CN104586828A - Application of chlorogenic acid in preparation of drug for treating choriocarcinoma - Google Patents
Application of chlorogenic acid in preparation of drug for treating choriocarcinoma Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
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Abstract
The invention discloses application of chlorogenic acid in preparation of a drug for treating choriocarcinoma, and belongs to the field of biological medicine. The drug is prepared from chlorogenic acid as an active constituent and used for treating choriocarcinoma. The chlorogenic acid has the function of inhibiting tumors, meanwhile is harmless to a human body, and can improve the immunity of the organism, the organism hematopoietic function and the hepatorenal function; furthermore, the chlorogenic acid can block or reduce the inhibiting function of CTLA-4 on T cell immunological competence, so as to stimulate the immune cells to be proliferated in quantity, and further enhance the immunoreaction of the organism to the tumors; meanwhile, the drug can be combined with other anti-tumor drugs to play a more prominent anticancer effect on choriocarcinoma.
Description
Technical field
The invention belongs to biomedicine field, be specifically related to the purposes of chlorogenic acid in the medicine of preparation treatment choriocarcinoma.
Technical background
Gestational trophoblastic tumor is caused by gestational trophoblast anormogenesis and propagation, it is one group of rare nourishing leaf texture disease, can be regarded as the allograft originating from and infiltrate parent (afterbirth) tissue and become pregnant, there is unique morphology and Clinical biochemistry test, mainly comprise invasive mole, choriocarcinoma and placental site trophoblastic tumor, wherein choriocarcinoma has extremely strong aggressivity and extensive transitivity, can Blood route metastasis occur and jeopardize patient vitals in early days.Many employing chemotherapy are main clinically, and operation is that auxiliary mode is treated, but still has part high-risk transfer patient to occur drug resistance and recurrence, is a great problem of trophoblastic tumor to the treatment of this kind of patient always.In recent years, the biological immune treatment of high targeting becomes the new focus of tumour immunity research, and is applied to the treatment of tumor.
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.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.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.The chlorogenic acid now reported has multiple pharmacological effect, but also rarely has report in treatment choriocarcinoma.
Summary of the invention
For the problems referred to above, the invention provides a kind of novelty teabag of chlorogenic acid, be specially the purposes of chlorogenic acid in the medicine of preparation treatment choriocarcinoma.
Alternately, in such use, described medicine take CTLA-4 as target spot prevention and therapy choriocarcinoma.Cellular immunization plays a significant role in the immunne response of body to malignant tumor, and the existence of Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) can combine with Antigen Presenting Cell surface costimulatory molecules (B7) competitively with T cell surface costimulatory molecules receptor (CD28), thus the activation of suppressor T cell, lower or stop t cell responses, hindering the biological immune therapeutic effect of tumor.Therefore, CTLA-4 is considered to suppress body antineoplastic immune factor.By great many of experiments, inventor finds that chlorogenic acid is conducive to blocking or alleviating CTLA-4 to the immunocompetent inhibitory action of T cell, thus a large amount of propagation of immune stimulatory cell, thus enhancing body is to the immunoreation of tumor.
Present invention also offers a kind of medicine being used for the treatment of choriocarcinoma, its active component includes the chlorogenic acid of effective amount.
Alternately, described medicine take CTLA-4 as target spot prevention and therapy choriocarcinoma.
Alternately, described medicine is effective ingredient with chlorogenic acid, adds the preparation that one or more pharmaceutically acceptable pharmaceutical excipients are prepared from.
Alternately, in described medicine, every preparation unit contains chlorogenic acid 1 ~ 1000mg.
Alternately, described medicine is oral formulations or ejection preparation.
Alternately, described medicine is oral formulations or the injection that chlorogenic acid accounts for the 1-100% of medicine gross mass.
Alternately, described drug oral preparation is tablet, capsule, powder, electuary, granule.
Alternately, described drug injection preparation is injectable powder, injection.
Present invention also offers a kind of chlorogenic acid and other common drugs are preparing the purposes in the combination medicine for the treatment of choriocarcinoma.Further other common drugs described are that other antitumor class medicine (as 5-fluorouracil) Huo and immunne response promote class medicine..
Alternately, the dosage ratio of described chlorogenic acid and other common drugs is 1:5 ~ 2:1.
