WO2022007832A1 - 组合物在治疗脑卒中的用途 - Google Patents

组合物在治疗脑卒中的用途 Download PDF

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WO2022007832A1
WO2022007832A1 PCT/CN2021/104933 CN2021104933W WO2022007832A1 WO 2022007832 A1 WO2022007832 A1 WO 2022007832A1 CN 2021104933 W CN2021104933 W CN 2021104933W WO 2022007832 A1 WO2022007832 A1 WO 2022007832A1
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composition
edaravone
stroke
use according
dexbornol
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PCT/CN2021/104933
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English (en)
French (fr)
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冯晓飞
诸舜伟
刘存存
王峰
任晋生
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先声药业有限公司
江苏先声药业有限公司
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Priority to CN202180048433.2A priority Critical patent/CN115803022A/zh
Priority to EP21836973.4A priority patent/EP4180038A4/en
Priority to US18/011,646 priority patent/US20240033247A1/en
Priority to JP2022578863A priority patent/JP2023533443A/ja
Publication of WO2022007832A1 publication Critical patent/WO2022007832A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to the use of a composition, furthermore, the present invention relates to the use of a composition in preparing a medicament for treating stroke in patients.
  • stroke is the second leading cause of death worldwide and the first cause of long-term and serious neurological disease in China.
  • risk factors for stroke mainly include blood pressure, blood sugar, cholesterol level, body mass index, smoking, physical activity and diet. These risk factors are strongly associated with stroke. Therefore, stroke patients with a history of underlying diseases may have higher morbidity, mortality, recurrence and disability rates.
  • drugs that have actually been confirmed for the acute and subacute stages of cerebral ischemia cannot fully meet the needs of clinical applications, especially those with multiple diseases or disease history.
  • Clinical needs of patients with ischemic stroke (such as history of hypertension, hyperlipidemia, diabetes, heart disease, etc.).
  • the present invention provides a method for treating stroke in patients with a history of hypertension.
  • the present invention relates to the use of a composition in preparing a medicine for treating stroke in patients, characterized in that the composition comprises edaravone (3-methyl-1-phenyl-2-pyrazoline-5 - ketone) and dexborneol (Dexborneol, also known as dexborneol), the patient has a history of hypertension.
  • edaravone 3-methyl-1-phenyl-2-pyrazoline-5 - ketone
  • dexborneol also known as dexborneol
  • the present invention relates to the use of a composition in the treatment of stroke in a patient, characterized in that the composition comprises edaravone and dexbornol, and the patient has a history of hypertension.
  • the present invention relates to a composition for treating cerebral apoplexy in a patient, characterized in that the composition comprises edaravone and dexbornol, and the patient has a history of hypertension.
  • the present invention relates to a method for treating stroke in a patient, the method comprising administering to the patient a therapeutically effective dose of a composition, wherein the composition comprises edaravone and dexbornol, and the patient has high History of blood pressure.
  • the weight ratio of edaravone to dexbornol in the composition is 1:1-8:1, 1:1-7:1, 1:1-6:1, 1:1 ⁇ 5:1, 1:1 ⁇ 4:1, 1:1 ⁇ 3:1, 1:1 ⁇ 2:1 or 1:1 ⁇ 1.5:1.
  • the weight ratio of edaravone to dexbornol in the composition is 1:1 to 5:1.
  • the weight ratio of edaravone to dexbornol in the composition is 1:1 to 4:1.
  • the weight ratio of edaravone to dexbornol in the composition is 4:1.
  • the plasma exposure ratio of edaravone to dexbornol in the patient is 1:1-8:1, 1:1-7 :1, 1:1 ⁇ 6:1, 1:1 ⁇ 5:1, 1:1 ⁇ 4:1, 1:1 ⁇ 3:1, 1:1 ⁇ 2:1 or 1:1 ⁇ 1.5:1 , preferably 1:1 to 5:1, more preferably 4:1.
  • the composition is administered 1-3 times daily for 3-21 consecutive days.
  • the composition is administered every 12 hours, twice a day, for 14 consecutive days.
  • the dose of edaravone administered in the composition is 10-30 mg/time.
  • the dose of edaravone administered in the composition is 10 mg/time.
  • the dose of edaravone administered in the composition is 20 mg/time.
  • the dose of edaravone administered in the composition is 30 mg/time.
  • the composition further comprises a pharmaceutically acceptable excipient.
  • the pharmaceutically acceptable adjuvant is selected from one or more of antioxidants, co-solvents or solvents.
