CN101120958A - Medicinal preparation for treating liver cancer and leukemia and producing technology thereof - Google Patents
Medicinal preparation for treating liver cancer and leukemia and producing technology thereof Download PDFInfo
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Abstract
The present invention discloses a pharmaceutical preparation for liver cancer treatment and leukemia treatment as well as the production technology, which is characterized in that the pharmaceutical preparation comprises three chief herbs of the abrotani herbal oil, the glycyrrhetate and the Tretinoin, or single abrotani herbal oil, or the combination of any two herbs together with proper medicinal excipient formulation. The dosage form available for clinical application is prepared. Pharmacodynamic test proves that the medical preparation in the present invention possesses targeting effect to the tumor cells and the present invention can significantly inhibit the cell growth and proliferation of liver cancer, lung cancer and leukemia. The present invention can also greatly prolong the survival period of the mice with liver cancer or lung cancer. The medical preparation in the present invention possesses properties of stable and controllable quality, little toxic and side effects, reliable therapy effect. Name of the production preparation is FuErKang plus the formulation name, such as the FuErKang injection and the FuErKang oral liquid.
Description
Technical field
The present invention relates to a kind of medicine novel formulation and its production technology for the treatment of malignant tumor such as hepatocarcinoma, leukemia.
Background technology
Hepatocarcinoma, leukemia all are common malignancy, at China's sickness rate the trend that rises are year by year arranged, and mortality rate is also high, according to statistics, dies from the hepatocarcinoma number every year more than 100,000.The leukemia sickness rate is about 2.76/10 ten thousand, and is in the majority with child and young patient, has a strong impact on people's health and life quality.
At present the method for treatment hepatocarcinoma is a lot, but best cure method is not all also found in home and abroad no matter.Except that early diagnosis found that small liver cancer (less than 5cm) row surgical resection plus adjuvant pharmacotherapy effect better, mid and late liver cancer adopted chemotherapy, radiotherapy and operative treatment all undesirable.Western medicine amycin, cisplatin etc. have very strong lethal effect to hepatoma carcinoma cell, but clinical use toxic and side effects is more, utilize cantharidin, camptothecine, paclitaxel of modern science extraction separation from natural animal-plant etc., stronger anticarcinogenesis is also arranged, but has the same bone marrow depression of Western medicine equally, toxicities such as GI irritation.By document, light disk retrieval and webpage inquiry, present clinical treatment hepatocarcinoma is medicine preferably, is Oleum Curcumae, Semen Coicis oil (Kang Caite) injection of developing listing the nineties from Chinese medicine.Though these two kinds of injection anticancer effects fail to surpass aforementioned all medicines, toxic and side effects is few, improving patient's clinical symptoms, improves the quality of living, and prolongs aspects such as life span, but obviously is better than the former.Leukemic treatment, except that bone marrow transplantation can prolong patient's life span, chemotherapy, radiotherapy were all undesirable at present, and most of patients leans on the Chinese medicine expectant treatment to improve its life quality.
Summary of the invention
The objective of the invention is to be the clinical malignant tumor determined curative effects such as a kind of treatment hepatocarcinoma, leukemia that provide, toxic and side effects is little, and is stable and controllable for quality, and tumor cell is had targeting, can anticancer proliferate, can play the medicine novel formulation of induction of differentiation again.
The present invention seeks to be achieved through the following technical solutions:
Any two kinds of combinations in the selected Herba Artemisiae Annuae oil of the present invention, glycyrrhetate, three kinds of principal agents of tretinoin or single Herba Artemisiae Annuae oil or three kinds, the pharmaceutic adjuvant prescription with suitable is prepared into injection and oral formulations.No matter single, two is distinguished the flavor of and three flavor principal agent combination formulas, and its consumption is respectively: Herba Artemisiae Annuae oil 1～15g, and glycyrrhetate 1～15g, tretinoin 0.5～2.0g makes 1000ml or 1000g.
