CN109731019B - A composition with chemotherapy synergistic effect comprises components, preparation and application - Google Patents
A composition with chemotherapy synergistic effect comprises components, preparation and application Download PDFInfo
- Publication number
- CN109731019B CN109731019B CN201910173032.4A CN201910173032A CN109731019B CN 109731019 B CN109731019 B CN 109731019B CN 201910173032 A CN201910173032 A CN 201910173032A CN 109731019 B CN109731019 B CN 109731019B
- Authority
- CN
- China
- Prior art keywords
- ethanol
- composition
- parts
- mannose
- curcumin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a composition with chemotherapy synergy, a medicine containing the composition, a preparation method and application of the composition. The composition with the chemotherapy synergistic effect is prepared from the following raw materials in parts by weight: 30-70 parts of nano turmeric extract, 5-30 parts of mannose, 10-50 parts of moringa seed powder and 1-20 parts of pepper. The natural medicine composition has high bioavailability, can enhance the treatment effect of the chemotherapeutic medicine on cancer through the synergistic effect with the chemotherapeutic medicine, and effectively reduces the drug resistance of cancer patients on the chemotherapeutic medicine, thereby prolonging the life cycle of the patients and improving the life quality of the patients.
Description
Technical Field
The invention relates to the field of biological medicine, in particular to a composition with chemotherapy synergistic effect, a medicine containing the composition, a preparation method and application.
Background
Cancer is one of the chief culprits in taking people away from life, and 1/5 deaths worldwide are caused by various types of cancer every year. According to the latest statistical data of 2019 by the national cancer research center: there were 7.5 individuals with cancer per minute, with an incidence of 285.83 people/10 ten thousand cancer and a mortality rate of 170.05 people/10 ten thousand in 2015. The incidence and mortality of cancer have both been on an increasing trend year by year and have become one of the most serious diseases in our country. Cancer is a hyperproliferative disease, and modern medicine often adopts various strategies for treatment, such as surgery, radiation therapy, chemotherapy, etc. Surgical removal of tumors is often the most direct treatment method, but the method cannot be implemented for people with large age or improper operation, the surgical removal usually treats the symptoms and the root causes, and cancer cell metastasis frequently occurs in the later stage. Radiation therapy, although it can directly irradiate and kill cancer cells, causes side effects such as radiodermatitis. In contrast, chemotherapy using cytotoxic antineoplastic drugs is a widely accepted and effective treatment, often preferred by physicians as a strategy for treating cancer. However, many chemical drugs are also toxic to normal cells while killing cancer cells, which results in a series of side effects such as vomiting, diarrhea, alopecia, weight loss and the like, seriously affects the life quality of patients and reduces the life cycle of patients with tumors. In addition, the cancer cells often have strong molecular heterogeneity, and after a period of chemotherapy treatment, the cancer cells have strong resistance to the drugs, and finally the treatment efficacy of the chemotherapy drugs is reduced. Therefore, the development of natural compounds capable of relieving the toxic and side effects of chemotherapeutic drugs and enhancing the specific efficacy of chemotherapeutic drugs is crucial to improving the treatment effect and the life quality of cancer patients.
Curcumin is a natural polyphenol extracted from plant turmeric, and is of great interest to people due to its excellent anti-inflammatory, antioxidant, hypolipidemic, hypoglycemic, anti-tumor, anti-depression effects. The national institute of tumor is classified as a third-generation chemopreventive agent. A large number of cell, in vivo and in vitro experiments show that curcumin can inhibit the growth and metastasis of tumor cells by regulating multiple targets. For example, many signal pathways such as nuclear transcription factor NF-kB, Protein Kinase C (PKC) and protein tyrosine kinase PTK, blood vessel growth factor, apoptosis factor, etc. are regulated, and clinical experimental results with good effect on the treatment of tumors such as breast cancer, colorectal cancer, gastric cancer, etc. are available. In addition, it was found that patients were well tolerated in curcumin when it was used for colon cancer and showed no toxicity at high doses. Therefore, curcumin is a very attractive potential candidate in the field of tumor drugs.
