JP4756493B2 - Topical skin preparation - Google Patents

Description

[0001]
[Industrial application fields]
The present invention relates to a skin external preparation having high skin permeability and high safety and stability of a preparation.
[0002]
[Prior art]
Naturally, various active ingredients are blended in the external preparation for skin. However, even if it is blended, if it is not absorbed by the skin, it will not be effective. Therefore, although a transdermal absorption enhancer is often used, there is a problem in safety and formulation stability.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to obtain a preparation that is safe and has extremely good stability of the preparation and excellent skin absorption of an active ingredient.
[0004]
[Means for Solving the Problems]
As a result of intensive investigations to solve the above-mentioned problems, the present inventors have carried out high-pressure emulsification treatment of an oil-soluble active ingredient, an oil component, a polyhydric alcohol, and a surfactant, and mixed and stirred into water and a water-soluble component. Has found that the above-mentioned problems can be solved.
[0005]
That is, the oil-soluble active ingredient is transdermally performed by performing the first stage in which the oil-soluble active ingredient, the oil, the polyhydric alcohol, and the surfactant are subjected to high-pressure emulsification treatment and the second stage in which the water and water-soluble ingredients are mixed and stirred. An external skin preparation having excellent percutaneous absorption and excellent safety and stability of the preparation was obtained without using an absorption accelerator or the like.
By adopting this method, the advantages of the high-pressure emulsification method are maximized and the formation of fine particles is promoted. In addition, this reduces the amount processed by the high-pressure emulsifier, effectively uses the equipment, and after the first stage treatment, it is stable and antiseptic, so it can be stored and only the necessary amount is treated in the second stage. This is also economically advantageous.
[0006]
The oil-soluble active ingredient is not particularly limited and is selected depending on the use of the preparation. Oil-soluble plants such as α-tocopherol and vitamin A palmitate and their derivatives, oil-soluble licorice, oil-soluble yokoinine and other oil-soluble plants Examples include extracts, γ-oryzanol, stearyl glycyrrhetinate.
[0007]
There is no particular limitation on the oil content, so it is arbitrarily selected, but it is selected depending on the feeling of use, application, and amount used. For example, natural animal and vegetable oils and fats such as olive oil, mink oil, castor oil, palm oil, beef tallow, evening primrose oil, coconut oil, castor oil, cacao oil, macadamia nut oil and the like; waxes such as jojoba oil, beeswax, lanolin, Carnauba wax, candelilla wax, etc .; higher alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, oleyl alcohol, etc .; higher fatty acids such as lauric acid, palmitic acid, stearic acid in, solid paraffin, squalane, petrolatum, ceresin, microcrystalline wax Synthetic ester oils such as butyl stearate, hexyl laurate, diisopropyl adipate, diisopropyl sebacate, octyldodecyl myristate, isopropyl myristate, isopropyl palmitate Propyl myristate, cetyl isooctanoate, neopentyl glycol dicaprate; silicone derivatives such as methyl silicone, and silicone oils such as methyl phenyl silicone.
[0008]
As the polyhydric alcohol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, diethylene glycol, triethylene glycol, glycerin, diglycerin, triglycerin, and the like can be used. As a result of their studies, it has been found that when glycerin, diglycerin, and 1,3-butylene glycol are blended mainly, the gist of the present invention is met.
[0009]
The surfactant is not particularly limited, but the following surfactants can be exemplified.
Sodium palmitate, sodium lauroyl sarcosine, N-myristoyl-N-methyltaurine sodium, POE oleyl ether sodium phosphate, monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, monosodium N-myristoyl-L-glutamate, cured Coconut oil fatty acid sodium glycerol sulfate, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, sorbitan monooleate , Sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, glyceryl sesquioleate, glyceryl monostearate, propylene glycol monostearate, glycerin alkyl ether, polyoxyethylene / methylpolysiloxane Polymer, POE sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, POE-sorbit monolaurate, POE-sorbit monooleate, POE-sorbit pentaoleate, POE-glycerin monostearate, POE-glycerin monoisostearate, POE monooleate, POE distearate, POE monodiolate, POE oleyl ether, PO Stearyl ether, POE behenyl ether, POE2-octyldodecyl ether, POE cholestanol ether, POE octyl phenyl ether, POE nonyl phenyl ether, POE dinonyl phenyl ether, POE / POP cetyl ether, POE / POP hydrogenated lanolin, POE castor Oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil triisostearate, POE hydrogenated castor oil monopyroglutamic acid monoisostearic acid diester.
[0010]
However, a mixture of one or more phospholipids (for example, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, lysophosphatidylethanolamine, etc.), a phospholipid mixture such as soybean lecithin, corn lecithin, egg yolk lecithin, or hydrogenation thereof. ) And sugar ceramides (sphingoglycolipids such as galactosylceramide, glucosylceramide, acyl cerebroside, cerebroside sulfate, or animal sphingolipids and plant sphingolipids containing these), among other surfactants, are the gist of the present invention. I found that it matched.
