CN110075006B - Method for promoting solution compatibility of hyaluronic acid type substance and type II collagen and composition containing the same - Google Patents
Method for promoting solution compatibility of hyaluronic acid type substance and type II collagen and composition containing the same Download PDFInfo
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- CN110075006B CN110075006B CN201910318433.4A CN201910318433A CN110075006B CN 110075006 B CN110075006 B CN 110075006B CN 201910318433 A CN201910318433 A CN 201910318433A CN 110075006 B CN110075006 B CN 110075006B
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- hyaluronic acid
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- collagen
- polyglutamate
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- 239000000203 mixture Substances 0.000 title claims abstract description 141
- 102000000503 Collagen Type II Human genes 0.000 title claims abstract description 108
- 108010041390 Collagen Type II Proteins 0.000 title claims abstract description 108
- 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 99
- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 89
- 229960003160 hyaluronic acid Drugs 0.000 title claims abstract description 89
- 239000000126 substance Substances 0.000 title claims abstract description 79
- 238000000034 method Methods 0.000 title claims abstract description 25
- 230000001737 promoting effect Effects 0.000 title claims abstract description 9
- 108010020346 Polyglutamic Acid Proteins 0.000 claims abstract description 93
- 239000000243 solution Substances 0.000 claims abstract description 87
- 229920000370 gamma-poly(glutamate) polymer Polymers 0.000 claims abstract description 83
- 239000002244 precipitate Substances 0.000 claims abstract description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 49
- 229920000831 ionic polymer Polymers 0.000 claims abstract description 47
- 239000007864 aqueous solution Substances 0.000 claims abstract description 27
- 239000002537 cosmetic Substances 0.000 claims abstract description 11
- 235000013305 food Nutrition 0.000 claims abstract description 9
- 239000000047 product Substances 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims description 36
- 229920002643 polyglutamic acid Polymers 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 16
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical class CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 claims description 8
- 239000006104 solid solution Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000002195 synergetic effect Effects 0.000 claims description 7
- 239000003381 stabilizer Substances 0.000 claims description 6
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 229940127557 pharmaceutical product Drugs 0.000 claims description 2
- 239000006084 composite stabilizer Substances 0.000 claims 1
- 229920001436 collagen Polymers 0.000 abstract description 22
- 102000008186 Collagen Human genes 0.000 abstract description 20
- 108010035532 Collagen Proteins 0.000 abstract description 20
- 230000007774 longterm Effects 0.000 abstract description 14
- 238000003860 storage Methods 0.000 abstract description 14
- 230000003020 moisturizing effect Effects 0.000 abstract description 12
- 230000008901 benefit Effects 0.000 abstract description 3
- 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 46
- 239000011734 sodium Substances 0.000 description 46
- 229910052708 sodium Inorganic materials 0.000 description 46
- 238000002834 transmittance Methods 0.000 description 40
- 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 29
- 229920002385 Sodium hyaluronate Polymers 0.000 description 28
- 229940010747 sodium hyaluronate Drugs 0.000 description 28
- 238000003756 stirring Methods 0.000 description 23
- 239000008213 purified water Substances 0.000 description 17
- 239000002131 composite material Substances 0.000 description 15
- 230000000052 comparative effect Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000000017 hydrogel Substances 0.000 description 7
- 238000004132 cross linking Methods 0.000 description 6
- 229940014041 hyaluronate Drugs 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000337 buffer salt Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 239000000806 elastomer Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000001815 facial effect Effects 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- SHKUUQIDMUMQQK-UHFFFAOYSA-N 2-[4-(oxiran-2-ylmethoxy)butoxymethyl]oxirane Chemical compound C1OC1COCCCCOCC1CO1 SHKUUQIDMUMQQK-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000037303 wrinkles Effects 0.000 description 2
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- UWJJYHHHVWZFEP-UHFFFAOYSA-N pentane-1,1-diol Chemical compound CCCCC(O)O UWJJYHHHVWZFEP-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- -1 tissue engineering Substances 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
- A23L29/045—Organic compounds containing nitrogen as heteroatom
-
- 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products 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
- A61K8/18—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
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/88—Polyamides
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/592—Mixtures of compounds complementing their respective functions
Abstract
The invention discloses a method for promoting the solution compatibility of hyaluronic acid substances and type II collagen and a composition containing the two substances. The invention can overcome the problem that the hyaluronic acid substances and the collagen substances are easy to form polyion type precipitates when meeting in water, so that the hyaluronic acid substances and the collagen substances can form uniform and transparent aqueous solution, flocculent precipitates can not appear after long-term storage, the stability is good, and the product quality is improved. Compared with the prior art, the composition has the advantages that the structures of the hyaluronic acid substances and the type II collagen are not damaged, the composition of the hyaluronic acid substances, the type II collagen and the polyglutamate also has a good moisturizing effect, the application field and the safety are expanded, and the composition has a good application prospect in the fields of food, cosmetics or medical instruments.
