CN109248171A - Composition containing Imatinib and plant polyose - Google Patents
Composition containing Imatinib and plant polyose Download PDFInfo
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- CN109248171A CN109248171A CN201811068563.9A CN201811068563A CN109248171A CN 109248171 A CN109248171 A CN 109248171A CN 201811068563 A CN201811068563 A CN 201811068563A CN 109248171 A CN109248171 A CN 109248171A
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- Prior art keywords
- imatinib
- plant polyose
- polysaccharide
- composition
- polyose
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The present invention provides a kind of composition containing Imatinib or its pharmaceutically acceptable salt and plant polyose, the plant polyose are selected from one of lentinan, grifola polysaccharide and cucurbit polysaccharide.Animal experiment shows that composition of the present invention can produce the antitumous effect cooperateed with lung cancer model to liver cancer, gastric cancer.
Description
Technical field
The present invention relates to pharmaceutical technology fields, and in particular to the composition containing Imatinib and plant polyose.
Background technique
Imatinib (imatinib, also known as STI-571, CGP57148B) is phenylamino pyrimidine (phenylamino
Pyrimidine) derivative, entitled (4- [(4- methyl-1-piperazine) methyl]-N- [4- methyl-3- { (4- (3- pyridine) 2- of chemistry
Pyrimidine) } amino] phenyl) aniline, its medicinal mesylate, structural formula is as follows.
Imatinib is a kind of selective tyrosine kinase inhibitor, by competitively and on BCR-ABL kinases
ATP-binding site combines, and inhibits its tyrosine kinase activity, blocks the autophosphorylation of kinases and substrate phosphorylation horizontal, from
And specifically inhibits the hyperplasia of BCR-ABL positive cell and induce its apoptosis.Imatinib obtains the idicatio packet of FDA approval
Include the entity tumors such as the hematological system tumors such as chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST), wherein she replaces at horse
Buddhist nun is especially noticeable in the application of the first-line treatment of CML chronic phase.Most of CML chronic phase patients have Imatinib aobvious
The hematology and cytogenetics of work are alleviated, but with the progress of the state of an illness, cells resistance phenomenon gradually shows, most accelerated periods
Secondary resistance is produced to Imatinib with rapid change period patient, and small number of patients has initial drug-resistant to the medical instrument.One by
The II phase test result that 181 CML accelerated period patients participate in is shown, after the treatment by 12 months, about 66% accelerated period
Patient is not up to complete hematologic response (CHR), and 76% patient is not up to Major cytogenetic and alleviates (MCy R).It is another
Then show respectively there is 84% and 93% rapid change period patient not by the II phase test result that 229 CML rapid change period patients participate in
Reach MCy R and complete cytogenetics alleviates (CCy R).In short, over time and the progress of the CML state of an illness, drug resistance
Phenomenon and recurrence rate are in rising trend, have seriously affected long-term treatment effects (Shao Shengjuan, Li Yan girl's target of Imatinib
To progress [J] Chinese Journal of New Drugs and Clinical Remedies of anticarcinogen imatinib-resistant, 2013,32 (07): 512-520.).
Although in addition, there is expression in the cell of the kinds of tumors of the action target spot of Imatinib, and cell assay in vitro, animal experiment
Or early studies in man is shown, Imatinib is to breast cancer (Wang Qimin, Yu Xiangli, Lv Li, Tang Ying, Feng Xiaohai, Wang Li sweet smell target
Expression and clinical meaning [J] oncology magazine of the molecular target albumen in triple negative breast cancer to therapeutic agent, 2014,
20 (09): 710-714.), prostate cancer (Zhu Jun, Song Yuqin, Sun Zhongshi oncotherapy rational use of medicines expert's roundtable conference summary
[J] Chinese Hospitals medication evaluation and analysis, 2007 (01): 1-5.), non-small cell lung cancer (Maj E et al.Vitamin D
Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human
A549Lung Tumor Model.Int J Mol Sci.2015；16 (11): 27191-207.) and oophoroma (meter peak ovary
Study of evidence based medicine [D] the Guangxi Medical University for the clinical early diagnosis recurred after epithelioma Normalized Treatment, 2012.) etc. real
Body tumor also has potential antitumor action, however since hazard and benefit feature is not good enough, Imatinib answers the treatment of above-mentioned tumour
Test cell line, animal experiment or early studies in man stage are stopped at exploitation
By improving Imatinib dosage or it being overcome its drug resistance with conventional cytotoxic drug combinations medication
Property problem effort produce little effect, and can increase occur adverse reaction risk.Therefore, other are found with synergistic antitumor
The combination of effect, it will help the hazard and benefit feature for improving treatment with imatinib CML and solid tumor realizes patient therefrom
Maximum benefit.
