CN100391441C - Matrine elaioplast drop ball and its preparation - Google Patents
Matrine elaioplast drop ball and its preparation Download PDFInfo
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- CN100391441C CN100391441C CNB2006100193029A CN200610019302A CN100391441C CN 100391441 C CN100391441 C CN 100391441C CN B2006100193029 A CNB2006100193029 A CN B2006100193029A CN 200610019302 A CN200610019302 A CN 200610019302A CN 100391441 C CN100391441 C CN 100391441C
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Abstract
A dripping pill of matrine liposome with high stability and disintegrating speed is prepared from the matrine liposome prepared from matrine, soybean lecithin and cholesterol, and water-soluble matrix through proportional mixing, and dripping in cooling liquid.
Description
Technical field
The present invention relates to a kind of matrine preparation and preparation method thereof.
Background technology
Matrine (matrine, MAT) derive among leguminous plant Radix Sophorae Flavescentis Sophora flavescens Ait, Herba Sophorae alopecuroidis S.alopecuroides L. and the root of subprostrate sophora S.subprostrata Chun et T.Chen, have many-sided pharmacological action and clinical function, as antitumor, antibiotic, parasiticide, antiviral, anti-arrhythmia, swelling diuretic, antiallergic with alleviate the effects such as leukopenia that cyclophosphamide causes.The antitumaous effect mechanism of matrine shows that matrine not only has direct lethal effect to tumor cell, induces some tumor cell to normal cell differentiation and apoptosis-promoting effect in addition.In addition, matrine does not produce destruction to normal cell at antineoplastic simultaneously, simultaneously can also leukocyte increasing, and the human body immunity improving function.
Liposome is used in the antineoplastic treatment as a kind of novel form, has the effect characteristics of many uniquenesses, as tumor cell is had passive targeting.This performance reduces untoward reaction and has crucial meaning for improving the antitumor drug clinical efficacy.
The dosage form that matrine is commonly used at present is an injection, considers drug administration by injection administrated method complexity, must be to hospital administration, and not very convenient concerning the patient, generally all there is the bad problem of stability in injection simultaneously.Matrine is prepared into liposome, can reaches target administration, yet be thermodynamic unstable system by the traditional liposomal that lecithin and cholesterol etc. is formed, weak stability has in vivo and in vitro limited its use, greatly influences its application as pharmaceutical carrier.
Drop pill be by medicine with after the solid matrix heating and melting becomes solution suspension or emulsion, splash in the not miscible condensing agent, owing to the interfacial tension effect of molten melt drop in condensed fluid is shrunk to ball, is condensed into solid-state subsequently and makes.Drop pill is a kind of form of solid dispersion.Because it has that stripping is fast, bioavailability is high, good effect, side effect are little, medicine stability reaches advantages such as preparation is simple, easy to control the quality well, therefore receives the extensive attention of the world of medicine.
Summary of the invention
The object of the present invention is to provide a kind of matrine elaioplast drop ball and preparation method thereof, this method solves the matrine elaioplast instability problem, has increased the oral novel form of matrine; The matrine elaioplast drop ball disintegration rate that this method obtains is fast, absorption is complete, has targeting.
To achieve these goals, technical scheme of the present invention is: a kind of matrine elaioplast drop ball, it is characterized in that it is mainly mixed to drip to make by matrine elaioplast and adjuvant raw material makes drop pill and forms in the liquid coolant, the weight proportion of matrine elaioplast and adjuvant is 1: 1-10, adjuvant are water-soluble base; Described matrine elaioplast is mainly formed by matrine, soybean lecithin and cholesterol feedstock production, and the weight proportion of matrine and soybean lecithin and cholesterol is 1: 1-5, wherein, the weight proportion of soybean lecithin and cholesterol is 1-5: 1.
Described water-soluble base is that molecular weight is that Polyethylene Glycol, gelatin, sodium stearate, glycerol, the molecular weight of 4000-6000 is any one or two or more the mixture arbitrarily in poloxamer of 188 etc., when two or more mixes arbitrarily, be any proportioning.