Alternately, described immunne response promotes class medicine to refer to can to promote or the medicine of active cell immunne response mechanism or immune factor, as one or more in interleukin 12, interleukin-22, IFN-γ.
Present invention also offers a kind of combination medicine for the treatment of choriocarcinoma, its active component includes chlorogenic acid and other common drugs of effective amount.
Alternately, described combination medicine be with chlorogenic acid and other common drugs for effective ingredient, add the preparation that one or more pharmaceutically acceptable pharmaceutical excipients are prepared from.
Alternately, the mass ratio of described chlorogenic acid and other common drugs is 1:5 ~ 2:1.
Drug combination refers to that two or more medicine adopted to reach therapeutic purposes is applied simultaneously or successively.Chlorogenic acid of the present invention and immunne response promote that the medication combined effect being used for the treatment of choriocarcinoma of class is what mutually promote, chlorogenic acid itself had both had the effect of Tumor suppression, simultaneously harmless to body again, and immunity of organisms can be improved, improve body hemopoietic function and hepatic and renal function; And chlorogenic acid can block or alleviate CTLA-4 to the immunocompetent inhibitory action of T cell, thus a large amount of propagation of immune stimulatory cell, thus enhancing body is to the immunoreation of tumor, improves the curative effect that immunne response promotes class medicine, there is good potential applicability in clinical practice.
All features disclosed in this description, or the step in disclosed all methods or process, except mutually exclusive feature and/or step, all can combine by any way.
Beneficial effect of the present invention:
The medicine that the present invention adopts chlorogenic acid to make as active component, is used for the treatment of choriocarcinoma.Chlorogenic acid itself had both had the effect of Tumor suppression, simultaneously harmless to body again, and can improve immunity of organisms, improves body hemopoietic function and hepatic and renal function; And chlorogenic acid can block or alleviate CTLA-4 to the immunocompetent inhibitory action of T cell, thus a large amount of propagation of immune stimulatory cell, thus enhancing body is to the immunoreation of tumor.Chlorogenic acid is blocked by two approach or alleviates CTLA-4 to the immunocompetent inhibitory action of T cell: 1. the target gene acting on CTLA-4, blocks the expression of CTLA-4, reduces the expression of CTLA-4 in body; 2. directly act on CTLA-4, make it lose activity.
Accompanying drawing illustrates:
Fig. 1 is the block diagram of each experimental group cell proliferative conditions in embodiment 1;
Fig. 2 is the block diagram of each experimental group cell proliferative conditions in embodiment 2;
Fig. 3 is the block diagram of each experimental group T cell activity in embodiment 3;
Fig. 4 is the block diagram of each experimental group tumour inhibiting rate in embodiment 4.
Detailed description of the invention:
Detailed description of the invention is by the following examples described in further detail foregoing of the present invention again.But this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following example.Not departing from any amendment made within the spirit and principles in the present invention, and the equivalent replacement made according to ordinary skill knowledge and customary means or improvement, all should be included in protection scope of the present invention.
Embodiment 1 chlorogenic acid take CTLA-4 as the simulation experiment of action target spot tumor killing effect
Cell culture
Choriocarcinoma cell line system JEG-3 Growth of Cells is containing in the DMEM in high glucose complete medium of 10% hyclone (adding 2mmol/L glutamine, 1mmol/L Sodium Pyruvate, 100U/ml penicillin and 100U/ml streptomycin), be placed in 37 DEG C, 5%CO2 incubator cultivates, within every 3 three days, change liquid once.When cell covers with about 70% ~ 80%, the pancreatin with 0.25% and 0.02%EDTA mixed liquor go down to posterity in 1:3 ratio.
