JPWO2021202084A5 - - Google Patents
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- JPWO2021202084A5 JPWO2021202084A5 JP2022558100A JP2022558100A JPWO2021202084A5 JP WO2021202084 A5 JPWO2021202084 A5 JP WO2021202084A5 JP 2022558100 A JP2022558100 A JP 2022558100A JP 2022558100 A JP2022558100 A JP 2022558100A JP WO2021202084 A5 JPWO2021202084 A5 JP WO2021202084A5
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- composition
- pulmonary
- use according
- rtx
- inflammatory disease
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- 239000000203 mixture Substances 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 35
- 230000002685 pulmonary effect Effects 0.000 claims description 22
- 208000027866 inflammatory disease Diseases 0.000 claims description 20
- DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 claims description 20
- IKYCZSUNGFRBJS-UHFFFAOYSA-N Euphorbia factor RL9 = U(1) = Resiniferatoxin Natural products COC1=CC(O)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 IKYCZSUNGFRBJS-UHFFFAOYSA-N 0.000 claims description 16
- DSDNAKHZNJAGHN-UHFFFAOYSA-N resinferatoxin Natural products C1=C(O)C(OC)=CC(CC(=O)OCC=2CC3(O)C(=O)C(C)=CC3C34C(C)CC5(OC(O4)(CC=4C=CC=CC=4)OC5C3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-UHFFFAOYSA-N 0.000 claims description 16
- 229940073454 resiniferatoxin Drugs 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 230000004054 inflammatory process Effects 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000025678 Ciliary Motility disease Diseases 0.000 claims description 4
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 208000009470 Ventilator-Associated Pneumonia Diseases 0.000 claims description 4
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 4
- 238000005399 mechanical ventilation Methods 0.000 claims description 4
- 201000009266 primary ciliary dyskinesia Diseases 0.000 claims description 4
- 206010001881 Alveolar proteinosis Diseases 0.000 claims description 2
- 208000025721 COVID-19 Diseases 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 claims description 2
- 102000004127 Cytokines Human genes 0.000 claims description 2
- 206010065563 Eosinophilic bronchitis Diseases 0.000 claims description 2
- 108090001005 Interleukin-6 Proteins 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 206010029888 Obliterative bronchiolitis Diseases 0.000 claims description 2
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 2
- 206010037457 Pulmonary vasculitis Diseases 0.000 claims description 2
- 201000010001 Silicosis Diseases 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 239000010425 asbestos Substances 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 201000003848 bronchiolitis obliterans Diseases 0.000 claims description 2
- 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 239000000428 dust Substances 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 201000009580 eosinophilic pneumonia Diseases 0.000 claims description 2
- 206010016629 fibroma Diseases 0.000 claims description 2
