WO2017028441A1 - 右旋龙脑作为抗肿瘤药物增敏剂的应用 - Google Patents
右旋龙脑作为抗肿瘤药物增敏剂的应用 Download PDFInfo
- Publication number
- WO2017028441A1 WO2017028441A1 PCT/CN2015/098535 CN2015098535W WO2017028441A1 WO 2017028441 A1 WO2017028441 A1 WO 2017028441A1 CN 2015098535 W CN2015098535 W CN 2015098535W WO 2017028441 A1 WO2017028441 A1 WO 2017028441A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cells
- cur
- drug
- curcumin
- tumor
- Prior art date
Links
Images
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Definitions
- the invention relates to the use of right-handed borneol, in particular to the application of right-handed borneol as an anti-tumor drug sensitizer.
- cancer is mainly based on surgical resection. Because cancer cells are prone to metastasis, surgery cannot be cured, often supplemented by radiotherapy and chemotherapy. Although radiotherapy is more effective than chemotherapy, it also brings a lot of side effects to patients. Therefore, chemical therapy (chemotherapy) is the main means to alleviate the suffering of patients.
- anti-tumor drugs such as doxorubicin, daunorubicin, cisplatin, 5-fluorouracil, and paclitaxel have been used in clinical practice, bringing good news to patients.
- chemotherapy also inevitably produces many toxic side effects.
- Anti-tumor drugs such as doxorubicin and daunorubicin can cause certain toxic side effects to the heart, which can cause sudden tachycardia and acute. Heart failure, difficulty breathing, etc.
- Paclitaxel can cause allergic reactions after application to the human body, and symptoms such as hypotension, urticaria, and respiratory distress appear. Therefore, how to maximize the anti-tumor effect of drugs and reduce their side effects has always been a hot issue. To this end, it is particularly important to seek a class of chemical sensitizers that not only improve the sensitivity of tumor cells against anti-tumor drugs, but also significantly improve the anti-tumor effect of anti-tumor drugs in therapy.
- Right-handed borneol is a natural compound extracted from the branches and leaves of the chemical-type plum-blossom of the genus Fructus sinensis. Its chemical structure is as follows:
- the primary object of the present invention is to overcome the shortcomings and deficiencies of the prior art and to provide the use of dextro-dragon as an anti-tumor drug sensitizer.
- Another object of the present invention is to provide an antitumor drug sensitizer.
- the application of the right-handed borneol as an anti-tumor drug sensitizer is to apply the right-handed borneol as an anti-tumor drug sensitizer auxiliary anti-tumor drug.
- the right-handed dinosaur is the natural right-handed borneol.
- the antitumor drug is preferably an antitumor chemical.
- the anti-tumor chemical drugs include: daunorubicin, doxorubicin, demethoxydaunorubicin, epirubicin, paclitaxel, lentinan, vinblastine, vincristine, tamoxifen, formestane, Anastrozole, flutamide, 5-fluorouracil, methotrexate, cisplatin, carboplatin, oxaliplatin, carmustine, toremifene, tegafur, curcumin, demethoxycurcum Ordinary, bis-demethoxycurcumin, thiotepa, etc.; preferably one or at least two of curcumin, demethoxycurcumin and bisdemethoxycurcumin.
- the tumor mainly refers to non-resistant tumors such as liver cancer, lung cancer, malignant melanoma, breast cancer, colon cancer, nasal cancer, bladder cancer, cervical cancer, gastric cancer, esophageal cancer and prostate cancer.
- An anti-tumor drug sensitizer is prepared based on the application of D-Dragon brain as an anti-tumor drug sensitizer, which consists of a dextro-borne brain and a drug-allowed excipient or carrier.
- An anti-tumor drug consisting of a tumor drug sensitizer and an anti-tumor drug, namely, a right-handed borneol, an excipient or a carrier, and an anti-tumor drug.
- the antitumor drug is preferably an antitumor chemical.
