JPH11130615A - Production of liposome dispersion and cosmetic using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a liposome dispersion excellent in feeling of use and further improved in effects of a dermal cell activator in spite of the dermal cell activator formulated therein at a high concentration in the liposome dispersion using a saturated phospholipid as a membrane lipid and to prepare a cosmetic containing the liposome dispersion obtained by the method for production and formulated therein. SOLUTION: This method for producing a liposome dispersion comprises formulating an ionic dermal cell activator in an amount of 0.1-10%, jetting a crude dispersion of he liposome as a single jet stream, changing the direction of the jet stream at an oppositely arranged base, allowing the jet stream to flow back along a sidewall so as to wrap the jet stream, thereby carrying out the microparticle forming treatment of the liposome crude dispersion with a shearing force produced in the interface between the jet stream and the backflow and providing about >=95% liposome having <=800 μm particle diameter in the liposome dispersion using a saturated phospholipid as a membrane lipid of the liposome.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a liposome dispersion and a cosmetic containing the liposome dispersion obtained by the production method. More specifically, the present invention uses a saturated phospholipid as a membrane lipid of the liposome. In the liposome dispersion, despite the fact that the compounding amount of the ionic skin cell activator is as high as 0.1 to 10%,
The present invention relates to a method for producing a liposome dispersion which is excellent in use feeling and further enhances the effect of a skin cell activator, and a cosmetic containing the liposome dispersion obtained by the production method.

[0002]

2. Description of the Related Art A liposome is a closed vesicle having a bilayer made of lipid and having an aqueous phase therein. Therefore, in the cosmetics field, the emollient effect of the lipid itself, the water retention effect of such a structure of the liposome, or the skin cell activator was retained in the inner aqueous phase of the liposome, between the bilayer membranes, or on the surface, and applied to the skin. With the expectation that the effect of the skin cell activator at that time will be enhanced, blending into cosmetics has been attempted.

[0003] On the other hand, phospholipids are mainly used as membrane lipids of liposomes, but since cosmetics are stored at room temperature for a long period of time, they are stable over time in color, smell and oxidation of lipids. Saturated phospholipids are commonly used. Production of liposome dispersions on an industrial scale is produced by preparing a crude liposome dispersion and treating it with a micronization device, for example, a Gaulin-type high-pressure homogenizer or an ultrasonic irradiation machine. ing.

[0004] However, the skin cell activator used as a raw material for cosmetics contains many ionic substances, and even if it is desired to obtain a liposome dispersion liquid containing the ionic substance at a high concentration, the liposome dispersion obtained by a conventional micronization apparatus can be used. Has a heavy use feeling and has a sticky feel, and therefore, when it is blended with cosmetics, the use feeling of the liposome dispersion tends to be affected.

Therefore, conventionally, when a liposome dispersion containing a high concentration of an ionic skin cell activator is added to a cosmetic, the liposome dispersion does not affect the feeling of use, which is an important factor of the cosmetic. The method is adopted.
However, in such a method, the feeling of use is improved, but the obtained cosmetic is hardly a compounding amount in which the effect of the skin cell activator can be expected.

[0006]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a liposome dispersion using a saturated phospholipid as a membrane lipid, even though an ionic skin cell activator is contained in a high concentration. It is an object of the present invention to provide a method for producing a liposome dispersion which is excellent in use feeling and further enhances the effect of a skin cell activator, and a cosmetic containing the liposome dispersion obtained by the production method.

The present inventors have conducted intensive studies to achieve the above object, and as a result, have completed the present invention. That is, the present invention provides (1) a liposome dispersion using a saturated phospholipid as a membrane lipid of a liposome, wherein the compounding amount of the ionic skin cell activator is 0.1 to 10%;
The coarse jet of the liposome is jetted as a single jet stream, the jet stream is turned at the oppositely located bottom surface, and the jet stream is counter-flowed along the side wall to envelop the jet stream. (2) a method for producing a liposome dispersion in which liposomes having a particle diameter of 800 nm or less are subjected to about 95% or more by subjecting the liposome coarse dispersion to micronization treatment by a shear force generated at an interface with the backflow;
About 95 liposomes having a particle size of 20 to 800 nm
% Of the liposome dispersion of (1),
(3) To provide a cosmetic containing a liposome dispersion obtained by the production method of (1) or (2).

