WO2016062286A1 - 脱克钙药物在用于制备治疗癌症的医药组合物中的用途 - Google Patents

脱克钙药物在用于制备治疗癌症的医药组合物中的用途 Download PDF

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WO2016062286A1
WO2016062286A1 PCT/CN2015/092776 CN2015092776W WO2016062286A1 WO 2016062286 A1 WO2016062286 A1 WO 2016062286A1 CN 2015092776 W CN2015092776 W CN 2015092776W WO 2016062286 A1 WO2016062286 A1 WO 2016062286A1
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cancer
10min
calcium
use according
cells
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PCT/CN2015/092776
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English (en)
French (fr)
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陈丘泓
庄秀美
魏宗德
萧乃文
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朗齐生物医学股份有限公司
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Priority to US15/521,504 priority Critical patent/US20170304228A1/en
Priority to CN201580057615.0A priority patent/CN107106523A/zh
Priority to EP15851742.5A priority patent/EP3235497A4/en
Publication of WO2016062286A1 publication Critical patent/WO2016062286A1/zh

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Definitions

  • the present invention is an application of a new indication for a calcium-removing drug, and in particular, the use of the calcium-removing drug has the effect of inhibiting various cancers.
  • Cancer has long been the leading cause of death worldwide, and the number of cancer patients has increased year by year. Therefore, treating cancer has become an important issue.
  • the treatment of cancer can be divided into surgical treatment, radiation therapy, chemotherapy and target treatment.
  • cancer drug treatment is intended to prevent cancer cells from replicating and dividing to block the spread and spread of tumors.
  • cancer drugs In the design of cancer drugs, they are also designed to target high-specific drug molecules or target antibodies. According to statistics, only about five out of every 10,000 new drugs can enter the first phase of clinical trials.
  • Calcium citrate (Cinacalcet HCl, Cinacalcet Hydrochloride or Parathyroid Hydrochloride) is a calcimimetic agent used to treat hypercalcemia caused by secondary parathyroidism in dialysis patients. Its principle of action is to increase the sensitivity of the calcium ion sensing receptor in the parathyroid gland, thereby reducing the secretion of parathyroid hormone and causing blood calcium to drop. low. Although both vitamin D and calcimimetic agents can inhibit parathyroid secretion, calcimimetic agents do not promote the absorption of calcium and phosphorus in the intestines, so they do not cause high blood calcium and high blood phosphorus. Wacker calcium is a drug that has long been approved by the FDA, with a large number of drug transfer and human research results.
  • the present invention aims at the development of new indications for the decalcification of calcium drugs, and achieves the goal of new use of old drugs.
  • the experimental design results show that the gram-free calcium drug has no or only minimal toxicity to normal cells, but whether the gram-free calcium has a selective effect between normal cells and tumor cells.
  • the present invention provides the use of a decalcified calcium drug for the preparation of a pharmaceutical composition for the treatment of cancer, wherein the pharmaceutical composition is selected from the group consisting of an effective amount of decalcified calcium and a pharmaceutically acceptable salt.
  • the cancer is one or more selected from the group consisting of a chest-related cancer, an abdominal cavity-related cancer, an endocrine-related cancer, and a digestive tract-related cancer.
  • the cancer is one or more selected from the group consisting of an osteosarcoma-related cancer, a skin cancer-related cancer, and a blood cancer-related cancer.
  • chest cavity related cancer refers to lung cancer
  • the abdominal cavity-related cancer is selected from the group consisting of bladder cancer or/and cervical cancer.
  • the endocrine-related cancer is one or more selected from the group consisting of prostate cancer, breast cancer, and ovarian cancer.
  • the endocrine-related cancer is one or more selected from the group consisting of gastric cancer, liver cancer, colon cancer, pancreatic cancer, and tongue cancer.
  • the effective dose concentration of the decalcified calcium drug is 20 to 500 mg/kg/day.
  • Fig. 1 shows the use of the drug of the present invention for inhibiting cancer cell analysis.
  • FIG. 1 shows the effect of decalcified calcium on tumor volume
  • Figure 3 shows the inhibitory effect of high-dose and low-dose calcium on tumor growth
  • Subculture of cell lines of different cancer types including cancerous lung cancer, gastric cancer, liver cancer, rectal cancer, skin cancer, cervical cancer, prostate cancer, bladder cancer, breast cancer, blood cancer, pancreatic cancer, ovarian cancer, tongue cancer Osteosarcoma, kidney cancer, and the control group also used normal cells of the kidney (HEK293 (Kidney)) and lung epithelial cells BEAS-2B (Lung Epithelial) for testing.
  • HEK293 Kidney
  • BEAS-2B Lung Epithelial
  • the cells corresponding to different species should be counted with the corresponding culture solution (Table 1), and the number of cells should be counted, and the number of cells should be 2 ⁇ 10 6 cells.
  • the culture medium to which the cell strain was cultured was added to a volume of 10 ml, and the culture was continued for 2-3 days. The cells were then counted and dispensed into 96-well plates where the number of cells per well was fixed at 3,000 and the volume was 100 ul.
