CN104758277A - Uses of chlorogenic acid in preparation of drugs treating multidrug resistance of cancer - Google Patents
Uses of chlorogenic acid in preparation of drugs treating multidrug resistance of cancer Download PDFInfo
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- CN104758277A CN104758277A CN201510098678.2A CN201510098678A CN104758277A CN 104758277 A CN104758277 A CN 104758277A CN 201510098678 A CN201510098678 A CN 201510098678A CN 104758277 A CN104758277 A CN 104758277A
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Abstract
The invention discloses new medicinal uses of chlorogenic acid, especially uses of chlorogenic acid in preparation of drugs treating multidrug resistance of cancer, and provides uses of chlorogenic acid and antitumor drugs in preparation of drugs treating cancer. By inhibiting activity and expression of drug pump protein on surfaces of tumor cells, tumor patients generating multidrug resistance can receive durable and effective treatment. A combination of the chlorogenic acid and a drug-resistant drug is provided, thus alleviating or eliminating drug resistance to multiple drugs for patients, allowing patients with drug resistance to receive durable and effective treatment, and overcoming the limitation problem at present that tumor patients cannot receive durable and effective treatment due to generation of drug resistance. The uses have important meaning in clinical use of antitumor treatment.
Description
Technical field
The invention belongs to the new pharmaceutical usage of chlorogenic acid, particularly relate to the purposes of chlorogenic acid in the medicine of multidrug resistance preparing Therapeutic cancer.
Background technology
Chemotherapy is the Main Means of current Therapeutic cancer the most frequently used clinically, and targeted therapy also more and more to receive the concern of people in recent years.But chemotherapy and targeted therapy all face a problem, what the drug resistance of tumor cell to medicine was serious have impact on medicine effect clinically.American Cancer Society estimates, the tumor patient of more than 90% dies from tumor cell drug resistance in various degree, therefore, alleviates or the drug resistance of reversing tumor cell, raising chemotherapy and target therapeutic agent, to the sensitivity of tumor cell, have positive meaning in the treatment of cancer.
There are some researches show, be the common causes that tumor cell produces drug resistance in the decline of intracellular accumulation.Typically, tumor cell mainly contains two kinds of modes to drug resistant: the inherited character of (1) tumor cell self changes, and makes tumor cell survival by apoptosis inhibit and minimizing DNA damage; (2) function of tumor cell transmission medicine is impaired, comprises the picked-up, detoxification etc. that increase drug efflux, reduce medicine.The MDR (Multi-drugs resistance) of tumor cell refers to that tumor cell is to while a kind of drug resistant, and also different with action target spot to other other structures multiple antitumor drug also has drug resistance.The complexity of tumor cell MDR Producing reason and Forming Mechanism exception and various, and single MDR cell can have several drug resistance mechanism simultaneously, wherein cell membrane affects abc transport albumen main P-GP, MRPs and BCRP of MDR.
P-GP is by a kind of transmembrane glycoprotein of MDR1 gene code, and the MDR of its mediation is called as classical MDR approach.Research shows, P-GP can suppress the activation of Caspase-3 and Caspase-8, and then the MDR apoptosis suppressing most of antitumor drug to be induced.When the medicament contact such as tumor cell and chemotherapy, medicine enters after cell through Concentraton gradient and is combined with P-GP Binding Capacity district, and ATP is attached on NBD simultaneously; Subsequently, through ATP hydrolysis, P-GP configuration changes, and medicine is transferred to low affine site from high affinity-sites and discharged extracellular etc.MRPs is also a class transmembrane glycoprotein, plays an important role in prokaryote and Eukaryotic transmembrane transport, and it is one of topmost reason causing tumor MDR cell that MRP1 expression is increased.The molecular mechanism of the existing drug resistance of BCRP ginseng and P-GP and MRP basic simlarity.
Chlorogenic acid (chlorogenic acid CGA) has another name called caffeotannic acid, the depside be made up of caffeic acid (caffeic acid CA) and quinic acid (quinic acid QA), its chemistry 3-o-caffeoyl guinic acid (3-o-caffeoylquinic acid CGA) by name.