Pharmaceutic adjuvant comprises: lecithin, fabaceous lecithin, cholesterol, soybean oil, vitamin E, polyoxyethylene sorbitan monoleate, glucose, glycerol, sorbitol, PVP etc.Because of the difference of adjuvant kind and consumption, preparation of the present invention can be Emulsion, liposome (multiphasic liposomes) liquid or solid preparation.The name of preparation finished product: Fu Erkang+dosage form title is as multiple that health injection, multiple that recovery oral liquid, multiple your health lyophilized formulations etc.
The extraction preparation method of principal agent Herba Artemisiae Annuae oil of the present invention and glycyrrhetate:
1, the extraction of Herba Artemisiae Annuae oil: get the Herba Artemisiae Annuae chopping, in the boiler of packing into, add 6～8 times of water gagings, soak 2h, add thermal distillation 2～3h, collect distillate, redistillation separates volatile oil, promptly.Also can adopt supercritical extraction method to prepare Herba Artemisiae Annuae oil.
2, the extraction of glycyrrhetate preparation: Radix Glycyrrhizae is broken into coarse powder, and it is moistening to add weak ammonia, and with 10 times of water gaging percolation, percolate adds rare H
2SO
4Acidify, the leaching precipitate adds 4 times of amount ethanol, and backflow 3h filters, and filtrate adds ammonia or 20%KOH, 10%NaOH ethanol liquid to alkalescence, places crystallize, and the leaching crystallization adds the glacial acetic acid heating for dissolving, puts the cold analysis crystalline substance, leaching crystal, dry glycyrrhetate.
The specific embodiment:
Embodiment 1:
A. get vitamin e1 g, soybean oil (injection) 5g, cholesterol 4g, tretinoin 0.5g, soybean phospholipid 16g, polyoxyethylene sorbitan monoleate 10g is heated to fusion, and is cold slightly, adds Herba Artemisiae Annuae oil 5g, stirs evenly.
B. extracting liquorice acid ammonium 2g puts into 400ml boiling water and stirs moltenly, transfers pH5～7, in tissue mashing machine, under 3000～6000 rev/mins of stirrings, slowly adds a fused solution, after adding, stirs 3 times with 8000 rev/mins, and each 3min is prepared into ropy milk liquid.
C. get glucose for injection 50g, be dissolved in the 500ml water, be heated to 40～60 ℃, under agitation add the b emulsion, add water, stir evenly, in high pressure homogenizer, with 300～400kg/cm to 1000ml
2Pressure homogenize 3 times repeatedly.Emit, decompression filters the degassing, and No. 4 filter bulbs of reuse or filtering with microporous membrane seal after filling and sealing or the lyophilization under nitrogen current, and 100 ℃ of sterilization 30min promptly.
Embodiment 2:
A. get vitamin E 0.5g, injection soybean oil 10g, cholesterol 5g, tretinoin 1g, soybean phospholipid 20g, Polysorbate 10g, cold slightly after the heated and stirred fusion, add Herba Artemisiae Annuae oil 10g, stir evenly.
B. get glycerol for injection 25g, add in the 400ml water, stir evenly, be preheated to about 60 ℃, in tissue mashing machine, under 3000～6000 rev/mins of stirrings, slowly add a liquid, add the back and stir 3 times with 8000 rev/mins, each 3min is prepared into emulsion.Take out, add water to 1000ml, below according to embodiment 1 high pressure homogenize, filter, fill is sterilized promptly.
Embodiment 3:
A. get soybean phospholipid 10g, Polysorbate 10g is dissolved in the 400ml boiling water, and is cold slightly, in tissue mashing machine, under 3000～6000 rev/mins of stirrings, successively slowly adds vitamin e1 g, and Herba Artemisiae Annuae oil 15g adds the back and stirs 10min with 8000 rev/mins.
B. get glucose or sorbitol 50g or glycerol 25g, be dissolved in the 500ml water, be preheated to 60 ℃, add a liquid, add water to 1000ml, stir evenly, below according to embodiment 1 high pressure homogenize, filter, fill is sterilized promptly.