Polysaccharide is to be gathered by 10 or more monosaccharide by the natural polymer containing aldehyde radical or ketone group that glucosides key connection is formed
Object is closed, is widely present in animal, plant, in microorganism.And in recent years the study found that polysaccharide have significant ground anti-tumor activity
And it is relatively small to the toxic side effect of human body, domestic and international expert is had become in medical domain to the bioactivity research of polysaccharide
The hot spot of scholar's research, be applied to clinic has lentinan, grifola polysaccharide, ganoderma lucidum polysaccharide, coriolan, astragalus polyose
Deng.
Data shows that polysaccharide mainly plays antitumor action in terms of 2: being inhibited indirectly by improving host immune function
Or kill tumour cell；By induction tumor cell differentiation or apoptosis, influence the direct antitumor actions of performances such as oncogene expression.
Reinforce research to anti-tumor activity of polysaccharides, specify polysaccharide in anti cancer mechanism to developing polysaccharide for tumor therapeutic agent or
Adjuvant therapy medicaments play a significant role.It has now been found that have the polysaccharide of anti-tumor activity mainly from animal polysaccharide, plant
Object polysaccharide, microbial polysaccharide.
Yu Yi is built et al. according to the report, can significantly reduce patients with lung cancer Ki- using Radix Astragali polysaccharide injection joint Gefitinib
67 and improve P53 protein expression significant effect.(Yu Yijian, Gan Meifu Radix Astragali polysaccharide injection combine Gefitinib to lung cancer
Influence [J] the China biochemical drug magazine of patient tissue P53 and Ki-67 protein expression, 2016,36 (03): 143-145.).Wu
Army et al. is according to the report, astragalus polyose S replaces Buddhist nun's anti-gastric cancer SGC-7901 cell by inhibiting p-AKT signal path to enhance Ah pa
Effect (Wu Jun, Zhang Junling, Wang Jing, Yu Junxian, the big astragalus polyose of Cao nation by inhibit Phosphorylated Protein Kinase B expression enhancing Ah
Research [J] Chinese Hospitals medication evaluation and analysis of the pa for Buddhist nun's anti-gastric cancer cytosis, 2017,17 (06): 731-734.).
The skill of synergistic antitumor effect is temporarily generated without the combination using Imatinib and plant polyose in the prior art
Art enlightenment.
Summary of the invention
One of the objects of the present invention is to provide a kind of composition containing Imatinib and plant, the composition have association
Same antitumor action.
In order to realize the purpose, one aspect of the present invention provides a kind of containing Imatinib or its is pharmaceutically acceptable
The composition of salt and plant polyose, which is characterized in that the plant polyose is selected from lentinan, grifola polysaccharide and cucurbit polysaccharide
One of.
Preferably, Imatinib pharmaceutically acceptable salt of the present invention is imatinib mesylate.
Preferably, in composition of the present invention the mass ratio of Imatinib and plant polyose in 1:(0.1~10) between.
Preferably, the plant polyose in composition of the present invention is the lentinan that molecular weight is 47kDa~310kDa.
Preferably, the plant polyose in composition of the present invention is the grifola polysaccharide that molecular weight is 4kDa~360kDa.