  • the original culture solution in the 96-well plate was aspirated, and a commercially available drug having a concentration of 10 ⁇ m and a volume of 100 ul was added to each well. After 72 hours, 100 ul of diluted WST-1 reagent was added to each well, and the dilution ratio was the culture solution and The volume ratio of the WST-1 stock solution is 9:1. Finally, the total volume of each well plate is 200 ul. Then, the 96-well plate is placed at 37 ° C for 30-90 minutes, using an elisa reader (ELISA) on the OD450. The absorbance values were detected and the survival rate of each cancer cell line was calculated.
  • ELISA elisa reader
  • the analysis of the inhibitory effect of gram-free calcium on pleural cavity-related cancer cells was mainly tested on two kinds of lung cancer cells.
  • the cancer cell lines were A549 and H1650, respectively, and the cancer cells were treated 4 times each.
  • the experimental results were prepared, and the average values were calculated, and the results are listed below. (Table II)
  • the cancer cell lines were tested.
  • the prostate cancer cell lines were PC-3 and LNCap, respectively.
  • the breast cancer cell lines were MCF7 and MDA-MB-231, respectively (Table 7), ovarian cancer.
  • the cell lines were NIH-OVCAR-3 cell line and TOV-21G (Table 8), respectively, and the results of cancer cell inhibition experiments were performed 4 times each, and the average value was calculated, and the results are shown below.
  • Table VII gram-free calcium cytostatic test for breast cancer-related cancer
  • mice were tested for five kinds of gastrointestinal-related cancer cell lines.
  • the gastric cancer cell lines were AGS and MKN-45, respectively (Table 9), liver cancer cell lines. They were HepG2 and Hep3B, respectively (Table 10), the colorectal cancer cell lines were HCT116-wt and LoVo cell lines (Table 11), and the pancreatic cancer cell lines were AsPC and BxPC cell lines, respectively (Table 12).
  • the tongue cancer cell line is a SAS cell line (Table 13), and the cancer cell suppression is performed 4 times each. The experimental results, and the average value is calculated, and the results are listed as follows.
  • the osteosarctic cancer cell line is U2OS cell line (Table 10) 4)
  • the skin cancer cell lines were A375 and BCC, respectively (Table 15), and the results of cancer cell inhibition experiments were performed 3 to 4 times each, and the average value was calculated. The results are shown below.
  • the normal kidney cell line is HEK293 cell line (Table 16)
  • the normal lung epithelial cell line is BEAS-2B cell line (Table 17)
  • each done 4 times The cancer cells inhibited the experimental results and calculated their average values, and the results are listed below.
  • mice Female BALB/cAnN.Cg-Foxn1nu/CrlNarl mice were used as samples (purchased from National Laboratory Animal Center), weighing 21 ⁇ 1g, subcutaneously injected into gastric cancer cells (AGS) and randomly divided into cages.
  • the test drugs were divided into three groups: Normal control group, low dose (100 mg/kg/day), high dose (200 mg/kg/day).
