Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1997-10-27
1999-04-27
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424436, 424464, 424489, 424494, A61K 948
Patent
active
058978755
DESCRIPTION:
BRIEF SUMMARY
The underlying object of the present invention is to demonstrate a substance which is suitable for the treatment of painful spasms and dyskinesia of the smooth musculature in the region of the abdominal cavity, particularly in the peritoneal cavity, such as gall-stone colic, stomach and intestinal spasms, irritable colon and pylorospasm, and in the retroperitoneal cavity also, such as renal colic and urethral stone colic.
Prior knowledge of the pharmacological action of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl) ester, which is also hereinafter termed the "ester", was substantially related to its cholinolytic activity, which has been known since 1943 (J. Am. Chem. Soc., 65 (1943) 262-267). In addition, publications from 1988-1990verify the high activity of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl) ester in relation to peripheral and central muscarine receptors of various organs (Eu. J. Pharmakol., 151 (1988) 83-96; Naunyn-Schmiedeberg's Arch. Pharmakol., 339 (1989) 145-151; Br. J. Pharmakol., 100 (1990) 395-397). German Patent Specification 42 05 843 C2 describes how .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl) ester has a strong neurotropic-spasmolytic effect, i.e. cholinolytic effect, on the urinary bladder muscle, which anatomically and physiologically forms part of the pelvic contents, as well as exhibiting a slight central cholinolytic activity.
An investigation of the further pharmaco-dynamic properties of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl) ester has surprisingly and unexpectedly shown a pronounced musculotropic-spasmolytic effect on the organs of the abdominal cavity (abdomen), as well as the considerable analgesic effects of this compound.
The present invention therefore relates to the use of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl) ester or salts thereof with physiologically compatible organic or inorganic acids for the therapy of painful muscular cramp conditions, and to the production of drugs for the therapy of painful muscular cramp conditions, in the region of the abdominal cavity, particularly of muscular cramp conditions in the region of the peritoneal cavity, such as pylorospasm, gall-stone colic, stomach and intestinal spasms and irritable colon, and also of those in the retroperitoneal cavity, such as renal colic and urethral stone colic. This use is applicable to human and veterinary medicine.
Examples of physiologically compatible acids which can be employed for the use of salts include the organic and inorganic acids which are customarily used in pharmacology, such as hydrochloric acid, sulphuric acid, phosphoric acid or carboxylic acids and dicarboxylic acids. Examples of suitable organic acids include acetic acid, fatty acids such as stearic acid, lauric acid, oleic acid or palmitic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, cyclamic acid, ascorbic acid, benzoic acid, 4-hydroxybenzoic acid, cinnamic acid, salicylic acid and mandelic acid. Sulphonic acids are also suitable, such as methanesulphonic acid, ethanesulphonic acid and hydroxyethanesulphonic acid. The salts can be formed in the usual manner.
FIG. 1 illustrates the musculotropic-spasmolytic efficacy of the ester on Taenia coli isolated from the guinea pig, compared with that of papaverine. Barium chloride in a bath concentration of 0.2 mg/ml was employed as the spasmodic. The dose effect relation is illustrated as a function of the relative spasmolysis.
The EC.sub.50 value for the ester was 12.6 .mu.g/ml and attained the effective strength of papaverine.
The fact that the effect of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl) ester also comprises a powerful analgesic component was particularly unexpected and surprising. FIG. 3 illustrates the analgesic effect of the ester compared with that of the reference substance tramadol. The analgesic activity of the ester was determined by employing the usual hot plate technique. When administered
REFERENCES:
patent: 4678780 (1987-07-01), Davis
patent: 5153205 (1992-10-01), Lotti
Laven Reinhard
Pein Eckhart
Ritter Helmut
Benston, Jr. William E.
Page Thurman K.
LandOfFree
Use of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of .alpha.,.alpha.-diphenylacetic acid-4-(N-methyl-piperidyl will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-684739