Mannose is a monosaccharide, is usually present in the pericarp of certain fruits, is the only carbohydrate nutrient applied to clinic at present, and is usually involved in immune regulation in vivo. Recent studies show that (Pablo Sierra Gonzalez, et al, Man nose tumours growth and enhancement chemotherapy, Nature,2018,563:719-723) Mannose can produce obvious inhibition effect on tumors because Mannose influences glucose metabolism, thereby cutting off glucose utilization by cancer cells and inhibiting growth of the tumor cells. In addition, animal experiments indicate that the combination of mannose and chemotherapy is of significant help in improving survival of mice.
Moringa is the most widely cultivated plant in the genus Moringa, and there has been a description of edible Moringa in ancient Roman, which is called a "magic tree" because of its medicinal function in leaves, flowers, pods, roots, seeds, bark and gums. The moringa seeds have the effects of protecting liver, improving the functions of liver and kidney and treating acute liver injury. Wherein the oleic acid, which is a monounsaturated Omega-9 fatty acid, is rich in oleic acid, which is a fatty acid and helps to reduce total cholesterol and harmful cholesterol in blood, and further contains VC and VA (14.0 +/-0.6) mg/100g and (24.8 +/-0.7) mg/100g, (Asghari G., Palizban A., et al, Quantitative analysis of the nutritional components in leaves and seeds of the human Moringa peregrina (Forssk.). Pharmacology Research,2015,7(3):242-248.) which can effectively help to supplement vitamins required by human body.
Although the patent (publication No. CN105476996A) reports that curcumin in combination with afatinib can synergistically treat non-small cell lung cancer while reducing its side effects. But curcumin has potential problems that it is a fat-soluble medicine, has low bioavailability and greatly limits the exertion of the effect of curcumin on the aspect of tumor resistance. The combination of mannose and moringa seeds with chemotherapeutic drugs is not reported in documents at present.
Disclosure of Invention
In order to solve the problems, the invention provides a composition with chemotherapy synergistic effect, a medicament comprising the composition, a preparation method and application thereof.
The invention relates to a composition with chemotherapy synergism, a medicine containing the composition, a preparation method and application of the composition. The medicine of the composition is characterized by comprising the following raw materials in parts by weight: 30-70 parts of nano turmeric extract, 5-30 parts of mannose and 10-50 parts of moringa seed powder.
The composition with the chemotherapy synergistic effect is characterized by also comprising 1-20 parts by weight of pepper.
The preparation method of the composition with chemotherapy synergy is characterized by comprising the following steps:
weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to a conventional method, adding mannose, mixing, adding pharmaceutically acceptable auxiliary materials or auxiliary components, and mixing to prepare an acceptable arbitrary dosage form:
(1) crushing turmeric into coarse powder, adding 5-8 times of 80-85% ethanol, heating and extracting for three times, wherein the amount of the ethanol is 1.5-2 hours each time, adding ethanol to soak an extracting solution, stirring, standing for 24-48 hours, taking supernatant, heating filtrate under reduced pressure (65-75 ℃) to concentrate to a saturated solution, standing, precipitating crystals, drying the crystals to obtain curcumin, adding the prepared curcumin powder into an aqueous solution containing a surfactant Tween 80, and performing spray drying by using a high-pressure homogenization technology to obtain curcumin nanoparticles with the diameter of 100-1000 nanometers for later use.
(2) Peeling moringa seeds, crushing into primary powder, sieving with a 50-100 mesh sieve, adding 5-8 times of ethanol, and heating and extracting for three times. Recovering ethanol under reduced pressure, concentrating to obtain saturated solution, standing, precipitating crystal, and drying to obtain Moringa seed powder.
(3) Pulverizing pepper into coarse powder, adding 5-8 times of 80-85% ethanol, heating and extracting for three times, wherein each time lasts for 1.5-2 hours, combining extracting solutions, filtering, adjusting the pH value to 7, recovering the ethanol until no alcohol smell exists, continuing to concentrate to the relative density of 1.25-1.30 at 70 ℃, then adding 8-10 times of water, uniformly stirring, standing, filtering, concentrating the filtrate to the relative density of 1.15-1.20 at 70 ℃, then adding the ethanol until the ethanol concentration reaches 70%, standing, filtering, recovering the ethanol from the filtrate, concentrating, and performing vacuum drying to obtain the pepper extract for later use.
