CN117838609A - Cosmetic preparation method for improving transdermal absorptivity - Google Patents
Cosmetic preparation method for improving transdermal absorptivity Download PDFInfo
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- CN117838609A CN117838609A CN202410253661.9A CN202410253661A CN117838609A CN 117838609 A CN117838609 A CN 117838609A CN 202410253661 A CN202410253661 A CN 202410253661A CN 117838609 A CN117838609 A CN 117838609A
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- transdermal absorption
- cosmetic
- gel
- gly
- preparing
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- 239000002537 cosmetic Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims abstract description 70
- 238000010521 absorption reaction Methods 0.000 claims abstract description 35
- 229940074391 gallic acid Drugs 0.000 claims abstract description 35
- 235000004515 gallic acid Nutrition 0.000 claims abstract description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000011159 matrix material Substances 0.000 claims abstract description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 20
- VMSNAUAEKXEYGP-YEUHZSMFSA-M sodium glycodeoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 VMSNAUAEKXEYGP-YEUHZSMFSA-M 0.000 claims abstract description 18
- 239000000654 additive Substances 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229940113116 polyethylene glycol 1000 Drugs 0.000 claims abstract description 15
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims abstract description 15
- 239000011259 mixed solution Substances 0.000 claims abstract description 14
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims abstract description 14
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 13
- 239000008363 phosphate buffer Substances 0.000 claims abstract description 13
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 13
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 13
- 239000008367 deionised water Substances 0.000 claims abstract description 11
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 11
- 239000012046 mixed solvent Substances 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 9
- 238000001704 evaporation Methods 0.000 claims abstract description 8
- 230000000887 hydrating effect Effects 0.000 claims abstract description 3
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- 238000000034 method Methods 0.000 claims description 11
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- 244000146462 Centella asiatica Species 0.000 claims 1
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- 241001071795 Gentiana Species 0.000 claims 1
- 240000004670 Glycyrrhiza echinata Species 0.000 claims 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims 1
- 241001349804 Juncus alpinoarticulatus Species 0.000 claims 1
- 244000042664 Matricaria chamomilla Species 0.000 claims 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 claims 1
- 240000007817 Olea europaea Species 0.000 claims 1
- 244000234609 Portulaca oleracea Species 0.000 claims 1
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- 241000727169 Prinsepia utilis Species 0.000 claims 1
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- 238000005538 encapsulation Methods 0.000 description 8
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000628997 Flos Species 0.000 description 4
- 230000036571 hydration Effects 0.000 description 4
- 238000006703 hydration reaction Methods 0.000 description 4
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 239000008055 phosphate buffer solution Substances 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
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- 229930003935 flavonoid Natural products 0.000 description 3
- -1 flavonoid compounds Chemical class 0.000 description 3
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- 235000001968 nicotinic acid Nutrition 0.000 description 3
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- 241001116389 Aloe Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229960000271 arbutin Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 229940009976 deoxycholate Drugs 0.000 description 2
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 2
- 229960004705 kojic acid Drugs 0.000 description 2
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
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- 239000000700 radioactive tracer Substances 0.000 description 2
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- 210000004003 subcutaneous fat Anatomy 0.000 description 2
- 238000004627 transmission electron microscopy Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 101710147108 Tyrosinase inhibitor Proteins 0.000 description 1
- 241001433070 Xiphoides Species 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
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- 229910052802 copper Inorganic materials 0.000 description 1
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- LBQIJVLKGVZRIW-ZDUSSCGKSA-N glabridin Chemical compound C1([C@H]2CC3=CC=C4OC(C=CC4=C3OC2)(C)C)=CC=C(O)C=C1O LBQIJVLKGVZRIW-ZDUSSCGKSA-N 0.000 description 1
- 229940093767 glabridin Drugs 0.000 description 1
- PMPYOYXFIHXBJI-ZDUSSCGKSA-N glabridin Natural products C1([C@H]2CC=3C=CC4=C(C=3OC2)CCC(O4)(C)C)=CC=C(O)C=C1O PMPYOYXFIHXBJI-ZDUSSCGKSA-N 0.000 description 1
- LBQIJVLKGVZRIW-UHFFFAOYSA-N glabridine Natural products C1OC2=C3C=CC(C)(C)OC3=CC=C2CC1C1=CC=C(O)C=C1O LBQIJVLKGVZRIW-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
