CN103599106B - Caesanines D在制备治疗或预防慢性心衰药物中的应用 - Google Patents
Caesanines D在制备治疗或预防慢性心衰药物中的应用 Download PDFInfo
- Publication number
- CN103599106B CN103599106B CN201310642893.5A CN201310642893A CN103599106B CN 103599106 B CN103599106 B CN 103599106B CN 201310642893 A CN201310642893 A CN 201310642893A CN 103599106 B CN103599106 B CN 103599106B
- Authority
- CN
- China
- Prior art keywords
- heart failure
- caesanines
- chronic heart
- application
- treatment
- 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.)
- Expired - Fee Related
Links
- 206010007558 Cardiac failure chronic Diseases 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title claims description 10
- 229940079593 drug Drugs 0.000 title claims description 6
- 238000002483 medication Methods 0.000 title claims description 6
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 abstract description 4
- 206010007556 Cardiac failure acute Diseases 0.000 abstract 1
- 230000001154 acute effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 4
- 206010019280 Heart failures Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 4
- 241000209639 Biancaea sappan Species 0.000 description 3
- 235000015162 Caesalpinia sappan Nutrition 0.000 description 3
- 229930002147 cassane Natural products 0.000 description 3
- 229930004069 diterpene Natural products 0.000 description 3
- 238000007914 intraventricular administration Methods 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000004217 heart function Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 208000006193 Pulmonary infarction Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000007575 pulmonary infarction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了Caesanines D在制备治疗或预防慢性心衰的药物中的应用，具体地提出了Caesanines D对急、慢性心力衰竭的治疗作用，属于首次公开，由于骨架类型属于全新的骨架类型，而且其治疗慢性心衰的活性强，具备突出的实质性特点，同时用于治疗慢性心衰显然具有显著的进步。
Description
技术领域
本发明涉及化合物Caesanines D的新用途，尤其涉及Caesanines D在制备治疗或预防慢性心衰药物中的应用。
背景技术
心衰（hear failure，HF）是指心脏功能异常导致心脏泵血量不能满足组织代谢需要的一种病理生理状态。病因诱因因为心脏负荷过重、心肌本身、舒张受限任何原因致初始心肌损伤引起结构功能低下而进行性发病；而感染、贫血、妊娠、分娩、心律紊乱、肺栓塞、甲亢、糖尿病、抑制心脏药诱发加重HF。发病机理过去认为HF发生发展的机制是血流动力学异常；20世纪80年代后期认识到神经-内分泌激素的激活起重要作用（交感↑NE↑RAS↑等激活）；90年代以后逐渐明确了“心肌重塑”（remodelling）是导致心衰的发生发展的基本机制。
本发明涉及的化合物Caesanines D是一个2013年发表（Jingyu Zhang，et al.,Caesanines AD,New Cassane Diterpenes with Unprecedented N Bridge from Caesalpinia sappan.Organic Letters，2013，15(18):4726–4729.）的新化合物，该化合物拥有全新的骨架类型，目前的用途发现其能抗菌（Jingyu Zhang，et al.,Caesanines AD,New Cassane Diterpenes with Unprecedented N Bridge from Caesalpinia sappan.Organic Letters，2013，15(18):4726–4729.），本发明涉及的Caesanines D在制备治疗或预防慢性心衰药物中的用途属于首次公开。
发明内容
本发明的目的在于根据现有Caesanines D研究中未发现其具有治疗或预防慢性心衰活性的报道的现状，提供了Caesanines D在制备治疗或预防慢性心衰药物中的应用。