  • the tumor formed more than 100 mm 3
  • the drug was administered by intraperitoneal injection every day; the tumor size was measured twice a week, and the tumor volume measurement formula was as follows: (L ⁇ W2); L represents the longest diameter of the tumor; W represents the shortest diameter of the tumor.
  • high and low doses of decalcified calcium can effectively slow the growth of tumor volume, and at the same time reduce the tumor volume, wherein high dose of gram calcium has a better effect.

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Abstract

一种脱克钙药物在用于制备治疗癌症的医药组合物中的用途，所述癌症是肺癌、膀胱癌、子宫颈癌、前列腺癌、乳癌、卵巢癌、胃癌、肝癌、大肠癌、胰脏癌、舌癌中的一种或多种。有效剂量浓度为每日20-500mg/Kg。

Description

脱克钙药物在用于制备治疗癌症的医药组合物中的用途 技术领域
本发明为脱克钙药物的新适应症的应用，尤其该脱克钙药物具有抑制多种癌症的用途。
背景技术
癌症长期高居全球死因之首，且罹患癌症人数更是逐年攀升，因此治疗癌症俨然成为重要的课题。癌症的治疗可区分为手术治疗、放射线治疗、化学治疗及标靶治疗。
一般来说，癌症药物治疗无论是化学治疗或标靶治疗，目的多是让癌细胞无法复制、分裂，来阻断肿瘤的蔓延扩张。
在癌症药物的设计上也是均朝向高专一性的药物分子开发或标靶型的抗体设计，根据统计，平均每一万个新药约只有五个能够进入第一期临床试验。
此外，除了药物本身是否能大量制造的难题外，还需克服药物安全性、病人筛选、试用剂量等问题，即便药物已经通过FDA的核准并上市，还是常遇到患者对于治疗药物的反应不佳。进一步，许多癌细胞相继产生抗药性，使药物的使用成效大幅降低，最终导致癌症治疗失败。由此可见药物开发具有一定的困难程度。
脱克钙(Cinacalcet HCl、盐酸西那卡塞或盐酸甲状旁腺激素)是一种拟钙剂，用于治疗洗肾病患的次发性副甲状腺亢进引起的血钙过高。其作用原理为增加副甲状腺中钙离子感应受器的敏感度，藉此降低副甲状腺素分泌，而使血钙降 低。虽然维生素D与拟钙剂都能抑制副甲状腺分泌，但拟钙剂不会促进肠道钙、磷的吸收，所以不会造成高血钙及高血磷。脱克钙是早已被FDA所认可的用药，具有大量药物机转及人体研究成果资料。
由于临床应用上的差异，因此从来没有人认为脱克钙具有抑制癌症细胞的可能性。
发明内容
为解决上述的问题，本发明针对脱克钙药物进行新适应症的研发，而达到老药新用的目标。
经过实验设计结果显示脱克钙药物对正常细胞没有或仅有微小的毒性，但至于脱克钙在正常细胞与肿瘤细胞之间是否具有选择性的影响。
本发明提供一种脱克钙药物在用于制备治疗癌症的医药组合物中用途，其中所述医药组合物是选自由有效剂量的脱克钙及药学上可接受的盐类所组成。
本发明一实施例中，其中所述癌症是选自由胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
本发明一实施例中，其中所述癌症是选自由骨肉瘤相关癌症、皮肤癌相关癌症、血癌相关癌症中的一种或多种。
本发明一实施例中，其中所述胸腔相关癌症是指肺癌。
本发明一实施例中，其中所述腹腔相关癌症是选自由膀胱癌或/和子宫颈癌。
本发明一实施例中，其中所述内分泌相关癌症是选自由前列腺癌、乳癌、卵巢癌中的一种或多种。
本发明一实施例中，其中所述内分泌相关癌症是选自由胃癌、肝癌、大肠癌、胰脏癌、舌癌中的一种或多种。
本发明一实施例中，其中所述脱克钙药物的有效剂量浓度为20～500mg/kg/天。
附图说明
图1显示本发明脱克钙用药应用于抑制癌细胞分析结果。
图2显示脱克钙用药可对肿瘤体积的效果
图3显示高剂量及低剂量脱克钙对肿瘤生长的抑制效果
具体实施方式
各种癌症细胞株建立
将不同癌症类型的细胞株进行继代培养，癌症细胞种类包含肺癌、胃癌、肝癌、直肠癌、皮肤癌、子宫颈癌、前列腺癌、膀胱癌、乳癌、血癌、胰腺癌、卵巢癌、舌癌、骨肉瘤、肾脏癌，并且对照组亦使用肾脏(HEK293(Kidney))、肺部上皮细胞BEAS-2B(Lung Epithelial)的正常细胞做测试。(表一)
先将各细胞于培养液培养后，由于各细胞的属性不同，因此针对不同种的细胞也要用相对应的培养液(表一)，计算细胞数目，回种2×106细胞数，然后加入培养该细胞株的培养液补至体积为10ml，继续培养2-3天。之后将细胞计数，并分装至96孔盘，其中每孔的细胞数目固定为3000颗，且体积为100ul。
表一、癌症测试细胞株及其培养所用的培养液
Figure PCTCN2015092776-appb-000001
Figure PCTCN2015092776-appb-000002
细胞存活分析方法
将96孔盘中原有的培养液吸掉，每孔加入浓度10um、体积100ul的市售药物，放置72小时后，每孔再加入100ul已稀释的WST-1试剂，该稀释比例为培养液与WST-1原液的体积比为9：1，最后每个孔盘的总体积为200ul，然后将96孔盘放置于37℃，30～90分钟，利用elisa reader(酶联免疫检测仪)于OD450侦测吸光值，并计算各癌症细胞株的存活率。
脱克钙药对于各种癌细胞分析结果
脱克钙对胸腔相关癌症细胞抑制效果的测试
本分析脱克钙对胸腔相关癌症细胞抑制效果的测试，主要针对两种肺癌细胞进行测试，癌细胞株分别为A549和H1650两个细胞株，各做4次的癌细胞抑 制实验结果，并且计算其平均值，结果表列如后。(表二)
表二、脱克钙对肺癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
A549 87.7 102.7 75.5 92.6 89.6
  1-10min 2-20min 3-20min 4-20min 平均
H1650 86.8 67.5 76.8 75.2 76.5
脱克钙对腹腔相关癌症细胞抑制效果的测试
本分析脱克钙对腹腔相关癌症细胞抑制效果的测试，主要针对两种腹腔相关癌症种类细胞进行测试，膀胱癌细胞株分别为TSGH和T24两个细胞株(表三)，子宫颈癌细胞株分别为HeLa细胞株(表四)，肾脏癌为786-O细胞株(表五)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表三、脱克钙对膀胱癌相关癌症细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
TSGH 57.3 73.2 74.7 33.9 59.8