The present invention is multiple, and your health injection pharmacodynamics test is as follows:
Experimental example one: multiple that health is to the test report of lotus hepatocarcinoma (H22) mouse tumor
1 test objective: observe multiple your health lotus H22 (S type) mice is had or not the anti-tumor in vivo effect, for exploitation Fu Er Kandy supplies experimental basis.
2 test materials:
2.1 tried thing: multiple that health injection, professor Feng Wenyu provides by Luzhou Medical College, lot number: 050629.
2.2 laboratory animal: kunming mice, SPF level animal are provided by Animal Experimental Study chamber, Chongqing Institute of Chinese Medicine.The quality certification number: SCXK (Chongqing) 20020004.
3 experimental situations: carry out the facility quality certification number at the primary standard Animal Lab.: SYXK (Chongqing) 20020002
4 test methods: under the aseptic condition, get 10～12 days solid tumor of inoculation, by homogenate in 1: 5, adjusting the oncocyte number was 10
7Individual/ml, it is subcutaneous to be inoculated in the right axil of mice, 0.2ml/ only, every mouse inoculation oncocyte quantity is 2 * 10
6, divide 7 groups next day at random, promptly multiple that health 25ml/kg, 12.5ml/ ton, three dosage groups of 6.25ml/kg, adjuvant 25ml/kg group, KANGLAITE 25ml/kg group, cyclophosphamide 25mg/kg group and matched group.10 every group of medication group and adjuvant groups, every day the tail intravenously administrable once, successive administration 10 days, matched group gives the respective volume normal saline.Drug withdrawal is one day after the last administration.Take off neck and put to death animal, weigh, cut open tumor and weigh, by formula calculate tumor control rate.
Curative effect judging standard: tumor control rate repeats 2 times (totally 3 times) continuously greater than 30%, learn to handle the person that has the notable difference by statistics for antitumor action is arranged.
5 result of the tests: see Table 1
The influence that multiple your health of table 1 is grown to H22 (S type) mouse tumor
| Group | Number of animals (only) | Body weight (g) | Tumor weight ± SD (g) | Suppression ratio (%) | The P value | ||
| Before the medicine | Behind the medicine | Before the medicine | Behind the medicine | ||||
| Matched group is the multiple that of multiple you the health 12.5ml/kg of you health 25ml/kg health 6.25ml/kg adjuvant 25ml/kg KANGLAITE 25ml/kg cyclophosphamide 25mg/kg again | 24 10 10 10 10 10 10 | 22 10 10 10 10 10 10 | 24.46 24.40 24.50 24.50 24.50 24.50 24.50 | 38.63 33.20 30.20 36.20 38.20 30.30 28.00 | 3.12±0.62 1.58±0.68 1.90±0.35 2.45±0.47 2.80±1.23 1.91±0.27 0.31±0.11 | 49.36 39.10 21.50 10.26 38.78 90.06 | P＜0.01 P＜0.01 P＜0.01 P＜0.01 P＜0.01 |
By table 1 as seen: multiple your each dosage group intravenous injection of health injection (iv) has the obvious suppression effect to lotus H22 mouse entity tumor.Repeat continuously 2 times (totally 3 times), the result is similar substantially.
6 conclusions: result of the test shows that under this experimental condition, multiple your health injection has the obvious suppression effect to lotus H22 mouse entity tumor.
Experimental example two: multiple that health is to the test report of lotus hepatocarcinoma (H22) ascites tumor mice
1 test objective: observe multiple your health lotus H22 (A type) mice is had or not the anti-tumor in vivo effect, for exploitation Fu Er Kandy supplies experimental basis.
2 experiment materials:
2.1 tried thing: multiple that health injection, professor Feng Wenyu provides by Luzhou Medical College, lot number: 050629.
2.2 laboratory animal: kunming mice, SPF level animal are provided by Animal Experimental Study chamber, Chongqing Institute of Chinese Medicine.The quality certification number: SCXK (Chongqing) 20020004.