The preparation method of above-mentioned matrine elaioplast drop ball is characterized in that it comprises the steps:
1), preparation matrine elaioplast: matrine elaioplast is mainly formed by matrine, soybean lecithin and cholesterol feedstock production, the weight proportion of matrine and soybean lecithin and cholesterol is 1: 1-5, wherein, the weight proportion of soybean lecithin and cholesterol is 1-5: 1; With preparation matrine elaioplasts such as fusion method, reverse evaporation, ether injection method or thin-film ultrasonic methods;
2), mixed melting: the weight proportion by matrine elaioplast and adjuvant is 1: 1-10 chooses matrine elaioplast and adjuvant, is heated to fusion more than 80 ℃, fully mixes stirring evenly, and gets fused mass, is incubated standby;
3), the system of dripping: preheating drop pill machine, the fluid reservoir that makes the drop pill machine is a constant temperature more than 80 ℃, and the above-mentioned fused mass that obtains is put into fluid reservoir, with 20-60 drip/minute the speed of dripping splash in the liquid coolant of drop pill machine, make drop pill;
4), manufactured goods: collect drop pill, the filtering liquid coolant, drying obtains product.
Described liquid coolant is methyl-silicone oil, dimethicone, liquid paraffin or other plant oil.
In the described step 3) the preferred 60-90 of the temperature of the water dropper of drop pill machine ℃; The preferred 70-90 of the temperature of the mouth of pipe of drop pill machine ℃; The optimum temperature gradation of liquid coolant is 20--10 ℃; Dripping apart from preferred range is 4-16cm.
Matrine elaioplast drop ball of the present invention can be used for treating diseases such as malignant tumor, arrhythmia, heart failure, viral myocarditis, coronary heart disease.
By the pharmacological experiment study matrine elaioplast respectively to mice S
180, EAC, H
22The inhibitory action of tumor and to the influence of immune organ.Use mice S respectively
180, EAC, H
22The transplanted tumor modeling is dissected and respectively to be organized tumor-bearing mice, gets tumor body, spleen, thymus and claims weight in wet base and calculate tumour inhibiting rate, detects lymhocyte transformation rate (LTT).The result shows that the dosage tumor-inhibiting action is the highest in the matrine elaioplast, compares with the Isodose matrine, to S
180, EAC, H
22Inhibitory action all be better than matrine, to H
22The LTT of mice is higher than matrine.Matrine is after liposome is handled, because the targeting of liposome makes the matrine orientation be gathered in tumor cell and discharges, than matrine stronger anti-tumor effect is arranged, and when pressing down tumor enhancing human body immunity power.With method relatively matrine elaioplast drop ball and matrine elaioplast to mice S
180, EAC, H
22The inhibitory action of tumor and the influence of immune organ found, because matrine elaioplast is scattered in the water-soluble base, increased the stability of matrine elaioplast, improved its bioavailability, the antitumor action and the matrine elaioplast of matrine elaioplast drop ball are suitable.
The 2.2.15 cell that is used for In vitro culture is the better model of external anti-HBV drug screening at present and evaluation, observation and comparison matrine elaioplast drop ball, matrine elaioplast, matrine three are to 2.2.15 emiocytosis HBsAg, the influence of HBeAg and the cytotoxicity of medicine, the anti-HBV effect of preliminary assessment matrine elaioplast.After the result shows that matrine elaioplast drop ball, matrine elaioplast, matrine act on 2.2.15 cell lld, the half toxic concentration (TC50) of pair cell is respectively 8.47mg/ml, 7.29mg/ml and 1.33mg/ml, medium effective concentration (IC50) to HBsAg and HBeAg inhibition is respectively 0.065mg/ml, 0.078 mg/ml, 3.35mg/ml matrine elaioplast is respectively 93.34,90.46 and 2.17 to the therapeutic index (TI) of HBsAg and HBeAg.Illustrate that matrine elaioplast drop ball secretion to HBsAg and HBeAg in cell in vitro is cultivated has good inhibitory effect, can improve the anti-HBV effect of matrine.
The present invention adopts oral form, oral three times of every day of adult, and each 0.1-0.2g, three months is a course of treatment.
The matrine elaioplast drop ball section of the present invention's preparation obtains matrine elaioplast complete form in drop pill with Luo Danlan dyeing with E200 type Nikon ECLIPSE biology microscope sem observation, sees Fig. 3, Fig. 4.
