JP2008266324A - Liposome composition and external preparation for skin containing liposome composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liposome composition which has encapsulation of a platinum group metal colloid, thereby expresses lipid peroxide-depressing effect, each of which originally has, further effectively. <P>SOLUTION: The liposome composition contains the following components (a)-(c): (a) phospholipid; (b) one or two kinds selected from cholesterol and/or phytosterol; and (c) the platinum group metal colloid; and (d) water, and has encapsulation of the component (c) into the liposome formed of the component (a) and the component (b). <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a liposome composition, and more particularly, to a liposome composition encapsulating a white metal metal colloid and a skin external preparation containing the liposome composition. Furthermore, the present invention relates to a method for suppressing lipid peroxide using the liposome composition.

  Various preparations having high added value are being actively developed by incorporating various medicinal and cosmetic ingredients into cosmetics and other external preparations for skin. Among these, ingredients having an antioxidative function are expected to have an effect of preventing skin aging and have many applications. Certain colloidal metal colloids including platinum colloid are known to have an antioxidant effect, and many cosmetics containing platinum colloid have been developed (see, for example, Patent Document 1).

Phospholipids are not only used as emulsifiers, but are also attracting attention as liposome bases for drug delivery, artificial blood, artificial cells, and the like. In addition, since phospholipids themselves have physiological activity and pharmacological action, their use in pharmaceuticals, health foods, food additives, cosmetics, etc. has been studied and widely used. There is also a technique that has been studied by improving the antioxidant properties of phospholipids that are widely used in this way (see, for example, Patent Document 2).
JP 2001-122723 A JP 09-110888 A

  However, in the technique of Patent Document 1, it is important that an electric double layer is formed in the skin. When an oily component is used as the base, the oil envelops the platinum colloid, and the electric colloid produced by the platinum colloid. In some cases, the negative electrode effect due to the multilayer structure may not be sufficiently exhibited. Therefore, it was necessary to develop a preparation containing a platinum group metal colloid that can sufficiently exert the lipid peroxide inhibitory effect on the above-mentioned external preparation for skin. In the technique of Patent Document 2. Although the phospholipid itself has antioxidant properties, it may not be fully exhibited.

Accordingly, an object of the present invention is to develop a composition that more effectively expresses the antioxidant ability of a white metal metal colloid, and to develop a preparation that can be used as a skin external preparation.

In view of this situation, as a result of intensive studies to solve the above problems, the present inventors have encapsulated a white metal metal colloid in a liposome formed by one or two types selected from phospholipid and cholesterol and / or phytosterol. By preparing the liposome composition, it was found that the antioxidant effect of the white metal metal colloid becomes more remarkable, and the present invention has been completed.

That is, the present invention provides the following components (a) to (d);
(A) Phospholipid (b) One or two kinds selected from cholesterol and / or phytosterol (c) Platinum group metal colloid (d) Water is contained, and component (c) comprises component (a) and component (b) The present invention provides a liposome composition characterized by being encapsulated in liposomes formed by the above.

In addition, the present invention provides the above-described liposome composition, wherein the component (c) is a platinum colloid.

  Furthermore, the present invention provides a skin external preparation characterized by containing the above-mentioned liposome composition.

  Furthermore, the present invention provides a method for inhibiting lipid peroxide, characterized by using the above-mentioned liposome composition.

The liposome composition of the present invention can effectively exhibit the lipid peroxide inhibiting effect inherent in each of the liposome compositions by encapsulating the platinum group metal colloid.

  The phospholipid of component (a) contained in the present invention is an essential component as a constituent component of the liposome. Examples of the component (a) include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, sphingophospholipid and the like. Examples include lecithin or hydrogenated products thereof. Preferred are phosphatidylcholine and phosphatidylinositol, and particularly preferred is phosphatidylcholine. In the present invention, the above phospholipids can be used singly or in combination.

Although content of the component (a) contained in this invention is not specifically limited, 0.005-10 mass% (henceforth "%" only) is preferable. If it is this range, the temporal stability of a liposome composition can be made more favorable.

The component (b) cholesterol and / or phytosterol contained in the present invention is contained as a membrane stabilizer for liposomes.

