CN110876801A - GM-CSF与Dencichine联用在制备治疗炎性肠病药物中的用途 - Google Patents
GM-CSF与Dencichine联用在制备治疗炎性肠病药物中的用途 Download PDFInfo
- Publication number
- CN110876801A CN110876801A CN201911111836.8A CN201911111836A CN110876801A CN 110876801 A CN110876801 A CN 110876801A CN 201911111836 A CN201911111836 A CN 201911111836A CN 110876801 A CN110876801 A CN 110876801A
- Authority
- CN
- China
- Prior art keywords
- csf
- mice
- dectichine
- inflammatory bowel
- control group
- 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.)
- Pending
Links
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 title claims abstract description 40
- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims abstract description 10
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 title claims abstract 6
- 239000003814 drug Substances 0.000 title abstract description 13
- 229940079593 drug Drugs 0.000 title abstract description 9
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 description 40
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 34
- 239000003651 drinking water Substances 0.000 description 15
- 235000020188 drinking water Nutrition 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 7
- 208000004232 Enteritis Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 231100000683 possible toxicity Toxicity 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 3
- 208000037817 intestinal injury Diseases 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000005534 hematocrit Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102100039064 Interleukin-3 Human genes 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000003143 Panax notoginseng Nutrition 0.000 description 1
- 241000180649 Panax notoginseng Species 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 241000983354 Parsonsia heterophylla Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229930182852 proteinogenic amino acid Natural products 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及生物医药领域，具体涉及GM‑CSF与Dencichine联用在制备治疗炎性肠病药物中的用途。
Description
技术领域
本发明涉及生物医药领域，具体涉及GM-CSF与Dencichine联用在制备治疗炎性肠病药物中的用途。
背景技术
炎性肠病(inflammatory bowel disease，IBD)是以肠道非特异性炎症损伤为特征的慢性复发性疾病，包括溃疡性结肠炎(ulcerative colitis，UC)和克罗恩病(Crohn'sdisease)。通过肠镜检查，可以观察到肠粘膜充血、水肿、颗粒样改变甚至溃疡形成；在组织病理学上病变区域广泛溃疡形成伴有大量中性粒细胞浸润和肠粘膜坏死。然而，炎性肠病的发病机理目前并没有明确的定论，可能与基因易感性、外界环境刺激、自身免疫以及肠道菌群失调有关。
Dencichin是从三七中分离得到的非蛋白氨基酸，能够抑制 HIF-prolylhydroxylase-2(PHD-2)的活性，并且显着抑制HBZY-1细胞的细胞增殖和细胞外基质(ECM)蛋白积聚，减少胶原蛋白I(Col I)， IV型胶原蛋白(Col IV)和纤维连接蛋白的分泌(FN)。同时，Dencichin 还可改善继发于II型糖尿病模型的糖尿病肾病的代谢紊乱。
粒细胞巨噬细胞集落刺激因子(GM-CSF)是一种造血生长因子，在体外可刺激中性粒细胞和巨噬细胞的集落形成，并具有促进早期红巨核细胞、嗜酸性祖细胞增殖和发育的功能。有公开文献报道 GM-CSF对DSS诱导的小鼠肠炎有一定预防和治疗作用。在我们的实验体系中，GM-CSF对DSS所导致的小鼠肠道损伤具有一定保护作用，但效果不稳定，在生存期实验中我们发现个别经GM-CSF处理小鼠比对照小鼠死亡更快。因此，发明人致力于寻找另一种药物与 GM-CSF联用，寄希望于其能与GM-CSF发挥协同效果，降低其潜在的毒性/风险。