2.3 positive control drug: Neosar, lot number: 05090721.
3 experimental situations: carry out the facility quality certification number at the primary standard Animal Lab.: SYXK (Chongqing) 20020002.
4 test methods:
Under the aseptic condition, get 7-8 days ascites tumor of inoculation by dilution in 1: 10, adjusting the oncocyte number is 10
7Individual/ml, be inoculated in mouse peritoneal, 0.2ml/, every mouse inoculation tumor cell quantity is 2 * 10
6, be divided into six groups next day at random, promptly multiple that health 25ml, three dosage groups of 12.5ml, 6.25ml/kg, adjuvant 25ml/kg group, cyclophosphamide 50mg/kg group and matched group; 20 animals of matched group, all the other respectively organize 10.Medication group and adjuvant group intraperitoneal administration every day once, successive administration 10 days, matched group gives the equal volume normal saline.Observed and recorded animal dead situation after the drug withdrawal surpasses 4 all persons and calculates by 4 weeks, by formula calculates increase in life span:
Curative effect judging standard: increase in life span repeats 2 times (totally 3 times) continuously greater than 50%, learn to handle the person that has the notable difference by statistics for antitumor action is arranged.
5 result of the tests: see Table 1
The influence of table 1 couple lotus H22 (A type) mice increase in life span
| Group | Body weight (g) | Number of animals | Average survival natural law ± SD | Increase in life span (%) | The P value |
| Matched group is the multiple that of multiple you the health 12.5ml/kg of you health 25ml/kg health 6.25ml/kg adjuvant 25ml/kg cyclophosphamide 50mg/kg again | 20.90 20.70 20.70 20.60 20.70 20.80 | 20 10 10 10 10 10 | 12.35±2.35 22.50±5.82 20.40±5.64 18.60±3.75 12.10±0.99 22.60±4.35 | 82.19 65.18 50.61 83.00 | P＜0.01 P＜0.01 P＜0.01 P＜0.01 |
By table 1 as seen, multiple your each dosage group lumbar injection (ip) of health injection has obvious prolongation effect to lotus H22 (A type) mice with tumor life.Repeat continuously 2 times (totally 3 times), the result is similar substantially.
6 conclusions: result of the test shows that multiple your each dosage group lumbar injection of health injection has obvious prolongation effect to lotus H22 (A type) mice with tumor life.
Experimental example three: multiple that health injection is to the vitro inhibition effect of pulmonary carcinoma A549 and leukemia CEM-C7 cell strain
1 material
1.1 the multiple that of medicine health injection, the institute of materia medica provides by Luzhou Medical College, lot number: 060313.Amycin, lot number: 051019, factory: Haizheng Medicine Stock Co., Ltd., Zhejiang Prov.
1.2 cell strain A549 (pulmonary carcinoma) and CEM-C7 (T chronic myeloid leukemia) cell strain (purchasing in Shanghai cell institute) is preserved by this laboratory.
1.3 reagent RPMI-1640 culture medium, U.S. Gibco company product; Penicillin, streptomycin, North China pharmaceutical Co. Ltd product; Calf serum, Lanzhou sino-america joint-venture people marine growth company product; Trypsin, U.S. Gibco company product; Trypan blue, U.S. Sigma company product; Other reagent is homemade analytical pure.
1.4 instrument and equipment CO
2Incubator, Japanese SANYO company product;
Inverted phase contrast microscope, German Olympus company product;
Superclean bench, SuZhou Antai Air Tech Co., Ltd.;
Full-automatic microplate reader, BIO-RAD product, Model550 (microplate reader);
2 methods
Test is divided into blank group (not celliferous complete medium), negative control group (without the A549 and the CEM-C7 cell of drug treating), experimental group (totally 12 Concentraton gradient), 3 every group multiple holes.Positive controls: amycin correspondingly with experimental group is divided into 12 Concentraton gradient.
