JPH0567605B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing a cosmetic containing a liposomal bioactive substance obtained by forming a bioactive substance into liposomes using phospholipids.

[Prior Art] Generally, biological membranes are formed by physical or chemical association of proteins, lipids, sugars, etc.
Their basic structure is a lipid bilayer membrane.

Regardless of their chemical composition, single or multiple rectangular or oval compartments surrounded by a double structure are called vesicles, and vesicles composed of natural or synthetic phospholipids are called liposomes (vesicles). liposome) {JHFendler, Membrane mimetic chemistry,
John Wiley & Sons Inc., p113, NY (1982)}.

Since Muller, P. et al. discovered that a double membrane is naturally formed in an aqueous lipid solution {Nature 194979 (1962)}, liposomes have been applied to drug delivery systems and cosmetics in biomembrane research. .

In particular, the application of liposomes in cosmetics makes it possible to more efficiently absorb bioactive substances that are difficult to absorb through the skin. This fact is proven by the attempts shown in the following documents. WSOliniacz,
U.S. Patent No. 3957971 (1976); Handjani-vila
et al., J. Cosmetics Sci. 1, 303 (1979); G.
Redziniak et al., Preprint of the 16th IFSCC
Cong ress 1, 299 (1986).

Liposomes have excellent affinity for skin cells because they are composed of phospholipids that are similar in structure to living cells and can also encapsulate water-soluble components. Therefore, by using liposomes, absorption into skin cells is efficiently improved.

Liposomes are mainly made from soybean or egg yolk lecithin by mechanical force, surfactant dialysis method (detergent
dialysis), solvent injection or reverse-phase evaporation
It can be manufactured by a method such as {G.
Gregoriadis, Liposome Technology Vol.1,
p250−252, CRC Press Inc., Boca Raton,
Florida (1984)}.

Mechanical force production of liposomes involves depositing a thin lipid film on the walls of the container from an organic solvent medium or by spray drying (Redziniak et al., U.S. Pat. No. 4,508,703 (1985)) followed by encapsulation. A lipid powder is obtained by stirring together with an aqueous solution of the desired substance. The liposomes thus obtained can be easily broken down into single, small unilamellar vesicles by ultrasonic disruption.
It is a multilamellar vesicle liposome that can be converted into a multilamellar vesicle liposome.

In addition, in the surfactant dialysis method, phospholipids and surfactants are first dispersed in an aqueous solution of the substance to be encapsulated to form mixed micelles, and then the mixed micelle dispersion is spread over a wide area. After dialysis and gradual removal of the surfactant, the phospholipids form small unilamellar vesicular structures (SUV structures).

Furthermore, the solvent injection method is a method in which an organic solution of lipid is injected into an aqueous solution at a sufficiently high temperature to quickly evaporate the solvent.

Furthermore, in the reverse phase evaporation method, a small amount of the aqueous solution to be filled into the capsule is first dispersed in a volatile organic solvent containing a lipid mixture, and then the solvent is evaporated under reduced pressure to obtain a water-in-oil ( W/O) emulsion becomes a liposome solution.

Ultimately, these various methods form a lipid bilayer membrane by dispersing lipids in an aqueous solution, and the size, encapsulation efficiency, and stability of the liposomes depend on the manufacturing method. Therefore, these manufacturing methods are appropriately selected depending on the purpose, use, and characteristics of the product.

By the way, in cosmetics technology, methods using mechanical force are widely used because they are simple.

Liposomes are used in cosmetics because they efficiently deliver water-soluble active substances to cells, strengthen the fluidity of cell membranes, and activate metabolism.

Despite the ease of manufacturing liposomes,
There are many difficulties in the application of liposomes due to stability issues in cosmetics.

Oil-soluble ingredients such as fragrances and oil-soluble vitamins are used in cosmetics as well as water-soluble ingredients.
Surfactants must be used to emulsify or dissolve these oil-soluble components. However, these surfactants reduce the stability of liposomes. Therefore, long-term stabilization of liposomes in cosmetics is extremely important in order to obtain the beneficial effects of liposome use.

