CN115279354A - 氯胺酮用于治疗恶病质的用途 - Google Patents
氯胺酮用于治疗恶病质的用途 Download PDFInfo
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- CN115279354A CN115279354A CN202080093125.7A CN202080093125A CN115279354A CN 115279354 A CN115279354 A CN 115279354A CN 202080093125 A CN202080093125 A CN 202080093125A CN 115279354 A CN115279354 A CN 115279354A
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
Abstract
本发明揭示一种氯胺酮用于制备改善恶病质的药物的用途，该药物给予接受5‑FU治疗的患者；其中氯胺酮的剂量至少约为5‑FU的剂量的60％。特定而言，本发明的药物可提高生存率以及改善恶病质所引起的体重降低。
Description
相关申请的交互引用
本非临时申请根据35U.S.C.§119(a)要求主张于2020年1月13日申请的美国临时申请第62/960,255号的优先权，其全部内容通过引用并入本文。
技术领域
本发明涉及氯胺酮用于治疗恶病质的用途；特定而言，氯胺酮用于接受5-FU治疗所导致的恶病质。
背景技术
5-氟尿嘧啶(5-FU)用于癌症治疗已有将近50多年的历史，可用于治疗多种癌症。虽其治疗癌症功效颇佳，但亦产生大量的副作用，例如恶心、呕吐、腹泻、黏膜发炎、头痛、肌肉无力、掉发、心肌梗塞、或肺炎等。因此服用5-FU对于癌症患者而言是极大负担。
恶病质(又称恶病体质)是由于疾病所产生的复合性代谢症候群，症候群中的代谢不良和神经性厌食症往往造成患者异常虚弱，主要症状包括肌肉耗损以及体重下降等。其他症状例如白蛋白、血红素降低，发炎因子(如，介素白-6(IL-6)、反应蛋白(CRP))上升等。恶病质的肌肉耗损病征无法单纯通过供给营养而恢复，即便增加进食量或提高营养的摄取，也无法预防或停止病患体重的持续下降。
目前的治疗方法仅能通过治疗导致恶病质的疾病(例如癌症)来舒缓症状，但往往成效不佳且难以痊愈，通常通过肌肉活动、给予刺激食欲或降低恶心感的药物、直接投予营养药剂、或其他支持性疗法来缓和恶病质的恶化。因此，本领域亟需研发一种可有效改善恶病质的症候群的药物或方法，使癌症患者的生存率可以提高。
发明内容
为解决前述问题并达成发明的目的，本发明的一实施方式提供一种氯胺酮用于制备改善恶病质的药物的用途，其中该药物给予接受5-FU治疗的患者。
于本发明的一实施例，其中氯胺酮的人体剂量为每周1-100mg/60kg。
于本发明的一实施例，其中该药物用于非肠胃道给药。
于本发明的一实施例，其中该药物用于改善因恶病质引起的体重降低。
于本发明的一实施例，其中该药物用于提高存活率。
本发明的另一实施方式提供一种治疗癌症的医药组合物，包括：5-FU、氯胺酮、和一医药上可接受的载剂；其中氯胺酮的人体剂量为每周1-100mg/60kg。
本发明的另一实施方式提供一种氯胺酮和5-FU的医药组合物用于制备治疗癌症的药物的用途。
于本发明的一实施例，其中氯胺酮的人体剂量为每周1-100mg/60kg。
于本发明的一实施例，其中该药物用于非肠胃道给药。
于本发明的一实施例，其中氯胺酮和5-FU同时或分别给予患者。
具体实施方式
以下参照实施例说明本发明，以明确阐释本发明的技术内容、特征、和功效。通过特定实施例的说明，本领域技术人员可进一步明了本发明采取的技术手段和功效，以达成前述发明目的。另，本说明书所公开的技术可为本领域技术人员理解并且实施，在不悖离发明概念的前提下，任何变更或改良均可被权利要求所涵盖。
本说明书及权利要求中所述的所有技术性及科学用语，除非另有所定义，皆为本发明所属技术领域具有通常知识者可知晓的定义。
本说明书及权利要求中所使用的单数用语“一”、“一个”、“该”、或其近似用语，除非另有说明，皆可指涉多于一个对象。本说明书使用的“或”、“以及”、“和”，除非另有说明，皆指涉“或/和”。此外，用语“包含”、“包括”皆非有所限制的开放式连接词。前述定义仅说明用语定义的指涉而不应解释为对发明内容的限制。除非另有说明，本发明所用的材料皆市售易于取得。
