CN113559007A - Preparation method of liposome with whitening and anti-aging effects - Google Patents
Preparation method of liposome with whitening and anti-aging effects Download PDFInfo
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- CN113559007A CN113559007A CN202110920374.5A CN202110920374A CN113559007A CN 113559007 A CN113559007 A CN 113559007A CN 202110920374 A CN202110920374 A CN 202110920374A CN 113559007 A CN113559007 A CN 113559007A
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- liposome
- whitening
- ammonium chloride
- hyaluronic acid
- trimethyl ammonium
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- 239000002502 liposome Substances 0.000 title claims abstract description 88
- 230000002087 whitening effect Effects 0.000 title claims abstract description 54
- 230000003712 anti-aging effect Effects 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 48
- VFKZECOCJCGZQK-UHFFFAOYSA-M 3-hydroxypropyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CCCO VFKZECOCJCGZQK-UHFFFAOYSA-M 0.000 claims abstract description 48
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 48
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 48
- 238000003756 stirring Methods 0.000 claims abstract description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 34
- 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 claims abstract description 23
- 229940093767 glabridin Drugs 0.000 claims abstract description 23
- 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 claims abstract description 23
- LBQIJVLKGVZRIW-UHFFFAOYSA-N glabridine Natural products C1OC2=C3C=CC(C)(C)OC3=CC=C2CC1C1=CC=C(O)C=C1O LBQIJVLKGVZRIW-UHFFFAOYSA-N 0.000 claims abstract description 23
- JXPHIHWXMBYJAU-UHFFFAOYSA-N 7-methoxy-2,2-dimethyl-3,4-dihydrochromen-6-ol Chemical compound O1C(C)(C)CCC2=C1C=C(OC)C(O)=C2 JXPHIHWXMBYJAU-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229940117973 dimethylmethoxy chromanol Drugs 0.000 claims abstract description 17
- SFFVATKALSIZGN-UHFFFAOYSA-N hexadecan-7-ol Chemical compound CCCCCCCCCC(O)CCCCCC SFFVATKALSIZGN-UHFFFAOYSA-N 0.000 claims abstract description 17
- OEWBEINAQKIQLZ-CMRBMDBWSA-N [(2s)-2-[(2r)-3,4-bis(2-hexyldecanoyloxy)-5-oxo-2h-furan-2-yl]-2-(2-hexyldecanoyloxy)ethyl] 2-hexyldecanoate Chemical compound CCCCCCCCC(CCCCCC)C(=O)OC[C@H](OC(=O)C(CCCCCC)CCCCCCCC)[C@H]1OC(=O)C(OC(=O)C(CCCCCC)CCCCCCCC)=C1OC(=O)C(CCCCCC)CCCCCCCC OEWBEINAQKIQLZ-CMRBMDBWSA-N 0.000 claims abstract description 16
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 14
- ZUVCYFMOHFTGDM-UHFFFAOYSA-N hexadecyl dihydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(O)=O ZUVCYFMOHFTGDM-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229940067606 lecithin Drugs 0.000 claims abstract description 14
- 235000010445 lecithin Nutrition 0.000 claims abstract description 14
- 239000000787 lecithin Substances 0.000 claims abstract description 14
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 claims abstract description 11
- 238000010438 heat treatment Methods 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 239000003921 oil Substances 0.000 claims description 20
- 235000019198 oils Nutrition 0.000 claims description 20
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 16
- 235000019864 coconut oil Nutrition 0.000 claims description 10
- 239000003240 coconut oil Substances 0.000 claims description 10
- 235000010323 ascorbic acid Nutrition 0.000 claims description 7
- 239000011668 ascorbic acid Substances 0.000 claims description 7
- 229960005070 ascorbic acid Drugs 0.000 claims description 7
- 239000003973 paint Substances 0.000 claims description 4
- XJFGDLJQUJQUEI-UHFFFAOYSA-N dodecyl decanoate dodecyl octanoate Chemical compound CCCCCCCCCCCCOC(=O)CCCCCCC.CCCCCCCCCCCCOC(=O)CCCCCCCCC XJFGDLJQUJQUEI-UHFFFAOYSA-N 0.000 claims description 3
- 238000000265 homogenisation Methods 0.000 claims description 3
- 239000013543 active substance Substances 0.000 abstract description 18
- 230000014759 maintenance of location Effects 0.000 abstract description 11
- 210000003491 skin Anatomy 0.000 description 23
- 230000001186 cumulative effect Effects 0.000 description 8
- 239000002245 particle Substances 0.000 description 7
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 210000004207 dermis Anatomy 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 210000002615 epidermis Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
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- 230000000052 comparative effect Effects 0.000 description 3
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- 230000008569 process Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 230000037303 wrinkles Effects 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000004209 hair Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003260 vortexing Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- AHMIDUVKSGCHAU-UHFFFAOYSA-N Dopaquinone Natural products OC(=O)C(N)CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-UHFFFAOYSA-N 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- AHMIDUVKSGCHAU-LURJTMIESA-N L-dopaquinone Chemical compound [O-]C(=O)[C@@H]([NH3+])CC1=CC(=O)C(=O)C=C1 AHMIDUVKSGCHAU-LURJTMIESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000005282 brightening Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- 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