MTT colorimetric method for determining cell proliferation
The JEG-3 cell getting exponential phase of growth is 3 × 10 by initial concentration
4/ ml is inoculated in 96 orifice plates, divides 6 groups to be respectively matched group, IL-12 group, CTLA-4+IL-12 group, 0.01 μM of chlorogenic acid+CTLA-4+IL-12 group, 0.1 μM of chlorogenic acid+CTLA-4+IL-12 group and 1 μM of chlorogenic acid+CTLA-4+IL-12 and organizes 37 DEG C, 5%CO
2changing serum-free medium after cultivating 48h in incubator into makes it continue hungry synchronization 24h; Then the CTLA-4 of IL-12,5ng/ml of 5ng/ml is given respectively and the green former of each dosage carries out exogenous intervention (the concrete means of intervention of each experimental group is in table 1) to JEG-3 cell, 36h stops cultivating and harvesting, matched group does not do exogenous intervention, and often group establishes 5 parallel holes.Discard culture medium in hole, gentle PBS washes 2 times, and every hole adds 180 μ L culture medium, the MTT solution of 20 μ L 5ng/ml, and gently shake culture plate, then the supernatant that carefully exhausts after putting back to incubator continuation cultivation 4h.Every hole adds 150 μ L dimethyl sulfoxide (DMSO), and vibration 10min, makes hyacinthine crystallization dissolve completely.Detect the OD value in each hole at microplate reader 492nm wavelength place after mixing.
Statistical procedures
SPSS 11.5 statistical package is adopted to carry out statistical analysis.Data all adopt mean ± standard deviation (-x ± s) to represent, adopt one factor analysis of variance to process data, adopt SNK-q inspection when comparing between two.Be significance test level with 0.05.
Result
MTT result shows: after the CTLA-4 of IL-12,5ng/ml of 5ng/ml and the green former of each dosage carry out effect 36h to JEG-3 cell, IL-12 significantly can suppress the propagation of JEG-3 cell; CTLA-4 can suppress the activity of IL-12, and after CTLA-4+IL-12 combined effect 36h, compared with matched group, the propagation of JEG-3 cell is not effectively suppressed; Chlorogenic acid+CTLA-4+IL-12 group, the propagation of JEG-3 cell obtains obvious suppression, and the dosage of the degree suppressed and chlorogenic acid is dose-dependence (table 1, Fig. 1).
Table 1.IL-12, CTLA-4 and chlorogenic acid are on the impact of JEG-3 cell proliferation
The impact that embodiment 2 is bred JEG-3 Choriocarcinoma cell line
Cell culture
Choriocarcinoma cell line system JEG-3 Growth of Cells is containing in the DMEM in high glucose complete medium of 10% hyclone (adding 2mmol/L glutamine, 1mmol/L Sodium Pyruvate, 100U/ml penicillin and 100U/ml streptomycin), be placed in 37 DEG C, 5%CO2 incubator cultivates, within every 3 three days, change liquid once.When cell covers with about 70% ~ 80%, the pancreatin with 0.25% and 0.02%EDTA mixed liquor go down to posterity in 1:3 ratio.
MTT colorimetric method for determining cell proliferation
The JEG-3 cell getting exponential phase of growth is 3 × 10 by initial concentration
4/ ml is inoculated in 96 orifice plates, divides 5 groups to be respectively matched group, IL-12 group, chlorogenic acid 0.01 μM, 0.1 μM, 1 μM group 37 DEG C, 5%CO
2changing serum-free medium after cultivating 48h in incubator into makes it continue hungry synchronization 24h; Then add IL-12 (5ng/mL) by the grouping situation described in table 2 and corresponding dosage respectively or chlorogenic acid carries out exogenous intervention to JEG-3 cell, 36h stops cultivating and harvesting, and matched group does not do exogenous intervention, and often group establishes 5 parallel holes.Discard culture medium in hole, gentle PBS washes 2 times, and every hole adds 180 μ L culture medium, the MTT solution of 20 μ L 5ng/ml, and gently shake culture plate, then the supernatant that carefully exhausts after putting back to incubator continuation cultivation 4h.Every hole adds 150 μ L dimethyl sulfoxide (DMSO), and vibration 10min, makes hyacinthine crystallization dissolve completely.Detect the OD value in each hole at microplate reader 492nm wavelength place after mixing.
Statistical procedures
SPSS 11.5 statistical package is adopted to carry out statistical analysis.Data all adopt mean ± standard deviation (-x ± s) to represent, adopt one factor analysis of variance to process data, adopt SNK-q inspection when comparing between two.Be significance test level with 0.05.
Result
Result shows, chlorogenic acid effectively can suppress the propagation of Choriocarcinoma cell line, and inhibition presents dose-dependence, and inhibition is better than IL-12 (as shown in table 2, Fig. 2).