  Although content of the component (b) contained in this invention is determined suitably according to the component (a) to be contained, it is generally 0.001 to 3%. Within this range, the white metal metal colloid can be stably encapsulated in the liposome.

The platinum group metal colloid of component (c) contained in the present invention refers to a state in which platinum group metal particles are dispersed in a liquid phase, and the platinum group metal includes ruthenium, osmium, rhodium, iridium, It is a generic name for transition metals consisting of palladium and platinum. In the present invention, among these, rhodium and platinum are preferable, and platinum is most preferable. The platinum group metal colloid of the component (c) of the present invention may be a kind of metal colloid selected from platinum group metals or a colloid of two or more kinds of metals. Metal species colloids are preferred, and platinum or rhodium colloids are preferred.

  In order to bring the platinum group metal into a stable colloidal state, the metal particles preferably have a large specific surface area and excellent surface reactivity. The average particle size of the platinum group metal particles is not particularly limited as long as it can be made into a colloidal state, but is preferably a nano unit. Specifically, the average particle diameter is preferably 1 to 5 nm, more preferably 1 to 3 nm, and particularly preferably 1.5 to 2.5 nm. The particle size distribution of the particles is preferably narrow. Specifically, the particle size of 90% by number or more of colloidal particles preferably falls within the range of 0.1 to 10 nm, and falls within the range of 1 to 3 nm. Is more preferable. The average particle size of the colloidal particles can be determined by observing with a transmission electron microscope.

  The main component of the liquid phase in which the platinum group metal particles are dispersed is preferably water, and may contain an organic solvent as long as the colloidal state is not destabilized. Examples of the organic solvent include alcohols such as methanol and ethyl alcohol; polyhydric alcohols such as glycerin, diglycerin, 1,3-butylene glycol and dipropylene glycol.

  In general, various methods for producing metal colloids or metal particles are known (for example, JP-B-57-43125, JP-A-59-120249, JP-A-9-225317, JP-A-10-176207). JP, 2001-79382, JP, 2001-122723, etc.) and those skilled in the art can easily prepare by referring to these methods. For example, a chemical method called a precipitation method or a metal salt reduction reaction method, or a physical method called a combustion method can be used. In the present invention, metal colloids and metal particles prepared by any method may be used, but metal colloids prepared by a metal salt reduction reaction method are used from the viewpoint of ease of production and quality, or the above-mentioned method. It is preferable to prepare and use the metal particles obtained by the above method as a colloid.

  In the metal salt reduction reaction method, for example, an aqueous solution or organic solvent solution of a water-soluble or organic solvent-soluble metal salt or metal complex is prepared, and after adding a water-soluble polymer to this solution, the pH is adjusted as necessary. The metal particles can be obtained by reduction by heating under reflux in an inert atmosphere. The type of the water-soluble or organic solvent-soluble salt of the metal is not particularly limited. For example, acetate, chloride, sulfate, nitrate, sulfonate, or phosphate can be used. It may be used.

  The type of water-soluble polymer used in the metal salt reduction reaction method is not particularly limited. For example, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylate, cyclodextrin, amylopectin, or methylcellulose can be used, and two of these can be used. A combination of the above may also be used. Preferably, polyvinylpyrrolidone and polyacrylate can be used, and more preferably, polyacrylate can be used. Further, various surfactants such as anionic, cationic, amphoteric or nonionic surfactants can be used instead of or together with the water-soluble polymer. When the reduction is performed using alcohol or glycol, ethyl alcohol, n-propyl alcohol, n-butyl alcohol, n-amyl alcohol, ethylene glycol or the like is used. These water-soluble polymers and surfactants are coordinated to platinum group metals after the formation of metal particles in the liquid phase, improving the solvophilicity of the metals, and in colloidal state as protective colloid agents. Contributes to stabilization.

  The metal particles generated in the liquid phase by the metal salt reduction reaction method may be used for the preparation of a skin external preparation such as cosmetics without being separated from the liquid phase as it is. For example, metal particles are produced in the liquid phase by a metal salt reduction reaction method, and if necessary, an appropriate purification step (for example, a step of distilling off the organic solvent used in the step of the metal salt reduction reaction method). Thereafter, by adding an arbitrary amount of water or removing an arbitrary amount of water, it is possible to prepare a whitening agent, a skin external preparation or the like comprising a stable colloid. If desired, surfactants, dispersants and the like that contribute to stabilization of the colloidal state may be added.