Description
Technical Field
The invention relates to a method for promoting the compatibility of a hyaluronic acid substance and type II collagen in an aqueous solution and avoiding the generation of polyion precipitates, in particular to a method for promoting the compatibility of the hyaluronic acid substance and the type II collagen in the aqueous solution by the existence of polyglutamate, and also relates to a composition containing the hyaluronic acid substance, the type II collagen and the polyglutamate and application thereof.
Technical Field
Hyaluronic Acid (HA) is a high-molecular mucopolysaccharide with N-acetylglucosamine and D-glucuronic acid as structural units, is a currently recognized best moisturizing component, can play a unique role in protecting skin when being used in cosmetics, can keep the skin moist, smooth, fine, tender and elastic, and HAs the effects of preventing wrinkles, resisting wrinkles, beautifying, protecting health and repairing the physiological functions of the skin.
Collagen (Collagen) is a biological macromolecule, is a main component in animal connective tissues, is also a functional protein with the largest content and the widest distribution in mammals, has the characteristics of good nutrition, repair, moisture preservation, compatibility, affinity and the like, also has the biological characteristics of low immunogenicity, biocompatibility and degradability, and is widely applied to the fields of food, medicine, tissue engineering, cosmetics and the like. The collagen is divided into I type, II type, III type, V type and XI type, is widely present in various parts of human body, and is a magical beauty component always sought in the beauty industry.
Polyglutamic acid (PGA) is an anionic biopolymer which has certain viscosity, water solubility, biodegradation and no toxicity, and the special molecular structure ensures that the Polyglutamic acid has extremely strong moisture retention, can effectively increase the moisture retention capacity of the skin and promote the skin health, is superior to common moisture retention components, and is a new generation of biological moisture retention agent. Meanwhile, PGA has super-strong adsorbability and biodegradability, the degradation product is pollution-free glutamic acid, and PGA has great commercial value and social value in industries such as cosmetics, foods, medicines and the like.