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- 238000000338 in vitro Methods 0.000 description 1
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- 235000005152 nicotinamide Nutrition 0.000 description 1
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- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 1
- 230000009013 pigment accumulation Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
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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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9794—Liliopsida [monocotyledons]
-
- 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
- A61K8/553—Phospholipids, e.g. lecithin
-
- 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
- A61K8/731—Cellulose; Quaternized cellulose derivatives
-
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- 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
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Botany (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
Abstract
The application relates to the technical field of cosmetics, and particularly discloses a preparation method of a cosmetic capable of improving transdermal absorptivity. A cosmetic preparation method for improving transdermal absorptivity comprises the following steps: dissolving sodium carboxymethyl cellulose in deionized water, and then sealing and storing for 24-36 hours at 4 ℃ to obtain a gel matrix; mixing the gel matrix with GA-P-GLY until completely uniform mixed gel is formed, and obtaining transdermal absorption gel; the preparation method of the GA-P-GLY comprises the following steps: firstly, placing a mixed solvent consisting of chloroform and methanol into a eggplant-shaped bottle, then adding phosphatidylcholine and gallic acid, and stirring for dissolution to obtain a mixed solution; rotary evaporating the mixed solution at 52-55deg.C to form a film; (3) Hydrating the film with phosphate buffer containing additives for 30-40 min; the additives include sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate. The cosmetic has improved transdermal absorption rate of gallic acid.
Description
Technical Field
The application relates to the technical field of cosmetics, in particular to a preparation method of cosmetics for improving transdermal absorptivity.
Background
The whitening agent mainly plays a whitening effect by blocking the transportation of melanin in cells and inhibiting the formation of melanin, and the components such as moisture retention, exfoliating, essence, perfume and the like are also added into the cosmetics, so that the whitening effect is enhanced by the synergistic effect of a plurality of whitening components. The whitening agent can reduce skin pigmentation or reduce pigmentation, and can also remove facial pigmentation spots caused by local hyperpigmentation.
The tyrosinase inhibitor can reduce melanin generation and improve skin pigment accumulation, and has wide application prospects in various industries. The raw materials with whitening effect on the market at present mainly comprise kojic acid, ascorbic acid and derivatives thereof, nicotinamide, arbutin, flavonoid compounds, gallic acid and derivatives thereof, and the like. Wherein the ascorbic acid itself has low stability in aqueous solution, and the concentration increase can generate irritation; niacinamide is synthesized by niacin, the dosage is large, the niacin needs to be used for a long time, and the residual niacin on the skin can generate irritation; decomposition of arbutin can produce hydroquinone, which is harmful to skin; kojic acid and its derivatives have good biological activity, but they can produce adverse side effects such as cytotoxicity, skin cancer and dermatitis; flavonoid compounds such as glabridin have good effect, but the cost for extracting the flavonoid compounds from natural plants is extremely high; gallic acid and its derivatives are very powerful whitening molecules, are powerful tyrosinase inhibitors and have excellent antioxidant effect, but cannot play a good role in whitening because they are highly unstable and insoluble in water.
Disclosure of Invention
In order to further exert the whitening effect of gallic acid, the application provides a preparation method of cosmetics for improving the transdermal absorption rate.
The application provides a cosmetic preparation method for improving transdermal absorptivity, which adopts the following technical scheme:
a cosmetic preparation method for improving transdermal absorptivity comprises the following steps: dissolving sodium carboxymethyl cellulose in deionized water under continuous stirring at 1000-1200rpm, and sealing and storing at 4deg.C for 24-36 hr to completely swell sodium carboxymethyl cellulose to obtain gel matrix; mixing the gel matrix with GA-P-GLY under continuous stirring at 1000-1200rpm until completely uniform mixed gel is formed to obtain transdermal absorption gel; the preparation method of the GA-P-GLY comprises the following steps: (1) Placing the mixed solvent composed of chloroform and methanol into a eggplant-shaped bottle, adding 90-100mg of phosphatidylcholine and 10-15mg of gallic acid, stirring and dissolving to obtain a mixed solution; (2) Rotary evaporating the mixed solution obtained in the step (1) at 52-55 ℃ in vacuum until a film is formed on the container wall; (3) Hydrating the obtained film with phosphate buffer containing additive for 30-40 min; the additive comprises sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate.