  T24-1-30min T24-2-20min T24-3-20min T24-4-20min 平均
T24 71.1 132.6 177.1 103.3 121.0
表四、脱克钙对子宫颈癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
HeLa 109.6 118.6 104.1 113.0 111.3
C-334 114.5 118.8 108.1 100.0 110.3
表五、脱克钙对肾脏癌相关癌症细胞抑制测试
  0524-10min 0526-10min 0529-10min 0531-10min 平均
786-O 81.3 71.6 80.2 87.1 80.0
脱克钙对内分泌相关癌症细胞抑制效果的测试
本分析脱克钙对腹腔相关癌症细胞抑制效果的测试，主要针对三种内分泌相 关癌症种类细胞进行测试，前列腺癌细胞株分别为PC-3和LNCap两个细胞株(表六)，乳癌细胞株分别为MCF7和MDA-MB-231两个细胞株(表七)，卵巢癌细胞株分别为NIH-OVCAR-3细胞株和TOV-21G(表八)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表六、脱克钙对前列腺癌相关癌症细胞抑制测试
Figure PCTCN2015092776-appb-000003
表七、脱克钙对乳癌相关癌症细胞抑制测试
  0612-10min 0614-10min 0616-10min 0619-10min 平均
MCF7 87.7 75.6 82.2 77.2 80.7
  0612-10min 0614-10min 0616-10min 0619-10min 平均
MDA-MB-231 92.35 84.94 60.81 92.75 82.71
表八、脱克钙对卵巢癌相关癌症细胞抑制测试
  7-3-30min 7-4-30min 7-7-30min -4-30min 平均
NIH-OVCAR-3 90.7 111.1 100.2 111.0 103.3
  7-3-30min 7-4-30min 7-7-30min -4-30min 平均
TOV-21G 128.7 109.4 104.1 108.2 112.6
脱克钙对消化道相关癌症细胞抑制效果的测试
分析脱克钙对消化道相关癌症细胞抑制效果的测试，主要针对五种消化道相关癌症种类细胞进行测试，胃癌细胞株分别为AGS和MKN-45两个细胞株(表九)，肝癌细胞株分别为HepG2和Hep3B两个细胞株(表十)，大肠癌细胞株分别为HCT116-wt和LoVo细胞株(表十一)，胰脏癌细胞株分别为AsPC和BxPC细胞株(表十二)，舌癌细胞株为SAS细胞株(表十三)，各做4次的癌细胞抑制 实验结果，并且计算其平均值，结果表列如后。
表九、脱克钙对胃癌相关癌症细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
AGS 26.6 20.0 52.3 14.50856943 28.3
  0510-10min 0512-10min 0515-10min 0517-10min 平均
MKN-45 82.1 101.5 103.6 69.1 89.1
表十、脱克钙对肝癌相关癌症细胞抑制测试
  0524-20min 0526-20min 0529-20min 0531-20min 平均
HepG2 105.7 132.6 116.5 89.5 111.1
  0612-20min 0614-20min 0616-20min 0619-20min 平均
Hep3B 143.2 125.1 151.5 116.8 134.1
表十一、脱克钙对大肠癌相关癌症细胞抑制测试
  0602-30min 0605-10min 0607-10min 0609-10min 平均
HCT116-wt 89.0 107.3 132.5 112.6 110.3
  0616-10min 0619-10min 0621-10min 0623-10min 平均
LoVo 73.9 125.0 90.4 84.2 93.4
表十二、脱克钙对胰脏癌相关癌症细胞抑制测试
  1-7-3-30min 1-7-4-30min 1-7-7-30min 1-4-30min 平均
AsPC 61.6 81.7 60.4 71.9 68.9
  3-7-3-30min 3-7-4-30min 3-7-7-30min 3-4-30min 平均
BxPC 64.6 78.8 100.1 76.2 79.9
表十三、脱克钙对舌癌相关癌症细胞抑制测试
  6-26-10min 6-28-10min 6-30-10min 7-3-10min 平均
SAS 45.7 88.9 96.2 98.9 82.4
脱克钙对其他癌症细胞抑制效果的测试
分析脱克钙对其他类型癌正进行测试，骨肉癌细胞株为U2OS细胞株(表十 四)，皮肤癌细胞株分别为A375和BCC两个细胞株(表十五)，各做3～4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表十四、脱克钙对骨肉瘤相关癌症细胞抑制测试
  6-26-10min 6-28-10min 6-30-10min 7-3-10min 平均
U2OS 82.6 86.7 64.9 75.3 77.4
表十五、脱克钙对皮肤癌相关癌症细胞抑制测试
Figure PCTCN2015092776-appb-000004
对照组实验设计
脱克钙对正常细胞抑制效果的测试
分析脱克钙对多种正常细胞进行测试，正常肾脏细胞株为HEK293细胞株(表十六)，正常肺部上皮细胞细胞株为BEAS-2B细胞株(表十七)，各做4次的癌细胞抑制实验结果，并且计算其平均值，结果表列如后。
表十六、脱克钙对正常肾脏细胞抑制测试
  平均
HEK293 114.1
表十七、脱克钙对正常肺部上皮细胞抑制测试
  0510-10min 0512-10min 0515-10min 0517-10min 平均
BEAS-2B 70.5 72.9 72.2 89.0 76.1
针对脱克钙对各种癌症细胞抑制效果汇整于表十八中，清楚看出脱克钙对于多项癌症有明显的抑制效果。经过发明人实验结果，脱克钙药物对于不同的癌 症细胞有明显的抑制效果。(图一)
表十八、脱克钙对各种癌症细胞抑制效果的汇整
癌症细胞 抑制效果
肺癌 83.09384194
膀胱癌 90.4
子宫颈癌 111.32
前列腺癌 87.53
乳癌 81.70
卵巢癌 107.9
胃癌 58.7
肝癌 122.60
大肠癌 101.85
胰脏癌 74.4
舌癌 82.44
骨肉癌 77.37
皮肤癌 107.32
肾脏癌 80.0
肾脏 114.06
肺部上皮细胞 76.13
动物实验分析
本实验使用雌性BALB/cAnN.Cg-Foxn1nu/CrlNarl小鼠为样本(购自国家实验动物中心)，体重为21±1g，皮下注射胃癌细胞(AGS)后随机分笼，测试药物分成三组:正常对照组、低剂量(100mg/kg/day)、高剂量(200mg/kg/day)。肿瘤形成超过100mm3后，每天采取腹腔注射方式给予药物；每周测量肿瘤大小两次，肿瘤体积测量公式如下：(L×W2)；L代表肿瘤最长直径；W代表肿瘤最短直径。