Matrine elaioplast drop ball of the present invention because matrine elaioplast is prepared into drop pill, has both solved the targeting of matrine, has solved the instability problem of Liposomal formulation again.Adopt the form of elaioplast drop ball agent simultaneously, increased novel form, filled up the dosage form blank.Preparation method of the present invention is simple, and the drop pill that obtains is smooth, rounding, color and luster are good, and this dosage form disintegration rate is fast, absorbs fully, has targeting, the bioavailability height.
Description of drawings
Fig. 1 is the picture (lot number: 20060410) of matrine elaioplast drop ball of the present invention
Fig. 2 is the picture (lot number: 20060412) of matrine elaioplast drop ball of the present invention
Fig. 3 is a matrine elaioplast drop ball of the present invention cross section microscope figure (lot number: 20060410)
Fig. 4 is a matrine elaioplast drop ball of the present invention cross section microscope figure (lot number: 20060412)
The specific embodiment
In order to understand the present invention better, further illustrate content of the present invention below in conjunction with embodiment, but content of the present invention not only is confined to the following examples.
Embodiment 1:
One, prepares matrine elaioplast with the ether injection method
(1) preparation matrine elaioplast
Phosphate buffered solution with pH6.8 is that solvent is prepared 1% matrine solution, gets 120ml in conical flask, and with soybean lecithin 1.2g, cholesterol 0.6mg is dissolved in the 60ml ether.Under the electromagnetic agitation slowly with diethyl ether solution with No. five syringe needles (needle point is under liquid level), inject matrine solution, the post-heating to 65 ℃ of stirring, ether is removed in volatilization, obtains matrine elaioplast.
The adding cryoprotective agent places the freezer dryer lyophilization in the liposome that makes, and forms the white powder material, faces with before adding water hydratable to get final product.
(2) mensuration of envelop rate
1. separation condition
Separation voltage: 20KV detects wavelength: 196～400 full wavelength scanners; Measure wavelength: 206nm input mode: pressure sample introduction; Sample size: 0.5Psi * 5s; Buffer: 0.25M/L sodium hydrogen phosphate, sodium dihydrogen phosphate, PH6.868; 25 ℃ of temperature.
2. the preparation of reference substance solution
Get the matrine reference substance that is dried to constant weight and be prepared into the solution of variable concentrations, cross the microporous filter membrane of 0.45 μ m, get final product with distilled water.
3. the preparation of need testing solution
The microporous filter membrane that the liposome of getting preparation is crossed 0.45 μ m carries out granulate, promptly.
4. the preparation of negative control product solution
Getting blank liposome prepares by last method
5. the preparation of standard curve
Get the matrine reference substance 0.6mg, 1.4mg, 2mg, 4mg, 8mg, the 12mg that are dried to constant weight, be prepared into the solution of 0.3mg/ml, 0.7mg/ml, 1mg/ml, 2mg/ml, 4mg/ml, 6mg/ml with distilled water, cross the microporous filter membrane of 0.45 μ m, sample introduction, high performance capillary electrophoresis (HPCE) is measured.The result is as follows, sees Table 1:
The peak area of table 1. matrine variable concentrations
Concentration with matrine is done one-variable linear regression to peak area, and regression equation and correlation coefficient are as follows: A=425787.2953C+151823.4011; R=0.99950.
The result shows that the linear relationship of concentration and peak area is good in 0.3～6.025mg/ml concentration range.
6. precision test
Get 4.005mg/ml matrine reference substance solution by above-mentioned deposition condition continuous sample introduction five times, peak area is respectively 1842036,1815226,1806812,1823052,1782494, RSD=1.21%.
(3) stability experiment
1. add heat damage:
Get matrine elaioplast, 100 ℃ of heating in water bath are observed layering, assemble the generation of phenomenons such as breakdown of emulsion.The sequencing of the appearance clustering phenomena of the liposome that is made by the whole bag of tricks is ammonium sulphate gradient, PH gradient method, Kirby method, film dispersion method, second emulsifying method, reverse phase evaporation successively, the time that clustering phenomena appears in the liposome of ammonium sulphate gradient preparation is 15min, and the time that clustering phenomena appears in reverse phase evaporation is 35min.
2. centrifuging:
Liposome is placed centrifuge tube, 1000r/min, the layering situation of test liposome, that layering situation as a result and the whole bag of tricks relate to is ultrasonic, mixing time is relevant, ultrasonic, the longer the better for mixing time, but ultrasonic, stirring heat production, so general ultrasonic 15min is irrelevant with dispersive method for well.
