CN103054881B - Traditional Chinese medicine active component compound preparation for treating lung cancer and preparation method thereof - Google Patents
Traditional Chinese medicine active component compound preparation for treating lung cancer and preparation method thereof Download PDFInfo
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- CN103054881B CN103054881B CN201310028251.6A CN201310028251A CN103054881B CN 103054881 B CN103054881 B CN 103054881B CN 201310028251 A CN201310028251 A CN 201310028251A CN 103054881 B CN103054881 B CN 103054881B
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Abstract
The invention discloses a traditional Chinese medicine active component compound preparation for treating lung cancer and a preparation method thereof. The compound preparation is a traditional Chinese medicine active component compound prepared from taxol, cinobufagin and triptolide according to a certain weight ratio. The preparation method comprises the steps of preparing a lipidosome by adopting an ethanol injection method or preparing a pill by taking polyethylene glycol as a substrate, thereby obtaining the traditional Chinese medicine active component preparation. The dosage forms of the compound preparation are compound lipidosomes and compound pills; found from animal internal anticancer pharmacological experiments, the traditional Chinese medicine active component compound preparation has obvious inhibition effect on development of lung cancer; and the anticancer activity of the compound preparation is obviously higher than that of a chemotherapeutic drug, namely 5-fluorouracil.
Description
Technical field
The present invention relates to technical field of Chinese medicines, specifically relate to a kind of active ingredient of Chinese herbs compound preparation for the treatment of pulmonary carcinoma and preparation method thereof.
Background technology
Cancer is the formidable enemy of harm humans health.The annual new cases of cancer of China approximately has 1,600,000 people, and that dies from every year cancer approximately has 1,300,000 people, rises year by year because of the dead number of cancer in the whole nation, and China is the region occurred frequently of the cancers such as pulmonary carcinoma, breast carcinoma, hepatocarcinoma, and cancer mortality is high.
There is no at present the most of cancer patients of effective cured substance.Though chemotherapeutics has certain curative effect to cancer, toxic and side effects is large, and Chinese patent medicine is generally lower to the curative effect of cancer, and curative effect is all undesirable.
The inventor is through the arduous Sirikaya of having studied decades, Herba Phyllanthi Urinariae, Ramulus et folium taxi cuspidatae, the anticancer active substance of the Chinese medicines such as dry maxima skin, therefrom extract multiple anti-cancer active compound, show through anticancer experimentation, to human breast carcinoma, pulmonary carcinoma, the cancerous cell such as hepatocarcinoma and zoografting carcinoma all have significant inside and outside anticancer therapy effect, and (patent No. is respectively: ZL02148474.0 to have applied for obtaining 7 antineoplastic product invention patent certificates, ZL02148475.9, ZL03112707.X, ZL200410041122.1, ZL200610085781.4, ZL200610085781.4, ZL200810124588.6).On the basis of above-mentioned research, the inventor studies again and has invented the anticarcinogen that a kind of active anticancer is high, anticancer spectrum is wide.
Summary of the invention
1, goal of the invention: the object of this invention is to provide the anticarcinogen that a kind of active anticancer is high, anticancer spectrum is wide, a kind of active ingredient of Chinese herbs compound preparation for the treatment of breast carcinoma and pulmonary carcinoma of specifically preparing as raw material taking paclitaxel, cinobufagin, triptolide and preparation method thereof.
2, technical scheme:
An active ingredient of Chinese herbs compound preparation for the treatment of pulmonary carcinoma, is characterized in that by the active ingredient of Chinese herbs of following weight portion proportioning made: 1～3 part of paclitaxel, 1～3 part of cinobufagin, 1～3 part of triptolide.
Each active ingredient of Chinese herbs brief introduction is as follows:
Paclitaxel (Paclitaxe, Taxol, TAX), (claiming again: taxol, Paclitaxe, Paclitaxe), molecular formula: C
47h
51nO
14, chemical structural formula:
Cinobufagin (Cinobufagin, CBG), (claiming again: cinobufacin, cinobufagin), molecular formula: C
26h
34o
6, chemical structural formula:
Triptolide (triptolide, TL), (claiming again: Radix Tripterygii Wilfordii lactone alcohol),, molecular formula: C
20h
24o
6, chemical structural formula:
Described active ingredient of Chinese herbs compound preparation, the dosage form that it is characterized in that this compound preparation is compound recipe liposome and compound dripping pill.