- A61K8/14—Liposomes; Vesicles
-
- 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
- A61K8/34—Alcohols
- A61K8/342—Alcohols having more than seven atoms in an unbroken chain
-
- 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
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- 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
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Emergency Medicine (AREA)
- Cosmetics (AREA)
Abstract
The invention discloses a preparation method of liposome with whitening and anti-aging effects, which comprises the following steps: mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, adding ascorbyl tetraisopalmitate, hexyldecanol and cocol-caprylate/caprate, heating and stirring for dissolving to obtain oil phase; adding the oil phase into water, stirring, and homogenizing and circulating to obtain liposome; adding hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water, and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution; and dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under the stirring state, and uniformly stirring to obtain the whitening and anti-aging liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid. The invention has the characteristics of effectively improving the stability, reducing the leakage of active substances, increasing the retention amount and retention time of the active substances in the skin and having good whitening effect.
Description
Technical Field
The invention relates to a preparation method of liposome, in particular to a preparation method of liposome with whitening and anti-aging effects.
Background
With the acceleration of social rhythm and the aggravation of environmental pollution, the demand of modern women on whitening and freckle removal is further improved, and compared with European and American women, Asian women have stronger demand on whitening and skin brightening due to the difference of inherent skin color. The maldistribution and accumulation of melanocytes in the surface layers of the skin can lead to dark skin tone and color spots. The main pathway leading to melanin formation is that tyrosinase converts tyrosine to dopa, which is further oxidized to dopaquinone, ultimately forming melanin. For many years, the cosmetic industry continuously seeks technical breakthrough and aims to research and develop safe and efficient whitening raw materials. At present, most of whitening products on the market are added with some traditional Chinese medicine extracts, vitamin C and derivatives thereof, glycolic acid and the like, because the formation reason of melanin is manifold, if only a single-component whitening component is added, the whitening effect is not obvious, and the stability of some whitening components is poor, and the whitening components are deteriorated and the activity of the whitening components is influenced by the external environment in the storage and use processes.
The liposome is a spherical vesicle composed of lipid bilayers, is commonly used for active substance delivery, not only can protect encapsulated substances from being degraded, but also can improve the physicochemical property of the active substances, minimize the adverse reaction and simultaneously increase the bioavailability of the active substances at action targets; therefore, researchers have studied how to encapsulate whitening components in liposomes, but the resulting liposomes have not been ideal in whitening effect. In addition, the existing liposome still has certain limitations, such as poor stability, early drug leakage, short retention time and the like. Therefore, there is an urgent need to develop a liposome having good stability, less leakage of active substances, increased retention and retention time of active substances in the skin, and good whitening anti-aging effects.
Disclosure of Invention
The invention aims to provide a preparation method of liposome with whitening and anti-aging effects. The invention has the characteristics of effectively improving the stability, reducing the leakage of active substances, increasing the retention amount and retention time of the active substances in the skin and having good whitening effect.
The technical scheme of the invention is as follows: a preparation method of liposome with whitening and anti-aging effects comprises the following steps:
firstly, mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, then adding ascorbic acid tetraisopalmitate, hexyl decanol and coconut oil alcohol-caprylate/caprate, heating to 50-80 ℃, stirring and dissolving to obtain an oil phase;
secondly, adding the oil phase into water with the temperature of 50-80 ℃, stirring for 10-30 minutes, and then carrying out homogenization circulation for 3-10 times by using a high-pressure homogenizer under the pressure of 500-1500bar to obtain liposome;
thirdly, adding the hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution;
and fourthly, dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under a stirring state, and then stirring for 10-40 minutes to obtain the whitening and anti-aging effect liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid.