Through adopting the technical scheme, gallic acid and phosphatidylcholine are mixed to prepare a film through a film hydration method, then the film is put into phosphate buffer solution containing additives of glycodeoxycholate sodium, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate to be hydrated to form vesicles, and finally the vesicles are mixed with carboxymethyl cellulose sodium salt to prepare gel matrix, so that the transdermal absorption gel with high transdermal absorption rate is obtained.
Preferably, the mass volume ratio of the sodium carboxymethyl cellulose to the deionized water is (10-15) g (100-200) mL.
By adopting the technical scheme, the gel matrix formed by swelling the sodium carboxymethyl cellulose in deionized water has proper viscosity.
Preferably, the mass ratio of the gel matrix to the GA-P-GLY is (100-120): 2-3.
By adopting the technical scheme, the GA-P-GLY can slowly diffuse in the polymer network of the hydrogel at the ratio.
Preferably, the volume ratio of the chloroform to the methanol is (7-9): 3-5; the mass volume ratio of the mixed solvent, the phosphatidylcholine and the gallic acid is (10-14) mL (90-100) mg (10-15) mg.
By adopting the technical scheme, the phosphatidylcholine and the gallic acid can be fully dissolved and mixed in the mixed solvent of chloroform and methanol at the proportion.
Preferably, the mass volume ratio of the film to the phosphate buffer is (100-110) mg (10-12) mL.
By adopting the technical scheme, the gallic acid can be fully encapsulated in the proportion.
Preferably, the mass concentration of the additive in the phosphate buffer solution is 1mg/mL; the pH of the phosphate buffer was 7.4.
By adopting the technical scheme, the encapsulation effect of the vesicle in the GA-P-GLY is good, and the leakage is not easy.
Preferably, the mass ratio of the sodium glycodeoxycholate to the isopropyl myristate to the D-alpha-tocopheryl polyethylene glycol 1000 succinate is (70-75): 50-60): 42-50.
By adopting the technical scheme, the vesicle in the GA-P-GLY is small in size and uniformly dispersed.
Preferably, the method further comprises the following steps: mixing the mixed gel and plant extract under continuous stirring at 1000-1200 rpm; the plant extract is selected from one or more of flos Caryophylli, herba Centellae, radix Gentianae, flos Matricariae Chamomillae, herba Portulacae, glycyrrhrizae radix, herba Apocyni Veneti, ginsenoside, aloe, fructus Prinsepiae utilis, fructus Canarii albi, radix Angelicae sinensis, herba Galii Teneri extract, and herba Speranskiae Tuberculatae.
By adopting the technical scheme, the skin care effect of the cosmetic can be further improved.
In summary, the present application has the following beneficial effects:
1. the preparation method comprises the steps of firstly preparing a film by mixing gallic acid and phosphatidylcholine through a film hydration method, then placing the film into a phosphate buffer solution containing additives of glycodeoxycholate sodium, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate for hydration to form vesicles, and finally preparing gel matrix by mixing the vesicles with carboxymethyl cellulose sodium salt to obtain the transdermal absorption gel with high transdermal absorption rate.
2. In the application, preferably, sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate are added into phosphate buffer solution, then the prepared film is treated to form vesicles, and under the stimulation of anionic surfactant sodium glycodeoxycholate, D-alpha-tocopheryl polyethylene glycol 1000 succinate is used as a surface emulsifier to self-assemble gallic acid and phosphatidylcholine into vesicles, so that the encapsulation rate is improved. In addition, electrostatic repulsion between vesicles due to negative charge on the surface of sodium glycodeoxycholate prevents aggregation among particles, so that physical stability of the vesicles is increased, vesicle size is reduced, and transdermal absorption rate of gallic acid is improved.
3. The transdermal absorption gel prepared by the preparation method has high transdermal absorption rate of the gallic acid, and is favorable for fully playing the whitening effect of the gallic acid.