3. the mensuration of percolation ratio
Four factors, three levels of orthogonal design through the test of nine prescriptions, are index with the envelop rate, select the optimum preparating condition of ether injection method.See Table 2:
Table 2. factor level table
A is the pH value of PBS, and B is the weight ratio of lecithin and cholesterol, and C is the amount of matrine, and D is the amount of aqueous phase solvent
Table 3. orthogonal table and experimental result
| Serial number | A | B | C | D | Envelop rate (%) |
| 1 | 1 | 1 | 1 | 1 | 7.66 |
| 2 | 1 | 2 | 2 | 2 | 35.22 |
| 3 | 1 | 3 | 3 | 3 | 47.37 |
| 4 | 2 | 1 | 2 | 3 | 11.76 |
| 5 | 2 | 2 | 3 | 1 | 20.95 |
| 6 | 2 | 3 | 1 | 2 | 11.30 |
| 7 | 3 | 1 | 3 | 2 | 7.75 |
| 8 | 3 | 2 | 1 | 3 | 50.48 |
| 9 | 3 | 3 | 2 | 1 | 31.61 |
After the liposome that makes was measured envelop rate the same day, be put in refrigerator and cooled and hide and preserve, measure envelop rate after 10 days, be calculated as follows percolation ratio:
Envelop rate * 100% of percolation ratio=(envelop rate that the envelop rate that recorded the same day one is regularly measured)/recorded the same day.The liposome of measuring nine prescription preparations of reverse phase evaporation is placed ten days percolation ratio, and the result is as follows, sees Table 4:
The percolation ratio of the different samples of table 4.
Lecithin as can be seen: cholesterol=4: 1 o'clock, the percolation ratio of liposome is bigger.
(4) lyophilization experiment
Liposome is a thermodynamic unstable system, is again the kinetics Unstable Systems, and conventional liposome is generally placed phenomenons such as an i.e. appearance in month deposits, darkens.So, with the liposome lyophilization that makes.
The lyophilization condition: the liposome that makes is added trehalose, and pre-freeze places specimen disc again to freezing reality, opens the refrigeration machine refrigeration earlier and is reduced to constant temperature-58.3 ℃ until temperature, and the freezing 24h of constant temperature forms the white powder material again.
The liposome that lyophilization is made adds water hydratable, surveys envelop rate.Its envelop rate is lower than not cryodesiccated sample, is 48.57%.
Two, preparation matrine elaioplast drop ball:
Take by weighing Polyethylene Glycol (6000) 15g, place beaker, heating and melting in 90 ℃ of last water-baths adds matrine elaioplast 2g, stirs heat preservation for standby use.Preheating drop pill machine, making fluid reservoir constant temperature is 85 ± 1 ℃, coolant is selected dimethicone for use, be chilled to 10 ℃ in advance, regulate drip nozzle and the distance of cooling off liquid level, pour medicinal liquid into fluid reservoir, start valve, to drip speed is 35 droplets/minute systems, collecting a mouthful collection drop pill, absorb surface cool agent, room temperature vacuum drying with gauze, promptly get matrine elaioplast drop ball of the present invention, see Fig. 1-2.The matrine elaioplast drop ball section of the present invention's preparation obtains matrine elaioplast complete form in drop pill with Luo Danlan dyeing with E200 type Nikon ECLIPSE biology microscope sem observation, sees Fig. 3, Fig. 4.Here do repeated experiments with a kind of proportioning, obtain two same drop pill that product batch number is different.
Embodiment 2:
One, reverse evaporation prepares matrine elaioplast
Get soybean lecithin 1.2g, cholesterol 0.6g is dissolved in the 200ml ether, places conical flask.Prepare 1% matrine solution with the phosphate buffered solution of pH7.4, under the electromagnetic agitation, the matrine solution 120ml with 1% slowly splashes in the conical flask, stirs to make with ether to form emulsion, and distilling under reduced pressure 1h steams ether and removes, and obtains matrine elaioplast.
