CN1178704A - 用于冠心病诊断的去甲乌药碱水针剂 - Google Patents

用于冠心病诊断的去甲乌药碱水针剂 Download PDF

Info

Publication number
CN1178704A
CN1178704A CN 97121801 CN97121801A CN1178704A CN 1178704 A CN1178704 A CN 1178704A CN 97121801 CN97121801 CN 97121801 CN 97121801 A CN97121801 A CN 97121801A CN 1178704 A CN1178704 A CN 1178704A
Authority
CN
China
Prior art keywords
water
acid
heart disease
demethyl
coronary heart
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN 97121801
Other languages
English (en)
Other versions
CN1069825C (zh
Inventor
陶忠华
刘秀杰
史蓉芳
曾凡彬
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fuwai Cardiovascular Hospital Of China Union Medical University Chinese Academy Of Medical Sciences
Institute of Materia Medica of CAMS
Original Assignee
Fuwai Cardiovascular Hospital Of China Union Medical University Chinese Academy Of Medical Sciences
Institute of Materia Medica of CAMS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fuwai Cardiovascular Hospital Of China Union Medical University Chinese Academy Of Medical Sciences, Institute of Materia Medica of CAMS filed Critical Fuwai Cardiovascular Hospital Of China Union Medical University Chinese Academy Of Medical Sciences
Priority to CN97121801A priority Critical patent/CN1069825C/zh
Publication of CN1178704A publication Critical patent/CN1178704A/zh
Application granted granted Critical
Publication of CN1069825C publication Critical patent/CN1069825C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Landscapes

  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

本发明涉及一种诊断冠心病的药剂的制备方法与用途,主药为去甲乌药碱盐酸盐,加适量溶剂,药用赋形剂为抗氧剂、金属离子络合剂、pH调节剂、惰性气体等制成无菌水针剂,能增加心率、加快管脉血流量等作用,具有起效快,对血压影响小,性质稳定不良反应少等特点,在冠心病诊断时用作心脏负荷试验药物。

