CN104127427A - Anticancer synergistic composition - Google Patents
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- CN104127427A CN104127427A CN201410361831.1A CN201410361831A CN104127427A CN 104127427 A CN104127427 A CN 104127427A CN 201410361831 A CN201410361831 A CN 201410361831A CN 104127427 A CN104127427 A CN 104127427A
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- daucosterol
- cyclophosphamide
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- 239000000203 mixture Substances 0.000 title claims abstract description 24
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 23
- 230000002195 synergetic effect Effects 0.000 title abstract description 6
- 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
- 206010028980 Neoplasm Diseases 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 11
- 201000011510 cancer Diseases 0.000 abstract description 5
- 239000000284 extract Substances 0.000 abstract description 4
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 2
- 230000006838 adverse reaction Effects 0.000 abstract 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 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
- 239000008215 water for injection Substances 0.000 description 6
- 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
- 210000004027 cell Anatomy 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 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
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000000963 osteoblast Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 206010003445 Ascites Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000006243 chemical reaction Methods 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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- 238000011081 inoculation Methods 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
- 230000007761 synergistic anti-cancer 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
- 241001597008 Nomeidae Species 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 240000005373 Panax quinquefolius Species 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
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- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
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- 235000002378 plant sterols Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
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- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229950011446 sitogluside Drugs 0.000 description 1
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- 229940126680 traditional chinese medicines 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 an anticancer synergistic composition. Active components of the anticancer synergistic composition comprise daucosterol and cyclophosphamide, and preferably, a weight ratio of daucosterol to cyclophosphamide is 10-50: 1. The daucosterol and cyclophosphamide can produce synergistic cancer-resistant effects. Daucosterol is natural extract and has very small toxicity, small side effects and a low adverse reaction rate. The use amount of cyclophosphamide in the anticancer synergistic composition is only 1/2 of the conventional use amount and thus a cost, side effects and an adverse reaction rate are low.
Description
Technical field
The invention belongs to medical technical field, in particular to a kind of anticancer synergia compositions.
Background technology
At present, cancer is that current serious affects human health, threatens one of principal disease of human life.Cancer together with contingency, forms world today's All Countries three large causes of death with cardiovascular and cerebrovascular disease.Therefore, World Health Organization (WHO) and hygiene department of national governments all classify capture cancer as a top priority as.The method for the treatment of in the world cancer mainly contains three kinds, and the one, adopt surgical excision, removal lesion tissue, prevents cancerous cell diffusion; But adopt chemotherapy or radiotherapy, to kill cancerous cell; The 3rd, use Drug therapy.Adopt the method for excision to increase patient's misery, hinder its vigour, expense is huge.By the method for radiotherapy, in killing cancerous cell, also injure erythrocyte and leukocyte, patient suffers untold misery.
Daucosterol (Daucosterol) claim again sitogluside, Daucosterol, is important plant sterol derivant, is distributed widely in nature, is present in root, stem, leaf, fruit and the seed of plant.Available alcohol heating reflux extracts, and separates acquisition through silica gel column chromatography or macroporous resin column chromatography.Report about daucosterol pharmaceutical research is also few, and it needs further to be excavated in the value aspect biology, medical science.There is bibliographical information daucosterol to there is significant facilitation (Meng Yanbin, Sun Sheng, Gao Wei to the propagation of osteoblast; In Radix Achyranthis Bidentatae, osteoblast UMR106 is had to the study of active components that promotes proliferation function; Time precious traditional Chinese medical science traditional Chinese medicines, 2007,18(12): 2947-2948.): when concentration is 1.2 × 10-6 mg/m l, it promotes that the effect of Osteoblast like Cells is the strongest, the positive controls for high proliferation rates average out to 45% of 3 experiments.Separately there are some researches show that daucosterol can prevent and treat the damage that OxLDL ELISA causes human microvascular endothelial cell (mvec): when daucosterol dosage 0.39 ~ 12.5 μ g/mL, have protective effect; Dosage 6.25 ~ 12.5 μ g/mL constantly, have very strong repair (He Qiuyan, Weng Xinchu.The preventive and therapeutic effect of Fructus Crataegi active component to 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 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).
Find by retrieving domestic and international prior art, also do not adopt the anticancer bibliographical information of daucosterol at present, more do not adopt the anticancer bibliographical information of daucosterol commissural arch phosphamide.
Summary of the invention
Cyclophosphamide is clinical conventional broad-spectrum anti-cancer drug, because it forces its clinical practice to be subject to certain restriction to hemopoietic system and immune toxic and side effects.In order to bring into play the anticancer function of cyclophosphamide, reduce its toxic and side effects simultaneously, the inventor creatively reduces the consumption of cyclophosphamide, and by itself and daucosterol use in conjunction, the unexpected anticancer effect of finding to have after the two medication Synergistic.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 as mentioned above, in wherein said active component, the weight consumption of daucosterol and cyclophosphamide is than being 10-50:1.
