Intestinal disease mucosal healing agent for subcutaneous administration

Abstract

To provide a therapeutic agent for inflammatory bowel disease and colorectal cancer that enables subcutaneous administration.SOLUTION: A combined preparation of peptides consisting of the following two amino acid sequences: an amino acid sequence (I) GVSGSCSL KTCWLQLADF RKVGDALKEK YDSAAAMR; and an amino acid sequence (II) Ac-RADARADARADARADA-NH2.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a prophylactic or therapeutic agent for inflammatory bowel disease for subcutaneous administration and a therapeutic agent for colorectal cancer.

Background Art

[0002] Inflammatory bowel disease (IBD), typified by ulcerative colitis and Crohn's disease, is a chronic relapsing gastrointestinal inflammatory disease of unknown cause. In recent years, it has been shown that obtaining'mucosal healing' which enables endoscopic evaluation of the disease state leads to maintenance of clinical remission and reduction of the surgical rate. IBD is a chronic disease that repeats remission and relapse, and since it is necessary to receive drug treatment throughout life, a method for more simply administering therapeutic drugs is required.

Prior Art Documents

[0003]

Patent Documents

Patent Documents

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide a drug sustained-release carrier that enables a Wnt5a peptide having a mucosal healing effect by intraperitoneal administration to exhibit effectiveness also in subcutaneous administration.

Means for Solving the Problems

[0006] As a result of intensive studies to solve the above problems, the present inventors surprisingly found that a combination of a self-assembling peptide composed of 16 amino acid residues and a Wnt5a peptide exhibits effectiveness in subcutaneous administration, and completed the present invention.

Effects of the Invention

[0007] The present invention provides a therapeutic agent for preventing or treating inflammatory bowel disease and treating colorectal cancer, which is a peptide mixture of Item 1 and Item 2 below. Item 1 The following amino acid sequence (I) Peptide GVSGSCSL KTCWLQLADF RKVGDALKEK YDSAAAMR (I) Item 2 The following amino acid sequence (II) An intestinal disease therapeutic agent comprising a mixture of Ac-RADARADARADARADA-NH2 (II).

[0008] The peptide of the present invention is effective for wound healing of the colonic mucosa in subcutaneous administration and is useful as a preventive or therapeutic agent for inflammatory bowel disease.

[0009] Examination of the optimal concentration of Wnt5a peptide Example 1 The anti-inflammatory effects of Wnt5a peptide at 20 mg / day / body, 140 mg / day / body, and 280 mg / day / body were compared and examined. Each concentration of Wnt5a peptide was dissolved in 150 μL of distilled water. It was mixed with 100 μL of 2.5% self-assembling peptide, and the final concentration of the self-assembling peptide aqueous solution was 0.5%. A colitis model was created by allowing 9-week-old C57BL6N mice to drink 2.0% DSS (sodium dextran sulfate). An aqueous solution of Wnt5a peptide / self-assembling peptide (250 μL) was administered once subcutaneously to the back of the mice. The body weight from 0 to 7 days after administration and the intestinal length and DAI score on the 7th day after administration were evaluated. No difference was observed in the body weight change rate at 140 mg / day / body and 280 mg / day / body (Figure 1). No difference was observed in the intestinal length and DAI score at 140 mg / day / body and 280 mg / day / body (Figure 2) (Figure 3). It was clarified that the anti-inflammatory effects of Wnt5a peptide at 140 mg / day / body and 280 mg / day / body, using self-assembling peptide as a drug delivery carrier, had equivalent results. TIFF2025113084000001.tif9668TIFF2025113084000002.tif110147

[0010] Examination of the number of administrations of Wnt5a peptide Example 2 The anti-inflammatory effects of single administration of 140 mg / day / body of Wnt5a peptide and twice-daily administration of 70 mg / day / body were compared and examined. Wnt5a peptide at each concentration was dissolved in 150 μL of distilled water. It was mixed with 100 μL of 2.5% self-assembling peptide, and the final concentration of the self-assembling peptide aqueous solution was made 0.5%. A colitis model was created by allowing 9-week-old C57BL6N mice to drink 2.0% DSS (sodium dextran sulfate). 140 mg / day / body / self-assembling peptide aqueous solution (250 μL) of Wnt5a peptide was administered once subcutaneously to the back of the mice. The group of 70 mg / day / body / self-assembling peptide aqueous solution (250 μL) of Wnt5a peptide was administered twice subcutaneously to the back of the mice (day 0 and day 3). The body weight from 0 to 7 days after administration, and the intestinal length, DAI score, and cytokine amount on the 7th day after administration were evaluated. Regarding the body weight change rate, equivalent effects were obtained with 140 mg / day / body (single administration) and 70 mg / day / body (twice administration) (Figure 4). Regarding the intestinal tract and DAI score, a tendency for equivalent effectiveness was recognized with 140 mg / day / body (single administration) and 70 mg / day / body (twice administration) (Figure 5)(Figure 6). Regarding the cytokine amount, a tendency to suppress inflammatory cytokines was recognized in both 140 mg / day / body (single administration) and 70 mg / day / body (twice administration) (Figure 7). TIFF2025113084000003.tif218133TIFF2025113084000004.tif206170

Claims

1. A therapeutic agent for treating intestinal diseases, comprising a mixture of peptide GVSSCSL KTCWLQLADF RKVGDALKEEK YDSAAAAMR (I) and self-assembling peptide Ac-RADARADARADARADA-NH2 (II).

2. The prophylactic or therapeutic agent for inflammatory bowel disease according to Claim 1, wherein the intestinal disease is inflammatory bowel disease

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