- the anti-tumor chemical drugs include: daunorubicin, doxorubicin, demethoxydaunorubicin, epirubicin, paclitaxel, lentinan, vinblastine, vincristine, tamoxifen, formestane, Anastrozole, flutamide, 5-fluorouracil, methotrexate, cisplatin, carboplatin, oxaliplatin, carmustine, toremifene, tegafur, curcumin, demethoxycurcum Ordinary, bis-demethoxycurcumin, thiotepa, etc.; preferably one or at least two of paclitaxel, curcumin, demethoxycurcumin and bisdemethoxycurcumin.
- the tumor mainly refers to a non-resistant tumor, that is, a cancer such as liver cancer, lung cancer, malignant melanoma, breast cancer, colon cancer, nasal cancer, bladder cancer, cervical cancer, gastric cancer, esophageal cancer, and prostate cancer.
- a cancer such as liver cancer, lung cancer, malignant melanoma, breast cancer, colon cancer, nasal cancer, bladder cancer, cervical cancer, gastric cancer, esophageal cancer, and prostate cancer.
- the anti-tumor drug preferably consists of dextro-borne brain, an excipient or carrier, and curcumin; it can be used to treat melanoma.
- the curcumin and the right-handed borneol are matched by a mass ratio of 73674 to 294696:400,000; preferably, the ratio is 73,740:400,000 by mass ratio.
- the antitumor drug preferably consists of a dextro-borne brain, an excipient or carrier, and a curcuminoid compound; it is useful for treating liver cancer.
- the curcumin compound is at least one of curcumin, demethoxycurcumin, and bisdemethoxycurcumin.
- the dextro-borne brain and the curcumin compound are in a molar ratio of 2 to 8 ⁇ g: 2 to 8 nmol.
- the right-handed borneol and the curcumin are in a molar ratio of 1 ⁇ g: 1 nmol; the right-handed borneol and the demethoxycurcumin are in a molar ratio of 1 ⁇ g: 2 nmol.
- the present invention has found a new application of dextro-dragon as an anti-tumor chemical sensitizer.
- Right-handed borneol has low toxicity to normal human cells and has no obvious influence. It is a potential high-efficiency and low-toxic chemical sensitizer.
- Figure 1 is a graph showing the results of detection of malignant melanoma A375 cells treated with curcumin and curcumin + dextro-dragon.
- Figure 2 is a graph showing the results of breast cancer cell MCF-7 cells treated with curcumin and curcumin + dextrorone.
- Figure 3 is a graph showing the effect of different treatment groups on intracellular curcumin content
- control group indicated that no NB or Cur treatment was added
- the NB group indicated that 40 ⁇ g/ml NB was added
- the Cur group indicated that 20 ⁇ M Cur was added
- the NB+Cur group indicated that 40 ⁇ g/ml NB was added for 12 hours and then 20 ⁇ M of MCur was added.
- Figure 4 is a graph showing the results of changes in SubG-1 content in A375 cells induced by different treatment groups
- Figure 5 is a graph showing the results of detection of Caspase 3/8/9 in A375 cells by different treatment groups
- control group indicated that no NB or Cur treatment was added
- NB group indicated that 40 ⁇ g/ml NB was added.
- the Cur group indicates that 20 ⁇ M Cur treatment was added
- the NB+Cur group indicated that 40 ⁇ g/ml NB was added first for 12 hours and then 20 ⁇ M Cur treatment was added.
- Figure 6 is a graph showing the results of detection of ROS content in A375 cells induced by different treatment groups
- the control group indicated that no NB or Cur treatment was added, the NB group indicated that 40 ⁇ g/ml NB was added, the Cur group indicated that 20 ⁇ M Cur was added, and the NB+Cur group indicated that 40 ⁇ g/ml NB was added for 12 hours and then 20 ⁇ M Cur was added.
- Figure 7 is a graph showing the effect of different treatments of dextro-dragon and curcumin on the survival rate of HepG2 cells; different letters indicate statistically significant differences (P ⁇ 0.05), and the same letters indicate statistically no significant differences. .