(4) And (3) combining the nano curcumin obtained in the step (1), the moringa seed powder obtained in the step (2) and the pepper extract obtained in the step (3), adding a certain amount of mannose, mixing, adding pharmaceutically acceptable auxiliary materials or auxiliary components, and preparing various dosage forms according to a general method in pharmaceutics.
The mannose is characterized by consisting of one or more of the following saccharides: d-mannose, oligomannose, preferably D-mannose.
The composition preparation is an oral preparation, wherein the oral preparation is prepared from the following components in parts by weight: tablet, capsule, decoction, pill, powder, unguent, liposome and granule, preferably tablet.
The preparation of the invention is a sustained-release, quick-release, buccal tablet, orally disintegrating tablet, dispersible tablet and the like.
The preparation is characterized in that the formulation also comprises excipients and auxiliary components necessary in pharmaceutics, and specifically comprises the following components: syrup, gum arabic, gelatin, sorbitol, xanthan gum, polyvinylpyrrolidone (PVP); lactose, sugars, corn starch, calcium phosphate, sorbitol, or anhydrous glucose; magnesium stearate, talc, polyethylene glycol or silica; potato starch, sodium carboxymethylcellulose, and the tablets may be coated according to known methods of conventional pharmaceutical practice.
The composition of the invention is used, and the chemotherapeutic agent comprises one or more of the following: alkylating agent, antimetabolite, anti-tumor antibiotic drug, anti-tumor animal and plant component drug, anti-tumor hormone drug, miscellaneous drug, PD- (L)1 monoclonal antibody drug, CAR-T drug, targeting drug, anti-angiogenesis targeting drug.
In the application of the invention, the alkylating agent of the chemotherapeutic drug is one or more of the following: nimustine, carmustine, lomustine, cyclophosphamide, ifosfamide, etc.; an antimetabolite which is one or more of: deoxyfluoroguanosine, doxycfloridine, 5-fluorouracil, mercaptopurine, thioguanine, cytarabine, fluoroguanosine, tegafur, gemcitabine, carmofur, hydroxyurea, methotrexate, eufordine, ancitabine; an anti-tumor antibiotic is one or more of the following: actinomycin D, doxorubicin, daunorubicin, epirubicin, mitomycin, pellomycin, pingyangmycin, pirarubicin; the antitumor animal and plant component medicine is one or more of the following medicines: irinotecan, cephalotaxine, hydroxycamptothecin, vinorelbine, taxol, taxotere, topotecan, vincristine, vindesine, vinblastine, teniposide, etoposide, elemene); anti-tumor hormones are one or more of the following: atamestane, anastrozole, aminoglutethimide, letrozole, formestane, megestrol, tamoxifen; miscellaneous, are one or more of the following: asparaginase, carboplatin, cisplatin, dacarbazine, oxaliplatin, loxapine, copaixol, mitoxantrone, procarbazine; PD- (L)1 monoclonal antibody medicine, which is one or more of the following: keytrudda, Opdivo, Tecntriq; a CAR-T drug that is one or more of: kymeriah, yescata; a targeted drug which is one or more of the following: gefitinib, crizotinib, ozatinib, arlinib; the anti-angiogenesis targeted drug is one or more of the following: rivatinib, Arvatinib, Bevacizumab, Fuquintinib, Apatinib.
The application of the invention is characterized in that the cancer comprises lung cancer, liver cancer, leukemia, breast cancer, esophagus cancer, stomach cancer, cervical cancer, prostatic cancer, colorectal cancer, gastric stromal tumor and ovarian cancer, and preferably lung cancer and stomach cancer.
Compared with the prior art, the invention has the beneficial effects that: through the improvement of the process, curcumin is subjected to nanocrystallization and piperine compounding to promote the absorption of curcumin, and a foundation is laid for improving the bioavailability of curcumin and improving the anti-tumor effect of curcumin. In addition, the invention further synergizes the nano curcumin, mannose and moringa seed powder, and finally realizes the excellent synergistic attenuation and synergism on chemotherapy.
The invention has the characteristics that:
1. the chemotherapeutical synergistic natural medicine composition is prepared by screening active substances from food-source plants and scientifically combining the active substances, and is safe, low in toxicity and excellent in effect.
