CN100348214C - Large specification vessel freeing drip pill and its preparation method - Google Patents
Large specification vessel freeing drip pill and its preparation method Download PDFInfo
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Abstract
The present invention relates to a medicinal composition for treating cardiovascular/cerebrovascular diseases, particularly to an oral medicinal composition preparation prepared by adopting the extracts of the active components of traditional Chinese medicines, such as red sage roots, chuanxiong rhizomes, pueraria roots, etc. as raw materials. The aim of the present invention is to cover the shortage in the prior art and to provide a large specification blood circulation promoting dripping pill and a preparation method thereof, wherein the large specification blood circulation promoting dripping pill has high bioavailability, rapid medicine releasing, obvious effectual effect, small toxic side effect and convenient administration.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease, is a kind of drug composition oral preparation that feedstock production forms with the extract that contains 3 flavor active ingredient of Chinese herbs such as Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae particularly.
Background technology
Cardiovascular and cerebrovascular disease is one of most threatening killer of mid-aged population.Common cardiovascular and cerebrovascular disease has cerebral arteriosclerosis, cerebral hemorrhage, cerebral thrombosis, coronary atherosclerosis etc. at present.Cerebrovascular morbidity back also often with the sequela of degree varies, as hemiplegia, unfavorable, the facial hemiparalysis of speech, causes white elephant for patient, family, society.Hypertension, diabetes, hyperlipemic patients, and cardiovascular and cerebrovascular disease takes place in crowd such as obesity, smoking easily, the Inheritance factor is also played an important role in the morbidity of cardiovascular and cerebrovascular disease.Mainly be to take blood vessel dilating, promote blood flow, prevent principle such as platelet aggregation at present for the treatment of cardiovascular and cerebrovascular disease.The medicine of treatment cardiovascular and cerebrovascular disease has a lot, wherein is no lack of some effective Chinese medicines, as Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Pheretima etc.Particularly, we can say that Chinese medicine has occupied the most important part for the treatment of apoplexy sequela.
1. the research to the salvia-soluble effective ingredient is the important content of studying Radix Salviae Miltiorrhizae over nearly 20 years, and the water soluble ingredient that initial separation goes out is a danshensu.Experiment showed, that danshensu can expand the mesentery arteriole, have antiplatelet aggregation, antithrombotic forms, and promotes fibrin degradation and function of resisting myocardial ischemia.In recent years find that danshensu has inhibitory action to the anaphylaxis that antigen causes, and have the synthetic and lipotropism protein oxidation effect of the cell of reduction inner cholesterol.Use to cultivate CHO and the fibroblast proof that experimentizes: danshensu synthesizes cholesterol in the above-mentioned cultured cell inhibitory action.Make MDA content minimizing in the oxidation lipoprotein, reduce the toxicity of oxidation lipoprotein pair cell, the prompting danshensu has the atherosclerotic effect of control.
The aqueous soluble active constituent of Radix Salviae Miltiorrhizae has the phenolic acid structure more, the danshensu chemistry β-3 by name that finds the earliest, and 4-dihydroxyphenyl lactic acid (3,4-hydroxybenyl lactic acid) is the basic chemical structure of various salvianolic acids.As salvianolic acid A (salvianolic acid A SalA) is that a part danshensu and two molecule caffeic acid condensations form; Salvianolic acid B (salvianolic acid B Sal B) is that three molecule danshensus and the condensation of a part caffeic acid form; Salvianolic acid C (saivianolic acid C Sal C) then is that two molecule danshensu condensations form, and other salvianolic acid also has similar structures.Rosmarinic acid in the red sage root water soluble ingredient (Rosmarinic Acid A Ros) is formed by a part danshensu and the condensation of a part caffeic acid.In addition, also has tetramethyl salvianolic acid (Tetramethyl salvianolic acid A Sal M) or the like.