Table 2. chlorogenic acid is on the impact of JEG-3 cell proliferation
Embodiment 3 chlorogenic acid suppresses the activity of CTLA-4
The Inhibitory Mechanism of CTLA-4 is realized by the T cell generation apoptosis of mediated activation.Researcher finds that CTLA-4 can mediate the t cell proliferation not relying on Fas approach.After the t cell proliferation of activation, effector T cell quantity reduces, and the cytokine of secretion reduces thereupon, and the immunologic function of body is suppressed naturally.
Mice CTLA-4 model, selects BALB/c mouse, male, 18-22g.Disposable injection CTLA-430mg/kg dosage, the situation of later evaluation model foundation in 14 days.Model is successfully established animal random packet rear next day, weighs, and starts administration.Chlorogenic acid injection (according to dosage, chlorogenic acid is dissolved in normal saline and makes a series of chlorogenic acid lumbar injection liquid with variable concentrations) administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 13 days, laboratory animal is divided into 4 groups, matched group (the administration volume intraperitoneal injection of saline by identical with other experimental grouies) and chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg medication three dosage groups.Often organize 20 animals.
In giving the spleen aseptically getting mice on the the 3rd, 6,9,14 day of chlorogenic acid, add appropriate Hank ' s liquid grinding, with 200 order cell sievings, centrifugal 5 minutes of 1500r/m, abandons supernatant, adds Hank ' s liquid repeated washing 2 times.Collect splenocyte, add appropriate RPMI1640 culture fluid suspendible, the platform with 0.4% expects that orchid refuses staining counting, and viable count is not less than 95%, adds the dilution of RPMI1640 complete culture solution, and adjusts cell concentration to 1x107/ml.In 96 hole micro plates, every hole adds 100 μ L splenocyte suspensions and isopyknic ConA solution (final concentration is 5 μ g/ml), LPS solution (final concentration is 10 μ g/ml) or RPMI1640 culture fluid, repeats 3 holes.Separately establish blank group.Then, then 37 DEG C, after 5%CO2 cultivates 4 hours, each hole adds 50 μ l MTT solution (2mg/ml), continues cultivation 4 hours.Then, more centrifugal 5 minutes of 1000r/m, discard each hole supernatant, add the acid DMSO solution of 150 μ l respectively, vibration, puts 15 minutes in room temperature dark place, with microplate reader in wavelength 578nm place mensuration OD value.
Result
Result shows, effectively can suppress the activity of CTLA-4 thus the activity of raising body T cell, and present dose-dependent relation, wherein the dosage of 20mg/kg is the most effective dosage (as shown in table 3, Fig. 3).
Table 3. chlorogenic acid is on the impact of T cell activity
Note: compared with matched group, * p<0.005.
The research of embodiment 4 chlorogenic acid treatment choriocarcinoma mice tumour inhibiting rate
The foundation of animal model
Mice choriocarcinoma JEG-3 model, selects BALB/c mouse, male, 18-22g.Choriocarcinoma cell line system JEG-3 Growth of Cells is containing in the DMEM in high glucose complete medium of 10% hyclone (adding 2mmol/L glutamine, 1mmol/L Sodium Pyruvate, 100U/ml penicillin and 100U/ml streptomycin), be placed in 37 DEG C, 5%CO2 incubator cultivates, within every 3 three days, change liquid once.The JEG-3 cell compound concentration getting exponential phase of growth is 3 × 10
4/ ml Cell sap, every mice axil back inoculation 0.2ml tumor liquid.Inoculation animal random packet rear next day, weighs, and starts administration.Chlorogenic acid injection (according to dosage, chlorogenic acid is dissolved in normal saline and makes a series of chlorogenic acid lumbar injection liquid with variable concentrations) administration volume is every 10g mouse peritoneal injection 0.2ml, every day 1 time, successive administration 13 days, the administration next day of IL-12, dosage is 25 μ g/kg.Laboratory animal is divided into 5 groups, matched group, IL-12 administration group and chlorogenic acid 5mg/kg, 10mg/kg, 20mg/kg medication three dosage groups.Often organize 20 animals.After chlorogenic acid drug withdrawal, next day puts to death animal, weighs, and stripping tumor also claims tumor weight.Tumor control rate (%) is calculated according to tumor weight.Body weight and tumor are reused means standard deviation (x ± SD) and are represented.