However, hyaluronic acid and type ii collagen have opposite charges, and when they are mixed in water, they are very likely to form polyionic complexes due to electrostatic attraction, resulting in flocculent precipitates, which affect the uniformity, structure and performance of the mixture, thereby limiting the use of the two compositions. Currently, in order to prevent or avoid the formation of such polyionic precipitates, crosslinking, pH adjustment or addition of buffer systems are generally employed. The document An improved method to prepare a cationic acid and type II collagen composition (Journal of biological materials research, vol.61, 2002, pp.330-6) dissolves type II collagen with hydrochloric acid, and sodium hyaluronate is added to the solution in the range of p H value 1-2 and dissolved with stirring to inhibit the formation of polyion precipitate. In the method, the lower p H value can damage the physical structures of collagen and hyaluronic acid to a certain extent, so that the molecular structures of collagen and hyaluronic acid are broken, thereby affecting the efficacy of the collagen and hyaluronic acid. Patent CN200910192977.7 provides a type II collagen and hyaluronic acid composite sponge scaffold and application thereof, mixing a hyaluronic acid solution with a high-purity type II collagen solution, homogenizing under a low-temperature condition after precipitation is generated, freeze-drying, and then crosslinking by using an EDC and NHS dual crosslinking agent to prepare the type II collagen and hyaluronic acid composite sponge scaffold. The patent avoids the formation of polyionic precipitates by means of crosslinking, but the method has the risk of residual crosslinking agent and is only suitable for partial products, thereby limiting the application range. Patent CN201710606133.7 provides a preparation method and application of a composite hyaluronic acid collagen hydrogel, under the condition of existence of a buffer system, hyaluronic acid and collagen are mixed according to a certain proportion to obtain hydrogel, the hydrogel has a low content (<0.05 wt%) of polyion precipitate, and the obtained hydrogel can improve the functions of moisturizing and lubricating skin of the hyaluronic acid hydrogel and can also exert the function of leading the collagen to repair tissues. Although the buffer salt system in the patent can effectively reduce the content of the ionic precipitates, the generation of the ionic precipitates cannot be completely avoided, and the addition of the buffer salt system can limit the application range of the ionic precipitates in cosmetics or pharmaceutical products, and generate the defects of incompatibility, anaphylactic reaction and the like.
Disclosure of Invention
Aiming at the defect that a hyaluronic acid substance and type II collagen are mixed in water and easily form white flocculent polyion type precipitates, the invention provides a method for promoting the solution compatibility of the hyaluronic acid substance and the type II collagen, the method improves the compatibility of the hyaluronic acid substance and the type II collagen in an aqueous solution by adding polyglutamate, and the obtained aqueous solution does not generate the polyion type precipitates.
The invention also provides a composition containing the hyaluronic acid substances and type II collagen, which contains polyglutamate, not only has good efficacy, but also can prevent the hyaluronic acid substances and the type II collagen from forming polyion precipitates.
The specific technical scheme of the invention is as follows:
a method for promoting the solution compatibility of hyaluronic acid-like substances and type II collagen by preventing the formation of flocculent polyion-type precipitates when hyaluronic acid-like substances and type II collagen meet in an aqueous solution by adding polyglutamate.
Further, the method specifically refers to: when an aqueous solution containing a hyaluronic acid-type substance and type II collagen is prepared in the presence of polyglutamate (i.e., when the hyaluronic acid-type substance and type II collagen are mixed in pure water or when an aqueous solution containing other components is mixed, preferably when the hyaluronic acid-type substance and type II collagen are mixed in pure water), the formation of polyion precipitates of the hyaluronic acid-type substance and type II collagen can be prevented.
Further, the polyglutamate, the hyaluronic acid-like substance and the collagen-like substance are mixed in one of the following manners:
a. dissolving polyglutamate in water, adding collagen solid or aqueous solution, and adding hyaluronic acid solid or aqueous solution;
b. dissolving collagen substances in water, adding polyglutamate solid or aqueous solution, and then adding hyaluronic acid substances solid or aqueous solution;
c. respectively preparing the hyaluronic acid substances and the collagen substances into aqueous solutions containing polyglutamate, and then mixing the two solutions.
Further, in the above method, the hyaluronic acid-like substance includes one or more of hyaluronic acid, a hyaluronic acid salt, and a hyaluronic acid derivative. The hyaluronic acid salt includes sodium salt, potassium salt, calcium salt, etc. of hyaluronic acid, and the hyaluronic acid derivative includes acetylated hyaluronic acid or a salt thereof, which may be directly purchased in the market, cross-linked hyaluronic acid or a salt thereof, which refers to cross-linked hyaluronic acid or a salt thereof that is subjected to a cross-linking reaction and may be dissolved in water, and the like.