[0011]
The ratio of the oil-soluble active ingredient, oil, polyhydric alcohol and surfactant varies depending on the nature of each ingredient, the use of the preparation, the amount and nature of water and water-soluble ingredients added in the second stage, etc. Soluble active ingredient: Oil content: Polyhydric alcohol: Surfactant = 1: 0.1-1: 1-100: It is preferable to mix | blend in the ratio of 0.02-100.
[0012]
These are processed in a high pressure emulsifier. Although various types of high-pressure emulsifiers are sold, the microfluidizer described in US Pat. No. 4,533,254 is excellent. This is used to emulsify.
Water and water-soluble components are added to this and mixed and stirred. At this stage, since it is not particularly related to percutaneous absorption, mixing and stirring may be performed using a conventional rotary stirrer.
There are no particular limitations on the water-soluble component, but it is necessary to refrain from blending those that destroy the emulsion or to reduce the amount in quantity.
In addition, the amount of the oil-soluble active ingredient, polyhydric alcohol, and surfactant mixed, and the amount of water and water-soluble components vary depending on various conditions. preferable.
[0013]
【Example】
Examples which are actual utilization methods will be described below, but the present invention is not limited to these examples.
[0014]
Example-1 Cream A Glycerin 5.0
Hydrogenated soybean lecithin 0.7
B Squalane 1.0
α Tocopherol 0.5
C Xanthan gum 0.1
Cargoxy vinyl polymer 0.1
1,3-butylene glycol 2.0
Purified water 90.3
Methyl paraoxybenzoate 0.1
10% aqueous sodium hydroxide solution 0.2
Preparation methods A and B were heated and dispersed at 80 ° C., and then treated at 1250 kg / cm 2 using a microfluidizer (manufactured by Microfluidics, M-210-E / H). C was heated and dispersed at 80 ° C., then added to the former with stirring, and cooled to room temperature.
[0015]
Example-2 Cream A Glycerin 5.0
Glycosphingolipid 0.5
B Squalane 1.0
Vitamin A palmitate 0.5
C Xanthan gum 0.1
Cargoxy vinyl polymer 0.1
1,3-butylene glycol 2.0
Purified water 90.5
Methyl paraoxybenzoate 0.1
10% aqueous sodium hydroxide solution 0.2
Preparation methods A and B were heated and dispersed at 80 ° C., and then treated at 1250 kg / cm 2 using a microfluidizer (manufactured by Microfluidics, M-210-E / H). C was heated and dispersed at 80 ° C., then added to the former with stirring, and cooled to room temperature.
Effectiveness confirmation test-1
A plastic cylindrical tube having an inner diameter of 28 mm was adhered to the abdominal skin of a hairless rat with an adhesive. 6 ml of Example-1 was injected into the tube. After 6 hours, the tube was removed, the sample was wiped off, and the skin surface was further wiped with absorbent cotton containing 70% ethanol. The skin administration site was extracted with a scissors and minced, and then α-tocopherol in the skin was extracted by stirring with 50 ml of petroleum ether (containing 100 ppm BHT) for 20 hours. After extraction, petroleum ether was distilled off, and the residue was dissolved in 20 ml of methanol and quantified by high performance liquid chromatography. Analysis conditions were as follows: column ODS-II (manufactured by Shimadzu Corporation), elution solvent = 1 ml of methanol per minute detector = fluorescence detector RF-550 (manufactured by Shimadzu Corporation), excitation wavelength 298 nm, fluorescence wavelength 325 nm, and 5 repetitions.
As a comparison, in the preparation method with the same formulation as Example-1, in a part using microfluidizer, it was replaced with 8000 rpm for 10 minutes with a homomixer type M SPEC (manufactured by Tokushu Kika Co., Ltd.). .
[0017]
As a result, the amount of α-tocopherol absorbed into the skin in the example was 5.2 ± 1.2 μg in the 18.2 ± 4.6 μg comparative example, and the percutaneous absorption of this example was very excellent. I understood it.
[0018]
Effectiveness confirmation test-2
Five women were divided into left and right faces of the creams of Example-2 and Comparative Example-2, and were used once or more daily, and wrinkles were evaluated after 6 months. In addition, Comparative Example-2 is a part using a microfluidizer in the preparation method with the same formulation as Example-2, and is 8000 rpm for 10 minutes with a homomixer type M SPEC (manufactured by Koki Co., Ltd.). This is a replacement.
[0019]
As a result of the evaluation, the wrinkle was significantly reduced in Example-2 as compared with Comparative Example-2, but the wrinkle was significantly reduced in one person, Example-2 compared with Comparative Example-2. Three people, Example-2, showed a slight decrease in wrinkles compared to Comparative Example-2, but only one.
Thus, although the vitamin A palmitate was blended in the same amount, Example-2 was more effective, indicating the effectiveness of the present invention.

Claims (2)

A skin external preparation characterized by high-pressure emulsification treatment of an oil-soluble active ingredient, oil, a polyhydric alcohol, and a surfactant, and mixing and stirring in water and a water-soluble ingredient. The skin external preparation according to claim 1, wherein the surfactant is phospholipid or / and glycosphingolipid.