JPWO2019186561A5

JPWO2019186561A5 -

Info

Publication number: JPWO2019186561A5
Application number: JP2020552781A
Authority: JP
Publication date: 2022-04-05
Anticipated expiration: 2039-03-28

Claims

Pharmaceuticals for use in reducing the release of at least one inflammatory cytokine or in inhibiting the activity of at least one inflammatory cytokine , or for use in reducing the release of at least one inflammatory mediator or chemokine. It ’s a composition,
Peptide according to formula I: pGlu-X ₁ -X ₂ -X ₃ -OH as an active ingredient or a pharmaceutically acceptable salt or derivative thereof (in the formula, X ₁ is selected from Asn and Thr; X ₂ is , Trp, Phe and Tyr; X3 is selected from Lys _, Lys derivatives and Thr) ,
With pharmaceutically acceptable carriers ,
A pharmaceutical composition comprising.

The at least one inflammatory cytokine is interferon gamma (IFN gamma), interleukin 1 beta (IL-1 beta), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF alpha), and interleukin 6 ( Selected from the group consisting of IL-6) ; or
The at least one inflammatory mediator or chemokine is selected from the group consisting of reactive oxygen species (ROS) and RANTES (regulated upon activation and expressed and possibly secreted in normal T cells);
The pharmaceutical composition according to claim 1.

Derivatives of the peptide include C4-C30 alkyl groups attached to the amino or terminal amino groups of the side chains of the peptide ; or
Derivatives of the peptide include C8 alkyl (octanoyl) attached to the side chain of Lys residues via an amide bond;
The pharmaceutical composition according to claim 1 or 2 .

The peptides are from pGlu-Asn-Trp-Lys (octanoyl) -OH (SEQ ID NO: 1) , pGlu-Asn-Trp-Thr-OH (SEQ ID NO: 2), and pharmaceutically acceptable salts and derivatives thereof. The pharmaceutical composition according to claim 1 or 2 , which is selected from the group consisting of.

The peptide has the amino acid sequence set forth in SEQ ID NO: 1 ; or
The peptide is a sodium salt of the peptide having the sequence shown in SEQ ID NO: 1;
The pharmaceutical composition according to claim 1 or 2 .

Has a pH in the range of about 4 to about 8 ; or
It is formulated for the route of administration selected from the group consisting of topical administration, eye drop administration, oral administration, nasal administration, and parenteral administration;
Formulated for topical administration as a cream, ointment, paste, lotion, gel, or in the form of eye drops; or
Formulated for administration to subjects with eye disease or damage as a liquid solution or suspension, emulsion, cream, ointment, spray, gel or intravitreal injection for use as an eye drop;
The pharmaceutical composition according to any one of claims 1 to 5 .

The pharmaceutical composition according to claim 6 , which is formulated as a cream containing 0.1 to 5% w / w of the peptide, derivative or pharmaceutically acceptable salt.

Select from the group consisting of asthma, bronchitis, pleural inflammation, alveolar inflammation, vasculitis, pneumonia, chronic bronchitis, bronchiectasis, diffuse panbronchiolitis, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis and cystic fibrosis. To be administered to subjects with inflammatory diseases or disorders of the lung, or
Inflammatory selected from the group consisting of inflammatory symptoms associated with vegetative inflammation, dry eye syndrome, infectious eye disease, allergic eye disease, keratitis, conjunctivitis, Mybohm gland dysfunction, and Sjogren's syndrome. To administer to a subject with a disease or disorder, an eye disease or injury, or
To be administered to subjects with inflammatory autoimmune diseases or disorders, selected from the group consisting of rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and lupus, or
Selected from the group consisting of Crohn's disease and ulcerative colitis, for administration to subjects with inflammatory bowel disease, or
To be administered to subjects with inflammatory diseases or disorders of the ear, selected from the group consisting of inflammatory symptoms associated with ear infections, otitis media, otitis externa, mastoiditis and mastoiditis.
The pharmaceutical composition according to any one of claims 1 to 7 .

Inflammatory diseases selected from the group consisting of inflammatory diseases or disorders of the eyes, inflammatory diseases or disorders of the ears, inflammatory diseases or disorders of the lungs, inflammatory diseases or disorders of the intestines, and inflammatory autoimmune diseases or disorders. Alternatively, a pharmaceutical composition for use in the treatment of a disorder, wherein a peptide according to formula I: pGlu-X ₁ -X ₂ -X ₃ -OH or a pharmaceutically acceptable salt or derivative thereof (in the formula). , X ₁ is selected from Asn and Thr; X ₂ is selected from Trp, Phe and Tyr; X ₃ is selected from Lys, Lys derivatives and Thr) as an active ingredient .

The pharmaceutical composition according to claim 9 , which is formulated for a route of administration selected from the group consisting of topical administration , eye drops , oral administration , nasal administration , and parenteral administration.

The eye inflammatory disease or disorder is selected from the group consisting of vegetative inflammation, dry eye syndrome, inflammatory symptoms associated with infectious eye disease, allergic eye disease, keratitis, conjunctivitis, meibomian gland dysfunction and Sjogren's syndrome. Will be ; or
The inflammatory autoimmune disease or disorder is selected from the group consisting of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Sjogren's syndrome and lupus; or
The intestinal inflammatory disease or disorder is selected from the group consisting of Crohn's disease and ulcerative colitis; or
The inflammatory disease or disorder of the lung is asthma, bronchitis, pleural inflammation, alveolar inflammation, vasculitis, pneumonia, chronic bronchitis, bronchiectasis, diffuse pneumonitis, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis. And selected from the group consisting of cystic fibrosis; or
The ear inflammatory disease or disorder is selected from the group consisting of inflammatory symptoms associated with ear infections, otitis media, otitis externa, mastoiditis and mastoiditis;
The pharmaceutical composition according to claim 9 or 10 .

Derivatives of the peptide include C4-C30 alkyl groups attached to the amino group or terminal amine of the side chain of the peptide via an amide bond ; or
Derivatives of the peptide include C8 alkyl (octanoyl) attached to the side chain of Lys residues;
The pharmaceutical composition according to any one of claims 9 to 11 .

The peptide is selected from the group consisting of pGlu-Asn-Trp-Lys (octanoyl) -OH ( SEQ ID NO: 1 ) , pGlu-Asn-Trp-Thr-OH ( SEQ ID NO: 2 ) , and salts and derivatives thereof. , The pharmaceutical composition according to any one of claims 9 to 11 .

The peptide has the amino acid sequence set forth in SEQ ID NO: 1; or
The peptide is a sodium salt of the peptide having the sequence shown in SEQ ID NO: 1;
The pharmaceutical composition according to any one of claims 9 to 11.

An isolated sodium salt of a peptide having the sequence set forth in SEQ ID NO: 1.