发明内容
本发明要解决的技术问题是：提供一种降低GM-CSF在治疗肠炎过程中潜在毒性/风险的药物联用方案。
在本发明的第一方面，提供了GM-CSF与Dencichine或其药学上可接受的盐联用在制备治疗炎性肠病药物中的用途。
GM-CSF对DSS所导致的小鼠肠道损伤具有一定保护作用，但效果不稳定，在生存期实验中我们发现个别经GM-CSF处理小鼠比对照小鼠死亡更快。发明人意外发现，将Dencichine与GM-CSF联用能够显著降低GM-CSF在治疗肠炎过程中潜在毒性/风险。
本发明的第二方面提供了一种药物组合物，其含有治疗量的 GM-CSF、Dencichine或其药学上可接受的盐及药学上可接受的辅料。
优选的，所述组合物中GM-CSF与Dencichine或其药学上可接受的盐的质量比为1：1×103～1×105；进一步的，所述组合物中 GM-CSF与Dencichine或其药学上可接受的盐的质量比为1：2×103～1 ×105。
本发明的有益效果在于首次发现并证实了GM-CSF与Dencichine 联用对Dss诱导的小鼠肠炎具有良好的治疗效果，且能够显著降低 GM-CSF在治疗肠炎过程中潜在毒性/风险。
附图说明
图1为第一对照组(n＝9)、第二对照组(n＝6)、第三对照组(n＝6) 与处理组(n＝6)小鼠从口服DSS饮用水开始的生存期折线图；
图2为第一对照组(n＝6)与处理组(n＝6)小鼠口服DSS饮用水7天后小鼠外周血中红细胞数量对比散点图；
图3为第一对照组(n＝9)与处理组(n＝6)小鼠口服DSS饮用水7天后小鼠外周血中红细胞红细胞比容对比散点图。
具体实施方式
以下结合实例说明本发明，但不限制本发明。在本领域内，技术人员对本发明所做的简单替换或改进均属于本发明所保护的技术方案内。
实施例1
材料与方法：
小鼠：雄性野生型C57小鼠(6-8周)购于中国科学院(上海)。所有小鼠均饲养于第二军医大学(上海)动物实验中心无特殊病原体 (SPF)实验室。
处理组小鼠连续4天给予100μg/kg/d GM-CSF(杭州开华生物科技有限公司)腹腔注射+5mg/ml Dencichine(上海源溪生物科技有限公司)饮用水喂养，4天后给予1.5％DSS(40,000kDa；ICN Biochemicals)饮用水口服7天后转为正常饮用水。GM-CSF的给药量根据小鼠体重差别每只约给药2～5μg；Dencichine给药量根据小鼠的饮水量约为10～200mg。
第一对照组小鼠与处理组小鼠同一时间给予1.5％DSS饮用水口服7天后转为正常饮用水。
第二对照组连续4天给予100ug/kg/d GM-CSF(杭州开华生物科技有限公司)腹腔注射，4天后给予1.5％DSS饮用水口服7天后转为正常饮用水。
第三对照组连续4天给予5mg/ml Dencichine(上海源溪生物科技有限公司)饮用水喂养，4天后给予1.5％DSS饮用水口服7天后转为正常饮用水。
生存期实验：记录对照组与处理组小鼠口服DSS饮用水15天后的生存期。具体的，实验组小鼠的平均生存时间为12.8天，其中，第一对照组小鼠的平均生存时间为9.2天；第二对照组小鼠的平均生存时间为11.5天；第三对照组小鼠的平均生存时间为11.5天。
外周血分析：第一对照组(n＝6)与处理组(n＝6)小鼠饮1.5％DSS 水第7天，小鼠在麻醉状态下，使用毛细管对小鼠进行眼球去除取血，将血置入带有K2-EDTA的离心管(EP管)。通过第二军医大学动物实验中心实验室的标准血液学分析仪确定红细胞和血细胞压积。
结果：GM-CSF+Dencichine小鼠生存期好于第一、第二和第三对照组小鼠(图1)。第一对照组小鼠贫血症状比GM-CSF+Dencichine 小鼠更严重，并且GM-CSF+Dencichine小鼠外周血RBC和HCT均高于对照组小鼠(图2、3)。
为了验证GM-CSF+Dencichine小鼠生存期改善是否由于单纯剂量原因导致，发明人再额外设置了第二对照组和第三对照组的高剂量组，其中第二对照组高剂量组连续4天给予150ug/kg/d GM-CSF腹腔注射，该组小鼠的平均生存时间为11.1天，较正常剂量组反而略有降低；第三对照组的高剂量组连续4天给予6mg/ml Dencichine饮用水喂养，该组小鼠的平均生存时间为11.7天。
实施例2
细胞毒性实验
材料与方法：将体外培养生长至90％汇合状态的IEC-6肠上皮细胞以0.25％胰酶/0.1％EDTA消化并接种于96孔细胞培养板，每孔细胞数为2×103。培养次日去除原培养基，每孔加入待测化合物工作液继续培养，其中处理组加入含1×10-5mol/L的Dencichine和1×10-5mol/L的GM-CSF的混合溶液；第二对照组加入含1×10-5mol/L 的GM-CSF；第三对照组加入含1×10-5mol/L的Dencichine。于IEC-6 细胞与待测药物共培养后的24h通过MTT法检测待测药物对细胞的毒性(n＝5)。其结果如表1所示：
表1
| 处理组 | 第二对照组 | 第三对照组 | |
| 24h细胞存活率 | 91％ | 75％ | 88％ |
结论：GM-CSF虽然对DSS所导致的小鼠肠道损伤具有一定保护作用，但效果不稳定，在生存期实验中我们发现个别经GM-CSF 处理小鼠比对照小鼠死亡更快，其原因可能是GM-CSF对IEC-6肠上皮细胞有一定的毒性。加入Dencichine后，两种药物组合后明显提高了IEC-6肠上皮细胞的存活率，甚至略高于仅加入Dencichine的第三对照组的存活率，这可能是GM-CSF+Dencichine联用对Dss诱导的小鼠肠炎具有良好的治疗效果的原因之一。
以上所述的仅是本发明的优选实施方式，应当指出，对于本领域的普通技术人员来说，在不脱离本发明创造构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。
Claims (3)
1.GM-CSF与Dencichine或其药学上可接受的盐联用在治疗炎性肠病中的用途。
2.一种药物组合物，其特征在于含有治疗量的GM-CSF、Dencichine或其药学上可接受的盐及药学上可接受的辅料。