Drawings
Fig. 1: transmission electron microscopy of GA-P-GLY prepared in example 1 of the present application.
Detailed Description
The present application is described in further detail below with reference to examples.
The raw materials of the examples and comparative examples herein are commercially available in general unless otherwise specified.
Examples
Example 1
A cosmetic preparation method for improving transdermal absorptivity comprises the following steps: under the continuous stirring of 1000rpm, 10g of sodium carboxymethyl cellulose is dissolved in 100mL of deionized water, and then sealed and stored for 24 hours at 4 ℃ to enable the sodium carboxymethyl cellulose to be fully swelled, thus obtaining gel matrix; 100g of gel matrix was mixed with 2g of GA-P-GLY under continuous stirring at 1000rpm until a completely uniform mixed gel was formed, to obtain a transdermal absorption gel.
The preparation method of the GA-P-GLY comprises the following steps: (1) Placing 10mL of a mixed solvent consisting of chloroform and methanol according to a volume ratio of 7:3 into a eggplant-shaped bottle, then adding 90mg of phosphatidylcholine and 10mg of gallic acid, stirring and dissolving to obtain a mixed solution; (2) Rotary evaporating the mixed solution obtained in the step (1) at 52 ℃ in vacuum until a film is formed on the container wall; (3) 100mg of the obtained film was hydrated with 10mL of a phosphate buffer (pH 7.4) containing an additive at a mass concentration of 1mg/mL for 30 minutes. The additive consists of sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate in a mass ratio of 70:50:42.
GA-P-GLY prepared with deionized water was diluted 100-fold to form a dispersion, which was observed by Transmission Electron Microscopy (TEM): a drop of the dispersion was dropped onto a copper mesh of a carbon coating, dried at room temperature for 15 minutes, then stained with a drop of 1% (w/v) phosphotungstic acid solution, left to stand for 3 minutes, the excess solution was removed with filter paper, and then placed in a microscope, and then the surface characteristics and shape were evaluated under an appropriate magnification, and the result was as shown in FIG. 1.
As can be seen from FIG. 1, the vesicles in GA-P-GLY have small size and uniform size distribution and are in a smooth sphere or spheroid shape.
Example 2
A cosmetic preparation method for improving transdermal absorptivity comprises the following steps: under continuous stirring at 1100rpm, 12g of sodium carboxymethyl cellulose is dissolved in 150mL of deionized water, and then sealed and stored at 4 ℃ for 30 hours to enable the sodium carboxymethyl cellulose to be fully swelled, thus obtaining a gel matrix; the gel matrix 110g was mixed with GA-P-GLY2.5g under continuous stirring at 1100rpm until a completely uniform mixed gel was formed, to give a transdermal absorption gel.
The preparation method of the GA-P-GLY comprises the following steps: (1) Placing 12mL of a mixed solvent consisting of chloroform and methanol according to a volume ratio of 8:4 into a eggplant-shaped bottle, then adding 95mg of phosphatidylcholine and 12mg of gallic acid, stirring and dissolving to obtain a mixed solution; (2) Rotary evaporating the mixed solution obtained in the step (1) at 53 ℃ in vacuum until a film is formed on the container wall; (3) The obtained film (105 mg) was hydrated with 11mL of a phosphate buffer (pH 7.4) containing an additive at a mass concentration of 1mg/mL for 35 minutes. The additive consists of sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate in a mass ratio of 72:56:45.
Example 3
A cosmetic preparation method for improving transdermal absorptivity comprises the following steps: under continuous stirring at 1200rpm, 15g of sodium carboxymethyl cellulose is dissolved in 200mL of deionized water, and then sealed and stored at 4 ℃ for 36 hours, so that the sodium carboxymethyl cellulose is fully swelled to obtain a gel matrix; 120g of gel matrix was mixed with 3g of GA-P-GLY under continuous stirring at 1200rpm until a completely homogeneous mixed gel was formed, to give a transdermal absorption gel.
