CN115006272A

CN115006272A - Submicron liposome

Info

Publication number: CN115006272A
Application number: CN202210739683.7A
Authority: CN
Inventors: 蔡文; 李立香; 刘楚华; 宋园
Original assignee: Guangzhou Jiarui New Material Technology Co ltd
Current assignee: Guangzhou Jiarui New Material Technology Co ltd
Priority date: 2022-06-28
Filing date: 2022-06-28
Publication date: 2022-09-06
Anticipated expiration: 2042-06-28
Also published as: CN115006272B

Abstract

The invention relates to the field of cosmetics, in particular to a submicron liposome. The invention provides a submicron liposome, which comprises the following components in percentage by mass: lecithin 0.5-2%, cholesterol 0.1-0.3%, polyglycerol-3 methyl glucose distearate 2-4%, methyl glucose sesquistearate 0.2-1%, polyalcohol 10-30%, oily component 1-20%, and water in balance. The submicron liposome has large drug-loading rate and high whiteness, maintains excellent biocompatibility and permeability of the liposome, and can be used as a carrier of active ingredients in the field of cosmetics.

Description

Submicron liposome

Technical Field

The invention relates to the field of cosmetics, in particular to a submicron liposome.

Background

Liposomes were first proposed by Alec Bangham, a scientist in the united kingdom in 1961 and are now widely used as delivery systems for actives. Liposomes are vesicles formed from one or more bilayer membranes, the main components of which are usually phospholipids and cholesterol. The phospholipid molecule is composed of a polar head group and a hydrophobic hydrocarbon chain, and the unique structure enables the phospholipid to spontaneously form a liposome in water, and encapsulates water-soluble and fat-soluble substances.

Liposomes are widely used as delivery vehicles for many active substances in the cosmetic, food and pharmaceutical industries due to their good biocompatibility, biodegradability, low toxicity and the ability to encapsulate hydrophilic/lipophilic drugs, achieve targeted drug delivery, etc. However, human skin has a barrier effect and the active is difficult to penetrate into the deep layers of the skin. In order to improve the utilization efficiency of active substances, new methods have been proposed, i.e., various novel liposomes have been prepared by changing the structure of the liposome bilayer membrane, such as adding ethanol as a penetration enhancer, lowering the melting point of stratum corneum lipids, increasing the drug permeation amount, or adding a surfactant as a marginal activator, increasing vesicle deformability, etc. These techniques help liposomes to better penetrate the skin barrier and penetrate deeper into the skin, achieving penetration enhancing effects.

In order to overcome the limitations of poor stability and permeability of the traditional liposome, researchers change the properties and performances of the liposome by adjusting the chemical composition, space structure, surface charge, size and the like of the liposome vesicle, and then find a series of novel liposomes, such as ethosome, niosome, transfersome and the like (Zhang Yaqi cosmetic emulsion and new emulsification technology (V) — application of liposome entrapment technology in transdermal delivery [ J ]. daily chemical industry, 2021,51(10): 939-.

The present inventors have made extensive studies in the field of liposomes, and have unexpectedly found that a combination of a specific nonionic surfactant known per se in the art with lecithin and cholesterol in a ratio within a well-defined range gives a submicron liposome-like body having a large drug loading amount, high whiteness, and maintaining excellent biocompatibility and permeability of the liposome, which can be used as a carrier for active ingredients in the field of cosmetics, thereby completing the present invention.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a submicron liposome completely different from the prior art, and a preparation method and application thereof.

The specific technical scheme is as follows:

in a first aspect, the invention provides a submicron liposome, which comprises the following components in percentage by mass: lecithin 0.5-2%, cholesterol 0.1-0.3%, polyglycerol-3 methyl glucose distearate 2-4%, methyl glucose sesquistearate 0.2-1%, polyalcohol 10-30%, oily component 1-20%, and water in balance.

Specifically, the lecithin is preferably egg yolk lecithin and/or soybean lecithin.

Specifically, the polyol is preferably a polyol having a valence of 2 or more, but is not particularly limited as long as it has a valence of 3 or more.

