JPH02261534A - Microcapsule and external preparation by blending the same - Google Patents

Abstract

PURPOSE:To improve the stability of an oily component contained in microcapsules and to make the microcapsules satisfactorily impermeable to the hydrophobic component by modifying the surfaces of the microcapsules with a basic amino acid or a polymer thereof. CONSTITUTION:A hydrophobic component, that is, fat-soluble component effective on the skin is microencapsuled with gelatin swollen with water to form microcapsules contg. the component and the surfaces of the microcapsules are modified with a basic amino acid or a polymer thereof such as lysine or polylysine. The contained hydrophobic component has superior stability and does not deteriorate over a long period of time and the microcapsules have satisfactory impermeability to the component. The external preparations obtd. by blending with the microcapsules import wetness to the skin has superior characteristics.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to gelatin membrane microcapsules encapsulating hydrophobic substances whose surfaces are modified and coated with basic amino acids or polymers thereof, and external preparations containing the same. By binding basic amino acids such as lysine and polylysine to the surface of gelatin membrane microcapsules containing hydrophobic components through pH adjustment and cross-linking with aldehyde for polymer modification, the encapsulated hydrophobic components are removed. Microcapsules have the advantage of exhibiting excellent stability without deteriorating over a long period of time, and external use products that are easy to use and have excellent effects in imparting lubricity and moisture to the skin due to the formulation of these microcapsules. Regarding drugs.

[Prior art] In general, external preparations include cosmetics, pharmaceuticals, quasi-drugs, etc. Among these, the function and purpose of cosmetics is to contain an appropriate amount of oil and oil according to skin or hair type. It helps the natural moisturizing mechanism of the skin and hair by providing moisturizing ingredients and moisture, and changes in external environmental conditions, such as those that depend on nature such as temperature and humidity, or artificial ones such as degreasing due to washing. The aim is to reduce the burden on the skin and hair caused by such factors and maintain a healthy and normal state (homeostasis).

In order to further improve this function, cosmetics have traditionally been formulated with various skin-active ingredients such as vitamins and unsaturated fatty acids. Some water-soluble substances such as vitamin C are known as these active ingredients, but most of these belong to the fat-soluble category. Many of these fat-soluble skin active ingredients are prone to auto-oxidation, and after losing hydrogen atoms due to light or heat to form activated radicals, they absorb oxygen to generate peroxy radicals, producing hydroperoxides (peroxides). ) and then decomposed or polymerized to produce carbonyl compounds, lower aldehydes, lower fatty acids, ketones, and other compounds, resulting in loss of activity.

[Problems to be Solved by the Invention] Disadvantages of the Prior Art Therefore, when these skin active ingredients are incorporated into cosmetics or other external preparations, it is necessary to prevent them from oxidizing. One way to prevent oxidation is to manufacture the external preparation in an inert gas such as nitrogen, and to remove the air in the space in contact with the external preparation when filling the product container.
A method of replacing the air with nitrogen or carbon dioxide gas is considered, but nitrogen gas replacement has little effect unless it completely replaces not only the space but also the dissolved oxygen in the topical preparation, and carbon dioxide gas replacement is rather effective over time. This is undesirable because it may cause an increase in the acid value of the active ingredient or the generation of off-flavors. It is also possible to carry out manufacturing and storage at as low a temperature as possible,
This is practically impossible from the standpoint of quality assurance, etc. Therefore, with regard to recent external preparations, the current situation is to stabilize them for a long period of time by adding antioxidants. However, since the properties and effective concentration of antioxidants vary depending on the type of skin active ingredient, they have the disadvantage of being difficult to handle, requiring sufficient investigation and experimentation before actual use.

It is also being considered to microcapsule fat-soluble components to isolate them from the outside world and stabilize them.

