CN104127427B - A kind of anticancer synergia compositions - Google Patents
A kind of anticancer synergia compositions Download PDFInfo
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- CN104127427B CN104127427B CN201410361831.1A CN201410361831A CN104127427B CN 104127427 B CN104127427 B CN 104127427B CN 201410361831 A CN201410361831 A CN 201410361831A CN 104127427 B CN104127427 B CN 104127427B
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- 239000000203 mixture Substances 0.000 title claims abstract description 23
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 21
- NPJICTMALKLTFW-OFUAXYCQSA-N daucosterol Chemical compound O([C@@H]1CC2=CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CC[C@@H](CC)C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O NPJICTMALKLTFW-OFUAXYCQSA-N 0.000 claims abstract description 42
- QXMNTPFFZFYQAI-IMDKZJJXSA-N beta-sitosterol 3-O-beta-D-glucopyranoside Natural products CC[C@H](CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@H](CC[C@]4(C)[C@H]3CC[C@]12C)O[C@@H]5C[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)C(C)C QXMNTPFFZFYQAI-IMDKZJJXSA-N 0.000 claims abstract description 37
- QDFKFNAHVGPRBL-UHFFFAOYSA-N daucosterol Natural products CCC(CCC(C)C1CCC2C1CCC3C2(C)CC=C4CC(CCC34C)OC5OC(CO)C(O)C(O)C5O)C(C)C QDFKFNAHVGPRBL-UHFFFAOYSA-N 0.000 claims abstract description 37
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229960004397 cyclophosphamide Drugs 0.000 claims abstract description 28
- 239000007924 injection Substances 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 10
- 238000006243 chemical reaction Methods 0.000 abstract description 4
- 239000000284 extract Substances 0.000 abstract description 4
- 230000008878 coupling Effects 0.000 abstract description 3
- 238000010168 coupling process Methods 0.000 abstract description 3
- 238000005859 coupling reaction Methods 0.000 abstract description 3
- 230000007761 synergistic anti-cancer Effects 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 206010028980 Neoplasm Diseases 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000000890 drug combination Chemical group 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000008215 water for injection Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 229940083466 soybean lecithin Drugs 0.000 description 4
- 235000012424 soybean oil Nutrition 0.000 description 4
- 239000003549 soybean oil Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000000963 osteoblast Anatomy 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
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- 206010003445 Ascites Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
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- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 2
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
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- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
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- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229950011446 sitogluside Drugs 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a kind of anticancer synergia compositions, in wherein said compositions, active component is made up of daucosterol and cyclophosphamide, and the weight consumption of preferred daucosterol and cyclophosphamide is than being 10-50:1.Have Synergistic anti-cancer effect after daucosterol and cyclophosphamide coupling, meanwhile, daucosterol is natural extract product, and toxicity is very little, side effect and untoward reaction rate low; Cyclophosphamide consumption is only 1/2nd of conventional amount used, and therefore expense, side effect and untoward reaction rate are also lower.
Description
Technical field
The invention belongs to medical art, in particular to a kind of anticancer synergia compositions.
Background technology
At present, cancer is that current serious affects one of human health, the principal disease threatening human life.Cancer and cardiovascular and cerebrovascular disease, together with contingency, form the large cause of death of world today's All Countries three.Therefore, World Health Organization (WHO) and hygiene department of national governments are all classified as capture cancer as a top priority.The method of Therapeutic cancer mainly contains three kinds in the world, and one is adopt surgical excision, and removal lesion tissue, prevents cancerous cell from spreading; But adopt chemotherapy or radiotherapy, to kill cancerous cell; Three is use Drug therapy.Adopt the method for excision to add the misery of patient, hinder its vigour, expense is huge.By the method for radiotherapy, while killing cancerous cell, also injure erythrocyte and leukocyte, patient suffers untold misery.