CAS No.：327-97-9
CAS Name：
[1S-(1a,3b,4a,5a)]-3-[[3-(3,4-Dihydroxyphenyl)-1-oxo-2-propenyl]oxy]-1,4,5-trihydroxycyclohexanecarboxylic acid
System name: 1,3,4,5-tetrahydroxy cyclohexane-carboxylic acid-(Caffeic acid ester)
Chemical structural formula:
Chlorogenic acid be plant in the process of carrying out aerobic respiration, through phosphopentose pathway intermediate product synthesis a kind of Phenylpropanoid Glycosides class material.It extracts (usually extracting from plant), synthetic technology is ripe, chlorogenic acid by open applications in food, health product, multiple field such as cosmetics and medicine.Because it is present in common various vegetable and fruits widely; there is multiple biological activity, as: cardiovascular protective effect, antioxidation, uvioresistant and radiation resistance, antimutagenic and antitumaous effect, antibacterial action, antivirus action, blood lipid-reducing blood sugar-decreasing effect, immunoregulation effect etc.All have a wide range of applications in the field such as medication chemistry and food.
Summary of the invention
The object of the invention is to: the new pharmaceutical usage that chlorogenic acid is provided, especially the purposes of chlorogenic acid in the medicine of multidrug resistance preparing Therapeutic cancer.
The present invention also aims to: chlorogenic acid and the antitumor drug purposes in the medicine preparing Therapeutic cancer is provided.
The object of the invention is realized by following technical proposals:
The purposes of chlorogenic acid in the medicine of multidrug resistance preparing Therapeutic cancer.
Chlorogenic acid and the antitumor drug purposes in the medicine preparing Therapeutic cancer.
Wherein, described cancer is the cancer having produced multidrug resistance.
In such scheme, multidrug resistance (multiple drug resistance), has another name called multiple drug resistance/multi-drug resistant, and multidrug resistance refers to while generation drug resistance, different to other structures, the different antitumor drug of action target spot also has drug resistance.Multidrug resistance is the one of the main reasons causing anti-infective therapy and chemotherapy of tumors failure.
Wherein, described cancer is breast carcinoma, small cell lung cancer or colon cancer etc.
Wherein, described antitumor drug is chemotherapeutics or targeting class medicine etc.
Wherein, described chemotherapeutics or targeting class medicine include but not limited to one or more in docetaxel, vinorelbine, amycin, oxaliplatin, etoposide, methotrexate and gemcitabine.
Wherein, the described medicine prepared by chlorogenic acid is the activity of Teat pipette albumen and the medicine of expression on inhibition tumor cell surface.
Wherein, the described medicine prepared by chlorogenic acid is the medicine activating apoptosis of tumor cells path.
Wherein, described medicine is effective ingredient by chlorogenic acid, adds the preparation that one or more pharmaceutically acceptable pharmaceutical excipients are prepared from.
In such scheme, chlorogenic acid both can as sole active ingredient, also can as one of effective ingredient.
Wherein, described preparation is oral formulations or ejection preparation.
Wherein, the unit formulation of described preparation is containing chlorogenic acid 1-1000mg.
Wherein, the Clinical practice dosage of described preparation is: 1-100mg/kg.
Aforementioned main formula case of the present invention and each further selection scheme thereof can independent assortment to form multiple scheme; be the present invention can adopt and claimed scheme; those skilled in the art can understand there is multiple combination according to prior art and common practise after understanding the present invention program; be the claimed technical scheme of the present invention, do not do exhaustive at this.
Beneficial effect of the present invention: the new pharmaceutical usage that the invention provides a kind of chlorogenic acid, by activity and the expression of the Teat pipette albumen on inhibition tumor cell surface, makes the tumor patient producing multidrug resistance obtain the treatment of continuous and effective; The conbined usage of a kind of chlorogenic acid and Drug resistance medicine is provided simultaneously, thus reach and alleviate or eliminate the drug resistance effect of patient to multi-medicament, drug resistance patient is made to obtain the treatment of continuous and effective, solve current tumor patient because produce drug resistance and cannot remain valid treatment limiting problem, the Clinical practice of antineoplaston has great importance.