[Problems to be Solved by the Invention] Therefore, an object of the present invention is to incorporate liposomes into cosmetics in a stable state, thereby creating cosmetics that can exhibit the effects of using liposomes over a long period of time. The purpose is to provide a manufacturing method.

[Means for Solving the Problems] That is, the present invention uses phospholipids to form bioactive substances into liposomes, and also uses the same phospholipids used to form liposomes from the bioactive substances to form oils. A method for producing cosmetics containing liposomes, in which a soluble substance is finely emulsified, the resulting two liquids are mixed, and then a water-soluble or water-dispersible polymeric thickener is added thereto and mixed uniformly. be.

In the present invention, bioactive substances that can be used in cosmetics include placenta extract protein, thymic peptide, fibronectin solution, sodium hyaluronate, hydrolyzed elastin, rosemary extract,
Examples include one or a mixture of two or more selected from various animal and plant extracts and derivatives thereof, such as Camille extract, ivy extract, and witch hazel extract.

Such bioactive substances are
Phospholipids were added at a rate of ~50% and kept at room temperature (20) ~
Strong mechanical force is applied by mixing or ultrasonic crushing at a temperature of 80°C to form liposomes,
It becomes a liquid of liposomal biological substances. The phospholipids used for this purpose include those conventionally known, but preferably selected from soybean phospholipids, brain phospholipids, egg yolk phospholipids, hydrogenated soy phospholipids, and hydrogenated egg yolk phospholipids. It is preferable to use one kind or a mixture of two or more kinds. The liposome particles produced at this time have a size of about 30 to 300 nm.

Next, the oil-soluble substances to be incorporated into cosmetics include conventionally known ones, but preferably one or two such as fragrances, oil-soluble vitamins, oil-soluble natural (animal and plant) extracts, etc. Mixtures of the above may be mentioned. These oil-soluble substances are prepared by adding phospholipids at a ratio of 10 to 500% of the amount and applying strong mixing or ultrasonic waves at a temperature of 40 to 80 degrees Celsius. The result is an oil-soluble substance emulsion in which particulate oil droplets are uniformly dispersed. The phospholipid used for this purpose is the same as that used to form the bioactive substance into liposomes. The size of the oil droplets in the emulsion produced at this time is about 200 to 2000 nm.

The thus prepared liposomal bioactive substance liquid and oil-soluble substance emulsion are then mixed, and during or after this mixing, water-soluble substances are added to improve the stability of the liposomes. Alternatively, a water-dispersible polymeric thickener is added to prepare the desired cosmetic. As the water-soluble or water-dispersible polymeric thickener used for this purpose, conventionally known ones used in this type of cosmetics can be used, but preferably polyvinyl alcohol, carboxyvinyl polymer, acrylic It is one type or a mixture of two or more types selected from vinyl polymer, carboxymethyl cellulose, hydroxyethyl cellulose, xanthan gum, and locust bean gum. The amount of the water-soluble or water-dispersible polymer thickener used is preferably about 0.01 to 20% of the total amount.

In the present invention, if necessary, wetting agents such as glycerin, propylene glycol, and 1,3-butylene glycol, preservatives such as paraben (paraben, paraoxybenzoic acid ester), pigments, and other product properties may be added. Other additives suitable for use in cosmetics are appropriately added and mixed uniformly to produce a cosmetic containing liposomes.

[Function] In the present invention, phospholipids are used to form water-soluble bioactive substances into liposomes, and the same phospholipids are used to emulsify oil-soluble substances, and the resulting liposome-formed bioactive substances are made into liposomes. By adding a water-soluble or water-dispersible polymer thickener that does not interact with phospholipids when mixing the liquid and the oil-soluble substance emulsion, stable liposomes that can be stored for a long period of time can be created. This method eliminates the need to use a separate surfactant to disperse oil-soluble ingredients, and produces cosmetics that contain liposomal bioactive substances in a stable state. can produce materials. Cosmetics produced by the method of the present invention have greater stability in liposomes than those obtained by simultaneously encapsulating water-soluble components and oil-soluble components in liposomes.