Further, in the above method, the hyaluronic acid-like substance may have any molecular weight, but when the molecular weight is 3kDa to 3000kDa, the usability is better.
Further, in the above method, the type II collagen refers to collagen having a molecular weight of 300kDa to 1500kDa, which is produced by chondrocytes.
Further, in the above method, the polyglutamate is preferably sodium polyglutamate, and the molecular weight of the polyglutamate is not less than 1000kDa, for example, 1000kDa-2000 kDa.
Further, in the above method, the mass ratio of the hyaluronic acid-type substance, the type ii collagen, and the polyglutamate is 1: 0.5-5: 1-5 times, the formation of polyion precipitates can be avoided, and the three components can be compounded to have obvious synergistic effect.
Furthermore, the content of hyaluronic acid substances and type II collagen in an aqueous solution can be increased by using the method of the invention, and the polyion type precipitate can not be generated even if the content is high. The content of hyaluronic acid substances in the whole mixed solution can reach 1wt% at most, and the content of type II collagen in the whole mixed solution can reach 5wt% at most.
The invention also provides a composition containing the hyaluronic acid substance and the type II collagen, which comprises the hyaluronic acid substance, the type II collagen and a synergistic stabilizer, wherein the synergistic stabilizer is polyglutamate, and the mass ratio of the hyaluronic acid substance to the type II collagen to the synergistic stabilizer is 1: 0.5-5: 1-5. Within the range, the formation of polyion precipitates can be avoided, and the three components can be compounded to have better efficacy, and the efficacy is particularly reflected in the moisturizing performance and stability of the product.
Furthermore, the content of the hyaluronic acid substances in the whole composition is less than or equal to 1wt% and can reach 1wt%, and the content of the type II collagen in the whole composition is less than or equal to 5wt% and can reach 5 wt%.
Further, in the above composition, the hyaluronic acid-like substance, type II collagen and polyglutamate are defined in accordance with the above method for promoting the solution compatibility of hyaluronic acid-like substance and type II collagen.
Furthermore, in the composition, the molecular weight of the hyaluronic acid substance is 3kDa-3000 kDa.
Further, in the above composition, the type II collagen has a molecular weight of 300kDa to 1500 kDa.
Further, in the above composition, the molecular weight of the polyglutamate is not less than 1000kDa, for example, 1000-2000 kDa.
Further, the invention provides an application of the composition containing the hyaluronic acid substances and the type II collagen in the fields of food, cosmetics or medicines. Preferably, the composition containing the hyaluronic acid type substance and the type II collagen is contained in the food, the cosmetics or the medicine instrument in an amount of 0.05wt% to 50wt%, and more preferably 0.1wt% to 10 wt%.
Further, the invention provides a preferable preparation method of the composition containing the hyaluronic acid type substances and the type II collagen, which comprises the following specific steps:
(1) preparing polyglutamate into an aqueous solution;
(2) gradually adding the type II collagen solid into the polyglutamate aqueous solution obtained in the step (1) under stirring (gradually dividing into batches or feeding), and uniformly mixing to obtain a type II collagen polyglutamate compound solution;
(3) preparing a hyaluronic acid substance aqueous solution;
(4) and (3) uniformly mixing the hyaluronic acid substance aqueous solution in the step (3) with the collagen II polyglutamic acid compound solution in the step (2) to obtain the composition containing the hyaluronic acid substance and the collagen substance.
According to the invention, through research, when the hyaluronic acid substances and the type II collagen form an aqueous solution, under the condition of existence of polyglutamate, the problem that the hyaluronic acid substances and the collagen substances are easy to form polyion type precipitates when meeting in water can be solved, so that the hyaluronic acid substances and the collagen substances can form a uniform and transparent aqueous solution, flocculent precipitates can not appear after long-term storage, the stability is good, and the product quality is improved. Compared with the measures of cross-linking, pH adjustment and buffer salt system reported in the prior art, the measure for avoiding the polyion precipitate has the advantage of not damaging the structures of the hyaluronic acid substance and the type II collagen, and the combination of the hyaluronic acid substance, the type II collagen and the polyglutamate has good moisturizing effect, thereby expanding the application field and safety and having good application prospect in the fields of food, cosmetics or pharmaceutical machinery.
