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Drug for inhibiting myometrial contraction

a technology of myometrial contraction and drug, which is applied in the direction of drug composition, peptides, peptides, etc., can solve the problems of premature labor and miscarriage, side effects similar to those of ritodrine, and the physiological role of am and the details of am function in these fetal and maternal tissues remain elusive. , to achieve the effect of preventing premature labor or miscarriag

Inactive Publication Date: 2007-07-12
SHIONOGI & CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016] A composition of the present invention for inhibiting spontaneous myometrial contraction or bradykinin-induced contraction comprises AM. The composition of the present invention may be used for selectively inhibiting spontaneous myometrial contraction or bradykinin-induced contraction, preventing premature labor, preventing miscarriage, arresting parturition prior to cesarean section, and treating dysmenorrhea.

Problems solved by technology

Other β2-adrenergic agents, such as for example terbutaline and albuterol, cause side effects similar to those of ritodrine.
Therefore, when renal function is impaired, this agent is not preferable.
However, bradykinin is inherently an inflammatory mediator, and it has been suggested that there is a possibility that premature labor and miscarriage is caused by abnormally increased bradykinin in the gravid uterus, (Reference 1; List of references are described at the end of this specification).
However, physiological roles of AM and details of AM function in these fetal and maternal tissues remain elusive.
However, the importance of galanin-induced uterine contraction is not understood at all.

Method used

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  • Drug for inhibiting myometrial contraction
  • Drug for inhibiting myometrial contraction
  • Drug for inhibiting myometrial contraction

Examples

Experimental program
Comparison scheme
Effect test

example 1

Effect of AM on Spontaneous Contraction of the Uterus of a Female Rat)

[0064] 1 μg of 17β-estradiol in 0.2 ml of 30% ethanol was subcutaneously injected to 10 to 12 week old female rats.

[0065] On the following day, the rats were sacrified by hammering their heads. Thereafter, the rats were decapitated, followed by exsanguination. The uteri were isolated from the rats. Each isolated uterus was cut into four fragments a to d (FIG. 1(A)). Portions of each strip to which blood vessels were attached were cut off, thereby obtaining uterine strips (FIG. 1(B)).

[0066] The effect of AM on the rat uterus was examined by measuring contractions of the uterine strips using an isotonic transducer TD-112S (manufactured by Nippon Kohden Corporation) where the tension was 1 g.

[0067] While the uterine strip was immersed in 30 ml of a modified Krebs-Ringer bicarbonate (KRB) solution with glucose) (hereinafter simply referred to as “modified KRB solution”), the uterine strip was attached to the isoto...

example 2

Concentration-Dependent Effect of AM on the Uterus of a Female Rat

[0072] In a manner similar to that of Example 1, uterine strips were prepared, and attached to an isotonic transducer in a modified KRB solution. Myometrial contraction was continuously measured. After it was confirmed that the spontaneous rhythm of uterine muscle became constant, 30 μl of 1×10−6, 2×10−6, 7×10−6, 2×10−5, or 7×10−5 M AM (experimental samples), or distilled water (control sample) was added to the modified KRB solution at time 0 min (initial addition), 5 min later, 12 min later, 22 min later, and 32 min later, where AM concentrations were 1, 3, 10, 30, and 100 nM, respectively. Thereafter, after 45 minutes from the initial addition of AM or distilled water, 300 μl of 4.5 M KCl was added to the solution to be a KCl concentration of 45 mM.

[0073] The results are shown in FIGS. 3(a) to 3(c). Here, FIGS. 3(a) to 3(c) correspond to the results obtained by using the uterine strips for the portions b to d in F...

example 3

Inhibition of Bradykinin-Induced Contraction by AM

[0075] In a manner similar to that of Example 1, uterine strips were prepared and attached to an isotonic transducer in a modified KRB solution. At the time when 10 nM bradykinin (Peptide Institute, Inc.) was added to the modified KRB solution, myometrial contraction was continuously measured. 20 minutes after the addition of bradykinin, 100 nM AM or distilled water was further added.

[0076] The results are shown in FIGS. 4(a) and 4(b). Here, FIGS. 4(a) and 4(b) correspond to the results obtained by using the uterine strips for the portions a and c in FIG. 1(A), respectively. FIG. 4(a) shows the results of addition of 100 nM AM. FIG. 4(b) shows the results of addition of distilled water. Arrows in each figure indicate times at which bradykinin, AM, or distilled water were added.

[0077] As shown in FIGS. 4(a) and 4(b), bradykinin-induced contraction was inhibited by the addition of AM.

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Abstract

A composition for inhibiting spontaneous myometrial contraction or bradykinin-induced contraction, comprising adrenomedullin. The composition of the present invention may be used to selectively inhibit spontaneous myometrial contraction or bradykinin-induced contraction to prevent premature labor, prevent miscarriage, arrest parturition prior to cesarean section, or to treat dysmenorrhea.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for inhibiting spontaneous myometrial contraction or bradykinin-induced contraction, comprising adrenomedullin. More specifically, the present invention relates to a composition for selectively inhibiting spontaneous myometrial contraction or bradykinin-induced contraction, comprising adrenomedullin. BACKGROUND ART [0002] The management of premature labor is one of the most important issues in the field of obsterics. Premature labor refers to parturition on or after 22 weeks and before 37 weeks of pregnancy, which accounts for 5 to 10% of the total number of childbirths. A neonate delivered by premature labor is called a pronatus, which is frequently a low birth weight infant. Recently, although the care of neonates has progressed significantly, the morbidity and mortality of pronatuses are higher compared to normally delivered neonates. Therefore, it is desired that premature labor is avoided to continue pregnanc...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/22A61P15/00A61P15/06A61P43/00
CPCA61K38/22A61P15/00A61P15/06A61P43/00
Inventor YANAGITA, TOSHIHIKO
Owner SHIONOGI & CO LTD
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