  The content of the platinum group metal colloid of the component (c) in the liposome composition of the present invention varies depending on the purpose of use and the like, but generally, the concentration of the platinum group metal is preferably 0. 1 nmol / L to 1 mmol / L, more preferably 10 nmol / L to 10 μmol / L. Within this range, the colloid can be blended stably and an excellent effect can be exhibited.

  The liposome composition of the present invention contains water as component (d). This is essential to form and disperse the liposome composition. As such water, purified water, hot spring water, plant-derived steam distilled water such as rose water and lavender water can be used. You may use 1 type, or 2 or more types from these.

As a method for producing the liposome composition of the present invention, various generally known methods can be used. Specific examples include the bangham method, pH gradient method, freeze-thaw method, reverse phase evaporation method, mechanochemical method, supercritical carbon dioxide method, film loading method and the like.

In addition to the above essential components, the liposome composition of the present invention generally includes components commonly used in cosmetics, such as water-soluble components, humectants, oils, surfactants, thickeners, powders, pigments, UV absorption Amounts that do not impair the effects of the present invention for ingredients used in normal skin external preparations such as agents, film-forming agents, pH adjusters, anti-fading agents, antioxidants, antifoaming agents, cosmetic ingredients, preservatives, and fragrances It can mix | blend suitably in a qualitative range. These components can be contained in the liposome composition, but can also be blended as components of a skin external preparation described later.

  The use of the liposome composition of the present invention can be used as the skin external preparation of the present invention as it is, but the present liposome composition is preferably used in the range of 0.1 to 90% by mass, It is also possible to formulate other ingredients into the external preparation for skin. In particular, it is possible to obtain excellent effects in skin care cosmetics and hair cosmetics.

  The use of the skin external preparation of the present invention can be exemplified by skin care cosmetics such as lotion, milky lotion, cream, cosmetic liquid, body cosmetics, packs, massages, etc., and cosmetic base cosmetics. Examples of the method include a method of using hands or cotton, a method of impregnating a nonwoven fabric, and the like.

  The method for inhibiting lipid peroxide using the liposome composition of the present invention has an effect superior to the effect of inhibiting lipid peroxide using only a platinum metal colloid. Liposomes are also expected to have various effects. For example, “New development of liposome application: Toward the development of artificial cells” (supervised by Kazunari Akiyoshi / Satoshi Sakurai, published in 2005, NT Corporation) -The sustained release effect described in S, p644-p650) can also be expected, and is useful as an external preparation for skin.

  In the method for producing an external preparation for skin of the present invention, after preparing a liposome composition in advance, it can be combined with other components to prepare an external preparation for skin. Is also possible.

  As a method for confirming that the colloidal platinum was encapsulated in the liposome composition of the present invention, a transmission electron microscope (JEM-1200EXII) manufactured by JEOL Ltd. was used from a microscope observation photograph.

The thiobarbitur method was used as a method for measuring the amount of lipid peroxide of the present invention.

  EXAMPLES Hereinafter, although a manufacture example and an Example are given and this invention is demonstrated further more concretely, the scope of the present invention is not limited to these.

[Production Example 1: Preparation of platinum colloid]
Poly (sodium polyacrylate) (0.31 g manufactured by Aldrich Co.) was placed in a 100 mL two-necked eggplant type flask connected with an Allen cooler and a three-way cock, and dissolved in 23 mL of distilled water. This solution was stirred for 10 minutes, in addition chloroplatinic acid _{(H 2 PtCl 6 · 6H 2} O, Wako Pure Chemical Industries, Ltd.) 1.66 × ^{10 -2} M solution dissolved in distilled water to a (2 mL) Stir for 30 minutes. The reaction system was purged with nitrogen, 25 mL of special grade ethanol was added, and the mixture was refluxed at 100 ° C. for 2 hours while maintaining a nitrogen atmosphere. The UV-visible light absorption spectrum of the reaction solution was measured to confirm the disappearance of the platinum ion peak and the saturation of the peak due to the scattering characteristic of the metal solid, and the reduction reaction was completed. The organic solvent was distilled off under reduced pressure to prepare a platinum colloid liquid (average particle size 2.4 ± 0.7 nm). The platinum concentration of the obtained platinum colloid was 1 mmol / L.