本说明书用语“约”是指测量的量，例如剂量，包括相对于在一个实施方案中指定量±15％或±10％的偏差；在较佳实施例中，相对于指定量±5％的偏差；在另一个较佳实施例中，相对于指定量±1％的偏差；或在最佳实施例中相对于指定量±0.1％的偏差；而该数量所涉及的物质的性质不因此受到影响。
5-氟尿嘧啶(fluorouracil，本说明书简称5-FU)是一种嘧啶类似物，主要用于治疗肿瘤。目前认为5-FU的作用方式是通过抑制胸苷酸合酶(Thymidylate synthase)的功能，进一步阻碍DNA的合成。
5-FU的副作用包括严重脱水、骨髓抑制、肠炎、口腔溃疡、皮炎、心绞痛以及心肌梗死、急性肾功能不全、间质性肺炎、肝功能损害、黄疸、腹泻等等。5-FU也可导致急性的中枢神经系统损伤(白质脑病)，以及中枢神经系统的退化。
氯胺酮(Ketamine，IUPAC：(R,S)-2-(2-氯苯基)-2-甲基胺-环己-1-酮((R,S)-2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one))，又称K他命，是一种非竞争性NMDA受体拮抗剂，自60年代起广泛地使用于麻醉、止痛、和镇静等用途。氯胺酮通过肝脏细胞色素(cytochrome)P450而代谢，以及与包括NMDA在内多种受体结合，形成麻醉的效果。
氯胺酮可抑制麸胺酸(中枢神经系统的神经传导物质)所诱发的NMDA受体活化，亦可抑制突触前神经元释放麸胺酸并增强抑制性神经传导物质：GABA的作用。
于本说明书，“氯胺酮”可指涉外消旋(racemic)或镜相异构富集(enantiomerically enriched)(例如镜相异构纯粹(enantiomerically pure))的形式。于一实施例，本发明所述的氯胺酮是外消旋氯胺酮。于另一实施例，本发明所述的氯胺酮是镜相异构富集氯胺酮。于一特定实施例，本发明所述的氯胺酮是S-镜相异构物或R-镜相异构物。
于本说明书，药物的剂量定义为每公斤体重给予的药物重量，例如：每公斤体重给予的药物克数(g/kg)或每公斤体重给予的药物毫克数(mg/kg)。
本说明书用语“约”或“近似”等词指涉本领域技术人员理解的可接受偏差程度，其可在一定程度上根据文中的使用而变化。一般而言，例如，“约”或“近似”可指引用值附近±10％、±5％、或±3％范围的数值。
本说明书用语“治疗”、“改善”、或其近似用语，包含以治疗或预防的方式缓和、减轻、或改善至少一项疾病症状或生理状况、预防新增的症状、抑制疾病或生理状况、阻止或减缓疾病发展、造成疾病或生理状况的复原、减缓因疾病造成的生理状况、停止疾病症状或生理状况。
本说明书用语“恶病质”(又称恶病体质)指涉因持续性体重严重流失、厌食、无力、贫血及蛋白质、脂肪和糖类代谢异常所造成的症候群。临床上把恶病质定义为一种以厌食、贫血、体重减轻为主要症状的综合症。恶病质可发生于多种病况，包括肿瘤、化疗、厌食症、严重创伤、肠胃吸收功能不良、体重下降、贫血、肥胖症及严重的败血症，其中以肿瘤诱发的恶病质最为常见，称为肿瘤恶病质。
本发明的医药组合物可用于治疗个体的恶病质。具体而言，本发明的医药组合物可施用于具有产生恶病质风险或感受恶病质相关病征的个体，以避免恶病质的发生或改善或延缓恶病质的进展。
本说明书用语“有效量(effective amount)”或“治疗(therapeutically)有效量”，指涉化合物或药物的一足够量，可于患者服药后减轻一或多项疾病症状或生理状况；其结果为降低和/或缓和征象(sign)、症状(symptom)、或病因，或为其他生理系统的有意图的改变。举例而言，治疗的“有效量”包含一本发明提供化合物的可于临床上显著降低疾病症状的剂量。
依据本发明，治疗有效量依据疾病严重程度、患者年龄、患者健康状态、癌症潜在风险、或其他因素而改变。
依据本发明，本说明书所述的组合物以及其他药剂成分不必以同一医药组合物给药；因不同的物理和化学特性，可以不同途径给药。
本说明书用语“组合物”或“医药组合物”指涉至少一种药物及其他载剂的混和，该载剂包含但不限于：安定剂、稀释剂、分散剂、悬浮剂、增厚剂、或赋形剂、或上述的组合。
本说明书用语“医药上可接受”指涉化合物、组合物、和/或剂型于合理的医疗判断范围中，适合用于与服药者(如人类)组织接触，并且无过量的毒性、刺激、过敏反应、或其他问题或并发症，以及具有相当合理的利益/风险比。各载剂必须在与其他配方成分相容的前提上，方为“可接受”。