Figure PCTCN2015092776-appb-000005
Figure PCTCN2015092776-appb-000006
依据第2图的结果，低剂量与高剂量的脱克钙平均对肿瘤具有良好的抑制效果，且于实验过程中各组小鼠的重量均未出现明显降低的现象，因此表示脱克钙不论高低剂量在治疗过程均能使受测小鼠具有良好的健康状态而不死亡。
依据第3图的结果，高低剂量的脱克钙可有效减缓肿瘤体积增长，并可同时减少肿瘤体积，其中以高剂量的脱克钙具有较佳的效果。
上列详细说明是针对本发明之一可行实施例的具体说明，惟该实施例并非用以限制本发明的专利范围，凡未脱离本发明技艺精神所为的等效实施或变更，均应包含于本发明的专利范围中。

Claims (8)

  1. 一种脱克钙药物在用于制备治疗癌症的医药组合物中的用途，其特征是，所述医药组合物是选自由有效剂量的脱克钙及药学上可接受的盐类所组成。
  2. 如权利要求1所述的用途，其特征是，所述癌症为胸腔相关癌症、腹腔相关癌症、内分泌相关癌症、消化道相关癌症中的一种或多种。
  3. 如权利要求1所述的用途，其特征是，所述癌症是选自骨肉瘤相关癌症、皮肤癌相关癌症、血癌相关癌症中的一种或多种。
  4. 如权利要求2所述的用途，其特征是，所述胸腔相关癌症是指肺癌。
  5. 如权利要求2所述的用途，其特征是，所述腹腔相关癌症是选自膀胱癌或/和子宫颈癌。
  6. 如权利要求2所述的用途，其特征是，所述内分泌相关癌症系选自由前列腺癌、乳癌、卵巢癌中的一种或多种。
  7. 如权利要求2所述的用途，其特征是，所述消化道相关癌症系选自由胃癌、肝癌、大肠癌、胰脏癌、舌癌中的一种或多种。
  8. 如权利要求1所述的用途，其特征是，所述有效剂量浓度为20～500mg/kg/天。
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PCT/CN2015/092777 WO2016062287A1 (zh) 2014-10-24 2015-10-23 山喜多药物在用于制备抑制癌症的医药组合物中的用途
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Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUE049976T2 (hu) 2005-12-28 2020-11-30 Vertex Pharma N-[2,4-bisz(1,1-dimetil-etil)-5-hidroxi-fenil]-1,4-dihidro-4-oxo-kinolin-3-karboxamid amorf alakjának gyógyászati kompozíciói
WO2016062278A1 (zh) * 2014-10-24 2016-04-28 朗齐生物医学股份有限公司 内分泌疾病用药在制备抑制癌症的医药组合物中的应用
EP3236967B1 (en) 2014-12-22 2019-10-16 SUDA Pharmaceuticals Ltd Prevention and treatment of metastatic disease in thrombocytotic cancer patients
WO2017116049A1 (ko) * 2015-12-31 2017-07-06 경북대학교 산학협력단 설폰아마이드계 화합물을 유효성분으로 포함하는 암의 치료 및 전이 억제용 약학적 조성물
EP3241562A1 (en) * 2016-05-02 2017-11-08 Fundació Institut Mar d'Investigacio Medica Zonisamide for use in the treatment of breast cancer
CN106074474A (zh) * 2016-06-15 2016-11-09 中南大学湘雅医院 羟苄丝肼及其在药学上可接受的盐在制备抗肿瘤药物方面的应用
WO2018072135A1 (zh) * 2016-10-19 2018-04-26 微菌方舟生物科技股份有限公司 二氢吡啶类钙拮抗剂用于治疗癌症的用途
CN108066345A (zh) * 2016-11-14 2018-05-25 武汉华杰世纪生物医药有限公司 一种具有抗肿瘤作用的化合物
CN115813888A (zh) 2016-12-20 2023-03-21 罗曼治疗系统股份公司 包含阿塞那平的透皮治疗系统
EP3558276A1 (en) 2016-12-20 2019-10-30 LTS Lohmann Therapie-Systeme AG Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene
WO2018227129A1 (en) * 2017-06-09 2018-12-13 Regents Of The University Of Minnesota Skin care formulations and skin cancer treatment
JP2020525545A (ja) 2017-06-26 2020-08-27 エルテーエス ローマン テラピー−ジステーメ アーゲー アセナピンおよびシリコーンアクリルハイブリッドポリマーを含有する経皮治療システム
EP3648764A4 (en) * 2017-07-03 2021-03-31 Menri Group Ltd. TREATMENT OF CANCER WITH DIHYDROPYRIDINES
JP2019064976A (ja) * 2017-10-03 2019-04-25 国立大学法人 熊本大学 抗がん剤
KR101933805B1 (ko) 2017-10-17 2018-12-28 성균관대학교산학협력단 옥셀라딘시트레이트를 유효성분으로 포함하는 뇌암 예방 또는 치료용 약학적 조성물
CN108186652A (zh) * 2017-12-28 2018-06-22 深圳大学 缝隙连接细胞间通迅抑制剂甘珀酸在制备预防和治疗肝细胞癌药物中的应用
US11911351B2 (en) 2018-01-30 2024-02-27 Apnimed, Inc. (Delaware) Methods for treating sleep apnea with combinations of atomoxetine and (R)-oxybutynin
US11931366B2 (en) * 2018-04-19 2024-03-19 Washington University Compositions and methods of use thereof for treatment of proteinopathies
MX2020014286A (es) 2018-06-20 2021-03-25 Lts Lohmann Therapie Systeme Ag Sistema terapeutico transdermico que contiene asenapina.