Except that danshensu, salvianolic acid is a prior effective ingredient in the red sage root water soluble ingredient, therefore also is the key content of research effective component in red sage pharmacological action.Research to salvianolic acid starts from the later stage eighties, and the effort of process more than ten years has obtained abundant experimental result and research data, proves that salvianolic acid shows pharmacologically active in many-side, has important theory and is worth and clinical meaning
[1]
2. Rhizoma Chuanxiong is one of blood-activating and stasis-removing commonly used, and the beginning is stated from Shennong's Herbal.Medicinal part is a Umbelliferae Ligustrum Rhizoma Chuanxiong Ligusticumwallichii rhizome.It is ligustrazine, ferulic acid, chuanxingol, cnidium lactone, ligustilide, vitamin A, vitamin E, folic acid, sterol etc. that its chemical constituent mainly contains tetramethylpyazine.Acrid in the mouth, little hardship, warm in nature, activating blood circulation to dissipate blood stasis, regulating QI to relieve pain effect are arranged.Be usually used in diseases such as headache, costalgia of chest, stomachache, rheumatic arthralgia.The Recent study Rhizoma Chuanxiong has effects such as blood pressure lowering, blood vessel dilating, antithrombotic, calmness and spasmolytic, is widely used in the treatment of cardio-cerebrovascular diseases
[2]
3. puerarin is the extract from the legume pueraria lobata dry root, main effective ingredient: 4, and 7-dihydroxy 8-
β-D glucose isoflavone.Have source investigation to show: after using puerarin injection, its deformable index obviously raises, and can obviously improve the cytomorphosis ability, reduces blood viscosity, removes erythrocyte aggregation, decomposes plasma fibrinogen and prevents effect such as platelet aggregation
[3]
A kind of is the TONGMAI CHONGJI that feedstock production forms with Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae, has significantly curative effect through relevant clinical introduction for the treatment ischemic cardio cerebrovascular diseases, and its brief introduction is as follows:
[name of product] TONGMAI CHONGJI;
[composition] Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae;
[character] this product is brown xanchromatic granule, feeble QI, sweet, little hardship of distinguishing the flavor of;
[function cures mainly] blood circulation and channel invigorating.Be used for ischemic cardio cerebrovascular diseases, arteriosclerosis, cerebral thrombosis, cerebral ischemia, coronary heart disease, angina pectoris.
Yet, owing to reasons such as technologies of preparing, exist all after the oral formulations of most drug is taken that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.In addition, conventional dosage forms such as oral liquid because the technology of granulation is arranged, therefore can produce bigger dust pollution in preparation process, can staff's health be worked the mischief to a certain extent, also can cause certain pollution to environment simultaneously.
The drop pill that adopts solid dispersion technology to be prepared from has just thoroughly changed the existing defective of conventional drug composition oral preparation from the frame mode of medicine.Owing to make the active component of medicine and substrate fusion be one and form liquid in advance, make active constituents of medicine fully dissolve and be dispersed in uniformly in the chemical lattice of substrate fused solution, thereby make the effective surface area of drug molecule (group) increase greatly, improved the contact area of active constituents of medicine dissolving back with gastrointestinal tract mucosa; Owing to the ease of solubility of substrate, make drop pill after taking, can dissolve rapidly, and absorbed simultaneously, played high speed, good effect efficiently by gastrointestinal tract mucosa.In addition, because the medicament contg height of drop pill, volume is little, dissolution velocity is fast, dissolving back mouthfeel is good, also can adopt the mode of sublingual administration, can make effective ingredient directly absorb and enter blood circulation by the Sublingual mucosa without gastrointestinal tract and liver, avoid the first pass effect of conventional oral formulations effectively, also avoided some drugs gastrointestinal tract to be produced the side effect that stimulates.Moreover the production technology of drop pill is simple, and production cost is lower, common according to measuring and calculating at about 50% of other oral formulations, patient's drug cost is reduced greatly, help improving the ability of seeking medical advice of extensive patients, also help improving the general health level of society.As seen drop pill is as a kind of new pharmaceutical preparation, the many disadvantages that can overcome conventional oral formulations to a great extent and had.
Yet, existing drop pill technology of preparing, its system principle all is to rely on the fused solution contain active constituents of medicine and substrate (or emulsion, suspension) the formed medicine of self gravitation to splash into to meet in the condensed fluid quenching to shrink to form, the size that the medicine that forms drips, rely on the characteristic of medicine itself to a great extent, as temperature, density and the viscosity etc. of fused solution; The selection of condensing agent also is difficult to satisfy the molding requirement of big specification drop pill in the existing drop pill technology of preparing of while, therefore can't prepare the above big specification drop pill of 100mg, as for surpassing 200 and even drop pill more than the 300mg, under existing processes and appointed condition, just can't realize more.
