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Body cavity effusion suppressant

An inhibitor, pleural effusion technology, applied in the direction of anti-inflammatory agents, blood diseases, extracellular fluid diseases, etc., can solve the problem of not getting it, and achieve the effect of reducing incorrect puncture and chest pain.

Inactive Publication Date: 2014-11-05
TORAY IND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effect of suppressing body cavity fluid that can be used clinically has not been obtained

Method used

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  • Body cavity effusion suppressant
  • Body cavity effusion suppressant
  • Body cavity effusion suppressant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] [Example 1] Preparation of covalent conjugates of interferon-β and PEG

[0086] According to the method described in Example 6 of Japanese Patent No. 4,850,514, a "covalent conjugate of interferon-β and PEG" was prepared, wherein a PEG molecule with a molecular weight of 42,000 was mixed with recombinant human interferon-β (SEQ ID NO : 1) The amino group of lysine at position 134 of the amino acid sequence is covalently bonded. Specifically, ethylene glycol (final concentration: 20%) was added to recombinant human interferon-β (final concentration: 200 μg / ml), and adjust the pH to 7.6 with 1 M disodium hydrogen phosphate solution. Hydroxysuccinimide ester-activated PEG (molecular weight: 42,000; product number 61G99122B01; NOF Corporation) was added thereto and mixed, and a binding reaction was performed overnight at 4°C. To this binding reaction solution was added 10 mM acetate buffer (pH 4.5) in an amount greater than 5 times its volume, and the resultant was appli...

Embodiment 2

[0093] [Example 2] Effect of PEG-IFN-β on inhibiting accumulation of ascites by topical application

[0094] A mouse model of gastric cancer peritoneal metastasis was generated, and the effect of PEG-IFN-β on inhibiting ascites accumulation by topical administration was evaluated according to the method of Nakanishi et al. (Cancer Science, 2003, Vol. 94, pp. 112-118).

[0095] At 37°C and 5% CO 2 Cultured in DMEM medium containing 10% fetal calf serum and maintained in a culture box, prepared by introducing pEGFP-C1 plasmid (Clontech) into GCIY human gastric cancer cells (No. RCB0555) obtained from Cell Bank, RIKEN BioResource Center GCIY-EGFP cells. GCIY-EGFP cells were harvested with trypsin / EDTA and washed with Hank's balanced salt solution (HBSS) to prepare GCIY-EGFP cell suspension. GCIY-EGFP cell suspension (2.5 x 10 6cells / mouse) into male KSN nude mice (obtained from Shizuoka Laboratory Animal Center), and the next day according to Ohashi et al. (International Journ...

Embodiment 3

[0100] [Example 3] Effect of systemic administration of PEG-IFN-β on inhibiting accumulation of ascites

[0101] In the same manner as in Example 2, a gastric cancer peritoneal metastasis mouse model was generated by intraperitoneally transplanting human gastric cancer cells, GCIY-EGFP cells, into male KSN nude mice.

[0102] Naturally occurring human interferon-β (Feron ? ; Toray Industries, Inc.), or PEG-IFN-β or PEG-mIFN-β prepared in Example 1 were subcutaneously administered to gastric cancer peritoneal metastasis mouse model (n=6) with the amount of 5,000 U / mouse / dose dorsal region (ie by systemic administration). Administration started the day after transplantation twice a week for 4 weeks. Phosphate buffered saline (PBS) was administered to the control group in the same manner. Ascitic fluid was collected under anesthesia from the gastric cancer peritoneal metastasis mouse model 2 weeks after the last administration, and the fluid volume was measured.

[0103] The ...

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PUM

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Abstract

The purpose of the present invention is to provide a body cavity effusion suppressant that is effective against body cavity effusions for which the administration of a diuretic fails to yield a therapeutic effect, and that can exercise a therapeutic effect even when systemically administered. The present invention provides a body cavity effusion suppressant containing a covalent conjugate of an interferon and a polyalkylene glycol as an active ingredient.

Description

technical field [0001] The present invention relates to body cavity effusion inhibitors. Background technique [0002] Water is present in large quantities in animals, and the extracellular fluid (such as interstitial fluid, body cavity fluid, blood or lymph fluid) that mainly fills the spaces between tissues or within body cavities, ducts or circulatory system is called "body fluid". In particular, fluids present in body cavities are referred to as "coelomic fluids" (eg, pleural, ascites, or pericardial effusions). Although a small amount of body cavity fluid exists in healthy people, it is known that a large amount of body cavity fluid is maintained in the body of patients suffering from, for example, liver disease, kidney disease, heart disease, cancer or inflammatory disease. As the body cavity effusion develops, symptoms such as chest pain, abdominal pain, fullness, and difficulty breathing occur. Since these symptoms greatly reduce the patient's quality of life (QOL)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/21A61P1/16A61P13/12A61P35/00A61P43/00
CPCA61K38/212A61K38/215A61K47/48215A61K38/21A61K47/60A61K38/217A61P1/16A61P13/12A61P29/00A61P35/00A61P43/00A61P7/00A61P7/10A61P9/00A61K45/06
Inventor 成见英树池原早苗
Owner TORAY IND INC
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