- Figure 8 is a graph showing the effect of different treatments of dextro-dragon and curcumin on the cell cycle of HepG2.
- Fig. 9 is a graph showing the effect of different treatments of dextro-dragon and curcumin on ROS changes in HepG2 cells.
- Figure 10 is a graph showing the effect of different treatments of dextrorone and demethoxycurcumin on the survival rate of HepG2 cells; different letters indicate statistically significant differences (P ⁇ 0.05), and the same letters indicate statistically significant There are no significant differences.
- Figure 11 is a graph showing the effect of different treatments of dextrorone and demethoxycurcumin on the cell cycle of HepG2.
- Figure 12 is a graph showing the effect of different treatments of dextrorone and demethoxycurcumin on ROS changes in HepG2 cells.
- Figure 13 is a graph showing the effect of different treatments of dextrorone and bis-demethoxycurcumin on the survival rate of HepG2 cells; different letters indicate statistically significant differences (P ⁇ 0.05), and the same letters indicate statistics. There are no significant differences.
- Figure 14 is a graph showing the effect of different treatments of dextro-dragon and bis-demethoxycurcumin on the cell cycle of HepG2.
- Figure 15 is a graph showing the effect of different treatments of dextrorone and bis-demethoxycurcumin on ROS changes in HepG2 cells.
- Example 1 dextro-dragon brain increases the sensitivity of non-resistant tumor cells to chemical drugs
- the malignant melanoma cell A375 used in this experiment was purchased from the American model culture collection bank (ATCC, Manassas, VA); the right-handed borneol, China National Institute for Pharmaceutical and Biological Products; curcumin, purchased from Sigma; Methyl methazole blue (MTT) powder and dimethyl sulfoxide (DMSO), Sigma, USA; DMEM medium and trypsin, Invitrogen (Carlsbad, CA), USA; 96-well plate, Corning, USA.
- ATCC American model culture collection bank
- VA Manassas, VA
- curcumin purchased from Sigma
- DMEM medium and trypsin, Invitrogen Carlsbad, CA
- 96-well plate Corning, USA.
- the A375 cells were cultured in DMEM medium containing 10% fetal bovine serum. After 3 days of cell culture, the growth state and cell density of the cells were observed. When the cells were grown to 80%, cell passage was performed. The cells digested with trypsin (conventional operation, working solution concentration: 0.25%, the same below) were transferred to a centrifuge tube, centrifuged at 1000 rpm for 3 min, and the supernatant was discarded, and 10% (v/v) fetal bovine serum was added. 3 ml of DMEM medium, and the gun is sucked more than 10 times. Make sure to resuspend the cells evenly.
- trypsin conventional operation, working solution concentration: 0.25%, the same below
- the concentration of D-Dragon brain used in this experiment had no obvious growth inhibition on A375.
- the concentration of D-Dragon brain was determined to be 40 ⁇ g/ml.
- the chemical drug Curcumin (Cur) greatly improved the sensitivity of A375 malignant melanoma cells in this experiment, and its sensitivity change index -
- the dose reduction index (DRI) was 1.72 (see Table 1), indicating that the sensitization effect was significant.
- Example 2 dextro-dragon brain increases the sensitivity of non-resistant tumor cells to chemical drugs
- the breast cancer cells MCF-7 used in this experiment were purchased from the American model culture collection library (ATCC, Manassas, VA); the right-handed borneol, China National Institute of Drugs and Biological Products; curcumin, purchased from Sigma; MTT powder and dimethyl sulfoxide (DMSO), Sigma, USA; DMEM medium and trypsin, Invitrogen (Carlsbad, CA), USA; 96-well plate, Corning, USA.
- ATCC American model culture collection library
- VA Manassas, VA
- curcumin purchased from Sigma
- DMEM medium and trypsin, Invitrogen Carlsbad, CA
- 96-well plate Corning, USA.