Yet Chinese medicine dosage form modern one big obstacle just is its prescription complexity, and dosage is big.In recent years the new product of Chinese medicine watered pill newly developed, drop pill etc., the single dose of many kinds is all more than 20.Need take 25 as FUFANG DANSHEN DIWAN, Qingkailing dripping pill need be taken 25 at every turn at every turn, and this takes to the patient and brings very big inconvenience.Especially gerontal patient, hands is trembled dim eyesight mostly, the number of their grain to go out tens pillers and puts mouth more smoothly into and swallow down by no means easy.
(Zhang Shanyu, Li Fenglong. the application of drop pill in Chinese medicine preparation. prolong limit medical college journal 1996,19 (1) P.59-62)
Summary of the invention
Purpose of the present invention is to remedy the deficiencies in the prior art, provides a kind of bioavailability height to extensive patients and medical personnel, release fast, and quick produce effects, toxic and side effects is littler, and the large specification vessel freeing drip pill of taking convenience and preparation method thereof.
Take following preparation method can make the above large specification vessel freeing drip pill of 100mg involved in the present invention.
[preparation method]
1. raw material: the extract thick paste or the dry powder that contain 3 flavor active ingredient of Chinese herbs such as Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae;
2. substrate: the mixture of one or more in pharmaceutically suitable carrier such as polyethylene glycols, sorbitol anhydride class, polyoxyethylene sorbitol acid anhydride class, polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac;
3. proportioning: with g or kg is unit, by weight, and drug extract: substrate=1: 0.5～1: 5;
4. according to the given ratio of prescription, accurately take by weighing drug extract and substrate, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;
5. adopt the big specification special drilling pill machine of we and Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing's co-design, production, the specification of pre-set required drop pill, and the temperature control system of adjustment drop pill machine, make the water dropper temperature heating of drop pill machine and remain on 80 ℃～100 ℃, the temperature cooling of condensing agent also forms the thermograde that decays gradually from top to bottom, upper temp is 15 ℃～35 ℃, and bottom temp is-5 ℃～10 ℃;
6. when treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively and reaching desired state of temperature, fused solution and/or the emulsion and/or the suspension that will contain drug extract and substrate, place in the water dropper jar of drop pill machine, splash in the condensing agent, condensing agent is selected the dimethicone greater than No. 100 for use;
7. will shrink the drop pill taking-up of molding by the outlet of drop pill machine, remove the surface condensation agent, be drying to obtain.
Annotate: preparation method 5 described " big specification special drilling pill machine ", wherein " special-purpose dripper device " sees the dripper device of disclosed a kind of special use among the CN 1586454A, but the remainder application reference number is 02233558.7 utility model patent, utilize the condensation portion of the disclosed drop pill machine in a dripper device and the back patent that discloses in the previous patent, can finish the preparation process of big specification LIUWEI DIHUANG WAN involved in the present invention.We and Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing adopt the big specification special drilling pill machine of the disclosed dripper device co-design of patent of the present invention, production simultaneously, have also formed formal production, and sell.This machine is except that the water dropper part, and is similar with common drop pill machine.
[appendix 1: a kind of 3 flavor active ingredient of Chinese herbs preparation method of extract such as Radix Salviae Miltiorrhizae that contain]
Get Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong and the Radix Puerariae of equivalent, decoct with water secondary, 1.5 hours for the first time, 1 hour for the second time, collecting decoction, filter, it is 1.08 that filtrate is concentrated into relative density, filters while hot, and it is 1.38～1.40 extractum that filtrate is concentrated into relative density, the perhaps direct spray-dried dry powder of making, promptly.
Main active constituents of medicine contained in the prepared extract has:
Danshensu: i.e. β-3,4-dihydroxyphenyl lactic acid (3, a 4-hydroxybenyl lactic acid) class,
As salvianolic acid A (salvianolic acid A Sal A),
Salvianolic acid B (salvianolic acid B Sal B),
Salvianolic acid C (saivianolic acid C Sal C),
Rosmarinic acid (Rosmarinic Acid A Ros),
Tetramethyl salvianolic acid (Tetramethyl salvianolic acid A Sal M) etc.;
Salvianolic acid;
Tetramethylpyazine: i.e. ligustrazine, ferulic acid, chuanxingol, cnidium lactone, ligustilide, vitamin A, vitamin E, folic acid, sterol etc.;
Puerarin: mainly be 4,7-dihydroxy 8-
β-D glucose isoflavone etc.
