HK1255152A1 - Liposome, liposome liquid and cosmetic, and method for producing the liposome - Google Patents

Abstract

The invention relates to a lipidosome, a lipidosome liquid and cosmetic, and a method for manufacturing the abovementioned lipidosome. The invention aims to provide a lipidosome which gives consideration to both increase of a water component of skin and improvement of skin compactness, a lipidosome liquid and cosmetic containing the abovementioned lipidosome, and a method for manufacturing the abovementioned lipidosome. The solution is a lipidosome of which a membrane contains proteoglycan, a lipidosome containing the abovementioned lipidosome, a cosmetic containing the abovementioned lipidosome, and a method for manufacturing the abovementioned lipidosome.

Description

Liposomes, liposome liquid and cosmetic, and method for producing the liposomes

Technical Field

The present invention relates to a liposome in which a membrane of the liposome contains proteoglycan, a liposome liquid and a cosmetic containing the liposome, and a method for producing the liposome.

Background

The skin includes epidermis, dermis, and subcutaneous tissue from the outside, and has the function of protecting the living body from external stimuli through its barrier function. The dermis and epidermis of the skin are composed of epidermal cells, fibroblasts, dermal extracellular matrix, and the like. Proteoglycan is a major biopolymer that forms a matrix in the extracellular matrix of connective tissue together with collagen and the like. Young skin maintains moisture, softness, elasticity, and the like by maintaining the interaction of these skin tissues constant, and maintains a state of looking tight and glossy.

The outermost layer of the epidermis is further present with an angular layer. The stratum corneum is the last part of a cell composed of 10 to 20 layers of keratinocytes to reach. Natural moisturizing factors such as amino acids, urea, and lactic acid exist in keratinocytes, and these substances bind to water to retain moisture and keep the skin soft. Dead cells without nuclei are visible on the outer side of the stratum corneum, but the barrier function of the stratum corneum, which functions to retain water and prevent dryness, is greatly related to the beauty of the skin.

However, the moisture content of the stratum corneum is decreased by external factors such as dryness and ultraviolet rays, and internal factors such as aging, visceral diseases and stress, and this causes a decrease in the barrier function of the skin, leading to rough skin, dry skin and various kinds of dermatitis. Therefore, in the cosmetic field and the dermatological field, the development of a moisturizing agent for maintaining the moisture content of the horny layer is essential.

On the other hand, in the field of cosmetics, as means for delivering active ingredients having a moisturizing function, an antioxidant effect, a whitening effect, and the like to the skin, the active ingredients are often encapsulated in liposomes. Liposomes are lipid bilayers or multilayers formed mainly of phospholipids, having a structure similar to a cell membrane. In the case of water-soluble drugs, the active ingredient is often encapsulated in the inner aqueous phase of liposomes.

Documents of the prior art

Patent document

Patent document 1: japanese laid-open patent publication No. 2012-236808

Disclosure of Invention

Problems to be solved by the invention

For example, patent document 1 describes: a cosmetic preparation containing a cell growth factor, which can effectively proliferate and replace skin cells and improve skin to a young skin having a firm feeling, is described as follows: from the viewpoint of appropriately suppressing water evaporation and preventing the inhibition of the function of cell growth factors and the like, proteoglycan is encapsulated in the liposome internal aqueous phase.

However, it is desired to achieve both an increase in skin moisture content and further improvement in skin firmness.

The present invention has been made in view of the above circumstances, and an object thereof is to provide a liposome which can increase the moisture content of the skin and improve the skin firmness, a liposome liquid and a cosmetic containing the liposome, and a method for producing the liposome.

Means for solving the problems

The present inventors have found that by using a liposome containing proteoglycan in the membrane (lipid layer) of the liposome, the skin firmness is remarkably improved, and have completed the present invention. Namely, the present invention is as follows.

(1) A liposome comprises proteoglycan in the membrane.

(2) A liposome liquid comprising the liposome according to (1) above.

(3) A cosmetic comprising the liposome according to the above (1).

(4) Use of the liposome of (1) above or the liposome liquid of (2) above for inclusion in cosmetics.