Accompanying drawing explanation
Fig. 1 is that the chlorogenic acid of the embodiment of the present invention 2 affects schematic diagram to multidrug-resistant carcinoma mould;
Fig. 2 is that the chlorogenic acid of the embodiment of the present invention 3 affects schematic diagram to small cell lung cancer multidrug-resistant carcinoma mould;
Fig. 3 is that the chlorogenic acid of the embodiment of the present invention 4 affects schematic diagram to colon cancer multidrug-resistant carcinoma mould;
Fig. 4 be the embodiment of the present invention 5 chlorogenic acid in multidrug-resistant carcinoma cell P-GP express affect schematic diagram;
Fig. 5 be the embodiment of the present invention 5 chlorogenic acid in multidrug-resistant carcinoma cell MRP1 express affect schematic diagram;
Fig. 6 be the embodiment of the present invention 5 chlorogenic acid in multidrug-resistant carcinoma cell BCRP express affect schematic diagram;
Fig. 7 is that the chlorogenic acid of the embodiment of the present invention 5 affects schematic diagram to P-GP, MRP1, BCRP protein expression in multidrug resistance breast cancer cell;
Fig. 8 is that the chlorogenic acid of the embodiment of the present invention 5 affects schematic diagram to P-GP, MRP1, BCRP protein expression in multidrug resistance small cell lung cancer cell;
Fig. 9 is that the chlorogenic acid of the embodiment of the present invention 5 affects schematic diagram to P-GP, MRP1, BCRP protein expression in multidrug resistance colon cancer cell;
Figure 10 is that the chlorogenic acid of the embodiment of the present invention 6 affects schematic diagram to the Multidrug resistance breast cancer cell cycle;
Figure 11 is that the chlorogenic acid of the embodiment of the present invention 6 affects schematic diagram to the Multidrug resistance small cell lung cancer cell cycle;
Figure 12 is that the chlorogenic acid of the embodiment of the present invention 6 affects schematic diagram to Multidrug resistance Cell Cycle of Colon Carcinoma.
Detailed description of the invention
Following non-limiting examples is for illustration of the present invention.
The foundation of embodiment one cells of resistant tumors model
Get the human breast carcinoma strain cell BCap37 being in exponential phase, use 0.25% trypsinization; Complete culture solution re-suspended cell, piping and druming evenly, makes single cell suspension; Cell counting, adjustment cell concentration is to 2x10
4individual/ml; By every hole 200 μ L cell suspension inoculation to being inoculated in 96 orifice plates (every hole is containing about 4000, cell); Move into containing 5%CO
2, saturated humidity, cultivates 12 hours in 37 DEG C of constant incubators; Add paclitaxel concentration 300nM, if 6 multiple holes; Move into containing 5%CO
2, saturated humidity, cultivates 72 hours in 37 DEG C of constant incubators.With breast cancer cell BCap37 for parental cell, take paclitaxel as screening of medicaments, successfully set up multidrug resistant cells Bats-72.Bats-72 has the drug resistance of wide spectrum, has stronger drug resistance to chemotherapeutics such as how western taxol, vinorelbine, amycin, etoposide, methotrexate and gemcitabines.
Embodiment two mice multidrug resistance breast cancer model tumour inhibiting rate is tested
(1) experimental technique
Mice multidrug resistance breast cancer model, selects C57BL/6 mice, male, 18-22g.During experiment, the Bats-72 cell of trophophase of taking the logarithm, making concentration is 2.5x10
4the tumor cell suspension of/ml, every mice axil back inoculation 0.2ml tumor liquid.Inoculation animal random packet rear next day, weighs, and starts administration.Laboratory animal is divided into 9 groups, comprises negative control group, matched group, docetaxel group, chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg group, docetaxel and chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg drug combination three dosage groups, often organizes 20 animals.Chlorogenic acid injection administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 24 days.Docetaxel dosage is 60mg/kg Mouse Weight, the next day administration.Administering drug combinations group is in giving chlorogenic acid second day to docetaxel.After drug withdrawal, next day weighs and adopts eye socket to take a blood sample and collects peripheral blood, and stripping tumor also claims tumor weight, calculates tumour inhibiting rate.
(2) experimental result
Table 1. chlorogenic acid is on the impact of mammary gland multidrug-resistant carcinoma mould
Note: * * * p<0.001, compares with matched group; ###p<0.001, compares with docetaxel group.
