JPWO2020209920A5

JPWO2020209920A5 -

Info

Publication number: JPWO2020209920A5
Application number: JP2021542520A
Authority: JP
Publication date: 2023-02-01

Description

当業者により、本発明の広範な概念から逸脱しない限りにおいて、上記で記載した実施形態に対して変化が施されうることが察知されるであろう。したがって、本発明は、開示される特定の実施形態に限定されるものではなく、本記載により規定される、本発明の精神および範囲内における改変も対象とするように意図されることが理解される。

以下に、本願の当初の特許請求の範囲に記載の発明を列挙する。
［発明１］
それを必要とする対象における発疱剤および苛性ガスのうちの少なくとも１つの毒性作用を緩和する方法であって、前記対象に、有効量の、配列番号１のアミノ酸配列を含むトロンボポエチン（ＴＰＯ）模倣剤を投与するステップを含む方法。
［発明２］
前記ＴＰＯ模倣剤が、ＲＷＪ－８０００８８である、発明１に記載の方法。
［発明３］
前記ＴＰＯ模倣剤が、ロミプロスチムである、発明１に記載の方法。
［発明４］
前記苛性ガスが、硫化水素、フッ化水素、塩化水素、臭化水素、シアン化水素、アルシン、ホスフィン、一酸化窒素、二酸化窒素、二酸化硫黄、オゾン、塩素、メチルアミン、およびアンモニアからなる群から選択される、発明１から３のいずれか一つに記載の方法。
［発明５］
前記発疱剤が、蒸留マスタード、マスタードガス、ルイサイト、マスタード／ルイサイト、マスタード／Ｔ、窒素マスタード、セスキマスタード、硫黄マスタード、ホスゲンオキシム、カンタリジン、およびフラノクマリンからなる群から選択される、発明１から４のいずれか一つに記載の方法。
［発明６］
前記対象が、前記発疱剤および前記苛性ガスのうちの少なくとも１つに曝露される前に、前記有効量のＴＰＯ模倣剤が前記対象に投与される、発明１から５のいずれか一つに記載の方法。
［発明７］
前記対象が、前記発疱剤および前記苛性ガスのうちの少なくとも１つに曝露されるときに、前記ＴＰＯ模倣剤が前記対象に投与される、発明１から５のいずれか一つに記載の方法。
［発明８］
前記対象が、前記発疱剤および前記苛性ガスのうちの少なくとも１つに曝露された後で、前記ＴＰＯ模倣剤が前記対象に投与される、発明１から５のいずれか一つに記載の方法。
［発明９］
前記対象が、前記発疱剤および前記苛性ガスのうちの少なくとも１つに曝露された後で、前記有効量のＴＰＯ模倣剤が前記対象に投与される、発明８に記載の方法。
［発明１０］
前記毒性作用が、前記発疱剤および前記苛性ガスのうちの少なくとも１つにより誘導される血管損傷である、発明１から９のいずれか一つに記載の方法。
［発明１１］
前記毒性作用が、前記発疱剤および前記苛性ガスのうちの少なくとも１つにより誘導される、出血、好ましくは微小出血であり、最も好ましくは肺微小出血、または細胞流入である、発明１から９のいずれか一つに記載の方法。
［発明１２］
前記毒性作用が、前記発疱剤および前記苛性ガスのうちの少なくとも１つにより誘導される肺線維症である、発明１から９のいずれか一つに記載の方法。
［発明１３］
前記毒性作用が、前記発疱剤および前記苛性ガスのうちの少なくとも１つにより誘導される、死亡または罹患である、発明１から９のいずれか一つに記載の方法。
［発明１４］
前記ＴＰＯ模倣剤の前記有効量が、前記対象に、静脈内注射、筋内注射、皮内注射、または皮下注射により投与される、発明１から１３のいずれか一つに記載の方法。
［発明１５］
それを必要とする対象における発疱剤および苛性ガスのうちの少なくとも１つの毒性作用を緩和するためのキットであって、有効量のトロンボポエチン（ＴＰＯ）模倣剤および薬学的に許容される担体を含む医薬組成物を含み、前記ＴＰＯ模倣剤が配列番号１のアミノ酸配列を含み、好ましくは、前記ＴＰＯ模倣剤がＲＷＪ－８０００８８またはロミプロスチムであり、任意選択で、前記キットが、前記ＴＰＯ模倣剤を前記対象に投与するためのツールをさらに含む、キット。
［発明１６］
前記毒性作用を緩和するための少なくとも１つのさらなる治療剤またはデバイスをさらに含む、発明１５に記載のキット。
［発明１７］
前記さらなる治療剤が、鎮痛剤、消毒剤、他のＴＰＯ模倣剤、他のサイトカイン、可溶性ｍｐｌ受容体、造血因子、インターロイキン、増殖因子または抗体、および化学療法剤からなる群から選択される、発明１６に記載のキット。 It will be appreciated by those skilled in the art that changes may be made to the above-described embodiments without departing from the broad concepts of the invention. It is therefore to be understood that this invention is not limited to the particular embodiments disclosed, but is intended to cover modifications within the spirit and scope of the invention as defined by this description. be.

