Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1993-11-22
1997-04-22
Cintins, Marianne M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
514172, 514177, 514180, 514181, 514182, A61K 3156
Patent
active
056229429
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT JP 92/00543, filed Apr. 24, 1992.
TECHNICAL FIELD
The present invention relates to a percutaneous absorptive anesthetic in which a local anesthetic is mixed with an absorption-promoting substance.
BACKGROUND ART
There have been proposed various medicines in the prior art which may be percutaneously absorbed and is effective when applied on the topical site in the human body. These medicines which are intended for topical anesthesia include, for example, an injection, and a liquid, jelly and spray, etc. for use as a surface anesthetic.
However, the latter surface anesthetic is known to provide a remarkable topical anesthetic effect against the mucous membrane of esophagus, stomach and mouth etc. but it is quite ineffective against the topical anesthesia of the skin.
Recently, in the field of anesthesia, the need of pain removal has become a matter of concern when a relatively thick needle is pierced through the skin in such a case where the vena must be punctured to get an access to the vessel, or when the epidural anesthesia and spinal anesthesia etc. must be effectuated. That is, an anesthetic such as lidocaine hydrochloride and procaine hydrochloride etc. have traditionally been dosed to the patient through the syringe, but such procedure cannot avoid causing pain to the patient during a dosing procedure.
With the above-described as a background, the inventor et al of the present patent application has been engaged in the developmental work to provide means which allow lidocaine etc. to be absorbed percutaneously, and tried various substances in order to shorten the time needed for the topical anesthesia to take effect, through an improved percutaneous absorptive effect. As a result, the inventor has found that glycyrrhizin and glycyrrhetic acid, and their derivatives have a remarkable percutaneous absorption improving effect, and thus the present invention has been achieved.
DISCLOSURE OF THE INVENTION
The percutaneous absorptive anesthetic in accordance with the present invention consists of one or more types of mixture which has/have been selected from the group made of compounds as listed below, and an anesthetic.
Typical compounds may be those to be represented by the general formula given below; ##STR1## [provided that R.sub.1 represents HOOC--. --H, ##STR2## --OCCH.sub.2 CH.sub.2 COOH, or a compound to be represented by ##STR3## In addition, a compound that has a pharmaceutically allowable salt as its effective ingredient, its derivative of the glycyrrhetic acid represented by the following formula, and its pharmaceutically allowable salt. ##STR4## [provided that X represents a remaining radical of 18.beta.-olean-12-ene-3 .beta., 30-diol, 18.beta.-olean-9, (11)12-diene-3 .beta., 30-diol, or olean-11,13(18)-diene-3.beta. and 30-diol]
Among the compounds which may belong to those represented by the above general formulas (I) and (II), the following substances can be listed. 30-dihemiphthalate
These compounds (1)-(7) are cited hereinbelow as compounds 1-7.
Such compounds as lidocaine, bupivacaine, tetracaine, prilocaine, etc. may be suggested for selection as an anesthetic.
The skeleton of the above-described compound is formed from an active ingredient which is contained in a glycyrrhiza, and displays a remarkable percutaneous absorption improving effect, whereas its side effect against the skin is extremely negligible. Consequently, the compound of the present invention may serve to substantially reduce the time needed for the anesthetic such as lidocaine, bupivacaine, tetracaine, prilocaine, etc. to take effect causing a skin anesthesia after being applied.
Besides, it may be well expected for the compound to absorb various other medicines used on the topical site more easily.
The disodium salt of the compounds 3-7 may be produced in the procedure to be described hereinbelow. glycyrrhetic acid. glycyrrhetic acid. 18.beta.-olean-12-ene-3 .beta., 30-diol. 18.beta.-olean-9, (11)12-diene-3 .beta., 30-diol. olean-11,13(18)-diene-3 .beta., 30-diol, and the compo
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Kano Tatsuhiko
Mishima Motohiro
Nagata Nobuyuki
Nakano Masahiro
Cintins Marianne M.
MacMillan Keith
Minophagen Pharmaceutical Company
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