The preparation method of the compound recipe liposome of active ingredient of Chinese herbs compound preparation of the present invention is: material and proportioning prepared by (1) compound recipe liposome are: lecithin respectively with mPEG2000-DSPE(amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine) mass ratio is 10:1～1.2, with the mass ratio of cholesterol be 10:1～1.2, with the mass ratio of active ingredient of Chinese herbs compound medicine be 30:0.8～1; (2) preparation method of compound recipe liposome is: adopt alcohol injection preparation: get the PBS buffer of pH7.4 in eggplant type bottle, in 50～55 DEG C of preheating 30～35min of water bath with thermostatic control; Get lecithin, cholesterol, Chinese medicine dispelling toxins and dredging collaterals composition compound medicine and mPEG2000-DSPE in beaker, add appropriate dehydrated alcohol to make its dissolving, after all dissolving, medicine is injected into rapidly in the eggplant type bottle that buffer solution is housed of constant temperature preheating, obtain milky liposome turbid liquor, continue to stir aquation 1～1.2h, evacuation is except ethanol, and 800P crosses 10～12 circulations of high pressure dispersing emulsification machine, obtains Chinese medicine dispelling toxins and dredging collaterals composition compound recipe liposome.
The preparation method of the compound dripping pill of active ingredient of Chinese herbs compound preparation of the present invention is: material prepared by (1) compound dripping pill and proportioning, condition are: polyethylene glycol 6000 (PEG6000) is substrate, liquid Paraffin is coolant, the ratio of active ingredient of Chinese herbs compound medicine and substrate is 1:2～3, fluid temperature is 80～85 DEG C, and chilling temperature is 10～15 DEG C; (2) compound dripping pill preparation method is: polyethylene glycol 6000 is put in water-bath and added Chinese medicine dispelling toxins and dredging collaterals composition compound medicine to stir in the ratio of medicine and substrate after heat fused, put in drop pill preparation facilities, insulation splashes into dripping in liquid Paraffin coolant and becomes ball, the drop pill making is removed to surperficial condensed fluid and obtain active ingredient of Chinese herbs compound dripping pill.
The application of active ingredient of Chinese herbs compound preparation of the present invention in preparation treatment lung-cancer medicament.
Active ingredient of Chinese herbs compound preparation of the present invention, has obvious inhibitory action to the growth of pulmonary carcinoma in vivo, and its active anticancer is apparently higher than chemotherapeutic 5-fluorouracil.
3, beneficial effect:
Active ingredient of Chinese herbs compound preparation of the present invention is tested through Anticancer in animal body, the growth of pulmonary carcinoma is had to obvious inhibitory action, the active ingredient of Chinese herbs compound preparation of 9mg/kg dosage can significantly suppress the growth (P<0.01) of mice Lewis lung carcinoma, and its tumour inhibiting rate is 72.84%; Its to the active anticancer of pulmonary carcinoma higher than chemotherapeutic 5-fluorouracil (5-Fu), also higher than the single composition (paclitaxel single, cinobufagin single, triptolide single) of prescription.Can be used for treating pulmonary carcinoma.
A kind of active ingredient of Chinese herbs compound preparation of the present invention is the active ingredient of Chinese herbs compound anti-cancer medicine of preparing as raw material taking paclitaxel, cinobufagin, triptolide.Animal vivo antitumor experimental result shows, active ingredient of Chinese herbs compound preparation has very high active anticancer to the growth of pulmonary carcinoma, and its vivo antitumor activity is higher than chemotherapeutic 5-fluorouracil (5-Fu), also higher than the single composition of prescription.This provides very promising efficient preliminary election medicine for improving anticancer clinical efficacy, also for the mechanism of Study of Traditional Chinese Medicine active component compatibility provides good component prescription.
Four, detailed description of the invention
Embodiment 1: active ingredient of Chinese herbs compound preparation, made by paclitaxel 1 part (10mg), cinobufagin 1 part (10mg) and triptolide 1 part (10mg), wherein the preparation method of liposome is as follows:
(1) active ingredient of Chinese herbs compound recipe liposome is prepared material and proportioning is: lecithin respectively with mPEG2000-DSPE(amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine) mass ratio is 10: 1, with the mass ratio of cholesterol be 10: 1, with the mass ratio of active ingredient of Chinese herbs compound medicine be 30: 1;
(2) active ingredient of Chinese herbs compound recipe method for preparing lipidosome is: adopt alcohol injection preparation, precision measures the PBS buffer 90mL of pH7.4 in eggplant type bottle, in 50 DEG C of preheating 30min of water bath with thermostatic control; Lecithin 900mg, cholesterol 90mg, active ingredient of Chinese herbs compound medicine 30mg and mPEG2000-DSPE90mg are accurately weighed in beaker, add appropriate dehydrated alcohol to make its dissolving, after all dissolving, medicine is injected into rapidly in the eggplant type bottle that buffer solution is housed of constant temperature preheating, obtain milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, and 800P crosses 10 circulations of high pressure dispersing emulsification machine, obtains active ingredient of Chinese herbs compound recipe liposome.