2. The natural plant compound selected by the invention can be used together with chemotherapeutic drugs by regulating related pathways of cell proliferation or metabolism, and is beneficial to improving the treatment effect of the chemotherapeutic drugs.
3. The invention improves the dissolution rate of the curcumin through the process, thereby improving the bioavailability of the curcumin.
4. The invention has the advantages of high curative effect, convenient taking, no toxic or side effect and high patient compliance. Can greatly save the treatment cost of cancer patients.
Drawings
FIG. 1 dissolution comparison of the example and curcumin drug substance
Detailed Description
The following is a further illustration of the invention in conjunction with specific examples and experimental examples. These examples are only illustrative and not intended to limit the scope of the invention. The experimental methods in the following examples, in which specific experimental conditions are not specified, are generally carried out under conventional conditions.
Example 1 (Capsule)
Weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to the method to respectively obtain respective extracts, taking 70 parts by weight of nano turmeric extract, 10 parts by weight of moringa seed kernel powder and 10 parts by weight of pepper powder, adding 10 parts by weight of mannose, adding magnesium stearate, aerosil and dextrin to adjust the total amount, mixing uniformly, preparing granules, sieving, and filling into capsules.
Example 2 (tablet)
Weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to the method to respectively obtain respective extracts, taking 50 parts by weight of nano turmeric extract, 20 parts by weight of moringa seed kernel powder and 5 parts by weight of pepper, adding 20 parts by weight of mannose, adding lactose and corn starch, uniformly mixing, adding a lubricant of magnesium stearate, uniformly mixing, granulating, and tabletting to prepare tablets.
Example 3 (granules)
Weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to the method to respectively obtain respective extracts, taking 30 parts by weight of nano turmeric extract, 30 parts by weight of moringa seed kernel powder and 20 parts by weight of pepper, adding 20 parts by weight of mannose, adding diluent lactose or corn starch, uniformly mixing, granulating, drying and preparing into granules.
Example 4 (Capsule)
Weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to the method to respectively obtain respective extracts, taking 40 parts by weight of nano turmeric extract, 20 parts by weight of moringa seed kernel powder and 10 parts by weight of pepper powder, adding 30 parts by weight of mannose, adding magnesium stearate, aerosil and dextrin to adjust the total amount, mixing uniformly, preparing granules, sieving, and filling into capsules.
Example 5 (tablet)
Weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to the method to respectively obtain respective extracts, taking 45 parts by weight of nano turmeric extract, 18 parts by weight of moringa seed kernel powder and 17 parts by weight of pepper, adding 20 parts by weight of mannose, adding lactose and corn starch, uniformly mixing, adding a lubricant of magnesium stearate, uniformly mixing, granulating, and tabletting to prepare tablets.
Example 6 (granules)
Weighing raw materials of turmeric, moringa seeds and pepper according to parts by weight, grinding, extracting according to the method to respectively obtain respective extracts, taking 33 parts by weight of nano turmeric extract, 40 parts by weight of moringa seed kernel powder and 15 parts by weight of pepper powder, adding 12 parts by weight of mannose, adding diluent lactose or corn starch, uniformly mixing, granulating, drying and preparing into granules.
The improvement of the bioavailability of the natural chemical pharmaceutical composition of the present invention and the synergistic effect in combination with cancer chemotherapeutic agents are further illustrated by experiments below.
The bioavailability of the invention is improved
The dissolution rate of curcumin is determined according to the second method of XC dissolution determination method in the fourth appendix of the pharmacopoeia 2015 edition of China. 900mL of phosphate buffer solution with the pH value of 6.8 is adopted as a dissolution medium, 5mL of samples are respectively sampled at 0, 10, 20, 30, 40, 50, 60 and 80min at the rotating speed of 50r/min and the temperature of 37 +/-0.5℃, the samples are filtered, 10 mu L of filtrate is precisely measured and injected according to chromatographic conditions, the cumulative dissolution rate of each time point is calculated, and the dissolution medium with the same volume and temperature is simultaneously supplemented. The results are shown in FIG. 1. As can be seen from the figures, the examples of the present invention possess faster dissolution rates and greater cumulative dissolution rates than curcumin drug substance.
