JPS584721A - External agent for skin - Google Patents

Abstract

PURPOSE:An external agent for the skin, containing pantetheine-S-sulfonic acid and/or a salt thereof, and capable of inhibiting then irritation of a base and an drug active constituent without affecting the pharmaceutical stability. CONSTITUTION:An external agent for the skin obtained by dissolving, dispersing or mixing a drug active constituent in a base, e.g. vaseline, liquid paraffin or fat, and incorporting pantetheine-S-sulfonic acid or a salt thereof in an amount of 0.5% or more, preferably 1-20%, and if necessary adding a penetrant or kerationous softening agent thereto. The dosage form thereof is a solution, ointment or powder. The pantetheine-S-sulfonate which is an active constituent is an easily handleable powder having a high solubility in water at a low cost. The compound is useful as a precursor for coenzyme A playing an important role in the energy metabolism in the living body.

Description

[Detailed description of the invention] The present invention relates to a skin external preparation.

In particular, it relates to a skin preparation for external use which is formulated into a hair base, and is particularly effective in suppressing skin layer irritation caused by drugs and cosmetic agents.

- Generally, external skin preparations, cosmetics, and other topical products applied to the outer skin are made up of a base of oil, surfactant, moisture, and medicinal ingredients, additives, fragrances, etc. Among these components, surfactants and trace additives are indispensable in the composition of the formulation, but it is not known that they cause adverse side effects due to their transdermal absorption. Even with fc medicinal ingredients, in addition to their original ``drug'' action, side effects such as irritation and redness are very often observed, and therefore, despite their excellent medicinal efficacy, they have a negative effect on the skin. There are many drugs that cannot be used in practice because they are too irritating, and VC, which mixes various medicinal ingredients, has its own limitations.

Conventionally, we have devised base formulations that are less irritating by refining and selecting pharmaceutical raw materials and conducting skin irritation tests, and we have actively added anti-inflammatory agents. However, there are strict restrictions on the use of base materials, so
There are many cases where the product does not meet expectations, such as the fundamental stability of the drug being compromised or the anti-inflammatory drug itself having side effects due to VC, and no fundamental solution has been reached at all. .

In view of this current situation, the present inventors (1) developed a vast number of compounds for the purpose of developing a skin irritation suppressant that suppresses the irritation of the base and medicinal ingredients and does not affect the stability of the formulation. , continued intensive studies on skin irritation (JII control effect, stability as a formulation, coexistence with medicinal ingredients, etc.) in external VC, and found that pantethine is a substance that reduces skin irritation. ) The present invention is an extension of that research, and as a result of a more detailed study of nonξntethin analogs, pantethin-
They found that 3-sulfonic acid and its salts are substances that have an effect equal to or greater than that of pantethine.

Furthermore, pantethine is a non-crystalline viscous substance, so it has the disadvantage of being sticky and difficult to handle, but ξ-ntetheine-S-sulfonate is an easy-to-handle powder and has a high tendency to leave flakes in water. It also lacks the characteristic (6) of being much lower in price than pantethine in terms of cost.

Pantethine-8-sulfonic acid and its salts are compounds that act before coenzyme A, which plays an important role in energy 4 in the living body, just like the presently used clinical drug, ``Nodetin''. It is known to be a useful compound as a chemical substance (JapanJ, Microb
iol, vol 16 (3) 239 (1972))
It is presumed that the requirements for coenzyme A can be sufficiently supplemented even when applied topically.

The present invention has been completed based on this new finding based on VC, and is an external skin preparation characterized by containing pantethine-8-sulfonic acid and its salt.

Nintetheine-S-sulfonic acid and its salts, which are the active ingredients in the present invention, are used as external preparations, but the dosage form is not limited to %.
Liquids, ointments, powders, and other various dosage forms can be used as appropriate.

There is no particular restriction on the amount used, and it can be selected as appropriate depending on the medicinal ingredients used and other compounding bases (4), but it is usually best to mix 0.5 or more, and preferably It is preferably within the range of 1 to 20%.

When preparing a formulation, the medicinal ingredients are dissolved, dispersed, or mixed in a suitable base, and pantetin-8-
In the case of sulfonic acid, add any salt that matches the base, and if necessary, add penetrants, keratin softeners, and emulsifiers and suspending agents to adjust the dosage form. Add agents and other ingredients to formulate a formulation.

In addition to the above, pantethine-8-sulfonic acid and its salts may be added and mixed at the same time as medicinal ingredients, if necessary.
May be added with other ingredients, and if necessary
It is also possible to add and mix all the ingredients at once. As the preparation method, conventional methods in the art can be used as appropriate.

As the ointment base, petrolatum, white petrolatum, liquid paraffin, fat (oil), lanolin, glycerin, wax, resin, higher alcohol, glycols, or mixtures thereof can be used. As a liquid agent, for example, medicinal ingredients 1 to 5
Weight parts and nonξ nteteine-S-sulfonic acid and its salts 1
~5 parts by weight of the compound may be dissolved in purified water to make a total of 100 parts by weight, and the like can be used as appropriate.

The method of use is not different from that of ordinary skin preparations, and it depends on the medicinal ingredients used, but in general, it is enough to apply an appropriate amount to the affected area 2 to 5 times a day, and when used as a cosmetic. However, there is no problem in using it just like regular cosmetics.

The fact that pantethine-8-sulfonic acid and its salts have an extremely outstanding effect as a skin irritation suppressant is shown in Test Examples 1 to 1 described below! As is clear from 1, pantethine-8-sulfonic acid and its salts are not only stable in aqueous solution, but also physicochemically very difficult to react with not only medicinal ingredients but also other ingredients. It has excellent advantages.

Therefore, by using pantethine-8-sulfonic acid and its salts, it has not been possible to provide a practical IC as an external preparation, although the medicinal ingredients themselves are excellent.
Since it is possible to freely use 1 ftu of compounds that did not come into existence, and it is also possible to use medicinal ingredients in combination, it is possible to manufacture external preparations with complex effects that could not be manufactured in the past, and the impact on the preparation is immeasurable. There is. By using gondetheine-S-sulfonic acid and its salts, it is possible to freely apply a desired drug to the sensitive skin of children, women, etc.

Even in the case of cosmetics, there has been no end to complaints about skin irritation, but such problems can be prevented by incorporating the external preparation according to the present invention.
Desired ingredients can be mixed freely.

[Test Examples 1, 2, and 6 demonstrating that F-pantethine ~ S-sulfonic acid and its salts are extremely effective in suppressing skin irritation caused by topical agents, were combined with commonly used base ingredients, medicinal ingredients, Among fragrances, sodium lauryl sulfate, resorcinol, and cinnamic aldehyde (7), which are particularly irritating to the skin, will be described (7), and then examples of the present invention will be further described.Test Example 1 Lauryl sulfate Sl・Rium (hereinafter referred to as [sT, SJ)
Preparation 1 to human batch tests were conducted using a 05% aqueous solution (N) and an aqueous solution (■1) in which one strip of sodium pantethine-8-sulfonate was mixed therein as a sample.

The test was carried out by applying each sample to a lint cloth with a 5-patch test bandage of approximately [], []'5 m1 (5 patches) and occluding the inner VC of the left upper arm of 10 male adults for 24 hours. After removing the bandage,
Thirty minutes after removing the residual sample, the skin reaction at the patched area was observed with the naked eye to determine the degree of irritation.

Number of subjects: 10 healthy male adults Judgment criteria: (-) No change ±) Slight erythema (+) Erythema (-1-10) Erythema, edema, or box examination (+-1-10)
Erythema, dilated pupils, and water marks were judged as (-1-), (-)
+) and (+Joshi) were positive, and both were tested at a ratio of (8).

Table 18 Ls Batch Test As is clear from the above results, the addition of 1% sulfonate (B) clearly caused S L
It suppresses the stimulus response of S. Furthermore, no serious cases were observed among the subjects who tested positive for (R).