The preparation method of the GA-P-GLY comprises the following steps: (1) Placing 14mL of a mixed solvent consisting of chloroform and methanol according to a volume ratio of 9:5 into a eggplant-shaped bottle, then adding 100mg of phosphatidylcholine and 15mg of gallic acid, stirring and dissolving to obtain a mixed solution; (2) Rotary evaporating the mixed solution obtained in the step (1) at 55 ℃ in vacuum until a film is formed on the container wall; (3) The obtained film (110 mg) was hydrated with 12mL of a phosphate buffer (pH 7.4) containing an additive at a mass concentration of 1mg/mL for 40 min. The additive consists of sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate in a mass ratio of 75:60:50.
Example 4
A cosmetic preparation method for improving transdermal absorptivity, based on example 1, further comprises the following steps: mixing the mixed gel with the plant extract under continuous stirring at 1000-1200 rpm.
The plant extract is selected from one or more of flos Caryophylli, herba Centellae, radix Gentianae, flos Matricariae Chamomillae, herba Portulacae, glycyrrhrizae radix, herba Apocyni Veneti, ginsenoside, aloe, fructus Prinsepiae utilis, fructus Canarii albi, radix Angelicae sinensis, herba Galii Teneri extract, and herba Speranskiae Tuberculatae.
Comparative example
Comparative example 1
The same as in example 1, except that "sodium glycodeoxycholate" was replaced with an equimolar amount of "deoxycholate".
Comparative example 2
The same as in example 1, except that "D-alpha-tocopheryl polyethylene glycol 1000 succinate" was removed.
Comparative example 3
The same as in example 1, except that the GA-P-GLY was prepared as follows: (1) Placing 10mL of a mixed solvent consisting of chloroform and methanol according to a volume ratio of 7:3 into a eggplant-shaped bottle, then adding 90mg of phosphatidylcholine and 10mg of gallic acid, stirring and dissolving to obtain a mixed solution; (2) Rotary evaporating the mixed solution obtained in the step (1) at 52 ℃ in vacuum until a film is formed on the container wall; (3) 100mg of the obtained film was hydrated with 10mL of a phosphate buffer (pH 7.4) containing no additives for 30 minutes.
Comparative example 4
1g of carbomer 940 is weighed and evenly dispersed in 50mL of distilled water, 4mL of phosphate buffer salt solution (pH 7.4) is added after the carbomer 940 is fully wetted, 2 percent of laurohydrone permeation promoter by mass of the carbomer 940 is added, the mixture is fully stirred, and the pH is regulated to 7.0 by triethanolamine and swelled for 24 hours, thus obtaining gel matrix; taking 5mL of ethanol solution containing 1mg/mL gallic acid, and mixing with 50g of gel matrix in equal amount to obtain mixed gel.
Performance test
A. Encapsulation efficiency test: the GA-P-GLY prepared in examples 1-3 and comparative examples 1-3 were centrifuged (7000 g) at 4℃for 80min using a refrigerated centrifuge, the unencapsulated gallic acid was separated from the GA-P-GLY system, and then the GA-P-GLY was washed once with 50mLPBS, the supernatant was collected, appropriately diluted with PBS (pH 7.4), and the amount of unencapsulated gallic acid was determined spectrophotometrically at 260 nm. GA-P-GLY encapsulation efficiency expressed as encapsulation efficiency (EE%) EE% = (total amount of gallic acid added-total amount of unencapsulated gallic acid/total amount of gallic acid added) ×100.
B. After diluting the GA-P-GLY prepared in examples 1-3 and comparative examples 1-3 100 times with deionized water, the average particle size, polydispersity index and Zeta Potential (ZP) of the prepared GA-P-GLY were evaluated by dynamic light scattering at 25℃using a nanoparticle potentiometer.
