WO2017080043A1 - 一种抗血栓组合物 - Google Patents
一种抗血栓组合物 Download PDFInfo
- Publication number
- WO2017080043A1 WO2017080043A1 PCT/CN2015/098869 CN2015098869W WO2017080043A1 WO 2017080043 A1 WO2017080043 A1 WO 2017080043A1 CN 2015098869 W CN2015098869 W CN 2015098869W WO 2017080043 A1 WO2017080043 A1 WO 2017080043A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antithrombotic composition
- prasugrel
- dabigatran etexilate
- effective dose
- antithrombotic
- Prior art date
Links
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
Definitions
- the invention relates to the field of medicine, in particular to an antithrombotic composition.
- Cardiovascular and cerebrovascular diseases are the most serious diseases threatening human health in the world today, and their incidence has surpassed that of tumors and ranked first.
- Thrombosis is a disease caused by blood clots and occlusion caused by blood clots, causing dysfunction caused by ischemia and infarction of major organs. It is a cardiovascular disease. Platelet aggregation has a key role in thrombosis, and thrombosis caused by platelet aggregation is an important cause of cardiovascular and cerebrovascular diseases.
- Antithrombotic drugs commonly used on the market include aspirin, indobufen, ticlopidine, and clopidogrel.
- Dabigatran Etexilate chemical name ⁇ -alanine, N-[[2-[[[4-[[[(hexyloxy)carbonyl]amino]iminomethyl]phenyl] Amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyrimidine-ethyl ester mesylate, the structural formula is shown below.
- It is an oral anticoagulant that is a thrombin inhibitor (DTIs) used to prevent stroke and systemic embolism in patients with non-valvular atrial fibrillation. Developed by Boehringer Ingelheim, Germany, it was launched in Europe in 2008.
- Dabigatran etexilate acts by oral administration of dabigatran from the digestive organs and esterase decomposition into active metabolites. It can directly and selectively inhibit thrombin, thereby exerting anticoagulant and antithrombotic effects.
- DTIs thrombin inhibitor
- prasugrel is also an inactive prodrug that undergoes a metabolic conversion of the cytochrome P450 enzyme to an active metabolite to irreversibly inhibit the P2Y12 adenosine diphosphate receptor on platelets.
- Prasugrel is superior to clopidogrel.
- Clopidogrel produces clopidogrel resistance during use, that is, although some patients take long-term use of conventional doses of clopidogrel, clinically, it is not effective to prevent thrombotic events, and platelet function tests confirm that platelet aggregation cannot be achieved. It is effectively suppressed.
- the present invention provides an antithrombotic composition.
- the antithrombotic composition of the present invention comprises an effective dose of 0.5-5 mg of an ADP receptor antagonist and an effective dose of 30-70 mg of dabigatran etexilate, both of which are in a free state or a pharmaceutically acceptable salt. Form exists.
- the effective dose of the ADP receptor antagonist in the antithrombotic composition is 1-4 mg, and the effective dose of dabigatran etexilate is 40-60 mg.
- the effective dose of the ADP receptor antagonist in the antithrombotic composition is 2 mg, and the effective dose of dabigatran etexilate is 50 mg.
- the ADP receptor antagonist is prasugrel.
- the antithrombotic composition of the present invention consists of dabigatran etexilate and prasugrel and at least one pharmaceutically acceptable carrier. Specifically, the antithrombotic composition is an oral preparation.
- the use of the antithrombotic composition of the present invention in the preparation of a medicament for the treatment and prevention of a disease induced by platelet aggregation includes stroke, acute coronary syndrome, interventional therapy and complications, and peripheral vascular embolism-related diseases.
- the "pharmaceutically acceptable salt” may be: hydrochloride, sulfate, tartrate, methanesulfonate, formate, acetate, benzoate, maleate, Fumarate, besylate, ethanesulfonate, p-toluenesulfonate, citrate, hydrobromide or lauryl sulfonate.