Listed below are the inventions originally claimed in this application.
[Invention 1]
A method of alleviating the toxic effects of at least one of blister and caustic gas in a subject in need thereof, comprising administering to said subject an effective amount of a thrombopoietin (TPO) mimetic comprising the amino acid sequence of SEQ ID NO: 1 A method comprising administering an agent.
[Invention 2]
The method of invention 1, wherein the TPO mimetic is RWJ-800088.
[Invention 3]
The method of invention 1, wherein the TPO mimetic is romiplostim.
[Invention 4]
said caustic gas is selected from the group consisting of hydrogen sulfide, hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen cyanide, arsine, phosphine, nitric oxide, nitrogen dioxide, sulfur dioxide, ozone, chlorine, methylamine, and ammonia; The method according to any one of Inventions 1 to 3.
[Invention 5]
The invention wherein said vesicant is selected from the group consisting of distilled mustard, mustard gas, lewisite, mustard/lewisite, mustard/T, nitrogen mustard, sesquimustard, sulfur mustard, phosgene oxime, cantharidin, and furanocoumarin. 5. The method according to any one of 1 to 4.
[Invention 6]
6. The method of any one of inventions 1-5, wherein said effective amount of a TPO mimetic is administered to said subject before said subject is exposed to at least one of said blister agent and said caustic gas. described method.
[Invention 7]
The method of any one of inventions 1-5, wherein the TPO mimetic is administered to the subject when the subject is exposed to at least one of the blister agent and the caustic gas. .
[Invention 8]
The method of any one of inventions 1-5, wherein the TPO mimetic is administered to the subject after the subject has been exposed to at least one of the blister agent and the caustic gas. .
[Invention 9]
The method of claim 8, wherein said effective amount of TPO mimetic is administered to said subject after said subject has been exposed to at least one of said blister agent and said caustic gas.
[Invention 10]
10. The method of any one of claims 1-9, wherein said toxic effect is vascular injury induced by at least one of said blister and said caustic gas.
[Invention 11]
Inventions 1 to 9, wherein said toxic effect is hemorrhage, preferably microhemorrhage, most preferably pulmonary microhemorrhage, or cell influx, induced by at least one of said blister and said caustic gas The method according to any one of
[Invention 12]
10. The method of any one of claims 1-9, wherein said toxic effect is pulmonary fibrosis induced by at least one of said blister agent and said caustic gas.
[Invention 13]
10. The method of any one of claims 1-9, wherein said toxic effect is mortality or morbidity induced by at least one of said blister agent and said caustic gas.
[Invention 14]
14. The method of any one of inventions 1-13, wherein the effective amount of the TPO mimetic is administered to the subject by intravenous, intramuscular, intradermal, or subcutaneous injection.
[Invention 15]
A kit for mitigating the toxic effects of at least one of blister and caustic gas in a subject in need thereof, comprising an effective amount of a thrombopoietin (TPO) mimetic and a pharmaceutically acceptable carrier wherein said TPO mimetic comprises the amino acid sequence of SEQ ID NO: 1; preferably said TPO mimetic is RWJ-800088 or romiplostim; optionally said kit comprises said TPO mimetic; A kit further comprising a tool for administration to a subject.
[Invention 16]
16. The kit of invention 15, further comprising at least one additional therapeutic agent or device for alleviating said toxic effects.
[Invention 17]
said additional therapeutic agent is selected from the group consisting of analgesics, antiseptics, other TPO mimetics, other cytokines, soluble mpl receptors, hematopoietic factors, interleukins, growth factors or antibodies, and chemotherapeutic agents; The kit according to invention 16.