Description

用于冠心病诊断的去甲乌药碱水针剂
本发明涉及一种诊断冠心病的药剂。
近年来对于冠心病的早期诊断,愈来愈受到人们的重视,负荷心肌灌注显像已广泛应用于冠心病的诊断,治疗方案的选择及冠心病预后的估价,常用的方法包括生理负荷的运动试验,药物介入的负荷试验。当静息时(不用药)心肌缺血难于检出,必须借助心脏负荷试验药剂的作用进行诊断,其中的多巴酚丁胺的应用最常见,多巴酚丁胺能加快心率,增加心肌收缩力,同时增加心肌耗氧量,冠脉流量也随之增加,但对冠心病患者,狭窄的冠状动脉限制了血流量的增加,使该血管供应的局部心肌氧供需不平衡,造成局部心肌缺血,因此多巴酚丁胺不适宜高血压病患者应用。经研究表明从中药中提取的去甲乌药碱(Higenamine,简称HG,化学名为:1-(对羟基-苄基)-6.7-二羟基-1,2,3,4-四氢异喹啉盐酸盐)有改善房室传导阻滞所致的心律失常,增加心率,增加心肌耗氧量,增加冠脉血流量等作用,其作用随着剂量的增加而增加,对外围收缩压的影响不大,并有起效快,对血压影响小的特点,因此去甲乌药碱既可起到与多巴酚丁胺相类似的增加心肌负荷作用,又可克服多巴酚丁胺不适于高血压患者应用的不足。去甲乌药碱制备过程中极易氧化影响药剂的纯度,影响了临床的使用。
本发明的目的是提供一种制备时不易氧化,纯度高,临床效果好,适于冠心病诊断的去甲乌药碱。
本发明的目的是通过去甲乌药碱水针剂来实现的。
用于冠心病诊断的去甲乌药碱水针剂含有去甲乌药碱盐酸盐,溶剂,包括水或水与乙醇的混合物,PH调节剂,包括磷酸、盐酸、硫酸、枸橼酸、酒石酸,还含有抗氧剂,包括亚硫酸氢钠、亚硫酸钠、焦亚硫酸钠、BHT、抗坏血酸、金属离子络合剂,包括依地酸,即EDTA,EDTA二钠盐、EDTA钙钠盐,其重量百分组方是:
去甲乌药碱盐酸盐              0.01-10%
抗氧剂                        0.01-5%
金属离子络合剂                0.01-5%
PH调节剂                      0.01-5%
溶剂                          85-99.95%
去甲乌药碱水针剂的制备工艺如下:
先称取抗氧剂、金属离子络合剂,加适量的水,搅拌,使药剂溶解。另外再称取去甲乌药碱盐酸盐,加适量的水搅拌,使药剂溶解,将所述两种溶液合并,加PH调节剂,使PH值达到2.5-5.0,加水至全量,搅拌均匀,再通入经过滤的二氧化碳约十分钟,将溶液过滤至清亮,分装于安瓶中,再通入经过滤的二氧化碳后封口,在100℃灭菌30分钟。
本发明用于冠心病诊断的去甲乌药碱水针剂有以下特点:1)因为在制备时采用了抗氧化剂,金属离子络合剂,惰性气体保护等措施在制备时不易氧化,制备工艺简单,性能稳定,纯度高。2)经药效学试验,急性毒性试验、临床试验证实,具备毒性低,副作用小和临床应用安全的特点,是理想的心脏负荷试验药物。
现用下列实施例对本发明用于冠心病诊断的去甲乌药碱水针剂作进一步说明。
实施例1,
成分                       用量     作用
去甲乌药碱盐酸盐(HG.Hcl)   2.0克    主药
焦亚硫酸钠                 0.4克    抗氧剂
依地酸二钠                 0.4克    金属离子络合剂
稀盐酸                     适量     PH调节剂
注射用水                   2000毫升 溶剂
制备:
1、称取抗氧剂焦亚硫酸钠,金属离子络合剂依地酸二钠,加适量水约500毫升,搅拌至溶解;
2、称取HG.Hcl细粉,加适量水约1000毫升,搅拌至溶解,
3、将1,2两溶液合并,加酸液调节PH值为2.5-5.0,加水至全量,搅拌均匀,通入经过滤的二氧化碳气约十分钟,将溶液过滤至清亮,分装于安瓶中,再通入经过滤的二氧化碳气后封口,在100℃灭菌30分钟。
实施例2
成分                        用量     作用
去甲乌药碱盐酸盐(HG.Hcl)    2.5克    主药
亚硫酸氢钠                  0.5克    抗氧剂
依地酸钙钠                  0.5克    金属离子络合剂
稀盐酸                      适量     PH调节剂
注射用水                    2000毫升 溶剂
制备:
1、称取抗氧剂亚硫酸氢钠,金属离子络合剂依地酸钙钠,加适量水约500毫升,搅拌至溶解;
2、称取HG.Hcl细粉,加适量的水约1000毫升,搅拌至溶解;
3、将1,2两溶液合并,加酸液调节PH值为2.5-5.0,加水至全量,搅拌均匀,通入经过滤的氮气约十分钟,将溶液过滤至清亮,分装于安瓶中,通入经过滤的氮气后封口,在100℃灭菌30分钟。
将本发明药物去甲乌药碱水针剂作心肌灌注显像负荷试验,检查12例,其中10例(男性8例,女性2例)平均年龄52.5岁,临床确诊(均有冠脉造影)为冠心病,另2例为正常对照,所有检查人员均作次极量运动试验,于运动高峰时静脉注射99mTC-MIBI 20mci,1-1.5小时后进行心肌断层显像,去甲乌药碱水针剂负荷试验,先静脉滴入HG,剂量从0.5μg/kg/min开始,逐渐加量,最高达3-4μg/kg/min,此时静脉注射99mTC-MIBI 20mci,1-1.5小时后进行心肌断层显像,在滴注HG过程中进行心率、血压及心电图监测。
结果10例冠心病人应用HG后显示心肌有33个左室心肌节段缺血,与冠脉造影检查的符合率为90%,同时进行的运动试验显示28个心肌节段缺血,HG与运动试验的相符率为85%,试验结果表时,HG可以用为心肌灌注显像的药物负荷试验,对冠心病诊断的敏感性特异性与运动试验相似,12例试验均未见任何副作用。

Claims (3)

1、用于冠心病诊断的去甲乌药碱水针剂,含有去甲乌药碱盐酸盐,溶剂、包括水或水与乙醇的混合物,PH调节剂,包括磷酸、盐酸、硫酸、枸橼酸、酒石酸,其特征为还含有抗氧剂,包括亚硫酸氢钠,亚硫酸钠,焦亚硫酸钠,BHT,抗坏血酸,金属离子综合剂,包括依地酸,即EDTA,EDTA二钠盐,EDTA钙钠盐,其重量百分组方是:
去甲乌药碱盐酸盐                  0.01-10%
抗氧剂                            0.01-5%
金属离子络合剂                    0.01-5%
PH调节剂                          0.01-5%
溶剂                              85-99.95%
2、根据权利要求1所述的用于冠心病诊断的去甲乌药碱水针剂,其特征为制备时先称取抗氧剂,金属离子络合剂,加适量的水,搅拌,使药剂溶解,另外再称取去甲乌药碱盐酸盐,加适量水搅拌,使药剂溶解,将所述两种溶液合并,加PH调节剂,使PH值达到2.5-5.0,加水至全量,搅拌均匀,再通入经过滤的二氧化碳约十分钟,将溶液过滤至清亮,分装于安瓶中,再通入经过滤的二氧化碳后封口,在100℃灭菌30分钟。
3、根据权利要求1或2所述的用于冠心病诊断的去甲乌药碱水针剂,其特征为用于心脏负荷试验药物。
CN97121801A 1997-11-28 1997-11-28 用于冠心病诊断的去甲乌药碱水针剂 Expired - Fee Related CN1069825C (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN97121801A CN1069825C (zh) 1997-11-28 1997-11-28 用于冠心病诊断的去甲乌药碱水针剂

