A kind of Silybum drip balls and preparation method thereof
Technical field
The present invention relates to field of medicaments, particularly, relating to Chinese medicine is that raw material is made a kind of medicine for the treatment of chronic persistent hepatitis.
Background technology
Silymarin (Silymarn) be by feverfew Silybum Herba Silybi mariani [Silybum marianum (L) Gaertn] fruit through extracting refining gained bulky powder, mildly bitter flavor has and draws moistly, water insoluble, significant protection is arranged and stablize the liver plasma membrane effect; The all kinds hepatic injury that hepatotoxic agents such as carbon tetrachloride, sulfuration acetamide, muscarine, pig urine bean alkali are caused has protection and therapeutical effect in various degree, and the rising of the caused alanine aminotransferase of carbon tetrachloride is had certain interception.Clinical chronic persistent hepatitis, the chronic active hepatitis of being used for, the treatment that first cirrhosis, liver poisoning etc. are sick is for the effect that all has clear improvement of symptom, sign, the liver function of acute and chronic hepatitis.
The Liver-Restoring Tablet that has silymarin tablet, silybin tablet and German MADAUS pharmaceutical factory to produce of selling in the market, because silymarin is water insoluble, hydrophobicity is strong, make the dissolution and the dissolution rate of silymarin tablet, Yiganling tablet, Liver-Restoring Tablet low, absorption difference, bioavailability is low, the supplementary product consumption ratio is big, child, old people, bed patient and dysphagia patients are taken inconvenience, and compliance is poor, have influenced the performance of silymarin therapeutical effect.Application number: 03159118.3, the applying date: 2003.9.8, applicant: Nanchang Hongyi Science Co., Ltd, denomination of invention: Silybum drip balls and preparation method thereof; Application number: 03112181.0, the applying date: 2003.04.21, application (patent right) people: Medicine Institute, Shandong Province, denomination of invention: a kind of medicine and preparation technology thereof who treats acute and chronic hepatitis, more than two pieces of patent documentations a kind of chronic persistent hepatitis, chronic active hepatitis are provided, the drop pill medicine of diseases such as first cirrhosis, liver poisoning also provides preparation method, and this drop pill drug use Polyethylene Glycol and other adjuvants are made drop pill with silymarin; Though this drop pill overcomes the defective of present tablet, has accelerated dissolution rate, there is the not high defective of natural degree of the adjuvant that uses in this drop pill.
Expansion and human back to nature requirement along with the market global range, use the low medicine of toxic and side effects, especially pure natural medical more and more becomes people's first-selection, dropping pill formulation be a kind of have efficient, quick-acting new medicine preparations, it has overcome the shortcoming and deficiency of Chinese medicine preparation in the past, but present dropping pill formulation generally faces following problem: 1, drop pill adjuvant pure natural degree is not high: at present, drop pill substrate adjuvant mostly is synthetic, natural degree is lower, the searching of new alternative substrate adjuvant, the searching of the alternative substrate adjuvant that particularly natural degree is high and preparation technology thereof determine, it is again very difficult thing, because the required preparation condition of at present common possible natural substrates adjuvant succedaneum is very harsh, it all is to influence the key that drop pill prepares molding that adjuvant temperature and drop pill thereof drip the system condition.The too high then viscosity of adjuvant melt temperature is low, and poor plasticity is though the adjuvant melt temperature is crossed lowplastcity by force, but drop pill has shortcomings such as easily sticking ball, distortion, therefore, seek pure natural degree height, and the adjuvant that is suitable for substituting existing drop pill substrate is a very job of hardships.2, the drop pill outlet encounters problems: along with expanding economy, more and more internationalize in market, China is also just making great efforts to adapt to this trend, present Chinese medicine dripping pills preparation as health food, successful export to many countries, but also face many problems at present, because different countries is different to the approval of the selected adjuvant of Chinese medicine dropping pill formulation, especially industrial flourishing Europe, more strict to food adjuvant and medical auxiliary materials, and as the selected chemosynthesis adjuvant (as Polyethylene Glycol) of the dropping pill formulation of health food outlet not in the catalogue of some national