Daucosterol (Daucosterol), also known as sitogluside, Daucosterol, is important phytosterol derivative, is distributed widely in nature, is present in the root of plant, stem, leaf, fruit and seed.Available alcohol heating reflux extracts, and is separated obtains through silica gel column chromatography or macroporous resin column chromatography.Few about the report of daucosterol pharmaceutical research, its value in biological, medical science needs to be excavated further.The propagation of bibliographical information daucosterol to osteoblast is had to have significant facilitation (Meng Yanbin, Sun Sheng, Gao Wei; In Radix Achyranthis Bidentatae, osteoblast like UMR106 cells is had to the study of active components promoting proliferation function; Time precious traditional Chinese medical science traditional Chinese medicines, 2007,18(12): 2947-2948.): when concentration is 1.2 × 10-6mg/ml, it promotes that the effect of Osteoblast like Cells is the strongest, the most positive controls for high proliferation rates average out to 45% of 3 experiments.Separately there are some researches show that daucosterol can the damage that causes human microvascular endothelial cell (mvec) of prevention and therapy OxLDL ELISA: during daucosterol dosage 0.39 ~ 12.5 μ g/mL, have protective effect; Dosage 6.25 ~ 12.5 μ g/mL constantly, has very strong repair (He Qiuyan, Weng Xinchu.Fructus Crataegi active component is to the preventive and therapeutic effect of OxLDL ELISA damage human microvascular endothelial cell (mvec).Shanghai University's journal (natural science edition), 2007,13(6): 751-756).In addition, daucosterol is also one of the composition of hypoglycemic activity in edible Radix et Caulis Opuntiae Dillenii (Gu Jiangxia, Dou Deqiang; Edible Radix et Caulis Opuntiae Dillenii hypoglycemic activity composition Study; Contemporary Chinese Chinese medicine, 2007,19(111): 15-16).
Finding by retrieving domestic and international prior art, also not adopting the bibliographical information that daucosterol is anticancer at present, more not adopting the bibliographical information that daucosterol commissural arch phosphamide is anticancer.
Summary of the invention
Cyclophosphamide is clinical conventional broad-spectrum anti-cancer drug, because it comparatively forces its clinical practice to receive certain restriction to hemopoietic system and immune toxic and side effects.In order to play the anticancer function of cyclophosphamide, reduce its toxic and side effects, the present inventor creatively reduces the consumption of cyclophosphamide simultaneously, and by itself and daucosterol use in conjunction, has the anticancer effect of Synergistic after unexpected both discoveries medication.Based on this research, the object of the present invention is to provide a kind of anticancer synergia compositions.
Particularly, the object of the present invention is achieved like this:
A kind of anticancer synergia compositions, in wherein said compositions, active component is made up of daucosterol and cyclophosphamide.
Preferably, anticancer synergia compositions described above, in wherein said active component, the weight consumption of daucosterol and cyclophosphamide is than being 10-50:1.
Further preferably, anticancer synergia compositions described above, in wherein said active component, the weight consumption of daucosterol and cyclophosphamide is than being 12-25:1.
Again further preferably, anticancer synergia compositions described above, in wherein said active component, the weight consumption of daucosterol and cyclophosphamide is than being 16:1.
Anticancer synergia compositions of the present invention, by playing drug effect after drug administration by injection, is therefore prepared as injection, and described injection comprises injection, lyophilized injectable powder.
With the cyclophosphamide of daucosterol and low dosage for object of study, oxter inoculation S
180the Kunming mouse of sarcoma is carrier, lumbar injection, not only has Synergistic anti-cancer effect, and reduce the toxic and side effects of cyclophosphamide after found that the two coupling.Therefore, the present invention also provides a kind of pharmaceutical applications, that is: the application of active component in the medicine that preparation is anticancer of daucosterol and cyclophosphamide composition.