The trophophase cell of taking the logarithm, the RPMI-1640 culture fluid suspends and adjusts concentration is 1 * 10
5Individual/ml, every hole 100 μ l.It is every hole 1 * 10
4Individual cell inoculation in 96 orifice plates, 5%CO
2, 37 ℃ of cultivations of saturated humidity.Treat that cell is adherent fully after 24 hours, multiple your health injection to the final concentration that experimental group adds the dilution of RPMI-1640 complete medium is respectively 0.00037,0.000735,0.00147,0.00294,0.0059,0.0117,0.0235,0.047,0.094,0.1875,0.375,0.75 μ g/ml, positive controls adds the amycin of RPMI-1640 complete medium dilution, and concentration is corresponding with experimental group.Negative control group adds complete medium again, cultivates 48 hours, stops preceding 4 hours adding MTT stock solution 20 μ l/ holes in experiment, continues at 5%CO
2, hatch in 37 ℃ of incubators of saturated humidity to experiment and stop, inhale and abandon supernatant, every hole adds dimethyl sulfoxide (DMSO) 100 μ l.Room temperature lucifuge vibration mixing and measure the OD value in each hole on 10 minutes inherent full-automatic microplate reader in the 490nm wavelength, by formula: growth inhibition ratio that GI (growth inhibition ratio)=1-(medicine group OD value/matched group OD value) * 100% calculating is respectively organized.Calculate the IC50 value with the Bliss method.
3 results
Do MTT altogether three times, the results are shown in Table 1-6
Table 1 is tested the effect of multiple that health to tumor cell A549 and CEM-C7 for the first time
| A549 (pulmonary carcinoma) | CEM-C7 (T chronic myeloid leukemia) | |||
| Multiple that health (μ g/ml) 0.75 0.375 0.1875 0.094 0.047 0.0235 0.0117 0.0059 0.00294 0.00147 0.000735 0.00037 | Cell inhibitory rate 0.94721 0.83579 0.52837 0.41449 0.08672 0.06463 0.04909 0.01750 0.09736 0.17820 0.17820 0.15218 | IC50 (μ g/ml) (IC5095% credibility interval) 0.1446 ± 0.0187 (0.1271-0.1645) | Cell inhibitory rate 0.967941 0.974515 0.970773 0.830805 0.354268 0.254652 0.193467 0.151598 0.062298 0.03125 0.04996-0.01881 | IC50 (μ g/ml) (IC5095% credibility interval) 0.0391 ± 0.0057 (0.0339-0.0452) |
Table 2 is tested the effect of multiple that health to tumor cell A549 and CEM-C7 for the second time
| A549 (pulmonary carcinoma) | CEM-C7 (T chronic myeloid leukemia) | |||
| Multiple that health (μ g/ml) 0.75 0.375 0.1875 0.094 0.047 0.0235 0.0117 0.0059 0.00294 0.00147 0.000735 0.00037 | Cell inhibitory rate 0.870398 0.851579 0.628375 0.414498 0.086729 0.064638 0.049092 0.017509 0.097365 0.178203 0.178203 0.152185 | IC50 (μ g/ml) (IC5095% credibility interval) 0.1431 ± 0.466 (0.1039-0.197) | Cell inhibitory rate 0.967319 0.972953 0.970861 0.966192 0.381792 0.374064 0.231104 0.138855 0.154955 0.207921 0.195041 0.137245 | IC50 (μ g/ml) (IC5095% credibility interval) 0.0239 ± 0.0201 (0.0111-0.0576) |
Table 3 is tested the effect of multiple that health to tumor cell A549 and CEM-C7 for the third time
| A549 (pulmonary carcinoma) | CEM-C7 (T chronic myeloid leukemia) | |||
