Adrenomedullin production enhancer

a technology of adrenomedullin and enhancing agent, which is applied in the direction of biocide, cardiovascular disorder, drug composition, etc., can solve the problems of high production cost, inability to exert the effect of significant amount, and inability to administer significant amount, so as to increase the amount of blood flow, promote the production of adrenomedullin, and increase the effect of blood flow

Inactive Publication Date: 2016-01-14
NAT UNIV ASAHIKAWA MEDICAL UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The adrenomedullin production-enhancing agent helps increase the production of adrenomedullin, which has many beneficial effects including increasing blood flow and fighting inflammation. It can be used to treat various diseases such as Crohn's disease and ischemic diseases of the digestive system. It is safe, effective, and can be taken orally.

Problems solved by technology

However, since adrenomedullin is a peptide, formulation of it is associated with high costs of production, and in the case of direct administration of adrenomedullin, a dosage form such as an injectable preparation or an intravenous drip preparation must be used.
Rigorous production technology and management excluding incorporation of foreign matter, such as endotoxin, is thus required.
Furthermore, since adrenomedullin has a half-life in blood of only tens of minutes, administration of significant amounts is required for exertion of its effects.
However, intravenous administration of a large amount of adrenomedullin may induce hypotension.
Moreover, when exposure of specific organs to adrenomedullin is expected, various problems may exist, such as the need for targeting technologies.
However, no such medicament has been available.

Method used

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Examples

Experimental program
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Effect test

example 1

[0035]Adrenomedullin Production-Enhancing Effect Of Daikenchutou:

[0036]Male SD rats (8 to 10 weeks of age, body weight 300 to 400 g) were used (n=16). Saccharum granorum was added to distilled water to a concentration of 480 mg / mL to prepare an aqueous solution of it. To this aqueous solution of Saccharum granorum, a powdered extract of Daikenchutou was added to a concentration of 60 mg / mL, by weighing immediately at the time of use, and the mixture was homogeneously dispersed by stirring for 30 minutes at room temperature for use as a test specimen. A 5 mL / kg portion of the test specimen, which had been kept warm at 37° C., was administered into the duodenum through a cannula, and blood was collected from the portal vein at 0, 15, 30, 60, and 90 minutes after administration. A control group was administered distilled water in the same fashion. Approximately 5 mL of the portal vein blood was inserted into a 15-mL centrifuge tube made of polypropylene (PP), in which an ethylenediamin...

example 2

[0040]Blood Flow-Increasing Effects Of Daikenchutou And Its Constituent Crude Drugs:

[0041]Male SD rats (9 to 11 weeks of age, body weight 260 to 350 g) were used (n=3 or 6). Saccharum granorum and a powdered extract of Daikenchutou were suspended in distilled water to obtain a concentration of 160 mg / mL of Saccharum granorum and to a concentration of 20 mg / mL for the powdered extract of Daikenchutou, and the suspension was used as a test specimen (Daikenchutou). Furthermore, test specimens respectively containing the individual crude drugs were prepared by adding the ginseng extract powder, dried ginger rhizome extract powder, and Japanese pepper extract powder to distilled water to obtain concentrations of 6 mg / mL, 10 mg / mL, and 4 mg / mL, respectively. Furthermore, test specimens containing two crude drugs among the aforementioned three crude drugs in combination were prepared by addition to distilled water to obtain concentrations of 6 mg / mL for the ginseng extract powder and 10 mg...

example 3

[0044]Effect Of ADM Antagonist Pretreatment On The Blood Flow-Increasing Effect Of Daikenchutou:

[0045]Male SD rats were divided into two groups: a Daikenchutou-treated group and an ADM antagonist-pretreated group (n=7 or 8). A solution with a 160 mg / mL concentration of Saccharum granorum was prepared using distilled water, and powdered Daikenchutou extract was weighed at the time of use to obtain a concentration of 20 mg / mL and homogeneously dispersed in the same solution by stirring at room temperature for 30 minutes or longer to obtain Daikenchutou (TJ-100). This was administered into the colon in the Daikenchutou-treated group in an amount of 900 mg / 5 mL / kg. On the other hand, for the ADM antagonist-pretreated group, a human ADM antagonist (h. ADM22-52, 4302-v, manufactured by Peptide Institute, Inc.) was dissolved in physiological saline at 30 μmol / L, and the solution was intravenously administered through a cannula placed under anesthesia, at a dose of 30 nmol / l mL / kg, and 15 m...

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PUM

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Abstract

It is an object of the invention to discover a substance that effectively increases the production of adrenomedullin, as well as to provide an adrenomedullin production-enhancing agent utilizing this substance. The adrenomedullin production-enhancing agent is characterized by inclusion of a ginsenoside, a sanshool, and / or a shogaol as active ingredients.

Description

TECHNICAL FIELD[0001]The present invention relates to an adrenomedullin production-enhancing agent, and more particularly to an adrenomedullin production-enhancing agent that is effective in preventing and treating diseases such as Crohn's disease by promoting the production of adrenomedullin, an intestinal peptide which increases blood flow and has anti-inflammatory effects.BACKGROUND ART[0002]Adrenomedullin was discovered in 1993 as a peptide involved in regulation of the circulatory system with strong vasodilatory effects (Patent Document 1). Adrenomedullin is produced by a variety of organs such as those of the circulatory system and the digestive system, and has important physiological effects such as vasodilatation, neovascularization, antibacterial effects, anti-enteritic effects, protection of the gastric mucosa, and suppression of thrombus formation. Administration of adrenomedullin has correspondingly been confirmed to be effective in the treatment of various diseases, and...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/704A61K31/12A61K31/164A61K31/575A61K36/258A61K36/75A61K36/9068
CPCA61K31/704A61K31/575A61K31/164A61K36/9068A61K36/258A61K36/75A61K31/12A61P1/00A61P1/04A61P1/16A61P9/00A61P9/12A61P11/00A61P13/00A61P15/00A61P19/00A61P29/00A61P43/00C07J9/00C07J17/005A61K2300/00
Inventor KONO, TORUKANEKO, ATSUSHIOMIYA, YUJI
Owner NAT UNIV ASAHIKAWA MEDICAL UNIV
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