the following examples. However, the following implementations are provided for the purpose of illustration only to aid understanding of the present invention, and the scope and scope of the present invention are not limited thereto.
실시예Example - 가교 히알루론산 조성물의 제조 -Preparation of cross-linked hyaluronic acid composition
실시예로서, 0.05N NaOH에 1 중량% 히알루론산염(Sodium Hyaluronate)를 녹인 후 동량의 0.05N HCl에 0.1 중량% 알루미늄 수화물(Aluminum Hydroxide)를 녹인 용액과 혼합하였으며, 최종 함량이 가교 히알루론산 조성물 총 중량을 기준으로 0.5 중량% 히알루론산 및 0.05 중량% 알루미늄 수화물(Aluminum hydroxide)이 되도록 제조하였다(실시예 1). 이의 FTIR 결과를 나타낸 도 3을 참조하면, 1615 cm-1에서 COO- 피크가 나타난다는 사실을 확인할 수 있다. As an example, after dissolving 1% by weight of sodium hyaluronate in 0.05N NaOH and mixing with a solution of 0.1% by weight of aluminum hydrate (Aluminum Hydroxide) in 0.05N HCl in the same amount, the final content of the crosslinked hyaluronic acid composition It was prepared to be 0.5% by weight of hyaluronic acid and 0.05% by weight of aluminum hydrate (Aluminum hydroxide) based on the total weight (Example 1). Referring to Figure 3 showing the FTIR results, it can be confirmed that the COO- peak appears at 1615 cm -1 .
비교예로서 히알루론산의 함량은 모두 동일하게 포함하고, 가교제를 첨가하지 않은 조성물(비교예 1), 가교제로서 1,4-부탄다이올다이글라이시딜에테르입니다. (1,4-Butanediol diglycidyl ether)를 포함한 가교 히알루론산 조성물(비교예 2), 가교제로서 염화철을 포함하는 Fe 이온 가교 히알루론산 조성물(비교예 3)을 제조하였다.As a comparative example, the contents of hyaluronic acid are all the same, and a composition without a crosslinking agent (Comparative Example 1) and 1,4-butanediol diglycidyl ether as a crosslinking agent. (1,4-Butanediol diglycidyl ether) containing a cross-linked hyaluronic acid composition (Comparative Example 2), a Fe ion cross-linked hyaluronic acid composition containing iron chloride as a cross-linking agent (Comparative Example 3) was prepared.
상기 실시예 1 및 비교예 1 내지 3에 대하여, 제조 후 색, 제조시간, 끈적임 정도 및 세척 전 자극도를 나누어 하기 표 1에 나타내었다. For Example 1 and Comparative Examples 1 to 3, the color after production, the production time, the degree of stickiness and the irritation before washing are shown in Table 1 below.
(HA)Hyaluronic acid
(HA)
상기 표 1 및 도 2를 참조하면, 알루미늄 이온을 포함하는 가교 히알루론산 조성물의 경우, 기존 히알루론산의 단점인 끈적임이 없으면서도, 제조가 간편하고 자극이 없으며 색깔도 띄지 않아서 화장품 제조에 적합함을 알 수 있었다. 또한, 추가적으로 실시예 1의 조성물의 점도를 측정한 결과 0.85 Pa.s로 나타났다. Referring to Tables 1 and 2, in the case of a cross-linked hyaluronic acid composition containing aluminum ions, there is no stickiness, which is a disadvantage of the existing hyaluronic acid, but it is easy to manufacture, has no irritation, and has no color, making it suitable for cosmetic production. Could know. In addition, the viscosity of the composition of Example 1 was additionally measured and found to be 0.85 Pa.s.
Claims (15)
A crosslinked hyaluronic acid composition comprising a crosslinked hyaluronic acid in which a metal cation of a divalent or higher and a hyaluronic acid ion are crosslinked by ion bonding.
상기 2가 이상의 금속 양이온은 알루미늄 이온인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The divalent or higher metal cation is characterized in that the aluminum ion, cross-linked hyaluronic acid composition.
상기 가교 히알루론산 조성물은 겔 형태인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The cross-linked hyaluronic acid composition is characterized in that it is in the form of a gel, cross-linked hyaluronic acid composition.
상기 가교 히알루론산 조성물의 점도는 0.75 내지 1 Pa·s 인 것을 특징으로 하는, 가교 히알루론산 조성물.According to claim 1,
The viscosity of the cross-linked hyaluronic acid composition is characterized in that 0.75 to 1 Pa · s, cross-linked hyaluronic acid composition.
상기 가교 히알루론산 조성물은 660nm에서 흡광도가 0.5 내지 1.5인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The crosslinked hyaluronic acid composition is characterized in that the absorbance at 660nm is 0.5 to 1.5, crosslinked hyaluronic acid composition.
상기 2가 이상의 금속 양이온의 농도는 상기 가교 히알루론산 조성물 총 중량 기준으로 0.01 내지 0.1 중량%인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The concentration of the divalent or higher metal cation is 0.01 to 0.1% by weight based on the total weight of the crosslinked hyaluronic acid composition, the crosslinked hyaluronic acid composition.
상기 히알루론산의 농도는 상기 가교 히알루론산 조성물 총 중량을 기준으로, 0.1 내지 1 중량%인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The concentration of the hyaluronic acid is based on the total weight of the cross-linked hyaluronic acid composition, characterized in that 0.1 to 1% by weight, cross-linked hyaluronic acid composition.
상기 2가 이상의 금속 양이온과 히알루론산 이온의 당량비는 1: 1 내지 1: 3인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The equivalent ratio of the metal cation and the hyaluronic acid ion of the divalent or higher is 1: 1 to 1: 3, characterized in that the crosslinked hyaluronic acid composition.