Result
Lumbar injection gives the growth of tumor-bearing mice chlorogenic acid to choriocarcinoma JEG-3 obvious inhibitory action, and in certain dose-effect relationship, chlorogenic acid 20mg/kg tumour inhibiting rate is close with IL-12 tumour inhibiting rate.When chlorogenic acid and IL-12 drug combination, the significant tumour inhibiting rate improving IL-12.Under dosage used, chlorogenic acid has no significant effect (see table 4, Fig. 4) the weight of animals.
Table 4. chlorogenic acid is to the antitumor action of choriocarcinoma JEG-3
Note: compared with matched group, * * * P<0.005.
Embodiment 5
Be effective ingredient with chlorogenic acid, add the medicine that one or more pharmaceutically acceptable pharmaceutical excipients are prepared into the different dosage forms such as oral formulations, ejection preparation or externally applied transdermal drug-delivery preparation.Controlling every preparation unit chlorogenic acid content in gained medicine is 1 ~ 1000mg.
The research of chlorogenic acid treatment choriocarcinoma mice tumour inhibiting rate is carried out according to the experimental technique described in embodiment 4.Difference is: intramuscular injection, intravenous injection, transdermal administration and filling hello the four kinds of modes that changed into by the administering mode of chlorogenic acid are respectively tested.Result shows: under above-mentioned four kinds of administering modes, chlorogenic acid all has obvious inhibitory action to the growth of choriocarcinoma JEG-3.Carry out drug combination with interleukin 12 and 5-fluorouracil and chlorogenic acid respectively in example 4, result display chlorogenic acid and interleukin 12,5-fluorouracil all can work in coordination with the growth suppressing mice choriocarcinoma tissue mutually, and synergism is remarkable.
Embodiment 6: prepare lyophilized injectable powder with chlorogenic acid
1. the extraction of chlorogenic acid:
Chlorogenic acid crude drug used in the present embodiment, be obtained by extraction, purification in Flos Lonicerae, purity is 99.52%.
2. the preparation of chlorogenic acid lyophilized injectable powder
2.1 prescriptions:
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 2ml injectable powder 1000 altogether according to the routine operation of sterile powder injection, often prop up containing chlorogenic acid 40mg.
Embodiment 7: prepare pill with chlorogenic acid
1. the extraction of chlorogenic acid
The chlorogenic acid used in the present embodiment, be obtained by extraction, purification in Folium Eucommiae, purity is 98.33%.
2. the preparation of chlorogenic acid pill
2.1 prescription
2.2. 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 8: prepare oral solution with chlorogenic acid
1. the extraction of chlorogenic acid
The chlorogenic acid used in the present embodiment, be obtained by extraction, purification in Herba Arctii leaf, purity is 99.04%.
1. the preparation of chlorogenic acid oral solution
2.1 prescription
2.2 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 9: prepare tablet with chlorogenic acid
1. the extraction of chlorogenic acid:
The chlorogenic acid used in the present embodiment, be obtained by extraction, purification in Flos Lonicerae, purity is 98.37%.
2. the preparation of chlorogenic acid tablet
2.1 prescriptions:
2.2 method for makings:
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 10: prepare capsule with chlorogenic acid
1. the extraction of chlorogenic acid:
The chlorogenic acid used in the present embodiment, be obtained by extraction, purification in Folium Eucommiae, purity is 99.25%.
2. the preparation of chlorogenic acid capsule:
2.1 prescriptions:
2.2 method for makings:
Get chlorogenic acid and the Icing Sugar of recipe quantity, mix homogeneously, add 80% alcoholic solution and make soft material, dry, prepare 2000 capsules according to the conventional fabrication process of capsule after granulate, every capsules is containing chlorogenic acid 50mg.
Embodiment 11: prepare granule with chlorogenic acid
1. the extraction of chlorogenic acid
The chlorogenic acid used in the present embodiment, be obtained by extraction, purification in Folium Eucommiae, purity is 98.74%.
2. the preparation of chlorogenic acid granule
2.1 prescriptions:
2.2 method for makings:
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 12: prepare powder with chlorogenic acid
2. the extraction of chlorogenic acid:
The chlorogenic acid crude drug that the present embodiment is used, be obtained by extraction, purification in Herba Arctii leaf, purity is 98.82%.