Further preferably, anticancer synergia compositions as mentioned 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 as mentioned 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 can be brought into play drug effect after by drug administration by injection, is therefore prepared as injection, and described injection comprises injection, lyophilized injectable powder.
Taking the cyclophosphamide of daucosterol and low dosage as object of study, oxter inoculation S
180the Kunming mouse of sarcoma is carrier, and lumbar injection found that after the two coupling and not only has Synergistic anti-cancer effect, and has reduced the toxic and side effects of cyclophosphamide.Therefore, the present invention also provides a kind of pharmaceutical applications, that is: the application of the active component of daucosterol and cyclophosphamide composition in the anticancer medicine of preparation.
Compared with prior art, the pharmaceutical composition tool the present invention relates to has the following advantages and marked improvement: after daucosterol and cyclophosphamide coupling, have Synergistic anti-cancer effect, meanwhile, daucosterol is natural extract product, toxicity is very little, and side effect and untoward reaction rate are 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 further description, but protection scope of the present invention is not limited to this embodiment.Every do not deviate from the change of the present invention design or be equal to substitute 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, by daucosterol, cyclophosphamide and injection soybean oil mix homogeneously, be mixed with oil phase again, then oil phase joined in water, 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 injections
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, by daucosterol, cyclophosphamide and injection soybean oil mix homogeneously, be mixed with oil phase again, then oil phase joined in water, 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 phosphamides are to S
180the impact test of tumor-bearing mice tumor control rate
40 of KM kind mices, 18～22 g, male and female half and half.S
180the kind Mus of sarcoma ascites inoculation 8d, extracts 5mL ascites, puts into sterile petri dish, and normal saline dilution becomes the tumor cell suspension of 1:3, mixes, and only inoculates S by 0.2 mL/
180sarcoma, in all KM kind mice right fores oxter, is divided into following four groups at random after 24 h: model control group, daucosterol group, cyclophosphamide group, drug combination group, 10 every group, female, hero half and half.From inoculating 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.
Administration every day 1 time, successive administration 10d, next day is put to death animal in drug withdrawal, takes respectively every mouse tumor piece weight, calculates tumor control rate, potentiation experimental result.Tumour inhibiting rate=(the average tumor weight of the average tumor weight/matched group of 1-experimental group) × 100%.
Q=E (A+B)/[EA+ (1-EA) × EB], E (A+B) is the suppression ratio of two medicines while share, EA, EB are the suppression ratio of each prescription used time, mutually pick up anti-when q<0.85 represents two medicines; Q>1.15 represents that two medicine effects strengthen, and q=0.85～1.15 represent that two medicine effects are added.
Result of the test by table 1 can find out, with model control group comparison, cyclophosphamide group and drug combination group all have significant inhibitory action to growth of tumour cell, and respectively organize 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 studies show that, 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 |
With model control group comparison,
★ p< 0.05,
★ ★ p< 0.01;
With the comparison of daucosterol group,
▼ p< 0.05,
▼ ▼ p< 0.01;
With the comparison of 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. according to the anticancer synergia compositions described in claim 1-4 any one, it is characterized in that: described compositions is injection, and described injection comprises injection, lyophilized injectable powder.
6. the application of the active component being formed by daucosterol and cyclophosphamide in the anticancer medicine of preparation.
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| Application Number | Priority Date | Filing Date | Title |
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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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| Publication Number | Publication Date |
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| CN104127427A true CN104127427A (en) | 2014-11-05 |
| CN104127427B CN104127427B (en) | 2016-02-24 |
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| CN201410361831.1A Expired - Fee Related CN104127427B (en) | 2014-07-28 | 2014-07-28 | A kind of anticancer synergia compositions |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106166291A (en) * | 2016-08-05 | 2016-11-30 | 吉林丰生制药有限公司 | Spleen polypeptide improves KLRK1 or LCK and treats immunosuppressant medical usage |
| CN113209114A (en) * | 2021-05-18 | 2021-08-06 | 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 |
|---|
| 李慧宁等: "《HPLC-ELSD同时测定链荚豆中胡萝卜苷和B-谷甾醇含量》", 《中国实验方剂学杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106166291A (en) * | 2016-08-05 | 2016-11-30 | 吉林丰生制药有限公司 | Spleen polypeptide improves KLRK1 or LCK and treats immunosuppressant medical usage |
| 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 |
| CN113209114A (en) * | 2021-05-18 | 2021-08-06 | 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 |
| 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 |
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