In particular, the oily formulation may be preferably selected from hydrocarbon oils, synthetic fatty acid esters, animal and vegetable oils, silicone oils and mixtures thereof.

Specifically, the submicron liposome can be added into an acceptable active matter in the skin external preparation as a preference. The active matter can be a cosmetic raw material with the effects of whitening, moisturizing, controlling oil, removing acnes, preventing sun, relieving, preventing alopecia, repairing or removing wrinkles, tightening and the like.

The active may be oil soluble or water soluble. The water-soluble active substance can be directly added into the submicron liposome and uniformly dissolved by stirring. The oil-soluble active substance needs to be uniformly mixed with the oily component, and is added in the production process of the submicron liposome to participate in emulsification.

For oil soluble actives, the amount added in conventional liposomes is typically 0.1-1 wt%. The addition amount of the oil-soluble active substance in the submicron liposome can reach 0.1-20wt% at most.

In a second aspect, the embodiment of the present invention provides a method for preparing a submicron liposome, specifically comprising the following steps: mixing cholesterol, polyglycerol-3-methylglucadiate, and oily component, heating to dissolve to obtain oil phase; heating polyalcohol, water and lecithin to 80-85 deg.C to obtain water phase; mixing the water phase and the oil phase, and stirring uniformly to obtain a mixed phase; putting the mixed phase into an emulsifying pot for homogenizing treatment for 5-10 minutes, and discharging; and then treating for 1-2 times by using a high-pressure homogenizer.

In a third aspect, the invention also provides the application of the submicron liposome in preparing cosmetics.

Specifically, the cosmetic can be shampoo, bath lotion, cosmetic water, essence, facial mask, skin cream, and skin lotion.

The technical scheme provided by the embodiment of the invention has the following beneficial effects:

(1) the submicron liposome provided by the embodiment of the invention has excellent biocompatibility, and the human skin patch experiment shows that the submicron liposome is mild and does not have irritation to human skin;

(2) the submicron liposome provided by the embodiment of the invention is stable and can pass heat-resistant cold-resistant and centrifugal stability tests;

(3) the average particle size of the submicron liposome provided by the embodiment of the invention is controlled to be between 100-200nm, the submicron liposome has good whiteness, a small amount of the submicron liposome is added into liquid cosmetics (such as astringent and facial mask essence) to endow the submicron liposome with good whiteness, and a suspending agent is not required to be additionally added;

(4) the submicron liposome provided by the embodiment of the invention contains 1-30% of oily components and 1-50% of polyhydric alcohol, and a small amount of the submicron liposome is added into cosmetics to endow the products with good instant absorption effect and long-acting skin moistening feeling;

(5) the medicine carrying amount of the submicron liposome provided by the embodiment of the invention for the oil-soluble active ingredients is up to 0.1-20wt%, and the medicine carrying amount of the conventional liposome is 0.1-1 wt%. Experiments prove that the permeability of the submicron liposome provided by the embodiment of the invention in the skin is close to that of the conventional liposome.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art are briefly introduced below.

FIG. 1 an example of a skin-enclosed patch;

FIG. 2 photographs of samples of stock solution and 1% water dilution of example 1.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in further detail below.

Materials, reagents and the like used in examples of the present invention are commercially available unless otherwise specified.

After a great deal of research work carried out by the inventors of the present invention in the previous field of liposomes, it was unexpectedly found that the combination of specific non-ionic surfactants known per se in the art with lecithin, cholesterol in ratios within well-defined ranges, results in a submicron niosome.