Detailed Description
The present invention will be further illustrated with reference to the following examples, but the present invention is not limited to the following examples.
In the examples described below, the hyaluronic acid-type substances used are from Huaxi Biotech, Inc., the type II collagen is from Shanghai Kenyin, Inc., and the sodium polyglutamate is from Huaxi Biotech, Inc.
Example 1
A composition containing sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of sodium hyaluronate (Mw: 200kDa-400 kDa), 0.5g of type II collagen (Mw: 300 kDa) and 0.5g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.5 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding a small amount of sodium hyaluronate (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.41.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 2
A composition containing potassium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of potassium hyaluronate (Mw: 200kDa-400 kDa), 0.5g of type II collagen (Mw: 300 kDa) and 0.5g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving type II collagen (0.5 g) into deionized purified water (98.5 g), adding sodium polyglutamate (0.5 g) while stirring, mixing uniformly, adding a small amount of potassium hyaluronate (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.42.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 3
A composition containing calcium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of calcium hyaluronate (Mw: 200k-400 kDa), 0.5g of type II collagen (Mw: 300 kDa) and 0.5g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.25 g) into deionized purified water (49.5 g), adding type II collagen (0.5 g) while stirring, and mixing to obtain solution A; dissolving sodium polyglutamate (0.25 g) into deionized purified water (49 g), adding calcium hyaluronate (0.5 g) for multiple times while stirring, mixing uniformly to obtain solution B, mixing solution A and solution B, and stirring uniformly to obtain the final composition, wherein the pH of the obtained composition solution is 6.51.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 4
A composition containing acetylated hyaluronic acid, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of acetylated hyaluronic acid (Mw: 2000-2500 kDa), 0.5g of type II collagen (Mw: 300 kDa) and 0.5g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.5 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding acetylated hyaluronic acid (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with pH of 6.21.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 5
A composition containing hyaluronic acid elastomer TL100, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: hyaluronic acid elastomer TL100(Mw:1000-1500 kDa, Huaxi Biotechnology Co., Ltd.) 0.5g, type II collagen (Mw:1000 kDa) 0.5g, and sodium polyglutamate (Mw:1000 kDa) 0.5 g.
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.5 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding a small amount of hyaluronic acid elastomer TL100 (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.46.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 6
A composition containing sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of sodium hyaluronate (Mw: 200k-400 kDa), 0.05g of type II collagen (Mw: 600 kDa) and 0.5g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.95 g), adding type II collagen (0.05 g) while stirring, mixing uniformly, adding a small amount of sodium hyaluronate (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.37.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 7
A composition containing sodium hyaluronate, high molecular weight type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of sodium hyaluronate (Mw: 200kDa-400 kDa), 0.5g of high molecular weight type II collagen (Mw: 1200 kDa) and 0.5g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.5 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding a small amount of sodium hyaluronate (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.34.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 8
A composition containing low molecular weight sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of low molecular weight sodium hyaluronate (Mw: 3-10 kDa), 0.5g of type II collagen (Mw: 300 kDa) and 0.5g of sodium polyglutamate (Mw: 1500 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.5 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding a small amount of low molecular weight sodium hyaluronate (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.40.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 9
A composition containing high molecular weight sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.1g of high molecular weight sodium hyaluronate (Mw: 2500-.
