CN105079005A - Lung cancer and breast cancer treatment compound preparation containing active ingredients of traditional Chinese medicine and preparation method of lung cancer and breast cancer compound preparation - Google Patents
Lung cancer and breast cancer treatment compound preparation containing active ingredients of traditional Chinese medicine and preparation method of lung cancer and breast cancer compound preparation Download PDFInfo
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- CN105079005A CN105079005A CN201510525088.3A CN201510525088A CN105079005A CN 105079005 A CN105079005 A CN 105079005A CN 201510525088 A CN201510525088 A CN 201510525088A CN 105079005 A CN105079005 A CN 105079005A
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Abstract
The invention discloses a lung cancer and breast cancer treatment compound preparation containing active ingredients of traditional Chinese medicine and a preparation method of the lung cancer and breast cancer compound preparation. The lung cancer and breast cancer treatment compound preparation is made from erianin, taxol, bufalin and bruceine D according to a certain weight ratio. According to the preparation method, liposomes are prepared according to an ethyl alcohol injection method or dropping pills are prepared by taking polyethylene glycol as a base material to obtain the lung cancer and breast cancer treatment compound preparation containing the active ingredients of the traditional Chinese medicine. The form of the compound preparation is compound liposomes and compound dripping pills. According to animal in-vivo anticancer pharmacological experiments, the lung cancer and breast cancer treatment compound preparation containing the active ingredients of the traditional Chinese medicine has obvious inhibiting effect on growth of lung cancer and breast cancer and has higher anticancer activity than chemotherapeutic drug 5-fluorouracil.
Description
Technical field:
The present invention relates to technical field of Chinese medicines, specifically relate to a kind ofly treat Chinese medicinal active ingredient compound preparation of pulmonary carcinoma and breast carcinoma and preparation method thereof.
Background technology:
Cancer is the formidable enemy of harm humans health.The annual new cancer cases of China about has 1,600,000 people, and that dies from cancer every year about has 1,300,000 people, and the number of whole nation death because of cancer rises year by year, and China is the region occurred frequently of the cancers such as pulmonary carcinoma, breast carcinoma, hepatocarcinoma, and cancer mortality remains high.
There is no the most of cancer patient of effective cured substance at present.Though chemotherapeutics has certain curative effect to cancer, toxic and side effects is large, and Chinese patent medicine is general lower to the curative effect of cancer, and curative effect is all undesirable.
The present inventor arduously have studied Sirikaya through 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 9 antineoplastic product invention patent certificates, ZL02148475.9, ZL03112707.X, ZL200410041122.1, ZL200610085781.4, ZL200610085781.4, ZL200810124588.6, ZL201210033666.8, ZL201310028251.6).On the basis of above-mentioned research, the present 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, that specifically prepares for raw material with EN, TAXOL, Toadpoison Medicine, bruceine D a kind ofly treats Chinese medicinal active ingredient compound preparation of pulmonary carcinoma and breast carcinoma and preparation method thereof.
2, technical scheme:
Treat a Chinese medicinal active ingredient compound preparation for pulmonary carcinoma and breast carcinoma, it is characterized in that it is made by the active ingredient of Chinese herbs of following weight proportion: EN 1-3 part, TAXOL 1-3 part, Toadpoison Medicine 1-3 part, bruceine D 1-3 part.
Each active ingredient of Chinese herbs brief introduction is as follows:
EN (Erianin), molecular formula: C
18h
22o
5; Chemical structural formula:
TAXOL (Paclitaxe, Taxol, TAX), (also known as: paclitaxel, taxol, Paclitaxe, Paclitaxe), molecular formula: C
47h
51nO
14; Chemical structural formula:
Toadpoison Medicine (Bufalin): molecular formula: C
24h
34o
4; Chemical structural formula:
Bruceine D (bruceineD): C
20h
26o
9; Chemical structural formula:
Described treatment pulmonary carcinoma and the Chinese medicinal active ingredient compound preparation of breast carcinoma, is characterized in that the dosage form of this compound preparation is compound recipe liposome and compound dripping pill.