상기 가교 히알루론산 조성물의 FTIR(fourier tranformation infra red) 분석시, 1615 cm-1 에서 COO- 피크가 나타나는 것을 특징으로 하는, 가교 히알루론산 조성물.According to claim 2,
When FTIR (fourier tranformation infra red) analysis of the cross-linked hyaluronic acid composition, characterized in that the COO- peak appears at 1615 cm -1 , cross-linked hyaluronic acid composition.
상기 가교 히알루론산 조성물 내에 Na+ 및 Cl- 이온을 제외한 이온의 농도는 0.001 ppm 이하인 것을 특징으로 하는, 가교 히알루론산 조성물.
According to claim 1,
The concentration of ions excluding Na + and Cl − ions in the crosslinked hyaluronic acid composition is 0.001 ppm or less, the crosslinked hyaluronic acid composition.
A cosmetic composition comprising the crosslinked hyaluronic acid composition according to any one of claims 1 to 10.
A composition for external application for skin comprising the crosslinked hyaluronic acid composition according to any one of claims 1 to 10.
2가 이상의 금속 양이온을 포함하는 산성 용액 및, 히알루론산 이온을 포함하는 염기성 용액을 준비하는 단계; 및
상기 산성 용액과 염기성 용액을 혼합하여 겔을 형성시키는 단계; 를 포함하는 가교 히알루론산 조성물 제조방법.
In the method for producing a cross-linked hyaluronic acid composition according to any one of claims 1 to 10,
Preparing an acidic solution containing a divalent or higher metal cation and a basic solution containing hyaluronic acid ions; And
Mixing the acidic solution and a basic solution to form a gel; Method for preparing a crosslinked hyaluronic acid composition comprising a.
상기 겔을 형성시키는 시간은 1시간 이내인 것을 특징으로 하는, 가교 히알루론산 조성물 제조방법.
The method of claim 13,
The time to form the gel is characterized in that within 1 hour, the method for producing a cross-linked hyaluronic acid composition.
상기 혼합하는 단계에서, pH는 5 내지 7인 것을 특징으로 하는, 가교 히알루론산 조성물 제조방법.The method of claim 13,
In the mixing step, the pH is 5 to 7, characterized in that the cross-linked hyaluronic acid composition production method.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20230165124A (en) | 2022-05-26 | 2023-12-05 | (주)아모레퍼시픽 | Method of prepairing hyaluronic acid nanoparticles |
| KR20230166560A (en) | 2022-05-31 | 2023-12-07 | (주)아모레퍼시픽 | Method of prepairing crosslinked hyaluronic acid gel |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100535319B1 (en) * | 1997-10-27 | 2006-04-21 | 히사미쓰 메디카루 가부시키가이샤 | Drug composition with controlled drug release rate |
| KR20090040979A (en) * | 2007-10-23 | 2009-04-28 | 주식회사유한양행 | Nano-particles for targeting comprising hyaluronic acid or its salt, metal ion, and water-insoluble biodegradable polymer and processes for the preparation thereof |
| CN101611063A (en) * | 2006-11-10 | 2009-12-23 | 施泰福实验室股份有限公司 | Cross-linked-hyaluronic acid and preparation method thereof |
| KR20110080690A (en) * | 2010-01-06 | 2011-07-13 | 한남대학교 산학협력단 | Tissue adhesion barrier and method for preparing of the same |
| KR101239037B1 (en) * | 2004-11-15 | 2013-03-04 | 가부시키가이샤 시세이도 | Method for producing crosslinked hyaluronic acid gel |
| KR20130057640A (en) | 2011-11-24 | 2013-06-03 | (주)아모레퍼시픽 | Water-insoluble gel composition and manufacturing method of the same |
| KR20150044862A (en) * | 2015-03-17 | 2015-04-27 | (주)웰빙해피팜 | Ionic cross-linked hyaluronic acid tissue restorative material |
-
2018
- 2018-10-30 KR KR1020180130623A patent/KR102610937B1/en active IP Right Grant
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100535319B1 (en) * | 1997-10-27 | 2006-04-21 | 히사미쓰 메디카루 가부시키가이샤 | Drug composition with controlled drug release rate |
| KR101239037B1 (en) * | 2004-11-15 | 2013-03-04 | 가부시키가이샤 시세이도 | Method for producing crosslinked hyaluronic acid gel |
| CN101611063A (en) * | 2006-11-10 | 2009-12-23 | 施泰福实验室股份有限公司 | Cross-linked-hyaluronic acid and preparation method thereof |
| KR20090040979A (en) * | 2007-10-23 | 2009-04-28 | 주식회사유한양행 | Nano-particles for targeting comprising hyaluronic acid or its salt, metal ion, and water-insoluble biodegradable polymer and processes for the preparation thereof |
| KR20110080690A (en) * | 2010-01-06 | 2011-07-13 | 한남대학교 산학협력단 | Tissue adhesion barrier and method for preparing of the same |
| KR20130057640A (en) | 2011-11-24 | 2013-06-03 | (주)아모레퍼시픽 | Water-insoluble gel composition and manufacturing method of the same |
| KR20150044862A (en) * | 2015-03-17 | 2015-04-27 | (주)웰빙해피팜 | Ionic cross-linked hyaluronic acid tissue restorative material |
Non-Patent Citations (1)
| Title |
|---|
| Journal of Tissue Engineering, Vol.8, 2017* * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20230165124A (en) | 2022-05-26 | 2023-12-05 | (주)아모레퍼시픽 | Method of prepairing hyaluronic acid nanoparticles |
| KR20230166560A (en) | 2022-05-31 | 2023-12-07 | (주)아모레퍼시픽 | Method of prepairing crosslinked hyaluronic acid gel |
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