See table 1 and Fig. 1, tumour inhibiting rate result shows, and docetaxel is substantially inoperative to the mouse breast cancer model producing drug resistance, and tumour inhibiting rate is 2.01%; Chlorogenic acid has obvious tumor killing effect to the mammary gland of mouse model producing drug resistance, and the tumor killing effect of chlorogenic acid is dose-dependence, and under the dosage of 20mg/kg, tumor killing effect is the most obvious; Obviously the tumour inhibiting rate of alone chlorogenic acid and alone docetaxel and sum thereof is high on year-on-year basis under the using dosage of any one chlorogenic acid for the tumour inhibiting rate of chlorogenic acid and docetaxel drug combination, illustrates that model mice docetaxel after use chlorogenic acid has played obvious tumor killing effect.Chlorogenic acid can alleviate the degree of tumor cell drug resistance in cancer treatment procedure.
Embodiment three mice multidrug resistance small cell lung cancer model tumour inhibiting rate is tested
(1) experimental technique
Mice multidrug resistance small cell lung cancer model, selects BALB/c mouse, male, 18-22g.The model cell that experiment adopts is the human small cell lung carcinoma multidrug resistant cells strain GLC4 induced by mitoxantrone (Mx).During experiment, the GLC4 cell of trophophase of taking the logarithm, making concentration is 2.5x10
4the tumor cell suspension of/ml, every mice axil back inoculation 0.2ml tumor liquid.Inoculation animal random packet rear next day, weighs, and starts administration.Laboratory animal is divided into 9 groups, comprises negative control group, matched group, amycin group, chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg group, amycin 60mg/kg and chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg drug combination three dosage groups, often organizes 20 animals.Chlorogenic acid injection administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 24 days.Amycin dosage is 60mg/kg Mouse Weight, the next day administration.Administering drug combinations group is in giving chlorogenic acid second day to amycin.After drug withdrawal, next day weighs and adopts eye socket to take a blood sample and collects peripheral blood, and stripping tumor also claims tumor weight, calculates tumour inhibiting rate.
(2) experimental result
Table 2. chlorogenic acid is on the impact of small cell lung cancer multidrug-resistant carcinoma mould
Note: * * * p<0.001, compares with matched group; ###p<0.001, compares with amycin group.
See table 2 and Fig. 2, tumour inhibiting rate result shows, and amycin is substantially inoperative to the mice small cell lung cancer model producing drug resistance, and tumour inhibiting rate is 3.87%; Chlorogenic acid has obvious tumor killing effect to the mice small cell lung cancer model producing drug resistance, and the tumor killing effect of chlorogenic acid is dose-dependence, and under the dosage of 20mg/kg, tumor killing effect is the most obvious; Obviously the tumour inhibiting rate of alone chlorogenic acid and alone amycin and sum thereof is high on year-on-year basis under the using dosage of any one chlorogenic acid for the tumour inhibiting rate of chlorogenic acid and adriamycin medication, illustrates that model mice amycin after use chlorogenic acid has played obvious tumor killing effect.Chlorogenic acid can alleviate the degree of tumor cell drug resistance in cancer treatment procedure.
Embodiment four mice multidrug resistance model of colon cancer tumour inhibiting rate is tested
(1) experimental technique
Mice multidrug resistance model of colon cancer, selects BALB/c mouse, male, 18-22g.The model cell that experiment adopts is the colon cancer multidrug resistant cells strain S1-M1-3.2 induced by mitoxantrone (Mx).During experiment, the S1-M1-3.2 cell of trophophase of taking the logarithm, making concentration is 2.5x10
4the tumor cell suspension of/ml, every mice axil back inoculation 0.2ml tumor liquid.Inoculation animal random packet rear next day, weighs, and starts administration.Laboratory animal is divided into 9 groups, comprises negative control group, matched group, oxaliplatin group, chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg group, oxaliplatin 1.5mg/kg and chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg drug combination three dosage groups, often organize 20 animals.Chlorogenic acid injection administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 24 days.Oxaliplatin dosage is 1.5mg/kg Mouse Weight, the next day administration.Administering drug combinations group is in giving chlorogenic acid second day to oxaliplatin.After drug withdrawal, next day weighs and adopts eye socket to take a blood sample and collects peripheral blood, and stripping tumor also claims tumor weight, calculates tumour inhibiting rate.