[0008]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail.
In the present invention, all particle diameters are particle diameters in “number conversion”, and “%” is “number%”, but all others are “weight%”. In the present invention, "phospholipid"
The term “having two or more hydrophobic groups consisting of a phosphoric acid group, an acyl group and / or an alkyl group” in the molecule means, for example, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (P
S), phosphatidylinositol (PI), phosphatidylglycerol (PG), phosphatidic acid (P
A), sphingomyelin (SPM), cardiolipin, or a mixture of one or more of these derivatives, and the like.

In the present invention, "saturated phospholipid"
The term “phospholipid” refers to a phospholipid in which the acyl group and / or alkyl group, which is a hydrophobic group, is saturated. When the phospholipid is analyzed according to the “Iodine value measurement method” of the general test method of Cosmetic Group 2, it is 5 or less. Also included. Such phospholipids include, for example, dipalmitoyl phosphatidylcholine (D
PPC), egg yolk phospholipids, and plant-derived ones such as soybean phospholipids reduced by hydrogenation.

In the present invention, the term "ionic skin cell activator" refers to a cation such as sodium ion or potassium ion, an anion such as chloride ion, or the like in the molecule.
An ionic substance that has a carboxyl group and is transparently soluble in water by itself, and refers to a substance that activates skin cells, or a mixture thereof. Examples of such substances include sodium hyaluronate, sodium chondroitin sulfate, sodium pyrrolidone carboxylate, collagen, placenta extract, various amino acids and peptides and mixtures thereof, humectants such as α-hydroxy acids, ascorbic acid phosphate, and the like. Water-soluble vitamins such as esters (salts), ascorbic acid sulfates (salts), pyridoxine hydrochloride, pantothenic acid and its salts, anti-inflammatory agents such as lysozyme chloride, dipotassium glycyrrhizinate, citric acid, succinic acid,
Organic acids such as lactic acid and salts thereof are exemplified. still,
The ionic skin cell activator of the present invention does not include substances usually used as surfactants.

In the present invention, the amount of the ionic skin cell activator is such that the liposome dispersion obtained according to the present invention is used in a cosmetic, and the skin cell activator is retained in a high-concentration liposome. For this reason, the blending amount is 0.1% or more, and the blending amount is 10% or less in order to obtain a liposome dispersion liquid excellent in usability. Although it depends on the type of the skin cell activator, a liposome dispersion having a blending amount of 0.1 to 6% is particularly preferred because a liposome dispersion having an excellent feeling upon use is easily obtained.

In the present invention, "crude liposome dispersion"
The term "liposome dispersion" means a liposome dispersion before being subjected to micronization treatment, and the method for preparing the liposome dispersion is not particularly limited. Examples of the method include dispersing the activator in an aqueous solution and then heating the mixture to a phase transition temperature or higher, and dispersing a saturated phospholipid in an aqueous solution heated to a phase transition temperature or higher.

[0013] In the present invention, "a crude dispersion of liposomes is jetted as a single jet stream, the jet stream is turned at the bottom face opposed to the jet stream, and a backflow is applied along the side wall so as to wrap the jet stream. Thereby subjecting the crude liposome dispersion to micronization by the shearing force generated at the interface between the jet stream and the backflow. " E. FIG. E. FIG. This refers to treating a crude liposome dispersion with DeBEE2000 manufactured by International Ltd. or an apparatus equivalent thereto. Hereinafter, the principle of the formation of fine particles will be described with reference to FIGS. The crude liposome dispersion liquid 1 is jetted from a nozzle 2 as a single jet stream 3, the jet stream 3 is changed in direction at an opposed bottom surface 4, and a side wall 5 is wrapped around the jet stream 3.
, The shearing force generated at the interface 7 between the jet stream 3 and the back stream 6 causes the coarse dispersion of the liposome to be atomized.