  • the pharmaceutically acceptable adjuvant is selected from antioxidants, cosolvents or solvents.
  • the antioxidant is sodium metabisulfite.
  • the co-solvent is propylene glycol.
  • the solvent is water for injection.
  • the stroke is ischemic stroke.
  • the stroke is acute ischemic stroke.
  • Beneficial effects of the present invention We unexpectedly found that the edaravone and dexcamphenol composition of the present invention has achieved a significant curative effect on stroke patients with a history of hypertension, and is a patient with acute ischemic stroke combined with hypertension Provides more effective treatment drugs and treatment options.
  • test objectives derived from clinical trials
  • test methods derived from test objectives, test methods and test results are as follows.
  • OBJECTIVE To study the subgroup efficacy of edaravone and dexbornol injection in stroke patients with a history of underlying diseases.
  • a multi-center, randomized double-blind, positive drug (edaravone injection) controlled phase III clinical trial was carried out, and 1200 patients with acute ischemic stroke with an onset time of ⁇ 48 hours were selected and randomly assigned to enter the hospital according to a ratio of about 1:1.
  • Pharmacodynamics and safety studies were conducted in the edaravone dexbornol injection group or the edaravone group. To study and analyze the efficacy of edaravone dextranyl alcohol injection in the treatment of acute ischemic stroke patients with underlying disease history.
  • each subgroup was included according to the following diagnostic criteria, and the patients in each subgroup were randomly assigned in an approximately 1:1 ratio to receive either edaravone dexbornol injection or edaravone injection
  • the fluid was continuously treated for 14 days and followed up to the 90th day.
  • the main criteria for subjects to be selected are age 35-80 years old, male or female, diagnosed as ischemic stroke (cerebral infarction) according to the Fourth National Cerebrovascular Disease Academic Conference "Key Points of Diagnosis of Various Cerebrovascular Diseases", and have a clear diagnosis of ischemic stroke (cerebral infarction).
  • the total cholesterol in the fasting serum of the subjects exceeds 5.72 mmol/L, and the triglyceride exceeds 1.70 mmol/L. L; or subjects currently using lipid-lowering drugs whose serum total cholesterol and triglyceride do not exceed the above standards (total cholesterol does not exceed 5.72 mmol/L and triglyceride does not exceed 1.70 mmol/L); and Diagnosis criteria of "Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China" (2016 Revised Edition).
  • Test drug name Edaravone Dexbornol Injection
  • 5mL 10mg (Edaravone 10mg);
  • test drug and the positive control drug are identical in color and shape.
  • the two groups of drugs have identical packaging and batch numbers, and the packaging and batch numbers are uniformly marked.
  • Each randomized subject will be assigned 1 large box of medicine, containing 14 small boxes, for a course of 14 days of medication, 1 small box per day, each small box contains 6 bottles of medicine, each use 3 bottles of medicine in a small box are administered once every 12 hours, 2 times a day.
  • the specific medicine packaging specifications and quantities are shown in the following table:
  • Test group Number of small boxes Each small box of medicines consists of Edaravone and Dexbornol Injection Group 14 6 bottles Edaravone control group 14 6 bottles
  • the subjects were randomly divided into groups, and the subjects in the experimental group received edaravone dexbornol injection 37.5 mg intravenously, twice a day for 14 consecutive days; subjects in the control group received edaravone injection 30mg, intravenous injection, 2 times a day for 14 consecutive days. Dosage adjustment is not allowed during the study period, and the cumulative delay in dosing cannot exceed 2 days. During the study period, the use of neuroprotective agents and thrombolytic drugs listed in the "Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke" (2010 edition) was prohibited.
  • Edaravone and Dexbornol Injection group before use, add 3 vials of medicine in a small box to 100 mL of 0.9% sodium chloride injection to dilute and infuse intravenously, finish the drip within 30 minutes, two times a day. times, 12 hours apart each time, for 14 consecutive days.
  • Edaravone group The administration method is the same as that of the experimental drug Edaravone Dexbornol Injection. Before use, add 3 vials of medicine in 1 small box to 100 mL of 0.9% sodium chloride injection to dilute and infuse intravenously, within 30 minutes, twice a day, 12 hours apart each time, for 14 consecutive days .
  • the primary efficacy endpoint was the proportion of patients with an mRS score ⁇ 1 on day 90 of treatment.
  • the overall outcome scale was assessed using the Modified Rankin Scale (mRS) for the overall assessment of disability and disability. Principles" recommended primary endpoint.