Examples include microencapsulation of fat-soluble vitamins (US Pat. No. 2,183,053 and US Pat. No. 3,819,838).
, a method of coating fats and oils with gelatin-agar, etc.
-78351) Method of converting sodium alginate into calcium chloride and using it for microcapsule membranes (JP-A-57-
150613) Method of adding hydrogenated fat to highly unsaturated fatty acid-containing fats and oils encapsulated in microcapsules (JP-A-63-
However, the microcapsules obtained by these methods dissolve in water-containing external preparations and cannot be used, and the stability of the encapsulated oil content is not practical. However, satisfactory results were not obtained.

Purpose of the Invention The present inventors conducted intensive studies to solve this problem, and as a result, they encapsulated a hydrophobic ingredient, that is, a fat-soluble skin active ingredient, in microcapsules made of a gelatin membrane swollen with water, and then By binding basic amino acids such as lysine and polylysine to the gelatin membrane of microcapsules using a crosslinking agent such as aldehyde, and modifying the membrane surface with a polymer, the deterioration of the fat-soluble substances contained therein can be suppressed for a long period of time. It was discovered that it exhibits stability, and furthermore, that the inclusions do not pass through the membrane and migrate to the outer aqueous layer, and that it can provide completely new functions, appearance, and usability that are not found anywhere else, and thus completed the present invention. It's arrived.

[Means for Solving the Problems] That is, the present invention provides gelatin membrane microcapsules that contain a hydrophobic component and whose surface is modified with a basic amino acid or a polymer thereof, and a gelatin membrane microcapsule for external use that is formulated with the same. It is a drug.

The configuration of the present invention will be described below.

The method for producing gelatin membrane microcapsules according to the present invention basically uses known methods such as simple coacervation and complex coacervation, and uses a novel method when modifying with basic amino acids. For example, when preparing by the complex coacervation method, in a heated aqueous gelatin solution,
After adding an aqueous solution of an anionic hydrophilic polymer substance with opposite charges to cause complex coacervation, one or more hydrophobic substances are added to disperse and emulsify. Furthermore, after cooling and gelling the capsules according to a conventional method, the pH of the system was adjusted to slightly alkaline (around pH 8).
Add an aqueous solution of basic amino acids, then cross-link gelatin and basic amino acids with aldehydes etc.
Cures to perform surface modification.