In the present invention, "the liposome having a particle diameter of 800 nm or less is about 95% or more" means that the particle diameter of the liposome of the liposome dispersion of the present invention is determined by NICOMP manufactured by Pacific Scientific which is a commercially available particle size distribution analyzer.
When measured with Model370 or an equivalent device,
About 95% of liposomes having a particle size of 800 nm or less
The above is mentioned. In particular, a liposome having a particle diameter of 800 nm or less having a particle diameter of about 98% or more is more preferable because a liposome dispersion having a more excellent use feeling and a more effective skin cell activator can be obtained. It should be noted that liposomes having a particle size of less than 20 nm are difficult to produce on an industrial scale, including the production method of the present invention,
In the liposome of the present invention, about 95% or more of the liposome has a particle diameter of 20 to 800 nm. Moreover, since the liposome dispersion obtained by the production method of the present invention contains a high concentration of an ionic skin cell activator, it is difficult to obtain a dispersion having a liposome maximum particle diameter of 300 nm or less.

In the present invention, the "cosmetic" is not particularly limited as long as it is applied to the skin including the scalp and mucous membranes and has a continuous aqueous phase. , Cream and the like. Further, in the present invention, "cosmetics containing a liposome dispersion" means that the liposome dispersion is used as it is as a cosmetic, or is incorporated as a component of the cosmetic, and the amount of the liposome dispersion is particularly Although not limited, it is desirable to add a considerable amount of the skin cell activator usually contained in cosmetics because the effect of the skin cell activator is enhanced.
For example, in the case of ascorbic acid phosphoric acid ester salt used as a whitening agent, the amount is about 0.5 to 3%, and in the case of sodium hyaluronate used as a humectant, about 0.001%.相当 0.5% equivalent.

The liposome dispersion obtained by the production method of the present invention is not particularly limited. In addition to the ionic skin cell activator, components used in cosmetics, for example, vitamin A and its derivatives, vitamin B And its derivatives, ascorbic acid fatty acid esters, vitamins D, vitamin E
And derivatives thereof, vitamins such as nicotinamide, sorbitol, xylitol, moisturizing agents such as maltitol,
Glycerin, propylene glycol, polyhydric alcohols such as 1,3-butylene glycol, evening primrose, avocado oil, olive oil, mink oil, fatty acids, lysophospholipids, sphingolipids, squalene, fats and oils such as squalane, sterols and derivatives thereof, Thickeners such as polyvinyl alcohol and methyl cellulose, organic solvents such as ethanol, DN
A, RNA nucleic acids, antioxidants such as butylhydroxytoluene, pH adjusters, preservatives, anti-inflammatory agents, natural extracts,
Chelating agents, fragrances, dyes, and the like can be added.

The liposome dispersion obtained by the production method of the present invention is excellent in the usability for any reason and it is not known whether the effect of the skin cell activator can be enhanced. It is presumed that by controlling the particle size to a certain level or less, the affinity with the skin was improved and such an effect was produced.

Hereinafter, a typical production method of the present invention will be described, but it is not particularly limited to this production method. Preparation of a crude dispersion of liposomes A saturated phospholipid is added to an aqueous solution of an ionic skin cell activator heated above a phase transition temperature and dispersed using a stirrer such as a homomixer, or a saturated phospholipid is added. Is added to an aqueous solution of an ionic skin cell activator, dispersed using a stirrer such as a homomixer, and then heated to a phase transition temperature or higher. In addition, when it is desired to obtain a liposome dispersion in which other components are also held in liposomes, and when the other components are water-soluble components, an aqueous solution dissolved together with an ionic skin cell activator should be used as a liposome solvent. Or, even if it is a water-soluble component such as a polyhydric alcohol,
A component that dissolves a saturated phospholipid is obtained by adding a solution in which a saturated phospholipid is dissolved with the component to an aqueous solution of an ionic skin cell activator, and preparing a crude liposome dispersion by the above method. Good. In addition, when the other component is a fat-soluble component, the component is dissolved in an organic solvent together with a saturated phospholipid, and then the solvent is removed and added to an aqueous solution of an ionic skin cell activator. When a crude liposome dispersion is prepared by the above method, or when a component that dissolves a saturated phospholipid and a fat-soluble component such as a polyhydric alcohol is used as an organic solvent, a saturated phospholipid and A solution in which a soluble component is dissolved with the component may be added to an aqueous solution of an ionic skin cell activator, and a crude liposome dispersion may be prepared by the above method. The phase transition temperature of the saturated phospholipid is determined in advance by a differential scanning calorimeter (DS
Measure in C).