Two, preparation matrine elaioplast drop ball
Take by weighing Polyethylene Glycol (6000) 10g, Polyethylene Glycol (4000) 5g places beaker, goes up heating and melting in the water-baths in 90 ℃, adds matrine elaioplast 3g, stirs heat preservation for standby use.Preheating drop pill machine, making fluid reservoir constant temperature is 90 ± 1 ℃, and coolant is selected soybean oil for use, is chilled to 5 ℃ in advance, regulate drip nozzle and the distance of cooling off liquid level, pouring medicinal liquid into fluid reservoir, start valve, is 45 droplets/minute systems to drip speed, collecting a mouthful collection drop pill, absorb the surface cool agent with gauze, the room temperature vacuum drying promptly gets matrine elaioplast drop ball of the present invention.
Embodiment 3:
One, membrane process prepares matrine elaioplast
Soybean lecithin 1.2g, cholesterol 0.6g is dissolved in the 200ml ether, remove organic solvent with the Rotary Evaporators decompression, in pears type bottle, form uniform immobilized artificial membrane, add the phosphate buffered solution that 120ml contains the pH7.4 of matrine 1%, soak, stir the eluting lipid film, can get matrine elaioplast.
Two, preparation matrine elaioplast drop ball
Take by weighing glycerol 10g, poloxamer 6g places beaker, goes up heating and melting in the water-baths in 88 ℃, adds matrine elaioplast 3g, stirs heat preservation for standby use.Preheating drop pill machine, making fluid reservoir constant temperature is 88 ± 1 ℃, and coolant is selected liquid paraffin for use, is chilled to 5 ℃ in advance, regulate drip nozzle and the distance of cooling off liquid level, pouring medicinal liquid into fluid reservoir, start valve, is 60 droplets/minute systems to drip speed, collecting a mouthful collection drop pill, absorb the surface cool agent with gauze, the room temperature vacuum drying promptly gets matrine elaioplast drop ball of the present invention.
Embodiment 4:
One, reverse evaporation prepares matrine elaioplast:
Get soybean lecithin 0.6g, cholesterol 0.6g is dissolved in the 200ml ether, places conical flask.Prepare 1% matrine solution with the phosphate buffered solution of pH7.4, under the electromagnetic agitation, the matrine solution 120ml with 1% slowly splashes in the conical flask, stirs to make with ether to form emulsion, and distilling under reduced pressure 1h steams ether and removes, and obtains matrine elaioplast.
Two, preparation matrine elaioplast drop ball:
Take by weighing gelatin 2g, place beaker, heating and melting in 90 ℃ of last water-baths adds matrine elaioplast 2g, stirs heat preservation for standby use.Preheating drop pill machine, making fluid reservoir constant temperature is 80 ± 1 ℃, and coolant is selected methyl-silicone oil for use, is chilled to-10 ℃ in advance, regulate drip nozzle and the distance of cooling off liquid level, pouring medicinal liquid into fluid reservoir, start valve, is 20 droplets/minute systems to drip speed, collecting a mouthful collection drop pill, absorb the surface cool agent with gauze, the room temperature vacuum drying promptly gets matrine elaioplast drop ball of the present invention.
Embodiment 5:
One, fusion method prepares matrine elaioplast:
With lecithin 2.5g, cholesterol 0.5g is dissolved in chloroform/methanol (2: 1) the 10ml mixed liquor, and 70 ℃ of water-baths volatilize solvent, adds oleic acid 0.1g, and polyoxyethylene sorbitan monoleate, sorbitan monooleate mixed liquor 0.5g (HLB is 9.05) constantly stir, and melt; In addition with matrine 0.6g, polyvinylpyrrolidone (PVP) 0.5g is dissolved in pH 7.4 phosphate buffers of an amount of new preparation, and heating in water bath to 70 ℃ mixes both again, and constant temperature stirs 1h, and pH 7.4 phosphate buffers that add new preparation are to 100ml, ultrasonic 0.5h.Promptly make matrine elaioplast.
Two, preparation matrine elaioplast drop ball:
Take by weighing sodium stearate 20g, place beaker, heating and melting in 90 ℃ of last water-baths adds matrine elaioplast 2g, stirs heat preservation for standby use.Preheating drop pill machine, making fluid reservoir constant temperature is 90 ± 1 ℃, and coolant is selected dimethicone for use, is chilled to 20 ℃ in advance, regulate drip nozzle and the distance of cooling off liquid level, pouring medicinal liquid into fluid reservoir, start valve, is 60 droplets/minute systems to drip speed, collecting a mouthful collection drop pill, absorb the surface cool agent with gauze, the room temperature vacuum drying promptly gets matrine elaioplast drop ball of the present invention.