Secondly, the influence of the combination of the invention and chemotherapeutic drugs on the mouse transplantation tumor
1. Experimental methods
1.1 purpose of experiment: determination of Effect of embodiment 1 of the invention on mouse transplantation tumor
2 materials and methods:
2.1 test substance and model control
Subject name and source: embodiment 1 of the present invention.
Model comparison: distilled water
2.2 Experimental animals
The BALB/c mice of 4-8 weeks old are 80 mice, 18-22g, half male and female, SPF grade, and purchased from Beijing Wittingle laboratory animal technology Co. Conventional basal feeds were given for 5-7 days before the start of the test. Human lung cancer A549 cells were purchased from Shanghai cell institute of Chinese academy of sciences, and the cells were washed with RPMI-1640 medium containing 10% fetal bovine serum, and after conventional digestion, with RPMI-1640 medium. The cells in logarithmic growth phase are taken in the experiment, counted and adjusted to 215 multiplied by 107At a concentration of 200. mu.L/mL, i.e., 5X 106A cell.
2.3 feeding Environment
The seeds are raised in a barrier environment, the temperature is 26-28 ℃ (78-820F), and the relative humidity is 40-60%.
2.4 tumor inoculation, grouping and administration
Each animal was inoculated subcutaneously with 5X 10 lung cancer A549 cells6And then grouped. The method comprises the following eight groups:
1. blank control group (daily injection 1 time physiological saline at 0.05mL/10 g)
2. Chemotherapy group (diluted with Iressa 20mg, normal saline to 0.2mg/mL, and injected with drug-containing normal saline 1 time per day at a dose of 0.05mL/10 g)
3. And (4) sample group. The sample components comprise six groups of curcumin raw material drug group, moringa seed group, mannose group, combined high dose group, combined medium dose group and combined low dose group.
In addition to daily administration according to a chemotherapy group, the sample group is simultaneously administered with curcumin bulk drug according to 100mg/kg of the curcumin raw material group, moringa seed group is administered with 100mg/kg of moringa seed group, mannose is administered according to 100mg/kg of the pure mannose group, mice are administered with corresponding samples according to 200mg/kg of a combined high dose group, 100mg/kg of a combined medium dose group and 50mg/kg of a combined low dose group for 30 days continuously, and weight change after administration is observed in 15 days and 30 days respectively. Each group was administered by continuous gavage for 30 days, 1 time/day, the toxic reaction and death of the animals were observed within 30 days, the mice were sacrificed by removing the neck after 30 days, the tumors were dissected, weighed and the tumor inhibition rate was calculated and statistically examined. The experimental results are shown in tables 1 and 2, respectively.
3. Results of the experiment
As can be seen from Table 1, the weight of the chemotherapy groups decreased significantly after 15 days and 30 days, while the combined group did not change significantly at the medium and high doses, and the weight of the combination group decreased but still higher than that of the chemotherapy groups at the low dose, and the effect of the medium dose group in inhibiting the weight decrease was better than that of the group prepared by only using curcumin bulk drugs, moringa seeds and mannose with the same content. The combination is therefore more beneficial in reducing the weight loss of the chemotherapeutic (p <0.01), especially when administered at high doses.
TABLE 1 Effect of compositions on body weight of mice transplanted with A549 Lung cancer
Note: p < 0.01A-solidup-
Table 2 shows the effect of the combination of the composition and chemotherapeutic drugs on the inhibition of tumor activity, and the average tumor weight and tumor inhibition rate of each group of tumor-bearing mice were calculated. It can be seen that the tumor inhibition rate of the combined group is much higher than that of the other groups, and is as high as 70.7%. The tumor inhibition rate of the low-dose group in the combined group is also obviously higher than that of the chemotherapy group, the blank control group, the curcumin bulk drug group, the moringa seed group and the mannose group. The effects of the present invention can be seen.
TABLE 2 Effect of the compositions on tumor weight and tumor suppression Rate in mice transplanted with A549 Lung cancer
Note: p < 0.01A-solidup-
Thirdly, the medicine of the invention is used for treating 50 cases of cancer patients by combining with chemotherapeutic drugs, and a certain curative effect is achieved.