The submicron liposome provided by the embodiment of the invention has excellent biocompatibility, and the human skin patch experiment shows that the submicron liposome is mild and does not have irritation to human skin; the submicron liposome provided by the embodiment of the invention is stable and can pass heat-resistant cold-resistant and centrifugal stability tests; the average particle size of the submicron liposome provided by the embodiment of the invention is controlled to be between 100-200nm, the submicron liposome has good whiteness, a small amount of the submicron liposome is added into liquid cosmetics (such as astringent and facial mask essence) to endow the submicron liposome with good whiteness, and a suspending agent is not required to be additionally added; the submicron liposome provided by the embodiment of the invention contains 1-30% of oily components and 1-50% of polyhydric alcohol, and a small amount of the submicron liposome is added into cosmetics to endow the products with good instant absorption effect and long-acting skin moistening feeling; the sub-micron liposome provided by the embodiment of the invention has the drug-loading capacity of 0.1-20wt% for oil-soluble active ingredients, and the conventional liposome has the drug-loading capacity of 0.1-1 wt%. Experiments prove that the permeability of the submicron liposome provided by the embodiment of the invention in the skin is close to that of the conventional liposome.

Specifically, the lecithin may be egg yolk lecithin and/or soybean lecithin.

Specific examples thereof include 2-valent alcohols (e.g., ethylene glycol, propylene glycol, trimethylene glycol, 1, 2-butanediol, 1, 3-butanediol, tetramethylene glycol, 2, 3-butanediol, pentamethylene glycol, 2-butene-1, 4-diol, pentanediol, hexanediol, octanediol, etc.); alcohols having a valence of 3 (e.g., glycerin, trimethylolpropane esters, etc.); alcohols having a valence of 4 (e.g., pentaerythritol such as 1, 2, 6-hexanetriol); 5-valent alcohols (e.g., xylitol, etc.); alcohols having a valence of 6 (e.g., sorbitol, mannitol, etc.); polyol polymers (e.g., diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerol, tetraglycerol, polyglycerin, and the like); 2-valent alcohol alkyl ethers (e.g., ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene glycol mono-2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, etc.); 2-valent alcohol alkyl ethers (e.g., diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol butyl ether, and the like); 2-valent alcohol ether esters (e.g., ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diadipate, ethylene glycol disuccinate, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, propylene glycol monophenyl ether acetate, etc.); glycerol monoalkyl ethers (e.g., chimyl alcohol, batyl alcohol, etc.); sugar alcohols (e.g., sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch degrading sugars, maltose, xylitol, starch degrading sugar reducing alcohols, etc.); GLYSOLID; tetrahydrofurfuryl alcohol; POE-tetrahydrofurfuryl alcohol; POP-butyl ether; POP POE butyl ether; glyceryl tripropylene oxide ether; POP-glycerol ether; POP-glyceryl ether phosphoric acid; POP, POE, pentane erythritol ether, and the like.

Among these, glycerin, 1, 3-propanediol, butanediol, and pentanediol are more preferable, and 1, 3-propanediol and pentanediol are particularly preferable.

Specific examples thereof include hydrocarbon oils such as: isododecane, isohexadecane, squalane, petrolatum, hydrogenated poly (C6-12 olefin), hydrogenated polyisobutene, and the like.

Specific examples thereof include synthetic fatty acid esters such as: caprylic/capric triglyceride, isononyl isononanoate, C12-15 alcohol benzoate, propylene glycol dicaprylate/dicaprate, tri (ethyl hexanoate) glyceride, tridecyl trimellitate, pentaerythritol tetra (ethyl hexanoate), diethylhexyl carbonate, isopropyl myristate, cetyl octanoate, octyldodecanol myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, cetyl stearate, cetyl isostearate, ethyl isostearate, cholesterol 12-hydroxystearate, ethylene glycol di-2-ethylhexanoate, dipentaerythritol fatty acid esters, N-alkyl glycol monoisostearate, ethylene glycol monoisostearate, propylene glycol dicaprylate/dicaprate, glyceryl dicaprylate, tridecyl trimellitate, pentaerythritol tetra (ethyl hexanoate), ethylhexyl carbonate, isopropyl myristate, cetyl myristate, lanolin acetate, cetyl stearate, cetyl isostearate, ethyl isostearate, ethylene glycol di-2-ethylhexanoate, and mixtures thereof, Neopentyl glycol didecanoate, diisostearyl malate, glycerol di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythrityl tetra-2-ethylhexanoate, glycerol tri-2-ethylhexanoate, trimethylolpropane triisostearate.