| Multiple that health (μ g/ml) 0.75 0.375 0.1875 0.094 0.047 0.0235 0.0117 0.0059 0.00294 0.00147 0.000735 0.00037 | Cell inhibitory rate 0.964811 0.946172 0.236443 0.225034 0.167028 0.11079 0.058729 0.010203 0.020808 0.025629 0.0094 0.005383 | IC50 (μ g/ml) (IC5095% credibility interval) 0.1644 ± 0.0221 (0.1438-0.188) | Cell inhibitory rate 0.94574 0.951961 0.944358 0.946432 0.467773 0.099361-0.1042-0.19025-0.17297-0.05858-0.13219-0.1671 | (IC50 (μ g/ml) (IC5095% credibility interval) 0.0499 ± 0.0072 (0.0431-0.0576) |
Table 4 is tested the effect of amycin to tumor cell A549 and CEM-C7 for the first time
| A549 (pulmonary carcinoma) | CEM-C7 (T chronic myeloid leukemia) | |||
| Amycin (μ g/ml) 0.75 0.375 0.1875 0.094 0.047 0.0235 0.0117 0.0059 0.00294 0.00147 0.000735 0.00037 | Cell inhibitory rate 0.786531 0.552679 0.253689 0.154789 0.036545 0.056794 0.076131 0.036794 0.024886 0.034675 0.004674 0.013497 | IC50 (μ g/ml) (IC5095% credibility interval) 0.3291 ± 0.0497 (0.2831-0.3825) | Cell inhibitory rate 0.931254 0.946311 0.410634 0.347922 0.115464 0.146741 0.103544 0.034541 0.031464 0.024164 0.003647 0.001564 | IC50 (μ g/ml) (IC5095% credibility interval) 0.1297 ± 0.0202 (0.1111-0.1515) |
Table 5 is tested the effect of amycin to tumor cell A549 and CEM-C7 for the second time
| A549 (pulmonary carcinoma) | CEM-C7 (T chronic myeloid leukemia) | |||
| Amycin (μ g/ml) 0.75 0.375 0.1875 0.094 0.047 0.0235 0.0117 0.0059 0.00294 0.00147 0.000735 0.00037 | Cell inhibitory rate 0.843216 0.65311 0.354133 0.178346 0.094613 0.087461 0.036544 0.005482 0.004154 0.001551 0.054036 0.001854 | IC50 (μ g/ml) (IC5095% credibility interval) 0.2445 ± 0.0399 (0.2079-0.2876) | Cell inhibitory rate 0.920236 0.894131 0.498113 0.246115 0.164125 0.164461 0.064413 0.046113 0.094131 0.034644 0.063464 0.001649 | IC50 (μ g/ml) (IC5095% credibility interval) 0.1347 ± 0.0213 (0.115-0.1577) |
Table 6 is tested the effect of amycin to tumor cell A549 and CEM-C7 for the third time
| A549 (pulmonary carcinoma) | CEM-C7 (T chronic myeloid leukemia) | |||
| Amycin (μ g/ml) 0.75 0.375 0.1875 0.094 0.047 0.0235 0.0117 0.0059 0.00294 0.00147 0.000735 0.00037 | Cell inhibitory rate 0.804665 0.762664 0.306695 0.201446 0.064994 0.024644 0.016623 0.066466 0.001644 0.000316 0.016546 0.011645 | IC50 (μ g/ml) (IC5095% confidence region) 0.2472 ± 0.0351 (0.2146-0.2848) | Cell inhibitory rate 0.941132 0.841332 0.503164 0.346411 0.164411 0.09413 0.120031 0.067113 0.016464 0.003467 0.034674 0.003644 | IC50 (μ g/ml) (IC5095% confidence region) 0.1912 ± 0.0362 (0.1584-0.2308) |
4 conclusions
Under this experiment condition, three IC50 that multiple your health injection is tested the inhibitory action of tumor cell A549 are respectively 0.1446 ± 0.0187 μ g/ml, 0.1431 ± 0.466 μ g/ml, 0.1644 ± 0.0221 μ g/ml.IC50 to tumor cell CEM-C7 then is 0.03914 ± 0.0057 μ g/ml, 0.0239 ± 0.0201 μ g/ml, 0.04994 ± 0.0072 μ g/ml.Show that multiple your health injection all has the inhibitory action of significance to tumor cell A549 (pulmonary carcinoma) and CEM-C7 cell (leukemia).