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN97121801A CN1069825C (zh) 1997-11-28 1997-11-28 用于冠心病诊断的去甲乌药碱水针剂

Publications (2)

Publication Number Publication Date
CN1178704A true CN1178704A (zh) 1998-04-15
CN1069825C CN1069825C (zh) 2001-08-22

Family

ID=5176454

Family Applications (1)

Application Number Title Priority Date Filing Date
CN97121801A Expired - Fee Related CN1069825C (zh) 1997-11-28 1997-11-28 用于冠心病诊断的去甲乌药碱水针剂

Country Status (1)

Country Link
CN (1) CN1069825C (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106389312A (zh) * 2016-09-18 2017-02-15 天津金耀药业有限公司 一种重酒石酸间羟胺注射液的药物组合物
CN113425678A (zh) * 2021-08-04 2021-09-24 珠海润都制药股份有限公司 一种盐酸去甲乌药碱注射液及其制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51125711A (en) * 1974-10-22 1976-11-02 Hokuriku Seiyaku Co Ltd A process for preparing higenamine organic acid salts

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106389312A (zh) * 2016-09-18 2017-02-15 天津金耀药业有限公司 一种重酒石酸间羟胺注射液的药物组合物
CN113425678A (zh) * 2021-08-04 2021-09-24 珠海润都制药股份有限公司 一种盐酸去甲乌药碱注射液及其制备方法
CN113425678B (zh) * 2021-08-04 2023-02-10 珠海润都制药股份有限公司 一种盐酸去甲乌药碱注射液及其制备方法

Also Published As

Publication number Publication date
CN1069825C (zh) 2001-08-22

Similar Documents

Publication Publication Date Title
Saarnivaara et al. QT interval of the ECG, heart rate and arterial pressure using propofol, methohexital or midazolam for induction of anaesthesia
Subramanian et al. Randomized double-blind comparison of verapamil and nifedipine in chronic stable angina
Grossman et al. Cardiovascular effects of infusion of lidocaine on patients with heart disease
Roberts et al. Effects of prolonged naloxone infusion in septic shock
Weesner et al. Cardiac arrhythmias in an adolescent following ingestion of an over-the-counter stimulant.
Poklis et al. Tissue distribution of lidocaine after fatal accidental injection
Kimura et al. Ropivacaine-induced toxicity with overdose suspected after axillary brachial plexus block
Winsor et al. Influence of pentaerythritol tetranitrate (peritrate) on acute and chronic coronary insufficiency
Thomson et al. The pharmacokinetics of R‐and S‐tocainide in patients with acute ventricular arrhythmias.
CN1178704A (zh) 用于冠心病诊断的去甲乌药碱水针剂
Sylvén et al. Provocation of chest pain in patients with coronary insufficiency using the vasodilator adenosine
Aguilera et al. Anaphylactic reaction after atropine
AU2001286092B2 (en) Reduction of the electrocardiographic OT interval
Salerno et al. Treatment of vasospastic angina pectoris at rest with nitroglycerin ointment: A short-term controlled study in the coronary care unit
RU2358732C2 (ru) Жидкие фармацевтические композиции, содержащие производные 3,7-диазабицикло(3,3,1)нонана, для лечения антиаритмических реакций
AU2001286092A1 (en) Reduction of the electrocardiographic OT interval
CN1187055C (zh) 薯蓣皂甙元在制备治疗心肌缺血、心绞痛和心肌梗死的药物中的用途
Fukushima et al. The cardiovascular effects of atracurium and it's metabolite
CN101732331B (zh) 一种单唾液酸四己糖神经节苷脂钠与谷氨酸的组合物
Lowenthal et al. Esmolol‐digoxin drug interaction
Singh et al. Beta-blocking potency and electrophysiologic effects of acebutolol
US4931470A (en) Antiarrhythmic method
Stewart et al. Systemic β-Blockade with Once Daily Betimol™ or Timoptic-XE™
Massie et al. Combined hemodynamic and scintigraphic assessment of piroximone (MDL 19,205) and comparison with dobutamine and nitroprusside
SU1635962A1 (ru) Способ определени индивидуальной чувствительности к бета-адреноблокатору у больных ишемической болезнью сердца

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee