JPH03120230A - Percutaneous absorbefacient of drug active ingredient and percutaneous absorption type pharmaceutical - Google Patents

Abstract

PURPOSE:To obtain a percutaneous absorbefacient capable of exhibiting ultrahigh percutaneous absorbefacient action on drug active ingredients by blending a straight-chain alkanesulfonate having a specific number of carbon atoms with other ingredients. CONSTITUTION:A percutaneous absorbefacient, obtained by using a straight- chain alkanesulfonate expressed by the formula (m and n are integers and m+n is 11-14) as a percutaneous absorbefacient of drug active ingredients and capable of excellently absorbing the drug active ingredients from the skin. Although an aqueous solution containing 0.001-60wt.% aforementioned compound is directly used as the above-mentioned absorbefacient, the compound may be blended in an amount of preferably 0.001-10wt.%, especially 0.01-5wt.% based on a suitable skin pharmaceutical for external use so as to improve usability, etc., and touch, etc., to the skin. Furthermore, 0.001-10wt.% aforementioned compound may be preferably blended with 0.001-10wt.% drug active ingredients and used as a percutaneous absorption type pharmaceutical.

Description

[Detailed description of the invention]

Field of Industrial Application] The present invention relates to an absorption enhancer and a transdermal preparation for transdermally administering a medicinal ingredient. [Prior art] In recent years, in order to avoid inactivation of pharmaceuticals by the digestive organs, liver, etc., excessive administration during long-term continuous administration, and associated side effects, transdermal absorption administration methods have been developed. The development of a formulation is underway. Various surfactants are known to have the effect of promoting transdermal absorption, and among these, sodium lauryl sulfate is listed in the Japanese Pharmacopoeia, making it one of the most widely used surfactants. There is. However, this sodium lauryl sulfate still cannot be said to have a sufficient transdermal absorption promoting effect, and has not been satisfactory. [Problem to be Solved by the Invention J] In view of the above-mentioned current situation, the present inventor conducted intensive research and found that, surprisingly, the higher the carbon number of linear alkanesulfonates, the higher the transdermal absorption promoting effect. , carbon number 1
It was found that compounds Nos. 4 to 17 exhibited an extremely higher transdermal absorption promoting effect than sodium lauryl sulfate. The present invention was made based on this knowledge, and an object of the present invention is to provide a transdermal absorption enhancer and a transdermal absorption type preparation that have an extremely high transdermal absorption promoting effect. [Means for Solving the Problems] The present invention has the following general formula (I) CH, (CH,)m-CH(So, Na)-(CH,)
nCH, (I) (where m and n represent integers, m+n
is a linear alkanesulfonate represented by 11 to 14), and a medicinal ingredient and a linear alkanesulfonate represented by the above general formula (I). This is a transdermal absorption preparation containing phonate. The linear alkanesulfonate represented by the above general formula (I) can be obtained by sulfoxylating or chlorosulfoxylating a linear alkane in the presence of light, and has 14 to 17 carbon atoms. Use the following: Those with less than 14 carbon atoms have a weak transdermal absorption promoting effect, and 1
This is because when it is 8 or more, the transdermal absorption promoting effect decreases. Note that this linear alkanesulfonate having a predetermined number of carbon atoms may be used alone, or two or more types of linear alkanesulfonates having different numbers of carbon atoms may be used as a mixture. The accelerator of the present invention can be used as it is by making the linear alkanesulfonate into an aqueous solution of 0.001 to 60% by weight, but in order to improve ease of use and feel on the skin, It can also be used by incorporating it into the base of suitable external skin preparations, such as cream preparations, lotion preparations, ointment preparations, aerosol preparations, and adhesive tape preparations. In addition, this accelerator contains ingredients that are generally used as compounding agents for pharmaceuticals, quasi-drugs, or cosmetics, such as alcohol, wax, fatty acids, surfactants, chelating agents, pigments, dyes, and preservatives. Agents, fungicides, antioxidants, ultraviolet absorbers, fragrances, etc. may be added. In this case, the content of the linear alkanesulfonate in the promoter is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight. Moreover, this linear alkanesulfonate can be mixed with a medicinal ingredient and used as a transdermal absorption type preparation. In this case, the medicinal ingredients can be widely applied, such as various therapeutic drugs, vitamins, hormones, diagnostic drugs, insect repellents, insecticides, and keratin softeners. In addition, the same bases and compounding agents used for the above-mentioned accelerator can be used in this transdermal preparation. It is preferable that the transdermal preparation contains a linear alkanesulfonate in an amount of 0.001 to 10% by weight, and a medicinal ingredient in an amount of 0.001 to 10% by weight, as appropriate. The transdermal absorption enhancer of the present invention can be applied directly to the skin, or after washing it off if necessary, and then applied together with the absorbent to quickly remove the medicinal ingredient from the skin. Absorbed. On the other hand, when the transdermal absorption type preparation of the present invention is applied to the skin, the medicinal ingredient is rapidly absorbed through the skin.

【Example】

The abdominal hair-free skin was removed from multiple Wistar male rats (body weight: 250-300 g) and placed into multiple Frantz-type cells.
1, effective transmission cross-sectional area = 1.13 m). The dermis-side receiving chamber of each cell was filled with 11.4 ml of isotonic phosphate buffer with a pH of 7.4, and the stratum corneum surface was filled with a carbon number of 10 (
SAS-CIO), l l (SAS-C1l), 12
(SAS-C12), 13 (SAS-C13), l
4 (SAS-C14) alone and a mixture of 15 to 17 (SAS-CI5 to 17) in an isotonic phosphate buffer solution of 20 mmolar sodium alkanesulfonate at pH 7.0 in the drug supply chamber. After washing the stratum corneum surface thoroughly with physiological saline, 2 liters of citric acid-phosphate buffer with pH 3.0 containing 5 molar salicylic acid dissolved in the drug supply chamber was administered. did. The concentration of salicylic acid in the receiving chamber after 12 hours was determined by high-performance liquid chromatography, and the amount of salicylic acid that permeated into the receiving chamber was calculated. (treated with isotonic phosphate buffer at pH 7.0). For comparison, the same operation was performed using sodium lauryl sulfate (SLS) in place of the linear sodium alkanesulfonate. These results are also listed in Table 1. It can be seen that the products in Table 1 have a significantly high transdermal absorption promoting effect. [Effects of the Invention] Since the present invention uses a linear alkanesulfonate having 14 to 17 carbon atoms in a transdermal absorption enhancer and a transdermal absorption type preparation, medicinal ingredients can be absorbed extremely well through the skin. It has a special effect.

Claims (2)

[Claims] (1) The following general formula (I) CH_2(CH_2)m-CH(SO_2Na)-(C
H_2) Transdermal absorption enhancer for medicinal ingredients containing a linear alkanesulfonate represented by nCH_2(I) (where m and n are integers, and m+n is 11 to 14) . (2) Medicinal ingredients and the following general formula (I) CH_2(CH_2)m-CH(SO_2Na)-(C
H_2) a linear alkanesulfonate represented by nCH_2(I) (where m and n are integers, and m+n is 11 to 14).