Of the liposome dispersion by the micronization treatment
Preparation A coarse dispersion of the above liposome is micronized using the micronization principle of the present invention, for example, a commercially available DeBE
Process at a pressure of 25000 psi or more using E2000,
Liposomes having a particle size of 800 nm or less are 95% or more.

Next, the present invention will be described based on Examples and Test Examples.
This will be described in more detail. The particle size was measured under the following conditions. Particle size distribution analyzer: NICOMP Model370 (Pacific Sc
Measurement mode: Solid Particles (in terms of number) Integration time: 10 minutes or more Residual: 2.0 or less In addition, the feeling of use of liposome dispersions or cosmetics containing them and the effect of ionic skin cell activators Was evaluated by 20 female panels. Whether or not the effect of the ionic skin cell activator was enhanced was evaluated by performing a use test for one month and comparing with the case where the liposome was not formed.

Example 1 Preparation of crude liposome dispersion Hydrogenated egg yolk phospholipid (IV = 4, lipid composition: PC = 8)
(5%, PE = 12%, SPM = 1%, LPC = 1%, other = 1%) 10 g is dissolved in 50 g of propylene glycol heated to about 75 ° C. On the other hand, methyl paraben 1
g and 1 g of sodium hyaluronate in 940 g of purified water were heated to about 75 ° C., and the above solution was gradually added thereto with stirring at 10,000 rpm using a homomixer (TK homomixer: TK homomixer). The mixture was stirred for 10 minutes to prepare a crude liposome dispersion. Preparation of liposome dispersion by micronization treatment The crude liposome dispersion was subjected to micronization treatment once using DeBEE2000 at a pressure of 35,000 psi.
A liposome dispersion containing about 98% of liposomes having a particle size of 00 nm or less was obtained.

Example 2 Preparation of crude liposome dispersion Hydrogenated egg yolk phospholipid (IV = 4, lipid composition: PC = 8)
(5%, PE = 12%, SPM = 1%, LPC = 1%, other = 1%) 10 g is dissolved in 50 g of propylene glycol heated to about 75 ° C. On the other hand, methyl paraben 1
g and 20 g of ascorbyl magnesium phosphate were dissolved in 940 g of purified water, heated to about 75 ° C., and mixed with a homomixer (TK homomixer: TK homomixer) by 10,000.
The above solution was gradually added while stirring at rpm, and further stirred for 10 minutes to prepare a crude liposome dispersion. Preparation of liposome dispersion by micronization treatment The crude liposome dispersion was subjected to micronization treatment once using DeBEE2000 at a pressure of 35,000 psi.
A liposome dispersion containing about 99% of liposomes having a particle size of 00 nm or less was obtained.

Example 3 Preparation of Crude Liposomal Dispersion 980 g of purified water in which 1 g of methyl paraben and 20 g of magnesium ascorbyl phosphate were dissolved was heated to about 75 ° C., and a homomixer (Tokuho Kika Kogyo: TK homomixer) was used.
And hydrogenated egg yolk phospholipids (IV = 1, lipid composition: PC = 88%, PE =
(10%, SPM = 0.5%, LPC = 0.5%, others = 1%) 20 g was gradually added, and the mixture was further stirred for 10 minutes to prepare a crude liposome dispersion. Preparation of Liposomal Dispersion by Micronization Treatment The crude liposome dispersion was subjected to micronization treatment twice using DeBEE2000 at a pressure of 40,000 psi.
A liposome dispersion containing about 99% of liposomes having a particle size of 00 nm or less was obtained. Almost all panelists of the obtained liposome dispersion liquid were evaluated as having a good feeling in use, and that the effect of improving skin whitening by magnesium ascorbyl phosphate was higher than that in the case of not forming liposomes.

Example 4 The following emulsion was prepared by a conventional method. The liposome dispersion was added when the product temperature was about 50 ° C. during the cooling after emulsification in the emulsion preparation step. Emulsion Liposomal dispersion of Example 1 10.0 Stearic acid 1.0 Cetanol 2.0 Vaseline 2.5 Squalane 4.0 L-Arginine 1.0 Lipophilic glyceryl monostearate 1.0 Glycerin 2.0 Hydroxide Potassium 0.1 Perfume A trace amount 100.0% of the emulsion obtained with purified water was evaluated by most panelists as having a good feeling in use and increasing the moisture of the skin as compared with the case without liposome formation. Was.