1 data and method
1.1 general data
Taking 50 patients, wherein 28 male patients are 28, 22 female patients are 22, the patients are 35-81 years old, the average age is 61.7 years old, and the course of disease is 1-3 years. The self-contrast test is adopted, namely, patients who are diagnosed as cancer and are currently undergoing chemotherapy are treated by the medicament. Cancer typing: lung cancer 25 cases, breast cancer 18 cases, liver cancer 7 cases.
1.2 methods of treatment
Oral administration of example 5 of the present invention, 3 times daily, 5 capsules each time, or following the physician's advice. After the medicine is taken for 3 months, the curative effect is evaluated by the conventional blood checking, the liver and kidney functions and the abdominal CT. The effective patients continue to take the medicine, and the related content is reviewed at 6 months to evaluate the curative effect. Then, the patients continue to take the medicines and observe the life cycle.
1.3 therapeutic criteria
Referring to the WHO therapeutic effect judgment standard,
complete Remission (CR): the tumor focus is completely absorbed;
partial Remission (PR): the tumor focus is continuously reduced, but the reduction volume is more than 50%;
stable (SD): the tumor focus is continuously reduced, but the reduction volume is less than 50%;
progression (PD): the tumor focus shows a continuous expansion trend, and the volume is expanded by more than 25 percent.
The objective effective rate of the treatment of the patient is (complete remission + partial remission)/the number of evaluable cases is multiplied by 100 percent,
patient disease control rate ═ complete remission + partial remission + mild remission)/number of evaluable cases × 100%.
The survival index is 3 months (human), 6 months (human), 1 year (human), 2 years (human) and 3 years (human).
2. Results
2.1 clinical efficacy
Of the 50 patients treated, there were 20 patients with complete remission, 18 patients with partial remission, 4 patients with mild remission and 8 patients with no efficacy. The objective effective rate is 76.00%, and the disease control rate is 84.00%.
The survival index is 3 months 8, 6 months 12, 1 year 10, 2 years 12, 3 years 8.
The data show that the objective effective rate and the disease control rate of the medicine are high.
Case 1: zhangjianju, male, 69 years old, lung cancer; after lung cancer is diagnosed by Beijing university tumor hospital, the lung focus disappears half a year after taking 9 capsules of example every day in combination with Yiruisha (gefitinib tablet).
Case 2: after taking the medicine for treating liver cancer in the age of 70 years old and women in the periwinkle, the patient has good complaints and no obvious side effects of chemotherapy 6 months after taking the medicine with sorafenib.
Case 3: liaohong, female, 67 years old, lung cancer. After the traditional Chinese medicine is taken for 5 months in the chemotherapy period, the tumor volume is reduced to 2.5 centimeters; the tumor volume is reduced to 1.4 cm in 12 months in the same year. No metastasis occurred in B-ultrasonic examination and no new tumor was observed.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (5)
1. A method for preparing a composition with chemotherapy synergy is characterized by comprising the following steps:
weighing raw materials of turmeric, moringa seeds and pepper according to the parts by weight, grinding, respectively extracting, adding mannose, mixing, adding pharmaceutically acceptable auxiliary components, and mixing to prepare any acceptable dosage form:
(1) crushing turmeric into coarse powder, adding 5-8 times of 80-85% ethanol, heating and extracting for three times, wherein the amount of the ethanol is 1.5-2 hours each time, adding ethanol to soak an extracting solution, stirring, standing for 24-48 hours, taking supernatant, heating filtrate under reduced pressure (65-75 ℃) to concentrate to a saturated solution, standing, precipitating crystals, drying the crystals to obtain curcumin, adding the prepared curcumin powder into an aqueous solution containing a surfactant Tween 80, and performing spray drying by using a high-pressure homogenization technology to obtain curcumin nanoparticles with the diameter of 100-1000 nanometers for later use;
(2) peeling moringa seeds, crushing into primary powder, sieving with a 50-100 mesh sieve, adding 5-8 times of ethanol, heating and extracting for three times, recovering ethanol under reduced pressure, concentrating to obtain saturated solution, standing, precipitating crystals, and drying the crystals to obtain moringa seed powder;
(3) crushing pepper into coarse powder, adding 5-8 times of 80-85% ethanol, heating and extracting for three times, wherein each time lasts for 1.5-2 hours, combining extracting solutions, filtering, adjusting the pH value to 7, recovering the ethanol until no ethanol smell exists, continuing to concentrate to 70 ℃ relative density of 1.25-1.30, then adding 8-10 times of water, uniformly stirring, standing, filtering, concentrating the filtrate to 70 ℃ relative density of 1.15-1.20, then adding the ethanol until the ethanol concentration reaches 70%, standing, filtering, recovering the ethanol from the filtrate, concentrating, and performing vacuum drying to obtain pepper extract for later use;
(4) and (3) combining the nano curcumin obtained in the step (1), the moringa seed powder obtained in the step (2) and the pepper extract obtained in the step (3), adding a certain amount of mannose, mixing, adding pharmaceutically acceptable auxiliary components, and preparing various dosage forms according to a general method in pharmaceutics.