- the "oral formulation” is a capsule or tablet.
- the "pharmaceutically acceptable carrier” is an excipient, a binder, a disintegrant, a lubricant and a film-forming material, a colorant, a fragrance, and a sweetener.
- the excipient may be starch, powdered sugar, dextrin, lactose, compressible starch, microcrystalline cellulose (MCC), mannitol, calcium sulfate dihydrate, calcium hydrogen phosphate or pharmaceutically acceptable calcium carbonate.
- the binder may be distilled water, ethanol, starch slurry, hydroxypropylmethylcellulose (HPMC), povidone (PVP), hydroxypropylcellulose (HPC), methylcellulose (MC), ethylcellulose. (EC), sodium carboxymethylcellulose (CMC-Na), 5% to 20% gelatin solution, 10% to 25% gum arabic solution or 50% to 70% sucrose solution.
- the disintegrant may be dried starch, sodium carboxymethyl starch (CMS-Na), low substituted hydroxypropyl cellulose (L-HPC), calcium carboxymethyl cellulose, sodium hydrogencarbonate and tannic acid or tartaric acid, surface Active agents such as Tween-80, cetyltrimethylammonium bromide, sodium lauryl sulfate, sodium stearate, etc., crospovidone (PVPP) or croscarmellose sodium ( CCNa).
- the lubricant may be water-insoluble magnesium stearate, talc, hydrogenated vegetable oil, high melting wax, stearic acid, micronized silica gel and water-soluble polyethylene glycol, magnesium lauryl sulfate.
- the antithrombotic composition of the invention adopts a combination of drugs with different targets, and the use of prasugrel, which is better than clopidogrel, fundamentally avoids the occurrence of clopidogrel resistance and can be used as a clopidogrel resistant patient.
- Another medication option It is commendable that the combination of prasugrel and dabigatran etexilate is better than a single drug, and at the same time reduces the amount of individual drugs, reducing the tendency of prasugrel to bleed more easily. Dabigatran etexilate has a fast onset of action, while prasugrel is more effective, and the combination of the two complements each other. Once-a-day use can improve patient compliance.
- Example 1 Drug compatibility test of prasugrel and dabigatran etexilate
- the two drugs, prasugrel and dabigatran etexilate were prepared and stored in two different temperature and humidity environments, namely 25 ° C / 10% RH and 30 ° C / 60% RH.
- the drug was divided into a mixed group and an unmixed group as a control, and placed at these two temperatures, respectively.
- the samples were evaluated for traits and chemical stability (HPLC method) on Day 1, Day 3, Day 7, Day 14, and Day 30. The results are shown in Table 1.
- the content of prasugrel in the mixed group was 98.3%-101.5%
- the content of dabigatran etexilate was 98.4%-102.5%.
- There was no significant difference between the physical shape and the HPLC analysis in the mixed group and the control group indicating that the physical and chemical properties of the two drugs were well compatible after mixing.
- Example 2 Compound tablet containing prasugrel 0.5 mg and dabigatran etexilate 70 mg
- the prescription prasugrel was mixed with 5 g of lactose uniformly, and the obtained powder was evenly mixed with the prescribed amount of dabigatran etexilate, and then the remaining amount of lactose, the prescribed amount of microcrystalline cellulose and talc powder were added, and the mixture was uniformly mixed and then used for 12 mm. Punch directly into the tablet, that is.
- Example 3 Compound tablet containing 1 mg of prasugrel and 60 mg of dabigatran etexilate
- the main drug and the auxiliary material are respectively passed through an 80 mesh sieve, and the prescribed amount of prasugrel and 10 g of pregelatinized starch are uniformly mixed, and the obtained powder is uniformly mixed with the prescribed amount of dabigatran etexilate, and then the remaining amount of pregelatinized starch is added.