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.5 g) into deionized purified water (98.9 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding a small amount of high molecular weight sodium hyaluronate (0.1 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.55.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 10
A composition containing sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.1g of sodium hyaluronate (Mw: 200k-400 kDa), 0.05g of type II collagen (Mw: 1500 kDa) and 0.1g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.1 g) into deionized purified water (99.75 g), adding type II collagen (0.05 g) while stirring, mixing uniformly, adding a small amount of sodium hyaluronate (0.1 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.82.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Example 11
A composition containing sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 1g of sodium hyaluronate (Mw: 200k-400 kDa), 5g of type II collagen (Mw: 300 kDa) and 5g of sodium polyglutamate (Mw: 2000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (5 g) into deionized purified water (89 g), adding type II collagen (5 g) while stirring, mixing uniformly, adding a small amount of sodium hyaluronate (1 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.23.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
Comparative example 1
A composition containing sodium hyaluronate, type II collagen and sodium polyglutamate comprises effective components and water, wherein the effective component content is as follows: 0.5g of sodium hyaluronate (Mw: 200k-400 kDa), 10g of type II collagen (Mw: 1200 kDa) and 0.1g of sodium polyglutamate (Mw:1000 kDa).
The preparation method of the composition comprises the following steps: dissolving sodium polyglutamate (0.1 g) into deionized purified water (89.4 g), adding type II collagen (10 g) while stirring, mixing uniformly, adding a small amount of sodium hyaluronate (0.5 g) into the mixed collagen-polyglutamic acid composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.83.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 92.9 percent, which indicates that the composition is not uniform and polyion precipitates are generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, white flocculent precipitate can be seen by naked eyes, and the stability is poor. This indicates that the production of polyion-type precipitates cannot be effectively shielded when the dosage of the type II collagen is too high and the dosage of the sodium polyglutamate is too low.
Comparative example 2
The composition was formulated as in example 1, except that: the Mw of the sodium polyglutamate was 500kDa, and the pH of the resulting composition solution was 6.78.
The transmittance, measured by UV spectrophotometer (550 nm), was 95.9%, indicating that the composition was heterogeneous and that a polyionic precipitate was formed. The prepared composition is kept stand for 3 months in a natural environment protected from light, white flocculent precipitate can be seen by naked eyes, and the stability is poor. This indicates that the molecular weight of the sodium polyglutamate has an effect on the effect of shielding the polyion type precipitation.
Comparative example 3
A composition was prepared according to the active ingredients of example 1, except that the composition was prepared by: dissolving sodium hyaluronate (0.5 g) into deionized purified water (98.5 g), adding type II collagen (0.5 g) while stirring, mixing uniformly, adding a small amount of sodium polyglutamate (0.5 g) into the mixed hyaluronic acid-collagen composite solution for multiple times, and mixing uniformly to obtain the composition solution with the pH of 6.58.
The prepared composition is measured by an ultraviolet spectrophotometer to obtain light transmittance of 550nm, the light transmittance is 87.5%, flocculent precipitate can be seen by naked eyes, and the content of polyion precipitate is high. This indicates that the timing of adding the sodium polyglutamate is very important, and if the sodium polyglutamate is added after the hyaluronic acid substance is contacted with the type II collagen, the generation of polyion type precipitation cannot be effectively shielded.
Comparative example 4
A composition was formulated according to the active ingredients of example 1, except that the composition was formulated by: dissolving type II collagen (0.5 g) into 100mL of purified water, adjusting the pH value of the solution to 1-2 by using hydrochloric acid, adding sodium hyaluronate (0.5 g), stirring for dissolving, adding sodium polyglutamate (0.5 g), and uniformly mixing to obtain the composition solution, wherein the pH value of the composition solution is 1.65.
The light transmittance of the prepared composition at 550nm is measured by an ultraviolet spectrophotometer and is 100 percent, which shows that the solution of the composition is uniform and transparent and no polyion precipitate is generated. The prepared composition is kept stand for 3 months in a natural environment protected from light, and then the light transmittance at 550nm is measured by using an ultraviolet spectrophotometer, and the light transmittance is still 100 percent, which shows that the solution of the composition has good stability, and the polyion type precipitate is not generated after long-term storage.