(2) experimental result
Table 3. chlorogenic acid is on the impact of colon cancer multidrug-resistant carcinoma mould
Note: * * * p<0.001, compares with matched group; ###p<0.001, compares with amycin group.
See table 3 and Fig. 3, tumour inhibiting rate result shows, and oxaliplatin is substantially inoperative to the mouse junction cancer model producing drug resistance, and tumour inhibiting rate is 5.03%; Chlorogenic acid has obvious tumor killing effect to the mouse junction cancer model producing drug resistance, and the tumor killing effect of chlorogenic acid is dose-dependence, and under the dosage of 20mg/kg, tumor killing effect is the most obvious; Obviously the tumour inhibiting rate of alone chlorogenic acid and oxaliplatin alone and sum thereof is high on year-on-year basis under the using dosage of any one chlorogenic acid for the tumour inhibiting rate of chlorogenic acid and oxaliplatin medication, illustrates that model mice oxaliplatin after use chlorogenic acid has played obvious tumor killing effect.Chlorogenic acid can alleviate the degree of tumor cell drug resistance in cancer treatment procedure.
Embodiment five chlorogenic acid is on the impact of P-GP, MRP1, BCRP protein expression in multidrug-resistant carcinoma cell
(1) experimental technique
The multidrug resistance breast carcinoma Bats-72 cell of exponential phase, small cell lung cancer GLC4 cell and colon cancer S1-M1-3.2 cell will be in, respectively by 1 ~ 5x10
4cells/well density is inoculated in six orifice plates.Cultivate after 24 hours, be divided into matched group and chlorogenic acid group, chlorogenic acid group adds chlorogenic acid (0.01,0.1 and 1 μM) effect 48 hours respectively, collecting cell, extract total protein, detect the expression of P-GP, MRP1 and BCRP albumen in cell by Western Blot method.What uses the expression of flow cytomery P-GP, MRP and BCRP simultaneously.
(2) experimental result
Experimental result shows, chlorogenic acid significantly can reduce the expression of P-GP, MRP1 and BCRP in multidrug-resistant carcinoma cell, thus impels the reverse of multidrug-resistant carcinoma, and presents dose-dependent relation, see Fig. 4 to 9.
Embodiment six chlorogenic acid is on the impact of multidrug resistant cells strain apoptosis
(1) experimental technique
By being in the multidrug resistance breast carcinoma of exponential phase, small cell lung cancer and colon cancer cell, by 1 ~ 5x10
4cells/well density is inoculated in six orifice plates.Cultivate after 24 hours, add chlorogenic acid (0.01 and 1 μM) effect 24 hours respectively, remove cell culture fluid, wash cell once with ice PBS.Add trypsinization, collecting cell, adopt the mono-dye of PI (apoptosis detects and adopts the two dye method of FITC-AnnexinV and PI), carry out cell cycle and apoptosis detection respectively with flow cytometer.Each identical experiment repeats 3 times.
(2) experimental result
See Figure 10 to 12, the cell cycle after flow cytometer showed drug treating changes: the G0/G1 phase catches to S, and G0/G1 phase percentage ratio obviously rises, and meanwhile, the S phase significantly declines; Show that chlorogenic acid effectively can control the division of multidrug-resistant carcinoma cell, promote the apoptosis of multidrug-resistant carcinoma cell, reach the effect for the treatment of multidrug-resistant carcinoma.Wherein, * * p<0.01, * * * p<0.001 compares with matched group, N=3.
Embodiment seven mice multidrug resistance small cell lung cancer model tumour inhibiting rate is tested
(1) experimental technique
Mice multidrug resistance small cell lung cancer model, selects BALB/c mouse, male, 18-22g.The model cell that experiment adopts is the human small cell lung carcinoma multidrug resistant cells strain GLC4 induced by mitoxantrone (Mx).During experiment, the GLC4 cell of trophophase of taking the logarithm, makes the tumor cell suspension that concentration is 2.5x104/ml, every mice axil back inoculation 0.2ml tumor liquid.Inoculation animal random packet rear next day, weighs, and starts administration.Laboratory animal is divided into 9 groups, comprises negative control group, matched group, Cetuximab group, chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg group, Cetuximab 60mg/kg and chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg drug combination three dosage groups, often organize 20 animals.Chlorogenic acid injection administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 24 days.Cetuximab dosage is 60mg/kg Mouse Weight, and Per-Hop behavior once.Administering drug combinations group in give chlorogenic acid second day to Cetuximab, once in a week.After drug withdrawal, next day weighs and adopts eye socket to take a blood sample and collects peripheral blood, and stripping tumor also claims tumor weight, calculates tumour inhibiting rate.