- the prescribed amount of microcrystalline cellulose and crospovidone are uniformly mixed and then granulated by a 20-mesh sieve dry granule, and talc powder is added. After the total mixed granules are qualified, the dry granules are obtained by using a 12 mm punching sheet.
- Example 4 Compound tablet containing 5 mg of prasugrel and 30 mg of dabigatran etexilate
- the prescribed amount of prasugrel and 20 g of starch are uniformly mixed, and the obtained powder is evenly mixed with the prescribed amount of dabigatran etexilate, and then the remaining amount of starch, the prescribed amount of hydroxypropylmethylcellulose and sodium carboxymethyl starch are added.
- Example 5 Compound capsule containing 2 mg of prasugrel and 50 mg of dabigatran etexilate
- the prescribed amount of prasugrel and 10 g of dextrin are uniformly mixed, and the obtained powder is evenly mixed with the prescribed amount of dabigatran etexilate, and then the remaining amount of dextrin is added and the prescribed amount of croscarmellose sodium is uniformly mixed.
- the granules were prepared by adding 70% ethanol, and the obtained granules were sufficiently dried at 65 ° C, sieved and sized, and capsules were obtained after the content was determined to be acceptable.
- Example 5 Compound soft capsule containing prasugrel 4 mg and dabigatran etexilate 40 mg
- the prescribed amount of prasugrel and dabigatran etexilate are evenly mixed, and then the prescribed amount of soybean oil and Tween-80 are added, and the soft capsule is pressed by the upper molding machine after being uniformly mixed.
- mice Forty normal mice were randomly divided into 4 groups and given normal saline, prasugrel (4 mg/kg), dabigatran etexilate (100 mg/kg), prasugrel + dabigatran etexilate (2 mg/).
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种抗血栓组合物，包含有效剂量为0.5-5mg的ADP受体拮抗剂和有效剂量为30-70mg的达比加群酯，这两种成分均以游离状态或药学上可接受的盐的形式存在。一种抗血栓组合物由达比加群酯和普拉格雷以及至少一种药学上可接受的载体组成。所述抗血栓组合物用于治疗和预防因血小板凝集诱导的疾病，包括脑卒中、急性冠脉综合征、介入治疗术及并发症、外周血管栓塞性相关的疾病。