- 230000002538 fungal effect Effects 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 230000004199 lung function Effects 0.000 claims description 2
- 210000005036 nerve Anatomy 0.000 claims description 2
- 230000003071 parasitic effect Effects 0.000 claims description 2
- 208000005333 pulmonary edema Diseases 0.000 claims description 2
- 201000009732 pulmonary eosinophilia Diseases 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims description 2
- 229910052895 riebeckite Inorganic materials 0.000 claims description 2
- 201000009890 sinusitis Diseases 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
Description
本明細書で開示される実施形態に対する種々の改変および変更は、本開示の範囲および趣旨から逸脱することなく、当業者に明らかになる。例証的な実施形態および例は、例として提供されるに過ぎず、本発明の範囲を限定することは意図されない。
特定の実施形態では、例えば、以下が提供される：
（項目１）
肺炎症性疾患を処置するための方法であって、前記方法は、肺炎症性疾患の処置の必要性のある被験体に、有効量のレシニフェラトキシン（ＲＴＸ）を硬膜外に、神経節周囲に、または神経節内に投与する工程を包含する方法。
（項目２）
肺炎症性疾患の処置の必要性のある被験体を処置する方法における使用のための、レシニフェラトキシン（ＲＴＸ）を含む組成物。
（項目３）
前記方法は、前記組成物を、前記被験体に硬膜外に、神経節周囲にまたは神経節内に投与する工程を包含する、項目２に記載の使用のための組成物。
（項目４）
前記有効量のＲＴＸは、ＩＬ－６、ＩＬ－１βおよび／またはＩＦＮγを含む１またはこれより多くのサイトカインの低減を生じる、項目１に記載の方法または項目２もしくは３に記載の使用のための組成物。
（項目５）
前記有効量のＲＴＸは、改善された肺機能を生じる、前述の項目のいずれか１項に記載の方法または使用のための組成物。
（項目６）
前記有効量のＲＴＸは、低減された肺浮腫を生じる、前述の項目のいずれか１項に記載の方法または使用のための組成物。
（項目７）
前記被験体は、成人である、前述の項目のいずれか１項に記載の方法または使用のための組成物。
（項目８）
前記ＲＴＸは、約０．１μｇ～約１００μｇの用量で投与される、前述の項目のいずれか１項に記載の方法または使用のための組成物。
（項目９）
前記用量は、約０．１μｇ～約１μｇ、約１μｇ～約５μｇ、約５μｇ～約１０μｇ、約１０μｇ～約２０μｇ、約２０μｇ～約５０μｇ、または約５０～約１００μｇである、項目８に記載の方法または使用のための組成物。
（項目１０）
前記方法は、硬膜外投与を含む、前述の項目のいずれか１項に記載の方法または使用のための組成物。
（項目１１）
前記方法は、神経節周囲神経ブロックを含む、項目１～９のいずれか１項に記載の方法または使用のための組成物。
（項目１２）
前記方法は、神経節内投与を含む、項目１～９のいずれか１項に記載の方法または使用のための組成物。
（項目１３）
前記ＲＴＸは、前記ＲＴＸおよび薬学的に受容可能なキャリアを含む薬学的製剤において投与される、前述の項目のいずれか１項に記載の方法または使用のための組成物。
（項目１４）
前記薬学的に受容可能なキャリアは、水を含む、項目１３に記載の方法または使用のための組成物。
（項目１５）
前記薬学的に受容可能なキャリアは、生理食塩水を含む、項目１３に記載の方法または使用のための組成物。
（項目１６）
前記ＲＴＸは、１μｇ／ｍｌ～１００μｇ／ｍｌの範囲に及ぶ濃度で前記薬学的製剤に存在する、項目１３～１５のいずれか１項に記載の方法または使用のための組成物。
（項目１７）
前記ＲＴＸは、１μｇ／ｍｌ～５μｇ／ｍｌ、５μｇ／ｍｌ～１０μｇ／ｍｌ、１０μｇ／ｍｌ～２０μｇ／ｍｌ、２０μｇ／ｍｌ～５０μｇ／ｍｌ、または５０μｇ／ｍｌ～１００μｇ／ｍｌの範囲に及ぶ濃度で前記薬学的製剤に存在する、項目１６に記載の方法または使用のための組成物。
（項目１８）
前記肺炎症性疾患は、急性呼吸窮迫症候群（ＡＲＤＳ）、慢性閉塞性肺疾患（ＣＯＰＤ）、肺動脈性高血圧症（ＰＡＨ）、慢性炎症性肺疾患、肺線維症、肺血管炎、肺サルコイドーシス、肺移植と関連する炎症および／もしくは感染症、急性または肺拒絶および／もしくは機能障害、気管支炎、副鼻腔炎、喘息、嚢胞性線維腫、細菌感染症、真菌感染症、寄生生物感染症、ウイルス感染症、閉塞性細気管支炎症候群（ＢＯＳ）、原発性線毛運動不全症（ＰＣＤ）、肺胞蛋白症、特発性肺線維症（ＩＰＦ）、好酸球性肺炎、好酸球性気管支炎、人工呼吸と関連する炎症および／もしくは感染症、人工呼吸器関連肺炎、アスベスト関連気道障害もしくは疾患、ダスト関連気道障害もしくは疾患、珪肺症、ならびに放射線もしくは化学物質関連気道疾患もしくは障害、ならびにこれらの任意の組み合わせからなる群より選択される、前述の項目のいずれか１項に記載の方法または組成物。
（項目１９）
前記肺炎症性疾患は、急性呼吸窮迫症候群（ＡＲＤＳ）である、前述の項目のいずれか１項に記載の方法または組成物。
（項目２０）
前記肺炎症性疾患は、慢性閉塞性肺疾患（ＣＯＰＤ）である、前述の項目のいずれか１項に記載の方法または組成物。
（項目２１）
前記肺炎症性疾患は、肺動脈性高血圧症（ＰＡＨ）である、前述の項目のいずれか１項に記載の方法または組成物。
（項目２２）
前記肺炎症性疾患は、人工呼吸と関連する炎症および／もしくは感染症、ならびに／または人工呼吸器関連肺炎である、前述の項目のいずれか１項に記載の方法または組成物。
（項目２３）
前記肺炎症性疾患は、ＣＯＶＩＤ－１９と関連する、前述の項目のいずれか１項に記載の方法または組成物。
Various modifications and changes to the embodiments disclosed herein will be apparent to those skilled in the art without departing from the scope and spirit of this disclosure. The illustrative embodiments and examples are provided by way of example only and are not intended to limit the scope of the invention.