Experimental example four: multiple that health is to the therapeutical effect of mouse leukemia P388
1 test objective: observe multiple your health lotus leukemia P388 mice is had or not the anti-tumor in vivo effect, for exploitation Fu Er Kandy supplies experimental basis.
2 experiment materials:
2.1 tried thing: multiple that health injection, professor Feng Wenyu provides by Luzhou Medical College, lot number: 061017.Multiple that health injection adjuvant solution, professor Feng Wenyu provides by Luzhou Medical College, lot number: 061025.
2.2 laboratory animal: Kunming mouse, SPF level animal are provided by Animal Experimental Study chamber, Chongqing Institute of Chinese Medicine.The quality certification number: SCXK (Chongqing) 20020004.
2.3 positive control drug: cisplatin injection, specification: 6ml:30mg, lot number: 060701.Factory: Gejiu Bio-Pharmaceutical Co., Ltd., Yunnan
2.4 tumor strain: mouse leukemia P388, introduce a fine variety in Medical University Of Chongqing (building strain by the Huaxi Medical Univ institute of oncology).
3 experimental situations: carry out the facility quality certification number at the primary standard Animal Lab.: SYXK (Chongqing) 20020002
4 test methods:
Under the aseptic condition, get and be inoculated in 7 days P388 leukemia ascites of mice, by dilution in 1: 15, adjusting leukaemia's number was 10
7Individual/ml, be inoculated in mouse peritoneal, 0.2ml/ is only, every mouse inoculation leukaemia quantity is 2 * 10
6, divide 6 groups next day at random: multiple that health 40ml, three dosage groups of 20ml, 10ml/kg, adjuvant 40ml/kg group, cisplatin group and matched group.Multiple each dosage group of that health, adjuvant group and every group of 10 mices of cisplatin group, 20 of matched groups.Answer each dosage group of that health, adjuvant group intraperitoneal administration every day once, successive administration 10 days, be administered once the next day of the cisplatin group (totally 5 times), matched group gives the equal volume normal saline.Observed and recorded animal dead situation after the drug withdrawal surpasses 30 days and calculated by 30 days, by formula calculates increase in life span:
Curative effect judging standard: increase in life span repeats 2 times (totally 3 times) continuously greater than 50%, learn to handle the person that has the notable difference by statistics for antitumor action is arranged.
5 result of the tests: see Table 1
Table 1, multiple your health are to the influence of lotus leukemia P388 mice increase in life span
| Group | Body weight (g) | Number of animals | Average survival natural law ± SD | Increase in life span (%) | The P value |
| Matched group is the multiple that of multiple you the health 20ml/kg of you health 40ml/kg health 10ml/kg adjuvant 40ml/kg cisplatin 2mg/kg again | 18.55 18.50 18.40 18.50 18.60 18.50 | 20 10 10 10 10 10 | 12.75±0.79 20.60±2.01 19.20±3.70 14.20±0.92 12.50±0.97 21.10±2.08 | 61.57 50.59 11.37 65.49 | P＜0.01 P＜0.01 P＜0.01 P＜0.01 |
Annotate: the P value is compared with matched group for each group
Table 1 is the result show, multiple you health injection 40ml/kg, 20ml/kg organize has tangible life prolongation effect to lotus leukemia P388 mice.Repeat continuously 2 times (totally 3 times), the result is similar substantially.
6 conclusions: result of the test shows that lumbar injection multiple you health injection 40ml/kg, 20ml/kg organize has tangible life prolongation effect to lotus leukemia P388 mice.
