CN109481688A - Pharmaceutical composition containing chemotherapeutics and Berbamine hydrochloride - Google Patents
Pharmaceutical composition containing chemotherapeutics and Berbamine hydrochloride Download PDFInfo
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- CN109481688A CN109481688A CN201811436483.4A CN201811436483A CN109481688A CN 109481688 A CN109481688 A CN 109481688A CN 201811436483 A CN201811436483 A CN 201811436483A CN 109481688 A CN109481688 A CN 109481688A
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- active constituent
- pharmaceutical composition
- chemotherapeutics
- berbamine hydrochloride
- berbamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a kind of pharmaceutical compositions, it is characterised in that: the pharmaceutical composition species contain active constituent (a) chemotherapeutics, active constituent (b) Berbamine hydrochloride and its pharmaceutically acceptable salt;And (c) pharmaceutically acceptable carrier.Berbamine hydrochloride and chemotherapy drugs in combination medication are improved into chemotherapeutics to the therapeutic effect of cancer patient in the present invention, and the side effect of chemotherapeutics can be reduced.
Description
Technical field
The present invention relates to biomedicine field, in particular to a kind of pharmaceutical composition containing chemotherapeutics and Berbamine hydrochloride
Object.
Background technique
Malignant tumour is always a global public health problem, greatly endangers the health of the mankind, and
Through the main reason for becoming new century human death.And the cure rate of cancer and the time-to-live of cancer patient are improved, it is existing
In the key points and difficulties of scientific research person's research.Most patients find to already belong to middle and advanced stage when malignant tumour, lose
The Best Times of surgical intervention, even if some patientss have carried out Operation in early stage, but recurrence rate is still high, changes at this time
Treatment becomes for its main therapeutic modality.Although common chemotherapy has obtained certain achievement, in practical applications still
There are anticancer drug poor biocompatibility, the absorption of patient's body cell is low, and the ill-effect that but will generate drug resistance is used for a long time,
Cause the actual medical function effect of anticancer drug unsatisfactory, in addition ordinary anticancer drugs are also different to human normal function
The side effect of degree, it is therefore desirable to the improvement of very big volume.
Researcher improves its anticancer effect, has conducted extensive research, taken at present to overcome the defect of chemotherapeutics
Obtain many achievements.
CN108191995A discloses a kind of amphiphilic polysaccharide derivative and its preparation method and application that reduction is sensitive, this
Kind amphiphilic polysaccharide derivative is a kind of excellent pharmaceutical carrier, unique excellent especially for having in insoluble anti-tumor medicament
Gesture.This reduction sensitivity characteristic can reach fast depolymerization derivative carrier in tumour cell, thus quick release vitamin E
Succinate and altogether carrying anti-tumor drug, enhance tumor locus drug accumulation, are conducive to promote curative effect, reduce side effect and reduce
Drug resistant generation.
CN108467439A discloses a kind of preparation method of water-soluble paclitaxel chemotherapeutics, is repaired in the invention with acid anhydrides
Hyaluronic acid is adornd, then is connected to taxol, which shows good injection safety, self aggregation characteristic and Drug loading capacity.
CN103043635A discloses a kind of preparation method of the cis-platinum mineralized liquid of anti-drug resistance, comprising the following steps: (1)
Cis-platinum is added in follow-on DMEM culture medium, reacts the midbody solution replaced under similar physiological condition;(2)
Calcic inorganic salts are added into obtained substituted midbody solution, under similar physiological condition reaction obtain nanometer it is cured in
Mesosome system;(3) fetal calf serum albumen is added into the obtained cured intermediate system of nanometer, obtains the cis-platinum mineralising
Liquid.The invention also discloses cis-platinum mineralized liquid and its application made from the preparation method, which has tumour cell
There is stronger lethality, and the tumour with obvious drug resistance difficult to treat for cis-platinum has apparent therapeutic effect.
CN104784700A discloses the preparation method that a kind of drug carries compound, micella and micella altogether, and drug carries multiple altogether
Object is closed to be combined by cis-platinum, adriamycin and multi-arm copolymer.The drug carries compound altogether and forms micella in an aqueous medium, more
PEG block is in the outer core of micella in arm copolymer, and polyglutamic acid block or aspartic acid block are in glue in multi-arm copolymer
The kernel of beam, cis-platinum and adriamycin are among this two parts and are protected, and keep its stability preferable, will not occur to discharge suddenly
Phenomenon.In addition, the carboxyl of cis-platinum and multi-arm copolymer is coordinated, there is crosslinked action, increase the stability of micella;Swollen
Tumor tissue or near tumor cells, adriamycin and Platinol cisplatin with quick release and can play drug effect, to improve curative effect of medication, reduce
Toxic side effect.
