Therapeutic medicine for fibrous disease

A technology for fibrotic diseases and drugs, applied in diseases, drug combinations, skin diseases, etc., can solve the problem that there is no radical treatment method for genetic diseases

Pending Publication Date: 2019-12-27
斯特姆里姆有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, until now, a safe and reliable method for normalizing genetic abnormalities has not been established, and there is no radical treatment for genetic diseases represented by epidermolysis bullosa.

Method used

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  • Therapeutic medicine for fibrous disease
  • Therapeutic medicine for fibrous disease
  • Therapeutic medicine for fibrous disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0106] Inhibitory effect of HMGB1 peptide (1-44) on forelimb adhesions in a mouse model of epidermolysis bullosa (1) Materials and methods

[0107] i) animals

[0108] A mouse model of epidermolysis bullosa was obtained from Prof. Leena Bruckner-Tuderman at the University of Freiburg (Germany) with a homotype of mutant allele in the collagen type VII alpha1 (Col7a1) gene (Fritsch, et al., Col7a1 as described in J Clin Invest. 2008 May;118(5):1669-79 flNeo / flNeo mouse, hereinafter referred to as "129SV / colVII homo mouse" in this specification). The 15 mice (male) were acclimated in the rearing room for 2 weeks, and were divided into 2 groups according to the adhesion score described later so as to achieve the same degree, and the test substance was administered from the next day (age at the start of administration: 5 to 6 weeks of age). When the adhesion score was evaluated one week after the administration of the test substance, one mouse in the HMGB1 peptide (1-44)-admin...

Embodiment 2

[0143] Inhibitory effect of HMGB1 peptide (1-44) on intestinal fibrosis and scarring in a mouse model of epidermolysis bullosa

[0144] (1) Materials and methods

[0145] i) animals

[0146] The 129SV / colVII homo mice (6 males) described in Example 1 were acclimated in the rearing room for 2 weeks, and divided into a solvent group (3 mice) and an HMGB1 peptide (1-44) administration group (3 mice), and then started. Administration of the test substance (age at the start of administration: 5 to 6 weeks of age).

[0147] ii) Test substance

[0148] As in Example 1, chemically synthesized HMGB1 peptide (1-44) was used as a test substance.

[0149] iii) Administration of test substance

[0150] A solvent (physiological saline, "Otsuka Raw Food Injection" manufactured by Otsuka Pharmaceutical Co., Ltd.) or HMGB1 peptide (1-44) (concentration: 0.2 mg / mL) was administered in a volume of 50 μL from the tail vein, respectively. The test substance was administered twice every week...

Embodiment 3

[0157] HMGB1 peptide (1-44) prolongs survival in a mouse model of epidermolysis bullosa

[0158] (1) Materials and methods

[0159] i) animals

[0160] The 129SV / colVII homo mice (male) described in Example 1 were acclimated in the rearing room for 2 weeks, and divided into the solvent group and the HMGB1 peptide (1-44) administration group, and the administration of the test substance was started (start of administration). Age: 5 to 6 weeks of age (weight 5 to 8 g).

[0161] ii) Test substance

[0162] As in Example 1, chemically synthesized HMGB1 peptide (1-44) was used as a test substance.

[0163] iii) Administration of test substance

[0164] The solvent (physiological saline, "Otsuka Raw Food Injection" manufactured by Otsuka Pharmaceutical Co., Ltd.) or HMGB1 peptide (1-44) (concentration: 0.2 mg / mL) was administered from the tail vein in a volume of 50 μL per one time. The test substance was administered twice every week from the next day of the grouping, and th...

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Abstract

The inventors of the present invention found that an HMGB1 peptide fragment having a specific amino acid sequence is effective at suppressing finger fusion and scarring of the digestive tract, and atprolonging survival in malnutrition-type epidermolysis bullosa model mice. The inventors also found that in a cutaneous ulcer model, administration of the specific HMGB1 peptide fragment suppresses the fibrosing of skin that occurs in the healing process of the ulcer. The present invention, on the basis of these findings, provides a pharmaceutical composition for fibrous disease treatment, which contains the specific HMGB1 peptide fragment.

Description

technical field [0001] The present application relates to a pharmaceutical composition for treating fibrotic diseases comprising fragmented peptides of HMGB1 (High mobility group box1, high mobility group box B1) protein. Background technique [0002] Fibrotic diseases, represented by fibrosis of various organs and tissues, are caused by excessive production and deposition of extracellular matrix proteins in various organs, organs, tissues, etc., such as the lungs and liver, resulting in tissue sclerosis or dysfunction. disease. In fibrotic diseases, the progression of tissue fibrosis is irreversible in many cases, and even though fibrotic diseases are serious diseases such as pulmonary fibrosis and liver cirrhosis, which progress to death, there is currently no effective treatment method. [0003] Epidermolysis bullosa refers to the breakdown of the adhesion function between the epidermis and the dermis due to the genetic abnormality of the adhesion structure control prote...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61P1/00A61P1/16A61P1/18A61P9/00A61P11/00A61P13/12A61P15/00A61P17/00A61P17/02A61P19/00A61P19/02A61P19/04A61P21/00A61P27/02
CPCA61P1/00A61P1/16A61P1/18A61P9/00A61P11/00A61P13/12A61P15/00A61P17/00A61P17/02A61P19/00A61P19/02A61P19/04A61P21/00A61P27/02A61K38/17A61K38/16A61P43/00A61K38/19
Inventor 玉井克人青户隆博山崎翔山崎尊彦
Owner 斯特姆里姆有限公司
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