- the concentration of D-Dragon brain used in this experiment had no obvious growth inhibition on MCF-7.
- the concentration of D-Dragon brain was determined to be 40 ⁇ g/ml.
- the chemical drug curcumin (Curcumin) greatly improved the sensitivity of MCF-7 breast cancer cells in this experiment, and its sensitivity change index -
- the dose reduction index (DRI) was 3.86 (see Table 1), indicating that the sensitization effect was significant.
- the A375 cells in the logarithmic growth phase were digested with trypsin, counted, and inoculated into a 96-well culture plate at 8 ⁇ 10 4 cells/well, and cultured in an incubator (37 ° C, 5% CO 2 ) for 24 hours.
- Add 40 ⁇ g/ml NB, 20 ⁇ M Cur and 40 ⁇ g/ml NB+20 ⁇ M Cur (this group was treated with NB for 12h and then add Cur) for 0.5h, 1h, 2h and 4h, then remove the medium and add 1mL PBS.
- the content of curcumin in the NB group did not change significantly, but the NB+Cur group significantly increased the intracellular Cur content in a time-dependent manner.
- the Cur content in the NB+Cur group increased from 2.57 in the control group to 3.23, 3.47, 3.99, and 4.36 (10 -9 ⁇ g), respectively, compared with 3.21, 3.40, and 3.55 in the Cur group.
- 3.86 (10 -9 ⁇ g) increased by 1.01, 1.02, 1.12 and 1.13 times, respectively.
- the experimental results show that D-Dragon has significantly enhanced the absorption of curcumin in cells.
- A375 cells in logarithmic growth phase were digested with trypsin, counted, seeded in 6-well plates at 2 ⁇ 10 4 cells/well, and cultured in an incubator (37 ° C, 5% CO 2 ) for 24 h. After adding 40 ⁇ g/ml NB, 20 ⁇ M Cur, and 40 ⁇ g/ml NB+20 ⁇ M Cur (this group was treated with NB for 12 h and then adding Cur), the medium was removed, and the medium was removed by adding 1 mL of PBS to remove the cells 3 times.
- the cells in the logarithmic growth phase were digested with trypsin, counted, and inoculated into a 10 cm dish at 10 ⁇ 10 4 cells/well, and cultured in an incubator (37 ° C, 5% CO 2 ) for 24 hours.
- the cells were treated with 40 ⁇ g/ml NB, 20 ⁇ M Cur and 40 ⁇ g/ml NB+20 ⁇ M Cur for 72 h, then the cells were collected and a certain amount of RIPA cell lysate was added (RIPA lysate from 50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 1 %Nonidet P-40 and 0.1% SDS were prepared, depending on the number of cells.
- the Caspase substrate (Caspase 3, 8, 9) was separately removed, and 4 ⁇ l per well was added to a 96-well fluorescent plate, and then 100 ⁇ g of the cell protein obtained after different treatment was added, and the total volume was adjusted to 160 ⁇ l/well with PBS, and placed at 37.
- the cells were cultured in the dark for 1 h, and the fluorescence intensity (excitation wavelength was 380 nm, emission wavelength was 460 nm) was measured by a fluorescent microplate reader, and each sample was run in parallel three times.
- the NB group or the Cur group reduced the activity of Caspase9 and slightly increased the activity of Caspase3 and Caspase8, while the NB+Cur combination significantly increased the activity of Caspase 3 and 8 and slightly increased the Caspase9 compared with the NB or Cur group.
- Activity indicating that NB can significantly increase the activity of Cur-activated Caspase 3, 8, and 9.
- Cur and NB+Cur were added to a 96-well plate at 100 ⁇ l per well, and then 100 ⁇ l of the loaded cell suspension was added, shaken and mixed, and the fluorescence intensity within 2 h was measured by a fluorescence microplate reader.
- the excitation wavelength and emission wavelength were 300 and respectively.
- cells treated with no drug were used as blank controls, and the results were calculated as 100% of the blank group.
