JP2002030001A - Percutaneous absorbefacient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a percutaneous absorbefacient effective for accelerating the percutaneous absorption of an oil solution and a pharmaceutical component, and excellent in safety and feeling in use, and a cosmetic containing the percutaneous absorbefacient. SOLUTION: This percutaneous absorbefacient for an oil solution and a pharmaceutical component soluble in the oil solution contains a powdery material or an oil-gelling agent which makes the longitudinal relaxation time of the NMR spectrum of the oil solution longer than that of the single case of the oil solution when the powdery material or oil-gelling agent is mixed with the oil solution, as an active ingredient, and another objective cosmetic contains the above percutaneous absorbefacient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a transdermal absorption enhancer.

[0002]

2. Description of the Related Art Conventionally, various substances have been used in cosmetics and the like as components that exert their effects by transdermal absorption. However, since the stratum corneum, which is the outermost layer of the skin, originally has a physiological function as a barrier to prevent invasion of foreign substances from outside the body, it is not sufficient to simply mix such a substance in an external preparation. It does not have skin absorbability and cannot show its original function.

[0003] In order to improve this, in recent years, dimethylsulfoxide, dimethylformamide, dimethylacetamide,
Transdermal absorption enhancers such as methyldecyl sulfoxide have been used.

[0004]

However, these percutaneous absorption enhancers do not always provide a sufficient percutaneous absorption promotion effect, and may cause erythema on the skin due to strong skin irritation. Such as its effects, safety,
It was not enough in terms of usability.

Accordingly, an object of the present invention is to provide a percutaneous absorption enhancer having an effect of promoting percutaneous absorption of an oil agent used for external use on the skin and a pharmacological component dissolved in the oil agent, and a cosmetic containing the same. And

[0006]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, the longitudinal relaxation time of the NMR spectrum of an oil agent can be made longer when mixed together than when the oil agent is used alone. It has been found that the use of a powder or an oil gelling agent can improve the transdermal absorbability of the oil agent or a pharmacological component dissolved in the oil agent, and completed the present invention.

That is, according to the present invention, the longitudinal relaxation time of the NMR spectrum when an oil agent and a powder or an oil gelling agent are mixed is made longer than that of the oil agent alone. It provides a skin absorption enhancer. The present invention also provides a pharmacological component dissolved in an oil agent comprising a powder or an oil gelling agent, which makes the NMR spectrum longitudinal relaxation time of a mixture of an oil agent and a powder or an oil gelling agent longer than that of the oil agent alone. To provide a percutaneous absorption enhancer. Further, the present invention provides a cosmetic containing these oils and a transdermal absorption enhancer for the oils.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The oil agent that can be used in the present invention may be any oil agent that can be incorporated into cosmetics and the like and absorbed percutaneously, and examples thereof include the following. Specific examples of the oil include ethyl arachidonic acid, ethyl linolenate, isononyl isononanoate, octyl isopalmitate, isopropyl linoleate, octyl isoperargonate, oleyl linoleate, isotridecyl isononanoate, ethyl linoleate, isopropyl isostearate, octane Isocetyl acid, oleyl eica, isostearyl octoate, isodecyl pivalate, isodecyl isononanoate, erucyl eica, octyl dodecyl oleate, isostearyl pivalate, isostearyl isostearate, isocetyl isostearate, isostearyl eicaate, eicaic acid Octyldodecyl, isopropyl oleate, octyldodecyl dimethyloctanoate, hexyldecyl dimethyloctanoate, oleyl myristate, Squid stearyl,
Ethyl oleate, Decyl oleate, Isocetyl stearate, Octyl stearate, Octyl dodecyl stearate, Isostearyl palmitate, Isocetyl palmitate, Octyl palmitate, Isostearyl myristate, Isocetyl myristate, Isotridecyl myristate, Octyl myristate Dodecyl, isostearyl laurate, hexyl isostearate, myristyl isostearate, lauryl isostearate, stearyl oleate, cetyl oleate, isobutyl stearate, isobutyl palmitate, isopropyl palmitate, octyl myristate, isodecyl laurate, butyl isostearate Octyl pelargonate, isopropyl myristate, isoamyl laurate, Fatty acid esters such as hexyl, myristyl neopentanoate, isobutyl pelargonate, lauryl palmitate, decyl myristate, ethyl stearate, ethyl palmitate, butyl myristate, ethyl laurate, methyl myristate, methyl laurate; diisopropyl sebacate Polycarboxylic acid esters such as diisobutyl adipate, dihexyl adipate, diisopropyl adipate, diethyl sebacate, butyl adipate, dibutyl adipate; propylene glycol dinonanoate, glyceryl trioctanoate, glyceryl tricaprate, neopentyl dicaprate Glycol, propylene glycol dicaprate,
Fatty acid polyhydric alcohol esters such as glyceryl triacetyl ricinoleate, glyceryl tricaprate, diglyceryl triisostearate, and diglyceryl monoisostearate; diisostearyl malate, octyl oxystearate, octyl dodecyl lactate, and isolactic lactate Stearyl, oleyl lactate, methyl ricinoleate, myristyl lactate, hydroxy acid esters such as lauryl lactate, other octyl methoxycinnamate,
Octyl paradimethylaminobenzoate, dl-α-tocopherol, dl-α-tocopherol nicotinate and the like can be mentioned.

In the present invention, the longitudinal relaxation time of an NMR spectrum is determined by an inversion recovery method (inversion recovery method).
on recovery).
This is a method using a pulse sequence of 180 °, −90 ° and −180 °. First, when a first 180 ° pulse is given, the magnetization M ₀ is tilted in the −Z direction. This magnetization recovers in the Z-axis direction over time. The magnetization M (t) at time t is given by the following equation (1).

(Equation 1) M (t) = M ₀ {1-2 EXP (−t / T ₁ )}

(Where M ₀ is the magnetization at time 0, M is the magnetization at time t, t is time and T ₁ is the longitudinal relaxation time). Next, when a second 90 ° pulse is given after a time t, the Z-axis magnetization is tilted on the Y-axis. At this time, the FID is sampled, and its magnitude is plotted against time t, whereby the longitudinal relaxation time T ₁ can be calculated from the slope. In the present invention, N
The longitudinal relaxation time of the ¹³ C spectrum was measured using MR-EX270 (manufactured by JEOL).

The powder and the oil gelling agent which can be used in the present invention, when mixed with the oil agent used, have a longitudinal relaxation time T _1b seconds of the NMR spectrum of the oil agent, and a longitudinal relaxation time T _{1b in} the case of the oil agent alone. Longer than _1a seconds, ie the difference ΔT ₁ =
T _1b -T _1a seconds is greater than 0 seconds. Further, it is preferable that the ΔT ₁ is longer than 0 second and shorter than 1 second. By using a powder or oil gelling agent,
It can promote the transdermal absorbability of the oil. These powder or oil gelling agents can be used alone or in combination of two or more.

When the oil agent is 1,3-dimethylbutylhexadecyl ether or tridecyl isononanoate, the powder or oil gelling agent may be dimethylsiloxane, methylhydrogensiloxane, or a homo- or copolymer thereof, or a spherical resin. Powder (eg, spherical nylon, etc.), dextrin fatty acid ester, fine particle zinc oxide, polymethylsilsesquioxane, silica, mica, dialkyl phosphate, sericite, kaolin, talc, titanium oxide, iron oxide, alumina, zirconia, preservative , Metal soap, 12 hydroxystearic acid,
Dibenzylidene sorbitol, amino acid-based oil gelling agents, and the like.

A part or all of the powder may have been subjected to a hydrophobic treatment such as a silicone treatment, a fluorine treatment, a metal soap treatment, or a fatty acid treatment. When two or more types of oils are used, if they are mixed with a mixture of oils, the longitudinal relaxation time of the NMR spectrum of the mixture of the oils is longer than the longitudinal relaxation time of the mixture of the oils alone. Good. The average particle size of the powder is 0.001 to 100.
μm is preferred. When the thickness is 0.001 to 100 µm, the percutaneous absorption of oils and pharmacological components is further promoted.

The pharmacological component used in the present invention is used in combination with the oil agent as long as it can be dissolved in the oil agent used in the present invention. For example, ceramides, ceramide-like structural substances, humectants, amino acids, Examples include whitening agents, anti-inflammatory agents, singlet oxygen scavengers, antioxidants, alcohols, sterols, and blood circulation promoters.

The percutaneous absorption enhancer of the present invention may be the above-mentioned powder or oil gelling agent itself. However, oil agents, pharmacological components, other surfactants, polyhydric alcohols, organic acids, water and the like are usually used. They may be mixed according to the method.

The cosmetic of the present invention contains such an oil and a transdermal absorption enhancer for the oil, and may further contain a pharmacological component dissolved in the oil. Thereby, the active ingredient in the cosmetic (the oil, the active ingredient dissolved in the oil)
Is rapidly absorbed from the skin. The content of the powder and / or oil gelling agent in such a cosmetic is 0.001 to 6
It is preferably 0% by weight, more preferably 0.1 to 55% by weight, and particularly preferably 10 to 50% by weight.