  • the mRS score is currently the most widely used functional outcome scale in stroke clinical trials, ranging from 0 for no symptoms to 5 for severe disability, with an additional 6 points added to indicate death in some trials.
  • an mRS score of 0 to 1 is generally chosen as the criterion for judging that subjects have no disability after a stroke, and some clinical trials choose an mRS score of 0 to 2 as the criterion. In this application, the mRS score of 0 to 1 was selected as the criterion.
  • Table 1 The test results are shown in Table 1.

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Abstract

一种组合物在制备治疗患者脑卒中药物中的用途，所述组合物包含依达拉奉和右莰醇，所述患者具有高血压病史。

Description

组合物在治疗脑卒中的用途 技术领域
本发明涉及一种组合物的用途，进一步地，本发明涉及一种组合物在制备治疗患者脑卒中药物中的用途。
背景技术
在过去的15年中脑卒中是世界范围内第二位、中国第一位导致死亡和引发长期且严重的神经系统疾病的原因。脑卒中的危险因素有很多，比较常见的危险因素主要包括血压、血糖、胆固醇水平、体质指数、吸烟、体力活动和饮食，这些危险因素和脑卒中均存在较强的关联性。因此，具有基础性疾病史的脑卒中患者可能会有更高的发病率、死亡率、复发率及致残率。尽管在临床上有大量药物应用于脑卒中的治疗，实际被确认用于脑缺血急性期和亚急性期的治疗药物还不能完全满足临床应用的需求，特别是不能满足伴随多重疾病或疾病史(如高血压史、高血脂史、糖尿病史、心脏病史等)的缺血性脑卒中患者的临床需求。
发明内容
为了解决上述问题，本发明提供了一种治疗具有高血压史患者脑卒中的方法。
本发明涉及一种组合物在制备治疗患者脑卒中药物中的用途，其特征在于，所述的组合物包含依达拉奉(3-甲基-1-苯基-2-吡唑啉-5-酮)和右莰醇(Dexborneol，也称右旋莰醇)，所述患者具有高血压病史。
本发明涉及一种组合物在治疗患者脑卒中的用途，其特征在于，所述的组合物包含依达拉奉和右莰醇，所述患者具有高血压病史。
本发明涉及一种治疗患者脑卒中的组合物，其特征在于，所述的组合物包含依达拉奉和右莰醇，所述患者具有高血压病史。
本发明涉及一种治疗患者脑卒中的方法，该方法包含给以患者治疗上有效剂量的组合物，其特征在于，所述的组合物包含依达拉奉和右莰醇，所述患者具有高血压病史。
在一些实施方案中，所述组合物中依达拉奉和右莰醇的重量比为1:1～8:1、1:1～7:1、1:1～6:1、1:1～5:1、1:1～4:1、1:1～3:1、1:1～2:1或1:1～1.5:1。
在一些实施方案中，所述组合物中依达拉奉和右莰醇的重量比为1:1～5:1。
在一些实施方案中，所述组合物中依达拉奉和右莰醇的重量比为1:1～4:1。
在一些实施方案中，所述组合物中依达拉奉和右莰醇的重量比为4:1。
在一些实施方案中，向有此需要的患者施用所述组合物后，所述患者体内依达拉奉和右莰醇的血浆暴露量比为1:1～8:1、1:1～7:1、1:1～6:1、1:1～5:1、1:1～4:1、1:1～3:1、1:1～2:1或1:1～1.5:1，优选为1:1～5:1，更优选为4:1。
在一些实施方案中，所述组合物每日给药1-3次，连续给药3-21天。
在一些实施方案中，所述组合物每12小时给药一次，每日给药2次，连续给药14天。
在一些实施方案中，所述组合物中依达拉奉的给药剂量为10-30毫克/一次。
在一些实施方案中，所述组合物中依达拉奉的给药剂量为10毫克/一次。