所述化合物Caesanines D结构如式（Ⅰ）所示：
式（Ⅰ）
本发明涉及的Caesanines D在制备治疗慢性心衰中的用途属于首次公开，由于骨架类型属于全新的骨架类型，而且其治疗慢性心衰的活性强，具备突出的实质性特点，同时用于治疗慢性心衰显然具有显著的进步。
具体实施方式
以下通过实施例对本发明作进一步详细的说明，但本发明的保护范围不受具体实施例的任何限制，而是由权利要求加以限定。
本发明所涉及化合物Caesanines D的制备方法参见文献（Jingyu Zhang，et al.,Caesanines AD,New Cassane Diterpenes with Unprecedented N Bridge from Caesalpinia sappan.Organic Letters，2013，15(18):4726–4729.），按照上述方法制备化合物Caesanines D。
实施例1：本发明所涉及化合物Caesanines D片剂的制备：
取5克化合物Caesanines D加入糊精195克，混匀，常规压片制成1000片。
实施例2：本发明所涉及化合物Caesanines D胶囊剂的制备：
取5克化合物Caesanines D加入淀粉195克，混匀，装胶囊制成1000粒。
下面通过药效学实验来进一步说明其药物活性。
实验例1：Caesanines D对慢性心衰大鼠的影响
试验方法与结果：大鼠100只，雌雄各半，取100只腹腔注射盐酸阿霉素2mg/kg，每周1次，共6周。随机分为10组，即NS组，卡托普利片12.5mg/kg组，灌胃给药Caesanines D0.2mg/kg组，灌胃给药Caesanines D2.5mg/kg组，灌胃给药Caesanines D5.0mg/kg组。第5周起每日给予Caesanines D灌胃各组，给药21天。20%乌拉坦1.1g/kg腹腔注射麻醉，手术剥离气管并插管，同时游离出右侧总动脉，经其插入自制的心室插管（直径1mm，充满1%肝素），描记血压曲线；再继续插入，使其通过左侧动脉瓣进入左心室，描记室内压曲线，自动分析处理左室收缩压（LVSP），心室内压最大上升速率（+dp/dtmax），心室内压最大下降速度（-dp/dtmax）和实测心肌最大收缩速度（Vpm）等数据。另取10只大鼠作为正常对照组，不给予盐酸阿霉素，其余操作同上述，组间T检验，进行统计学处理。
表1Caesanines D对慢性心衰大鼠心功能的影响（n=10）
与NS组比较，△：p<0.05，△△：p<0.01
表1试验结果表明Caesanines D灌胃给药0.2mg/kg组能升高由盐酸阿霉素导致的心衰大鼠的LVSP，+dp/dtmax，-dp/dtmax和Vpm的降低（与NS组比较，P<0.05）；Caesanines D灌胃给药2.5mg/kg、5.0mg/kg能显著升高由盐酸阿霉素导致的心衰大鼠的LVSP，+dp/dtmax，-dp/dtmax和Vpm的降低（与NS组比较，P<0.01）。
结论：Caesanines D具有显著的治疗或预防慢性心衰的作用，可以用来制备治疗或预防慢性心衰的药物。
Claims (1)
1.Caesanines D在制备治疗或预防慢性心衰药物中的应用，所述化合物CaesaninesD结构如式(Ⅰ)所示：
式(Ⅰ)。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310642893.5A CN103599106B (zh) | 2013-12-04 | 2013-12-04 | Caesanines D在制备治疗或预防慢性心衰药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310642893.5A CN103599106B (zh) | 2013-12-04 | 2013-12-04 | Caesanines D在制备治疗或预防慢性心衰药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103599106A CN103599106A (zh) | 2014-02-26 |
| CN103599106B true CN103599106B (zh) | 2015-07-29 |
Family
ID=50117415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310642893.5A Expired - Fee Related CN103599106B (zh) | 2013-12-04 | 2013-12-04 | Caesanines D在制备治疗或预防慢性心衰药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103599106B (zh) |
-
2013
- 2013-12-04 CN CN201310642893.5A patent/CN103599106B/zh not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Caesanines A-D,New Cassane Diterpenes with Unprecedented N Bridge from Caesalpinia sappan;Zhang Jingyu et al.;《Organic Letters》;20130920;第15卷(第18期);4726-4729 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103599106A (zh) | 2014-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105412101A (zh) | Virosaines A在制备治疗或预防慢性心衰药物中的应用 | |
| CN103585148B (zh) | Nitrosporeusines A在治疗或预防慢性心衰药物中的应用 | |
| CN103599106B (zh) | Caesanines D在制备治疗或预防慢性心衰药物中的应用 | |
| CN103610672B (zh) | Hippolachnin A在治疗或预防慢性心衰药物中的应用 | |