The basic amino acids related to this microcapsule include:
For example, lysine, ornithine, hydroxylysine, and homopolymers or copolymers thereof are used. An example of a polymer is polylysine. Next, the hydrophobic ingredients contained in the modified gelatin membrane capsule include fat-soluble skin active ingredients, such as animal and vegetable oils,
Hydrocarbon oil, ester oil, silicone oil, higher fatty acid,
Higher alcohols, vitamins and vitamin-like substances,
Various fragrances are mentioned, and to give more specific examples of these, animal and vegetable oils include mink oil, tardle oil, safflower oil, grapeseed oil, soybean oil, sesame oil, corn oil, rapeseed oil, sunflower oil, cottonseed oil, and avocado oil. Oil, olive oil, sasanqua oil, camellia oil, basic oil, castor oil, jojoba oil, peanut oil, orange oil, camellia oil, macadamian nut oil, egg yolk oil, wheat germ oil, linseed oil, eno oil, tea seed oil, Kaya oil, rice bran oil, Shinakiri oil, Japanese tung oil, germ oil, triglycerin, trioctanoic acid, cacao butter, coconut oil, horse tallow, hydrogenated coconut oil, palm oil, beef tallow,
Mutton tallow, hydrogenated beef tallow, palm kernel oil, pork fat, beef bone fat, Japanese oak kernel oil, Japanese oak oil, hydrogenated castor oil, etc. Hydrocarbon oils include squalene, blistane, liquid paraffin, osikerite,
Paraffin, ceresin, squalane, vaseline, microcrystalline wax, topentadecene, tohexadecene, lauran, etc. Ester oils include decyl oleate,
Oleyl oleate, trioleyl phosphate, methyl linoleate, ethyl linoleate, ethyl linoleate, propyl linoleate, propylene glycol dioleate, etc. Silicone oils include fatty acid-modified polysiloxane, fatty acid alcohol-modified polysiloxane, and polyoxyalkylene-modified polysiloxane. Siloxane, dimethylpolysiloxane, dimethylcyclopolysiloxane, dialkylpolysiloxane such as dimethylpolysiloxane, alkylarylpolysiloxane such as methylphenylpolysiloxane, higher alcohol-modified polysiloxane, amino-modified polysiloxane, higher fatty acids such as lauric acid and myristic acid. , stearic acid, tolic acid, lanolin fatty acid, isostearic acid, oleic acid, undecylenic acid, linoleic acid, liluic acid, eicosapentaenoic acid, erucic acid, parinaric acid, arachidonic acid, curbanodonic acid, etc., and higher alcohols such as lauryl alcohol and cetyl alcohol. , stearyl alcohol,
Behenyl alcohol, myristyl alcohol, cetostearyl alcohol, monostearyl glycerin ether, 2-decyltetrazosinol, lanolin alcohol,
Cholesterol, hexyldodecanol, isostearyl alcohol, octyltothicanol, oleyl alcohol, lylyl alcohol, phytosterol, etc. Waxes include lanolin, cotton wax, sugarcane wax, etc. Vitamins include retinol, retinol acetate, palmitic acid retinol, dehydroretinol,
Ergocalciphenol, cholecalciphenol, tocopherol, tocopherol acetate, tocopherol calcium succinate, ubiquinone, phytonadione, menaquinone, menadione, riboflavin butyrate, pyridoxine caprilate, pyridoxine diparnitate, pyridoxine civalmitate, vantothenyl alcohol,
Dicarboethoxypantothenic acid ethyl ester, acetyl bantothenyl ethyl ether, bantothenyl ethyl ether, ascorbyl stearate, ascorbyl valmitate, ascorbyl cybalmitate, etc. Vitamin-like active substances include α-riboic acid, ferulic acid, etc. Various fragrances include These include natural and synthetic fragrances, but are generally applicable to external preparations such as cosmetics, pharmaceuticals, and quasi-drugs, and have the property of being peroxidized by inducing activated radicals under the action of light or heat. Any fat-soluble raw material may be used, and the raw material is not limited to these.

The particle size of the capsule applied to the present invention is 0.1 to 20
00 μm is preferred. Capsules with a particle size smaller than 0.1 μm are extremely difficult to manufacture and are therefore undesirable. In addition, if the particle size is larger than 2000 μm, it will be destroyed by stirring during the preparation of the external preparation, and the encapsulated fat-soluble active ingredient will leak into the external preparation base, making it easy for autooxidation or hydrolysis to occur. In addition, if you try to break the capsule by compressing it with your fingers or palm when using the product, the capsule may escape.
When you touch your fingers or palm together, the capsule will noticeably break through your fingers or palm (this is a state where it can't be crushed because it can't be crushed), making it impossible to destroy it easily, and even if it is destroyed, there will be a feeling of foreign body due to the capsule membrane remaining. This results in unsatisfactory results in terms of usability.

Further, the amount of the capsule containing the hydrophobic component of the present invention in the external preparation is preferably within the range of 0.1 to 95% by weight.

The weight ratio of the hydrophobic component forming the capsule to the gelatin is selected in the range of 1:10 to 100:1. When the weight ratio of hydrophobic component to gelatin is greater than 1:10, the capsule wall becomes extremely thick and cannot be easily broken when applied to the skin. Furthermore, if the weight ratio is less than 100:1, the strength of the capsule film will be significantly reduced, and there is a possibility that the capsule will break during product manufacture, making it unsuitable for practical use.

The above-mentioned gelatin membrane capsule of the present invention is itself non-porous and transparent, and further has sufficient impermeability to the contents contained therein.

Since the external preparation of the present invention has extremely harsh usage characteristics, it is particularly preferable to use it as a cosmetic product that places emphasis on usage characteristics. Makeup such as cosmetics, foundation, lipstick, etc.'M1. Alternatively, it may be incorporated into hair cosmetics such as hair tonics and hair creams.

[Example] The present invention will be described in detail below with reference to Examples, but the present invention is not limited thereto.

Production Example 1 40°C aqueous solution containing 10g of acid-treated gelatin 600ml
A 40°C aqueous solution of 5 g of gum arabic dissolved in 60 g of
0g were mixed, and a 10% acetic acid aqueous solution was added dropwise to adjust the pH to 4.
3, add 100 g of mixed oil in the ratio of liquid paraffin: cetyl isooleate: vitamin A palmitate = 60 = 35:5, and mix with a propeller stirrer for 400 g.
The mixture was stirred at rpm. Next, while stirring, the liquid was cooled from outside the container to 8°C, the pH was adjusted to 8.0, 10g of 10'X polylysine aqueous solution was added, and 2
A 5% glutaraldehyde aqueous solution Log was added and stirred for 2 hours to modify and harden the capsule membrane.

The product obtained in this way is separated from the aqueous phase by a decantation method and washed repeatedly with water, so that the weight ratio of the encapsulated hydrophobic component to the modified gelatin film is 60:1.
Capsules having an average particle diameter of 500 μm were obtained.

Production Example 2 50°C aqueous solution containing 10g of acid-treated gelatin 600ml
71 in water at 50°C with 6 g of gum arabic dissolved in
Mix 1,600 g of 10% acetic acid and adjust the pH by dropping 10% acetic acid aqueous solution.
After adjusting the ratio to 4.5, 100 g of mixed oil having a ratio of squalane: vaseline = 7-lylunic acid = 70,726:4 was added, and the mixture was stirred at 11,000 rpm using a propeller stirrer. Next, while stirring, the mixture was cooled from outside the container to bring the liquid temperature to 10°C, then the pH was adjusted to 8.0, 10% ornithine aqueous solution Log was added, and 10 g of 25% glutaraldehyde aqueous solution was further added and stirred for 2 hours. Do not modify or harden the capsule membrane.

The product thus obtained is separated from the aqueous phase by the decantation method and washed repeatedly with water.
The weight ratio of the encapsulated hydrophobic component to the modified gelatin film is 20:
1 to obtain capsules with an average particle diameter of 50 μm.

Example 1 The capsules prepared in Production Example 1 were blended in the following formulation to prepare an 0/W type emollient lotion.

[Oil phase] (Parts by weight) Squalane 5.0 Vaseline
2.0 beeswax
0.5 Sorbitan sesquioleate 0.8 Polyoxyethylene (20 mol) Oleyl ether 1.2 Fragrance
0.5 preservative
Appropriate amount [Aqueous phase 1 Microcapsules containing hydrophobic components 10.0 Propylene glycol 5.0 Ethanol
5.0 Carboxyvinyl polymer (1.0% aqueous solution') 20.0 Potassium hydroxide o, i Purified water
The remainder and as a comparative example, 1 by the above method.
Capsules containing 0% polylysine aqueous solution (ilog and no modification treatment (Comparative Example 1) were prepared, and the stability of vitamin A palmitate when stored in water was evaluated in comparison with Examples.

In the experiment, containers containing each capsule dispersion liquid were stored in a 50° C. incubator, and the remaining amount of vitamin A palmitate was examined after 7, 14, 30, and 60 days.

The results are shown in Figure 1. In each case, the amount immediately after microcapsule preparation is expressed as 100χ, but in Example 1, the decrease in vitamin A palmitate over time was slower than in Comparative Example 1, and the stability was poor.

Example 2 The capsules prepared in Production Example 1 were blended in the following formulation to prepare an 0/W type emollient lotion.