在一些实施方案中，所述组合物中依达拉奉的给药剂量为20毫克/一次。
在一些实施方案中，所述组合物中依达拉奉的给药剂量为30毫克/一次。
在一些实施方案中，所述组合物还包含药学上可接受的辅料。
在一些实施方案中，所述药学上可接受的辅料选自抗氧化剂、助溶剂或溶剂中的一种或多种。
在一些实施方案中，所述药学上可接受的辅料选自抗氧化剂、助溶剂或溶剂。
在一些实施方案中，所述抗氧化剂为焦亚硫酸钠。
在一些实施方案中，所述助溶剂为丙二醇。
在一些实施方案中，所述溶剂为注射用水。
在一些实施方案中，所述脑卒中为缺血性脑卒中。
在一些实施方案中，所述脑卒中为急性缺血性脑卒中。
本发明的有益效果：我们意外地发现，本发明的依达拉奉和右莰醇组合物对具有高血压病史的脑卒中患者取得了显著的疗效，为急性缺血性脑卒中合并高血压患者提供了更为有效的治疗药物和治疗方案。
具体实施方式
以下实施例详细说明发明的技术方案，但本发明的保护范围包括但不限于此。
实施例
本发明实施例方法和数据来源于临床试验，其试验目的、试验方法和试验结果如下。
试验目的：依达拉奉右莰醇注射液针对具有基础疾病史的脑卒中患者的亚组药 效研究
开展了多中心、随机双盲、阳性药(依达拉奉注射液)对照的III期临床试验,入选1200例发病时间≤48h的急性缺血性卒中患者，按照约1:1比例随机分配进入依达拉奉右莰醇注射液组或依达拉奉组进行药效学及安全性研究。对依达拉奉右旋崁醇注射液用于治疗具有基础疾病史的急性缺血性卒中患者的疗效进行了研究和分析。在入选的1200例卒中患者中，按下述诊断标准纳入各亚组，各亚组患者按照约1:1比例随机分配的方式接受了依达拉奉右莰醇注射液或依达拉奉注射液连续治疗14天并随访至第90天。
受试者入选标准：
受试者入选的主要标准为年龄35～80岁，男性或女性，根据第四届全国脑血管病学术会议《各类脑血管病诊断要点》诊断为缺血性卒中(脑梗塞)，有明确神经系统定位体征，神经功能缺损评分：4≤NIHSS≤24，并且NIHSS第五项上肢和第六项下肢评分之和≥2分；排除已经接受过静脉溶栓、动脉溶栓和神经保护药物治疗的受试者。
上述入选的受试者中，如满足以下条件之一则被认定具有高血压病史：入组前或入组期间，在未使用降压药物的情况下，非同日3次测量诊室血压，收缩压(SBP)≥140mmHg(1mmHg＝0.133kPa)和/或舒张压(DBP)≥90mmHg。SBP≥140mmHg和DBP<90mmHg；或者收缩压和舒张压虽分别低于140mmHg和90mmHg的目前正在使用降压药物的受试者。
上述入选的受试者中，如满足以下条件则被认定为具有高血脂病史：入组前或入组期间，受试者空腹血清中总胆固醇超过5.72mmol/L，甘油三酯超过1.70mmol/L；或者血清中总胆固醇和甘油三酯虽不超过上述标准(总胆固醇不超过5.72mmol/L，甘油三酯不超过1.70mmol/L)的目前正在使用降脂药物的受试者；以及符合《中国成人血脂异常防治指南》(2016年修订版)诊断标准的。
药物规格与来源：
1)试验药品名称：依达拉奉右莰醇注射液；
规格：5mL:12.5mg(依达拉奉10mg、(+)-2-莰醇2.5mg)，辅料成分为焦亚硫 酸钠、丙二醇和注射用水；其中右莰醇的结构为
Figure PCTCN2021104933-appb-000001
保存条件：避光，密封，在阴凉处(不超过20℃)保存；
生产单位：南京先声东元制药有限公司
2)阳性对照药品名称：依达拉奉注射液；
规格：5mL:10mg(依达拉奉10mg)；
保存条件：避光，密封，在阴凉处(不超过20℃)保存；
生产单位：南京先声东元制药有限公司
试验药与阳性对照药在颜色、形状方面完全相同，为保证盲法，两组药物包装、批号均完全相同，包装批号统一标注。每例随机化入组的受试者将分配1个大盒药物，内装14个小盒，用于一个疗程14天的用药，每天1小盒，每小盒内含6瓶药物，每次使用1个小盒内的3瓶药物，每12h给药1次，一日2次，具体药物分装规格及数量见下表：
试验组别 小盒数量 每个小盒药物组成
依达拉奉右莰醇注射液组 14 6瓶
依达拉奉对照组 14 6瓶
试验方法：