Specific examples thereof include animal and vegetable oils such as: emu oil, horse oil, avocado oil, camellia oil, turtle oil, macadamia integrifolia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg butter oil, sesame oil, persic oil, wheat germ oil, camellia oil, castor oil, linseed oil, safflower oil, cottonseed oil, perilla oil, soybean oil, peanut oil, tea seed oil, coconut oil, rice bran oil, tung oil, jatropha oil, jojoba oil, corn germ oil, and the like.

Specific examples thereof include silicone oils such as: cyclopentasiloxane, decamethylcyclopentasiloxane, octylmethylpolysiloxane, polydimethylsiloxane, (polydimethylsiloxane/vinylpolydimethylsiloxane) crosspolymer, (polydimethylsiloxane/phenylvinylpolydimethylsiloxane) crosspolymer, and the like.

Specifically, the submicron liposome can be added into an acceptable active matter in the skin external preparation as a preference. The active matter can be a cosmetic raw material with the effects of whitening, moisturizing, controlling oil, removing acne, preventing sun, relieving, preventing alopecia, repairing, removing wrinkles, tightening and the like.

Specific examples thereof include whitening actives such as: niacinamide, vitamin C and its derivatives, glabridin, phenethyl resorcinol, 4-butyl resorcinol, arbutin, kojic acid and its derivatives, tranexamic acid, pterostilbene, etc.

Specifically, moisturizing actives are listed, for example: sodium hyaluronate, chondroitin sulfate, amino acid, betaine, trehalose, erythritol, xylitol-based glucoside, dehydrated xylitol, glucose, saccharide isomerate, sodium polyglutamate, and the like.

Specifically, oil control actives may be mentioned, for example extracts of the following plants: astragalus root (root), ganoderma lucidum (fruit body), climbing fern spore (spore), anemarrhena rhizome (root), motherwort (overground part), cacumen biotae (leaf), garden balsam stem (overground part), glossy privet fruit (fruit), lightyellow sophora root (root), salvia miltiorrhiza (root), safflower (flower), prepared fleece flower root (tuber), Chinese prickly ash (fruit), dried ginger (root), ginseng (root), bletilla striata (tuber), costus root (root), dwarf lilyturf root (root), cynomorium songaricum (fleshy stem), dittany bark and the like.

Specific examples of the acne-removing active include: salicylic acid and its derivatives, azelaic acid, paeonol, cymene, sulfonated shale oil, white willow bark extract, Saviae Miltiorrhizae radix extract, etc.

Specific examples of sunscreen actives include: ethylhexyl methoxycinnamate, hexyl diethylaminobenzoyl benzoate, ethylhexyl triazone, benzophenone-3, benzophenone-4, ethylhexyl salicylate, homosalate and the like.

Specifically, soothing actives may be cited, for example: dipotassium glycyrrhizinate, stearyl glycyrrhetinate, oat kernel extract, gentian extract, green tea extract, kava extract, black tea extract, acetyl chitosamine, and the like.

Specifically, anti-hair loss actives are listed, for example: biotin, radix Ginseng (Panax GINSENG) root extract, rhizoma anemarrhenae (ANEMARRHENA ASPHODELOIDES) root extract, rhizoma Zingiberis recens (Zingiber OFFICINALE) root extract, radix Angelicae SINENSIS (Angelica POLYMORPHA SINENSIS) root extract, cacumen Platycladi (BIOTA ORIENTALIS) leaf extract, radix Polygoni Multiflori (Polygonum MULTIFLORUM) root extract, etc.

Specific examples of such a repair active include: ceramide, asiaticoside, beta-glucan, allantoin, ectoin, phytosterol oleate, etc.

Specifically, wrinkle-removing firming actives may be cited, for example: tocopheryl acetate, acetyl hexapeptide-8, palmitoyl pentapeptide-4, palmitoyl tripeptide-1, dipeptide diaminobutyrylbenzylamide diacetate, carnosine, vitronectin, retinol propionate, palmitoyl tripeptide-5, and the like.