(5) A method for producing a liposome, which is a method for producing a proteoglycan-containing liposome as a membrane of a liposome,

wherein the liposome is produced by bringing a film, which is formed by removing a solvent from a solution containing proteoglycan and a lipid dissolved or dispersed in the solvent, into contact with an aqueous solution or water.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, it is possible to provide liposomes which can increase the moisture content of the skin and improve the skin firmness, a liposome liquid and a cosmetic containing the liposomes, and a method for producing the liposomes.

Detailed Description

[ proteoglycan-containing liposomes as membranes of liposomes ]

In the liposome of the present invention, the membrane (lipid layer) of the liposome contains proteoglycan. The proteoglycan can be a membrane component of the liposome, or can be taken into the space between membranes of the liposome. Among them, proteoglycan is preferably present in the form of a membrane component of liposome.

The proteoglycan-containing liposome membrane may be a monolayer lipid bilayer or a multilayer comprising a plurality of lipid bilayers.

The inner aqueous phase of the liposome of the present invention may be water alone, may or may not contain proteoglycan, and may contain other physiologically active components.

The source of proteoglycan in the present invention is not particularly limited, and proteoglycan derived from fish cartilage, etc. can be mentioned. The fish is not particularly limited, and specific examples thereof include trout (Oncorhynchus marmoschatus, Oncorhynchus masou, Oncorhynchus mackerel (Oncorhynchus masou), salmon (salmon, red salmon, silver salmon, Oncorhynchus marmosou, etc.), shark, cod, and the like. The fish of the genus Salmonidae is preferred, and salmon or trout is particularly preferred. The cartilage is not particularly limited, and is preferably cervical cartilage, and particularly preferably nasal cartilage. Further, since fish is usually discarded in the neck when processed into food products and the like, there is also an advantage that the cost for starting the neck cartilage is low and a large amount of the neck cartilage can be stably supplied.

The content of proteoglycan in the liposome of the present invention is not particularly limited as long as the effect of the present invention is not impaired, but is preferably 0.1 to 30% by mass, more preferably 0.5 to 20% by mass, still more preferably 1 to 15% by mass, and particularly preferably 3 to 10% by mass, based on the total mass of the liposome membrane components.

The lipid membrane component constituting the lipid membrane of the liposome of the present invention contains at least phospholipids, glycolipids, sterols, glycols, cationic lipids, polyethylene glycol (PEG) -modified lipids (e.g., PEG-phospholipids), and the like. Among them, phospholipids and/or glycolipids are preferably used.

As the phospholipid that can be used, for example, phosphatidylcholine (lecithin), phosphatidylserine, phosphatidic acid, phosphatidylglycerol, dioleoylphosphatidylcholine, distearoylphosphatidylcholine, dipalmitoylphosphatidylcholine, palmitoyloleoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, dicetyl phosphate, lysophosphatidylcholine (lysolecithin), egg yolk lecithin, soybean lecithin, or hydrogenated phospholipids thereof can be used without particular limitation.

The phospholipid may be used in combination of 1 or 2 or more.

As glycolipids, there may be mentioned: and glycosphingolipids such as diglyceride digalactosylate, diglyceride sulfate digalactosylate, galactosylceramide sulfate, lactosylceramide, ganglioside G7, ganglioside G6, and ganglioside G4.

Other substances may be added as necessary to the liposome membrane as a constituent component in addition to the above lipids. Examples thereof include: examples of sterols acting as lipid membrane stabilizers include cholesterol, dihydrocholesterol, cholesterol esters, phytosterols, sitosterol, stigmasterol, campesterol, cholestanol, and lanosterol. In addition, sterol derivatives such as 1-O-sterol glucoside, 1-O-sterol maltoside or 1-O-sterol galactoside are known to have an effect of stabilizing liposomes. Among them, cholesterol is particularly preferable.

The sterol is preferably used in a molar ratio of phospholipid (excluding PEG-phospholipid)/sterol of 100/60 to 100/90, more preferably 100/70 to 100/85. The molar ratio is based on the amount of phospholipids other than PEG-phospholipids. When the molar ratio is 100/60 to 100/90, the sterol-based stabilization can be sufficiently exhibited to improve the dispersibility of the mixed lipid of the phospholipid (excluding PEG-phospholipid) and the sterol.

In addition to the sterols, glycols may be added as a constituent of the liposome membrane. When a diol is added together with a phospholipid or the like in the preparation of a liposome, the retention efficiency of a water-soluble compound in the liposome is improved. The glycols include ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, trimethylene glycol, and 1, 4-butanediol. The amount of the diol to be used is preferably 0.01 to 20% by mass, more preferably 0.5 to 10% by mass, based on the total mass of the lipid.