(2) experimental result
Chlorogenic acid is on the impact of small cell lung cancer multidrug-resistant carcinoma mould
Note: * * * p<0.001, compares with matched group; ###p<0.001, compares with Cetuximab group.
Tumour inhibiting rate result shows, and Cetuximab is substantially inoperative to the mice small cell lung cancer model producing drug resistance, and tumour inhibiting rate is 3.87%; Chlorogenic acid has obvious tumor killing effect to the mice small cell lung cancer model producing drug resistance, and the tumor killing effect of chlorogenic acid is dose-dependence, and under the dosage of 20mg/kg, tumor killing effect is the most obvious; Obviously the tumour inhibiting rate of alone chlorogenic acid and alone Cetuximab and sum thereof is high on year-on-year basis under the using dosage of any one chlorogenic acid for the tumour inhibiting rate of chlorogenic acid and Cetuximab drug combination, illustrates that model mice Cetuximab after use chlorogenic acid has played obvious tumor killing effect.Chlorogenic acid can alleviate the degree of tumor cell drug resistance in cancer treatment procedure.
Embodiment 8: lyophilized injectable powder
Prescription:
Method for making:
Above prescription is dissolved in water for injection completely, after filtration, then uses the degerming microporous filter membrane fine straining of 0.22 μm, after regulating pH, make 3ml injectable powder 1000 altogether according to the routine operation of sterile powder injection, often prop up containing chlorogenic acid 40mg.
Embodiment 9: pill
Prescription:
Method for making:
Get appropriate PVP K30, solution is mixed with dehydrated alcohol, get chlorogenic acid and the starch of recipe quantity again, after adopting equivalent dilution method mix homogeneously, add in the alcoholic solution of PVP K30, abundant stirring is obtained soft material afterwards, and adopt stranding ball legal system to obtain chlorogenic acid pill 1000, every pill is containing chlorogenic acid 1mg.
Embodiment 10: oral solution
Prescription:
Method for making:
Get chlorogenic acid and the sodium sulfite of recipe quantity, be dissolved in 10L water for injection, according to the conventional fabrication process of oral liquid, after filtration, sterile filling becomes 1000 oral liquids, and often propping up oral liquid is 10mL, containing chlorogenic acid 200mg.
Embodiment 11: tablet
Prescription:
Method for making:
The present embodiment adopts wet granular compression produces chlorogenic acid tablet processed.(1) measure hypromellose by prescription and make aqueous solution; (2), after getting the chlorogenic acid of recipe quantity, starch and lactose mix homogeneously, add hypromellose aqueous solution, after stirring, make soft material; (3) rule of operation of soft material wet granulation routinely will prepared, sieves, obtains uniform granule after dry and granulate; (4) tabletting after being mixed homogeneously with magnesium stearate by obtained granule, makes 1000 tablets altogether, and every sheet is containing chlorogenic acid 100mg.
Embodiment 12: capsule
Prescription:
Method for making:
Get chlorogenic acid and the Icing Sugar of recipe quantity, mix homogeneously, add 80% alcoholic solution and make soft material, dry, prepare 1000 capsules according to the conventional fabrication process of capsule after granulate, every capsules is containing chlorogenic acid 100mg.
Embodiment 13: granule
Prescription:
Method for making:
Get PVP K30, add water for injection, make solution.After getting the chlorogenic acid of recipe quantity, mannitol and sucrose mix homogeneously, add PVP K30 solution, make soft material.According to the conventional fabrication process of granule, soft material is sieved, after dry and granulate, obtains granule.Aseptically subpackage granule, prepares 400 bags of granules, and every bag of granule is containing chlorogenic acid 500mg.
Embodiment 14: powder
Prescription:
Purity is the chlorogenic acid 1000g of 98.62%
Method for making:
Get after recipe quantity chlorogenic acid sieves, according to the conventional fabrication process of powder, aseptic subpackaged one-tenth is containing 1000 bottle/bag powders, and every bottle/bag powder is containing chlorogenic acid 1000mg.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. the purposes of chlorogenic acid in the medicine of multidrug resistance preparing Therapeutic cancer.