A liposome composition was prepared by the formulation shown in Table 1 and the production method described below, and stored for 2 weeks at a constant temperature of 25 ° C. as a sample. The lipid peroxide inhibitory effect of platinum colloids encapsulated in liposomes was evaluated by the following evaluation method. The results are also shown in Table 1.

(Manufacturing method): Invention products 1 to 4, comparative products 1 and 2
A: Components (1) to (8) are heated to 70 ° C.
B: Component (9) is heated to 70 ° C.
C: Add B to A and disperse with a disperser mixer.
D: C was cooled to room temperature to obtain a liposome composition.

(Manufacturing method): Comparative product 3
A: Components (2) to (8) are heated to 70 ° C.
B: Component (9) is heated to 70 ° C.
C: Add B to A and disperse with a disperser mixer.
D: C was cooled to room temperature to obtain a liposome composition.
E: Component (1) was added to D and dispersed with a disperser mixer.

<Confirmation of platinum colloid encapsulated in liposome composition>
(Test method)
Whether or not platinum colloid was encapsulated in the liposome composition obtained above was confirmed by a transmission electron microscope. If platinum colloid is encapsulated in the liposome, a black shadow is observed between the membranes having a lamellar structure. Table 1 also shows the presence or absence of platinum colloid inclusion in the liposome composition from the transmission electron micrograph. As a representative, a transmission electron micrograph of the product 1 of the present invention is shown in FIG.

  In FIG. 1, it was confirmed that the platinum colloid was encapsulated in the liposome composition containing phospholipid and cholesterol. The black shaded portion in the photographic liposome is platinum colloid.

<Patium colloid lipid peroxide inhibitory effect test>
(Test method)
Evaluation was performed by having 10 female panel members in their 20s and 40s use each sample shown in Table 1 every morning and evening for 2 weeks and measuring the amount of lipid peroxide by the following method.

(1) 15 ml of an acetone / ether mixed solution was weighed into a cylindrical bottle having a diameter of 3 cm.
(2) The bottle mouth of (1) was immersed inside the forearm of the female panel, and lipid was extracted.
(3) Of the lipids extracted in (2), use the thiobarbitur method for the amount of lipid peroxide (quantified as the amount of malondialdehyde reacted with thiobarbituric acid under hydrochloric acid acidity). Measured.
(4) The amount of lipid peroxide when nothing is applied in the measurement on the same panel is P 2 _O , the amount of lipid peroxide when the present product 1 is applied is Ps, and the lipid peroxide reduction rate (%) is It calculated | required by the following formula (A).
Peroxide reduction rate (%) = (P _O −Ps) / P _O (A)

(Evaluation criteria for lipid peroxide reduction rate)
Lipid peroxide reduction rate 5.5% or more: ○
Lipid peroxide reduction rate of 3% or more and less than 5.5%: Δ
Lipid peroxide reduction rate <3%: ×

As is clear from the results in Table 1, the inventive products 1 to 4 have a higher rate of lipid peroxide reduction than the comparative products, and the liposome composition encapsulating platinum colloid suppresses lipid peroxide more effectively. It was proved. In contrast, Comparative Product 1 that did not contain platinum colloid and Comparative Product 2 that did not contain phospholipid had a small reduction rate of lipid peroxide. Further, the comparison product 3 containing platinum colloids separately without encapsulating them in liposomes also had a lower rate of lipid peroxide reduction than the product of the present invention.

Liposome composition-containing external preparation for skin (skin lotion)
(Ingredient) (%)
(1) Invention product 1 40 manufactured in Example 1
(2) Sorbitol 5
(3) Sodium pyrrolidonecarboxylate 0.5
(4) Polyoxyethylene (60) hydrogenated castor oil 0.1
(5) Fragrance 0.05
(6) Ethanol 5
(7) Purified water 49.35

(Manufacturing method)
A: The product 1 of the present invention is prepared in advance according to the above description.
B: Components (2) to (6) are mixed and dissolved, and then added to and mixed with component (7) while stirring.
C: A is mixed with B while stirring with a disper mixer.
D: C was filtered to obtain a lotion.