The particle size of the liposome of the present invention is not particularly limited as long as the effect of the present invention is not impaired, and may be 10nm to 100 μm, and from the viewpoint of more reliably achieving the effect of the present invention, the particle size is preferably 50nm to 50 μm, and more preferably 100nm to 10 μm. The Particle Size of the liposome can be measured, for example, by a Coulter counter (product of BeckmanCoulter Co., Ltd.: Submicron Particle Size Analyzer N5).

< method for producing liposome >

The method for producing the liposome is not particularly limited as long as the effect of the present invention is not impaired, and examples thereof include: (1) a method for producing the liposome by bringing a thin film, which is formed by removing an organic solvent (chloroform, methanol, or the like) from a mixture of proteoglycan, lipid, and the organic solvent, into contact with an aqueous solution or water (so-called Bangham method) (japanese patent laid-open publication No. 2011-032230); (2) a method in which proteoglycan and lipid are mixed with an organic solvent such as ether or ethanol, the resulting mixture is poured into an aqueous solution such as a buffer or water, and the organic solvent is removed; further, as a mechanized method, (3) a method using ultrasonic treatment (japanese patent laid-open No. 2005-41869); (4) a method of using a high-pressure homogenizer and a high-speed rotation disperser (Japanese patent laid-open No. 11-139961); (5) a method of high-pressure filtration using a polycarbonate membrane filter; (6) a method in which an oil phase containing proteoglycan and lipid in the upper part of an aqueous phase is prepared, droplets are introduced into the oil phase, and the droplets are brought into the aqueous phase by centrifugal separation force; (7) a method in which proteoglycan and lipid are mixed with an organic solvent such as ethanol which is miscible with water, and the organic solvent is replaced with water through a dialysis membrane (Japanese patent application laid-open No. H01-224042).

As a particularly preferable method, a method of producing liposomes by bringing a film formed by removing the solvent from a solution in which proteoglycan and lipid are dissolved or dispersed into contact with an aqueous solution or water is preferable.

Examples of the solvent include water, lower alcohols such as ethanol and butanol, and organic solvents such as chloroform. In particular, when water is used, proteoglycan and lipid are difficult to dissolve, and therefore, it is preferable to disperse them by ultrasonic waves or the like to form a solution. When a thin film is formed from the solution, the solution may be dried while being brought into contact with a substrate. For example, the solution may be added to a glass flask, and the solvent may be removed by a rotary evaporator while heating, thereby forming a thin film of proteoglycan and lipid on the inner wall (substrate) of the flask.

Further, as a method for bringing the film into contact with an aqueous solution or water, there can be mentioned a method in which after forming the film on the wall (substrate) of an arbitrary container, the film is shaken (swelled) in the presence of an aqueous solution such as a buffer or water.

The vessel forming the wall is not particularly limited, and examples thereof include a flask.

If necessary, the liposome can be produced by further peeling the film from the wall by a mechanical stirring means.

< lipid body fluid >

The liposome liquid of the present invention is a liquid containing the above-mentioned liposome.

The liposome liquid of the present invention may be a liquid obtained by adding the isolated liposome to an arbitrary liquid, or may be a liposome-containing liquid itself prepared by the above-described method for producing a liposome.

The liposome fluid of the present invention may contain other components, for example, anionic surfactants, amphoteric surfactants, nonionic surfactants, viscosity modifiers, oils, powders (pigments, resins, pigments, etc.), preservatives such as phenoxyethanol, perfumes, moisturizers such as 1, 3-butanediol, physiologically active ingredients, salts, solvents, antioxidants, chelating agents, pearlizing agents, neutralizing agents, pH modifiers, enzymes, and the like, as appropriate, within a range that does not impair the effects of the present invention. Specific examples of the components to be blended are shown below, but the present invention is not limited to these.

examples of the anionic surfactant include α -acyl sulfonate, alkylsulfonate, alkylallyl sulfonate, alkylnaphthalene sulfonate, alkylsulfate, alkylethersulfate, alkylamide sulfate, polyoxyethylene alkylethersulfate, polyoxyethylene alkylamide ether sulfate, alkylphosphate, alkylamide phosphate, alkanoylalkyltaurate, N-acylamino acid salt, sulfosuccinate, perfluoroalkyl phosphate, and the like.