FR3090084B1 (fr) 2018-12-18 2023-10-13 Securengy Projectile pour armes à feu ou air comprimé pour emport liquide ou pulvérulent.
WO2020132253A1 (en) * 2018-12-19 2020-06-25 University Of Vermont And State Agricultural College Cancer therapeutic compositions and methods
US20220193020A1 (en) * 2019-04-04 2022-06-23 Daegu-Gyeongbuk Medical Innovation Foundation Pharmaceutical Composition Comprising Trimebutine or Pharmaceutically Acceptable Salt Thereof as an Active Ingredient For Prevention or Treatment of Cancer
US20220202771A1 (en) * 2019-04-05 2022-06-30 University Of North Texas Health Science Center At Fort Worth Antidepressants for the Treatment or Prevention of Memory Loss and/or Cognitive Decline or Dysfunction in Aging
CA3136353A1 (en) * 2019-04-11 2020-10-15 Ian Basil Shine Cell membrane permeability restoring therapy
CN110179803A (zh) * 2019-05-31 2019-08-30 天津科技大学 一种噻吨溴类化合物的应用
CN110742890A (zh) * 2019-10-24 2020-02-04 暨南大学 洛美利嗪在制备抗结肠癌药物中的应用
CN110876800B (zh) * 2019-11-18 2023-06-27 中南大学 米卡芬净在制备抗肿瘤药物中的应用及抗肿瘤药物
CN110840887A (zh) * 2019-11-18 2020-02-28 杭州彗搏科技有限公司 三氯苯达唑在制备治疗乳腺癌的药物中的应用
CN111067899B (zh) * 2020-01-08 2021-03-05 温州医科大学 一种抗疟药物磷酸伯氨喹在制备治疗白血病药物上的应用
US11304969B2 (en) * 2020-01-24 2022-04-19 The Florida International Univeristy Board Of Trustees Treatments of prostate cancer
CN111973593A (zh) * 2020-05-09 2020-11-24 深圳市罗湖区人民医院 硝唑尼特及其药学上可接受的盐在制备治疗膀胱癌药物中的用途
CN111557941A (zh) * 2020-06-15 2020-08-21 浙江大学 Plod2的小分子抑制剂米诺地尔在肿瘤治疗中的应用
CN111848717A (zh) * 2020-08-07 2020-10-30 四川大学 靶向调控线粒体能量代谢的化合物及其应用和药物
WO2022033459A1 (zh) * 2020-08-10 2022-02-17 萧乃文 双非癌药物用于制备治疗癌症的医药组合物的用途
CN112274525B (zh) * 2020-12-04 2022-04-08 遵义医科大学 一种化疗药物组合物及其应用
CN112336725A (zh) * 2020-12-11 2021-02-09 吴照球 甲氧苄啶的医药新用途
CN112569342A (zh) * 2020-12-21 2021-03-30 中南大学 卡泊芬净和/或其可药用盐在制备抗肿瘤药物中的应用及抗肿瘤药物
CN112569215A (zh) * 2020-12-30 2021-03-30 东莞市人民医院 度米芬在制备防治结直肠癌的药物中的应用
EP4108244A1 (en) * 2021-06-25 2022-12-28 Universität Regensburg Ss-lactam antibiotic with significant activity against cancer e.g. colon malignancies
CN113663071B (zh) * 2021-06-28 2022-12-30 四川大学 Fbxl2激活剂在制备治疗egfr驱动的肺癌的药物中的用途
WO2023006954A1 (en) 2021-07-30 2023-02-02 Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) Asenapine for use in cancer
CN117642164A (zh) * 2021-09-09 2024-03-01 中国福利会国际和平妇幼保健院 五氟利多在制备治疗子宫内膜癌的药物中的应用
CN115887455B (zh) * 2022-08-04 2024-04-05 北京大学人民医院 钙离子通道阻滞剂阿折地平在制备治疗子宫内膜癌的药物中的应用
CN115778957B (zh) * 2022-11-04 2024-06-21 天津中医药大学 千金藤素及包含其的组合物用于预防或治疗酒精性肝病的应用
CN116570579A (zh) * 2023-06-13 2023-08-11 深圳市泛谷药业股份有限公司 一种含有阿戈美拉汀和氟伏沙明的药物组合物及其应用
CN118059099B (zh) * 2024-04-19 2024-06-14 四川大学华西医院 帕罗西汀联合asct2抑制剂用于制备治疗肝癌的药物中的应用及药物组合物

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007112280A1 (en) * 2006-03-23 2007-10-04 Amgen Inc. Methods and compositions for making and using polymorphs of cinacalcet
WO2009002427A2 (en) * 2007-06-21 2008-12-31 Amgen Inc. Methods of synthesizing cinacalcet and salts thereof
US20110287065A1 (en) * 2010-05-19 2011-11-24 Elan Pharma International Limited Nanoparticulate cinacalcet compositions
WO2013071262A1 (en) * 2011-11-10 2013-05-16 Kai Pharmaceuticals, Inc. Calcimimetics and methods for their use

Family Cites Families (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3844491B2 (ja) * 1993-10-01 2006-11-15 シンテックス（ユー・エス・エイ）インコーポレイテッド ミコフェノール酸モフェチル高用量経口用懸濁剤
CN1167418C (zh) * 1994-12-28 2004-09-22 詹森药业有限公司 奈必洛尔作为抗动脉粥样化剂的用途
SI1113797T1 (sl) * 1998-09-15 2010-02-26 Lilly Co Eli Uporaba duloksetina pri zdravljenju fibromialgije
US6927223B1 (en) * 2000-05-26 2005-08-09 Washington State University Research Foundation Use of serotonin agents for adjunct therapy in the treatment of cancer
ATE544745T1 (de) * 2000-07-07 2012-02-15 Tufts College 9-substituierte minocyclinverbindungen
IL139975A0 (en) * 2000-11-29 2002-02-10 Univ Ramot Anti proliferative drugs
US20040072824A1 (en) * 2001-06-01 2004-04-15 Adam Telerman Methods and compositions for the treatment of cancer
GB0202337D0 (en) * 2002-02-01 2002-03-20 Univ Birmingham Cancer treatment
US7135575B2 (en) * 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
JP2007505914A (ja) * 2003-09-18 2007-03-15 コンビナトアールエックス インコーポレーティッド 新生物の治療のための薬物の併用方法
ZA200603718B (en) * 2003-11-06 2007-09-26 Celgene Corp Methods and compositions using thalidomide for the treatment and management of cancers and other diseases
EP1753425A4 (en) * 2004-05-12 2009-08-05 Biorunx Co Ltd THERAPEUTIC AGENT COMPRISING A NICOTINIC ACID OR DERIVATIVES AS AN EFFECTIVE INGREDIENT FOR THE PREVENTION OR TREATMENT OF CANCER
AU2005244988C1 (en) * 2004-05-21 2012-06-28 President And Fellows Of Harvard College Synthesis of tetracyclines and analogues thereof
CN1279980C (zh) * 2004-10-14 2006-10-18 孔庆忠 一种抗实体肿瘤药物组合物
JP2006298781A (ja) * 2005-04-15 2006-11-02 Geno Membrane:Kk エストロン３硫酸トランスポーター活性阻害剤
TW200716141A (en) * 2005-05-05 2007-05-01 Combinatorx Inc Compositions and methods for treatment for neoplasms
CN101223149A (zh) * 2005-07-05 2008-07-16 特瓦制药工业有限公司 制备缬沙坦的方法
AU2005334836B2 (en) * 2005-07-28 2012-04-12 Academisch Ziekenhuis Leiden H.O.D.N. Lumc Sensitization of immune system against haptenized melanoma antigens
US8148356B2 (en) * 2005-08-24 2012-04-03 Cumberland Pharmaceuticals, Inc. Acetylcysteine composition and uses therefor
CN101099724A (zh) * 2006-07-07 2008-01-09 上海复旦复华药业有限公司 一种微粉化来曲唑及其组合物
CN101103976A (zh) * 2006-07-14 2008-01-16 海南盛科生命科学研究院 一种含阿那曲唑的口服药物组合物及其制备工艺
US20100273868A1 (en) * 2007-01-05 2010-10-28 Cornerstone Therapeutics Inc. R-Zileuton for Use in Conditions Associated with Increased 5-Lipoxygenase and/or Leukotriene Activity (EG Asthma)
CN101730526A (zh) * 2007-03-07 2010-06-09 阿布拉科斯生物科学有限公司 作为抗癌剂的包含雷帕霉素和白蛋白的纳米颗粒
WO2009025854A1 (en) * 2007-08-22 2009-02-26 Burnham Institute For Medical Research Smips: small molecule inhibitors of p27 depletion in cancers and other proliferative diseases
US20120082659A1 (en) * 2007-10-02 2012-04-05 Hartmut Land Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations
CN100563645C (zh) * 2007-12-06 2009-12-02 济南帅华医药科技有限公司 一种治疗实体肿瘤的蓓萨罗丁缓释植入剂
US20090270397A1 (en) * 2008-04-08 2009-10-29 Orlow Seth J Methods and compositions for the treatment of cancers, such as melanomas and gliomas
CN101569624A (zh) * 2008-04-29 2009-11-04 石药集团中奇制药技术（石家庄）有限公司 氨氯地平在制备治疗细胞增生性疾病药物中的用途
EP2123626A1 (en) * 2008-05-21 2009-11-25 Laboratorios del Dr. Esteve S.A. Co-crystals of duloxetine and co-crystal formers for the treatment of pain
WO2009147169A1 (en) * 2008-06-03 2009-12-10 Universite Paris Diderot-Paris 7 Pharmaceuticl compositions useful for the treatment of cancers, in particular acute myeloid leukemia and acute promyelocytic leukemia
CN101612400A (zh) * 2009-07-22 2009-12-30 陈志龙 血管紧张素ⅱ的1型受体拮抗剂在抗肿瘤中的应用
