JPS6144814A - Dermal drug for external use - Google Patents

Abstract

PURPOSE:A drug for external use, containing a germanium-containing fatty acid, alkali metal salt, ammonium salt, amide derivative etc. thereof, having improved stability and percutaneous absorbability, having particularly improving effect on pigmentation and skin beutifying effect, and useful for treating dermatopathy. CONSTITUTION:A drug for external use obtained by incorporating a germanium- containing fatty acid expressed by the formula, an alkali metal salt, ammonium salt, organic amine salt or amide derivative thereof, e.g. carboxyethylgermanium sesquioxide or sodium carboxyethylgermanium sesquioxide, in an amount of preferably 0.1-1.0% with other components. The compound expressed by the formula is found to have improved stability and percutaneous absorbability as compared with the conventional vitamin C derivatives, glutathione derivatives, etc. and further improving effect on various dermatopathies, particularly pigmentation, and skin beautifying effect such as improving luster, color, fine wrinkles, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a skin external preparation effective for treating skin diseases.

The skin external preparation of the present invention is a germanium-containing fatty acid represented by the formula % (1), or its alkali metal salt, ammonium salt, organic amine salt, or amide derivative of the fatty acid represented by the above formula (summer). α to the base
α1 to 5%, preferably α1 to 1.0%.

It has already been recognized that these organic gels have the effect of suppressing the growth of Ehrlich ascites cancer cells, and are also effective against various intractable diseases such as various visceral pains, leukemia, liver dysfunction, hypertension, and menopausal disorders. It is also known that it is highly effective in improving the condition of skin diseases, but there is still nothing known about its effects and effects when used externally for the treatment of skin diseases.

The present inventors have continued to conduct intensive research on the effectiveness of these organic germanium compounds when applied externally, transdermal absorption, stability as a formulation, etc., and have found that these organic germanium compounds can improve various skin diseases, especially pigmentation disorders. In addition, when formulated, it has been compared with known skin whitening substances such as vitamin 0 derivatives, glutathione derivatives, hydrogen peroxide, etc. They found that it has excellent stability and transdermal absorbability that supports its effectiveness.

The present invention has been completed based on this knowledge.

The present invention will be described below in detail based on specific examples to confirm its effects.

The skin cream according to the present invention described in Example 1 below is designated as Sample I, and vitamin 0 distearate is blended in place of sodium carboxyethyl germanium sesquioxide in the formulation of this Sample IO skin cream.
A skin cream prepared in the same manner as Sample I was used as Sample ■, and the same amount of distilled water was used in place of the sodium chloride oxide in the formulation of Sample IO skin cream. The following tests were conducted using the sample creams 1-moss.

As subjects, 16 people between the ages of 62 and 60 with pigmented skin were selected and divided into three groups.

The 8 people in the first group used Sample I, the 4 people in Group 2 used Sample ■, and the 4 people in Group 5 used Sample ■ for 6 months. During this time, the use of other cosmetic creams was prohibited. The degree of improvement after six months of continuous use was judged by myself and by a dermatologist, and the results are summarized as shown in Table I. As is clear from Table 1, Sample I containing sodium carboxyethyl germanium sesquioxide caused facial melasma and
Postpartum or sunburn shows a clearly superior improvement effect on stains, etc. compared to Sample 2 and Sample 2, and furthermore, when using Sample 1, the skin feels especially moisturized, shiny, and
Significant skin beautification effects were found, including recovery of firmness and improvement of fine wrinkles, and no worsening of symptoms or side effects were observed during the test period.

The acute toxicity of the carboxyethyl germanium sesquioxide used in this test when administered orally to rats was 10 f/Kf or more in both sexes, and in a 6-month oral chronic toxicity test, the dose was 30 sv/K per day.
No abnormalities were observed in general conditions, body weight changes, blood, organ weights, or various functional tests in any group within the range of f to 5,000 capes/V4, and all test animals survived during the experiment period. In addition, the local irritation of this compound was investigated by rabbits.
When examined using the isie method, there was almost no skin irritation such as erythema, edema, or hyperemia in the A1-10 range, and furthermore, in the Nogutsuchi test conducted by humans, there was no local irritation at concentrations of 1 or less. It was confirmed that there was no such thing.

Regarding the percutaneous absorption of this compound, the skin cream of Example 1 described below was used, and this was applied to the back of a rabbit that was fitted with a neck shackle to prevent ``licking'', and the rabbit was kept in a metabolic cage. When urine was collected over time and germanium in the urine was analyzed using atomic absorption spectrometry, it was found that germanium was excreted over several days from 1 hour after administration, and the transdermal absorption of this compound was qualitatively confirmed. confirmed.