Claims (3)
1. matrine elaioplast drop ball is characterized in that it is mainly mixed to drip to make by matrine elaioplast and adjuvant raw material to make drop pill in the liquid coolant and form that the weight proportion of matrine elaioplast and adjuvant is 1: 1-10, adjuvant are water-soluble base; Described matrine elaioplast is mainly formed by matrine, soybean lecithin and cholesterol feedstock production, and the weight proportion of matrine and soybean lecithin and cholesterol is 1: 1-5, and wherein, the weight proportion of soybean lecithin and cholesterol is 1-5: 1;
Described water-soluble base is that molecular weight is that Polyethylene Glycol, gelatin, sodium stearate, glycerol, the molecular weight of 4000-6000 is any one or two or more the mixture arbitrarily in 188 the poloxamer, when two or more mixes arbitrarily, be any proportioning.
2. the preparation method of matrine elaioplast drop ball as claimed in claim 1 is characterized in that it comprises the steps:
1), preparation matrine elaioplast: matrine elaioplast is mainly formed by matrine, soybean lecithin and cholesterol feedstock production, the weight proportion of matrine and soybean lecithin and cholesterol is 1: 1-5, wherein, the weight proportion of soybean lecithin and cholesterol is 1-5: 1; Be equipped with matrine elaioplast with fusion method, reverse evaporation, ether injection method or thin-film ultrasonic legal system;
2), mixed melting: the weight proportion by matrine elaioplast and adjuvant is 1: 1-10 chooses matrine elaioplast and adjuvant, is heated to fusion more than 80 ℃, fully mixes stirring evenly, and gets fused mass, is incubated standby;
3), the system of dripping: preheating drop pill machine, the fluid reservoir that makes the drop pill machine is a constant temperature more than 80 ℃, the temperature of the water dropper of drop pill machine is 60-90 ℃; The temperature of the mouth of pipe of drop pill machine is 70-90 ℃; The thermograde of liquid coolant is 20--10 ℃; The scope of dripping distance is 4-16cm; The above-mentioned fused mass that obtains is put into fluid reservoir, with 20-60 drip/minute the speed of dripping splash in the liquid coolant of drop pill machine, make drop pill;
4), manufactured goods: collect drop pill, the filtering liquid coolant, drying obtains product.
3. the preparation method of a kind of matrine elaioplast drop ball according to claim 2, it is characterized in that: described liquid coolant is methyl-silicone oil, dimethicone, liquid paraffin.
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| CN112121003B (en) * | 2020-09-29 | 2022-02-01 | 江苏集萃新型药物制剂技术研究所有限公司 | Drug-carrying material of sustained-release preparation, composition of drug-carrying material, sustained-release preparation and preparation method of sustained-release preparation |
| CN115957351B (en) * | 2022-11-15 | 2023-06-27 | 中国人民解放军海军第九七一医院 | Iohexol injection and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1520815A (en) * | 2003-01-27 | 2004-08-18 | 永 张 | Flavescent sophora root drop pills for treating hepatitis B |
| CN1557305A (en) * | 2004-01-17 | 2004-12-29 | 张以成 | Matrine drop pills and its preparation method |
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2006
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1520815A (en) * | 2003-01-27 | 2004-08-18 | 永 张 | Flavescent sophora root drop pills for treating hepatitis B |
| CN1557305A (en) * | 2004-01-17 | 2004-12-29 | 张以成 | Matrine drop pills and its preparation method |
Non-Patent Citations (6)
| Title |
|---|
| 中药滴丸剂的研究进展. 张利民，倪健.中国中医药信息杂志，第10卷第10期. 2003 |
| 中药滴丸剂的研究进展. 张利民，倪健.中国中医药信息杂志，第10卷第10期. 2003 * |
| 滴丸剂的发展概况. 田晓丽.新疆医科大学学报，第25卷第1期. 2002 |
| 滴丸剂的发展概况. 田晓丽.新疆医科大学学报，第25卷第1期. 2002 * |
| 苦参碱脂质体的制备工艺研究. 魏铭，刘小平，李惠，唐自元，李航森.中国药物与临床，第6卷第5期. 2006 |
| 苦参碱脂质体的制备工艺研究. 魏铭，刘小平，李惠，唐自元，李航森.中国药物与临床，第6卷第5期. 2006 * |
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