Claims

A pharmaceutical composition used to alleviate the toxic effects of at least one of blister and caustic gas in a subject in need thereof, comprising an effective amount of thrombopoietin comprising the amino acid sequence of SEQ ID NO: 1 ( Said pharmaceutical composition comprising a TPO) mimetic.

2. The pharmaceutical composition of claim 1, wherein said TPO mimetic is RWJ-800088.

2. The pharmaceutical composition of claim 1, wherein said TPO mimetic is romiplostim.

said caustic gas is selected from the group consisting of hydrogen sulfide, hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen cyanide, arsine, phosphine, nitric oxide, nitrogen dioxide, sulfur dioxide, ozone, chlorine, methylamine, and ammonia; 4. The pharmaceutical composition according to any one of claims 1-3.

3. The vesicant is selected from the group consisting of distilled mustard, mustard gas, lewisite, mustard/lewisite, mustard/T, nitrogen mustard, sesquimustard, sulfur mustard, phosgene oxime, cantharidin, and furanocoumarin. Item 5. The pharmaceutical composition according to any one of items 1 to 4.

6. The method of claims 1-5, wherein the effective amount of TPO mimetic is used to administer to the subject before the subject is exposed to at least one of the blister agent and the caustic gas. A pharmaceutical composition according to any one of claims.

6. Any one of claims 1-5, wherein the TPO mimetic is used to be administered to the subject when the subject is exposed to at least one of the blister agent and the caustic gas. The pharmaceutical composition according to the paragraph.

6. Any one of claims 1-5, wherein the TPO mimetic is used to be administered to the subject after the subject has been exposed to at least one of the blister agent and the caustic gas. The pharmaceutical composition according to the paragraph.

9. The method of claim 8 , wherein the effective amount of the TPO mimetic is employed to be administered to the subject after the subject has been exposed to at least one of the blister agent and the caustic gas. pharmaceutical composition .

10. The pharmaceutical composition of any one of claims 1-9, wherein said toxic effect is vascular injury induced by at least one of said blister and said caustic gas.

from claim 1, wherein said toxic effect is hemorrhage, preferably microhemorrhage, most preferably pulmonary microhemorrhage, or cell influx, induced by at least one of said blister and said caustic gas 10. The pharmaceutical composition according to any one of 9.

10. The pharmaceutical composition of any one of claims 1-9, wherein said toxic effect is pulmonary fibrosis induced by at least one of said blister agent and said caustic gas.

10. The pharmaceutical composition of any one of claims 1-9, wherein said toxic effect is mortality or morbidity induced by at least one of said blister and said caustic.

14. Any one of claims 1-13, wherein the effective amount of the TPO mimetic is used to be administered to the subject by intravenous, intramuscular, intradermal, or subcutaneous injection. pharmaceutical composition of

A kit for mitigating the toxic effects of at least one of blister and caustic gas in a subject in need thereof, comprising an effective amount of a thrombopoietin (TPO) mimetic and a pharmaceutically acceptable carrier wherein said TPO mimetic comprises the amino acid sequence of SEQ ID NO: 1; preferably said TPO mimetic is RWJ-800088 or romiplostim; optionally said kit comprises said TPO mimetic; A kit further comprising a tool for administration to a subject.

16. The kit of claim 15, further comprising at least one additional therapeutic agent or device for alleviating said toxic effects.

said additional therapeutic agent is selected from the group consisting of analgesics, antiseptics, other TPO mimetics, other cytokines, soluble mpl receptors, hematopoietic factors, interleukins, growth factors or antibodies, and chemotherapeutic agents; 17. A kit according to claim 16.