[Example] Hereinafter, examples of the present invention are as follows.

Example 1 (Preparation of beauty serum 1) Add raw material No. 4 to the mixture of raw materials Nos. 1 to 3 and heat at 45°C.
Stir strongly while heating to form liposomes.
A liposomal bioactive substance solution (a) was prepared.

In addition, raw material No. 7 was added to the mixture of raw materials No. 5 and 6, heated to 50°C, and then a part of raw material No. 12 was added to 50°C.
The mixture was heated to 0.degree. C. and added, and stirred vigorously to emulsify the whole, thereby preparing a liquid (b) of an oil-soluble substance.

Next, the liquid (a) and liquid (b) were mixed, and all the remaining raw materials were added thereto and mixed thoroughly to prepare a beauty serum 1 of the present invention.

The composition of the obtained serum 1 is shown in Table 1.

Table 1 Ingredients Compounding amount No. Ingredient name (wt%) 1 Hyaluronic acid extract 20.0 2 Thymus peptide extract 10.0 3 Rosemary extract 2.0 4 Soybean phospholipid 3.0 5 Fragrance 0.2 6 Tocoperol acetoate 0.1 7 Soybean phospholipid 0.7 8 Propylene glycol 5.0 9 Glycerin 5.0 10 Methyl paraoxybenzoate 0.2 11 Hydroxyethyl cellulose (2wt% solution) 0.2 12 Purified water to100 Example 2 (Preparation of serum 2) Add raw material No. 4 to the mixture of raw materials No. 1 to 3 In addition, 40℃
A liposome-formed bioactive substance solution (a) was prepared by heating the substance to liposomes using ultrasonic waves.

Further, a part of raw material No. 10 was added to the mixture of raw materials No. 5 and 6, heated to 55° C., and strongly stirred to emulsify the whole to prepare a liquid (b) of an oil-soluble substance.

Next, the liquid (a) and liquid (b) were mixed, and all the remaining raw materials were added thereto and mixed thoroughly to prepare a beauty serum 2 of the present invention.

The composition of the obtained serum 2 is shown in Table 2.

Table 2 Raw materials Ingredients No. Raw material name (wt%) 1 Fibronectin solution 5.0 2 Rosemary extract 5.0 3 Camille extract 5.0 4 Egg yolk phospholipid 3.0 5 Flavoring 0.2 6 Egg yolk phospholipid 0.5 7 Glycerin 10.0 8 Methyl paraoxybenzoate 0.2 9 Xanthan gum (2wt% solution 0.2 10 Purified water to100 Example 3 (Preparation of serum 3) Add raw materials Nos. 3 and 4 to raw materials Nos. 1 and 2, heat to 40°C, and apply ultrasonic waves while stirring strongly. was used to form liposomes to prepare a liposomal bioactive substance solution (a).

In addition, a part of raw material No. 13 was added to the mixture of raw materials No. 5 to 6 and raw materials No. 7 to 8, and the mixture was heated to 55°C and stirred strongly to emulsify the whole and make the oil-soluble substance liquid (rotate). ) was prepared.

Next, the liquid (a) and liquid (b) were mixed, and all the remaining raw materials were added thereto and mixed thoroughly to prepare a beauty serum 3 of the present invention.

The composition of the obtained serum 3 is shown in Table 3.

Table 3 Ingredients Compounding amount No. Ingredient name (wt%) 1 Hyaluronic acid extract 10.0 2 Placenta extract 5.0 3 Soy phospholipid 2.0 4 Hydrogenated soy phospholipid 1.0 5 Fragrance 0.2 6 Carrot oil 0.1 7 Soybean Phospholipid 0.6 8 Hydrogenated soybean phospholipid 0.3 9 Propylene glycol 10.0 10 Glycerin 10.0 11 Sodium carboxyvinyl polymer (2wt% solution) 10.0 12 Methyl paraoxybenzoate 0.2 13 Purified water to100 Example 4 (Preparation of softening lotion) Raw materials Raw material No. 5 was added to Nos. 1 to 4 and strongly stirred at room temperature to form liposomes, thereby preparing a liposome-formed bioactive substance liquid (a).