Further, as the amphoteric surfactant, glycine type, amino acid type, carboxybetaine type, sulfobetaine type, sulfonic acid type, sulfuric acid type, phosphoric acid type and the like can be cited, and as preferable examples, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, coconut oil fatty acid amide propyl betaine and the like can be cited. In addition to the purpose of forming liposomes, phospholipids such as lecithin can be used as the amphoteric surfactant.

Examples of the nonionic surfactant include fatty acid alkanolamides, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, sucrose fatty acid esters, polyglycerol fatty acid esters, and alkylamine oxides.

Examples of the viscosity modifier include: acrylamide and its derivatives, carboxyvinyl polymers, alkyl-modified carboxyvinyl polymers, cellulose, keratin and collagen or its derivatives, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, dextran, and the like.

The oil agent includes volatile and nonvolatile oil agents, solvents and resins which are generally used in cosmetics, and may be liquid, pasty or solid at room temperature. Examples of the oil agent include: higher alcohols such as cetyl alcohol, isostearyl alcohol, lauryl alcohol, cetyl alcohol, and octyldodecanol; fatty acids such as isostearic acid, undecylenic acid, and oleic acid; esters such as myristyl myristate, hexyl laurate, octyl dodecyl myristate, decyl oleate, isopropyl myristate, cetyl dimethyloctanoate, glyceryl monostearate, glyceryl trioctoate, diethyl phthalate, ethylene glycol monostearate, octyl hydroxystearate and the like, cholesterol esters such as cholesterol stearate, cholesterol oleate, cholesterol branched fatty acid esters and the like; hydrocarbons such as liquid paraffin, vaseline, and squalane; waxes such as lanolin, reduced lanolin, and carnauba wax; mink oil, cacao butter, coconut oil, palm kernel oil, camellia oil, sesame oil, castor oil, olive oil, etc.; silicone oils such as dimethylpolysiloxane, cyclic dimethylpolysiloxane, and methylphenylpolysiloxane.

Examples of the powder include: pigments such as red 201, yellow 4, blue 1, and black 401; lake pigments such as yellow No. 4 aluminum lake, yellow No. 203 Ba lake, and the like; nylon powder, silk powder, organic silicon powder, cellulose powder, organic silicon elastomer spherical powder, polyethylene powder and other resins; colored pigments such as yellow iron oxide, red iron oxide, chromium oxide, carbon black, ultramarine, prussian blue and the like; white pigments such as zinc oxide and titanium dioxide; bulk pigments such as talc, mica, sericite, kaolin, and the like; pigments such as pearlescent pigments such as mica titanium; metal salts such as barium sulfate, calcium carbonate, magnesium carbonate, and magnesium silicate; inorganic powders such as silica and alumina; bentonite; montmorillonite; boron nitride, and the like. The shape of these powders (spherical, rod-like, needle-like, plate-like, irregular, scale-like, spindle-like, etc.) is not particularly limited.

Examples of the physiologically active ingredient include substances that provide any physiological activity to the skin when applied to the skin. Examples thereof include: anti-aging agent, ultraviolet ray protective agent, skin firming agent, antioxidant, humectant, blood circulation promoter, antibacterial agent, bactericide, desiccant, cold feeling agent, warm feeling agent, vitamins, amino acids, wound healing promoter, irritation alleviator, analgesic, cell activator, enzyme component, etc.

< cosmetics >

The cosmetic of the present invention contains the liposome.

The aforementioned liposome liquid may be used as it is as the cosmetic of the present invention, but it is preferable to use the liposome liquid in a cosmetic.

The cosmetics include, but are not limited to, various cosmetics, cosmetic products, and the like, and include basic cosmetics such as lotions, milky lotions, essences, masks, scrubs, and face lotions; makeup cosmetics such as lipsticks and foundation; cosmetic products such as body soaps, shampoos, conditioners (rinses), conditioners, and hair conditioners such as hair conditioners.

Examples

The present invention will be specifically described below with reference to examples, but these examples are not intended to limit the scope of the present invention.

Using each raw material having the composition shown in table 1 below, liposome liquids 1 to 4 were prepared by the following preparation method.