Preferably, the plant polyose in composition of the present invention is the cucurbit polysaccharide that molecular weight is 16kDa~340kDa.
Another aspect of the present invention is provided comprising the oral of the composition as previously described containing plant polyose and Imatinib
Solid pharmaceutical preparation, the oral solid formulation further contain diluent and lubricant, and ordinary skill people can be used
Prepared by formulation method known to member, specific preparation method can refer to but be not limited to " pharmacy " of Cui Fude chief editor
(the 7th edition, People's Health Publisher publishes).
The dosage form of the preparation of Orally administered composition of the present invention is preferably selected from one in granule, capsule and tablet
Kind.Wherein, the preparation method of granule of the present invention be by Imatinib, plant polyose, diluent, mix lubricant,
Obtain the granule comprising plant polyose and Imatinib.
The preparation method of capsule of the present invention is by Imatinib, plant polyose, diluent, mix lubricant
Afterwards, filling capsule to get arrive the capsule comprising plant polyose and Imatinib.
The preparation method of tablet of the present invention be by after Imatinib, plant polyose, diluent, mix lubricant,
Tabletting is carried out to get the tablet comprising plant polyose and Imatinib is arrived.
Diluent of the present invention be selected from pregelatinized starch, starch, dextrin, sucrose, microcrystalline cellulose, sorbierite,
One of mannitol, lactose, calcium sulfate, calcium monohydrogen phosphate and calcium phosphate；Wherein, most preferably pregelatinized starch.
Lubricant of the present invention be selected from sodium stearyl fumarate, stearic acid, magnesium stearate, calcium stearate, paraffin oil,
Paraffin, glycerin monostearate, monopalmitin, sodium acetate, sodium chloride, DL-leucine, sldium lauryl sulfate, laurel
One of alcohol magnesium sulfate, polyethylene glycol, polyoxyl 40 stearate and Brij30；Wherein, preferably stearic
Fumaric acid sodium.
The content of plant polyose and Imatinib in solid pharmaceutical preparation of the present invention and be thus related to medicament
Amount can be screened and be optimized by pharmacological testing well known to those of ordinary skill in the art, and the present invention is to this without special limit
System.
Another aspect of the present invention provides more containing Imatinib or its pharmaceutically acceptable salt and plant as previously described
Sugar is preparing the purposes in the drug for treating tumour.
Preferably, tumour of the present invention is selected from one of lung cancer, liver cancer and gastric cancer.
Animal test results show, with tumor weight inhibiting rate (WIR) for index, it is provided by the invention containing methanesulfonic acid she
The combination of imatinib and plant polyose is significantly higher than the two independent medication to the antitumous effect of liver cancer, gastric cancer and lung cancer model
The sum of effect, produce the antitumous effect of collaboration.
Specific embodiment
Below with reference to the embodiment of the present invention, description that is clear, finishing is carried out to technical solution of the present invention, it is clear that retouched
The embodiment stated is only a part of the embodiments of the present invention, instead of all the embodiments.Based on the embodiments of the present invention,
Every other embodiment obtained by those of ordinary skill in the art without making creative efforts, belongs to this hair
The range of bright protection.
The antihepatocarcinoma effect that 1 imatinib mesylate of test example is combined with plant polyose
192 second level male mice in kunming (18~22g of weight, 6~8 week old) are taken, 64 groups, including one are randomly divided into
Model group and 63 test groups as shown in Table 1, every group 3, be inoculated under the right side armpit of animal H22 liver cancer cells (about 2 ×
106It is a), prepare bearing mouse model.After inoculation for 24 hours, model group physiological saline stomach-filling, test group medicine as shown in Table 1
Object stomach-filling, two groups are administered once daily, and the 7 day cervical dislocation day after tomorrow of successive administration puts to death mouse, take tumor tissue, claim quality, according to
Following formula calculates tumor weight inhibiting rate (WIR), and the results are shown in Table 1.