Description
本发明涉及医药领域，特别涉及一种抗血栓组合物。
随着人们生活水平的提高，饮食结构中肉食的比例也越来越大。随之而来的得富贵病的人也越来越多。心脑血管疾病是当今世界上威胁人类身体健康的最严重疾病，其发病率已超过肿瘤而跃居第一。血栓病是由于血栓引起的血管狭窄与闭塞，使主要脏器缺血和梗塞而引发机能障碍的各种疾病，属于心脑血管疾病。血小板聚集血栓形成中具有关键的作用，血小板聚集引起血栓形成是心脑血管疾病发生的重要原因。目前市场上常用的的抗血栓药物有阿司匹林、吲哚布芬、噻氯匹定、氯吡格雷等。
达比加群酯(Dabigatran Etexilate)，化学名为β-丙氨酸,N-[[2-[[[4-[[[(己氧基)羰基]氨基]亚氨基甲基]苯基]氨基]甲基]-1-甲基-1H-苯并咪唑-5-基]羰基]-N-2-嘧啶-乙酯甲磺酸盐，结构式如下所示。其为口服抗凝药物，是凝血酶抑制剂(DTIs)，用于预防非瓣膜性房颤患者的卒中和全身性栓塞。由德国Boehringer Ingelheim研发，于2008年在欧洲上市。达比加群酯经口服给药后从消化器官吸收、酯酶分解成活性代谢物的达比加群而起作用。它可以直接而且选择性抑制凝血酶，从而发挥抗凝、抗血栓的作用。
普拉格雷(Prasugrel)，化学名为2-[2-(乙酰氧基)-6,7-二氢噻吩并[3,2-c]吡啶-5(4H)-基]-1-环丙基-2-(2-氟苯基)乙酮，结构式如下所示。日本Sankyo公司和美国Eli Lilly公司共同开发，并于2009年2月23日获欧盟批准上市，应用于治疗动脉粥样硬化和急性冠状动脉综合征。其为一新的口服有效噻吩并吡啶类药物。与氯吡格雷一样，普拉格雷也是一个无活性的前体药物，需经细胞色素P450酶系代谢转化至活性代谢物后才能不可逆地抑制血小板上的P2Y12二磷酸腺苷受体。普拉格雷的疗效优于氯吡格雷。
普拉格雷达比加群酯
氯吡格雷在使用过程中会产生氯吡格雷抵抗，即尽管部分患者长期服用常规剂量的氯吡格雷，但临床上仍不能有效防止血栓事件的发生，而且血小板功能检测证实血小板聚集不能
被有效抑制。
发明内容
针对上述技术问题，本发明提供一种抗血栓组合物。本发明的抗血栓组合物包含有效剂量为0.5-5mg的ADP受体拮抗剂和有效剂量为30-70mg的达比加群酯，这两种成分均以游离状态或药学上可接受的盐的形式存在。
进一步地，所述抗血栓组合物中的ADP受体拮抗剂的有效剂量为1～4mg，达比加群酯的有效剂量为40～60mg。
更进一步地，所述抗血栓组合物中的所述ADP受体拮抗剂的有效剂量为2mg，达比加群酯的有效剂量为50mg。
具体地，所述ADP受体拮抗剂为普拉格雷。
本发明的抗血栓组合物由达比加群酯和普拉格雷以及至少一种药学上可接受的载体组成。具体地，所述的抗血栓组合物为口服制剂。
本发明的抗血栓组合物在制备用于治疗和预防因血小板凝集诱导的疾病的药物中的应用。具体地，所述因血小板凝集诱导的疾病包括脑卒中、急性冠脉综合征、介入治疗术及并发症、外周血管栓塞性相关的疾病。
根据本发明，所述“药学上可接受的盐”可以为：盐酸盐、硫酸盐、酒石酸盐、甲磺酸盐、甲酸盐、乙酸盐、苯甲酸盐、马来酸盐、富马酸盐、苯磺酸盐、乙磺酸盐、对甲苯磺酸盐、柠檬酸盐、氢溴酸盐或月桂基磺酸盐。
根据本发明，所述“口服制剂”为胶囊剂或片剂。
根据本发明，所述“药学上可接受的载体”为赋形剂、粘合剂、崩解剂、润滑剂和成膜材料、着色剂、芳香剂和甜味剂。
其中赋形剂可以是淀粉、糖粉、糊精、乳糖、可压性淀粉、微晶纤维素(MCC)、甘露醇、二水合硫酸钙、磷酸氢钙或药用碳酸钙。粘合剂可以是蒸馏水、乙醇、淀粉浆、羟丙甲基纤维素(HPMC)、聚维酮(PVP)、羟丙基纤维素(HPC)、甲基纤维素(MC)、乙基纤维素(EC)、羧甲基纤维素钠(CMC-Na)、5％～20％的明胶溶液、10％～25％的阿拉伯胶溶液或50％～70％的蔗糖溶液。崩解剂可以是干燥淀粉、羧甲基淀粉钠(CMS-Na)、低取代羟丙基纤维素(L-HPC)、羧甲基纤维素钙、碳酸氢钠和枸橼酸或酒石酸、表面活性剂如吐温-80、溴化十六烷基三甲铵、十二烷基硫酸钠、硬脂酸磺酸钠等、交联聚维酮(PVPP)或交联羧甲基纤维素钠(CCNa)。润滑剂可以是水不溶性的硬脂酸镁、滑石粉、氢化植物油、高熔点蜡、硬脂酸、微粉硅胶和水溶性的聚乙二醇、十二烷基硫酸镁。