In certain embodiments, for example, the following is provided:
(Item 1)
A method for treating a pulmonary inflammatory disease, the method comprising administering an effective amount of resiniferatoxin (RTX) epidurally to a subject in need of treatment for a pulmonary inflammatory disease. A method comprising periganglionic or intraganglionic administration.
(Item 2)
A composition comprising resiniferatoxin (RTX) for use in a method of treating a subject in need of treatment for a pulmonary inflammatory disease.
(Item 3)
3. A composition for use according to item 2, wherein said method comprises administering said composition to said subject epidurally, periganglionically or intraganglionically.
(Item 4)
For the method according to item 1 or the use according to items 2 or 3, wherein said effective amount of RTX results in a reduction of one or more cytokines including IL-6, IL-1β and/or IFNγ. Composition.
(Item 5)
A method or composition for use according to any of the preceding items, wherein said effective amount of RTX results in improved lung function.
(Item 6)
A method or composition for use according to any of the preceding items, wherein said effective amount of RTX results in reduced pulmonary edema.
(Item 7)
A method or composition for use according to any of the preceding items, wherein the subject is an adult.
(Item 8)
A composition for a method or use according to any of the preceding items, wherein the RTX is administered at a dose of about 0.1 μg to about 100 μg.
(Item 9)
Item 8, wherein the dose is about 0.1 μg to about 1 μg, about 1 μg to about 5 μg, about 5 μg to about 10 μg, about 10 μg to about 20 μg, about 20 μg to about 50 μg, or about 50 to about 100 μg. METHODS OR COMPOSITIONS FOR USE.
(Item 10)
A method or composition for use according to any of the preceding items, wherein said method comprises epidural administration.
(Item 11)
10. A method or composition for use according to any one of items 1 to 9, wherein the method comprises a periganglionic nerve block.
(Item 12)
A method or composition for use according to any one of items 1 to 9, wherein the method comprises intraganglionic administration.
(Item 13)
A composition for a method or use according to any of the preceding items, wherein said RTX is administered in a pharmaceutical formulation comprising said RTX and a pharmaceutically acceptable carrier.
(Item 14)
14. A composition for a method or use according to item 13, wherein the pharmaceutically acceptable carrier comprises water.
(Item 15)
14. A method or composition for use according to item 13, wherein the pharmaceutically acceptable carrier comprises saline.
(Item 16)
A composition for the method or use according to any one of items 13 to 15, wherein the RTX is present in the pharmaceutical formulation at a concentration ranging from 1 μg/ml to 100 μg/ml.
(Item 17)
The RTX is present at a concentration ranging from 1 μg/ml to 5 μg/ml, 5 μg/ml to 10 μg/ml, 10 μg/ml to 20 μg/ml, 20 μg/ml to 50 μg/ml, or 50 μg/ml to 100 μg/ml. 17. A composition for the method or use according to item 16, present in said pharmaceutical formulation.