- Example 5 The detection operation of Example 5 is basically the same as that of Embodiment 3, except that the Cur concentration is different, and the detection results are as follows:
- the hepatoma cell HepG2 used in this experiment was purchased from the American model culture collection library (ATCC, Manassas, VA); curcumin (Cur), purchased from Sigma; dextro-borne brain (NB), purchased from Chinese medicine and Bioproducts Laboratory; MTT powder and dimethyl sulfoxide (DMSO) were purchased from Sigma, USA; DMEM medium and trypsin were purchased from Invitrogen (Carlsbad, CA).
- ATCC American model culture collection library
- Curcumin Curcumin
- NB dextro-borne brain
- MTT powder and dimethyl sulfoxide (DMSO) were purchased from Sigma, USA
- DMEM medium and trypsin were purchased from Invitrogen (Carlsbad, CA).
- HepG2 cells in logarithmic growth phase were passaged, cell density was adjusted, and seeded in 96-well culture plates at 2 ⁇ 10 4 cells/ml, 100 ⁇ l per well; after 24 h, the cells were treated differently, and the control group was not.
- the curcumin and/or the right-handed borneol were added.
- the experimental group was as follows: a group of 100 ⁇ l of curcumin at a concentration of 20, 40, and 80 ⁇ M was treated for 24 hours, and a group of 100 ⁇ l was added at a concentration of 20, 40, and 80 ⁇ g/ml, respectively.
- FIG. 7 (concentration in Figure 7 indicates the final concentration of NB and/or Cur in the cells in different treatment groups; a, b, c, and d on the bar graph indicate statistically significant differences between the two groups, respectively
- the liver cancer cells were most toxic after being treated with 20 ⁇ g/ml NB for 12 h and 20 ⁇ M Cur for 24 h.
- concentration of curcumin (Cur) was 20 ⁇ M
- the survival rate of HepG2 cells was 91.87%.
- the cells were treated with 20 ⁇ g/ml NB for 12h and then treated with 20 ⁇ M Cur for 24h, the cell viability was 91.87%. It dropped to 54.25%, a drop of 37.62%. It was shown that the addition of NB significantly increased the cytotoxicity of curcumin on HepG2 cells.
- HepG2 cells in logarithmic growth phase were digested by trypsin (conventional operation, working solution concentration: 0.25%, the same below), counted, inoculated into 6-well plates at 2 ⁇ 10 4 cells/well, and placed in an incubator.
- trypsin conventional operation, working solution concentration: 0.25%, the same below
- the apoptosis peak in the NB+Cur group was not significantly increased, only 4.1%, while the G2/M phase cells increased from 31.3% to 44.6%, indicating that the addition of NB significantly increased the cell cycle of G2/M phase induced by Cur, but the number of SubG1 peaks did not increase significantly, indicating that NB And Cur does not inhibit cell proliferation by inducing apoptosis.
- the log phase HepG2 cells with good growth status were collected, washed twice with PBS, centrifuged to remove supernatant, resuspended in serum-free medium, counted, adjusted to a cell density of 10 ⁇ 10 4 cells/ml, and then added with a certain amount of DHE.
- the final concentration was 10 ⁇ M, incubated in a 37 ° C incubator for 30 min, shaking once every 5 min. After the arrival time, the cells were removed for centrifugation, the supernatant was decanted, and the same amount of PBS was resuspended, and PBS was prepared in different concentrations.
- Cur and NB+Cur (the group was treated with 50 ⁇ l NB and then treated with 50 ⁇ l of Cur, the total volume was 100 ⁇ l), added to a 96-well plate at 100 ⁇ l per well, and then 100 ⁇ l of the loaded cell suspension was added, and the mixture was shaken and mixed. Fluorescence intensity was measured by fluorescence microplate reader for 2 hours, and the excitation wavelength and emission wavelength were 300 and 610 nm, respectively. The cells without drug treatment were used as blank control, and the experimental results were calculated according to 100% of the blank group. Repeat three times for each experiment.
