WO2012163088A2 - 肾病和心脏病的治疗药物及其用途 - Google Patents

肾病和心脏病的治疗药物及其用途 Download PDF

Info

Publication number
WO2012163088A2
WO2012163088A2 PCT/CN2012/001010 CN2012001010W WO2012163088A2 WO 2012163088 A2 WO2012163088 A2 WO 2012163088A2 CN 2012001010 W CN2012001010 W CN 2012001010W WO 2012163088 A2 WO2012163088 A2 WO 2012163088A2
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
kidney disease
disease
heart disease
Prior art date
Application number
PCT/CN2012/001010
Other languages
English (en)
French (fr)
Other versions
WO2012163088A3 (zh
Inventor
梁广
潘勇
王怡
赵承光
李校堃
蔡露
Original Assignee
温州医学院
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 温州医学院 filed Critical 温州医学院
Publication of WO2012163088A2 publication Critical patent/WO2012163088A2/zh
Publication of WO2012163088A3 publication Critical patent/WO2012163088A3/zh

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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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

Definitions

  • the present invention relates to the field of medical technology, and in particular to the use of a compound of the formula (I) or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment or prevention of kidney disease and heart disease.
  • Heart disease and kidney disease are among the leading causes of death and disease in patients with diabetes today.
  • kidney disease and heart disease There are many causes of kidney disease and heart disease, including chemical, congenital, and concomitant (such as long-term hyperglycemia or other abnormal metabolism).
  • Nephropathy is characterized by progressive glomerulosclerosis and tubulointerstitial fibrosis, which is accompanied by a decrease in proteinuria and GFR, which ultimately leads to end stage renal failure.
  • Cardiomyopathy is characterized by its early abnormal diastolic function, accompanied by a slight abnormality of contractile function, which reduces longitudinal fiber function. Histological studies have shown that extracellular matrix deposition in the heart of patients with long-term hyperglycemia is increased, mainly fibrillar collagen, accompanied by cardiac hypertrophy.
  • the compound of formula (I) can effectively treat heart disease and kidney disease, especially kidney disease and heart disease in patients with long-term blood sugar, and can inhibit sugar-induced kidney and heart damage, especially Surprisingly, the compound is not treated by lowering blood sugar, and it is more directly treated for kidney disease and heart disease, and can be foreseen in combination with other drugs that lower blood sugar. Summary of the invention
  • the object of the present invention is to provide a novel use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (a compound of formula (I)) and other drugs use.
  • the present invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment or prevention of kidney disease or heart disease
  • the use of the invention is in the manufacture of a medicament for the treatment or prevention of kidney disease.
  • the present invention also provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for ameliorating the symptoms of kidney disease or heart disease.
  • the use of the invention is in the manufacture of a medicament for ameliorating the symptoms of kidney disease.
  • the kidney disease is induced by hyperglycemia.
  • the symptom of nephropathy is renal fibrosis.
  • the compound of formula (I) or a pharmaceutically acceptable salt thereof does not statistically significantly lower blood glucose. That is, it is preferred that the use in the present invention is in the preparation of a medicament which does not statistically significantly lower blood glucose, for example, the present invention provides a compound of the formula (I) or a pharmaceutically acceptable salt thereof for use in preparation for use in preparation Use in medicines that treat or prevent kidney disease or heart disease but do not statistically significantly lower blood sugar.
  • the compound of the formula (I) or a pharmaceutically acceptable salt thereof is not statistically significantly reduced in body weight. That is, it is preferred that the use in the present invention is in the preparation of a medicament which does not statistically significantly reduce body weight, for example, the present invention provides a compound of the formula (I) or a pharmaceutically acceptable salt thereof for use in preparation for use in preparation Use in a drug that treats or prevents kidney disease or heart disease but does not statistically significantly reduce body weight.
  • the use of the invention is the use of a compound of formula (I).
  • the medicament in the use of the invention contains an effective amount of a compound of formula (I).
  • the effective dose may be the amount of the drug in a unit dosage form (e.g., one tablet, one needle, one pill, or one dose), or may be the unit dose (e.g., unit weight dose) of the patient in need of treatment/prevention.
  • the drug manufacturer can easily convert the unit weight dose of the patient to be treated/prevented into the amount of the drug in a unit dosage form by the average body weight of the patient population to be treated/prevented, for example, the average of the adult patient.
  • the body weight can be 60 kg, so by multiplying the average body weight by the unit weight dose of the adult, the content in the drug for the unit dosage form for the adult can be obtained.
  • the patient may be a mammal such as a human, rabbit, dog or mouse.