[0024]

Test Example 1 In the subsequent micronization treatment using the liposome crude dispersion of Example 2, the ratio of the liposome having a particle diameter of 800 nm or less is shown in Table 1 by changing the treatment pressure, the number of treatments and the atomization device. The indicated liposome dispersions were prepared and evaluated.

[0025]

[Table 1]

The test results are shown in Table 1. A liposome prepared according to the microparticle principle of the present invention and having a particle size of 800 nm or less has 95% or more of the product of the present invention. Control Nos. 1 to 6 were prepared according to the micronization principle of the present invention and had less than 95% of liposomes having a particle diameter of 800 nm or less. 1,
No. 2 and control product No. 2 prepared by a conventional micronization device. 3,
Compared to 4, most panelists evaluated that the usability was good or slightly good. Also, in the lotion using the obtained liposome dispersion liquid, the effect of improving skin whitening by ascorbyl magnesium phosphate is higher or slightly higher than in the case where most panelers do not form liposomes. Was evaluated. Than this,
The liposome dispersion obtained in the present invention is excellent in use feeling,
It can be understood that the effect of the skin cell activator is further enhanced. In particular, it is prepared according to the micronization principle of the present invention and
The liposome having a particle size of not more than 98% of the present product No. Nos. 4 to 6 were evaluated by most panelists as having a good feeling in use, and also in the lotion, more than half of the panelers evaluated that the whitening improving effect was high.

Test Example 2 A liposome dispersion was prepared in the same manner as in Example 2 except that the amount of ascorbyl magnesium phosphate was changed variously, and the feeling under use was evaluated. The liposome dispersion of Example 1 was used as it was.

[0028]

[Table 2]

Table 2 shows the test results. When the amount of the ionic skin cell activator in the liposome dispersion liquid exceeds 10%, the control product No. 5 was less than 95% of liposomes having a particle diameter of 800 nm or less, and most of the panelists were evaluated that the feeling of use was poor or somewhat poor, whereas the amount of the skin cell activator was 10% or less. Of the present invention N
o. In Nos. 7 to 12, 95% or more of the liposomes having a particle size of 800 nm or less were evaluated by most of the panelists as having a good or moderate feeling of use, and in particular, the content of the skin cell activator was 6% or less. Of the present invention No. 7-10
Was evaluated as having a good feeling of use. Thus, even with the micronization principle of the present invention, a liposome dispersion in which the blending amount of the ionic skin cell activator exceeds 10% makes it difficult to obtain a good feeling in use, and the blending amount is 6% or less. It is understood that those having good usability are relatively easy to obtain.

[0030]

As described above, a liposome dispersion which is excellent in usability and cannot be obtained by the conventional production method and further enhances the effect of the ionic skin cell activator can be obtained by the production method of the present invention. Therefore, in the cosmetics field,
Further expansion of the application is expected.

[0031]

[Brief description of the drawings]

FIG. 1 is a side sectional view for explaining the principle of forming fine particles of the present invention.

FIG. 2 is a cross-sectional view taken along the line AA of FIG.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Crude liposome dispersion 2 Nozzle 3 Jet flow 4 Bottom surface 5 Side wall 6 Reverse flow 7 Interface

Claims (3)

[Claims] In a liposome dispersion using a saturated phospholipid as a membrane lipid of a liposome, the blending amount of an ionic skin cell activator is 0.1 to 10%, and a crude dispersion of the liposome is simply used. Injected as one jet stream, the jet stream is turned at the bottom surface located opposite,
By causing the jet flow to flow back along the side wall so as to wrap the jet flow, the coarse dispersion of the liposome is subjected to micronization by the shearing force generated at the interface between the jet flow and the reverse flow.
A method for producing a liposome dispersion, wherein the content of liposomes having a particle size of 00 nm or less is about 95% or more. 2. The method for producing a liposome dispersion according to claim 1, wherein the liposome having a particle diameter of 20 to 800 nm accounts for about 95% or more. 3. A cosmetic comprising a liposome dispersion obtained by the production method according to claim 1 or 2.