These test results support the safety and effectiveness of the above-mentioned organic germanium compound as an external skin preparation.

Conventionally, vitamin C derivatives, glutathione derivatives, hydrogen peroxide, hydroquinone derivatives, etc. have been used as external preparations for skin pigmentation, but all of these compounds are susceptible to oxidation and dehydration, and are susceptible to heat. It is unstable to light, acids, alkalis, etc., and even when formulated as an external preparation, it tends to decompose and lose its activity over time, and it also causes discoloration and odor, etc., and has various disadvantages. existed. On the other hand, the organic germanium compound, which is the active ingredient of the topical skin preparation of the present invention, is extremely stable against heat and light as described below, and even when it is made into a preparation, there are changes over time such as discoloration, odor, and decomposition and inactivation. It is extremely advantageous in that it can be stably and easily blended into various external use bases because it does not cause.

α6% of carboethoxygermanium sesquioxide
The aqueous solution was sealed in a colorless and transparent glass ampoule, exposed to direct sunlight for about 3 hours a day, and changes in the content of germanium compounds over time were investigated. As shown in Table 2, the content of the germanium compound remained stable even after 12 months. Similarly, when it was left in a constant temperature bath at 50°C, it showed good stability, with layer separation and deterioration occurring even after 3 months, as shown in Table 3. Even after being left at 50°C for 6 months, no change in infrared absorption appeared.

Table ■ $I N710 Determined by titration with NaOH *2
Quantitative Table by Atomic Absorption Spectrophotometry ■ The organic germanium compound which is the active ingredient of the skin external preparation of the present invention can be produced, for example, by the method described in Japanese Patent Publication No. 46-2964 or a modified method thereof, and includes carboxyethylgermanium sesquioxide. is synthesized by hydrolysis of trichlorogermanium ethyl carboxylic acid, hydrolysis of trichlorogermanium ethyl nitrile, etc., and its alkali salts and amide derivatives can be easily produced, for example, from the above-mentioned carboxyethyl germanium sesquioxide by conventional chemical methods. When the organic germanium compound obtained in this way is formulated as a skin preparation for external use, it may be formulated in either crystalline or solution form, and it may be formulated in either free form, alkali salt form, or amide derivative form. These can be appropriately selected and used depending on the base used.

As mentioned above, the skin external preparation of the present invention is extremely useful as a pharmaceutical since it has an effect of improving pigmentation and has an excellent skin beautifying effect.

Although the mechanism of action of this effect has not been fully elucidated, it is possible that the germanium compound has an ability to adjust the surface membrane potential of abnormal cells in the body, and that the germanium sesquioxide group can easily react with dehydrogenation in the body. It is estimated that it improves the healing ability of the living body by promoting oxidation, smoothing redox reactions, and inhibiting peroxidation. However, such estimation itself is not directly related to the establishment of the present invention.

Next, examples of the skin external preparation according to the present invention will be shown.

The numerical values in the examples represent weight %.

Example 1 Skin cream (A) Squalane 1α0 Vaseline 10.0 Mitsuwax
50 micro socks
9゜Whale 7 Umuroisozolopeel myristate 12. [lNitsukol MYB-454,5 Sunozon 60 5.0) ξ Methyl oxybenzoate 0.1 (B) Propylene glycol 10.0 Distilled water
32.4(O) Fragrance (1
5. The oil layer of the above formulation) and the water layer of the above formulation 03) are heated to 80°C, and the two are combined and emulsified. During cooling, add the flavoring agent (0) above and cool to 30°C to obtain a product.

Example 2 For skin/Guda (4) Talc 95 (%)
Zinc White 2 Zinc Stearate 2 (B) Fragrance Appropriate amount After thoroughly mixing the powder components of the above formulation, add the above (B)
) is added and further mixed to make the product.

Example 3 Skin ointment (A) Beeswax 8 Cetanol 6 White petrolatum 85 03) Cholesterol 3 Carboxyethyl germanium sesquioxide The above (N) prescription ingredients were heated on a water bath and kneaded, and this was added with the above (B). After stirring and mixing the prescription ingredients, heating is stopped and the product is kneaded.

Patent applicant Asai Germanium Research Institute Pola Chemical Industries, Ltd.

Claims (1)

[Scope of Claims] A product for treating skin diseases characterized by containing a germanium-containing fatty acid represented by the formula (Ge.CH_2CH_2.COOH)_2O_3, or an alkali metal salt, ammonium salt, organic amine salt, or amide derivative thereof. Topical preparation.