  • a mammal such as a human, rabbit, dog or mouse.
  • the human body weight dose can be derived from the dose of experimental animals.
  • the conversion relationship with an adult is about 12:1; for a commonly used experimental animal rat, according to the above document, Its conversion relationship with adults is about 6:1.
  • the effective dose in terms of content may be 10ug-lg, preferably 0.1 mg to 500 mg, more preferably 1 mg to 100 mg.
  • the medicament in the use of the invention will usually also contain a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable carrier refers to a non-toxic filler, stabilizer, diluent, adjuvant or other formulation adjuvant.
  • diluents, excipients such as water, physiological saline, etc.
  • fillers such as starch, sucrose, etc.
  • binders such as cellulose derivatives, alginates, gelatin and/or polyvinylpyrrolidone
  • humectants such as Glycerin
  • a disintegrant such as agar, calcium carbonate and/or sodium hydrogencarbonate
  • an absorption enhancer such as a quaternary ammonium compound
  • a surfactant such as hexadecanol
  • an adsorbent carrier such as kaolin and/or soap clay
  • talcum powder calcium stearate/magnesium, polyethylene glycol, and the like.
  • the pharmaceutical composition of the present invention may further contain other excipients such as a flavoring agent, a sweetener and the like.
  • the pharmaceutical composition can be formulated into various dosage forms depending on the purpose of the treatment, the route of administration, preferably in the form of a unit dosage form, such as a lyophilizate, a tablet, a capsule, a powder, according to a technique known in the art.
  • the emulsion composition, the aqueous injection or the spray, more preferably the pharmaceutical composition is an injection dosage form (e.g., lyophilized powder injection) or an oral dosage form (e.g., tablet, capsule).
  • the medicament may be administered by conventional routes, in particular enterally, for example orally, for example in the form of a tablet or capsule, or parenterally, for example in the form of an injectable solution or suspension, topically applied, for example as a lotion or Gel, or in the form of a nasal or test.
  • Figure 1 shows the effect of compounds of formula (I) on the metabolism of hyperglycemic rats.
  • Figure 2 shows the effect of the compound of formula (I) on renal tissue abnormalities and renal fibrosis in hyperglycemia rats.
  • Example 1 The compounds of the present invention did not affect blood glucose and body weight of rats. SD rats were randomly divided into 5 groups of 5 rats each, respectively: Blank control group (referred to as SD or con): healthy rats;
  • Kidney disease control group (abbreviated as DM): According to the method described by Wang Kang et al. (Chinese Journal of Integrated Traditional and Western Nephrology, 2010, 11(1): 14-17), mice were pathogenic with streptozotocin. ;
  • Low-dose treatment group (abbreviated as 0.2): same as DM, causing disease in rats, and administering the compound of formula (I) to rats at a dose of 0.2 mg/kg/day 7 days after the disease;
  • the medium-dose treatment group (referred to as 1): the same as DM, causing the disease of the mice, and administering the compound of the formula (I) to the rats at a dose of lmg/kg/day 7 days after the disease;
  • High-dose treatment group (abbreviated as 1): The same as DM, causing the disease in rats, and the compound of formula (I) was administered orally to the rats at a dose of 5 mg/kg/day 7 days after the disease.
  • the serum glucose, serum creatinine, body weight, and kidney/weight ratio were measured during the period. The results are shown in Figure 1. There was no significant difference in blood glucose levels between the treatment group and the diabetic group, and there was no significant difference in body weight. Meanwhile, the kidney/body weight ratio of the nephrotic control group was significantly increased relative to the normal group ( ⁇ 0.05). ), indicating that hyperglycemia is harmful to the kidneys, but administration of the compound of formula (I) significantly reduced the kidney/body weight ratio (especially 5 mg/kg/d a y ) of each treatment group (p ⁇ 0.05).
  • Example 2 The compounds of the present invention significantly improved rat kidney disease and fibrosis. Grouped and tested according to Example 1. After 6 weeks of administration, each group of rats was sacrificed, and kidney tissues were taken and fixed with 4% formalin solution. Paraffin-embedded, 5 ⁇ sections were stained with glycogen (PAS), sapphire red (Sirius red) and hematoxylin & eosin (H&E) and microscopically examined.
  • PAS glycogen
  • sapphire red Sirius red
  • H&E hematoxylin & eosin
  • the results are shown in Figure 2.
  • the renal tissue has obvious glycogen accumulation, increased IV collagen and structural abnormalities (including glomerular sclerosis, enlargement and thickening of the basement membrane, and severe inflammatory cell infiltration).
  • the administration of the compound of formula (I) significantly improved the symptoms of renal tissue damage, inflammatory cell infiltration and mesangial matrix expansion in the rats of each treatment group. This indicates that the compound of formula (I) is capable of preventing the deterioration of renal fibrosis due to hyperglycemia.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明提供了(2E，6E)-2，6-二(2-(三氟甲基)苯亚甲基)环己酮或其药学上可接受的盐在制备用于治疗或预防肾病或心脏病的药物，或者用于改善肾病或心脏病症状的药物中的用途。