[Oil phase] (Parts by weight) Squalane 5.0 Vaseline
2.0 beeswax
0.5 Sorbitan sesquioleic acid ester 0.8 Polyoxyethylene (20 mon) oleyl ether 1.2 Fragrance
0.5 preservative
Appropriate amount [Aqueous phase] Microcapsules containing hydrophobic components 10.0 Propylene glycol 5.0 Ethanol
5.0 carboxyvinyl polymer (1,0X aqueous solution) 20.0 potassium hydroxide 0.1 purified water
For the remainder, as a comparative example, the above formulation was blended with microcapsules that were not treated with polylysine (Comparative Example 2), and the above formulation was not blended with microcapsules, but the same amount of liquid paraffin and vitamin A palmitate as the encapsulated amount was added. An emollient lotion (Comparative Example 3) blended into the oil phase was prepared, and the stability of vitamin A palmitate over time was evaluated in comparison with the above example.

The experiment consisted of 50 containers containing each emollient lotion.
It was stored in a temperature chamber at °C, and the residual amount of vitamin A palmitate was examined after 7, 14, 30, and 60 days.

The results are shown in Figure 2. In each case, the amount immediately after the preparation of the emollient lotion is expressed as 100%, but compared with Comparative Examples 2 and 3, the decrease in vitamin A palmitate over time in Example 2 was gradual, and the stability was excellent.

Example 3 The capsules obtained in Production Example 2 were blended according to the following formulation to prepare a W2O type makeup base cream.

[Oil phase] (Parts by weight) Squalane 23.0 Cyclic silicone 5.00.5 g Bentone
Organically modified clay mineral obtained by treating 38 with 0.1 g of cimilistoyl lecithin 0.6 Microcrystalline wax 2.0 Butyl hydroxybenzoate 0.1 Fragrance
0.1 titanium oxide 1.
0 Colored pigment 0.1 [Aqueous phase 1 Microcapsules containing hydrophobic components 5.0 Dipropylene glycol 5.0 Purified water
For the remainder, as a comparative example, a makeup base cream (Comparative Example 4) in which capsules not treated with ornithine were added to the above formulation, and a makeup base cream without microcapsules and the same amount of 7-lylunic acid as the encapsulated amount was added to the oil phase. A makeup base cream (Comparative Example 5) was prepared, and by the same experimental method as in Example 2, the stability of γ-lylunic acid over time was evaluated in comparison with the above example.

The results are shown in Figure 3, where Example 3 is different from Comparative Examples 4 and 5.
It had better stability compared to

[Effects of the Invention] The microcapsules of the present invention have the effect of maintaining excellent efficacy without deteriorating the fat-soluble skin active ingredients contained therein by modifying the membrane surface of the capsule with a polymer. External preparations containing microcapsules do not allow the contents to pass through the membrane and migrate to the external aqueous and fat layer, and when trying to break them by compression with the palm of the hand during use, the microcapsules do not require strong force. There is no leakage, and the contents can be easily destroyed with the palm of your finger to crystallize, and the oil and moisture can be easily spread onto the skin, and there is no foreign body sensation due to the capsule membrane remaining after destruction. It has completely new functions and appearance that have never been seen before, and has excellent usability in that it imparts lubricity and wettability to the skin.

[Brief explanation of drawings]

FIG. 1 is a diagram showing the stability over time of vitamin A palmitate of Example 1 and Comparative Example 1. FIG. 2 is a diagram showing the stability over time of vitamin A palmitate of Example 2 and Comparative Examples 2 and 3. FIG. 3 is a diagram showing the stability over time of 7-lylunic acid of Example 3 and Comparative Examples 4 and 5. Patent applicant Shisei Co., Ltd. School District-1 Figure-2 Time (days) Time (days)

Claims (2)

[Claims] (1) Gelatin membrane microcapsules containing a hydrophobic component and whose surface is modified with a basic amino acid or its polymer. (2) An external preparation containing the microcapsule according to claim 1.