EXAMPLE 12 skin moisturizing efficacy of composition solutions
Skin moisturizing efficacy was examined using the change in moisture content of the skin before and after application of the composition.
1. Experimental Material
Composition solutions of example 1, comparative example 3 and comparative example 4, base moisturizing emulsion (Huaxi Biotech Co., Ltd.).
2. Laboratory apparatus
Skin moisture tester Corneometer CM 825 (Courage Khazaka, Germany).
3. Experimental methods
3.1 moisturizing emulsion sample preparation
The composition solutions of example 1, comparative example 3 and comparative example 4 were added to the base moisturizing emulsion in an amount of 10wt%, respectively, as sample a, sample B and sample C.
Measurement of moisture Retention
26 volunteers aged 20-50 years, male and female halves, were recruited for each sample. The samples were applied to test areas marked 4cm × 4cm on the left and right forearm flexor sides of the subject. The coating amount is 3.0 mg/cm2Gently massage until the sample is absorbed. Measuring the skin moisture content before and after 1, 3 and 5 hours by using a skin moisture tester, calculating the skin moisture content increase rate according to the following formula, and averaging the skin moisture content increase rates of volunteers using the samples to obtain the average skin moisture content increase rate of the sample.
The moisturizing effect of each sample was calculated as shown in table 1.
As can be seen from the data in Table 1, the skin moisture content increase rate is higher for sample A than for samples B and C, indicating that the composition of example 1 provides the best moisturization benefits. Therefore, the composition compounded by the method has high activity, does not generate polyion precipitates, and has excellent moisturizing effect.
EXAMPLE 13A mask pack containing a composition of hyaluronic acid-type substances and type II collagen
Preparing hyaluronic acid (Mw: 1200kDa, Mw: 200k-400kDa, Mw < 10 kDa) with three molecular weights into hyaluronic acid mixed solution with the mass fraction of 0.5wt% according to the mass ratio of 1:1: 1; gradually dissolving 0.5wt% type II collagen (Mw: 300 kDa) into 0.5wt% polyglutamic acid (Mw: 1500 kDa) water solution, mixing well, adding the solution into the hyaluronic acid mixed solution while stirring, and stirring at constant speed to mix well; and finally, adding the composition solution into a basic facial mask essence (comprising 1.5 wt% of urea, 1wt% of triethanolamine, 5wt% of pentanediol, 0.5wt% of acrylic acid copolymer and deionized water to make up to 100 wt%), and adding a non-woven fabric facial mask for packaging to obtain the facial mask.
EXAMPLE 14 hydrogel of hyaluronic acid-type substance-collagen type II-containing composition
Dissolving sodium polyglutamate (Mw: 1500 kDa) into proper deionized purified water to prepare 0.5wt% solution, adding 0.5wt% type II collagen (Mw: 1100 kDa) into the solution while stirring, uniformly mixing, adding a small amount of the dissolved 0.5wt% sodium hyaluronate (Mw: 1200 kDa) solution into the mixed collagen polyglutamic acid compound, fully stirring to uniformly mix the three, and adjusting the pH value to 12 by using sodium hydroxide.
Adding 0.005wt% of 1, 4-butanediol diglycidyl ether (BDDE, sigma) of sodium hyaluronate into the mixed solution, stirring uniformly, reacting at 30 ℃ for 8 hours, precipitating the reaction solution by using 95wt% of ethanol with the volume being three times of the reaction solution, adding glacial acetic acid to adjust the pH of the reaction solution to 7.0, carrying out suction filtration and precipitation, and carrying out vacuum drying at 50 ℃ to obtain a powdery crosslinking product.
The crosslinked product was dissolved in deionized purified water to give a 0.2wt% hydrogel.