The preparation method of the liposome with the whitening and anti-aging effects comprises the following steps:
firstly, mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, then adding ascorbic acid tetraisopalmitate, hexyl decanol and coconut oil alcohol-caprylate/caprate, heating to 60 ℃, stirring and dissolving to obtain an oil phase;
secondly, adding the oil phase into water with the temperature of 60 ℃, stirring for 20 minutes, and then homogenizing and circulating for 6 times by using a high-pressure homogenizer under the pressure of 800bar to obtain liposome;
thirdly, adding the hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution;
and fourthly, dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under a stirring state, and then stirring for 30 minutes to obtain the whitening and anti-aging effect liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid.
In the preparation method of the liposome with the whitening and anti-aging effects, in the first step, the liposome comprises the following components in parts by weight: 10-15 parts of lecithin; 0.5-2 parts of cetyl phosphate; 0.1-1 part of glabridin; 0.01-0.1 part of dimethyl methoxy chromanol; 0.5-4 parts of ascorbyl tetraisopalmitate; 1-6 parts of hexyldecanol; 15-30 parts of coconut oil alcohol-caprylate/caprate.
In the preparation method of the liposome with the whitening and anti-aging effects, in the first step, the liposome comprises the following components in parts by weight: 10 parts of lecithin; 1 part of cetyl phosphate; glabridin 0.4 weight portions; 0.04 part of dimethyl methoxy chromanol; 2 parts of ascorbyl tetraisopalmitate; 4 parts of hexyldecanol; coco-caprylate/caprate, 20 parts.
In the preparation method of the liposome with whitening and anti-aging effects, in the second step, the weight ratio of the oil phase to the water is (27.11-58.10): (41.9-72.89).
In the preparation method of the liposome with whitening and anti-aging effects, in the second step, the weight ratio of the oil phase to the water is 37.44: 62.56.
In the preparation method of the liposome with whitening and anti-aging effects, in the third step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid to the water is (0.5-5): (95-99.5).
In the preparation method of the liposome with whitening and anti-aging effects, in the third step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid to water is 1: 99.
In the fourth step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution to the liposome is (0.5: 1) - (2: 1).
In the fourth step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution to the liposome is 1: 1.
compared with the prior art, the invention adopts a specific process to prepare four oil-soluble active ingredients: glabridin, dimethyl methoxy chromanol, ascorbyl tetraisopalmitate and hexyldecanol are wrapped in the liposome to play a synergistic effect, so that an excellent whitening effect is realized, and the anti-aging effect is achieved. Meanwhile, the hydroxypropyl trimethyl ammonium chloride hyaluronic acid is used for coating the liposome, so that the surface of the liposome is positively charged, the stability of the liposome is improved, the leakage of active substances is reduced, and the retention amount and retention time of the active substances in skin are increased.
Tests show that the liposome prepared by the process and the component proportion has uniform particle size and good stability; the particle size of the liposome is 152-213nm, PDI is 0.18, and Zeta potential is 58.5 mV.
In conclusion, the invention has the characteristics of effectively improving the stability, reducing the leakage of the active substances, increasing the retention amount and retention time of the active substances in the skin and having good whitening effect.
Detailed Description
The present invention is further illustrated by the following examples, which are not to be construed as limiting the invention.
Example 1. A preparation method of liposome with whitening and anti-aging effects comprises the following steps:
firstly, mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, then adding ascorbic acid tetraisopalmitate, hexyl decanol and coconut oil alcohol-caprylate/caprate, heating to 50-80 ℃, stirring and dissolving to obtain an oil phase;
secondly, adding the oil phase into water with the temperature of 50-80 ℃, stirring for 10-30 minutes, and then carrying out homogenization circulation for 3-10 times by using a high-pressure homogenizer under the pressure of 500-1500bar to obtain liposome;
thirdly, adding the hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution;
and fourthly, dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under a stirring state, and then stirring for 10-40 minutes to obtain the whitening and anti-aging effect liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid.