本说明书用语“载剂(carrier)”，指涉不具毒性的化合物或药剂，其具有协助细胞或组织吸收药物的功能。
适当赋形剂的例示包括但不限于：乳糖、右旋糖、蔗糖、山梨糖、甘露糖、淀粉、阿拉伯胶、磷酸钙、褐藻酸盐、黄蓍树胶、明胶、硅酸钙、微晶纤维素、聚乙烯吡咯啶酮、纤维素、灭菌水、糖浆和甲基纤维素。
组合物可另外包括润滑剂，例如，滑石粉、硬脂酸镁和矿物油；湿润剂；乳化和悬浮剂；保存剂，例如，羟基苯甲酸甲酯和丙酯；甜味剂；以及调味剂。
依据本发明，本发明的药物可应用于多种给药技术，包括但不限于静脉注射、口服、非消化道给药、眼部给药、肺部给药、或局部给药、或上述给药途径的组合。
依据本发明，本发明的药物用于腹腔注射。
依据本发明，医药组合物的形式可为锭剂、药丸、粉末、糖锭、药包、药片、酏剂、悬浮液、乳剂、溶剂、糖浆、软和硬明胶胶囊、栓剂、灭菌注射液和包装粉末。
本发明提供一种治疗5-FU引起的恶病质的方法，包括：给予患者一治疗有效量的氯胺酮，其中该患者接受5-FU的治疗。
本发明另提供一种氯胺酮用于制备改善恶病质的药物的用途，其中该药物给予接受5-FU治疗的患者。
于一较佳实施例，该药物用于改善因恶病质引起的体重降低。
于一较佳实施例，该药物用于提高存活率。
本发明另提供一种治疗癌症的方法，包括：给予患者一治疗有效量的医药组合物，其中该医药组合物包括：5-FU、氯胺酮、和一医药上可接受的载剂。
于一较佳实施例，该癌症包括但不限于：肛门癌、乳癌、大肠直肠癌、口咽癌、胃癌、胰脏癌、皮肤癌、或头颈癌。
于一较佳实施例，其中该氯胺酮和该5-FU同时或分别给予患者。
本发明另提供一种治疗癌症的医药组合物，包括：5-FU、氯胺酮、和一医药上可接受的载剂。
于一较佳实施例，该医药组合物的氯胺酮的剂量至少约为5-FU的剂量的60％。
于一较佳实施例，氯胺酮的人体剂量为每周1-100mg/60kg。
于一更佳实施例，氯胺酮的人体剂量为每周1-50mg/60kg。
于一较佳实施例，氯胺酮的人体剂量为每周约25mg/60kg。
抗肿瘤药物卡培他滨(Capecitabine)经口服吸收后在组织内被转化成5-FU从而发挥抗肿瘤的作用。因此于一特定实施例，该5-FU可以卡培他滨的形式给予患者。
去甲基氯胺酮(norketamine，IUPAC：(R,S)-2-(2-氯苯基)-2-(胺)环己酮((R,S)-2-(2-chlorophenyl)-2-(amino)cyclohexanone))是氯胺酮去甲基后的代谢产物，并相较于氯胺酮具有较低且较缓生效的活性。
因此，于一特定实施例，该氯胺酮可以去甲基氯胺酮的形式给予患者。于本说明书，“去甲基氯胺酮”可指涉外消旋或镜相异构富集(例如纯粹镜相异构)的形式。
实施例
材料与方法
6至12周大的小鼠(取自国家实验动物中心)个别饲养于温控房，其饲养条件为12小时光照/12小时黑暗的循环，温度为24±1℃。
将小鼠区分为4组，每组4只。
将5-FU配制为小鼠每公斤50毫克(50mg/kg)的剂量，每日于腹腔内(i.p.)注射一次并连续注射3日。
另将氯胺酮(Ketamine)配置为15mg/kg或30mg/kg的剂量，并于5-FU的最后一剂注射后24小时注射于小鼠腹腔(i.p.)。
使用食盐水作为5-FU和氯胺酮的载剂以及控制组。
上述注射完成后，观察小鼠存活率、体重、和进食量。
实验结果
本实施例的实验结果揭示于表1至表3。
可由结果得知，全部组别的小鼠均接受50mg/kg的5-FU腹腔注射，但于注射5-FU后第17日，注射50mg/kg的5-FU以及15mg/kg的氯胺酮的组别仅存25％的存活率。但于50mg/kg的5-FU以及30mg/kg的氯胺酮的组别仍有100％的存活率。
其次，关于进食量，控制组摄取235.2克(g)的食物(标准差：4.0)。注射5-FU的组别摄取189.6g的食物(标准差：7.5)。而给予5-FU和氯胺酮的二组别摄取量相近，氯胺酮15mg/kg的组别摄取215.0g的食物(标准差：8.3)；氯胺酮30mg/kg的组别摄取219.1g的食物(标准差：5.7)。
再者，关于体重变化，注射50mg/kg的5-FU以及15mg/kg的氯胺酮的组别的小鼠平均体重下降19.9％，与仅注射5-FU的组别的小鼠下降幅度相近。相对地，于50mg/kg的5-FU以及30mg/kg的氯胺酮的组别，体重仅下降7.5％，与控制组(下降0.2％)较为接近。