2. The method according to claim 1, wherein the mannose is one or more of the following sugars: d-mannose and oligomannose.
3. The preparation containing the composition of claim 1, wherein the composition is an oral preparation, and the oral preparation is in the form of: tablet, capsule, decoction, pill, powder, unguent, liposome and granule.
4. The preparation of claim 3, wherein the tablet is a sustained-release, immediate-release, buccal tablet, orally disintegrating tablet, dispersible tablet.
5. The preparation according to claim 3, wherein the formulation further comprises pharmaceutically necessary auxiliary components, in particular: syrup, gum arabic, gelatin, sorbitol, xanthan gum, polyvinylpyrrolidone; lactose, sugars, corn starch, calcium phosphate, sorbitol, or anhydrous glucose; magnesium stearate, talc, polyethylene glycol or silica; potato starch, sodium carboxymethylcellulose, and the tablets may be coated according to known methods of conventional pharmaceutical practice.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910173032.4A CN109731019B (en) | 2019-03-07 | 2019-03-07 | A composition with chemotherapy synergistic effect comprises components, preparation and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910173032.4A CN109731019B (en) | 2019-03-07 | 2019-03-07 | A composition with chemotherapy synergistic effect comprises components, preparation and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109731019A CN109731019A (en) | 2019-05-10 |
| CN109731019B true CN109731019B (en) | 2021-07-16 |
Family
ID=66369794
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910173032.4A Active CN109731019B (en) | 2019-03-07 | 2019-03-07 | A composition with chemotherapy synergistic effect comprises components, preparation and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109731019B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20220387417A1 (en) * | 2019-11-11 | 2022-12-08 | Cstone Pharmaceuticals (Suzhou) Co., Ltd. | Pharmaceutical Combination and Use Thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1736369A (en) * | 2004-08-12 | 2006-02-22 | 山东绿叶天然药物研究开发有限公司 | Curcumin emulsion, its preparation process and use |
| CN1973834A (en) * | 2006-12-15 | 2007-06-06 | 中国科学院长春应用化学研究所 | Application of curcumin in preparing medicine for inventing drug resistance of malignant tumor |
| CN101164534A (en) * | 2007-07-24 | 2008-04-23 | 浙江大学 | Application of curcumin in preparing tumor multi-medicine drug-resistant prevention agent |
| CN101361713A (en) * | 2008-09-08 | 2009-02-11 | 山东大学 | Curcumin nano crystallization preparation and preparation method thereof |
| CN106798892A (en) * | 2017-03-09 | 2017-06-06 | 北京康蒂尼药业有限公司 | A kind of chemotherapy combined antitumor Chinese and its application with Synergy and attenuation effect |
-
2019
- 2019-03-07 CN CN201910173032.4A patent/CN109731019B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1736369A (en) * | 2004-08-12 | 2006-02-22 | 山东绿叶天然药物研究开发有限公司 | Curcumin emulsion, its preparation process and use |
| CN1973834A (en) * | 2006-12-15 | 2007-06-06 | 中国科学院长春应用化学研究所 | Application of curcumin in preparing medicine for inventing drug resistance of malignant tumor |
| CN101164534A (en) * | 2007-07-24 | 2008-04-23 | 浙江大学 | Application of curcumin in preparing tumor multi-medicine drug-resistant prevention agent |
| CN101361713A (en) * | 2008-09-08 | 2009-02-11 | 山东大学 | Curcumin nano crystallization preparation and preparation method thereof |