2. chlorogenic acid and the antitumor drug purposes in the medicine preparing Therapeutic cancer.
3. purposes as claimed in claim 2, is characterized in that: described cancer is the cancer having produced multidrug resistance.
4. purposes as claimed in claim 3, is characterized in that: described cancer is breast carcinoma, small cell lung cancer or colon cancer.
5. purposes as claimed in claim 2, is characterized in that: described antitumor drug is chemotherapeutics.
6. purposes as claimed in claim 5, is characterized in that: described chemotherapeutics be selected from docetaxel, vinorelbine, amycin, oxaliplatin, etoposide, methotrexate and gemcitabine one or more.
7. the purposes as described in claim arbitrary in claim 1 to 6, is characterized in that: the described medicine prepared by chlorogenic acid is the activity of Teat pipette albumen and the medicine of expression on inhibition tumor cell surface.
8. the purposes as described in claim arbitrary in claim 1 to 6, is characterized in that: the described medicine prepared by chlorogenic acid is the medicine activating apoptosis of tumor cells path.
9. the purposes as described in claim arbitrary in claim 1 to 8, is characterized in that: described medicine is effective ingredient by chlorogenic acid, adds the preparation that one or more pharmaceutically acceptable pharmaceutical excipients are prepared from.
10. purposes as claimed in claim 9, is characterized in that: described preparation is oral formulations or ejection preparation.
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| CN106038531A (en) * | 2016-05-31 | 2016-10-26 | 湖南农业大学 | Application of chlorogenic acid to induction of HepG2 cell apoptosis |
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| CN107441075A (en) * | 2017-08-18 | 2017-12-08 | 四川九章生物科技有限公司 | A kind of antineoplastic combination medicine and its purposes in cancer therapy drug is prepared |
| CN107441076B (en) * | 2017-08-21 | 2020-06-12 | 四川九章生物科技有限公司 | Combined medicine for treating cancer |
| WO2019037671A1 (en) * | 2017-08-21 | 2019-02-28 | 四川九章生物科技有限公司 | Medicine for combined use in cancer treatment |
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| CN107441076A (en) * | 2017-08-21 | 2017-12-08 | 四川九章生物科技有限公司 | A kind of combination medicine for the treatment of cancer |
| US11628199B2 (en) | 2017-08-21 | 2023-04-18 | Sichuan Jiuzhang Biological Science And Technology Co., Ltd | Medicine for combined use in cancer treatment |
| WO2019042170A1 (en) * | 2017-08-28 | 2019-03-07 | 四川九章生物科技有限公司 | Combined drug for treating diseases related to tumor necrosis factor family |
| WO2019129135A1 (en) * | 2017-12-28 | 2019-07-04 | 四川九章生物科技有限公司 | Use of chlorogenic acid in preparation of drug for treating chordoma |
| CN109966280A (en) * | 2017-12-28 | 2019-07-05 | 四川九章生物科技有限公司 | Purposes of the chlorogenic acid in the drug of preparation treatment chordoma |
| US11547715B2 (en) * | 2017-12-28 | 2023-01-10 | Sichuan Jiuzhang Biological Science And Technology Co., Ltd. | Use of chlorogenic acid in preparation of drug for treating chordoma |
| CN108159038A (en) * | 2018-03-13 | 2018-06-15 | 四川九章生物科技有限公司 | A kind of pharmaceutical composition and its purposes in the drug for preparing treatment multi-drug resistance of the tumor |
| WO2019174571A1 (en) * | 2018-03-13 | 2019-09-19 | 四川九章生物科技有限公司 | Pharmaceutical composition and use thereof in preparing drug for treating tumor multi-drug resistance |
| CN108159038B (en) * | 2018-03-13 | 2020-06-12 | 四川九章生物科技有限公司 | Pharmaceutical composition and application thereof in preparation of medicine for treating tumor multidrug resistance |
| CN111568890A (en) * | 2020-05-28 | 2020-08-25 | 刘玉琳 | Application of chlorogenic acid, isomer or pharmaceutically acceptable salt in preparing tumor chemotherapy sensitization medicine |
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