2. the preparation of chlorogenic acid powder:
2.1 prescription
Purity is the chlorogenic acid 1000g of 98.82%
2.2 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 the preferred embodiments of the present invention, is only illustrative for the purpose of the present invention, and nonrestrictive; Those of ordinary skill in the art understand, and can carry out many changes in the spirit and scope that the claims in the present invention limit to it, amendment, and even equivalence is changed, but all will fall into protection scope of the present invention.
Claims (10)
1. the purposes of chlorogenic acid in the medicine of preparation treatment choriocarcinoma.
2. purposes according to claim 1, is characterized in that, described medicine take CTLA-4 as target spot prevention and therapy choriocarcinoma.
3. treat a medicine for choriocarcinoma, it is characterized in that, its active component includes the chlorogenic acid of effective amount.
4. medicine according to claim 3, is characterized in that, described medicine is effective ingredient with chlorogenic acid, adds the preparation that one or more pharmaceutically acceptable pharmaceutical excipients are prepared from.
5. medicine according to claim 3, is characterized in that, in described medicine, every preparation unit contains chlorogenic acid 1 ~ 1000mg.
6. medicine according to claim 3, is characterized in that, described medicine is oral formulations or ejection preparation preparation.
7. chlorogenic acid and other common drugs are preparing the purposes in the combination medicine for the treatment of choriocarcinoma.
8. purposes according to claim 7, is characterized in that, the dosage ratio of described chlorogenic acid and other common drugs is 1:5 ~ 2:1.
9. purposes according to claim 7, is characterized in that, other medicines described are one or more in 5-fluorouracil, interleukin 12, interleukin-22, IFN-γ.
10. treat a combination medicine for choriocarcinoma, it is characterized in that, its active component includes other common drugs of chlorogenic acid of effective amount.
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| CN201510080133.9A CN104586828A (en) | 2015-02-13 | 2015-02-13 | Application of chlorogenic acid in preparation of drug for treating choriocarcinoma |
| PCT/CN2016/073127 WO2016127850A1 (en) | 2015-02-13 | 2016-02-02 | Application of chlorogenic acid in preparing medicines for treating choriocarcinoma |
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| WO2016127850A1 (en) * | 2015-02-13 | 2016-08-18 | 四川九章生物科技有限公司 | Application of chlorogenic acid in preparing medicines for treating choriocarcinoma |
| CN106890169A (en) * | 2016-10-11 | 2017-06-27 | 四川九章生物科技有限公司 | The purposes of chlorogenic acid and its derivative in the sensitizer for preparing immunotherapy of tumors medicine |
| CN109420167A (en) * | 2017-08-28 | 2019-03-05 | 四川九章生物科技有限公司 | A kind of combination medicine for treating tumour |
| CN109674042A (en) * | 2019-02-02 | 2019-04-26 | 北京振东光明药物研究院有限公司 | A kind of nutriment and preparation method thereof improving immunity |
| CN115177609A (en) * | 2022-06-09 | 2022-10-14 | 河南科技大学 | Application of chlorogenic acid in preparation of product for relieving chicken immune stress |
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| WO2016127850A1 (en) * | 2015-02-13 | 2016-08-18 | 四川九章生物科技有限公司 | Application of chlorogenic acid in preparing medicines for treating choriocarcinoma |
| CN106890169A (en) * | 2016-10-11 | 2017-06-27 | 四川九章生物科技有限公司 | The purposes of chlorogenic acid and its derivative in the sensitizer for preparing immunotherapy of tumors medicine |
| CN109420167A (en) * | 2017-08-28 | 2019-03-05 | 四川九章生物科技有限公司 | A kind of combination medicine for treating tumour |
| CN109420167B (en) * | 2017-08-28 | 2022-02-11 | 四川九章生物科技有限公司 | Combined medicine for treating tumor |
| CN109674042A (en) * | 2019-02-02 | 2019-04-26 | 北京振东光明药物研究院有限公司 | A kind of nutriment and preparation method thereof improving immunity |
| CN109674042B (en) * | 2019-02-02 | 2022-05-27 | 北京振东光明药物研究院有限公司 | Nutrient for improving immunity and preparation method thereof |
| CN115177609A (en) * | 2022-06-09 | 2022-10-14 | 河南科技大学 | Application of chlorogenic acid in preparation of product for relieving chicken immune stress |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016127850A1 (en) | 2016-08-18 |
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