Claims (4)
1. treat hepatocarcinoma, leukemic pharmaceutical preparation and its production technology for one kind, it is characterized in that: it is by any two kinds of combinations in Herba Artemisiae Annuae oil, glycyrrhetate, three kinds of principal agents of tretinoin or single Herba Artemisiae Annuae oil or three kinds, with suitable pharmaceutic adjuvant prescription, injection of making and oral formulations.No matter single, two is distinguished the flavor of and three flavor principal agent combination formulas, and its consumption is respectively: Herba Artemisiae Annuae oil 1～15g, and glycyrrhetate 1～15g, tretinoin 0.5～2.0g makes 1000ml or 1000g.
2. the described glycyrrhetate of claim 1 can be ammonium, potassium, the sodium salt of glycyrrhizic acid; The described pharmaceutic adjuvant of claim 1 comprises: lecithin, fabaceous lecithin, cholesterol, soybean oil, vitamin E, polyoxyethylene sorbitan monoleate, glucose, glycerol, sorbitol, PVP etc.
3. treatment hepatocarcinoma according to claim 1, leukemic pharmaceutical preparation, because of the difference of adjuvant kind and consumption, the preparation finished product can be Emulsion, liposome liquid or solid preparation.
4. the production technology of treatment hepatocarcinoma according to claim 1, leukemia medicament preparation:
A. get vitamin E 1g, injection soybean oil 5g, cholesterol 4g, tretinoin 0.5g, soybean phospholipid or lecithin 16g, polyoxyethylene sorbitan monoleate 10g, Hybrid Heating stirs fusion, and is cold slightly, adds Herba Artemisiae Annuae oil 5g, stirs evenly.
B. extracting liquorice acid ammonium 5g puts into 400ml boiling water and stirs moltenly, transfers pH5～7, in tissue mashing machine, stirs down with 3000～6000 commentariess on classics/min, slowly adds a fused solution, adds the back with 8000 commentariess on classics/min stirring 3 times, and 3min is prepared into ropy milk liquid at every turn.
C. get glucose for injection 50g or glycerol 25g, be dissolved in the 500ml water, be heated to 30～60 ℃, under agitation add b ropy milk liquid, add water, stir evenly, in high pressure homogenizer, with 300～400kg/cm to 1000ml
2Pressure homogenize 3 times is emitted, and decompression filters the degassing, and No. 4 filter bulbs of reuse or filtering with microporous membrane seal after perfusion sealing or the lyophilization under nitrogen current, and 100 ℃ of sterilization 30min promptly.
What above production technology adopted is that fusion method adds even newborn method of two steps, and preparation technology of the present invention still can adopt film dispersion method, ultrasonic dispersing method etc.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2007100486081A CN101120958B (en) | 2007-03-13 | 2007-03-13 | Medicinal preparation for treating liver cancer and leukemia and producing technology thereof |
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| CN2007100486081A CN101120958B (en) | 2007-03-13 | 2007-03-13 | Medicinal preparation for treating liver cancer and leukemia and producing technology thereof |
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| CN101120958A true CN101120958A (en) | 2008-02-13 |
| CN101120958B CN101120958B (en) | 2010-11-10 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178651A (en) * | 2011-05-05 | 2011-09-14 | 山东大学 | Tretinoin fat emulsion injection and preparation method thereof |
| WO2023168608A1 (en) * | 2022-03-08 | 2023-09-14 | Mastery Biotech Co., Ltd. | Pharmaceutical composition including retinoic acid and carbohydrate and use thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1839899A (en) * | 2006-01-19 | 2006-10-04 | 四川大华亿信药物科技有限公司 | Liver disease-treating medicine |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102178651A (en) * | 2011-05-05 | 2011-09-14 | 山东大学 | Tretinoin fat emulsion injection and preparation method thereof |
| CN102178651B (en) * | 2011-05-05 | 2012-09-26 | 山东大学 | Tretinoin fat emulsion injection and preparation method thereof |
| WO2023168608A1 (en) * | 2022-03-08 | 2023-09-14 | Mastery Biotech Co., Ltd. | Pharmaceutical composition including retinoic acid and carbohydrate and use thereof |
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| Publication number | Publication date |
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| CN101120958B (en) | 2010-11-10 |
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