(Item 18)
The pulmonary inflammatory diseases include acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), chronic inflammatory pulmonary disease, pulmonary fibrosis, pulmonary vasculitis, pulmonary sarcoidosis, and pulmonary inflammatory disease. Transplant-related inflammation and/or infection, acute or pulmonary rejection and/or dysfunction, bronchitis, sinusitis, asthma, cystic fibroma, bacterial, fungal, parasitic, viral infections bronchiolitis obliterans syndrome (BOS), primary ciliary dyskinesia (PCD), alveolar proteinosis, idiopathic pulmonary fibrosis (IPF), eosinophilic pneumonia, eosinophilic bronchitis, Inflammation and/or infection associated with mechanical ventilation, ventilator-associated pneumonia, asbestos-related airway disorders or disorders, dust-related airway disorders or disorders, silicosis, and radiation- or chemical-related airway disorders or disorders, and any of these. A method or composition according to any one of the preceding items, selected from the group consisting of a combination of.
(Item 19)
A method or composition according to any of the preceding items, wherein the pulmonary inflammatory disease is acute respiratory distress syndrome (ARDS).
(Item 20)
A method or composition according to any of the preceding items, wherein the pulmonary inflammatory disease is chronic obstructive pulmonary disease (COPD).
(Item 21)
The method or composition according to any of the preceding items, wherein the pulmonary inflammatory disease is pulmonary arterial hypertension (PAH).
(Item 22)
The method or composition according to any of the preceding items, wherein the pulmonary inflammatory disease is inflammation and/or infection associated with mechanical ventilation, and/or ventilator-associated pneumonia.
(Item 23)
A method or composition according to any of the preceding items, wherein said pulmonary inflammatory disease is associated with COVID-19.
Claims (23)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063002165P | 2020-03-30 | 2020-03-30 | |
| US63/002,165 | 2020-03-30 | ||
| US202063122858P | 2020-12-08 | 2020-12-08 | |
| US63/122,858 | 2020-12-08 | ||
| PCT/US2021/022089 WO2021202084A1 (en) | 2020-03-30 | 2021-03-12 | Treating pulmonary inflammatory disease associated with covid-19 by administering resiniferatoxin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2023519853A JP2023519853A (en) | 2023-05-15 |
| JPWO2021202084A5 true JPWO2021202084A5 (en) | 2024-03-22 |
Family
ID=75340289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022558100A Pending JP2023519853A (en) | 2020-03-30 | 2021-03-12 | Treatment of pulmonary inflammatory disease associated with COVID-19 by administering resiniferatoxin |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20230143545A1 (en) |
| EP (1) | EP4125871A1 (en) |
| JP (1) | JP2023519853A (en) |
| KR (1) | KR20220161423A (en) |
| CN (1) | CN115666551A (en) |
| AU (1) | AU2021248861A1 (en) |
| CA (1) | CA3173611A1 (en) |
| WO (1) | WO2021202084A1 (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2187193B (en) | 1986-02-27 | 1989-11-08 | Gerald Scott | Controllably and swiftly degradable polymer compositions and films and other products made therefrom |
| US5021450A (en) | 1989-05-30 | 1991-06-04 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | New class of compounds having a variable spectrum of activities for capsaicin-like responses, compositions and uses thereof |
| US5232684A (en) | 1990-06-29 | 1993-08-03 | The United States Of America As Represented By The Department Of Health And Human Services | Labelled resiniferatoxin, compositions thereof, and methods for using the same |
| EP2879660A1 (en) | 2012-08-03 | 2015-06-10 | Mestex AG | Resiniferatoxin solution |
-
2021
- 2021-03-12 CN CN202180025683.4A patent/CN115666551A/en active Pending
- 2021-03-12 CA CA3173611A patent/CA3173611A1/en active Pending
- 2021-03-12 KR KR1020227037621A patent/KR20220161423A/en active Search and Examination
- 2021-03-12 WO PCT/US2021/022089 patent/WO2021202084A1/en unknown
- 2021-03-12 US US17/915,444 patent/US20230143545A1/en active Pending
- 2021-03-12 AU AU2021248861A patent/AU2021248861A1/en active Pending
- 2021-03-12 JP JP2022558100A patent/JP2023519853A/en active Pending
- 2021-03-12 EP EP21716045.6A patent/EP4125871A1/en active Pending
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