The results are shown in Table 1:
TABLE 1 encapsulation efficiency, particle size and other parameter test results
As can be seen from Table 1, the GA-P-GLY prepared in examples 1-3 of the present application has a high encapsulation efficiency, up to 79.3%, which indicates that the matrix in GA-P-GLY has a good binding ability with gallic acid; the average particle size of GA-P-GLY is 579-591nm, the particle size is obviously smaller than that of comparative examples 1-3, and the size is more favorable for gallic acid to penetrate through the stratum corneum and reach the deep layer of skin; the polydispersity index was as low as 0.014, indicating uniform particle size dispersion, zeta Potential (ZP) from-70.3 mV to-81.6 mV, indicating good stability. From the above data, it can be seen that GA-P-GLY is dimensionally stable and reproducible. Combining comparative examples 1-3, it is hypothesized that this is probably due to the moderate negative charge of the surface of sodium glycodeoxycholate, such that electrostatic repulsion between charged particles hinders inter-particle polymerization, resulting in an increase in physical stability, while deoxycholate has excessive negative charge, such that the water solubility of the lipid layer on the surface of the particles increases, resulting in a disorder of the lipid bilayer structure on the surface of the particles, resulting in an increase in fluidity of the particle membrane, having permeability, resulting in leakage, resulting in a decrease in encapsulation efficiency. In addition, sodium glycodeoxycholate is used as a surfactant, and more negative charges are provided on the outer layer of the particles, so that the space repulsive force between charged molecules is caused, and the size of the particles is reduced; d-alpha-tocopheryl polyethylene glycol 1000 succinate is used as a surface emulsifier, sodium glycodeoxycholate can help to form micelles, and isopropyl myristate can be used as an oil phase, so that more stable and better-dispersible particles are formed.
C. In vitro transdermal absorption test:
(1) Firstly, preparing isolated skin: collecting about 20g healthy mice, killing the mice after neck breakage, and separating the xiphoid processRemoving hair from lower skin and sodium sulfide, separating abdominal skin, removing subcutaneous tissue and fat, cleaning with physiological saline, cutting small pieces with proper size, and storing in refrigerator at-15deg.C for use. Thawing at room temperature before use, cleaning with normal saline, and spreading on a receiving tank. (2) Fixing the prepared isolated skin between the administration tank and the receiving tank by using a modified Franz diffusion device, wherein the effective permeation area of the diffusion tank is 2.80cm 2 The stratum corneum faces the supply chamber, and the dermis side is in contact with a receiving liquid for removing bubbles, and the receiving liquid is physiological saline. 1g of the transdermal absorption gel prepared in examples 1-3 and comparative examples 1-4 was precisely weighed and coated on the skin so as to be in close contact with the skin, and a small glass bead was placed in the receiving tank for helping to agitate the receiving liquid in the tank, and the supply chamber was sealed with a preservative film to prevent the gel and skin from drying due to evaporation of water, which is unfavorable for the experiment. The outside of the receiving tank is kept at a constant temperature by adopting a water bath, and the temperature of the water bath is 37 ℃. After 6h, all the received solutions were taken out as sample solutions, filtered with a 0.22 μm microporous filter membrane, 20 μl was taken and injected into a high performance liquid chromatograph, the concentration and maximum release of gallic acid were determined, and the absorbance was calculated, absorbance = total absorbance/maximum release 100%.
D. Penetration was measured using a laser scanning confocal microscope. Preloaded with lipophilic fluorescent tracer RhB (examples 1-3 and comparative examples 1-3): the preparation method of GA-P-GLY comprises the steps of (1) adding RhB, gallic acid and phosphatidylcholine together, and then preparing; in comparative example 4, rhB was mixed with 5mL of ethanol solution containing 1mg/mL gallic acid, and then mixed with 50g of gel matrix in equal amounts to obtain a mixed gel. 21 rats (3 rats per group) were shaved off the back hair, and the prepared transdermal absorption gel was applied to the back skin for 8 hours. The rats were then sacrificed for cervical dislocation, the back skin was surgically excised, washed with PBS and air dried. Excised skin sections (thickness; 5 μm) were fixed on a glass slide, and observed under light excitation of λex=488 nm with an argon laser beam under CLSM, while fluorescence emission was detected at λem=595 nm, and the deepest part of the fluorescent layer was observed, and the fluorescence of the deepest part was relatively strong and weak.