The submicron liposome prepared by the invention is very convenient to use, can be directly added into a water phase of a cosmetic preparation in proportion and uniformly stirred, and can also be added into a water-in-oil system to form a multi-layer system of oil-in-water-in-oil. Specific examples thereof include cosmetics such as: shampoo, shower gel, lotion, essence, facial mask, skin cream, skin lotion, BB cream, foundation liquid, CC cream, hair conditioner, etc.

Example 1

The niosomes of examples 1-3 and comparative examples 1-3 were prepared according to the formulation shown in Table A, respectively. Specifically, the preparation method comprises the following steps: mixing the oil phase raw materials, heating and dissolving to obtain an oil phase; mixing the water phase raw materials, and heating to 80-85 ℃ to obtain a water phase; mixing the water phase and the oil phase, and stirring uniformly to obtain a mixed phase; putting the mixed phase into an emulsifying pot for homogenizing treatment for 5-10 minutes, and discharging; and then treating for 1-2 times by using a high-pressure homogenizer.

[ TABLE A ]

Test example 1 evaluation of mildness

The skin-closed patch test was carried out according to "human skin patch test" in chapter 2 of the seventh chapter of the technical Specification for cosmetic safety "(2015 edition). 31 test persons were organized, the lipoid bodies prepared in example 1 were subjected to a patch test, observed at 0.5h, 24h, and 48h according to the evaluation criteria of Table 1, and the results are recorded as shown in Table 2.

TABLE 1 skin reaction judgment standard table for skin repetitive open smearing test

TABLE 2 closed patch test results

As can be seen from Table 2, the lipoid body provided by the embodiment of the invention has excellent biocompatibility, and the skin patch experiment of a human body shows that the submicron lipoid body is mild and does not show irritation to the skin of the human body.

Test example 2 evaluation of stability

The heat resistance, cold resistance and centrifugation tests are technical means which are commonly used in the field of cosmetics and used for measuring whether products have long-term stability. The lipoid provided by the embodiment of the invention is a special emulsion consisting of water, oil and a surfactant. The lipoid liposomes prepared in example 1 were tested for heat resistance, cold resistance and centrifugation according to the standard of GB/T29665 skin care lotion, and the results are reported in Table 3.

TABLE 3 stability records

As can be seen from table 3, the submicron liposome provided by the embodiment of the present invention is stable and can pass the heat and cold resistance and centrifugal stability tests; while the comparative groups 1-3 failed.

Test example 3 measurement by laser particle size analyzer

The laser particle size analyzer is an important device for evaluating the quality of the microemulsion, can measure the average distribution particle size of the microemulsion and the PDI index, and shows that the dispersion of the microemulsion is good and the adhesion and aggregation conditions are less when the PDI is lower than 0.3 according to the industrial experience. The measurement was carried out on the niosome obtained in example 1 using water as a dispersion medium and the measurement temperature was 25 degrees, and the results are reported in table 4.

TABLE 4 laser particle size Analyzer measurement results

As can be seen from Table 4, the average particle size of the lipoid provided by the embodiment of the invention is controlled to be between 100nm and 200nm, and the particle size is in the submicron range of 100nm to 1000 nm. The PDI value of the lipoid liposome provided by the embodiment of the invention is lower than 0.3, and the lipoid liposome is good in dispersion and less in adhesion and aggregation.

Test example 4 evaluation of whiteness

Visual evaluation was performed on the lipoid bodies prepared in example 1 and 1% water dilution thereof, as shown in fig. 2, the lipoid bodies prepared in the examples of the present invention had good whiteness, and a small amount of the lipoid bodies was added to the transparent product to impart good whiteness.

Test example 5 evaluation of feeling of use

The feeling of use of the niosome prepared in example 1 was evaluated. Samples from the execution groups 1-3 and commercially available emulsions were evaluated by 12 female volunteers according to the requirements of table 5, with a sample size of 1mL, test site: medial of the forearm. The average score of 12 volunteers is shown in table 6.