Compared with prior art, the pharmaceutical composition tool that the present invention relates to has the following advantages and marked improvement: have Synergistic anti-cancer effect after daucosterol and cyclophosphamide coupling, and meanwhile, daucosterol is natural extract product, toxicity is very little, side effect and untoward reaction rate low; Cyclophosphamide consumption is only 1/2nd of conventional amount used, and therefore expense, side effect and untoward reaction rate are also lower.
Detailed description of the invention
Be below specific embodiments of the invention, technical scheme of the present invention is done to describing further, but protection scope of the present invention be not limited to this embodiment.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
The preparation of embodiment 1 injection
Daucosterol 1.6g
Cyclophosphamide 0.1g
Injection soybean oil 18g
Glycerol 2.6g
Soybean lecithin 1.5g
Water for injection adds to 100ml
Preparation technology: by soybean lecithin, glycerol, be scattered in 60ml water for injection, again by daucosterol, cyclophosphamide and injection soybean oil mix homogeneously, be mixed with oil phase, then oil phase joined in aqueous phase, limit edged stirs, ultrasonic 1h evenly, is settled to 100ml with water for injection afterwards, after proceed to high pressure dispersing emulsification machine, emulsifying 30min, fill, sterilizing, to obtain final product.
The preparation of embodiment 2 injection
Daucosterol 3.2g
Cyclophosphamide 0.1g
Injection soybean oil 18g
Glycerol 2.0g
Propylene glycol 5.0g
Soybean lecithin 1.5g
Water for injection adds to 100ml
Preparation technology: first soybean lecithin, glycerol, propylene glycol are scattered in 60ml water for injection, again by daucosterol, cyclophosphamide and injection soybean oil mix homogeneously, be mixed with oil phase, then oil phase joined in aqueous phase, limit edged stirs, ultrasonic 1h evenly, is settled to 100ml with water for injection afterwards, after proceed to high pressure dispersing emulsification machine, emulsifying 30min, fill, sterilizing, to obtain final product.
Embodiment 3 daucosterol commissural arch phosphamide is to S
180tumor-bearing mice tumor control rate impact test
KM kind mice 40,18 ~ 22g, male and female half and half.S
180the kind Mus of sarcoma ascites inoculation 8d, extract 5mL ascites, put into sterile petri dish, normal saline dilution becomes the tumor cell suspension of 1:3, and mixing, only inoculates S by 0.2mL/
180sarcoma, in all KM kind mice right fore oxters, is divided into following four groups: model control group, daucosterol group, cyclophosphamide group, drug combination group at random after 24h, often organize 10, female, hero half and half.From inoculation the 2nd day, intraperitoneal injection, tested material and the dosage of each group are as follows:
Model control group: equal-volume normal saline;
Daucosterol group: 200mg/ (kgd) daucosterol;
Cyclophosphamide group: 25mg/ (kgd) cyclophosphamide
Drug combination group: 200mg/ (kgd) daucosterol+12.5mg/ (kgd) cyclophosphamide.
Daily 1 time, successive administration 10d, next day is put to death animal in drug withdrawal, takes every mouse tumor block weight respectively, calculates tumor control rate, potentiation experimental result.Tumour inhibiting rate=(the average tumor weight of 1-experimental group average tumor weight/matched group) × 100%.
Q=E (A+B)/[EA+ (1-EA) × EB], E (A+B) are the suppression ratio of two medicines when share, and EA, EB are the suppression ratio of each prescription used time, when q<0.85 represents that two medicines are picked up anti-mutually; Q>1.15 represents that two medicine effects strengthen, and q=0.85 ~ 1.15 represent that two medicine effects are added.
Can be found out by the result of the test of table 1, compare with model control group, cyclophosphamide group and drug combination group all have significant inhibitory action to growth of tumour cell, and each group difference have statistical significance (
p< 0.01); Compared with each single medicine group (daucosterol group, cyclophosphamide group), the tumour inhibiting rate difference of drug combination group have statistical significance (
p< 0.01).Daucosterol commissural arch phosphamide is to S
180tumor-bearing mice potentiation research display, the q value of drug combination group is respectively 1.62, q>1.15, represents that two medicine synergy strengthen for collaborative.