Description

肾病和心脏病的治疗药物及其用途 技术领域
本发明属于医药技术领域， 具体涉及式 （I) 的化合物或其药学上可接受的盐在 制备用于治疗或预防肾病和心脏病的药物中的用途。
Figure imgf000003_0001
背景技术
心脏病和肾病是糖尿病当今患病人群的主要死亡和发病原因之一。 肾病和心脏 病的诱因很多， 包括化学药物性的， 先天性的， 以及并发性的 （如长期高血糖或其 他代谢不正常而引起的） 。 肾病的特征在于进行性肾小球硬化和肾小管间质纤维化， 其伴随蛋白尿和 GFR下降， 最后导致末期肾衰竭。 心肌病的特征在于其早期异常的 舒张功能， 伴随收缩功能的轻微异常， 减少纵向纤维功能。 组织学研究显示， 长期 高血糖的病人心脏的细胞外基质沉积增加， 主要是纤维状胶原， 伴随心肌肥大。
本发明人在多年的工作基础上， 发现了式 （I) 的化合物能够有效治疗心脏病和 肾病， 尤其是长期髙血糖患者的肾病和心脏病， 能够抑制糖诱导的肾和心脏损伤， 尤其令人惊奇的是， 该化合物不是通过降低血糖来进行治疗的， 本身对肾病和心脏 病的治疗更为直接， 而且可以预见与降低血糖的其他药物联合使用。 发明内容
本发明的目的在于提供了 (2E,6E)-2,6-二 (2- (三氟甲基） 苯亚甲基） 环己酮（式（I) 的化合物） 的新的用途以及其他药用。
具体而言， 本发明提供了式（I)的化合物或其药学上可接受的盐在制备用于治疗 或预防肾病或心脏病的药物中的用途
Figure imgf000003_0002
优选本发明的用途是在制备用于治疗或预防肾病的药物中的用途。
本发明还提供了式（I)的化合物或其药学上可接受的盐在制备用于改善肾病或心 脏病症状的药物中的用途。
优选本发明的用途是在制备用于改善肾病症状的药物中的用途。
优选在本发明的用途中， 肾病是由高血糖诱发的。
优选在本发明的用途中， 肾病症状是肾纤维化。
优选在本发明的用途中， 式 （I) 的化合物或其药学上可接受的盐是不在统计学 上显著降低血糖的。 也就是说， 优选在本发明的用途是在制备不在统计学上显著降 低血糖的药物中的用途， 例如， 本发明提供了式 （I) 的化合物或其药学上可接受的 盐在制备用于治疗或预防肾病或心脏病但不在统计学上显著降低血糖的药物中的用 途。
另外优选在本发明的用途中， 式 （I) 的化合物或其药学上可接受的盐是不在统 计学上显著降低体重的。 也就是说， 优选在本发明的用途是在制备不在统计学上显 著降低体重的药物中的用途， 例如， 本发明提供了式 （I) 的化合物或其药学上可接 受的盐在制备用于治疗或预防肾病或心脏病但不在统计学上显著降低体重的药物中 的用途。
优选本发明的用途是是式 （I) 的化合物的用途。
本发明的用途中的药物含有有效剂量的式（I)的化合物。有效剂量可以是单位给 药剂量形式 （如， 一片、 一针、 一丸或一剂） 的药物中的含量， 也可以是所需治疗 / 预防的患者的单位剂量（如， 单位体重剂量）。 药物制造商能够很容易地通过所需治 疗 /预防的患者群体的平均体重将所需治疗 /预防的患者的单位体重剂量换算成单位 给药剂量形式的药物中的含量， 例如， 成人患者的平均体重可以是 60kg, 因此通过 平均体重乘以成人的单位体重剂量， 即可得到用于成人的单位给药剂量形式的药物 中的含量。
在本发明中， 患者可以是哺乳动物， 如人、 兔、 狗或鼠。 根据本领域普通技术人 员所公知的实验动物与人的等效剂量换算关系 （通常可参见 FDA、 SFDA等药品管理 机构的指导意见， 也可参见 "黄继汉等.药理试验中动物间和动物与人体间的等效剂 量换算. 中国临床药理学与治疗学， 2004， 9 (9) : 1069 - 1072" ) 可从实验动物的 剂量推导出人的单位体重剂量。 例如， 对于常用的实验动物小鼠而言， 根据上述文 献，其与成人的换算关系约为 12: 1；对于常用的实验动物大鼠而言，根据上述文献， 其与成人的换算关系约为 6: 1。在本发明中， 有效剂量（以含量计）可以是 lOug-lg 优选是 0.1mg-500mg， 更优选是 lmg-100mg。