Wherein the preparation method of compound dripping pill is as follows:
(1) active ingredient of Chinese herbs compound dripping pill is prepared material and proportioning, condition is: polyethylene glycol 6000 (PEG6000) is substrate, liquid Paraffin is coolant, the ratio of active ingredient of Chinese herbs compound medicine and substrate is 1:2, and fluid temperature is 85 DEG C, and chilling temperature is 12～14 DEG C;
(2) active ingredient of Chinese herbs compound dripping pill preparation method is: the polyethylene glycol 6000 of 60mg is put in water-bath and added active ingredient of Chinese herbs compound medicine 30mg to stir in the ratio of compound medicine and substrate 1:2 after heat fused, put in drop pill preparation facilities, insulation splashes into dripping in liquid Paraffin coolant and becomes ball, the drop pill making is removed to surperficial condensed fluid and obtain active ingredient of Chinese herbs compound dripping pill.
Embodiment 2: active ingredient of Chinese herbs compound preparation, made by paclitaxel 2 parts (20mg), cinobufagin 2 parts (20mg) and triptolide 2 parts (20mg), wherein the preparation method of liposome is as follows:
(1) active ingredient of Chinese herbs compound recipe liposome is prepared material and proportioning is: lecithin respectively with mPEG2000-DSPE
(amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine) mass ratio is 10: 1, with the mass ratio of cholesterol be 10: 1, with the mass ratio of active ingredient of Chinese herbs compound medicine be 30: 1;
(2) active ingredient of Chinese herbs compound recipe method for preparing lipidosome is: adopt alcohol injection preparation, precision measures the PBS buffer 180mL of pH7.4 in eggplant type bottle, in 50 DEG C of preheating 30min of water bath with thermostatic control; Lecithin 1800mg, cholesterol 180mg, active ingredient of Chinese herbs compound medicine 60mg and mPEG2000-DSPE180mg are accurately weighed in beaker, add appropriate dehydrated alcohol to make its dissolving, after all dissolving, medicine is injected into rapidly in the eggplant type bottle that buffer solution is housed of constant temperature preheating, obtain milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, and 800P crosses 12 circulations of high pressure dispersing emulsification machine, obtains active ingredient of Chinese herbs compound recipe liposome.
Wherein the preparation method of compound dripping pill is as follows:
(1) active ingredient of Chinese herbs compound dripping pill is prepared material and proportioning, condition is: polyethylene glycol 6000 (PEG6000) is substrate, liquid Paraffin is coolant, the ratio of active ingredient of Chinese herbs compound medicine and substrate is 1:2, and fluid temperature is 85 DEG C, and chilling temperature is 12～14 DEG C;
(2) active ingredient of Chinese herbs compound dripping pill preparation method is: the polyethylene glycol 6000 of 120mg is put in water-bath and added active ingredient of Chinese herbs compound medicine 60mg to stir in the ratio of compound medicine and substrate 1:2 after heat fused, put in drop pill preparation facilities, insulation splashes into dripping in liquid Paraffin coolant and becomes ball, the drop pill making is removed to surperficial condensed fluid and obtain active ingredient of Chinese herbs compound dripping pill.
Embodiment 3: active ingredient of Chinese herbs compound preparation, made by paclitaxel 3 parts (30mg), cinobufagin 3 parts (30mg) and triptolide 3 parts (30mg), wherein the preparation method of liposome is as follows:
(1) active ingredient of Chinese herbs compound recipe liposome is prepared material and proportioning is: lecithin respectively with mPEG2000-DSPE(amphipathic ethylene glycol 2000-distearyl phospholipid ethanolamine) mass ratio is 10: 1.2, with the mass ratio of cholesterol be 10: 1.2, with the mass ratio of active ingredient of Chinese herbs compound medicine be 30: 0.8;
(2) active ingredient of Chinese herbs compound recipe method for preparing lipidosome is: adopt alcohol injection preparation, precision measures the PBS buffer 270mL of pH7.4 in eggplant type bottle, in 50 DEG C of preheating 30min of water bath with thermostatic control; Lecithin 2700mg, cholesterol 324mg, active ingredient of Chinese herbs compound medicine 90mg and mPEG2000-DSPE324mg are accurately weighed in beaker, add appropriate dehydrated alcohol to make its dissolving, after all dissolving, medicine is injected into rapidly in the eggplant type bottle that buffer solution is housed of constant temperature preheating, obtain milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, and 800P crosses 12 circulations of high pressure dispersing emulsification machine, obtains active ingredient of Chinese herbs compound recipe liposome.