TABLE 5 sensory evaluation Table

TABLE 6 sensory evaluation records

As can be seen from table 6, the niosomes provided in the examples of the present invention are easily pushed away and rapidly absorbed on the skin, are fresh and cool in use, have light touch, are weak in sticky feeling, and have a long-lasting skin moisturizing effect.

Example 2

An anti-aging lipoid containing tocopheryl acetate was prepared according to the formulation shown in table B. The preparation method is the same as example 1.

[ TABLE B ]

Example 3

A whitening effect niosome containing glabridin was prepared according to the formulation shown in Table C. The preparation method is the same as that of example 1.

[ TABLE C ]

Comparative example 1

A whitening effect liposome containing glabridin is prepared according to a formula shown in a table D, and the index method is as follows: mixing lecithin, cholesterol, glabridin and absolute ethyl alcohol, wherein the amount of the absolute ethyl alcohol is half of the amount of water added in the formula; heating to dissolve, placing in a rotary evaporator, and removing ethanol by rotary evaporation; and then adding the water phase, treating for 5-8 minutes by using a homogenizer, uniformly stirring, and standing for defoaming.

[ TABLE D ]

Test example 6 evaluation of permeability

Most actives are difficult to pass through due to the human skin barrier. Therefore, it is of great importance to study the transdermal properties of the active. The in vitro research method of the transdermal drug delivery preparation is mainly Franz transdermal diffusion cell method. The Franz diffusion cell method is to cut the skin of an animal (such as rabbit, guinea pig, fragrant pig, human, etc.) into a suitable size and clamp the skin in the diffusion cell, the skin in vitro divides the diffusion cell into a supply chamber and a receiving chamber, the stratum corneum faces the supply chamber, the medicine is tightly attached to the stratum corneum, the dermis faces the receiving chamber, and the dermis completely contacts with the receiving liquid, so as to avoid the generation of bubbles. A certain volume of receiving liquid is taken at a specified time point for detection, and effective components contained in the liquid are calculated, so that the in-vitro transdermal performance of the liquid is evaluated.

The method is carried out by referring to a method recorded in a literature (preparation, in-vitro evaluation and transdermal action mechanism research [ D ] of kuh-seng total alkali nano-emulsion gel, Beijing university of traditional Chinese medicine), and the specific test process is as follows:

male SD rats were sacrificed by cervical dislocation, abdominal hair was removed and abdominal skin was immediately peeled off, subcutaneous fat and muscle tissue were removed, and the rats were washed with physiological saline for future use.

A Franz diffusion cell is adopted, a receiving medium is 30% ethanol-physiological saline, 5g of each sample of example 3 and comparative example 1 is weighed and placed in a supply cell at 37 ℃ at 200 r/min, 2mL of receiving liquid is taken at 1, 4 and 8h respectively (simultaneously, 30% ethanol-physiological saline with the same temperature and the same quantity is supplemented), a 0.45-micrometer microporous filter membrane is filtered, and then the receiving liquid is injected into a liquid chromatograph to measure the content of the glabridin (the liquid phase method refers to Huxinhua, Chenglan, Jinsong, HPLC method to measure the content of the glabridin in the liquorice of different production places [ J ]. Chinese pharmacy, 2016,27(06): one 826). The specific results are shown in Table 7.

TABLE 7 transdermal behavior of the samples

As can be seen from Table 7, the submicron liposome provided in the examples of the present invention has skin permeability close to that of the conventional liposome.

Comparative example 2

A whitening effect niosome was prepared according to the formula shown in Table E. The preparation method is the same as that of example 1.

[ TABLE E ]

Comparative example 3

A whitening effect niosome containing glabridin was prepared according to the formulation shown in Table F. The preparation method is the same as that of example 1.

[ TABLE F ]

Test 7 evaluation of human efficacy

The whitening effect liposome prepared in example 3 and comparative examples 2-3 was tested on human body trial by using a freckle-removing whitening effect test method in accordance with the notice of the national drug administration that 7 test methods such as a test method of preservatives in cosmetics are brought into the technical safety standard (2015 edition).