Also, add raw materials No. 6 to 7 to a part of raw material No. 12,
Stir vigorously to emulsify the entire mixture and extract the oil-soluble substance liquid (b).
was prepared.

Next, the liquid (a) and liquid (b) were mixed, and all the remaining raw materials were added thereto and mixed well to prepare the softening lotion of the present invention.

The composition of the obtained softening lotion is shown in Table 4.

Table 4 Ingredients Compounding amount No. Ingredient name (wt%) 1 Thymus peptide extract 2.0 2 Fibronectin solution 2.0 3 Witness hazel extract 2.0 4 Rosemary extract 2.0 5 Soybean phospholipid 1.0 6 Flavoring 0.2 7 Soybean phospholipid 0.2 8 Glycerin 2.0 9 Methyl paraoxybenzoate 0.15 10 Xanthan gum (2% solution) 15.0 11 Ethanol 5.0 12 Purified water to100 Example 5 (Preparation of pack agent) Add raw materials No. 4 to 5 to raw materials No. 1 to 3, and add 50 The mixture was vigorously stirred at ℃ to form liposomes, thereby preparing a liposomal bioactive substance solution (a).

Also, add raw materials No. 6 to 7 to a part of raw material No. 14,
The mixture was vigorously stirred at 50°C to emulsify the entire mixture to prepare a liquid (b) of an oil-soluble substance.

Next, the above solutions (a) and (b) were mixed, and all the remaining raw materials were added thereto and mixed well to prepare the pack agent of the present invention.

The composition of the obtained pack is shown in Table 5.

Table 5 Raw materials Ingredients No. Raw material name (wt%) 1 Rosemary extract 3.0 2 Camille extract 3.0 3 Witsch hazel extract 3.0 4 Sterol 0.3 5 Egg yolk phospholipid 2.5 6 Flavor 0.2 7 Tocopheryl acetate 0.1 8 Egg yolk phospholipid 0.3 9 Propylene glycol 1.0 10 Methyl paraoxybenzoate 0.2 11 Panthenol 0.1 12 Ethanol 3.0 13 Polyvinyl alcohol (2wt% solution)
35.0 14 Purified water to100 [Effects of the invention] According to the present invention, liposomal bioactive substances can be contained in cosmetics in a stable state, so the effects of using liposomes can be exerted over a long period of time. At the same time, the absorption efficiency of bioactive substances into skin cells can be increased, and the performance as a cosmetic can be improved.

Claims (1)

[Claims] 1. A bioactive substance is made into liposomes using phospholipids, and an oil-soluble substance is microemulsified using the same phospholipid used to make the bioactive substances into liposomes. A method for producing cosmetics containing liposomes, which comprises mixing these two liquids and then adding a water-soluble or water-dispersible polymeric thickener thereto and mixing uniformly. 2. The bioactive substance is one or a mixture of two or more selected from fibronectin solution, placenta extract, thymic peptide, hydrolyzed elastin, hyaluronic acid solution, rosemary extract, Camille extract, and derivatives thereof. A method for producing a cosmetic containing the liposome according to claim 1. 3. The liposome according to claim 1, wherein the phospholipid is one or a mixture of two or more selected from soybean phospholipid, brain phospholipid, egg yolk phospholipid, hydrogenated soybean phospholipid, and hydrogenated egg yolk phospholipid. Cosmetic manufacturing method. 4. The method for producing a liposome-containing cosmetic according to claim 1, wherein the oil-soluble substance is one or a mixture of two or more selected from fragrances, oil-soluble vitamins, and oil-soluble animal and plant extracts. 5 The water-soluble or water-dispersible polymeric thickener is polyvinyl alcohol, carboxyvinyl polymer,
A method for producing a cosmetic containing the liposome according to claim 1, which is one or a mixture of two or more selected from acrylic vinyl polymer, carboxymethyl cellulose, hydroxyethyl cellulose, xanthan gum, and locust bean gum.