| CN103550225B (zh) | Phyllanthoid A在制备治疗或预防慢性心衰药物中的应用 | |
| CN103356673B (zh) | Houttuynoid A在制备治疗或预防慢性心衰的药物中的应用 | |
| CN103356671B (zh) | Houttuynoid C在制备治疗或预防慢性心衰的药物中的应用 | |
| CN103356686B (zh) | Houttuynoid B在制备治疗或预防慢性心衰的药物中的应用 | |
| CN103393698B (zh) | Chukrasone A在制备治疗或预防慢性心衰的药物中的应用 | |
| CN103372000B (zh) | Chukrasone B在制备治疗或预防慢性心衰的药物中的应用 | |
| CN103768050B (zh) | Eryngiolide A在治疗或预防慢性心衰的药物中的应用 | |
| CN105287452A (zh) | Periconianone A在制备治疗或预防慢性心衰药物中的应用 | |
| CN105412064A (zh) | Salvadione C在制备治疗或预防慢性心衰药物中的应用 | |
| CN104997766A (zh) | 一种治疗或预防慢性心衰药物及其应用 | |
| CN105395543A (zh) | Verrulactone C在制备治疗或预防慢性心衰药物中的应用 | |
| CN103479621A (zh) | Neonectrolide A在制备治疗或预防慢性心衰药物中的应用 | |
| CN103463006A (zh) | Racemosins A在制备治疗或预防慢性心衰药物中的应用 | |
| CN103356570A (zh) | Sarcaboside B在治疗或预防慢性心衰的药物中的应用 | |
| CN103356548A (zh) | Sarcaboside A在治疗或预防慢性心衰的药物中的应用 | |
| CN103381180A (zh) | Houttuynoid E在治疗或预防慢性心衰的药物中的应用 | |
| CN103316028A (zh) | Polyflavanostilbene A在制备治疗或预防慢性心衰药物中的应用 | |
| CN103372007B (zh) | Chukrasone B在制备治疗或预防急性心衰的药物中的应用 | |
| CN102988347A (zh) | Aphanamixoid A在制备治疗或预防慢性心衰的药物中的应用 | |
| CN103356670A (zh) | Houttuynoid D在治疗或预防慢性心衰的药物中的应用 | |
| CN103479610A (zh) | Scopariusins在制备治疗或预防慢性心衰药物中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Sun Shuyin Inventor after: Wang Yingcui Inventor after: Pan Xiaoyan Inventor before: Li Qiang |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: LI QIANG TO: SUN SHUYIN WANG YINGCUI PAN XIAOYAN |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20171023 Address after: 226500 Jiangsu city of Nantong province Rugao City, Dong Chen Zhen Hong Bridge neighborhood 4 groups Patentee after: Rugao Chengdong hospital Address before: 266000 Shandong province Qingdao City Red Road No. 31 North Building 201 Patentee before: Li Qiang |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191213 Address after: 063000 No.75, caoxiqin East Road, Fengrun District, Tangshan City, Hebei Province Patentee after: Hebei Sanshi Pharmaceutical Co.,Ltd. Address before: 226500 Jiangsu city of Nantong province Rugao City, Dong Chen Zhen Hong Bridge neighborhood 4 groups Patentee before: Rugao Chengdong hospital |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20211101 Address after: 063000 No. 75, Cao Xueqin East Road, Fengrun District, Tangshan City, Hebei Province (304, Sanshi pharmaceutical experimental building) Patentee after: Tangshan Liubai Pharmaceutical Technology Co.,Ltd. Address before: No.75, East CaoXueqin Road, Fengrun District, Tangshan City, Hebei Province 063000 Patentee before: Hebei Sanshi Pharmaceutical Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150729 Termination date: 20211204 |