- Step 1 of Example 6 The procedure was the same as in Step 1 of Example 6, except that it was inoculated into a 96-well culture plate at 1.8 ⁇ 10 4 cells/ml, and the curcumin was replaced with demethoxycurcumin.
- the toxicity of liver cancer cells was the highest after treatment with 20 ⁇ g/ml NB for 12 h and 40 ⁇ M DCur for 24 h.
- concentration of demethoxycurcumin (DCur) was 40 ⁇ M
- the cell viability was 58.03%.
- the cell viability decreased from 58.03% to 38.69. %, down 19.34%. It was shown that the addition of NB significantly increased the cytotoxicity of demethoxycurcumin on HepG2 cells.
- HepG2 cells in logarithmic growth phase were digested with trypsin, counted, seeded in 6-well plates at 2 ⁇ 10 4 cells/well, and placed in an incubator (37 ° C, 5% CO 2 ) for 24 h, respectively.
- the liver cancer cells were most toxic after being treated with 20 ⁇ g/ml NB for 12 h and 40 ⁇ M BDCur for 24 h.
- concentration of bis-demethoxycurcumin (BDCur) was 40 ⁇ M
- the cell viability was 78.98%.
- the cell viability decreased from 78.98% to 55.41%, down by 23.57%. Indicating that Tim After adding NB, the cytotoxicity of bis-demethoxycurcumin on HepG2 cells was significantly increased.
- the intracellular ROS of the NB group had no obvious trend, and the intracellular ROS of the BDCur group increased, whereas compared with the BDCur group, the NB and BDCur combined treatment group had further ROS. Increased and time dependent.
- the experimental results show that NB can significantly increase the production of ROS in BDCur induced cells.
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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims (10)
- 右旋龙脑作为抗肿瘤药物增敏剂的应用。
- 根据权利要求1所述的右旋龙脑作为抗肿瘤药物增敏剂的应用,其特征在于:所述的抗肿瘤药物为抗肿瘤化学药物。
- 根据权利要求2所述的右旋龙脑作为抗肿瘤药物增敏剂的应用,其特征在于:所述的抗肿瘤化学药物为柔红霉素、阿霉素、去甲氧柔红霉素、表阿霉素、紫杉醇、香菇多糖、长春花碱、长春新碱、三苯氧胺、福美司坦、阿那曲唑、氟他胺、5-氟尿嘧啶、甲氨蝶呤、顺铂、卡铂、奥沙利铂、卡莫司汀、托瑞米芬、替加氟、姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素和塞替派中的至少一种。
- 根据权利要求1所述的右旋龙脑作为抗肿瘤药物增敏剂的应用,其特征在于:所述的肿瘤为肝癌、肺癌、恶性黑色瘤、乳腺癌、结肠癌、鼻癌、膀胱癌、宫颈癌、胃癌、食管癌或前列腺癌。
- 一种抗肿瘤药物增敏剂,其特征在于:由右旋龙脑和药物允许的赋形剂或载体组成。
- 一种抗肿瘤药物,其特征在于:由权利要求5所述的肿瘤药物增敏剂和抗肿瘤药物组成,成分组成为右旋龙脑、赋形剂或载体、和抗肿瘤药物。
- 根据权利要求6所述的抗肿瘤药物,其特征在于:所述的抗肿瘤药物为抗肿瘤化学药物。
- 根据权利要求6所述的抗肿瘤药物,其特征在于:所述的抗肿瘤化学药物为柔红霉素、阿霉素、去甲氧柔红霉素、表阿霉素、紫杉醇、香菇多糖、长春花碱、长春新碱、三苯氧胺、福美司坦、阿那曲唑、氟他胺、5-氟尿嘧啶、甲氨蝶呤、顺铂、卡铂、奥沙利铂、卡莫司汀、托瑞米芬、替加氟、姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素和塞替派中的至少一种。
- 根据权利要求8所述的抗肿瘤药物,其特征在于:所述的抗肿瘤药物由右旋龙脑、赋形剂或载体、和姜黄素组成;所述的姜黄素与所述的右旋龙脑按质量比73674~294696:400000配比。
- 根据权利要求8所述的抗肿瘤药物,其特征在于:所述的抗肿瘤药物由右旋龙脑、赋形剂或载体、和姜黄素类化合物组成;所述的右旋龙脑和所述的姜黄素类化合物按质量摩尔比2~8μg:2~8nmol配比。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510511663.4 | 2015-08-19 | ||
CN201510511663.4A CN105147647A (zh) | 2015-08-19 | 2015-08-19 | 右旋龙脑作为抗肿瘤药物增敏剂的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2017028441A1 true WO2017028441A1 (zh) | 2017-02-23 |
Family
ID=54788938