本发明的用途中的药物通常还含有药学上可接受的载体。本文中使用的药学上可 接受的载体指无毒的填充剂、 稳定剂、 稀释剂、 佐剂或其他制剂辅料。 例如， 稀释 剂、 赋形剂， 如水、 生理盐水等； 填充剂， 如淀粉、 蔗糖等； 粘合剂， 如纤维素衍 生物、 藻酸盐、 明胶和 /或聚乙烯吡咯烷酮； 湿润剂， 如甘油； 崩解剂， 如琼脂、 碳 酸钙和 /或碳酸氢钠； 吸收促进剂， 如季铵化合物； 表面活性剂， 如十六垸醇； 吸附 载体， 如高岭土和 /或皂粘土； 润滑剂， 如滑石粉、硬脂酸钙 /镁、 聚乙二醇等。 另外， 本发明的药物组合物还可以进一步含有其它辅料， 如香味剂、 甜味剂等。 根据本领 域的公知技术， 可以根据治疗目的、 给药途径的需要将药物组合物制成各种剂型， 优选该组合物为单位给药剂量形式， 如冻干剂、 片剂、 胶囊、 粉剂、 乳液剂、 水针 剂或喷雾剂， 更优选该药物组合物为注射剂型 （如， 冻干粉针剂） 或口服剂型 （如， 片剂、 胶囊）。 药物可以通过常规途径施用， 特别是肠内， 例如口服， 例如以片剂或 胶囊剂形式， 或非肠道施用， 例如以可注射溶液剂或混悬剂形式， 局部施用， 例如 以洗剂或凝胶剂， 或以鼻剂或检剂形式。
为了便于理解， 本发明引用了公开文献， 这些文献是为了更清楚地描述本发明， 其全文内容均纳入本文进行参考。 以下将通过具体的实施例和附图对本发明进行详 细地描述。 需要特别指出的是， 这些描述仅仅是示例性的描述， 并不构成对本发明 范围的限制。 依据本说明书的论述， 本发明的许多变化、 改变对所属领域技术人员 来说都是显而易见了。 附图说明
图 1 式 （I) 的化合物影响对高血糖鼠代谢情况的影响。
图 2 式 （I) 的化合物对高血糖鼠肾脏组织异常和肾纤维化的改善效果。 具体实施方式
本发明在以下的实施例中进一步说明。 这些实施例只是为了说明的目的， 而不 是用来限制本发明的范围。 实施例 1 本发明的化合物不影响大鼠血糖和体重水平 将 SD大鼠随机分为 5组， 每组 5只， 分别为： 空白对照组 （简称为 SD或 con): 健康鼠；
肾病对照组 （简称为 DM ) : 根据王康等 （中国中西医结合肾病杂 志, 2010,11(1):14-17) 所述的方法用链脲佐菌素使鼠致病， 不给药；
低剂量治疗组（简称为 0.2): 同 DM, 使鼠致病， 在致病 7天后以 0.2mg/kg/day 的剂量给鼠灌胃给药式 （I) 的化合物；
中剂量治疗组 （简称为 1 ): 同 DM， 使鼠致病， 在致病 7天后以 lmg/kg/day的 剂量给鼠灌胃给药式 （I) 的化合物；
高剂量治疗组 （简称为 1 ): 同 DM， 使鼠致病， 在致病 7天后以 5mg/kg/day的 剂量给鼠灌胃给药式 （I) 的化合物。
期间测定各组鼠的血糖（serum glucose ) 血肌酸酐（serum creatinine),体重（body weight)和肾 /体重比（kidney/weight ratio)等参数。 结果如图 1所示， 治疗组大鼠血 糖水平与糖尿病组没有明显差异性， 并且体重也不存在显著性差异； 同时， 肾病对 照组的肾 /体重比相对于正常组明显增加 (^<0.05)，表明高血糖对肾脏有危害，但是给 予式（I)的化合物后可显著降低各治疗组的肾 /体重比 (尤其是 5 mg/kg/day )(p<0.05)。 这表明， 式 （I) 的化合物不影响高血糖的大鼠血糖及体重水平， 其治疗效应不受血 糖值的影响； 式 （I) 的化合物对由于高血糖而引起的肾脏病变有治疗作用， 防止肾 脏实质性病变。 实施例 2本发明的化合物明显改善大鼠肾脏病变和纤维化 按照实施例 1分组并进行试验， 给药 6周后， 处死各组鼠， 取肾脏组织， 以 4% ***液固定、 石蜡包埋、 5μιη切片后进行糖原 （PAS)、 天蓝猩红 （Sirius red) 和苏木素 &伊红 （H&E) 染色并镜检。 结果如图 2所示， 肾病对照组大鼠肾组织有 明显糖原聚集， IV胶原增加和结构异常 （包括， 肾小球硬化、 肿大和基底膜增厚， 以及炎症细胞浸入严重） ， 而同时给予式 （I) 的化合物后， 明显改善了各治疗组的 大鼠肾组织的损伤、 炎症细胞浸润和肾小球膜基质扩张等症状。 这表明， 式 （I) 的 化合物能够阻止由于高血糖而引起的肾脏纤维化的恶化。