Preferably: the method comprises the following steps:
firstly, mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, then adding ascorbic acid tetraisopalmitate, hexyl decanol and coconut oil alcohol-caprylate/caprate, heating to 60 ℃, stirring and dissolving to obtain an oil phase;
secondly, adding the oil phase into water with the temperature of 60 ℃, stirring for 20 minutes, and then homogenizing and circulating for 6 times by using a high-pressure homogenizer under the pressure of 800bar to obtain liposome;
thirdly, adding the hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution;
and fourthly, dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under a stirring state, and then stirring for 30 minutes to obtain the whitening and anti-aging effect liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid.
In the first step, the paint comprises the following components in parts by weight: 10-15 parts of lecithin; 0.5-2 parts of cetyl phosphate; 0.1-1 part of glabridin; 0.01-0.1 part of dimethyl methoxy chromanol; 0.5-4 parts of ascorbyl tetraisopalmitate; 1-6 parts of hexyldecanol; 15-30 parts of coconut oil alcohol-caprylate/caprate.
Preferably: in the first step, the paint comprises the following components in parts by weight: 10 parts of lecithin; 1 part of cetyl phosphate; glabridin 0.4 weight portions; 0.04 part of dimethyl methoxy chromanol; 2 parts of ascorbyl tetraisopalmitate; 4 parts of hexyldecanol; coco-caprylate/caprate, 20 parts.
In the second step, the weight ratio of the oil phase to the water is (27.11-58.10): (41.9-77.89).
Preferably: in the second step, the weight ratio of oil phase to water was 37.44: 62.56.
In the third step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid to the water is (0.5-5): (95-99.5).
Preferably: in the third step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid to the water is 1: 99.
In the fourth step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution to the liposome is (0.5: 1) - (2: 1).
Preferably: in the fourth step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution to the liposome is 1: 1.
example 2. A preparation method of liposome with whitening and anti-aging effects comprises the following specific steps:
firstly, weighing 10g of lecithin, 1g of cetyl phosphate, 0.4g of glabridin and 0.04g of dimethyl methoxy chromanol, mixing, then adding 2g of ascorbic acid tetraisopalmitate, 4g of hexyldecanol and 20g of coconut oil alcohol-caprylate/caprate, heating to 60 ℃, stirring and dissolving to obtain the oil phase.
And secondly, adding the oil phase into 62.56g of water (60 ℃), stirring for 20 minutes, and then homogenizing for 6 times by using a high-pressure homogenizer at 800bar to obtain the liposome.
And step three, weighing 1g of hydroxypropyl trimethyl ammonium chloride hyaluronic acid, adding 99g of water, and stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution.
And fourthly, weighing 50g of hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution, dropwise adding 50g of liposome under stirring, and stirring for 30 minutes to obtain the liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid and having the whitening and anti-aging effects.
The liposomes prepared in example 2 were subjected to stability testing
The particle size distribution and PDI of the prepared liposomes were determined with a laser particle sizer. The particle size of the liposome is 152-213nm, PDI is 0.18, and Zeta potential is 58.5 mV.
After standing at 4 ℃ for 30 days, the particle size was 183-254nm and the PDI was 0.25.
The result shows that the prepared polypeptide liposome has uniform particle size and good stability.
Test trials were conducted on the stability of encapsulation of glabridin and ascorbyl tetraisopalmitate:
the whitening and anti-aging effect liposome prepared in the example 2 is dissolved in deionized water, the liposome is placed in a sealing way at room temperature, the leakage rate of glabridin and ascorbyl tetraisopalmitate in the solution is measured at 0, 7, 14 and 30 days after the liposome is placed, the leakage rate of glabridin is 5.31 percent and the leakage rate of ascorbyl tetraisopalmitate is 6.83 percent after 30 days.
Dissolving liposomes (prepared by the first two steps of the liposome preparation method and the component ratio in example 2) which are not coated by hydroxypropyl trimethylammonium chloride hyaluronic acid in deionized water, placing the liposomes in a sealed manner at room temperature, measuring the leakage rate of glabridin and ascorbyl tetraisopalmitate in the solution after 0, 7, 14 and 30 days of placing, wherein the leakage rate of glabridin and ascorbyl tetraisopalmitate is 23.56% and 28.78% after 30 days.
The result shows that the glabridin and the ascorbyl tetraisopalmitate in the whitening and anti-aging liposome prepared by the invention have less leakage.
Comparative example 1: the liposomes obtained were prepared according to the first two steps in example 2.
