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Compositions and methos for treatment of anorectal disorders

A technique for rectal disease and anus, which is applied in the directions of drug combinations, active ingredients of nitro compounds, active ingredients of heterocyclic compounds, etc.

Inactive Publication Date: 2004-05-19
思特肯有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the occurrence of side effects such as headaches limits the single use of NO donors, especially for high-dose therapeutic use

Method used

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  • Compositions and methos for treatment of anorectal disorders
  • Compositions and methos for treatment of anorectal disorders
  • Compositions and methos for treatment of anorectal disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0136] This example illustrates the effect of cGMP alone, and in combination with a NO donor, using a rat internal anal sphincter (IAS) relaxation model.

[0137]Female Sprague-Dawley rats (300-400 g) were anesthetized with ketamine (90 mg / kg), injected intramuscularly with xylazine (9 mg / kg), and supplemented with 1 / 3 dose as needed. During the experiment, rats were loosely restrained supine on a warm operating table (Harvard Apparatus). A 24-gauge vascular cannula (VWR, San Francisco, CA) was inserted intraperitoneally and rehydrated with saline to counteract the diuretic effect of the anesthetic. The contraction / relaxation measurement kit includes: Millar cannula / sensor (diameter 1.67 mm), connected to a Digi-Med low pressure analyzer (Micro-Med), with a range of -50-150 mmHg. Data integration was performed with Digi-Med system integration software and converted into waveforms. Blood changes were monitored with an arterial cannula / sensor and a Digi-Med blood pressure anal...

Embodiment 2

[0143] In this example, a rat internal anal sphincter relaxation model is used to illustrate the effect of phosphodiesterase inhibitors.

[0144] Using the above experimental method, use of 20 μl of a 5% solution of zaprinast in 1-methyl-2-pyrrolidone reduced the mean IASP by 21% after 32 minutes compared to vehicle alone. A very small amount of NO donors, such as nitroglycerin, can further enhance the effect of phosphodiesterase inhibitors. Nitroglycerin can accelerate the onset of action and maintain sphincter relaxation, but it does not cause headaches that occur when high-dose NO donors are used alone. side effect.

Embodiment 3

[0146] In this example, a rat internal anal sphincter relaxation model is used to illustrate the effect of a potassium channel opener (minoxidil).

[0147] Using the above experimental method, a single use of 20 μl of 4% minoxidil solution prepared with 62.5% propylene glycol reduced the IASP by 64% after 2.5 hours. Carrier alone has almost no effect on IASP ( Figure 5 ).

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Abstract

Compositions and methods for the treatment of anorectal disorders are provided in which certain combinations of NO donors, PDE inhibitors, superoxide (O2-) scavengers, beta-adrenergic agonists, cAMP-dependent protein kinase activators, alpha1-adrenergic antagonists, L-type Ca2+ channel blockers, estrogens, ATP-sensitive K+ channel activators and smooth muscle relaxants are used.

Description

[0001] related application [0002] This application claims priority to US Provisional Applications 60 / 112,325, filed December 14, 1998, 60 / 139,916, filed June 17, 1999, and 60 / 155,318, filed September 21, 1999. [0003] Statement Concerning Inventors' Rights Under Federally Funded Research and Development None. Background of the invention [0004] The present invention relates to compositions and methods for the treatment of anorectal disorders, such as anal fissures, anal ulcers, hemorrhoids and levator spasms, comprising administering a relaxable internal anal sphincter at the corresponding site (eg, within the anus) of the patient's anus one or more drugs. More specifically, the composition and method for treating anorectal diseases described in the present invention can induce the increase of cyclic nucleotides in the diseased sphincter tissue, or simulate the effect of cyclic nucleotides, or induce intracellular ca...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61KA61K9/02A61K9/06A61K31/00A61K31/04A61K31/13A61K31/137A61K31/195A61K31/198A61K31/21A61K31/34A61K31/40A61K31/4015A61K31/4245A61K31/44A61K31/47A61K31/472A61K31/50A61K31/505A61K31/517A61K31/522A61K31/55A61K31/565A61K38/00A61K38/44A61K45/00A61P1/00A61P9/14A61P17/04A61P43/00
CPCA61K31/198A61K31/505A61K31/21A61K31/52A61P1/00A61P17/04A61P43/00A61P9/14A61K38/22
Inventor T·P·帕克斯V·马克J·C·李C·李
Owner 思特肯有限公司
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