本发明的抗血栓组合物采用不同作用靶点的药物联合组方，采用比氯吡格雷效果更好的普拉格雷从根本上避免了氯吡格雷抵抗现象的产生，可以作为氯吡格雷抵抗患者的又一用药选择。难能可贵的是，普拉格雷和达比加群酯的联合应用的效果要好于单个药物，并且同时减少了单个药物的用量，将普拉格雷易出血的倾向降至更低。达比加群酯起效快，而普拉格雷更为长效，两者联合应用相得益彰，一日一次的用量可以提高患者的依从性。
为了更好地理解和实施，下面详细说明本发明。
实施例1普拉格雷和达比加群酯的药物相容性实验
将普拉格雷和达比加群酯这两种药物准备和贮存于2种不同的温度湿度环境下，即25℃/10％RH和30℃/60％RH。将药物分为混合组和未混合组作对照，分别置于这两种温度下。样品在第1天、第3天、第7天、第14天、第30天进行性状和化学稳定性(HPLC法)的评价。结果如表1所示。混合组普拉格雷含量为98.3％-101.5％，达比加群酯含量为98.4％-102.5％。观察中混合组和对照组在物理形状和HPLC法分析上无明显差别，说明这两种药物的组合物混合后，二者的物理性和化学性仍具有很好的相容性。
<表1>
实施例2含有普拉格雷0.5mg和达比加群酯70mg的复方片剂
1)处方：
2)制备方法：直接压片法
将处方量普拉格雷与5g乳糖混合均匀，所得粉末再与处方量的达比加群酯混合均匀，再加入剩余量的乳糖、处方量的微晶纤维素和滑石粉，混合均匀后用12mm冲直接压片，即得。
实施例3含有普拉格雷1mg和达比加群酯60mg的复方片剂
1)处方：
2)制备方法：干法制粒压片法
将主药和辅料分别过80目筛，将处方量普拉格雷与10g预胶化淀粉混合均匀，所得粉末再与处方量的达比加群酯混合均匀，再加入剩余量的预胶化淀粉、处方量的微晶纤维素和交联聚维酮，混合均匀后用20目筛干法制粒，加入滑石粉，总混颗粒经含量测定合格后，将干颗粒用12mm冲压片，即得。
实施例4含有普拉格雷5mg和达比加群酯30mg的复方片剂
1)处方：
2)制备方法：湿法制粒压片法
将处方量普拉格雷与20g淀粉混合均匀，所得粉末再与处方量的达比加群酯混合均匀，再加入剩余量的淀粉、处方量的羟丙甲基纤维素和羧甲基淀粉钠，混合均匀，加适量水制粒，所得颗粒在65℃下充分干燥，过筛整粒后与处方量的滑石粉混合均匀，总混颗粒经含量测定合格后，将干颗粒用12mm冲压片，即得。
实施例5含有普拉格雷2mg和达比加群酯50mg的复方胶囊剂
1)处方：
2)制备方法：
将处方量普拉格雷与10g糊精混合均匀，所得粉末再与处方量的达比加群酯混合均匀，再加入剩余量的糊精和处方量的交联羧甲基纤维素钠混合均匀，加70％乙醇制粒，所得颗粒在65℃下充分干燥，过筛整粒，经含量测定合格后装胶囊，即得。
实施例5含有普拉格雷4mg和达比加群酯40mg的复方软胶囊剂
1)处方：
2)制备方法：
处方量的普拉格雷和达比加群酯混合均匀后加入处方量的大豆油和吐温-80，混合均匀后上压模机压制软胶囊，即得。
实施例6体外血栓含量测定
将40只正常大白鼠随机分4组，分别灌胃给予生理盐水、普拉格雷(4mg/kg)、达比加群酯(100mg/kg)、普拉格雷+达比加群酯(2mg/kg+50mg/kg)，每天一次，连续给药20天后最后一次给药后一小时，称重，麻醉，仰卧位固定，分离双侧颈动、静脉，取穿有丝线的聚乙烯管，注满肝素生理盐水，将聚乙烯管的一端插入左侧颈静脉，再将管的另一端插入右侧颈动脉，造成动静脉旁路，开放血流15分钟，取出聚乙烯管，抽出含血栓的丝线，按编号置于培养皿中，称量血栓湿重，减去丝线重量即得血栓重量，结果见表2。
<表2>
| 生理盐水组 | 普拉格雷组 | 达比加群酯组 | 普拉格雷+达比加群酯组 | |
| 血栓重量(mg) | 30.3±7.5 | 18.6±5.6* | 17.4±4.8* | 12.1±2.2# |
#：与普拉格雷组和达比加群酯组比，p<0.05,*：与生理盐水组比，p<0.05
实施例7血小板凝集率测定
将40只正常大白鼠随机分4组，按实施例6的方法连续给药20天后颈动脉采血3.5～4.0mL，置于含有0.4～0.5mL的3.8％枸橼酸钠的离心管中，以1000r/min离心5min，取其上清液即富含血小板血浆(PRP)，在PRP中加诱导剂ADP 10μL(162μmol/L)，用血小板聚集仪测定血小板聚集率。结果见表3.
<表2>
#：与普拉格雷组和达比加群酯组比，p<0.05,*：与生理盐水组比，p<0.05
本发明并不局限于上述实施方式，如果对本发明的各种改动或变形不脱离本发明的精神和范围，倘若这些改动和变形属于本发明的权利要求和等同技术范围之内，则本发明也意图包含这些改动和变形。