Wherein the preparation method of compound dripping pill is as follows:
(1) active ingredient of Chinese herbs compound dripping pill is prepared material and proportioning, condition is: polyethylene glycol 6000 (PEG6000) is substrate, liquid Paraffin is coolant, the ratio of active ingredient of Chinese herbs compound medicine and substrate is 1:2, and fluid temperature is 85 DEG C, and chilling temperature is 12～14 DEG C;
(2) active ingredient of Chinese herbs compound dripping pill preparation method is: the polyethylene glycol 6000 of 180mg is put in water-bath and added active ingredient of Chinese herbs compound medicine 90mg to stir in the ratio of compound medicine and substrate 1:2 after heat fused, put in drop pill preparation facilities, insulation splashes into dripping in liquid Paraffin coolant and becomes ball, the drop pill making is removed to surperficial condensed fluid and obtain active ingredient of Chinese herbs compound dripping pill.
Embodiment 4: the inhibitory action of active ingredient of Chinese herbs compound preparation to Lewis lung carcinoma
1, laboratory animal and tumor strain
Male and healthy C57BL/6 mice, body weight 18-22g, Mus 6-8 in age week, purchased from zoopery center, this school; Lewis cells of lung cancer is purchased from zoopery center, institute of oncology of Jiangsu Province.
1, modeling and experimental technique
70 of C57BL/6 mices, stay 10 negative matched groups in proportion at random, and all the other 60 are carried out modeling.Prepare Lewis lung cancer tumor-bearing mice, peel off the tumor tissue of growth animated period, choose well-grown lump 1.5mm
3left and right, in tumor (g): normal saline (ml) is ratio homogenate in 1: 3, adjusting cell number is 2 × 10
6/ ml.Choose healthy mice, every right side of mice axillary fossa subcutaneous vaccination 0.2ml under aseptic condition.Whole seeded process must be carried out with sterile working in aseptic cover, completes inoculation in 1h.
After inoculation, be divided at random 6 groups, 10 every group, be respectively tumor model matched group, active ingredient of Chinese herbs compound recipe and 4 test group of composition single thereof, 5-fu positive controls, separately add negative control group, totally 6 groups.After inoculation oncocyte 24h, test group lumbar injection active ingredient of Chinese herbs compound recipe, paclitaxel single, cinobufagin single, triptolide single, dosage is 9mg/kg, negative control group and tumor model matched group equal-volume injectable drug solvent, 5-FU matched group is taking normal saline as solvent, dosage is 20mg/kg, each treated animal all by 0.2ml at lumbar injection, successive administration 10d.Next day after last administration, observe as follows:
Completely peel off tumor piece, and the calculating tumor control rate of weighing, tumor control rate=(matched group tumor weight-treatment group tumor weight)/matched group tumor weight × 100%.
3, experimental result:
The inhibitory action of active ingredient of Chinese herbs compound recipe to mice Lewis lung carcinoma: 9mg/kg active ingredient of Chinese herbs compound recipe can significantly suppress the growth (P<0.01) of mice Lewis lung carcinoma, its anti-lung cancer activity is higher than chemotherapeutic 5-fluorouracil (5-Fu), also higher than the single composition (paclitaxel single, cinobufagin single, triptolide single) of prescription, in table 1.
Table 1 active ingredient of Chinese herbs compound recipe is to mice Lewis lung carcinoma Lewis exercising result
Claims (2)
1. the application of active ingredient of Chinese herbs compound preparation in preparation treatment lung-cancer medicament, is characterized in that it is made by the active ingredient of Chinese herbs of following weight proportion:
1～3 part of paclitaxel, 1～3 part of cinobufagin, 1～3 part of triptolide.
2. application according to claim 1, the dosage form that it is characterized in that this compound preparation is compound recipe liposome or compound dripping pill.
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