The lotion of Example 2 was a lotion excellent in the lipid peroxide inhibitory effect.

Liposome composition-containing external preparation for skin (beauty liquid)
(Ingredient) (%)
(1) 1,3-butylene glycol 5.0
(2) Xanthan gum 0.1
(3) Purified water 40.0
(4) Invention product 2 produced in Example 1 1.0
(5) Sorbitan sesquioleate 0.2
(6) Ethanol 5.0
(7) Sodium lactate 0.5
(8) Disodium edetate 0.2
(9) Polyoxyethylene (60) hydrogenated castor oil 0.5
(10) Methyl paraoxybenzoate 0.2
(11) Glycerin 10.0
(12) Purified water remaining amount (13) Perfume appropriate amount

(Manufacturing method)
A: The product 2 of the present invention is prepared in advance according to the above description.
B: Ingredients (1) to (3) are heated to 70 ° C. and mixed.
C: Cool B to room temperature.
D: Stir and mix components (5) to (11) and (13).
E: C and D were mixed with component (12) while stirring with a disper mixer, and component (4) was further mixed to obtain a cosmetic liquid.

The essence of Example 3 was an essence excellent in lipid peroxide inhibiting effect.

Liposome composition-containing external preparation for skin (milky lotion)
(Ingredient) (%)
(1) Squalane 3.0
(2) Dimethylpolysiloxane (20 mm ² / m) 1.0
(3) Polyoxyethylene (60) hydrogenated castor oil 1.5
(4) Cetostearyl alcohol 0.3
(5) Invention product 1 manufactured in Example 1 15.0
(6) Dipropylene glycol 7.0
(7) Glycerin 5.0
(8) Acrylic acid-alkyl methacrylate copolymer (Note 2) 0.1
(9) Preservative appropriate amount (10) Sodium hydroxide 0.03
(11) Edetate disodium 0.02
(12) Purified water Remaining amount (13) Fragrance Appropriate amount (Note 2) Pemulen TR-2 (manufactured by NOVEON)

(Production method)
A: Components (1) to (4) were heated and mixed at 70 ° C.
B: Components (6) to (12) were heated and mixed at 70 ° C.
C: A and B were mixed while being stirred with a disper mixer, then cooled to room temperature, and components (5) and (13) were added and mixed to obtain an emulsion.

  The milky lotion of Example 4 was a milky lotion excellent in lipid peroxide inhibiting effect.

Lipid composition-containing external preparation for skin (cream)
(Ingredient) (%)
(1) Stearic acid 1.5
(2) cetostearyl alcohol 3.0
(3) Glyceryl monostearate 1.5
(4) Squalane 20.0
(5) Vaseline 5.0
(6) Glycerin 7.0
(7) 1,3-butylene glycol 5.0
(8) Invention product 1 manufactured in Example 1 30.0
(9) Sodium lactate 1.0
(10) Xanthan gum 0.05
(11) Preservative appropriate amount (12) Sodium hydroxide 0.05
(13) Edetate disodium 0.02
(14) Purified water remaining amount (15) Perfume appropriate amount

(Production method)
A: Components (1) to (5) were heated and mixed at 70 ° C.
B: Components (6), (7) and (9) to (14) were heated and mixed at 70 ° C.
C: After mixing B with A with stirring with a disper mixer, the mixture was cooled to room temperature, and components (8) and (15) were added and mixed to obtain a cream.

The cosmetic liquid of Example 5 was a cream excellent in lipid peroxide inhibiting effect.

Photo of transmission electron microscope of product 1 of the present invention, which is a liposome encapsulating platinum colloid

Claims (4)

The following components (a) to (d);
(A) phospholipid (b) cholesterol and / or phytosterol (c) platinum group metal colloid (d) water is contained, and component (c) is encapsulated in liposomes formed by component (a) and component (b) Liposome composition characterized by being made. The liposome composition according to claim 1, wherein the component (c) is a platinum colloid.   An external preparation for skin comprising the liposome composition according to claim 1 or 2.   A method for inhibiting lipid peroxide, wherein the liposome composition according to claim 1 or 2 is used.