Claims (8)
- 一种抗血栓组合物，其特征在于：它包含有效剂量为0.5-5mg的ADP受体拮抗剂和有效剂量为30-70mg的达比加群酯，这两种成分均以游离状态或药学上可接受的盐的形式存在。
- 根据权利要求1所述的抗血栓组合物，其特征在于：所述ADP受体拮抗剂的有效剂量为1～4mg，达比加群酯的有效剂量为40～60mg。
- 根据权利要求2所述的抗血栓组合物，其特征在于：所述ADP受体拮抗剂的有效剂量为2mg，达比加群酯的有效剂量为50mg。
- 根据权利要求1～3任意一项所述的抗血栓组合物，其特征在于：所述ADP受体拮抗剂为普拉格雷。
- 根据权利要求4所述的抗血栓组合物，其特征在于：所述的抗血栓组合物由达比加群酯和普拉格雷以及至少一种药学上可接受的载体组成。
- 根据权利要求5所述的抗血栓组合物，其特征在于：所述的抗血栓组合物为口服制剂。
- 根据权利要求4所述的抗血栓组合物，其特征在于：所述的抗血栓组合物在制备用于治疗和预防因血小板凝集诱导的疾病的药物中的应用。
- 根据权利要求7所述的抗血栓组合物，其特征在于：所述因血小板凝集诱导的疾病包括脑卒中、急性冠脉综合征、介入治疗术及并发症、外周血管栓塞性相关的疾病。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510783061.4A CN105250286A (zh) | 2015-11-13 | 2015-11-13 | 一种抗血栓组合物 |
| CN201510783061.4 | 2015-11-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2017080043A1 true WO2017080043A1 (zh) | 2017-05-18 |
Family
ID=55090423
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2015/098869 WO2017080043A1 (zh) | 2015-11-13 | 2015-12-25 | 一种抗血栓组合物 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN105250286A (zh) |
| WO (1) | WO2017080043A1 (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101151030A (zh) * | 2005-03-29 | 2008-03-26 | 贝林格尔·英格海姆国际有限公司 | 用于治疗血栓的包括至少一种直接凝血酶抑制剂的组合物 |
| CN101686959A (zh) * | 2007-05-02 | 2010-03-31 | 波托拉医药品公司 | 作为血小板adp受体抑制剂的化合物的组合疗法 |
| CN102625658A (zh) * | 2009-05-13 | 2012-08-01 | 锡德克斯药物公司 | 包含普拉格雷和环糊精衍生物的药物组合物及其制备和使用方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102755336A (zh) * | 2011-04-26 | 2012-10-31 | 符靠 | 包含格雷类药物和阿司匹林盐的药物组合物 |
| CN103505465A (zh) * | 2012-06-27 | 2014-01-15 | 天津拓飞生物科技有限公司 | 含有达比加群酯和抗血栓的药物组合物 |
-
2015
- 2015-11-13 CN CN201510783061.4A patent/CN105250286A/zh active Pending
- 2015-12-25 WO PCT/CN2015/098869 patent/WO2017080043A1/zh active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101151030A (zh) * | 2005-03-29 | 2008-03-26 | 贝林格尔·英格海姆国际有限公司 | 用于治疗血栓的包括至少一种直接凝血酶抑制剂的组合物 |
| CN101686959A (zh) * | 2007-05-02 | 2010-03-31 | 波托拉医药品公司 | 作为血小板adp受体抑制剂的化合物的组合疗法 |