Claims

权 利 要 求 书
1、式（I)的化合物或其药学上可接受的盐在制备用于治疗或预防肾病或心脏病的药 物， 或者用于改善肾病或心脏病症状的药物中的用途
Figure imgf000007_0001
(I) 。
2、 根据权利要求 1所述的用途， 其是在制备用于治疗或预防肾病， 或者用于改善肾 病症状的药物中的用途。
3、 根据权利要求 2所述的用途， 其中肾病是由高血糖诱发的。
4、 根据权利要求 2所述的用途， 其中肾病症状是肾纤维化。
5、 根据权利要求 1-4之任一项所述的用途， 其是在制备不在统计学上显著降低血糖 的药物中的用途。
6、根据权利要求 1所述的用途， 其中式（I)的化合物或其药学上可接受的盐是不在 统计学上显著降低血糖的。
7、根据权利要求 1所述的用途， 其中式（I)的化合物或其药学上可接受的盐是不在 统计学上显著降低体重的。
8、 根据权利要求 5或 6所述的用途， 其是式 （I) 的化合物的用途。
9、式（I)的化合物或其药学上可接受的盐， 其用于治疗或预防肾病或心脏病的药物 或者用于改善肾病或心脏病症状， 而且其不在统计学上显著降低血糖
Figure imgf000007_0002
(I) 。
10、根据权利要求 9所述的化合物或其药学上可接受的盐，其用于治疗或预防肾 病或者用于改善肾病症状， 优选其中肾病是由高血糖诱发的， 也优选其中肾病症状 是肾纤维化。
PCT/CN2012/001010 2011-06-01 2012-07-27 肾病和心脏病的治疗药物及其用途 WO2012163088A2 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201110146331.2 2011-06-01
CN201110146331.2A CN102293763B (zh) 2011-06-01 2011-06-01 肾病和心脏病的治疗药物及其用途

Publications (2)

Publication Number Publication Date
WO2012163088A2 true WO2012163088A2 (zh) 2012-12-06
WO2012163088A3 WO2012163088A3 (zh) 2013-01-24

Family

ID=45354601

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2012/001010 WO2012163088A2 (zh) 2011-06-01 2012-07-27 肾病和心脏病的治疗药物及其用途