It is temporarily had not seen in the prior art by Berbamine hydrochloride and chemotherapeutic drugs to improve chemotherapeutics chemotherapy effect,
Reduce the report of its ill effect.
Summary of the invention
The purpose of the present invention is to provide a kind of purposes of Berbamine hydrochloride, i.e., for improving chemotherapeutics to cancer patient
Therapeutic effect, or the side effect for reducing chemotherapeutics.
Another object of the present invention is to provide the pharmaceutical compositions and its application of a kind of chemotherapeutics and Berbamine hydrochloride.
The technical solution used in the present invention is:
A kind of pharmaceutical composition, it is characterised in that: the pharmaceutical composition species contain
Active constituent (a) chemotherapeutics,
Active constituent (b) Berbamine hydrochloride and its pharmaceutically acceptable salt;And
(c) pharmaceutically acceptable carrier.
Further, the total content of active constituent (a) and active constituent (b) is 1~99wt% of pharmaceutical composition.
Further, active constituent (a) is cis-platinum or derivatives thereof.
Further, the mass ratio of active constituent (a) and active constituent (b) is (0~2): (10~300), and activity at
The amount for dividing (a) is not 0.
Further, the mass ratio of active constituent (a) and active constituent (b) is (0.1~1): (100~300).
Further, active constituent (a) is taxol or derivatives thereof.
Further, active constituent (a), active constituent (b) mass ratio be (0~2): (10~300), and active constituent
(a) amount is not 0.
Further, active constituent (a), active constituent (b) mass ratio be (1~2): (80~300).
Further, pharmaceutical composition is at least one of injection, tablet, capsule.
A kind of purposes of Berbamine hydrochloride is used to prepare a kind of preparation or a kind of medicine box, and the preparation or medicine box are for mentioning
High chemotherapeutics is to the therapeutic effect of cancer patient, or the side effect for reducing chemotherapeutics.
The beneficial effects of the present invention are:
Berbamine hydrochloride and chemotherapy drugs in combination are used in the present invention, compared to independent medication, lung carcinoma cell is killed
Power is stronger, more promotion Increase Apoptosis of Lung Cancer Cells, has stronger inhibiting effect to the growth of knurl.
Berbamine hydrochloride and chemotherapy drugs in combination are used in the present invention, enhance cancer cell to the sensitivity of chemotherapeutics
Property, the drug resistance of chemotherapeutics is greatly reduced, makes it possible that it is clinically widely used.
Berbamine hydrochloride and chemotherapy drugs in combination are used in the present invention, reduce the side effect of chemotherapeutics, improves and suffers from
The life quality of person.Cisplatin chemotherapy people digest road side effect is serious, and Berbamine hydrochloride can improve people digest road function.And
And cisplatin chemotherapy patient will appear bone marrow suppression, the quantity of leucocyte and blood platelet can continue to decline, when reducing to a certain extent
Shi Bixu is discontinued, and also will affect the treatment of tumour.And Berbamine hydrochloride plays the role of increasing leukocyte, can alleviate to a certain extent
The generation of the side effect.Therefore, Berbamine hydrochloride and Cisplatin can effectively improve the life quality of patient.
Berbamine hydrochloride is a kind of Common drugs, and by it, easy to use and economic benefit is extremely good with chemotherapy drugs in combination
It is good.
Detailed description of the invention
Fig. 1 is inhibiting rate of the various concentration Berbamine hydrochloride to H1299;
Fig. 2 is cell experiment figure;
Fig. 3 is zoopery figure.
Specific embodiment
Below in conjunction with specific experiment, the present invention is further explained, it should be appreciated that following experiment be merely to illustrate the present invention and
It is not used in and limits the scope of the invention.
It is whether statistically significant using t inspection statistics analysis group difference, hydrochloric acid barberry is evaluated using the equal q value method of Nintaus
The concertedness of amine and cis-platinum drug effect, specific formula are as follows: Q=RA+B/ (RA+RB-RA × RB).Q < 0.85 is antagonism, 0.85≤Q
< 1.15 is to be added, and Q >=1.15 are concertedness synergistic effect.Wherein, RA+B is the tumor control rate of drug combination group, and RA is salt
The tumor control rate of sour berbamine, RB are the tumor control rate of cis-platinum.