| CN102625658A (zh) * | 2009-05-13 | 2012-08-01 | 锡德克斯药物公司 | 包含普拉格雷和环糊精衍生物的药物组合物及其制备和使用方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105250286A (zh) | 2016-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101518143B1 (ko) | 저장 안정성 제제를 제조하기 위한 결합제의 용도 | |
| TWI660746B (zh) | 一種替格瑞洛固體分散體及其製備方法 | |
| US20110038931A1 (en) | Composite preparation | |
| JP2010090168A (ja) | 医薬組成物 | |
| KR20200013258A (ko) | 레날리도마이드의 경구용 정제 조성물 | |
| JP7246384B2 (ja) | 遅延放出デフェリプロン錠剤及びその使用法 | |
| AU2016224503A1 (en) | Solid preparation | |
| JPWO2010147169A1 (ja) | 溶出性の改善された医薬組成物 | |
| JPWO2011115067A1 (ja) | 抗凝固剤の溶出改善方法 | |
| KR20170108874A (ko) | 클로피도그렐 및 아스피린을 포함하는 복합제제 | |
| JP2020532517A (ja) | 高濃度プリドピジン製剤 | |
| JP2019523258A (ja) | エソメプラゾール、又は薬学的に許容可能なその塩を含むｐＨ依存性薬物放出特性が改善した剤形 | |
| AU2014299447A1 (en) | Pharmaceutical capsule composite formulation comprising tadalafil and tamsulosin | |
| US20120141586A1 (en) | Thrombin receptor antagonist and clopidogrel fixed dose tablet | |
| CN115518066A (zh) | 一种用于治疗抗凝血的药物组合物及应用 | |
| CN114209667A (zh) | 包含丙戊酸的延迟释放药物制剂和其用途 | |
| KR20160141314A (ko) | 약제학적 복합제제 | |
| CA3169318A1 (en) | Pharmaceutical composition for oral administration | |
| CN105395504A (zh) | 一种盐酸氟桂利嗪骨架缓释片及其制备方法 | |
| KR102120720B1 (ko) | 날푸라핀 함유 구강붕해정 | |
| KR101587140B1 (ko) | 위장관 질환 치료용 모사프리드 구연산염 미니정제 함유 서방성 캡슐 제제 및 이의 제조 방법 | |
| CN106994121B (zh) | 一种用于治疗癌症的药物组合物 | |
| WO2017080043A1 (zh) | 一种抗血栓组合物 | |
| CN103800336A (zh) | 一种具有抗血栓活性药物的组合物 | |
| CN107648237B (zh) | 氨基嘧啶类化合物的药物组合物及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 15908173 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 15908173 Country of ref document: EP Kind code of ref document: A1 |
|
| 32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 23/11/2018) |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 15908173 Country of ref document: EP Kind code of ref document: A1 |