阅读说明：本技术 用于治疗、改善或预防脑出血的肽及其用途 (Peptides for treating, ameliorating or preventing cerebral hemorrhage and uses thereof ) 是由 韩化敏 芦颖 田雨佳 于 2017-07-05 设计创作，主要内容包括：本申请提供了用于治疗脑出血的药物组合物,所述药物组合物包含含有氨基酸序列YEKLLDTEI(SEQ ID NO:1)或其功能性变体的肽或者所述肽的药学可接受的盐。本申请还提供了所述药物组合物的医学应用。(The present application provides a pharmaceutical composition for treating cerebral hemorrhage comprising a peptide comprising amino acid sequence YEKLLDTEI (SEQ ID NO:1) or a functional variant thereof, or a pharmaceutically acceptable salt of said peptide. The application also provides medical applications of the pharmaceutical composition.)

A pharmaceutical composition for treating cerebral hemorrhage, comprising a peptide comprising amino acid sequence YEKLLDTEI (SEQ ID NO:1) or a functional variant thereof, or a pharmaceutically acceptable salt thereof.

The pharmaceutical composition of claim 1, wherein the peptide is a chimeric peptide comprising amino acid sequence YEKLLDTEI (SEQ ID NO:1) or a functional variant thereof and an internalization peptide that promotes uptake of the chimeric peptide by a cell.

The pharmaceutical composition of claim 2, wherein the internalization peptide comprises the amino acid sequence YGRKKRRQRRR (SEQ ID NO: 2).

The pharmaceutical composition of claim 2, wherein the chimeric peptide comprises the amino acid sequence YGRKKRRQRRRYEKLLDTEI (SEQ ID NO: 3).

The pharmaceutical composition of any of the preceding claims, wherein the functional variant is a variant of the LDTEI moiety of SEQ ID No. 1 with one or more conservative substitutions, preferably the conservative substitutions are selected from the group consisting of a substitution between D and E, a substitution between L, V and I and a substitution between T and S.

The pharmaceutical composition of claim 5, wherein the functional variant is a variant of the LDTEI moiety of SEQ ID NO. 1 substituted with any one of the following sequences: LDTEL, LDTEV, LDTDI, LDTDL, LDTDV, LDSEI, LDSEL, LDSEV, LDSDI, LDSDL, LDSDV, LETEI, LETEL, LETEV, LETDI, LETDL, LETDV, VDTEI, VDTEL, VDTEV, VDTDI, VDTDL, VDTDV, IDTEI, IDTEL, IDTEV, IDTDI, IDTDL, IDTDV, IETEI, IETEL, IETEV, IETDI, IETDL, IETDV.

The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable carrier, diluent and/or excipient.

A pharmaceutical composition according to any one of the preceding claims, which is a pre-lyophilized formulation, preferably comprising histidine and trehalose.

Pharmaceutical composition according to any one of claims 1 to 7, which is a lyophilized formulation, preferably prepared by lyophilizing the prelyophilized formulation of claim 8.

The pharmaceutical composition according to any one of claims 1 to 7, which is a reconstituted formulation, preferably prepared by combining the lyophilized formulation according to claim 9 with an aqueous solution.

A method of treating, ameliorating, or preventing cerebral hemorrhage in a subject, the method comprising administering to a subject in need thereof the pharmaceutical composition of any one of claims 1-10.

Use of a peptide comprising amino acid sequence YEKLLDTEI (SEQ ID NO:1) or a functional variant thereof, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating, ameliorating, or preventing cerebral hemorrhage in a subject.

The use of claim 12, wherein the peptide is a chimeric peptide comprising amino acid sequence YEKLLDTEI (SEQ ID NO:1) or a functional variant thereof and an internalization peptide that promotes uptake of the chimeric peptide by a cell.

The use of claim 13, wherein the internalization peptide comprises the amino acid sequence YGRKKRRQRRR (SEQ ID NO: 2).

The use of claim 13, wherein said chimeric peptide comprises the amino acid sequence YGRKKRRQRRRYEKLLDTEI (SEQ ID NO: 3).

Use according to any one of claims 12 to 15, wherein the functional variant is a variant resulting from one or more conservative substitutions in the LDTEI part of SEQ ID No. 1, preferably the conservative substitution is selected from the group consisting of a substitution between D and E, a substitution between L, V and I and a substitution between T and S.

The use of claim 16, wherein the functional variant is a variant of SEQ ID No. 1 wherein the LDTEI moiety is replaced with any of the following sequences: LDTEL, LDTEV, LDTDI, LDTDL, LDTDV, LDSEI, LDSEL, LDSEV, LDSDI, LDSDL, LDSDV, LETEI, LETEL, LETEV, LETDI, LETDL, LETDV, VDTEI, VDTEL, VDTEV, VDTDI, VDTDL, VDTDV, IDTEI, IDTEL, IDTEV, IDTDI, IDTDL, IDTDV, IETEI, IETEL, IETEV, IETDI, IETDL, IETDV.

The pharmaceutical composition, method or use of any one of the preceding claims, wherein the cerebral hemorrhage is selected from traumatic cerebral hemorrhage and non-traumatic cerebral hemorrhage.

The pharmaceutical composition, method or use of any of the preceding claims, wherein the cerebral hemorrhage is selected from the group consisting of basal ganglia hemorrhage, putamen hemorrhage, thalamic hemorrhage, caudate nucleus hemorrhage, ventricular hemorrhage, lobar hemorrhage, cerebral hemorrhage, cerebellar hemorrhage, brainstem hemorrhage and subarachnoid hemorrhage.

The pharmaceutical composition, method or use of any one of the preceding claims, wherein the cerebral hemorrhage is caused by any one or a combination of the following factors: microaneurysms or microaneurysms, cerebral arteriovenous malformations, amyloid cerebrovascular diseases, cystic hemangiomas, intracranial venous thrombosis, epidural arterial fistula, specific arteritis, fungal arteritis, smog diseases, arterial anatomical variations, carotid arteriovenous fistula, hypertension, migraine, anticoagulation, antiplatelet or thrombolytic therapy, haemophilus infection, leukemia, thrombotic thrombocytopenia, intracranial tumors, alcohol, amphetamine, ***e, sympathetic stimulants.