food additive, it is very unfavorable that this moves towards the international market to the Chinese medicine dropping pill formulation, becomes the stumbling-block that Chinese medicine enters the international market, therefore, seek the new of one or more, can be particularly important, also very urgent for the substrate adjuvant that the international market is accepted.3, the shortcoming of mouthfeel and onset speed: the mouthfeel of Chinese medicine and preparation thereof is relatively poor to be the big characteristics of one, people when taking some drugs to the frightened of disagreeable taste that medicine had even be better than fear far away to disease, What is more, some patients are because can not overcome the poor taste of Chinese medicine or its preparation or abnormal smells from the patient and abandon the treatment of Chinese medicine, though can improve mouthfeel as medicine being made capsule or sugar coated tablet, reducing stimulates, but disintegration rate prolongs, be unfavorable for the rapid onset of medicine, to some disease, particularly need the disease of the rapid onset of medicine inapplicable.4, the preparation process difficulty of drop pill suitability for industrialized production: in the replacement process of dropping pill formulation adjuvant, determining of the preparation process of its suitability for industrialized production is very difficult something, as the ratio of the melt temperature of substrate adjuvant, the proportioning of dripping system temperature, adjuvant and medicine, dropper bore, condensing agent etc. all are the factors that influence drop pill, therefore, the replacement of substrate and to be suitable for suitability for industrialized production be a job consuming time, as to expend substantial contribution.
In order to change drop pill substrate adjuvant for a long time based on the situation of chemosynthesis adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and can not satisfy more and more that people require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect; Also can solve some problems that Chinese medicine preparation, particularly dropping pill formulation are run in exit procedure, strengthen the competitiveness of international market; The present invention has invented the pure Chinese medicine dripping pills preparation that a kind of toxic and side effects is low, evident in efficacy, moderate, adapt to industrialized great production by a large amount of tests and the research of preparation process.
Summary of the invention
The medicine that the purpose of this invention is to provide a kind of treatment chronic persistent hepatitis with new type natural substrate adjuvant preparation.
Another object of the present invention provides a kind of preparation method for the treatment of the chronic persistent hepatitis medicine.
The selected substrate adjuvant of the present invention is resulting by a large amount of tests, it is little to have molecular weight, soluble in water, and molten diffusing speed is faster, pure natural degree height, toxic and side effects is low, and can reduce the medicine irritation abnormal smells from the patient, has the oral cavity of improvement acid-base value during the buccal of oral cavity, improve the characteristics of oral cavity smell, the used substrate adjuvant of the present invention is the agent of food sedan-chair flavor, takes that mouthfeel is good, the acceptant characteristics of patient, is the direction of following substrate adjuvant development.
The consumption of drug component of the present invention and the selection of adjuvant thereof also grope to sum up to draw through the inventor in a large number, this medicine is formed and is comprised: silymarin, appropriate amount of auxiliary materials, wherein adjuvant comprises filler and plasticity substrate, filler adjuvant wherein is selected from the natural adjuvant of following one or more plant origins: sorbitol, xylitol, lactose, maltose, and they contain the water of crystallization chemical compound; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: pregelatinized Starch, carboxymethyl starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, arabic gum, alginic acid, dextrin, cyclodextrin, agar, lactose;
The adjuvant of preferred drug component of the present invention is following one or more the natural adjuvant of plant origin for the filler adjuvant is selected from: xylitol, lactose; Plasticity substrate wherein is selected from following one or more the natural adjuvant of plant origin: starch, arabic gum;
Best substrate adjuvant of the present invention is xylitol and starch, and xylitol is 1: 0.2~1: 0.3 with the ratio of the weight of starch; Or be lactose and starch, lactose is 1: 0.2~1: 0.3 with the ratio of the weight of starch; Or be xylitol and arabic gum, the ratio of the weight of xylitol and arabic gum is 1: 0.2~1: 0.4.
Adjuvant is 1: 0.1~1: 1 with the ratio of the weight of silymarin in the pharmaceutical composition of the present invention;
Adjuvant is 1: 0.1~1: 0.6 with the ratio of the weight of silymarin in the preferred pharmaceutical composition of the present invention;
Adjuvant is 1: 0.2~1: 0.4 with the ratio of the weight of silymarin in the best pharmaceutical composition of the present invention.
Herba Silybi mariani prime system among the present invention by the fruit of feverfew Silybum Herba Silybi mariani through extracting the bulky powder of refining gained, English Silymam by name.
Medicine mesostroma adjuvant of the present invention and amount of drug are than being the scope that allows on the galenic pharmacy, and medicine described here can be that crude drug also can be the effective ingredient extract.
Medicine of the present invention can adopt the preparation of Chinese medicine preparation conventional method; make common any preparation at present; but, preferably adopt following method to be prepared into dropping pill formulation, but this can not limit protection scope of the present invention in order to make each crude drug of this medicine bring into play drug effect better.
The preparation method of medicine of the present invention is as follows:
(a) water intaking flies silibin, adjuvant is standby;
(b) in appropriate amount of auxiliary materials, add silymarin, fully mix, mixture is at 45~115 ℃ of heating and meltings, stir, mixing time is 1~120 minute, insulation, at 45~95 ℃ of temperature following system, dropper bore is 1.0~4.0 millimeters, splash in-20~25 ℃ liquid paraffin, methyl-silicone oil or the vegetable oil, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Further preferred manufacturing procedure is:
The mixture heated melt temperature is 60~85 ℃ in the step (b), and mixing time is 10~30 minutes, and dripping a system temperature and be 60~85 ℃, dropper bore is 1.1~3.5 millimeters, and condensing agent is 0~18 ℃ liquid paraffin or a methyl-silicone oil.
Best preparation method is:
The mixture heated melt temperature is 64 ℃ in the step (b), and dripping a system temperature and be 64 ℃, dropper bore is 1.2~2.5 millimeters, and condensing agent is 0 ℃ a methyl-silicone oil.
More than form when producing and to increase or to reduce according to corresponding ratio, as large-scale production can be unit with kilogram or with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the crude drug material weight proportion constant rate between each composition.
Medicine of the present invention can be determined usage and dosage according to patient's situation in use, but every day 1-3 time, and every day, each crude drug consumption was as the criterion with the state-promulgated pharmacopoeia dosage, was no more than the pharmacopeia ormal weight.
The drop pill that the present invention is prepared, conventional drop pill advantage is simple as preparing except having, steady quality, can make liquid medicine solidification, convenient drug administration, efficient, quick-acting, its biggest advantage is:
1, the selected adjuvant pure natural of the present invention degree height: the substrate adjuvant that employed substrate adjuvant derives from natural plants or originates based on natural plants among the present invention, for example: selected substrate adjuvant is xylitol and starch or lactose and starch or xylitol and arabic gum, this substrate adjuvant has pure natural degree height, toxic and side effects is low, mouthfeel is good, dissolve scattered time limit is short, rapid-action, it is a kind of new medium adjuvant, can be used for substituting present chemosynthesis substrate adjuvant, the drop pill made from this kind adjuvant, it is low to solve the pure natural degree that present drop pill substrate faced, and more and more can not satisfy people and require back to nature, take low toxicity, the problem of the pure natural medical that has no side effect.
2, some problems in the outlet of solution Chinese medicine: medicine of the present invention also can solve Chinese medicine preparation, some problems of in exit procedure, being run into of dropping pill formulation particularly, solve because different countries, especially the European countries of industry prosperity are to the difference identification of the selected adjuvant of Chinese medicine dropping pill formulation, overcome as the selected adjuvant Polyethylene Glycol of the dropping pill formulation of the health food outlet defective in some national food additive catalogue not, improve the Chinese medicine dripping pills preparation and move towards the international market, strengthen the competitiveness of international market.
3, solve the relatively poor problem of drop pill taste and further improve drug effect speed (dissolve scattered time limit): the medicinal dropping ball made from this kind substrate adjuvant of the present invention, can improve Chinese medicine preparation, the particularly present not good shortcoming of dropping pill formulation taste, improve mouthfeel, more easy for patients to accept, and the drop pill that adopts the selected adjuvant of medicine of the present invention to make has shorter dissolve scattered time limit, making drug effect faster, is the medicine that chronic persistent hepatitis is treated in a kind of onset faster.
4, higher safety and solve some problems in the drop pill storage process: the selected substrate of the present invention is not only additive, nutrient commonly used in the food industry, and can do medicinal, but do not see that it uses as the drug matrices adjuvant, therefore, with regard to substrate, be perfectly safe, have no side effect, a large amount of evidences, the drop pill that this adjuvant is made can reduce effective ingredient separating out in storage process, the sticking ball of drop pill, easy shortcomings such as moisture absorption deliquescing, but the big production of suitability for industrialized.
The present invention is under instruction of Chinese Medicine theory, tests resulting preparation through a large amount of preparation technologies.The present invention is used for the treatment of chronic persistent hepatitis clinically, overcome that western medicine chronic persistent hepatitis toxic and side effects is big, expense is high, the Chinese medicine curative effect is low, flavour of a drug are many, the shortcoming of incompatibility large-scale production, is the medicine of the treatment chronic persistent hepatitis determined of a kind of economy, material benefit, curative effect.
To those skilled in the art, technology contents disclosed according to the present invention, those skilled in the art will very clear other embodiment of the present invention, and the embodiment of the invention is only as example.Under the situation of not violating purport of the present invention and scope, can carry out various changes and improvements to the present invention.For example, use different crude drug or extract or active constituents of medicine or effective ingredient and adjuvant provided by the present invention to make various different preparations, particularly drop pill, but as long as use adjuvant of the present invention, all within protection domain of the present invention.
In order to understand the present invention better, the Silybum drip balls made from the new substrate of the present invention (according to embodiment 1 preparation, hereinafter to be referred as new Silybum drip balls) below; Test explanation advantages of the present invention such as the dissolve scattered time limit of the drop pill of making for the substrate adjuvant with the Polyethylene Glycol (according to application number be: 03159118.3 specific embodiment 2 prepares, hereinafter to be referred as old Silybum drip balls), drop pill soft durometer, the sticking ball of drop pill.
Test example 1: dissolve scattered time limit, weight differential contrast experiment's example
In vitro tests
New Silybum drip balls and old Silybum drip balls compare, and by measuring dissolve scattered time limit, investigate its good releasing effect; By measuring indexs such as the ball method of double differences is different, whether ripe, whether be fit to suitability for industrialized production if investigating its preparation technology.
1. test medication: new Silybum drip balls, old Silybum drip balls.
2. method and result:
Dissolve scattered time limit: by " method is measured under this item of Chinese pharmacopoeia; The ball method of double differences is different: by " method is measured under this item of Chinese pharmacopoeia.Result of the test sees Table 1.
Three batches in table 1 with new Silybum drip balls and old Silybum drip balls dissolve scattered time limit, weight differential relatively
| 0 month | January | February | March | June | December | 18 months |
1 batch | Criterion | The result |
Weight differential (± 15%) | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% |
Dissolve scattered time limit (newly) (old) | 4′31″ 5′05″ | 4′31″ 5′05″ | 4′33″ 5′10″ | 4′33″ 5′11″ | 4′35″ 5′11″ | 4′35″ 5′11″ | 4′37″ 5′12″ |
2 batches | Weight differential (± 15%) | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% |
Dissolve scattered time limit (newly) (old) | 4′30″ 4′05″ | 4′32″ 5′04″ | 4′34″ 5′08″ | 4′34″ 5′11″ | 4′37″ 5′12″ | 4′39″ 5′14″ | 4′38″ 5′14″ |
3 batches | Weight differential (± 15%) | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% | All in 10% |
| Dissolve scattered time limit (newly) (old) | 4′32″ 5′00″ | 4′32″ 5′02″ | 4′33″ 5′05″ | 4′34″ 5′09″ | 4′35″ 5′14″ | 4′32″ 5′14″ | 4′37″ 5′14″ |
Above-mentioned experimental data shows, different being controlled in the pharmacopeia prescribed limit of the older Silybum drip balls of the dissolve scattered time limit ball method of double differences few, new, old Silybum drip balls of new Silybum drip balls.The result of the test explanation, the new Silybum drip balls that the new medium adjuvant is made is more conducive to medicine and plays a role in the shortest time, different all being controlled in the pharmacopeia prescribed limit of the ball method of double differences new, old Silybum drip balls, but suitability for industrialized production.
Test example 2: the comparative observation of new Silybum drip balls and old Silybum drip balls soft durometer, the sticking ball of drop pill
Compare by new Silybum drip balls and old Silybum drip balls, measure indexs such as above-mentioned, investigate its effect.
1. test medication: new Silybum drip balls; Old Silybum drip balls.
2. method and result:
Get each three batches of new Silybum drip balls and old Silybum drip balls, be loaded in the porcelain vase respectively, and use the bottle stopper good seal.Putting it into the bottom has in the exsiccator of saturated Nacl (humidity 75%) solution, exsiccator is put into 40 ℃ of drying baker of constant temperature again, and timing sampling is observed situations such as drop pill soft durometer, the sticking ball of drop pill, the results are shown in Table 2.1, table 2.2.
Three batches of old Silybum drip balls reserved sample observings of table 2.1 relatively
| 0 month | January | February | March | June | December | 18 months |
1 batch | Criterion | The result |
Sticking ball | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Sticking slightly | Sticking slightly |
Soft durometer | Firmly | Firmly | Firmly | Firmly | Firmly | Firmly | Harder |
2 batches | Sticking ball | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Sticking slightly |
Soft durometer | Firmly | Firmly | Firmly | Firmly | Firmly | Firmly | Harder |
3 batches | Sticking ball | Not sticking | Not sticking | Not sticking | Not sticking | Not sticking | Sticking slightly | Sticking slightly |
Soft durometer | Firmly | Firmly | Firmly | Firmly | Firmly | Harder | Harder |
Table 2.2: three batches of new Silybum drip balls and old Silybum drip balls character observation are relatively
| 0 month | January | February | March | June | December | 18 months |
| Criterion | The result |
1 batch | Sticking ball | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) slightly | Sticking (old) glues (newly) slightly slightly | Sticking (old) be sticking (newly) slightly |
Soft durometer | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | Hard (old) hard (newly) | Hard slightly (old) be hard (newly) slightly | Hard slightly (old) be hard (newly) slightly |
2 batches | Sticking ball | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) slightly | Sticking (old) glues (newly) slightly slightly |
Soft durometer | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | Hard (old) hard (newly) | Hard slightly (old) hard (newly) | Hard slightly (old) be hard (newly) slightly |
3 batches | Sticking ball | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) | Sticking (old) do not glue (newly) slightly | Sticking (old) glues (newly) slightly slightly | Sticking (old) be sticking (newly) slightly |
Soft durometer | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | (old) hard (newly) firmly | Hard slightly (old) hard (newly) | Hard slightly (old) be hard (newly) slightly |
Table 2.1,2.2 test data show that new Silybum drip balls soft durometer changes similar to old Silybum drip balls, strong slightly; New Silybum drip balls glues the ball variation, firmness change is similar to old Silybum drip balls.The result of the test explanation, the sticking ball of new, old Silybum drip balls changes, firmness change is similar, and the alternative present chemosynthesis adjuvant of this natural substrates adjuvant is described, but suitability for industrialized production.
The specific embodiment
Embodiment 1
(a) water intaking flies silibin 6.0g, xylitol 18.3g, starch 6.7g is standby;
(b) get xylitol and starch mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 2
(a) water intaking flies silibin 20g, lactose 76.9g, starch 23.1g is standby;
(b) get lactose and starch mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 3000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 3
(a) water intaking flies silibin 40g, xylitol 71.4g, arabic gum 28.6g is standby;
(b) get xylitol and arabic gum mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 4000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 4
(a) water intaking flies silibin 60g, xylitol 80g, starch 20g is standby;
(b) get xylitol and starch mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 45~70 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 60~70 ℃ of temperature following system, dropper bore is 1.21~2.5 millimeters, splashes in-10~10 ℃ the methyl-silicone oil, makes 5000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 5
(a) water intaking flies silibin 25g, xylitol 62.5g, starch 37.5g is standby;
(b) get xylitol and starch mix homogeneously, add above-mentioned silymarin, mixture stirs at 45~115 ℃ of heating and meltings, and mixing time is 1~30 minute, insulation, at 45~95 ℃ of temperature following system, dropper bore is 1.0~4.0 millimeters, splashes in-20~25 ℃ the vegetable oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 6
(a) water intaking flies silibin 15g, maltose 100g is standby;
(b) get maltose and add above-mentioned silymarin, mixture is at 55~75 ℃ of heating and meltings, stir, mixing time is 5~12 minutes, and insulation is 1.20~3.0 millimeters at 55~75 ℃ of temperature following system, dropper bore, splash in 0~15 ℃ the liquid paraffin, make 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly
Embodiment 7
(a) water intaking flies silibin 20g, xylitol 80g, cyclodextrin 20g is standby;
(b) get xylitol and cyclodextrin mixing mixing, add above-mentioned silymarin, mixture stirs at 45~115 ℃ of heating and meltings, mixing time is 5~20 minutes, and insulation is dripped system 58~70 ℃ of insulations, splash in 12 ℃ of liquid paraffin, make 1000 drop pill of drop pill, promptly.
Embodiment 8
(a) water intaking flies silibin 3.0g, xylitol 19.9g, pregelatinized Starch 8.0g is standby;
(b) get xylitol and pregelatinized Starch mix homogeneously, add above-mentioned silymarin, mixture stirs at 60~75 ℃ of heating and meltings, and mixing time is 10~60 minutes, insulation, at 55~65 ℃ of temperature following system, dropper bore is 1.0~3.5 millimeters, splashes in-20~25 ℃ the vegetable oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 9
(a) water intaking flies silibin 3.5g, lactose 26.6g, starch 3.4g is standby;
(b) get mixing of lactose and starch, add above-mentioned silymarin, mixture stirs at 60~85 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 60~85 ℃ of temperature following system, dropper bore is 1.1~3.5 millimeters, splashes in 0~18 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 10
(a) water intaking flies silibin 4.0g, xylitol 25.5g, arabic gum 3.5g is standby;
(b) get the mixing mixing of xylitol and arabic gum, add above-mentioned silymarin, mixture stirs at 60~85 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 60~85 ℃ of temperature following system, dropper bore is 1.1~3.5 millimeters, splashes in 0~18 ℃ the liquid paraffin, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 11
(a) water intaking flies silibin 4.5g, xylitol 28.0g, alginic acid 2.0g is standby;
(b) get xylitol and alginic acid mixing mixing, add above-mentioned silymarin, mixture stirs at 60~85 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 60~85 ℃ of temperature following system, dropper bore is 1.21~3.5 millimeters, splashes in 0~15 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 12
(a) water intaking flies silibin 5.0g, xylitol 16.6g, sodium carboxymethyl cellulose 14.0g is standby;
(b) get xylitol and sodium carboxymethyl cellulose mix homogeneously, add above-mentioned silymarin, mixture stirs at 60~85 ℃ of heating and meltings, and mixing time is 10~20 minutes, insulation, at 60~75 ℃ of temperature following system, dropper bore is 1.5~3.5 millimeters, splashes in 10~18 ℃ the liquid paraffin, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 13
(a) water intaking flies silibin 5.5g, lactose 24.0g, agar 10.0g is standby;
(b) get lactose and agar mix homogeneously, add above-mentioned silymarin, mixture stirs at 60~70 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 62~67 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splashes in 4 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 14
(a) water intaking flies silibin 6.5g, xylitol 85g, arabic gum 15g is standby;
(b) get xylitol and arabic gum mix homogeneously, add above-mentioned silymarin, mixture stirs at 55~85 ℃ of heating and meltings, and mixing time is 5~30 minutes, insulation, at 58~68 ℃ of temperature following system, dropper bore is 1.21~2.5 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 3000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 15
(a) water intaking flies silibin 60g, lactose 70g, hydroxypropyl emthylcellulose 20g is standby;
(b) getting lactose and hydroxypropyl emthylcellulose mixes, add above-mentioned silymarin, fully mix, mixture is at 64 ℃ of heating and meltings, stir, mixing time is 10~30 minutes, and insulation is 1.2~2.5 millimeters at 64 ℃ of temperature following system, dropper bore, splash in 0 ℃ the methyl-silicone oil, make 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 16
(a) water intaking flies silibin 7.0g, xylitol 16.0g, methylcellulose 4.5g is standby;
(b) get xylitol and methylcellulose mixing, adding above-mentioned silymarin fully mixes, mixture stirs at 60~70 ℃ of heating and meltings, and mixing time is 10~30 minutes, insulation, at 62~66 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 17
(a) water intaking flies silibin 150g, sorbitol 150g, carboxymethyl starch 50g is standby;
(b) get sorbitol and carboxymethyl starch mixing, adding above-mentioned silymarin fully mixes, mixture stirs at 58~78 ℃ of heating and meltings, and mixing time is 20~50 minutes, insulation, at 58~68 ℃ of temperature following system, dropper bore is 1.2~2.5 millimeters, splashes in 0~10 ℃ the methyl-silicone oil, makes 10000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 18
(a) water intaking flies silibin 55g, xylitol 55g, lactose 5g is standby;
(b) get xylitol and lactose mixing, adding above-mentioned silymarin fully mixes, mixture stirs at 60~70 ℃ of heating and meltings, and mixing time is 15~25 minutes, insulation, at 62~66 ℃ of temperature following system, dropper bore is 1.21~2.5 millimeters, splashes in 0~15 ℃ the liquid paraffin, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 19
(a) it is standby that water intaking flies silibin 5.5g, xylitol 20.5, starch 7.5g;
(b) get xylitol and starch mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 30 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 2.0 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 20
(a) water intaking flies silibin 6.0g, lactose 19.5g, starch 4.5g is standby;
(b) get lactose and starch mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 10 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 1.2 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 21
(a) water intaking flies silibin 4.0g, xylitol 20.0g, arabic gum 5.0g is standby;
(b) get xylitol and arabic gum mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 64 ℃ of heating and meltings, and mixing time is 20 minutes, insulation, at 64 ℃ of temperature following system, dropper bore is 2.5 millimeters, splashes in 0 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 22
(a) water intaking flies silibin 6.0g, xylitol 18.0g, starch 10.0g is standby;
(b) get xylitol and starch mix homogeneously, adding above-mentioned silymarin fully mixes, mixture stirs at 70 ℃ of heating and meltings, and mixing time is 25 minutes, insulation, at 65~66 ℃ of temperature following system, dropper bore is 1.21 millimeters, splashes in 6 ℃ the methyl-silicone oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.
Embodiment 23
(a) water intaking flies silibin 7.5g, xylitol 26.4g, starch 7.6g is standby;
(b) get xylitol and starch mix homogeneously, add above-mentioned silymarin, mixture stirs at 115 ℃ of heating and meltings, and mixing time is 30 minutes, insulation, at 95 ℃ of temperature following system, dropper bore is 1.0 millimeters, splashes in 15 ℃ the vegetable oil, makes 1000 drop pill, with the drop pill drop to the greatest extent and wipe liquid coolant, promptly.