The compound recipe method for preparing lipidosome of Chinese medicinal active ingredient compound preparation of the present invention is:
(1) compound recipe liposomal preparation material and proportioning are: lecithin is 10:1 ~ 1.2 with mPEG2000-DSPE (amphipathic ethylene glycol 2000-distearyl phosphatidyl ethanolamine) mass ratio respectively, being 10:1 ~ 1.2 with the mass ratio of cholesterol, is 30:0.8 ~ 1 with the mass ratio of active ingredient of Chinese herbs compound medicine;
(2) preparation method of compound recipe liposome is: adopt alcohol injection preparation.The PBS buffer getting pH7.4 in eggplant type bottle, in water bath with thermostatic control 50 ~ 55 DEG C of preheating 30 ~ 35min; Get lecithin, cholesterol, active ingredient of Chinese herbs compound medicine and mPEG2000-DSPE in beaker, adding appropriate dehydrated alcohol makes it dissolve, what after complete drug dissolution, be injected into rapidly constant temperature preheating is equipped with in the eggplant type bottle of buffer solution, obtain milky liposome turbid liquor, continue to stir aquation 1 ~ 1.2h, evacuation is except ethanol, and 800P crosses high pressure dispersing emulsification machine 10 ~ 12 circulation, obtains active ingredient of Chinese herbs compound recipe liposome.
The method for preparing drop pills of Chinese medicinal active ingredient 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) preparation method of compound dripping pill is: to be put by polyethylene glycol 6000 in water-bath and add active ingredient of Chinese herbs compound medicine in the ratio of medicine and substrate after heat fused and stir, put in drop pill preparation facilities, in insulation instillation liquid Paraffin coolant, dripping becomes ball, and namely the condensed fluid that obtained drop pill removes surface is obtained active ingredient of Chinese herbs compound dripping pill.
The application of Chinese medicinal active ingredient compound preparation of the present invention in preparation treatment pulmonary carcinoma and breast cancer medicines.
Chinese medicinal active ingredient compound preparation of the present invention, have obvious inhibitory action to the growth of pulmonary carcinoma and breast carcinoma in vivo, its active anticancer is apparently higher than chemotherapeutic 5-fluorouracil.
3, beneficial effect:
Chinese medicinal active ingredient compound preparation of the present invention is through Anticancer experiment in animal body, obvious inhibitory action is had to the growth of pulmonary carcinoma and breast carcinoma, the Chinese medicinal active ingredient compound preparation of 9mg/kg dosage significantly can suppress the growth (P<0.01) of mice Lewis lung carcinoma and transplanted breast carcinoma, and its tumour inhibiting rate is respectively 73.32%, 68.61%.Its to the active anticancer of pulmonary carcinoma and breast carcinoma all higher than chemotherapeutic 5-fluorouracil (5-Fu), also higher than the single composition (EN single, TAXOL single, Toadpoison Medicine single, bruceine D single) of prescription, can be used for treatment pulmonary carcinoma and breast carcinoma.
A kind of Chinese medicinal active ingredient compound preparation of the present invention is the active ingredient of Chinese herbs compound anti-cancer medicine prepared for raw material with EN, TAXOL, Toadpoison Medicine, bruceine D.Animal vivo antitumor experimental result show, the growth of Chinese medicinal active ingredient compound preparation to pulmonary carcinoma and breast carcinoma all has very high active anticancer, its anti-cancer activity in vivo higher than chemotherapeutic 5-fluorouracil (5-Fu), also higher than the single composition of prescription.This provides very promising efficient proposed drug for improving anticancer clinical efficacy, also for the mechanism of Study of Traditional Chinese Medicine components compatibility provides good component prescription.
Detailed description of the invention:
Embodiment 1: a kind of Chinese medicinal active ingredient compound preparation for the treatment of pulmonary carcinoma and breast carcinoma, made by EN 1 part (10mg), TAXOL 1 part (10mg), Toadpoison Medicine 1 part (10mg) and bruceine D 1 part (10mg), wherein the preparation method of liposome is as follows:
(1) active ingredient of Chinese herbs compound recipe liposomal preparation material and proportioning are: lecithin is 10: 1 with mPEG2000-DSPE (amphipathic ethylene glycol 2000-distearyl phosphatidyl ethanolamine) mass ratio respectively, being 10: 1 with the mass ratio of cholesterol, is 30: 1 with the mass ratio of active ingredient of Chinese herbs compound medicine.
(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 water bath with thermostatic control 50 DEG C of preheating 30min; Lecithin 900mg, cholesterol 90mg, active ingredient of Chinese herbs compound medicine 30mg and mPEG2000-DSPE90mg are accurately weighed in beaker, adding appropriate dehydrated alcohol makes it dissolve, what after complete drug dissolution, be injected into rapidly constant temperature preheating is equipped with in the eggplant type bottle of buffer solution, obtain milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, and 800P crosses high pressure dispersing emulsification machine 10 circulation, 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 prepares 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, 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: to be put by 60mg polyethylene glycol 6000 in water-bath and add active ingredient of Chinese herbs compound medicine 30mg in the ratio of medicine and substrate 1:2 after heat fused and stir, put in drop pill preparation facilities, in insulation instillation liquid Paraffin coolant, dripping becomes ball, and namely the condensed fluid that obtained drop pill removes surface is obtained active ingredient of Chinese herbs compound dripping pill.