表1试验结束时最后观察值推估(Last Observation Carried Forward，LOCF)群体的小鼠体重
s.d.:标准差(Standard deviation)
表2试验结束时LOCF群体的小鼠体重变化量
表3试验结束时LOCF群体的小鼠体重变化百分比
依据本申请揭示的内容，可于动物实验得知注射5-FU后可能引起体重降低、摄食和饮水量降低、以及存活率降低等恶病质的症状及并发症，而共同给予氯胺酮可改善上述症状。因此，本领域技术人员可依据本说明书得知，氯胺酮可用于改善或治疗5-FU所引起的恶病质。
于本说明书实施例揭示的内容，本发明所属领域具有通常知识者可明显得知前述实施例仅为例示而非限制；本发明所属技术领域具有通常知识者可通过诸多变换、替换而实施，并不与本发明的技术特征有所差异。依据说明书实施例，本发明可有多种变换仍无碍于实施。本说明书提供的权利要求界定本发明的范围，该范围涵盖前述方法与结构及与其相等的申请。
Claims (10)
1.一种氯胺酮用于制备改善恶病质的药物的用途，其中该药物给予接受5-FU治疗的患者。
2.如权利要求1所述的用途，其中氯胺酮的人体剂量为每周1-100mg/60kg。
3.如权利要求1所述的用途，其中该药物用于非肠胃道给药。
4.如权利要求1所述的用途，其中该药物用于改善因恶病质引起的体重降低。
5.如权利要求1所述的用途，其中该药物用于提高存活率。
6.一种治疗癌症的医药组合物，包括：5-FU、氯胺酮、和一医药上可接受的载剂；其中氯胺酮的人体剂量为每周1-100mg/60kg。
7.一种氯胺酮和5-FU的医药组合物用于制备治疗癌症的药物的用途。
8.如权利要求7所述的用途，其中氯胺酮的人体剂量为每周1-100mg/60kg。
9.如权利要求7所述的用途，其中该药物用于非肠胃道给药。
10.如权利要求7所述的用途，其中氯胺酮和5-FU同时或分别给予患者。
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| US202062960255P | 2020-01-13 | 2020-01-13 | |
| US62/960,255 | 2020-01-13 | ||
| PCT/US2020/061187 WO2021145952A1 (en) | 2020-01-13 | 2020-11-19 | Use of ketamine in the treatment of cachexia |
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| US20100074955A1 (en) * | 2006-09-19 | 2010-03-25 | Laboratorios Del Dr. Esteve, S.A. | Combination of NMDA-Receptor Ligand and a Compound With 5-HT6 Receptor Affinity |
| US20200002412A1 (en) * | 2018-06-29 | 2020-01-02 | Cedars-Sinai Medical Center | Interleukin-1 inhibition for combination treatment of pancreatic cancer cachexia |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH09323930A (ja) * | 1996-04-04 | 1997-12-16 | Takeda Chem Ind Ltd | 悪液質の予防・治療剤 |
| ATE491474T1 (de) * | 2001-06-07 | 2011-01-15 | Sang Christine Dr | Behandlung von neuropathischen schmerzen mittels eines n-methyl-d-aspartate (nmda)-rezeptor- antagonists |
| WO2006091862A2 (en) * | 2005-02-24 | 2006-08-31 | Kemia, Inc. | Cytokine inhibitors and their use in therapy |