The cosmetic of the present invention can be used in any form such as emulsifying type, dispersing type, two-layer type, solubilizing type and gel, lotion, emulsion,
Creams, packs, foundations, lipsticks and lipsticks can be used. The cosmetic of the present invention is a powder or an oil gelling agent, an oil agent, a medicinal ingredient, and a surfactant, a pigment generally used in a lotion, and the like.
It can be produced according to a conventional method by appropriately adding a fragrance, water and the like.

[0019]

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the following examples.

Examples 1 to 13 and Comparative Examples 1 to 6 Transdermal absorption enhancers were produced according to the conventional methods using the formulations shown in Tables 1 and 2. Tables 1 and 2 show ΔT ₁ of these transdermal absorption enhancers.

[0021]

[Table 1]

[0022]

[Table 2]

Test Example 1 50 mg of each of the transdermal absorption enhancers obtained above was applied to the skin surface of 2 cm ² of Yucatan micropig and left in a thermo-hygrostat at 37 ° C. and saturated humidity for 18 hours. Thereafter, the unpermeated components remaining on the skin surface were removed, and the permeated components were extracted and recovered, and the amount of transdermal absorption of the spiroether compound was measured by HPLC. The results are shown in Tables 1 and 2. The numerical values are shown as relative values when the numerical value when all the coating amounts permeate is set to 100.

[0024] From Table 1 and Table 2, △ if T ₁ is a certain Examples 1-13 positive, the percutaneous absorbability is better than that of Comparative Example 1 to 6 △ T ₁ is a negative Was confirmed.

Formulation Example 1 An emulsion was prepared according to a conventional method with the formulations shown in Table 3. The percutaneous absorbability of the obtained emulsion was superior to the conventional one.

[0026]

[Table 3]

Formulation Example 2 Emulsions were prepared according to the conventional method with the formulations shown in Table 4. The percutaneous absorbability of the obtained emulsion was superior to the conventional one.

[0028]

[Table 4]

Formulation Example 3 A cream was prepared according to a conventional method with the formulation shown in Table 5.
The transdermal absorbability of the obtained cream was superior to the conventional one.

[0030]

[Table 5]

A creamy foundation was prepared according to the conventional method with the composition shown in Table 6. The transdermal absorbability of the obtained creamy foundation was superior to the conventional one.

[0032]

[Table 6]

A powder foundation was prepared according to a conventional method with the composition shown in Table 7. The percutaneous absorbability of the obtained powder foundation was superior to the conventional one.

[0034]

[Table 7]

A stick was prepared according to a conventional method with the composition shown in Table 8. The transdermal absorbability of the obtained stick was superior to the conventional one.

[0036]

[Table 8]

[0037]

The percutaneous absorption enhancer of the present invention can enhance the percutaneous absorption of oils and pharmacological components dissolved in the oils. Further, the cosmetic of the present invention has excellent transdermal absorbability.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Seiji Yama- ▲ ▼ 2-1-3 Bunka, Sumida-ku, Tokyo F-term in Kao Corporation Research Institute F-term (reference) 4C076 AA06 BB31 DD29 EE13 EE27 EE51 FF34 4C083 AA072 AA112 AB032 AB052 AB172 AB212 AB232 AB242 AB432 AC022 AC072 AC102 AC122 AC172 AC242 AC302 AC352 AC392 AC432 AC442 AC622 AC682 AC892 AD022 AD072 AD092 AD152 AD252 AD332 AD492 BB13 BB26 CC02 CC05 CC12 CC13 DD11 DD17 DD31 EE12

Claims (6)

[Claims] 1. A percutaneous absorption enhancer for an oil agent, comprising a powder or an oil gelling agent that makes the longitudinal relaxation time of the NMR spectrum of the oil agent when mixed with the oil agent longer than that of the oil agent alone. 2. Percutaneous absorption of a pharmacological component dissolved in an oil agent, comprising a powder or an oil gelling agent that makes the NMR spectrum longitudinal relaxation time of the oil agent when mixed with the oil agent longer than that of the oil agent alone. Accelerator. 3. The NMR spectrum longitudinal relaxation time of the oil agent when the powder or oil gelling agent is mixed with the powder or oil gelling agent, and the NMR spectrum longitudinal relaxation time of the oil agent alone. The percutaneous absorption enhancer according to claim 1 or 2, wherein the difference is more than 0 second and not more than 1 second. 4. An average particle diameter of the powder is 0.001 to
The transdermal absorption enhancer according to any one of claims 1 to 3, which is 100 µm. 5. A cosmetic comprising an oil and a percutaneous absorption enhancer for the oil according to any one of claims 1 to 4. 6. The cosmetic according to claim 5, wherein the compounding amount of the powder and / or the oil gelling agent is 0.001 to 60% by weight.