Angiogenesis promotion by prostaglandin compositions and methods

A prostaglandin and composition technology, applied in the direction of drug combination, cardiovascular system diseases, anhydride/acid/halide active ingredients, etc.

Inactive Publication Date: 2006-05-17
尼克美制药控股有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This improvement is attributed to improved oxygenation in the cavernosum by the regimen of injectable alprostadil, limiting the development of hypoxia-induced tissue damage

Method used

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  • Angiogenesis promotion by prostaglandin compositions and methods
  • Angiogenesis promotion by prostaglandin compositions and methods
  • Angiogenesis promotion by prostaglandin compositions and methods

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0146] exemplary composition

[0147] Composition A was prepared as follows. by dissolving 0.4 parts of prostaglandin E in 5 parts of ethanol 1 (Alprostadil USP) to obtain Part A. Then, 2.5 parts of (N,N-dimethylamino)-dodecyl propionate were mixed with alcohol-prostaglandin E 1 The solutions were mixed, followed by the addition of 5 parts of ethyl laurate.

[0148] Part B begins by preparing the water / buffer at pH 5.5. Water / buffer was prepared by adding sufficient potassium monohydrogen phosphate to pure water to obtain a 0.1M solution. The pH of the water / buffer was adjusted to 5.5 with a strong base solution (1 N sodium hydroxide) and a strong acid (1 N phosphoric acid). The buffer comprises about 80 parts of the total composition. All parts are by weight.

[0149] Add 0.5 parts of ethyl laurate to the buffer. Then, locust bean gum (in powder form) was dispersed in the buffer and homogenized with a stirring device. Table 1 is a list of ingredients.

[0150] The r...

Embodiment 2

[0154] Discover PGE 1 Promotes the growth of microvessels in primary cultures of the rat iliac artery region. Each sample was plated on a coverslip covered with growth factor-free Matrigel matrix in a Petri dish containing no serum. PGE 1 (Sigma) was added to the medium at a final concentration of 1, 10, 20, 30, 60 or 100 μmol (uM). 37°C with 5% CO 2 Cultures were incubated in humid air. After 96 hours, growth was recorded with a digital camera. Control group (6 samples) incubated on Matrigel matrix in serum-free medium without PGE 1 .

[0155] Growth factor-free Matrigel (Passaniti, A., et al., Lab. Invest. 199267:518-528) was purchased from Becton Dickinson (Mountain View, CA). Cell Culture Grade PGE 1 Available from Sigma Chemical. (St. Louis, MO). RPIM-1640 and other cell culture reagents were purchased from GIBCO Invitrogen Corp. (Grand Island, NY).

[0156] Animals used in this study were two-month-old male Sprague-Dawley rats. All animal husbandry, handling a...

Embodiment 3

[0164] Treatment of patients with erectile dysfunction associated with vascular disease

[0165] Semisolid prostaglandin topical compositions, such as Composition H, are used to promote restoration of erectile function in patients with erectile dysfunction associated with vascular disease, such as diabetic vascular disease. Treatment was carried out according to a regimen of topical prostaglandin compositions administered to the penis orifice prior to coitus.

[0166] Instruct each patient to erect the penis and open the opening of the penis when administering the drug, and drip the drug into the scaphoid fossa without placing the drug container in the opening of the penis. Treatment with a prostaglandin composition such as composition H of Example 1 generally produces vaginal penetrable erections. See, US Patent No. 6,323,241, the contents of which are incorporated herein in their entirety.

[0167] In another treatment group, each patient received a dose of a vasoactive pr...

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Abstract

The present invention provides a composition and method for promoting recovery of vascular function in patients with erectile dysfunction associated with vascular disease by administering a composition comprising a vasoactive prostaglandin and a biocompatible polymer. In a preferred embodiment, the prostaglandin composition is a topical composition comprising prostaglandin E1, a biocompatibility and a penetration enhancer, which topical composition is applied to the orifice of the penis. In another embodiment, the present invention provides a method for promoting the growth of microvessels on the target arterial area, which comprises applying a prostaglandin E1 composition at the adjacent target arterial area, so that the extracellular concentration of prostaglandin E1 is kept from about 1 μmol to Between about 10 μmol for a period of about 4 days.

Description

[0001] Related literature [0002] This application claims priority to US Provisional Application No. 60 / 456,605, filed March 21, 2003, which is incorporated in its entirety by this application. Background technique [0003] Arterial blood to erectile tissue comes from the cavernous arteries (deep arteries of the penis) and spinal arteries (superficial arteries of the penis), which are terminal branches of the internal pudendal arteries. The internal pudendal artery usually originates from the anterior hypogastric or internal iliac artery. The spiral arteries winding inside the penis are the terminal branches of the deep and superficial penile arteries. Parasympathetic stimulation causes the spiral arteries to stretch, thereby filling the erectile tissue with blood under arterial pressure, resulting in an erection. Normal erectile function requires the availability of functional arterial blood and smooth muscle cells as well as corresponding functions of the penile vasculatu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K9/00A61K9/70A61K31/557A61K31/5575A61K47/02A61K47/10A61K47/14A61K47/18A61K47/26A61K47/36
CPCA61K9/0014A61K9/0034A61K31/557A61K31/5575A61K47/02A61K47/10A61K47/14A61K47/18A61K47/26A61K47/36A61P15/10A61P23/02A61P9/00
Inventor 林桂亭约瑟夫·Y·莫吕明启郭应禄
Owner 尼克美制药控股有限公司
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