3.如权利要求1所述的药物组合物，其特征在于所述组合物中GM-CSF与Denichine或其药学上可接受的盐的质量比为1： 1×103~1×105。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911016870 | 2019-10-24 | ||
| CN2019110168707 | 2019-10-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110876801A true CN110876801A (zh) | 2020-03-13 |
Family
ID=69729686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911111836.8A Pending CN110876801A (zh) | 2019-10-24 | 2019-11-14 | GM-CSF与Dencichine联用在制备治疗炎性肠病药物中的用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110876801A (zh) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104771387A (zh) * | 2014-01-15 | 2015-07-15 | 上海中医药大学 | 三七素的用途 |
-
2019
- 2019-11-14 CN CN201911111836.8A patent/CN110876801A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104771387A (zh) * | 2014-01-15 | 2015-07-15 | 上海中医药大学 | 三七素的用途 |
Non-Patent Citations (1)
| Title |
|---|
| 林艳等: "应用粒-巨噬细胞集落刺激因子治疗小鼠炎症性肠病的疗效研究", 《解剖科学进展》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210322407A1 (en) | Use of Trimetazidine in Preparation of Drugs for Preventing and Treating Liver Diseases | |
| CN108641988B (zh) | 植物乳杆菌na136及其在缓解非酒精性脂肪肝病中的应用 | |
| JP5744213B2 (ja) | 赤血球減少に関連する疾病の予防又は治療用薬物の製造におけるアルクチゲニンの用途 | |
| EP3031456A1 (en) | Application of andrographolide in the preparation of a pharmaceutical for treatment of inflammatory bowel disease, andrographolide enteric targeting micropellet, and method for preparation thereof | |
| CN113679731B (zh) | 野黑樱苷在制备治疗脂肪性肝病和肝纤维化的药物中的应用 | |
| Shiba et al. | p-Cresyl sulfate decreases peripheral B cells in mice with adenine-induced renal dysfunction | |
| CN110934879B (zh) | 靶向组织微环境中衰老细胞的抗衰老药物d/a及其应用 | |
| CN110960539A (zh) | 桑皮苷a及其衍生物在制备保护肠道屏障的药物中的应用 | |
| CN108295085B (zh) | 原薯蓣皂苷在制备抗耐药性骨肉瘤药物中的应用 | |
| CN110876801A (zh) | GM-CSF与Dencichine联用在制备治疗炎性肠病药物中的用途 | |
| CN115154505A (zh) | 香连丸在制备用于免疫治疗泛癌患者减毒增效的药物中的应用 | |
| CN111249274B (zh) | 银杏内酯b在制备胶质瘤细胞活性抑制剂中的应用 | |
| EP4248964A1 (en) | Pharmaceutical composition for treating sepsis, and use thereof | |
| CN109985030B (zh) | 醌式查尔酮化合物在制备抗肿瘤药物中的应用 | |
| CN112618569A (zh) | 一种用于治疗尿路上皮癌的药物 | |
| CN111728990A (zh) | 一种八宝丹在制备预防及治疗肝癌药物中的应用 | |
| CN112587545A (zh) | 枸杞多糖在制备舒张胸主动脉药物中的用途 | |
| CN111393278A (zh) | 一种长松萝衍生物及其在制备治疗胆囊癌药物中的用途 | |
| CN107260752B (zh) | 一种协同抗胰腺癌的药物组合物 | |
| WO2023061446A1 (zh) | 一种增强ezh2抑制剂抗肿瘤作用的药物组合物及其用途 | |
| LU505195B1 (en) | Use of Carvedilol in the Preparation of Drugs for the Treatment of Leukaemia | |
| US11617729B2 (en) | Uses of guanidine hydrochloride as a drug for treating cancers/tumors | |
| CN114191450B (zh) | 普鲁士蓝及其类似物在制备预防、延缓或治疗骨质疏松症药物中的应用 | |
| CN114617969A (zh) | 乐伐替尼和Aurora-A激酶抑制剂在制备抑制癌症的药物中的应用 | |
| CN114699426A (zh) | 一种改善胰岛素抵抗症状的药物组合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200313 |
|
| RJ01 | Rejection of invention patent application after publication |