| CN106798892A (en) * | 2017-03-09 | 2017-06-06 | 北京康蒂尼药业有限公司 | A kind of chemotherapy combined antitumor Chinese and its application with Synergy and attenuation effect |
Non-Patent Citations (5)
| Title |
|---|
| Mannose impairs tumour growth and enhances chemotherapy;Pablo Sierra Gonzalez et al;《nature》;20181130;第563卷(第7733期);文章第719页左栏第1段，右栏最后一段，Fig. 2a- b, Fig.4a-c * |
| 姜黄提取物对畜禽病原菌的抑制作用;周云晓等;《饲料博览》;20160325(第3期);文章第45页左栏1.2.3 * |
| 姜黄素纳米混悬剂制备及体外溶出度研究;张小飞等;《辽宁中医药大学学报》;20161107;第15卷(第12期);文章第53页摘要，第54页左栏最后一段，右栏第1段 * |
| 胡椒中总生物碱提取工艺的研究;杨自朋;《齐鲁药事》;20061130;第25卷(第11期);文章第685页左栏第1段，右栏2.1，2.2，表1，第686页左栏表2和（4），右栏3讨论 * |
| 辣木籽的综合研究;杜同同等;《大众科技》;20171220;第19卷(第220期);第46页摘要，左栏第2段，右栏2.1，第47页右栏3.3 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109731019A (en) | 2019-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1878471A (en) | Hippophae rhamnoides compositions for cancer therapy | |
| Liang et al. | The synergism of natural compounds and conventional therapeutics against colorectal cancer progression and metastasis | |
| CN103179967A (en) | Anti-tumor pharmaceutical composition | |
| WO2015192758A1 (en) | Anti-tumor pharmaceutical application of pentacyclic triterpene saponin compounds of szechuan melandium root | |
| JP4944380B2 (en) | Extracts with antitumor and antitoxic activity | |
| US20210100860A1 (en) | Use of compositions of water/alcohol extracts of antrodia cinnamomea cut-log wood cultivated fruiting body and solid-state cultivated mycelium as auxiliaries for anti-cancer agents | |
| CN109731019B (en) | A composition with chemotherapy synergistic effect comprises components, preparation and application | |
| CA2700338C (en) | Anti-aids, anti-tumor, immune system stimulating herbal composition and production method | |
| JP6234553B2 (en) | Anticancer agent and side effect reducing agent | |
| CN104940241B (en) | A kind of selenium worm grass compound preparation of prevention climacteric metancholia of women | |
| CN101229175A (en) | Medical applications of couple protopanoxadiol derivatives and compound body thereof | |
| EP3441076A1 (en) | Pharmaceutical product for treating tumor and combined immune defect, and preparation and application thereof | |
| CN108815463A (en) | Natural drug, preparation method and application with cancer prevention effect | |
| WO2021185292A1 (en) | Use of astragalus medicinal composition for preparing drug for enhancing cancer therapy | |
| CN109662968A (en) | The liter white preparation of -5 α androstane hydride compounds of carbon loss containing A- and its application | |
| CN102423384B (en) | Traditional Chinese drug preparation for treating lung cancer, and preparation method thereof | |
| CN109010495A (en) | A kind of Chinese medicine composition and its preparation method and application | |
| CN106038566B (en) | A kind of pharmaceutical composition and its application for curing gastric cancer | |
| WO2004048358A1 (en) | Control of cancer with annonaceous extracts | |
| KR100485936B1 (en) | Anticarcinogenic constituents of ginsenoside Rh2 and Rg3 | |
| CN103191268B (en) | Traditional Chinese medicinal composition for treating lung cancer | |
| CN103142909B (en) | Orally traditional Chinese medicine composition for treating lung cancers | |
| WO2015090139A1 (en) | Antitumor drug, preparation method and use thereof | |
| CN107998142B (en) | A kind of combination of oral medication for treating myocardial ischemia-reperfusion injury | |
| CN106727512B (en) | Circular cone beggarweed alkali application in preparation of anti-tumor drugs and pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |