CN1250216C - Medication for treating acute hepatitis and chronic hepatitis and preparation technique - Google Patents
Medication for treating acute hepatitis and chronic hepatitis and preparation technique Download PDFInfo
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- CN1250216C CN1250216C CN 03112181 CN03112181A CN1250216C CN 1250216 C CN1250216 C CN 1250216C CN 03112181 CN03112181 CN 03112181 CN 03112181 A CN03112181 A CN 03112181A CN 1250216 C CN1250216 C CN 1250216C
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- drop pill
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- silymarin
- polyethylene glycol
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- 238000000034 method Methods 0.000 title description 12
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Abstract
The present invention relates to a pure Chinese herb preparation for treating acute and chronic hepatitis and a preparation method thereof. The pure Chinese herb preparation of the present invention is a dripping pill which uses silymarin as an effective ingredient, and is preferably prepared from the following raw materials: 4 to 13g of silymarin, 27 to 36g of polyethylene glycol and right amount of tween 80. The preparation method comprises: melted silymarin is mixed with the polyethylene glycol, and the mixture is dripped into condensed fluid to prepare the dripping pill. The medicine of the present invention has the characteristics of high dissolution speed and high bioavailability, and the preparation technology of the present invention has the advantages of simple equipment, high yield and low cost.
Description
(1) technical field
The invention belongs to the technical field of the medicine of the acute and chronic hepatitis of treatment, particularly a kind of pure Chinese medicinal preparation and production method thereof for the treatment of acute and chronic hepatitis.
(2) background technology
Yiganling tablet is that the 8th in China's the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation records kind; be silymarin single preparation; because it has the liver function of improvement, the effect of protection liver plasma membrane is used for acute, chronic hepatitis and chronic persistent hepatitis as hepatic for many years always.Through investigation, this medicine sales volume is lower at present, is first constantly to come out for the new drug for the treatment of hepatitis, and old medicine is impacted, and more chief reason is because silymarin itself is the slightly water-soluble flavone compound, but has been made into Tabules.The preparation technology of this tablet be with this medicine with after several adjuvants mix through compression moulding, dosage form itself exists the problem of aspects such as the dissolution that influences medicine and bioavailability.Literature research the has been arranged dissolution of silybin tablet, its result is: the dissolution of the Liver-Restoring Tablet that the silybin tablet of domestic 6 manufacturer production and German MADAUS pharmaceutical factory produce: the stripping of 30min Yiganling tablet all is lower than 30%, and sharp liver is grand to be 50%; The maximum stripping silybin of 120min is no more than 43%, sharp liver grand about 55%.This result has shown that the Yiganling tablet stripping is slow, and dissolution rate is low, so bioavailability is poor.Simultaneously, pointed out and made tablet for the silymarin of slightly water-soluble and owe rationally, should carry out form improvement.
(3) summary of the invention
The present invention provides a kind of by the medicine that silymarin is an effective ingredient, dissolution rate is fast, stripping quantity is big, bioavailability is high in order to overcome the shortcoming of above medicine, and the preparation technology of this medicine.
The object of the present invention is achieved like this:
A kind of medicine for the treatment of acute and chronic hepatitis is the drop pill of being made as effective ingredient by silymarin.
The medicine of the acute and chronic hepatitis of treatment of the present invention, its best proportioning is to be made by the following weight proportion raw material
Silymarin 4-13g
Polyethylene Glycol 27-36g
Tween 80 is an amount of
The medicine of the acute and chronic hepatitis of treatment of the present invention, described Polyethylene Glycol are one or more in Macrogol 4000, polyethylene glycol 6000 or the cetomacrogol 1000 0.
The preparation technology of medicine of the present invention carries out successively according to the following steps
1. silymarin crushing screening is put in the appropriate vessel and the Polyethylene Glycol mix homogeneously, put be heated to the substrate fusing on the boiling water bath after, high-speed stirred is incubated 20～40 minutes, makes it to become the melt of mix homogeneously;
2. above melt is transferred in the fluid reservoir of drop pill device, sealing makes it be in suitable vacuum state, and 70～85 ℃ are incubated 30 minutes, stir with 10～20 rev/mins of speed simultaneously;
3. add dimethicone in the cooling column, the temperature of the hypomere of condensed fluid is about 10 ℃;
4. the water dropper internal diameter is 2-5mm, and dripping speed is 25～35 droplets/minute, and melt is splashed in the condensed fluid from top to bottom, collects drop pill, removes the condensed fluid on surface, and arrangement promptly.
Solid dispersion technology is the new technique of solid dispersion in solid.A kind of poorly water soluble drugs that is wherein is with molecule, colloidal state, crystallite or amorphous state, is dispersed in the another kind of water-solubility carrier material to be solid dispersion, and this is a kind of new technique efficient, quick-effective preparation for preparing.Its theoretical foundation is, the absorbance of medicine depends on dissolution rate, and according to the Noges-Whitneg equation, dissolution rate improves with the increase of dispersion.If medicine is formed molecular dispersoid, and carrier material is water miscible, then can improve the stripping and the absorption of medicine greatly, thereby improve its bioavailability, becomes efficient, quick-effective preparation.Drop pill means solid or liquid medicine and carrier material mixing, be heated to fusion, under vigorous stirring, make it abundant mixing after, splash in the not miscible condensed fluid, make it to shrink to solidify rapidly to form pill, this dosage form is to utilize fusion method to prepare the optimum dosage form of solid dispersion.Still select to change the silybin tablet into drops.
Prepare drop pill of the present invention, we select the water-soluble high-molecular compound PEG4000 that uses always, PE6000, and PEG10000 is as carrier.This carrier material molecular weight is big, molecule is made up of the parallel spiral chain of two row, and during resolidification, the damaged of character caused in the space of spiral after fusion, this damaged crystalline character that changes is as dissolubility, dissolution rate, absorbability and hygroscopicity etc.The molecular weight of silymarin main component is 482.43, and molecular weight is little, can insert to form the filled-type solid solution in the coiled strand when fusion, promptly disperses with molecularity.The dissolution rate height of this solid dispersion, good absorbing.The preparation method of solid dispersion, we select fusion method, about 100 ℃ of the fusion temperature of medicine and carrier, about 80 ℃ of holding temperature, about 10 ℃ of the temperature of condensed fluid, when melt splashes in the condensed fluid, because quenching, viscosity increases rapidly, has just blocked the crystallization that reassociates of dispersed silymarin molecule, become amorphous state or metastable state, its dissolubility and dissolution rate are all big than polymorphous other state.PEG4000,6000,10000 all has fusing point low (55-60 ℃) in addition, and toxicity is little, is not absorbed in gastrointestinal tract, not the advantages such as content analysis of interference medicament.In sum, select for use water miscible PEG4000,6000,10000 as carrier, adopt fusion method to prepare drop pill, because carrier has improved the wettability of silymarin, guaranteed that the medicine high dispersion reaches the crystallinity that presses down to medicine, all the stripping to medicine has produced facilitation, has reached raising silymarin bioavailability, improves the purpose of its curative effect.
1. the comparison of drop pill of the present invention and former dosage form-silybin tablet disintegration
Check that according to an appendix XIIA of Chinese Pharmacopoeia version in 2000 inspection technique disintegration this method is used to check the disintegrate situation of solid preparation under rated condition, all disintegrates in 1 hour of this law regulation sugar coated tablet; Drop pill should be all molten diffusing in 30 minutes.We utilize LB-881B type six pipe disintegration testers (Keda Instrument Plant, Wuxi), inspection method according to the pharmacopeia regulation is checked respectively the Yiganling tablet (coated tablet) and the drop pill of the present invention of domestic three manufacturer production, its result is: 0108014 batch of tablet that east wind pharmaceutical factory in Jinan produces, 6 whole disintegrates in 34 minutes; 000501 batch of tablet that Jinan Min Kang pharmaceutical factory produces, in 30 minutes, 6 whole disintegrates, 000629 batch of tablet that Huanyin Pharmaceutical Co., Ltd., Shanghai produces, 6 are sugarcoating layer and split along circumference in 1 hour, the part sugarcoating layer comes off, tablet does not all have disintegrate, drop pill of the present invention, and three batches (021024,021028,021029) is totally 18 equal all molten loosing in 8 minutes, above result shows that be more than 4 times of drop pill dissolve scattered time limit the disintegration of tablet.
2. the comparative study of drop pill of the present invention and former dosage form-silybin tablet dissolution in vitro
Dissolution is meant speed and the degree in the stripping from solid preparations such as tablet of regulation medium Chinese medicine.The stripping of insoluble drug is the limit procedure of its absorption.But the disintegration of tablet and intravital absorption also not all exist parallel relation, and the reliable method of understanding the body absorption is the bioavailability mensuration of these goods being carried out live body, but mensuration blood drug level, method such as urine excreion rate and metabolite thereof more complicated, difficulty is bigger, control the quality of product with this, cost is too high, can not be as the conventional method of quality examination.The external stripping of tablet that experimental results show that a lot of medicines be absorbed with dependency, so dissolution method has significance as the test method of absorbing state in reflection or the analogue body on the evaluation tablet quality.So in tablet except that regulation has disintegration, to containing the medicine of indissoluble in Digestive system; Interactional medicine takes place easily with other compositions; For a long time little, the strong drug action of the medicine, the dosage that reduce of storage back dissolubility, medicinal tablet that side effect is big need carry out dissolution determination with control or estimate its quality.
The silybin tablet is the tablet that poorly water soluble drugs is pressed into, and should carry out dissolution determination to it, to reflect the quality of this product.
According to two ones of Chinese Pharmacopoeia versions in 2000, appendix XC dissolution method first method (changeing the basket method) regulation instrument and method are measured, wherein solvent is the sour water 900ml of PH1-2,100 rev/mins of rotating speeds, 37 ± 0.3 ℃ of bath temperatures, tablet drops into 1, the suitable silibinin 38.5mg of drop pill input amount is respectively at 10,20,30,60,90,120,240 minutes, get solution 5ml, 0.8um membrane filtration, replenish synthermal solvent 5ml simultaneously,, calculate the content of silymarin with the absorption value of ultraviolet spectrophotometry in each sample liquid of above-mentioned each time point taking-up of wavelength 288nm place mensuration, and calculate every stripping quantity and dissolution, experimental result sees Table 1
Table 1 drop pill and Yiganling tablet dissolution experimental data
| Dissolution (%) | ||||||||
| 10(min) | 20(min) | 30(min) | 60(min) | 90(min) | 120(min) | 240(min) | ||
| Drop pill | 58.17 | 66.84 | 70.43 | 71.19 | 71.39 | 71.76 | 70.89 | |
| Yiganling tablet | Min Kang pharmaceutical factory, Jinan | Do not have and absorb | 0.99 | 4.02 | 10.22 | 20.56 | 25.91 | 28.39 |
| East wind pharmaceutical factory, Jinan | 1.03 | 1.12 | 1.74 | 9.49 | 16.32 | 20.23 | 28.03 | |
| Shanghai Chinese Yin Dynasty pharmaceutical factory | Do not have and absorb | Do not have and absorb | 2.45 | 20.74 | 36.40 | 39.77 | 43.44 | |
Above result shows, drop pill of the present invention is that the speed and the degree of stripping in the sour water solvent of 1-2 is far longer than the silybin tablet at PH.The dissolution rate of drop pill of the present invention is quite fast, and dissolution reaches 58.6% in the time of 10 minutes, and the tablet of three pharmaceutical factory productions does not almost have stripping; In the time of 20 minutes, the dissolution of drop pill reaches 68-71%, and the stripping of the tablet of three producers seldom or does not almost have stripping; The dissolution of drop pill reaches nearly 70.0% in the time of 30 minutes, is respectively 17 times of tablet that Min Kang pharmaceutical factory, Jinan produces, 40 times of the tablet that east wind pharmaceutical factory, Jinan produces, 28 times of the tablet that Shanghai Chinese Yin Dynasty pharmaceutical factory produces; In the time of 60 minutes, the dissolution of drop pill is followed successively by 7,7.5,3.43 times of three manufacturer production tablets; In the time of 120 minutes, be followed successively by 2.76,3.53,1.8 times.In sum, the external dissolution rate of drop pill of the present invention is faster than tablet, and stripping quantity is more than tablet, and this helps the absorption of body, thereby improves bioavailability of medicament, guarantees the curative effect of medicine.
3. pharmacological toxicology research
The Herba Silybi mariani drop pill has the effect that improves liver function, protection liver plasma membrane, is used for acute and chronic hepatitis and chronic persistent hepatitis.For verifying its curative effect and clinical application safety, it is as follows that we have carried out acute toxicity test in mice, rat long term toxicity test and main pharmacodynamics experiment:
3.1 studies on acute toxicity:
Because of drop pill of the present invention is a pure Chinese medicinal preparation, can't measure LD50 through prerun, so measure maximum dosage-feeding.Give mouse stomach Silybum drip balls 11.44g/kg (being equivalent to moisture flying silibin 1.88g/kg day) in one day, be equivalent to more than 480 times of clinical Coming-of-Age Day consumption; At viewing duration, animal diet followed, activity are all normal, and hair color is bright and clean, and large and small just no abnormality seen was observed seven days continuously, and the weight of animals increases, none death, and the filling stomach maximum tolerated dose that shows the drop pill mice is at 11.44g/kg more than day.
3.2 long term toxicity research:
Select 160 of Wistar rats for use, in age in 5-6 week, about body weight 65g, male and female half and half are divided into 4 groups at random: blank group, the high, medium and low dosage group of drop pill, 40 every group.Blank group is irritated the stomach tap water, and the administration group is heavily irritated stomach by 1.4g/kg, 0.7g/kg, 0.35g/kg Mus respectively, irritates gastric capacity 1ml/100g body weight.Be equivalent to 60 times, 30 times, 15 times of the clinical consumption per day of 60kg people, successive administration 6 months, observe the general situation of animal, body weight change, appetite, the water yield, duration of test is respectively at the 7th week of administration, 20 weekends, from matched group and high dose group, get 15 rats at random and get blood, detect blood routine, blood biochemical indexes through jugular vein; Each is lived at random and kills 15 of animals in every group of the 13rd week of administration, 26 weekends, gets blood examination and surveys the histological examination of routine blood test, blood biochemistry and main organs and calculate organ coefficient.The result shows: there is no obvious change with blank comparison routine blood test, the every index of blood biochemistry for continuously 6 months each administration groups of drop pill, each main organs there is no obvious pathological changes.Each organizes remaining 10 animals, and drug withdrawal also continues to observe after 2 months, and the above index of duplicate detection is not found the reaction of toxic and side effects and delayed toxicity yet, illustrates that the clinical medicine dose and the course of treatment that this medicine is intended adopting are safe.
3.3 main pharmacodynamics experiment:
3.3.1 drop pill of the present invention is to the protective effect of mice D-galactosamine hydrochlorate acute liver damage:
Get about 96 body weight 30g of healthy male mice in kunming, be divided into 8 groups at random, normal control group, model control group, the high, medium and low dosage group of drop pill, the high, medium and low dosage group of tablet, every group 12, by table 1 dosage (capacity is the 0.2ml/10g body weight) gastric infusion 5 days.In the 4th day lumbar injection D-galactosamine hydrochlorate 650mg/kg, pluck eyeball after 20 hours and get blood survey serum glutamic pyruvic transminase and total bilirubin, get liver and do histological examination.The results are shown in Table 2.
Table 2: to the influence of acute liver damage mice serum ALT, Tibl: (n=2, x ± s)
| Group | Dosage mg/kg | ALT | TIBL |
| Normal group model group dripping pill dripping pill dripping pill Yiganling tablet Yiganling tablet Yiganling tablet | N.S N.S 92.4 46.2 23.1 92.4 46.2 23.1 | 49.4±23.2*** 267.8±212 72.9±25.8** 88.9±34.7* 108.9±57.3* 77.1±61.4* 88.2±57.0* 149.1±98.7 | 10.6±8.0 9.6±2.4 9.11±5.3 10.1±5.9 12.4±8.1 10.1±5.7 8.0±3.1 8.1±3.1 |
With model group than * p＜0.05; * p＜0.01; * * p＜0.001;
Find out that by table 2 ALT of model group mice serum shows the modeling success apparently higher than normal group.ALT in three dosage groups of drop pill and sheet height, the middle dosage group mice serum is starkly lower than model group, and this effect of drop pill has the trend that is better than sheet.
3.3.2 drop pill of the present invention is to CCl
4The protective effect of rat chronic hepatic injury:
Get 96 of rats, male, about body weight 28g, be divided into 8 groups at random, normal control group, model control group, the high, medium and low dosage group of drop pill, the high, medium and low dosage group of sheet, 12 every group, all the other each groups are with 20%CCL except that matched group
4Olive oil solution 0.2ml/100g lumbar injection, 2 totally 7 weeks weekly, and give relative medicine simultaneously, with the experiment end, Animal Anesthesia is got hydroxyproline (HYP) content of hematometry serum glutamic pyruvic transminase (ALT), glutamic oxaloacetic transaminase, GOT (AST), total protein (TP), albumin (ALB) content and liver, and does histological examination.The results are shown in Table 3,4:
Table 3: to the influence of CCL4 chronic hepatic injury rat blood serum ALT, AST, TP, ALB
| Group | Dosage (mg/kg) | ALT(IU/L) | AST(IU/L) | TP(g/L) | ALB(g/L) |
| Normal group model group dripping pill dripping pill dripping pill Yiganling tablet Yiganling tablet Yiganling tablet | N.S N.S 69.3 34.6 17.3 69.3 34.6 17.3 | 32.5±5.5*** 1169.5±659.1 57.1±34.2 ***Δ 217.8±109.7 ***ΔΔ 544.1±283.7 **ΔΔ 139.7±117.8 *** 389.7±150.7 ** 1054.4±489.9 | 92.4±19.5 *** 743.6±462.3 128.5±27.8 ***Δ 236.6±88.4 **Δ 376.3±159.6 *ΔΔ 163.1±57.8*** 335.9±117.6** 695.0±295.3 | 47.1±6.8 44.6±4.0 56.0±6.9*** 53.6±10.1** 49.7±3.9** 58.4±6.9 *** 60.3±7.2 *** 55.8±7.9*** | 26.2±3.5 26.4±2.1 30.7±4.2 *** 29.9±5.1* 28.0±1.7* 30.8±2.5 *** 31.9±3.3 *** 30.2±3.7** |
With model group than * p＜0.05; * p＜0.01; * * p＜0.001;
With with the positive drug Yiganling tablet of dosage than Δ P＜0.05; Δ Δ P＜0.01; Δ Δ Δ P＜0.001
Find out by table 3, all can significantly reduce ALT in the rat blood serum, AST content with model group than the height of high, medium and low dosage group of drop pill and tablet, middle dosage group, the content of TP, ALB in the serum that significantly raises; And the effect of drop pill reduction ALT, AST obviously is better than the tablet with dosage.
Table 4: to the influence of liver coefficient and the HYP content of chronic hepatic injury rat (n=10, x ± s)
| Group | Dosage (mg/kg) | Liver coefficient (g/100g) | Hyp(μg/10mg) |
| Normal group model group dripping pill dripping pill dripping pill Yiganling tablet Yiganling tablet Yiganling tablet | N.S N.S 69.3 34.6 17.3 69.3 34.6 17.3 | 3.401±0.438*** 5.052±0.492 4.079±0.300*** 4.471±0.557* 4.614±0.528* 4.081±0.350*** 4.507±0.712* 4.519±0.498* | 0.01095±0.0036** 0.01589±0.0035 0.0133±0.0014* 0.01315±0.0022* 0.01591±0.0039 0.0139±0.0003 0.01599±0.003 0.01585±0.0021 |
With model group than * p＜0.05; * p＜0.01; * * p＜0.001
Find out by table 4, all can obviously reduce the content of the hydroxyproline in liver coefficient and the hepatic tissue than drop pill and sheet with model group.
4. brief summary and evaluation
The dissolve scattered time limit of drop pill of the present invention be significantly smaller than tablet disintegration.And the speed of the external stripping of drop pill of the present invention is more faster than tablet, and stripping quantity is bigger than tablet, and this helps the absorption of body, thereby has improved bioavailability of medicament, has guaranteed curative effect.
Simultaneously, the pharmacology poison by drop pill of the present invention studies show that: the maximum tolerated dose of mouse stomach is at 11.44g/kg more than day.6 months long term toxicity of rat is studied and 2 months convalescent period observation there is no obvious toxic-side effects, shows that it is safe using its usual amounts clinically; Pharmacodynamics shows drop pill of the present invention, and hepatic injury has significant protective effect to D-galactosamine hydrochlorate induced mice, to CCl
4Cause the rat chronic hepatic injury and have obvious protective effect, and be better than the silybin tablet.
Therefore, medicine of the present invention has the advantages that dissolution rate is fast, bioavailability is high.Simultaneously, preparation technology of the present invention, it is simple to have equipment, yield rate height, the advantage that cost is low.
(4) specific embodiment
1. embodiment
Water intaking flies silibin 10.5g, pulverizes and is fine powder, puts in the container and poly-7 ethylene glycol, 4000 mix homogeneously of 31.5g, put be heated to the substrate fusing on the boiling water bath after, high-speed stirred is incubated 20 minutes, makes it to become the uniform pale brown color melt of color and luster; Above melt is transferred in the fluid reservoir of drop pill machine, sealing makes it be in suitable vacuum state, and 70 ℃ of insulations 30 minutes are stirred with 15 rev/mins speed simultaneously; Add dimethicone in the cooling column, the temperature of condensed fluid is downward successively 1/3 place from the top, and 1/2 place's gradient cooling is respectively 40 ℃, and 28 ℃, 10 ℃; The water dropper internal diameter is 3mm, and outer warp is 4mm.Dripping speed is 25 droplets/minute, and melt is splashed in the condensed fluid from top to bottom, collects drop pill, removes the condensed fluid on surface, puts in order promptly, and making drop pill is 1000.
Usage and consumption: oral, three times on the one, one time 9.
2. embodiment
Water intaking flies silibin 6g, pulverizes and is fine powder, puts in the container and 36g cetomacrogol 1000 0 and an amount of tween 80 mix homogeneously, put be heated to the substrate fusing on the boiling water bath after, high-speed stirred is incubated 40 minutes, makes it to become the uniform pale brown color melt of color and luster; Above melt is transferred in the fluid reservoir of drop pill machine, sealing makes it be in suitable vacuum state, and 80 ℃ of insulations 30 minutes are stirred with 10 rev/mins speed simultaneously; Add dimethicone in the cooling column, the temperature of condensed fluid is downward successively 1/3 place from the top, and 1/2 place's gradient cooling is respectively 50 ℃, and 30 ℃, 10 ℃; The water dropper internal diameter is 3mm, and outer warp is 4mm.Dripping speed is 25 droplets/minute, and melt is splashed in the condensed fluid from top to bottom, collects drop pill, removes the condensed fluid on surface, puts in order promptly, and making drop pill is 1000.
Usage and consumption: oral, three times on the one, one time 12.
3. embodiment
Water intaking flies silibin 8g, pulverizes and is fine powder, puts in the container and 34g polyethylene glycol 6000 mix homogeneously, put be heated to the substrate fusing on the boiling water bath after, high-speed stirred is incubated 30 minutes, makes it to become the uniform pale brown color melt of color and luster; Above melt is transferred in the fluid reservoir of drop pill machine, sealing makes it be in suitable vacuum state, and 70 ℃ of insulations 30 minutes are stirred with 15 rev/mins speed simultaneously; Add dimethicone in the cooling column, the temperature of condensed fluid is downward successively 1/3 place from the top, and 1/2 place's gradient cooling is respectively 40 ℃, and 28 ℃, 10 ℃; The water dropper internal diameter is 3mm, and outer warp is 4mm.Dripping speed is 30 droplets/minute, and melt is splashed in the condensed fluid from top to bottom, collects drop pill, removes the condensed fluid on surface, puts in order promptly, and making drop pill is 1000.
Usage and consumption: oral, three times on the one, one time 12.
Claims (3)
- One kind the treatment acute and chronic hepatitis medicine, it is characterized in that: it is the drop pill of being made as effective ingredient by silymarin, is to be made by the following weight proportion raw materialSilymarin 4-13gPolyethylene Glycol 27-36gTween 80 is an amount of.
- 2. the medicine of the acute and chronic hepatitis of treatment according to claim 1 is characterized in that: described Polyethylene Glycol is one or more in Macrogol 4000, polyethylene glycol 6000 or the cetomacrogol 1000 0.
- 3. the preparation technology of the medicine of the acute and chronic hepatitis of treatment according to claim 1 is characterized in that: carry out according to the following steps successively1. silymarin crushing screening is put in the appropriate vessel and the Polyethylene Glycol mix homogeneously, be heated to 100 ℃ make the substrate fusing after, high-speed stirred is incubated 20～40 minutes, makes it to become the melt of mix homogeneously;2. above melt is transferred in the fluid reservoir of drop pill device, sealing makes it be in suitable vacuum state, and 70～85 ℃ are incubated 30 minutes, stir with 10～20 rev/mins of speed simultaneously;3. add dimethicone in the cooling column, the temperature of the hypomere of condensed fluid is 10 ℃;4. the water dropper internal diameter is 2-5mm, and dripping speed is 25～35 droplets/minute, and melt is splashed in the condensed fluid from top to bottom, collects drop pill, removes the condensed fluid on surface, and arrangement promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03112181 CN1250216C (en) | 2003-04-21 | 2003-04-21 | Medication for treating acute hepatitis and chronic hepatitis and preparation technique |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03112181 CN1250216C (en) | 2003-04-21 | 2003-04-21 | Medication for treating acute hepatitis and chronic hepatitis and preparation technique |
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| CN1250216C true CN1250216C (en) | 2006-04-12 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1301665C (en) * | 2005-05-18 | 2007-02-28 | 成刚 | Blood fat-regulating liver-protecting health food |
| CN1872050B (en) * | 2005-06-01 | 2010-12-01 | 天津天士力制药股份有限公司 | Drop pills of silymarin, and preparation method |
| CN100409838C (en) * | 2006-09-04 | 2008-08-13 | 南昌弘益科技有限公司 | Method for producing medicine Yigan dipping-pills for tonifying liver |
| CN104127407B (en) * | 2014-08-15 | 2015-06-24 | 朗天药业(湖北)有限公司 | Silymarin compound and pharmaceutical composition containing extract thereof |
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