(1) cell experiment
A) MTT experiment:
Drug is detected to the inhibiting rate of tumour cell H1299 by MTT experiment, setting drug concentration gradient is respectively 0 μM,
It is thin to tumour to detect drug under various concentration for 1.5 μM, 3.125 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM, 100 μM, 200 μM
The inhibiting rate of born of the same parents H1299, as a result as shown in Figure 1, the toxicity of display Berbamine hydrochloride is very low.
B) CCK8 is tested:
The effect that detection Berbamine hydrochloride enhanced sensitivity cis-platinum kills lung carcinoma cell is tested by CCK8.CCK8 experiment can be accurate
Drug is detected to the inhibiting rate of tumour cell, H1299 lung cancer cell line is selected in this experiment, and it is small that grouping is set as control group, hydrochloric acid
Bark of a cork tree amine independent role group, cis-platinum independent role group, Berbamine hydrochloride and cisplatin combined medication group, wherein Berbamine hydrochloride concentration is set
It is set to 5 μM;Cis-platin concentrations are respectively set to 12.5 μM, 25 μM, 50 μM.That is the mixed proportion of cis-platinum and Berbamine hydrochloride are as follows: 5:
2;5:1;10:1.Determine whether Berbamine hydrochloride kills lung carcinoma cell tool to cis-platinum by detecting the survival condition of group of cells
There is sensitization.Wherein Fig. 2A is that the cell state with Cisplatin Berbamine hydrochloride is applied alone in microscopically observation cis-platinum, is found
Obviously there is apoptosis in drug combination group cell.Fig. 2 B is that CCK8 detects different cis-platin concentrations combination Berbamine hydrochlorides to cell inhibition
Effect, joint group apoptosis rate is higher than cis-platinum list medicine group (P < 0.01) as the result is shown, and enhanced sensitivity Q value > 1.15, it is seen that hydrochloric acid barberry
Amine has sensitization to cis-platinum and taxol killing lung carcinoma cell.
C) streaming apoptosis is tested:
The effect that detection Berbamine hydrochloride enhanced sensitivity cis-platinum kills lung carcinoma cell is tested by streaming apoptosis.Cultivate H1299 lung
Cancer cell line, according to control group, Berbamine hydrochloride independent role group, cis-platinum independent role group, Berbamine hydrochloride and cisplatin combined
Four medication group, Berbamine hydrochloride and paclitaxel plus medication group groupings carry out bed board and feeding operations, wherein Berbamine hydrochloride
It is 5 μM that concentration, which is arranged, and it is 25 μM that concentration, which is arranged, in cis-platinum, and it is 1 μM that concentration, which is arranged, in taxol.According to Annexin-V-PI apoptosis reagent
Box is using step process sample and carries out machine testing in streaming, the apoptosis rate of group of cells is obtained, so that it is determined that Berbamine hydrochloride
Whether there is effect of enhanced sensitivity to cis-platinum killing lung carcinoma cell.Fig. 2 C is that Flow cytometry experiments detect Apoptosis: Berbamine hydrochloride
Combination group apoptosis rate, which is apparently higher than, is applied alone a group apoptosis rate, with statistically significant (the P < of cis-platinum list medicine group comparing difference
0.01), the enhanced sensitivity Q value > 1.15 of Berbamine hydrochloride and Cisplatin, Berbamine hydrochloride and Cisplatin have synergistic effect (left
Figure);Berbamine hydrochloride combination group apoptosis rate, which is apparently higher than, is applied alone a group apoptosis rate, has system with taxol list medicine group comparing difference
Meter learns meaning (P < 0.01), enhanced sensitivity Q value > 1.15 associated with berbamine and taxol, and Berbamine hydrochloride and taxol combination have
It acts synergistically (right figure).Berbamine hydrochloride has sensitization to cis-platinum and taxol killing lung carcinoma cell as the result is shown.