Country Status (2)

Country Link
CN (1) CN102293763B (zh)
WO (1) WO2012163088A2 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021088495A1 (zh) * 2019-11-07 2021-05-14 温州医科大学 一种姜黄素衍生物的晶型i及其制备方法和应用

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102293763B (zh) * 2011-06-01 2014-10-29 温州医学院 肾病和心脏病的治疗药物及其用途
CN110664790A (zh) * 2019-07-10 2020-01-10 温州医科大学 一种2,6-二(2-(三氟甲基)苯亚甲基)环己酮在药物制备中的应用
CN115998687A (zh) * 2022-11-04 2023-04-25 温州医科大学 一种姜黄素衍生物的固体分散体及其制备和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102038666A (zh) * 2009-10-18 2011-05-04 温州医学院 治疗或预防代谢疾病的药物及其应用
CN102293763A (zh) * 2011-06-01 2011-12-28 温州医学院 肾病和心脏病的治疗药物及其用途

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102038666A (zh) * 2009-10-18 2011-05-04 温州医学院 治疗或预防代谢疾病的药物及其应用
CN102293763A (zh) * 2011-06-01 2011-12-28 温州医学院 肾病和心脏病的治疗药物及其用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GUANG LIANG ET AL.: 'Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents' BIOORGANIC & MEDICINAL CHEMISTRY vol. 17, 2009, page 2625 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021088495A1 (zh) * 2019-11-07 2021-05-14 温州医科大学 一种姜黄素衍生物的晶型i及其制备方法和应用

Also Published As

Publication number Publication date
WO2012163088A3 (zh) 2013-01-24
CN102293763A (zh) 2011-12-28
CN102293763B (zh) 2014-10-29

Similar Documents

Publication Publication Date Title
KR101868991B1 (ko) 피라졸 유도체 및 그 의약용도
PT2086535E (pt) Antagonista do receptor de angiotensina ii para o tratamento de doenças sistémicas em gatos
JPH0920659A (ja) 炎症性腹部疾患のためのカッパ−アヘン製剤作働薬
KR101516677B1 (ko) 지방성 간 질환의 치료용 의약 조성물
RU2729630C2 (ru) Терапевтическое средство для фиброза
WO2012163088A2 (zh) 肾病和心脏病的治疗药物及其用途
EP4009982A1 (en) Ganaxolone for use in treatment of status epilepticus
CN110664790A (zh) 一种2,6-二(2-(三氟甲基)苯亚甲基)环己酮在药物制备中的应用
BR112019026029A2 (pt) Formulações farmacêuticas orais de remogliflozina
KR20230143978A (ko) 시클로-히스프로를 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약제학적 제제
BR112020017056A2 (pt) Composição farmacêutica compreendendo remogliflozina e um agente antidiabético
ITMI20100260A1 (it) Composizione farmaceutica contenente un farmaco per ridurre gli effetti collaterali dei farmaci antipsicotici
JP6454436B1 (ja) ペマフィブラートを含有する医薬
IL298833A (en) Methods for treating or preventing chronic kidney disease
JPWO2017217071A1 (ja) セレノプロテインｐ活性阻害作用を有する成分を含有する、肺高血圧症の予防又は治療剤
CN116113408A (zh) 治疗慢性肾病的方法和药物组合物
WO2016092060A1 (en) Veterinary composition comprising torasemide for the treatment of pulmonary edema associated with heart failure in domestic animals
JP6294773B2 (ja) 口腔粘膜疾患の予防または治療用経口製剤
MX2008012867A (es) Uso de n-(dibenz(b,f)oxepin-10-ilmetil)-n-metil-n-prop-2-inilamina (omigapil) para la profilaxis y/o tratamiento de distrofia muscular o miopatia congenita resultado de la deficiencia de colageno vi.
CN108295067B (zh) 防治肾间质纤维化的化合物
BRPI0617184A2 (pt) formulação de pralnacasan com liberação retardada
JP2003500353A (ja) 処置方法
JP2017128545A (ja) 併用医薬
RU2690372C2 (ru) Лекарственные средства, содержащие диацереин, и способы снижения уровней мочевой кислоты в крови с его использованием
WO2013051330A1 (ja) ビダラビンによる心房細動治療

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: 12792006

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12792006

Country of ref document: EP

Kind code of ref document: A2