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Prophylactic or therapeutic agent and medicinal composition for il-31 mediated disease

A therapeutic agent and mediated technology, applied in the field of preventive or therapeutic agents and pharmaceutical compositions of IL-31 mediated diseases

Pending Publication Date: 2021-07-30
KYUSHU UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

On the other hand, T cells expressing AND differentiated and matured normally in the mouse thymus expressing I-Ab molecule, but AND TCR showed high autoreactivity to I-Ab molecule

Method used

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  • Prophylactic or therapeutic agent and medicinal composition for il-31 mediated disease
  • Prophylactic or therapeutic agent and medicinal composition for il-31 mediated disease
  • Prophylactic or therapeutic agent and medicinal composition for il-31 mediated disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0210] In one embodiment, the present invention provides a method for preventing or treating IL-31-mediated diseases, which includes the step of administering an effective amount of a neurokinin B signal blocker to a patient in need of treatment.

[0211] In one embodiment, the present invention provides neurokinin B signaling blockers for preventing or treating IL-31-mediated diseases.

[0212] In one embodiment, the present invention provides a neurokinin B signaling blocker for use in the manufacture of a prophylactic or therapeutic agent for IL-31-mediated diseases.

[0213] In each of the above embodiments, the neurokinin B signal blocker may be a neurokinin 3 receptor antagonist. The aforementioned neurokinin B signal blocking agent may be an inhibitor of tachykinin processing enzyme or a decomposition promoter of tachykinin processing enzyme. The aforementioned neurokinin B signal blocker may also be an expression inhibitor of neurokinin B (NKB), neurokinin 3 receptor,...

Embodiment

[0218] Hereinafter, although an Example demonstrates this invention, this invention is not limited to the following Example.

[0219] [Materials and methods]

[0220] (mouse)

[0221] Tac2 - / - Mice were created by genome editing based on the CRISPR / Cas9 system. Target sites were selected within exon 4 of the mouse Tac2 gene using the CHOPCHOP web design tool (https: / / chopchop.rc.fas.harvard.edu / ). The oligonucleotides shown in SEQ ID NO: 3 and SEQ ID NO: 4 and the BbsI ligation adapter (LigationAdapter) were synthesized. The sequences shown in SEQ ID NO: 5 and SEQ ID NO: 6 are guide sequences. In order to co-express the sgRNA and the Cas9 protein, these two nucleotides were synthesized, annealed, and ligated into the px330 vector digested with BbsI. The prepared px330 vector (concentration 5ng / μL, Dulbecco's PBS (Dulbecco's phosphate buffer solution)) was injected into the pronuclei of C57BL / 6 mouse zygotes fertilized in vitro in M2 medium (sigma company) middle. Inject...

experiment example 1

[0238] (the neural circuit that transmits the itching sensation)

[0239] Neural circuits activated by IL-31 that convey the itch sensation were analyzed. Most itch-causing substances are mediated by natriuretic polypeptide b (Nppb) or gastrin-releasing peptide (GRP) in spinal nerves to transmit itching sensation.

[0240] In order to remove nerve cells expressing GRP receptors or Nppb receptors, wild-type C57BL / 6 mice were injected intramedullary with saporin-conjugated GRP or Nppb (GRP-saporin, Nppb-saporin, respectively). 2 weeks later, IL-31 was administered to these mice, and the scratching behavior of each mouse was analyzed.

[0241] Saporin is a kind of ribosome-inactivating protein (RIP).

[0242] The protein conjugated to the receptor ligand expressed in the target nerve cell and RIP is captured by the target nerve cell and swallowed into the cell through endocytosis. The engulfed protein conjugated to RIP inhibits translation and kills target neuronal cells.

[...

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Abstract

A prophylactic or therapeutic agent for an IL-31 mediated disease, said agent comprising a neurokinin B signal blocker.

Description

technical field [0001] The invention relates to a preventive or therapeutic agent and a pharmaceutical composition for IL-31-mediated diseases. [0002] This application claims priority based on Japanese Patent Application No. 2018-215017 filed in Japan on November 15, 2018 and Japanese Patent Application No. 2019-144913 filed in Japan on August 6, 2019, and their contents are cited here. Background technique [0003] Interleukin-31 (IL-31) is a cytokine expressed in various human tissues, and it has been reported to be associated with chronic skin pruritus such as atopic dermatitis (for example, see Non-Patent Documents 1 and 2) . [0004] Atopic dermatitis is a chronic condition in which itchy eczema repeatedly exacerbates and diminishes. Most of its patients hyperresponse to allergens. In recent years, the number of patients with atopic dermatitis has increased, and atopic dermatitis significantly impairs the quality of life of patients. Therefore, it is urgent to dev...

Claims

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Application Information

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IPC IPC(8): A61K31/4545A61K31/47A61K31/4985A61K45/00A61P43/00A61P17/04A61K47/64A61K38/16
CPCA61K31/4545A61K31/4985A61P17/04A61K31/47A61K38/164A61K38/168A61P17/00A61K31/519A61K31/5377A61K45/06
Inventor 福井宣规坂田大治宇留野武人安东嗣修
Owner KYUSHU UNIV
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