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2015/098535 WO2017028441A1 (zh) | 2015-08-19 | 2015-12-23 | 右旋龙脑作为抗肿瘤药物增敏剂的应用 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN105147647A (zh) |
WO (1) | WO2017028441A1 (zh) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105147647A (zh) * | 2015-08-19 | 2015-12-16 | 华南理工大学 | 右旋龙脑作为抗肿瘤药物增敏剂的应用 |
CN110613703A (zh) * | 2018-10-17 | 2019-12-27 | 暨南大学 | 右旋龙脑作为阿霉素钝化剂的应用 |
CN110613704B (zh) * | 2018-10-17 | 2023-06-13 | 广东华清园生物科技有限公司 | 右旋龙脑作为阿霉素或其衍生物增敏剂在制备抗肺癌药物中的应用 |
CN112915087B (zh) * | 2019-12-05 | 2023-01-24 | 浙江大学 | 一种基于5-羧基-8-羟基喹啉的抗肿瘤药物增敏剂及其应用 |
CN113121810B (zh) * | 2019-12-31 | 2022-05-24 | 华南理工大学 | 一种基于龙脑的聚合物及其制备方法与应用 |
CN113362965B (zh) * | 2021-06-28 | 2023-09-15 | 中国人民解放军疾病预防控制中心 | 用于医院病原菌耐药性监测系统及方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101193682A (zh) * | 2005-05-13 | 2008-06-04 | 先进科学发展公司 | 包含一种抗病毒、一种抗肿瘤或一种抗寄生虫药以及一种选自香芹醇、麝香草酚、丁香酚、樟醇和香芹酚的活性物质的药物组合物 |
CN105147647A (zh) * | 2015-08-19 | 2015-12-16 | 华南理工大学 | 右旋龙脑作为抗肿瘤药物增敏剂的应用 |
-
2015
- 2015-08-19 CN CN201510511663.4A patent/CN105147647A/zh active Pending
- 2015-12-23 WO PCT/CN2015/098535 patent/WO2017028441A1/zh active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101193682A (zh) * | 2005-05-13 | 2008-06-04 | 先进科学发展公司 | 包含一种抗病毒、一种抗肿瘤或一种抗寄生虫药以及一种选自香芹醇、麝香草酚、丁香酚、樟醇和香芹酚的活性物质的药物组合物 |
CN105147647A (zh) * | 2015-08-19 | 2015-12-16 | 华南理工大学 | 右旋龙脑作为抗肿瘤药物增敏剂的应用 |
Non-Patent Citations (3)
Title |
---|
CHEN, JIANPING: "Molecular mechanism underlying natural borneol potentiated curcuminoids inhibiting HepG2 human hepatocellular carcinoma cells growth", CNKI CHINESE DOCTORAL DISSERTATION DATABASE, 6 June 2015 (2015-06-06) * |
LI, LIN ET AL.: "Molecular mechanism underlying natural borneol enhanced curcuminoids inducing melanoma cell apoptosis", PROCEEDINGS OF THE ACADEMIC SYMPOSIUM OF BIOPHYSICS SOCIETY OF GUANGDONG PROVINCE, 30 September 2014 (2014-09-30) * |
ZHENG, XIAOWEI: "Effect of borneol on reverse the multidrug resistance in cancer", SICHUAN JOURNAL OF PHYSIOLOGICAL SCIENCE, vol. 29, no. 3, 31 December 2007 (2007-12-31) * |
Also Published As
Publication number | Publication date |
---|---|
CN105147647A (zh) | 2015-12-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2017028441A1 (zh) | 右旋龙脑作为抗肿瘤药物增敏剂的应用 | |
Tamayo et al. | Copper (II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action | |
Sivanantham et al. | Combinatorial effects of curcumin with an anti-neoplastic agent on head and neck squamous cell carcinoma through the regulation of EGFR-ERK1/2 and apoptotic signaling pathways | |
Liu et al. | β-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway | |
Tseng et al. | Aloe-emodin enhances tamoxifen cytotoxicity by suppressing Ras/ERK and PI3K/mTOR in breast cancer cells | |
Ma et al. | In-vitro and in-vivo anti-breast cancer activity of synergistic effect of berberine and exercise through promoting the apoptosis and immunomodulatory effects | |
Li et al. | Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells | |
Bo et al. | Allyl isothiocyanate induces cell toxicity by multiple pathways in human breast cancer cells | |
Maciejczyk et al. | Quercetin inhibits proliferation and increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel | |
Manogaran et al. | Neferine and isoliensinine enhance ‘intracellular uptake of cisplatin’and induce ‘ROS-mediated apoptosis’ in colorectal cancer cells–a comparative study | |
Suh et al. | Anticancer activities of ethanol extract from the Antarctic freshwater microalga, Botryidiopsidaceae sp. | |
Tian et al. | Scoulerine promotes cell viability reduction and apoptosis by activating ROS-dependent endoplasmic reticulum stress in colorectal cancer cells | |
Am et al. | Imperatorin shows selective antitumor effects in SGC-7901 human gastric adenocarcinoma cells by inducing apoptosis, cell cycle arrest and targeting PI3K/Akt/m-TOR signalling pathway | |
Osman et al. | Modulatory role of resveratrol on cytotoxic activity of cisplatin, sensitization and modification of cisplatin resistance in colorectal cancer cells | |
Tan et al. | Pterostilbene inhibits lung squamous cell carcinoma growth in vitro and in vivo by inducing S phase arrest and apoptosis | |
Zhao et al. | The induction of apoptosis and autophagy in human hepatoma SMMC-7721 cells by combined treatment with vitamin C and polysaccharides extracted from Grifola frondosa | |
Duan et al. | Selenium nanoparticles coupling with Astragalus Polysaccharides exert their cytotoxicities in MCF-7 cells by inhibiting autophagy and promoting apoptosis | |
Shahriary et al. | Phyto-mediated synthesis of CuO nanoparticles using aqueous leaf extract of Artemisia deserti and their anticancer effects on A2780-CP cisplatin-resistant ovarian cancer cells | |
Rukkijakan et al. | A synthetic 2, 3-diarylindole induces cell death via apoptosis and autophagy in A549 lung cancer cells | |
Sorg et al. | Antitumor effects of curcumin in pediatric rhabdomyosarcoma in combination with chemotherapy and phototherapy in vitro | |
Yoon et al. | A novel synthetic analog of Militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells | |
Hosseini et al. | Aloe-emodin induces apoptosis through the up-regulation of fas in the human breast cancer cell line MCF-7 | |
Li et al. | Paradol inhibits proliferation and migration of human hepatocellular carcinoma cells | |
Zhu et al. | Anticancer effect of thalidomide in vitro on human osteosarcoma cells | |
Hamami et al. | Nano transdermal delivery potential of fucoidan from Sargassum sp.(Brown Algae) as chemoprevention agent for breast cancer treatment |
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: 15901642 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
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 30/05/2018) |
|
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 30/05/2018) |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 15901642 Country of ref document: EP Kind code of ref document: A1 |