CN101690816A (zh) * 2009-08-16 2010-04-07 王丽燕 含钙拮抗剂、aⅱ受体拮抗剂和他汀类药的药物组合物
CN101991553B (zh) * 2009-08-21 2015-02-25 北京以岭生物工程技术有限公司 一种依西美坦片及其制备方法
CN101863806B (zh) * 2010-03-18 2013-02-13 湖北省医药工业研究院有限公司 抗前列腺癌药物(r)-比卡鲁胺的制备方法
WO2012015023A1 (ja) * 2010-07-29 2012-02-02 国立大学法人京都大学 抗がん剤のスクリーニング方法
US20130261142A1 (en) * 2010-12-15 2013-10-03 Hung-Cheng Lai Compounds used for treating cancer and the use thereof
CN102631354B (zh) * 2011-02-11 2015-01-21 广东泰禾医药科技有限公司 含维生素d3和二甲双胍的药物组合物
CN102688493B (zh) * 2011-03-25 2014-09-10 鼎泓国际投资（香港）有限公司 含有白藜芦醇及白藜芦醇类衍生物和Bc1-2抑制剂的药物组合物及其应用
CN102813643B (zh) * 2011-06-10 2014-09-24 北京蛋白质组研究中心 bumetanide在抑制肝癌细胞转移中的应用
US9757424B2 (en) * 2011-09-27 2017-09-12 Biomed Valley Discoveries, Inc. Compositions and methods of treating gliomas
CN102600077B (zh) * 2012-03-29 2013-06-05 江苏豪森药业股份有限公司 吉西他滨或其盐纳米乳剂注射液及其制备方法
ES2384069B1 (es) * 2012-03-29 2013-07-04 Hospital Sant Joan De Déu Cinacalcet y tumores neuroblásticos
CN103536607A (zh) * 2012-07-10 2014-01-29 邵金辉 土霉素，普罗帕酮和安乃近的抗肿瘤作用
WO2014018563A2 (en) * 2012-07-23 2014-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods for the treatment of cancer
WO2014036654A1 (en) * 2012-09-06 2014-03-13 Mcmaster University Compounds and methods for selectively targeting cancer stem cells
AU2013318338B2 (en) * 2012-09-21 2017-05-25 Intensity Therapeutics, Inc Method of treating cancer
AU2013326463B2 (en) * 2012-10-04 2018-01-18 Ab Science Use of masitinib for treatment of cancer in patient subpopulations identified using predictor factors
CN102872066B (zh) * 2012-10-19 2014-07-02 厦门大学 伊维菌素及其衍生物的用途
US9622982B2 (en) * 2013-01-14 2017-04-18 Health Clinics Limited Cancer drug and uses
CN103933569B (zh) * 2013-01-22 2017-01-11 复旦大学 一种抗肺癌药物组合物及其应用、药盒和包装件
WO2014164704A2 (en) * 2013-03-11 2014-10-09 The Broad Institute, Inc. Compounds and compositions for the treatment of cancer
US20140271727A1 (en) * 2013-03-18 2014-09-18 National Yang-Ming University Method of using an antidepressant for increasing immunity of a subject and treating cancer
CN104161759B (zh) * 2013-05-16 2019-10-08 中国科学院上海药物研究所 阿那格雷及其衍生物的抗肿瘤用途
CN103396419A (zh) * 2013-08-13 2013-11-20 海宁市绿升医药科技有限公司 肿瘤光动力治疗药二氢卟吩e6-15-乙酯及其制备方法
CN103536925B (zh) * 2013-10-28 2015-07-01 中国医学科学院基础医学研究所 强心苷化合物在非小细胞肺癌治疗中的应用
CN103622975B (zh) * 2013-11-07 2016-06-15 广东药学院 格列吡嗪在制备治疗肿瘤药物中的应用
CN106572988B (zh) * 2014-04-08 2022-04-08 卫理公会医院 Inos抑制性组合物及其作为乳腺癌治疗剂的用途
WO2016062278A1 (zh) * 2014-10-24 2016-04-28 朗齐生物医学股份有限公司 内分泌疾病用药在制备抑制癌症的医药组合物中的应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007112280A1 (en) * 2006-03-23 2007-10-04 Amgen Inc. Methods and compositions for making and using polymorphs of cinacalcet
WO2009002427A2 (en) * 2007-06-21 2008-12-31 Amgen Inc. Methods of synthesizing cinacalcet and salts thereof
US20110287065A1 (en) * 2010-05-19 2011-11-24 Elan Pharma International Limited Nanoparticulate cinacalcet compositions
WO2013071262A1 (en) * 2011-11-10 2013-05-16 Kai Pharmaceuticals, Inc. Calcimimetics and methods for their use

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LI, HUAIFU ET AL.: "The calcimimetic R-568 induces apoptotic cell death in prostate cancer cells", JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 14 July 2009 (2009-07-14), pages 1, XP021060871, DOI: doi:10.1186/1756-9966-28-100 *
See also references of EP3235497A4 *

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