[ TABLE 1 ]

	Liposomal fluid 1	Liposomal fluid 2	Lipid body fluid 3	Lipid body fluid 4
					Lecithin content	1	1	1	1
Proteoglycan content	0.05	0.05	-	0.05
					Proteoglycan sites	Film	Encapsulation	-	Outside the membrane
Purified water content	Balance of	Balance of	Balance of	Balance of

[ unit: mass% ]

Proteoglycans: nasal cartilage from salmon (manufactured by Heguang pure drug Co., Ltd.)

(1) Liposomal fluid 1

Liposome membrane components (lecithin and proteoglycan) were mixed in a water/ethanol mixed solvent (1/9 (volume ratio)), and then the solvent was removed by an evaporator to prepare a membrane. Purified water was added thereto, and shaking was performed to peel the membrane, thereby preparing a liposome solution containing proteoglycan in the membrane.

(2) Liposomal fluid 2

The liposome membrane component (lecithin) was mixed with a water/ethanol mixed solvent (1/9 (volume ratio)), and then the solvent was removed by an evaporator to prepare a membrane. An aqueous solution obtained by dissolving proteoglycan with purified water was added thereto, and the membrane was peeled off by shaking to prepare a proteoglycan-encapsulated liposome liquid.

(3) Lipid body fluid 3

The liposome membrane component (lecithin) was mixed with a water/ethanol mixed solvent (1/9 (volume ratio)), and then the solvent was removed by an evaporator to prepare a membrane. Purified water was added thereto, and the membrane was peeled off with shaking to prepare a proteoglycan-free liposome liquid 3.

(4) Lipid body fluid 4

The liposome membrane component (lecithin) was mixed with a water/ethanol mixed solvent (1/9 (volume ratio)), and then the solvent was removed by an evaporator to prepare a membrane. Purified water was added thereto, and the membrane was peeled off by shaking to prepare a liposome. In which proteoglycan is dissolved, and a liposome fluid 4 in which proteoglycan exists outside the liposome membrane is prepared.

< examples and comparative examples 1 to 4 >

Using the liposome fluids 1 to 4, lotions of examples and comparative examples 1 to 4 having compositions shown in table 2 below were prepared according to a conventional method.

[ TABLE 2 ]

[ unit: mass% ]

The lotions of examples and comparative examples 1 to 4 were evaluated.

< evaluation method >

10 examiners were randomly selected, and the application site was set on the inner side of the forearm, and the appropriate amount of test sample was applied twice in the morning and evening. The lifetime was set to 1 week.

The water content of the horny layer was measured by SKICON-200EX (manufactured by I.B.S.) which is a water content meter for the horny layer at the time of non-coating and 1 week after coating each evaluation sample. The increase/decrease ratio of the moisture content after coating was calculated assuming that the moisture content before coating was 100.

Note that a questionnaire is also checked for improvement in "skin tightness" using the following criteria.

The improvement is that: 1 point, no improvement: score 0, evaluated by sum of scores.

The evaluation results are shown in table 3.

[ TABLE 3 ]

From the results shown in table 3, it is understood that the lotions of the examples containing proteoglycan in the liposome membranes achieve both an increase in skin moisture content and an improvement in skin firmness feeling, as compared with comparative example 2 using the liposome fluid 3 containing no proteoglycan, comparative example 3 using the liposome fluid 4 containing proteoglycan outside the liposome membranes, and comparative example 4 containing no proteoglycan and liposomes.

It is found that the lotion of example 1 containing proteoglycan in the liposome membrane achieves both an increase in the moisture content of the skin and an improvement in the skin firmness feeling, in particular, as compared with the lotion of comparative example 1 in which proteoglycan is encapsulated in liposomes.

Claims (5)

1. A liposome, wherein the membrane of the liposome comprises proteoglycan.

2. A liposome fluid comprising the liposome of claim 1.

3. A cosmetic comprising the liposome according to claim 1.

4. Use of the liposome of claim 1 or the liposomal fluid of claim 2 for inclusion in a cosmetic product.

5. A method for producing a liposome, which is a method for producing a proteoglycan-containing liposome as a membrane of a liposome,

wherein the liposome is produced by bringing a film, which is formed by removing a solvent from a solution in which proteoglycan and lipid are dissolved or dispersed in the solvent, into contact with an aqueous solution or water.