In vitro transdermal experiments: taking a fresh, complete and undamaged mouse skin, removing hairs on the skin by using a hair shaver, and washing the skin by using a small amount of clear water; removing subcutaneous fat with a sharp knife, and washing with PBS solution; finally, the treated skin is wrapped with tinfoil, laid flat in a box and stored at-20 ℃ for later use. The mouse skin was fixed on a Franz diffusion cell with an effective permeation area of 1.766cm2The receiving cell was filled with 15mL of PBS buffer, and the temperature of the water bath was 37 ℃. 0.5mL of liposome coated with hydroxypropyl trimethylammonium chloride hyaluronic acid (namely the liposome with whitening and anti-aging effects prepared in example 2) and 0.5mL of non-coated liposome (namely the liposome prepared in comparative example 1 in the first two steps in example 2) are respectively taken in a diffusion cell and sealed. The magnetic stirrer was started and 0.5mL was sampled at different time points. After sampling, equal volume of constant temperature PBS liquid was supplemented in time. After the reaction was over 24h, the device was carefully removed, the skin applied between the two chambers was removed, rinsed with clear water, wiped with ethanol to remove the sample on the surface, and finally the water on the surface was adsorbed with filter paper for use.
Determination of the active content in the epidermis: spreading the skin in a glass dish, removing 21 layers of the skin by using an adhesive tape, removing the first layer to avoid the sample remaining on the surface of the skin, combining the remaining 20 layers, placing the combined layer in a 10mL centrifuge tube, adding 2mL methanol, vortexing for 3min, centrifuging at 2000r/min for 5min, taking the clear liquid, passing through a 220nm organic membrane, and measuring the content of the active substances by using HPLC.
Determination of the active content in the dermis: shearing 21 layers of skin adhered to the skin with scissors, placing in a 10mL centrifuge tube, adding 1mL methanol, vortexing for 3min, centrifuging at 2000r/min for 5min, collecting supernatant, repeating twice, combining the supernatants, passing through 220nm organic membrane, and measuring the content of active substances by HPLC.
Example 2:
the cumulative transmission of glabridin is 203 mug/cm2Epidermal content of 195. mu.g/cm2Dermis content of 276. mu.g/cm2。
Cumulative permeation of dimethylmethoxychromanol of 28. mu.g/cm2The epidermis containsThe amount was 17. mu.g/cm2Dermis content 22 μ g/cm2。
The cumulative penetration of ascorbyl tetraisopalmitate is 298. mu.g/cm2Epidermal content 305. mu.g/cm2Dermis content 378 mug/cm2。
Cumulative permeation of hexyldecanol 329. mu.g/cm2Epidermal content 389 μ g/cm2The content of dermis is 457. mu.g/cm2。
Comparative example 1:
the cumulative transmission of glabridin is 281 mug/cm2The epidermis contains 135 μ g/cm2Dermis content 143 mug/cm2。
Cumulative penetration of dimethylmethoxychromanol of 35. mu.g/cm2Epidermal content 9. mu.g/cm2Dermis content of 12 μ g/cm2。
The cumulative penetration of ascorbyl tetraisopalmitate was 355. mu.g/cm2Epidermal content 237. mu.g/cm2The content of dermis is 256 mu g/cm2。
Cumulative permeation of hexyldecanol 407. mu.g/cm2Epidermal content 287. mu.g/cm2Content of dermis 353. mu.g/cm2。
And (4) conclusion: the hydroxypropyl trimethyl ammonium chloride hyaluronic acid coated liposome reduces the penetration of active substances into the skin and the participation in the in vivo circulation, so that the content of the active substances in the epidermis and the dermis is increased, more active substances are remained in the skin, and the effect can be exerted for a longer time.
Human body experiment for anti-aging and whitening effects
Human body experiment: 40 female subjects with the age of 35-55 years are selected and randomly divided into 2 groups, the experimental group is coated with 10% of the face cream containing the liposome with the whitening and anti-aging effects prepared in example 2 twice a day, and the control group is provided with a placebo cream containing no liposome.
VISIA-CR skin image analysis wrinkles, 2 weeks: the number of wrinkles was reduced by 5.3% in the experimental group, 1.2% in the control group, four weeks: the reduction of the experimental group is 8.9 percent, and the reduction of the control group is 3.1 percent. The wrinkle area test group was reduced by 5.8%, the control group by 1.9%, four weeks: the experimental group is reduced by 12.9%, and the control group is reduced by 2.4%.