Table 1 daucosterol commissural arch phosphamide is to S
180the impact of tumor weight
| Group | Sample size (only) | Tumor heavy (g) | Suppression ratio (%) | Q value |
| Model control group | 10 | 1.4085±0.1840 | - | - |
| Daucosterol group | 10 | 1.1261±0.1570 | 20.05 | - |
| Cyclophosphamide group | 10 | 0.7554±0.0943 ★★ | 46.37 | - |
| Drug combination group | 10 | 0.1078±0.0216 ★★▼▼●● | 92.35 | 1.62 |
Compare with model control group,
★ p< 0.05,
★ ★ p< 0.01;
Compare with daucosterol group,
▼ p< 0.05,
▼ ▼ p< 0.01;
Compare with cyclophosphamide group,
● p< 0.05,
● ● p< 0.01.
Claims (6)
1. an anticancer synergia compositions, is characterized in that: in described pharmaceutical composition, active component is made up of daucosterol and cyclophosphamide.
2. anticancer synergia compositions according to claim 1, is characterized in that: in described active component, the weight consumption of daucosterol and cyclophosphamide is than being 10-50:1.
3. anticancer synergia compositions according to claim 2, is characterized in that: in described active component, the weight consumption of daucosterol and cyclophosphamide is than being 12-25:1.
4. anticancer synergia compositions according to claim 3, is characterized in that: in described active component, the weight consumption of daucosterol and cyclophosphamide is than being 16:1.
5. the anticancer synergia compositions according to any one of claim 1-4, is characterized in that: described compositions is injection, and described injection comprises injection, lyophilized injectable powder.
6. the application of the active component be made up of daucosterol and cyclophosphamide in the medicine that preparation is anticancer.
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| CN201410361831.1A CN104127427B (en) | 2014-07-28 | 2014-07-28 | A kind of anticancer synergia compositions |
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| CN201410361831.1A CN104127427B (en) | 2014-07-28 | 2014-07-28 | A kind of anticancer synergia compositions |
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| CN106166291B (en) * | 2016-08-05 | 2020-06-30 | 融致丰生制药有限公司 | Medical application of spleen polypeptide in improving KLRK1 or LCK treatment immunosuppression |
| CN113209114B (en) * | 2021-05-18 | 2022-04-19 | 华中农业大学 | Application of PGC-1 alpha activator daucosterol in preparation of medicine for preventing and treating blood brain barrier injury |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087276A (en) * | 1992-11-25 | 1994-06-01 | 黑龙江省肿瘤医院 | A kind of chemotherapy of tumors Chinese medicine synergist and preparation method thereof |
| CN102755343A (en) * | 2012-08-08 | 2012-10-31 | 南京中医药大学 | Application of daucosterol in preparing medicines for promoting proliferation of neural stem cells |
| CN103804448A (en) * | 2012-11-07 | 2014-05-21 | 惠铁军 | Extraction method of chemical components of viburnum plicatum |
-
2014
- 2014-07-28 CN CN201410361831.1A patent/CN104127427B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1087276A (en) * | 1992-11-25 | 1994-06-01 | 黑龙江省肿瘤医院 | A kind of chemotherapy of tumors Chinese medicine synergist and preparation method thereof |
| CN102755343A (en) * | 2012-08-08 | 2012-10-31 | 南京中医药大学 | Application of daucosterol in preparing medicines for promoting proliferation of neural stem cells |
| CN103804448A (en) * | 2012-11-07 | 2014-05-21 | 惠铁军 | Extraction method of chemical components of viburnum plicatum |
Non-Patent Citations (1)
| Title |
|---|
| 《HPLC-ELSD同时测定链荚豆中胡萝卜苷和B-谷甾醇含量》;李慧宁等;《中国实验方剂学杂志》;20130131;第19卷(第1期);权利要求书 * |
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