The antihepatocarcinoma effect that 1 imatinib mesylate of table (IM) is combined with plant polyose
According to the data of table 1, imatinib mesylate compares model with the quality that plant polyose generates the antihepatocarcinoma effect cooperateed with
It encloses as shown in table 2.
2 imatinib mesylate of table (IM) cooperates with the quality of antihepatocarcinoma effect to compare range with plant polyose generation
The anti-gastric cancer effect that 2 imatinib mesylate of test example (IM) is combined with plant polyose
192 second level male mice in kunming (18~22g of weight, 6~8 week old) are taken, 64 groups, including one are randomly divided into
Model group and 63 test groups as shown in table 3, every group 3.Each group mouse inoculates 1 × 10 in right side armpit6MFC is thin
Born of the same parents.After inoculation 24 hours, model group physiological saline stomach-filling, once a day；Test group drug shown in table 3 and dosage form fill
Stomach, once a day.Successive administration puts to death all mouse after 7 days, win knurl, with the weight of electronic balance weighing tumour.And it adopts
Each test group tumor weight inhibiting rate (WIR) is calculated with following formula, the results are shown in Table 3.
The anti-gastric cancer effect that 3 imatinib mesylate of table (IM) is combined with plant polyose
According to the data of table 3, the quality that imatinib mesylate generates the anti-gastric cancer effect cooperateed with plant polyose compares model
It encloses as shown in table 4.
4 imatinib mesylate of table (IM) generates the quality for cooperateing with anti-gastric cancer to act on plant polyose and compares range
The effect of anti-lung cancer that 3 imatinib mesylate of test example (IM) is combined with plant polyose
192 second level male mice in kunming (18~22g of weight, 6~8 week old) are taken, 64 groups, including one are randomly divided into
Model group and 63 test groups as shown in table 5, every group 3.Each group mouse inoculates 1 × 10 in right side armpit6Lewis
Cell.After inoculation 24 hours, model group physiological saline stomach-filling, once a day；Test group drug shown in table 5 and dosage form fill
Stomach, once a day.Successive administration puts to death all mouse after 7 days, win knurl, with the weight of electronic balance weighing tumour.And it adopts
Each test group tumor weight inhibiting rate (WIR) is calculated with following formula, the results are shown in Table 5.
The effect of anti-lung cancer that 5 imatinib mesylate of table (IM) is combined with plant polyose
According to the data of table 5, imatinib mesylate compares model with the quality that plant polyose generates the effect of anti-lung cancer cooperateed with
It encloses as shown in table 6.
6 imatinib mesylate of table (IM) cooperates with the quality of effect of anti-lung cancer to compare range with plant polyose generation
Embodiment 1 includes the preparation of the capsule of imatinib mesylate and lentinan
Prescription (is counted) according to 100
Preparation method
Imatinib mesylate, lentinan, pregelatinized starch and the sodium stearyl fumarate for taking recipe quantity, are sufficiently mixed,
Filling capsule, packing, obtains 100 capsules.
Embodiment 2 includes the preparation of the capsule of imatinib mesylate and grifola polysaccharide
Prescription (is counted) according to 100
Preparation method
Imatinib mesylate, grifola polysaccharide, pregelatinized starch and the sodium stearyl fumarate for taking recipe quantity, are sufficiently mixed,
It is pressed into 100.
Embodiment 3 includes the preparation of the capsule of imatinib mesylate and cucurbit polysaccharide
Prescription
Preparation method
Imatinib mesylate, cucurbit polysaccharide, pregelatinized starch and the sodium stearyl fumarate for taking recipe quantity, are sufficiently mixed,
Packing.
Claims (10)
1. a kind of composition containing Imatinib or its pharmaceutically acceptable salt and plant polyose, which is characterized in that described
Plant polyose is selected from one of lentinan, grifola polysaccharide and cucurbit polysaccharide.
2. composition according to claim 1, which is characterized in that the Imatinib pharmaceutically acceptable salt be methanesulfonic acid she
Imatinib.