The ITA angle was calculated by measuring b x value of skin by chromameter, 2 weeks: the increase of the ITA angle experimental group is 3.1 percent, the increase of the control group is-1.9 percent, the increase of the four-week ITA angle experimental group is 6.7 percent, and the increase of the control group is-2.4 percent.
Claims (10)
1. A preparation method of liposome with whitening and anti-aging effects is characterized by comprising the following steps:
firstly, mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, then adding ascorbic acid tetraisopalmitate, hexyl decanol and coconut oil alcohol-caprylate/caprate, heating to 50-80 ℃, stirring and dissolving to obtain an oil phase;
secondly, adding the oil phase into water with the temperature of 50-80 ℃, stirring for 10-30 minutes, and then carrying out homogenization circulation for 3-10 times by using a high-pressure homogenizer under the pressure of 500-1500bar to obtain liposome;
thirdly, adding the hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution;
and fourthly, dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under a stirring state, and then stirring for 10-40 minutes to obtain the whitening and anti-aging effect liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid.
2. The preparation method of the liposome with the whitening and anti-aging effects as claimed in claim 1, which is characterized by comprising the following steps:
firstly, mixing lecithin, cetyl phosphate, glabridin and dimethyl methoxy chromanol, then adding ascorbic acid tetraisopalmitate, hexyl decanol and coconut oil alcohol-caprylate/caprate, heating to 60 ℃, stirring and dissolving to obtain an oil phase;
secondly, adding the oil phase into water with the temperature of 60 ℃, stirring for 20 minutes, and then homogenizing and circulating for 6 times by using a high-pressure homogenizer under the pressure of 800bar to obtain liposome;
thirdly, adding the hydroxypropyl trimethyl ammonium chloride hyaluronic acid into water and uniformly stirring to obtain a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution;
and fourthly, dripping the liposome in a hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution under a stirring state, and then stirring for 30 minutes to obtain the whitening and anti-aging effect liposome coated by the hydroxypropyl trimethyl ammonium chloride hyaluronic acid.
3. The preparation method of the liposome with whitening and anti-aging effects according to claim 1 or 2, characterized in that,
in the first step, the paint comprises the following components in parts by weight: 10-15 parts of lecithin; 0.5-2 parts of cetyl phosphate; 0.1-1 part of glabridin; 0.01-0.1 part of dimethyl methoxy chromanol; 0.5-4 parts of ascorbyl tetraisopalmitate; 1-6 parts of hexyldecanol; 15-30 parts of coconut oil alcohol-caprylate/caprate.
4. The preparation method of the liposome with whitening and anti-aging effects as claimed in claim 3, wherein,
in the first step, the paint comprises the following components in parts by weight: 10 parts of lecithin; 1 part of cetyl phosphate; glabridin 0.4 weight portions; 0.04 part of dimethyl methoxy chromanol; 2 parts of ascorbyl tetraisopalmitate; 4 parts of hexyldecanol; coco-caprylate/caprate, 20 parts.
5. The preparation method of the liposome with the whitening and anti-aging effects according to claim 1 or 2, which is characterized in that: in the second step, the weight ratio of the oil phase to the water is (27.11-58.10): (41.9-72.89).
6. The preparation method of the liposome with the whitening and anti-aging effects according to claim 5, characterized by comprising the following steps: in the second step, the weight ratio of oil phase to water was 37.44: 62.56.
7. The preparation method of the liposome with the whitening and anti-aging effects according to claim 1 or 2, which is characterized in that: in the third step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid to the water is (0.5-5): (95-99.5).
8. The preparation method of the liposome with the whitening and anti-aging effects according to claim 7, is characterized in that: in the third step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid to the water is 1: 99.
9. The preparation method of the liposome with the whitening and anti-aging effects according to claim 1 or 2, which is characterized in that: in the fourth step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution to the liposome is (0.5: 1) - (2: 1).
10. The preparation method of the liposome with the whitening and anti-aging effects according to claim 9, is characterized in that: in the fourth step, the weight ratio of the hydroxypropyl trimethyl ammonium chloride hyaluronic acid solution to the liposome is 1: 1.
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| CN113975215A (en) * | 2021-11-18 | 2022-01-28 | 广州梵之容化妆品有限公司 | Whitening cream and preparation method thereof |
| CN115670951A (en) * | 2022-11-11 | 2023-02-03 | 上海世领制药有限公司 | High-permeability ascorbyl tetraisopalmitate elastomer and preparation method and application thereof |
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