| WO2009132050A2 (en) * | 2008-04-21 | 2009-10-29 | Otonomy, Inc. | Auris formulations for treating otic diseases and conditions |
| WO2019169165A1 (en) * | 2018-02-28 | 2019-09-06 | Novocine Therapeutics, Llc | Ketamine and ketamine-related compounds for the treatment of neurological disorders |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100074955A1 (en) * | 2006-09-19 | 2010-03-25 | Laboratorios Del Dr. Esteve, S.A. | Combination of NMDA-Receptor Ligand and a Compound With 5-HT6 Receptor Affinity |
| US20200002412A1 (en) * | 2018-06-29 | 2020-01-02 | Cedars-Sinai Medical Center | Interleukin-1 inhibition for combination treatment of pancreatic cancer cachexia |
Non-Patent Citations (3)
| Title |
|---|
| SALIH N A, AL-BAGGOU B K: "Effect of memantine hydrochloride on cisplatin-induced neurobehavioral toxicity in mice", 《 ACTA NEUROLOGICA BELGICA》, vol. 120 * |
| 佴永军;江志伟;姚平;黎介寿;: "PDTC调控癌性恶病质肌肉萎缩的实验研究", 现代生物医学进展, no. 06 * |
| 佴永军;江志伟;汪志明;黎介寿;: "核因子-κB抑制剂调控癌性恶病质的实验研究", 肠外与肠内营养, no. 05 * |
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| JP2023500172A (ja) | 2023-01-04 |
| AU2020422620A1 (en) | 2022-08-25 |
| MX2022008628A (es) | 2022-09-26 |
| KR102530724B1 (ko) | 2023-05-09 |
| EP4090326A4 (en) | 2024-01-17 |
| JP7353687B2 (ja) | 2023-10-02 |
| IL294709A (en) | 2022-09-01 |
| ZA202208468B (en) | 2023-04-26 |
| TW202135788A (zh) | 2021-10-01 |
| KR20220127852A (ko) | 2022-09-20 |
| TWI786498B (zh) | 2022-12-11 |
| EP4090326A1 (en) | 2022-11-23 |
| WO2021145952A1 (en) | 2021-07-22 |
| US11400060B2 (en) | 2022-08-02 |
| CA3167710A1 (en) | 2021-07-22 |
| IL294709B1 (en) | 2023-03-01 |
| IL294709B2 (en) | 2023-07-01 |
| BR112022013755A2 (pt) | 2022-10-11 |
| CA3167710C (en) | 2023-03-28 |
| US20210212965A1 (en) | 2021-07-15 |
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