(2) nude mice lotus knurl is tested
The nude mice of 5-8 week old, weight 18-22g is bought, is inoculated with first with H1299 cell strain, subcutaneous transplantation knurl model is carried out
Building, proposed adoption lung cancer cell line H1299 is inoculated with, every 5,000,000 cells of inoculation, carries out drug to nude mice after tumor formation
Abdominal cavity drug injection, 1 time/d of frequency of injection, grouping are set as control group, Berbamine hydrochloride independent role group (30mg/kg), suitable
Platinum independent role group (0.5mg/kg), Berbamine hydrochloride and Combined with Cisplatin for The Treatment group, the i.e. mixing ratio of cis-platinum and Berbamine hydrochloride
Example is 1:60.The volume that tumor is measured while administration, puts to death mouse after tumor reaches certain volume, takes pictures, remove tumour, claims
Taking tumor weight, wherein Fig. 3 A takes pictures for the grouping of tumor bearing nude mice and subcutaneous knurl;Fig. 3 B is gross tumor volume grouped comparison, Fig. 3 C
For tumor weight grouped comparison.The knurl inhibiting effect of joint group is significantly stronger than single medicine group, and Berbamine hydrochloride and Cisplatin
Enhanced sensitivity Q value > 1.15, Berbamine hydrochloride and Cisplatin have synergistic effect.The tumor control rate of drug combination group as the result is shown
Maximum, and Berbamine hydrochloride and cis-platinum have synergistic effect to inhibition tumour.
Claims (10)
1. a kind of pharmaceutical composition, it is characterised in that: the pharmaceutical composition species contain
Active constituent (a) chemotherapeutics,
Active constituent (b) Berbamine hydrochloride and its pharmaceutically acceptable salt;And
(c) pharmaceutically acceptable carrier.
2. pharmaceutical composition according to claim 1, it is characterised in that: active constituent (a) always contains with active constituent (b)
Amount is 1~99wt% of pharmaceutical composition.
3. pharmaceutical composition according to claim 1 or 2, it is characterised in that: active constituent (a) is cis-platinum or its derivative
Object.
4. pharmaceutical composition according to claim 3, it is characterised in that: the quality of active constituent (a) and active constituent (b)
Than for (0~2): (10~300), and the amount of active constituent (a) is not 0.
5. pharmaceutical composition according to claim 4, it is characterised in that: the quality of active constituent (a) and active constituent (b)
Than for (0.1~1): (100~300).
6. pharmaceutical composition according to claim 1 or 2, it is characterised in that: active constituent (a) is taxol or its derivative
Object.
7. pharmaceutical composition according to claim 6, it is characterised in that: the quality of active constituent (a), active constituent (b)
Than for (0~2): (10~300), and the amount of active constituent (a) is not 0.
8. pharmaceutical composition according to claim 7, it is characterised in that: the quality of active constituent (a), active constituent (b)
Than for (1~2): (80~300).
9. pharmaceutical composition according to claim 1, it is characterised in that: pharmaceutical composition is injection, tablet, capsule
At least one of.
10. a kind of purposes of Berbamine hydrochloride, it is characterised in that: be used to prepare a kind of preparation or a kind of medicine box, the preparation or
Medicine box is for improving chemotherapeutics to the therapeutic effect of cancer patient, or for reducing the side effect of chemotherapeutics.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111265545A (en) * | 2020-02-18 | 2020-06-12 | 广州中医药大学(广州中医药研究院) | Composition for treating lung tumor |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103181896A (en) * | 2011-12-30 | 2013-07-03 | 沈阳药科大学 | Liposome preparation comprising berbamine medicine, and preparation method thereof |
CN106031726A (en) * | 2016-03-17 | 2016-10-19 | 上海交通大学 | Docetaxel and berbamine double-load drug chitosan nanoparticles and preparation method thereof |
-
2018
- 2018-11-28 CN CN201811436483.4A patent/CN109481688A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103181896A (en) * | 2011-12-30 | 2013-07-03 | 沈阳药科大学 | Liposome preparation comprising berbamine medicine, and preparation method thereof |
CN106031726A (en) * | 2016-03-17 | 2016-10-19 | 上海交通大学 | Docetaxel and berbamine double-load drug chitosan nanoparticles and preparation method thereof |
Non-Patent Citations (3)
Title |
---|
JIA, FENG 等: "Synergistic Antitumor Effects of Berbamine and Paclitaxel through ROS/Akt Pathway in Glioma Cells.", 《EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE》 * |
朱陵君: "小檗胺与紫杉醇纳米微球的构建及其体外协同抑瘤效应评价", 《中国博士学位论文全文数据库. 医药卫生科技辑》 * |
赵勇: "小檗胺诱导前列腺癌细胞凋亡及其机制的研究.", 《中国优秀博硕士学位论文全文数据库 (博士).医药卫生科技辑》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111265545A (en) * | 2020-02-18 | 2020-06-12 | 广州中医药大学(广州中医药研究院) | Composition for treating lung tumor |
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