JPH03184922A - Skin drug for external use - Google Patents

Abstract

PURPOSE:To obtain a skin drug for external use, capable of promoting percutaneous absorption and useful for stabilizing a radiation injury protective substance and reducing injuries due to exposure to radiation at a low dose for a long period by using capsules enclosing the radiation injury protective substance and a percutaneous absorption adjuvant in combination. CONSTITUTION:A skin drug for external use obtained by using capsules enclosing a radiation injury protective substance such as a sulfur-containing amino acid (e.g. glutathione or cysteine) or an active oxygen eliminator (e.g. superoxide dismutase or catalase) and a percutaneous absorption adjuvant, preferably glycerol, polyethylene glycol or lecithin in combination. A salt of alginic acid or compression disintegrable soft spherical resin is used as a coating layer for the aforementioned capsules. The capsules are broken with pressure of fingers, etc., to discharge the radiation injury protective substance enclosed therein and the percutaneous absorption adjuvant is mixed therewith. The resultant mixture is then applied to the objective part of a living body.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to a topical preparation for skin, and more specifically, the present invention relates to a skin preparation for external use, and more specifically, to reduce damage caused by long-term exposure to low-dose radiation, an unstable radiation protection substance is encapsulated in a capsule. This is an external preparation for skin that has been stabilized by using a transdermal absorption agent, and has enhanced its radiation damage protection effect in vivo by being used in combination with a transdermal absorption aid.

[Conventional technology] Recently, the deterioration of the global environment due to the destruction of the ozone layer, acid rain, accidents at nuclear power plants, and the effects of medical X-ray irradiation have become a hot topic. exposed to low-dose radiation such as natural radiation, cosmic rays and ionizing radiation.

J: Participated in an epidemiological survey conducted by the Radiation Effects Research Institute (Hiroshima City).
There are also reports that cancer deaths are increasing even with low-level radiation exposure.

In addition to this, some people point out the effects on aging and hair loss as late-onset disorders.

Therefore, in order to reduce radiation damage, research has been conducted on substances that protect against radiation damage. , Miwako Tamenaga et al., Nursing Journal, 51 [6], 580 (19
87).

Shigeru Kitayama, Chemistry and Biology, 27[5], 297 (1989
),, JP-A-54-138130, JP-A-57-97
No. 58, JP-A No. 62-174021, etc.).

[Problems to be solved by the invention] However, all of these radiation hazard protection substances are unstable and easily decompose even when left in the air, giving off a peculiar odor and reducing their effectiveness. was bad.

Furthermore, even if these radiation damage protective substances were applied to the skin, their percutaneous absorption was low and their effects could not be expected to be much.

The present inventor stabilizes a known radiation protection substance,
The objective was to create an easy-to-use external skin preparation with enhanced transdermal absorption.

[Means for Solving the Problems] The present invention provides a capsule containing a radiation protection substance;
It is a skin external preparation characterized by being used in combination with a transdermal absorption aid, and in a preferred embodiment, the radiation damage protective substance is a sulfur-containing amino acid or/and an active oxygen scavenger, and the capsule coating layer is an alginate. Alternatively, it is a soft spherical resin that disintegrates under compression, and the transdermal absorption aid is an external preparation for skin comprising one or more of glycerin, polyethylene glycol, and lecithin.

The present invention will be explained in detail below.

As the radiation protection substance used in the present invention, any known substance can be used as is.

For example, glutathione is a sulfur-containing amino acid.

, cysteine, cysteamine, and their derivatives, etc.; amines include serotonin; active oxygen scavengers include superoxide dismutase and derivatives thereof (hereinafter abbreviated as SOD), catalase, peroxidase, metallothionein, etc., and these species or a mixture of two or more species can be used.

Among these substances that protect against radiation damage, glutathione, cysteine, SOD, and catalase are particularly excellent when considering whether they are components in the body and whether they have few side effects.

Next, the coating layer used in the present invention may be a natural polymer or a synthetic polymer.

As the natural polymer, alginates derived from seaweed can be used, and as the synthetic polymers, methacrylic acid esters, cyanoacrylic acids, etc. can be used.

To manufacture the capsules of the present invention, the method for manufacturing artificial salmon roe may be referred to (for example, Japanese Patent Publication No. 61-4
No. 3029, JP-A-58-16649, JP-A-61-
No. 4509, JP-A-61-21070, JP-A-01-
91762, JP-A-01-123625, etc.>
. The thickness and strength of the capsule coating layer can be adjusted by adjusting the concentrations of alginate and calcium ions and reaction time. In addition, in order to improve the stability of capsules, it is necessary to improve the compatibility, fluidity, specific gravity, and osmotic pressure of the inclusions.
Conversely, it is important to consider disintegration during use.

Furthermore, as a method for producing the capsules of the present invention, encapsulation using a compression-disintegrable soft spherical resin can also be referred to (see, for example, JP-A-60-224609, JP-A-64-43343Q, etc.).

Next, the transdermal absorption aids used in the present invention include glycerin,
These include polyhydric alcohols such as polyethylene glycol, moisturizing ingredients for the stratum corneum such as hyaluronic acid, surfactants, and lecithins, but glycerin, polyethylene glycol, and lecithin are superior in terms of safety and dispersibility.

Next, the product of the present invention stabilizes the radiation hazard protection substance,
This article describes that it is an external preparation for skin with enhanced transdermal absorption.

(1) Stability test (i) Storage stability of radiation protection substance (glutathione) Experimental method and results The dispersion in polyethylene glycol 400 and Example 1 of the present invention (external skin preparation (1)) were each sealed and left at 40'C for one month, then opened and the degree of odor was sensory evaluated. .

(Results) All of the products in which glutathione was dispersed in various solvents had a sulfur odor, but when the product of the present invention was placed in the palm of the hand and the capsule was broken with finger pressure, there was almost no sulfur odor.