The test results are shown in Table 2:
TABLE 2 percutaneous absorption test results
As can be seen from Table 2, the transdermal absorption gel prepared in comparative example 4 using laurohydrin as a permeation enhancer had less effect on the absorption rate of gallic acid than the transdermal absorption gel prepared in examples 1 to 3 of the present application. The transdermal absorption gel prepared in the embodiment 1-3 has excellent transdermal penetration promoting effect, and the absorption rate of gallic acid is up to 72.1%; the fluorescence tracer RhB shows that after 8 hours, fluorescence of the examples 1-3 and the comparative examples 1-4 is observed in all skin layers and reaches subcutaneous adipose tissues, and the fluorescence of the deepest part of the transdermal absorption gel prepared in the examples 1-3 is strongest, which indicates that the transdermal absorption gel prepared in the examples 1-3 has the best transdermal penetration promoting effect. This is probably due to the addition of sodium glycodeoxycholate, D-alpha-tocopheryl polyethylene glycol 1000 succinate and isopropyl myristate during the GA-P-GLY preparation, whereby the surface lipids of the obtained GA-P-GLY vesicles disrupt the skin ordered lipid structure, reduce its structural density and increase the mobility of the stratum corneum, altering the lipids between skin cells, thus contributing to the penetration of gallic acid. In addition, the lipids of the GA-P-GLY vesicle surface have a tendency to avoid a dry environment, and at the partially dehydrated skin surface they tend to move deep relative to being rich in moisture, maintaining adequate hydration.
The present embodiment is merely illustrative of the present application and is not intended to be limiting, and those skilled in the art, after having read the present specification, may make modifications to the present embodiment without creative contribution as required, insofar as they are protected by the patent laws within the scope of protection of the present application.
Claims (9)
1. A method for preparing a cosmetic product for improving transdermal absorption rate, comprising the steps of: dissolving sodium carboxymethyl cellulose in deionized water under continuous stirring at 1000-1200rpm, and sealing and storing at 4deg.C for 24-36 hr to completely swell sodium carboxymethyl cellulose to obtain gel matrix; mixing the gel matrix with GA-P-GLY under continuous stirring at 1000-1200rpm until completely uniform mixed gel is formed to obtain transdermal absorption gel; the preparation method of the GA-P-GLY comprises the following steps: (1) Placing the mixed solvent composed of chloroform and methanol into a eggplant-shaped bottle, adding 90-100mg of phosphatidylcholine and 10-15mg of gallic acid, stirring and dissolving to obtain a mixed solution; (2) Rotary evaporating the mixed solution obtained in the step (1) at 52-55 ℃ in vacuum until a film is formed on the container wall; (3) Hydrating the obtained film with phosphate buffer containing additive for 30-40 min; the additive comprises sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate.
2. The method for preparing cosmetics for improving transdermal absorption rate according to claim 1, wherein the mass-volume ratio of the carboxymethyl cellulose sodium salt to deionized water is (10-15) g (100-200) mL.
3. The method for preparing a cosmetic for improving transdermal absorption according to claim 2, wherein the mass ratio of the gel matrix to GA-P-GLY is (100-120): 2-3.
4. A cosmetic preparation method for improving transdermal absorption according to claim 3, wherein the volume ratio of chloroform to methanol is (7-9): 3-5; the mass volume ratio of the mixed solvent, the phosphatidylcholine and the gallic acid is (10-14) mL (90-100) mg (10-15) mg.
5. The method for preparing a cosmetic for improving transdermal absorption according to claim 4, wherein the mass-to-volume ratio of the film to the phosphate buffer is (100-110) mg (10-12) mL.
6. The method for preparing a cosmetic for improving transdermal absorption according to claim 5, wherein the mass concentration of the additive in the phosphate buffer is 1mg/mL; the pH of the phosphate buffer was 7.4.
7. The method for preparing a cosmetic for improving transdermal absorption rate according to claim 6, wherein the mass ratio of sodium glycodeoxycholate, isopropyl myristate and D-alpha-tocopheryl polyethylene glycol 1000 succinate is (70-75): 50-60): 42-50.
8. A method for preparing a cosmetic product for enhancing transdermal absorption according to any one of claims 1 to 7, further comprising the steps of: mixing the mixed gel with the plant extract under continuous stirring at 1000-1200 rpm.
9. The method for preparing a cosmetic for improving transdermal absorption according to claim 8, wherein the plant extract is one or more selected from the group consisting of clove, centella asiatica, gentian, chamomile, purslane, licorice, apocynum venetum, ginsenoside, aloe vera, prinsepia utilis royle, olive, angelica sinensis, alpine rush extract and speranskia herb.
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