3. composition according to claim 1, which is characterized in that the mass ratio of Imatinib and plant polyose 1:(0.1~
10) between.
4. the composition of any one according to claim 1~3, which is characterized in that the plant polyose is lentinan, and
Its molecular weight is 47kDa~310kDa.
5. the composition of any one according to claim 1~3, which is characterized in that the plant polyose is grifola polysaccharide, and
Its molecular weight is 4kDa~360kDa.
6. the composition of any one according to claim 1~3, which is characterized in that the plant polyose is cucurbit polysaccharide, and
Its molecular weight is 16kDa~340kDa.
7. a kind of oral solid formulation containing composition according to claim 1, which is characterized in that the solid pharmaceutical preparation is into one
Step contains diluent and lubricant.
8. oral solid formulation according to claim 7, which is characterized in that the dosage form of the oral solid formulation is selected from capsule
One of agent, tablet and granule.
9. the purposes of composition according to claim 1 in the preparation of antitumor drugs.
10. purposes according to claim 9, the tumour is selected from one of liver cancer, gastric cancer and lung cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811068563.9A CN109248171A (en) | 2018-09-13 | 2018-09-13 | Composition containing Imatinib and plant polyose |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811068563.9A CN109248171A (en) | 2018-09-13 | 2018-09-13 | Composition containing Imatinib and plant polyose |
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| Publication Number | Publication Date |
|---|---|
| CN109248171A true CN109248171A (en) | 2019-01-22 |
Family
ID=65046872
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN201811068563.9A Withdrawn CN109248171A (en) | 2018-09-13 | 2018-09-13 | Composition containing Imatinib and plant polyose |
Country Status (1)
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113491771A (en) * | 2020-03-18 | 2021-10-12 | 苏州大学 | Application of small molecular compound in preparation of GLUT5 inhibitor for uptake and transportation of fructose |
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| CN104586902A (en) * | 2013-10-31 | 2015-05-06 | 江苏学府生物工程有限公司 | A method of producing cordyceps militaris-ganoderma spore powder soft capsule by a supercritical technique |
| CN104922181A (en) * | 2014-12-09 | 2015-09-23 | 林强 | Preparation composition containing broccoli extract with effects of improving immunity and suppressing tumors and preparation method of preparation composition |
| CN105175575A (en) * | 2015-10-30 | 2015-12-23 | 上海市农业科学院 | Ganoderma lucidum beta-glucan and preparing method and application thereof |
-
2018
- 2018-09-13 CN CN201811068563.9A patent/CN109248171A/en not_active Withdrawn
Patent Citations (4)
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|---|---|---|---|---|
| CN103096924A (en) * | 2010-04-16 | 2013-05-08 | 动量制药公司 | Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization |
| CN104586902A (en) * | 2013-10-31 | 2015-05-06 | 江苏学府生物工程有限公司 | A method of producing cordyceps militaris-ganoderma spore powder soft capsule by a supercritical technique |
| CN104922181A (en) * | 2014-12-09 | 2015-09-23 | 林强 | Preparation composition containing broccoli extract with effects of improving immunity and suppressing tumors and preparation method of preparation composition |
| CN105175575A (en) * | 2015-10-30 | 2015-12-23 | 上海市农业科学院 | Ganoderma lucidum beta-glucan and preparing method and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| 宫丹等: "植物多糖的免疫调节及抗肿瘤活性研究", 《北华大学学报（自然科学版）》 * |
| 虞义建等: "黄芪多糖注射液联合吉非替尼对肺癌患者组织P53及Ki-67蛋白表达的影响", 《中国生化药物杂志》 * |
| 褚珊珊等: "植物多糖抗肿瘤作用机制研究进展", 《中国民族民间医药》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113491771A (en) * | 2020-03-18 | 2021-10-12 | 苏州大学 | Application of small molecular compound in preparation of GLUT5 inhibitor for uptake and transportation of fructose |
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Application publication date: 20190122 |