Test Example 2 Table H Resorcinol prescription (C) Prescription (D) Lupulsin 5g5. ! 92 Pantetine-8- Sodium sulfonate 33 Purified water 554 Macrogol soft
Total amount: 100.9 g Total: 1100 g Resorcinol ointment was prepared I7 according to the prescription in Table H, and a human patch test was conducted in the same manner as in Test Example 1 (however, the applied sample was approximately 0.059 mm, the number of subjects was 12 males).

In this test, as a pretreatment, the epidermis of the application site was peeled off using Seronoa/tape.

Table 1 Resorcin ointment patch test From the above results, the irritating reaction of resorcin ointment is suppressed by resorcin ointment containing 6% ξ tatetin-S-sulfonate sodium (D).

Actual hm example 6 Table 1v Cinnamomum aldehyde solution prescription (E) Prescription (F) Prescription fG11 Cinnamic aldehyde 1ml ml i
mA6 Bantetin -19- 4 Bantetin -84- Calcium sulfonate -19 According to the formulation in Table IV, cinnamic aldehyde common solution was prepared and a human patch test was conducted in the same manner as in Test Example 1 (however, the number of test subjects was 2, 12 males). went. -1 was also compared with pantethine.

Table ■ Cinnamaldehyde patch test From the above results, pantethine-8-calcium sulfonate (1) has an efficacy equal to or greater than that of pantethine, and inhibits the irritating response of cinnamaldehyde 3.

In parallel with each test, we conducted a batch test of 1% Nitetin-S-sulfonic acid carunium and Natriuno 4 aqueous solution, but all 10 people tested negative (→
It was confirmed that calcium nonatine-S-sulfonate and sulium itself do not cause skin irritation.

As described in detail below, the present invention is capable of sufficiently suppressing the skin irritation that is a problem when using topical preparations, and relates to new uses of pantethine-S-sulfonic acid and its salts that were previously unknown. It is.

Examples of external skin preparations (drugs, quasi-drugs, and cosmetics) according to the present invention will be shown next, and the numerical values in the examples represent weight %.

Example 1 Salicylic acid bandage 1 Salicylic acid 50 2Pantetin-8- Calcium sulfonate 1 6. Add 100 g of Kizuna Soho base.

Melt and mix 6, and when it has cooled halfway, add 1.2 and stir until it is evenly distributed throughout the room, knead to form a sticky substance, and spread this evenly on a cloth to make a product.

Example 2 Urea solution 1 Urine element 5 2 Pantetin-8~ Calcium sulfonate 2 Filter preservatives Appropriate amount 4. Add purified water to make 100ml.

- The above components are mixed and dissolved to form a product.

Example 3 Hair Shampoo 2 Sodium Lauryl Sulfate 103 Lauric Acid Diethanolamide 5 4 Propylene Glycol 2 5 Pantethine-8- Sodium Sulfonate 2 6, Preservatives, Colorants, Fragrances Appropriate amount 7, M# Water Add 100+++4'.

The above ingredients are mixed and dissolved to form a product.

(1ro) -1Q9-Example 4 Calamine lotion 1, ethanol 14.02 Glycerin 5゜6 red iron 02 4 Zinc oxide 05 5, Kaolin 16 Camphor
02 1 Pantethine-8- Sodium sulfonate 15 8, fragrance, preservative Appropriate amount 9 Purified water Add to make the total volume 100ml.

The above ingredients are mixed uniformly to form a product.

Example 5 Resorcin ointment 1, Resorcin 5 2 Pantethine-8- Sodium sulfonate 6 6 Purified water 5 6 Preservative appropriate amount Z Macrogol 400 52 8, Macrogol 4 [10035-(14) 1.2 dissolved in 3 , 6, 7.8 is heated in advance and added to it, stirred and cooled to make a product 1. Agent Patent Attorney 1) Parent (15) 133-

Claims (1)

[Claims] A skin external preparation characterized by the following formula (% formula % (where M is hydrogen, alkali gold maple, or 1/2 a)