Embodiment 2: a kind of Chinese medicinal active ingredient compound preparation for the treatment of pulmonary carcinoma and breast carcinoma, made by EN 2 parts (20mg), TAXOL 2 parts (20mg), Toadpoison Medicine 2 parts (20mg) and bruceine D 2 parts (20mg), wherein the preparation method of liposome is as follows:
(1) active ingredient of Chinese herbs compound recipe liposomal preparation material and proportioning are: lecithin is 10: 1 with mPEG2000-DSPE (amphipathic ethylene glycol 2000-distearyl phosphatidyl ethanolamine) mass ratio respectively, being 10: 1 with the mass ratio of cholesterol, is 30: 1 with the mass ratio of active ingredient of Chinese herbs compound medicine.
(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 water bath with thermostatic control 50 DEG C of preheating 30min; Lecithin 1800mg, cholesterol 180mg, active ingredient of Chinese herbs compound medicine 60mg and mPEG2000-DSPE180mg are accurately weighed in beaker, adding appropriate dehydrated alcohol makes it dissolve, what after complete drug dissolution, be injected into rapidly constant temperature preheating is equipped with in the eggplant type bottle of buffer solution, obtain milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, and 800P crosses high pressure dispersing emulsification machine 12 circulation, 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 prepares 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, 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: to be put by 120mg polyethylene glycol 6000 in water-bath and add active ingredient of Chinese herbs compound medicine 60mg in the ratio of medicine and substrate 1:2 after heat fused and stir, put in drop pill preparation facilities, in insulation instillation liquid Paraffin coolant, dripping becomes ball, and namely the condensed fluid that obtained drop pill removes surface is obtained active ingredient of Chinese herbs compound dripping pill.
Embodiment 3: a kind of Chinese medicinal active ingredient compound preparation for the treatment of pulmonary carcinoma and breast carcinoma, made by EN 3 parts (30mg), TAXOL 3 parts (30mg), Toadpoison Medicine 3 parts (30mg) and bruceine D 3 parts (30mg), wherein the preparation method of liposome is as follows:
(1) active ingredient of Chinese herbs compound recipe liposomal preparation material and proportioning are: lecithin is 10: 1.2 with mPEG2000-DSPE (amphipathic ethylene glycol 2000-distearyl phosphatidyl ethanolamine) mass ratio respectively, being 10: 1.2 with the mass ratio of cholesterol, is 30: 0.8 with the mass ratio of active ingredient of Chinese herbs compound medicine.
(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 water bath with thermostatic control 50 DEG C of preheating 30min; Lecithin 2700mg, cholesterol 324mg, active ingredient of Chinese herbs compound medicine 90mg and mPEG2000-DSPE180mg are accurately weighed in beaker, adding appropriate dehydrated alcohol makes it dissolve, what after complete drug dissolution, be injected into rapidly constant temperature preheating is equipped with in the eggplant type bottle of buffer solution, obtain milky liposome turbid liquor, continue to stir aquation 1h, evacuation is except ethanol, and 800P crosses high pressure dispersing emulsification machine 12 circulation, 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 prepares 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, 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: to be put by 180mg polyethylene glycol 6000 in water-bath and add active ingredient of Chinese herbs compound medicine 90mg in the ratio of medicine and substrate 1:2 after heat fused and stir, put in drop pill preparation facilities, in insulation instillation liquid Paraffin coolant, dripping becomes ball, and namely the condensed fluid that obtained drop pill removes surface is obtained active ingredient of Chinese herbs compound dripping pill.
Embodiment 4: Chinese medicinal active ingredient compound preparation is to the inhibitory action of 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 this school animal experimental center; Lewis cells of lung cancer is purchased from institute of oncology of Jiangsu Province animal experimental center.
2, modeling and experimental technique
C57BL/6 mice 80, stay 10 in proportion at random for negative control group, all the other 70 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 1: 3 ratio homogenate, adjusts cell number to be 2 × 10
6/ ml.Choose healthy mice, aseptically every right side of mice axillary fossa subcutaneous vaccination 0.2ml.Whole seeded process must be carried out with sterile working in aseptic cover, completes inoculation in 1h.