In other words, it can be seen that glutathione is stably maintained in the product of the present invention.

(ii) Storage stability of capsules <Experimental method and results> (Sample and evaluation method) Three capsule bodies of Example 1 of the present invention were placed in a weighing bottle,
Add 1/2 amount of the following dispersion medium to disperse the capsules,
The container was sealed and left at room temperature for 2 weeks, and changes in the state of contact were observed with the naked eye.

(Results) As is clear from the above table, glycerin and polyethylene glycol are superior in preserving capsule bodies.

(2) Transdermal absorption test <Experimental method and results> (a) Sample sample 1: Glutathione from Example 1 was converted into labeled glutathione (
30-Geltadeone>, take the skin external preparation (1) in the palm of your hand, break the capsule body with finger pressure, and mix well with glycerin.

Sample 2: The glutathione of Example 1 was labeled as glutathione (30-glutathione), and the capsule alone (not containing glycerin) was crushed with fingers.

(b) Experimental method Five Hartley guinea pigs were selected as experimental animals.

Immediately before administration, hair removal sites were created on the left and right sides of the dorsal midline using electric clippers and an electric razor, and sample 1 was placed on the left site and sample 2 was placed on the left side.
Apply to the right area.

Reapply after 24 hours, sacrifice the guinea pigs after 48 hours, collect skin tissue from each administration site, and immediately
Freeze in dry ice.

Frozen sections of 50 μm are made using a rotome.

Transfer the sections onto glass slides and cover with odoradiographic stripping film in the dark.

After developing and fixing the film, perform nuclear staining with Harris hematoxylin.

Observe the distribution state of silver particles with the naked eye.

(C) Results In the case of sample 1, the silver particles are distributed along the hair shaft of the hair follicle, but in the case of sample 2, they mostly remain at the administration site.

That is, it can be seen that by using glutathione and glycerin together, glutathione, which is a substance that protects against damage to the copper wire, is easily absorbed through the skin by glycerin, which is a transdermal absorption aid.

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

Incidentally, the blending amount is in parts by weight.

Example 1. External skin preparation (1) ■ Preparation of capsule 0 Component (8) to be encapsulated is entrained at room temperature and uniformly dispersed to form a sol.

This sol-like material is dropped into the solution (B) from a tubular nozzle with an inner diameter of 5M. Furthermore, the granules are taken out and placed in solution (C) to obtain spherical capsules with a strong coating layer. Wash lightly with water.

(2) Preparation of external skin preparation (1) Place the capsule in a container and add the same weight of glycerin to disperse it to obtain a product.

(Space below) Example 2゜External skin preparation (2) ∎ Preparation of capsule [ ) Take (A) into an inclusion homomixer, mix at room temperature, and dissolve uniformly. Along with this, uniformly dispersed (8) is added and emulsified to obtain a highly viscous emulsion.

(ii) Preparation of capsules This emulsion is dropped into a 1% aqueous sodium alginate solution through a tubular nozzle with an inner diameter of 5M to obtain granules.

Furthermore, this granule is transferred to a 2% calcium chloride aqueous solution to obtain a capsule body with a strong coating layer.

Wash lightly with water.

(2) Preparation of external skin preparation (2) Place the capsules in a container, add 172 weight of polyethylene glycol 400, and shake lightly to disperse the capsules to obtain a product.

■ How to use: Place one capsule in the palm of your hand and break the capsule with finger pressure to release the stably contained SOD, a radiation protection substance, and polyethylene glycol 40, a transdermal absorption aid.
0 and apply to the desired biological site, removing the coating layer if necessary.

3 Example 3. Skin external preparation (3) ■ Preparation of compression-disintegrable soft spherical resin capsules Place (A) in a homomixer, rotate at high speed at 8.0007 Um at room temperature, slowly add (B), and add water-in-oil esulsion. Set the rotation speed of the homomixer to 1,000 γpm and slowly add (c) to make a water-in-water type multiple emulsion.

Aspirator - Distill the toluene under reduced pressure.

4 Filtered methyl methacrylate containing cysteine/
A capsule body coated with vinyl acetate copolymer is obtained.

(2) Preparation of external skin preparation (3) Place (A) in a Henschel mixer, mix at low speed for 5 minutes, and then grind and mix in a grinder. Next, transfer this pulverized mixture to a Henschel mixer, and slowly add (8) while rotating at high speed at room temperature. Rotate at low speed, add (C), and mix for 2 minutes. This is passed through a blower sifter and packed into a container to form a powdered product.

■ How to use During makeup operation, the resin coating layer of the capsule is destroyed by pressure from fingers, etc., and the stably contained cysteine, a substance that protects against radiation damage, is released, and mixed with glycerin, which is a transdermal absorption aid, Apply to body parts.

[Effect of the invention] The product of the present invention stabilizes the radiation damage protection substance, and
This is an external preparation for skin that promotes transdermal absorption.

Claims (1)

[Scope of Claims] 1) A skin preparation for external use, characterized in that a capsule containing a radiation protection substance and a transdermal absorption aid are used together. 2) The skin external preparation according to claim 1), wherein the radiation damage protective substance comprises a sulfur-containing amino acid or/and an active oxygen scavenger. 3) The skin external preparation according to claim 1) or 2), wherein the sulfur-containing amino acid is glutathione or cysteine, and the active oxygen scavenger is superoxide dismutase or a derivative thereof, or catalase, and comprises one or more of these. . 4) The skin external preparation according to claim 1), wherein the capsule coating layer is made of alginate or a compressible soft spherical resin. 5) Claim 1 in which the transdermal absorption aid comprises one or more of glycerin, polyethylene glycol, and lecithin.
) External skin preparations listed in ).