对受试者进行随机分组，试验组受试者接受依达拉奉右莰醇注射液37.5mg，静脉注射，每日2次，连续14天；对照组受试者接受依达拉奉注射液30mg，静脉注射，每日2次，连续14天。研究期间不允许调整剂量，累计推迟给药时间不能超过2天。研究期间禁止使用《中国急性缺血性卒中诊治指南》2010年版列出的神经保护剂和溶栓药物。
更为具体的，本临床试验两组的给药方案如下：
依达拉奉右莰醇注射液组：临用前将1个小盒内的3瓶药物加入到100mL的0.9％氯化钠注射液中稀释后静脉滴注，30分钟内滴完，一天两次，每次间隔12小时，连续14天。
依达拉奉组：给药方法与试验药依达拉奉右莰醇注射液相同。临用前将1个小 盒内的3瓶药物加入到100mL的0.9％氯化钠注射液中稀释后静脉滴注，30分钟内滴完，一天两次，每次间隔12小时，连续14天。
评价指标：
主要疗效终点为治疗第90天mRS评分≤1分的患者比例。
整体结局量表评定采用对残疾和残障的总体评定的改良Rankin评分量表(ModifiedRankinScale，mRS)，此研究终点也是国家食品药品监督管理总局发布的“急性缺血性脑卒中治疗药物临床试验技术指导原则”推荐的主要终点指标。mRS评分是目前脑卒中临床试验采用最多的功能结局评估量表，等级分为从0分的没有症状到5分的重度残疾，在某些试验中会增加额外的6分表示死亡。在临床试验中，一般选择mRS评分0～1分为判定受试者发生脑卒中后没有残疾的标准，也有部分临床试验选择mRS评分0～2分为判定标准。本申请试验选择mRS评分0～1分为判定标准。试验结果参见表1。
表1治疗第90天的mRS评分情况
Figure PCTCN2021104933-appb-000002
表1的结果显示，依达拉奉注射液对有高血压病史的脑卒中患者的治疗效果不如对无高血压病史的脑卒中患者的治疗效果，第90天的mRS评分分别为52.8％和66.1％。而使用依达拉奉右莰醇注射液能明显提高对有高血压病史的脑卒中患者的治疗效果，从52.8％提高到64.6％，相对于依达拉奉注射液，提高了22％(100％*(64.6-52.8)/52.8＝22％)。对有高血脂史的脑卒中患者，依达拉奉右莰醇注射液与依达拉奉注射液效果无显著区别。以上结果说明，依达拉奉右莰醇对有高血压病史的脑卒中患者有良好的治疗效果，且其效果优于依达拉奉。

Claims (13)

  1. 一种组合物在制备治疗患者脑卒中药物中的用途，其特征在于，所述的组合物包含依达拉奉和右莰醇，所述患者具有高血压病史。
  2. 根据权利要求1所述的用途，其特征在于，所述组合物中依达拉奉和右莰醇的重量比为1:1～8:1、1:1～7:1、1:1～6:1、1:1～5:1、1:1～4:1、1:1～3:1、1:1～2:1或1:1～1.5:1，优选为1:1～5:1。
  3. 根据权利要求1所述的用途，其特征在于，所述组合物中依达拉奉和右莰醇的重量比为4:1。
  4. 根据权利要求1所述的用途，其特征在于，所述组合物每日给药1-3次，连续给药3-21天。
  5. 根据权利要求1所述的用途，其特征在于，所述组合物每12小时给药一次，每日给药2次，连续给药14天。
  6. 根据权利要求1所述的用途，其特征在于，所述组合物中依达拉奉的给药剂量为10-30毫克/一次。
  7. 根据权利要求1所述的用途，其特征在于，所述组合物中依达拉奉的给药剂量为10毫克/一次、20毫克/一次或30毫克/一次。
  8. 根据权利要求1所述的用途，其特征在于，所述组合物还包含药学上可接受的辅料。
  9. 根据权利要求8所述的用途，其特征在于，所述药学上可接受的辅料选自焦亚硫酸钠、丙二醇和注射用水。
  10. 根据权利要求1-9任一项所述的用途，其特征在于，所述脑卒中为缺血性脑卒中。
  11. 根据权利要求1-9任一项所述的用途，其特征在于，所述脑卒中为急性缺血性脑卒中。
  12. 一种治疗脑卒中的方法，所述方法包括向有此需要的患者施用包含依达拉奉和右莰醇的组合物，所述患者具有高血压病史。
  13. 根据权利要求12所述的方法，其特征在于，施用所述组合物后，所述 患者体内依达拉奉和右莰醇的血浆暴露量比为1:1～8:1、1:1～7:1、1:1～6:1、1:1～5:1、1:1～4:1、1:1～3:1、1:1～2:1或1:1～1.5:1，优选为1:1～5:1，更优选为4:1。
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