Claims (10)
1. A method for promoting the solution compatibility of hyaluronic acid substances and type II collagen, which is characterized by comprising the following steps: by adding polyglutamate, the hyaluronic acid substances and the type II collagen are prevented from forming polyion precipitates when meeting in an aqueous solution;
the polyglutamate, the hyaluronic acid-type substance and the type II collagen are mixed by one of the following methods:
a. dissolving polyglutamate in water, adding type II collagen solid or aqueous solution, and adding hyaluronic acid solid or aqueous solution;
b. dissolving type II collagen in water, adding polyglutamate solid or water solution, and then adding hyaluronic acid type substance solid or water solution;
c. respectively preparing a hyaluronic acid substance and type II collagen into aqueous solution containing polyglutamate, and then mixing the two solutions;
the molecular weight of the hyaluronic acid substances is 3-3000 kDa; the molecular weight of the type II collagen is 300kDa-1500 kDa; the molecular weight of the polyglutamate is not less than 1000 kDa;
the mass ratio of the hyaluronic acid substances to the type II collagen to the polyglutamate is 1: 0.5-5: 1-5;
the hyaluronic acid-like substance comprises one or more of hyaluronic acid, a hyaluronate salt and a hyaluronic acid derivative, and the hyaluronic acid derivative comprises acetylated hyaluronic acid or a salt thereof or cross-linked hyaluronic acid or a salt thereof.
2. The method of claim 1, further comprising: the polyglutamate is polyglutamic acid sodium salt.
3. The method of claim 2, wherein: the hyaluronic acid salt comprises sodium salt, potassium salt or calcium salt of hyaluronic acid.
4. A composition containing hyaluronic acid substances and type II collagen is characterized in that: the collagen type II and hyaluronic acid composite stabilizer comprises a hyaluronic acid type substance, collagen type II and a synergistic stabilizer, wherein the synergistic stabilizer is polyglutamate, and the mass ratio of the hyaluronic acid type substance to the collagen type II to the synergistic stabilizer is 1: 0.5-5: 1-5;
the polyglutamate, the hyaluronic acid-type substance and the type II collagen are mixed by one of the following methods:
a. dissolving polyglutamate in water, adding type II collagen solid or aqueous solution, and adding hyaluronic acid solid or aqueous solution;
b. dissolving type II collagen in water, adding polyglutamate solid or water solution, and then adding hyaluronic acid type substance solid or water solution;
c. respectively preparing a hyaluronic acid substance and type II collagen into aqueous solution containing polyglutamate, and then mixing the two solutions;
the molecular weight of the hyaluronic acid substances is 3-3000 kDa; the molecular weight of the type II collagen is 300kDa-1500 kDa; the molecular weight of the polyglutamate is not less than 1000 kDa;
the hyaluronic acid-like substance comprises one or more of hyaluronic acid, a hyaluronate salt and a hyaluronic acid derivative, and the hyaluronic acid derivative comprises acetylated hyaluronic acid or a salt thereof or cross-linked hyaluronic acid or a salt thereof.
5. The composition as set forth in claim 4, wherein: the content of hyaluronic acid substances in the whole composition is less than or equal to 1wt%, and the content of type II collagen in the whole composition is less than or equal to 5 wt%.
6. The composition according to claim 4 or 5, characterized in that: the polyglutamate is polyglutamic acid sodium salt.
7. The composition as set forth in claim 6, characterized in that: the hyaluronic acid salt comprises sodium salt, potassium salt or calcium salt of hyaluronic acid.
8. Use of a composition comprising a hyaluronic acid-type substance and type II collagen according to any of claims 4 to 7 for the preparation of a food, cosmetic or pharmaceutical product.
9. Use according to claim 8, characterized in that: the content of the composition containing the hyaluronic acid substances and the type II collagen in food, cosmetics or medical instrument products is 0.05wt% -50 wt%.
10. Use according to claim 8, characterized in that: the content of the composition containing the hyaluronic acid substances and the type II collagen in food, cosmetics or medical instrument products is 0.1wt% -10 wt%.
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