Be divided into 7 groups at random after inoculation, often organize 10, be respectively tumor model matched group, active ingredient of Chinese herbs compound recipe and composition single thereof 5 test group, 5-fu positive controls, totally 7 groups, separately add negative control group.After inoculation oncocyte 24h, test group lumbar injection active ingredient of Chinese herbs compound recipe, EN single, TAXOL single, Toadpoison Medicine single, bruceine D single, dosage is 9mg/kg, negative control group and tumor model matched group equal-volume injectable drug solvent, 5-FU matched group take 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:
Complete stripping tumor block, and calculating tumor control rate of weighing, tumor control rate=(matched group tumor weight-treatment group tumors weight)/matched group tumor weight × 100%.
3, experimental result:
Active ingredient of Chinese herbs compound recipe is to the inhibitory action of mice Lewis lung carcinoma: 9mg/kg active ingredient of Chinese herbs compound recipe significantly can 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 (EN single, TAXOL single, Toadpoison Medicine single, bruceine D single) of prescription, in table 1:
Table 1 active ingredient of Chinese herbs compound recipe is to mice Lewis lung carcinoma Lewis exercising result
Embodiment 5: active ingredient of Chinese herbs compound recipe is to the inhibitory action of transplanted breast carcinoma
1, laboratory animal and tumor strain
Female Sexual health TA2 mice, body weight 18-22g, Mus 6-8 in age week, purchased from this school animal experimental center; Mouse mastopathy cell strain MA-891 is purchased from institute of oncology of Jiangsu Province animal experimental center;
2, modeling and experimental technique
TA2 mice 80, stay 10 in proportion at random for negative control group, all the other 70 are carried out modeling.Get the exponential phase MA-891 mouse mastopathy cell of In vitro culture, cell concentration is adjusted to 1 × 10
7/ ml.Under aseptic condition, MA-891 mouse mastopathy cell is inoculated in the right armpit of TA2 mice subcutaneous, inoculum concentration is that only (cell number is 2 × 10 to 0.2ml/
6/ only).Whole seeded process must be carried out with sterile working in aseptic cover, completes inoculation in 1h;
Be divided into 7 groups at random after inoculation, often organize 10, be respectively tumor model matched group, active ingredient of Chinese herbs compound recipe and composition single thereof 5 test group, 5-fu positive controls, totally 7 groups, separately add negative control group.After inoculation oncocyte 24h, test group lumbar injection active ingredient of Chinese herbs compound recipe, EN single, TAXOL single, Toadpoison Medicine single, bruceine D single, dosage is 9mg/kg, negative control group and tumor model matched group equal-volume injectable drug solvent, 5-FU matched group take 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:
Complete stripping tumor block, and calculating tumor control rate of weighing, tumor control rate=(matched group tumor weight-treatment group tumors weight)/matched group tumor weight × 100%;
3, experimental result:
Active ingredient of Chinese herbs compound recipe is to the inhibitory action of Implanted breast cancer in mouse: 9mg/kg active ingredient of Chinese herbs compound recipe significantly can suppress the growth (P<0.01) of Implanted breast cancer in mouse, its anti-breast cancer activity is higher than chemotherapeutic 5-fluorouracil (5-Fu), also higher than the single composition (EN single, TAXOL single, Toadpoison Medicine single, bruceine D single) of prescription, in table 2:
Table 2 active ingredient of Chinese herbs compound recipe is to Implanted breast cancer in mouse exercising result
Claims (3)
1. treat a Chinese medicinal active ingredient compound preparation for pulmonary carcinoma and breast carcinoma, it is characterized in that it is made by the active ingredient of Chinese herbs of following weight proportion:
EN 1-3 part, TAXOL 1-3 part, Toadpoison Medicine 1-3 part, bruceine D 1-3 part.
2. the Chinese medicinal active ingredient compound preparation for the treatment of pulmonary carcinoma according to claim 1 and breast carcinoma, is characterized in that the dosage form of this compound preparation is compound recipe liposome or compound dripping pill.
3. the application of Chinese medicinal active ingredient compound preparation as claimed in claim 1 in preparation treatment pulmonary carcinoma and breast cancer medicines.
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Cited By (2)
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| CN111329870A (en) * | 2020-03-16 | 2020-06-26 | 广西中医药大学 | Application of Yadanzigan in preparing medicine for treating and/or preventing lung injury |
| CN112618558A (en) * | 2020-09-23 | 2021-04-09 | 浙江工业大学 | Erianin-adriamycin-containing double-drug co-carried liposome as well as preparation and application thereof |
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