The main operation process is as follows:

(1) volunteers: selecting qualified 99 subjects according to the standard subject selection and exclusion standard, and dividing into 3 test groups according to a random table, wherein each group comprises 33 persons;

(2) subject restriction: during the test, the tested part must use the test product or the control product provided by the test mechanism, and any other product with the freckle removing and whitening effects or possibly influencing the test result cannot be used; the sun exposure condition can not occur during the test period, and the sun protection work of the test part should be done;

(3) the test substance: the whitening effect liposome prepared in the example 3 and the comparative examples 2 to 3 are respectively added into the facial mask essence. The facial mask essence comprises the following components in percentage by mass: 5% of glycerin, 3% of butanediol, 0.05% of sodium hyaluronate, 0.05% of xanthan gum, 0.1% of carbomer, 0.1% of arginine, 0.5% of hexanediol, 0.5% of p-hydroxyacetophenone, 5% of the whitening effect liposome and the balance of water;

(4) the using method comprises the following steps: the test product is issued by the staff according to the random table, and the use instruction is given to the subject according to the use instruction, so that the subject can be ensured to correctly and continuously use the product for 8 weeks;

(5) test sites: a face;

(6) the instrument equipment comprises: skin colorimeter: instruments that can measure L a b color space data as specified by the international commission on illumination (CIE);

(7) the test process comprises the following steps: performing product pre-use skin instrument testing and recording on qualified subjects who enter the group; the same evaluations and tests were performed again 4 weeks and 8 weeks after the product was used. At each visit point, the skin colorimeter was used to measure L, a, b values of the skin in the test site plaque area of the test group and the control group, each test area was tested three times, and the ITA ° value was recorded and calculated. The larger the ITA DEG value of the tested skin area is, the lighter the skin color is, and vice versa.

And (4) performing data statistics, wherein statistical analysis is performed on the data by using statistical analysis software, and the data statistics is shown in table 8.

TABLE 8 ITA DEG value statistics before, 4 weeks and 8 weeks after product use

As can be seen from table 8, the ITA ° values of the face of the volunteer using example 2 were increased by 7.42 and 9.6, respectively, after using the product for 4 weeks and 8 weeks, compared to the initial values, and good whitening and spot-removing effects were achieved. On the other hand, the whitening effect of the comparative example 2 and the comparative example 3 only containing the glabridin or the pterostilbene is weaker, which shows that the whitening and freckle removing effect of the compounded glabridin and the pterostilbene is better.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. The submicron liposome is characterized by comprising the following components in percentage by mass: lecithin 0.5-2%, cholesterol 0.1-0.3%, polyglycerol-3 methyl glucose distearate 2-4%, methyl glucose sesquistearate 0.2-1%, polyalcohol 10-30%, oily component 1-20%, and water in balance.

2. The submicron niosome according to claim 1, wherein the lecithin is egg yolk lecithin and/or soybean lecithin.

3. The submicron liposome according to claim 1, wherein the polyol is a polyol having a valence of 2 or more.

4. The submicron liposome according to claim 1, wherein the oily formulation is selected from hydrocarbon oil, synthetic fatty acid ester, animal and vegetable oil, silicone oil and their mixture.

5. The submicron liposome according to claim 1, wherein the active substance is a cosmetic material with whitening, moisturizing, oil-controlling, acne-removing, sun-screening, soothing, alopecia-preventing, repairing, wrinkle-removing and tightening effects.

6. The submicron liposome according to any one of claims 1-5, wherein the preparation method of the submicron liposome comprises the following steps: mixing cholesterol, polyglycerol-3-methylglucadiate, and oily component, heating to dissolve to obtain oil phase; heating polyalcohol, water and lecithin to 80-85 deg.C to obtain water phase; mixing the water phase and the oil phase, and stirring uniformly to obtain a mixed phase; putting the mixed phase into an emulsifying pot for homogenizing treatment for 5-10 minutes, and discharging; and then treating for 1-2 times by using a high-pressure homogenizer.

7. Use of a submicron niosome according to any of claims 1-5 for the preparation of a cosmetic product.