[appendix 2: different size uses the reference of dimethicone label and temperature]
| Drop pill weight | The silicone oil label | The condensing agent temperature | |
| Large specification vessel freeing drip pill | 100mg | 100～200 | 20 ℃ of (top)～5 ℃ (bottom) |
| Large specification vessel freeing drip pill | 200mg | 200～300 | 25 ℃ of (top)～5 ℃ (bottom) |
| Large specification vessel freeing drip pill | 300mg | 300～400 | 28 ℃ of (top)～0 ℃ (bottom) |
| Large specification vessel freeing drip pill | 400mg | 400～500 | 35 ℃ of (top)～-5 ℃ (bottom) |
Above data for reference, under different raw materials and environmental condition, may be slightly different.
[beneficial effect]
Cardiovascular and cerebrovascular disease is one of most threatening killer of mid-aged population.Common cardiovascular and cerebrovascular disease has cerebral arteriosclerosis, cerebral hemorrhage, cerebral thrombosis, coronary atherosclerosis etc. at present.Cerebrovascular morbidity back also often with the sequela of degree varies, as hemiplegia, unfavorable, the facial hemiparalysis of speech, causes white elephant for patient, family, society.Hypertension, diabetes, hyperlipemic patients, and cardiovascular and cerebrovascular disease takes place in crowd such as obesity, smoking easily, the Inheritance factor is also played an important role in the morbidity of cardiovascular and cerebrovascular disease.Mainly be to take blood vessel dilating, promote blood flow, prevent principle such as platelet aggregation at present for the treatment of cardiovascular and cerebrovascular disease.The medicine of treatment cardiovascular and cerebrovascular disease has a lot, wherein is no lack of some effective Chinese medicines, as Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Flos Carthami, Pheretima etc.Particularly, we can say that Chinese medicine has occupied the most important part for the treatment of apoplexy sequela.
Yet, owing to reasons such as technologies of preparing, exist all after the oral formulations of most drug is taken that dissolve scattered time limit is long, dissolution is low, absorption is relatively poor, problem such as liver sausage first pass effect and bioavailability are lower, thereby influence the performance of drug effect, also directly affect therapeutic effect.In addition, conventional dosage forms such as oral liquid because the technology of granulation is arranged, therefore can produce bigger dust pollution in preparation process, can staff's health be worked the mischief to a certain extent, also can cause certain pollution to environment simultaneously.
The drop pill that adopts solid dispersion technology to be prepared from has just thoroughly changed the existing defective of conventional drug composition oral preparation from the frame mode of medicine.Owing to make the active component of medicine and substrate fusion be one and form liquid in advance, make active constituents of medicine fully dissolve and be dispersed in uniformly in the chemical lattice of substrate fused solution, thereby make the effective surface area of drug molecule (group) increase greatly, improved the contact area of active constituents of medicine dissolving back with gastrointestinal tract mucosa; Owing to the ease of solubility of substrate, make drop pill after taking, can dissolve rapidly, and absorbed simultaneously, played high speed, good effect efficiently by gastrointestinal tract mucosa.In addition, because the medicament contg height of drop pill, volume is little, dissolution velocity is fast, dissolving back mouthfeel is good, also can adopt the mode of sublingual administration, can make effective ingredient directly absorb and enter blood circulation by the Sublingual mucosa without gastrointestinal tract and liver, avoid the first pass effect of conventional oral formulations effectively, also avoided some drugs gastrointestinal tract to be produced the side effect that stimulates.Moreover the production technology of drop pill is simple, and production cost is lower, common according to measuring and calculating at about 50% of other oral formulations, patient's drug cost is reduced greatly, help improving the ability of seeking medical advice of extensive patients, also help improving the general health level of society.As seen drop pill is as a kind of new pharmaceutical preparation, the many disadvantages that can overcome conventional oral formulations to a great extent and had.
Yet, existing drop pill technology of preparing, its system principle all is to rely on the fused solution contain active constituents of medicine and substrate (or emulsion, suspension) the formed medicine of self gravitation to splash into to meet in the condensed fluid quenching to shrink to form, the size that the medicine that forms drips, rely on the characteristic of medicine itself to a great extent, as temperature, density and the viscosity etc. of fused solution; The selection of condensing agent also is difficult to satisfy the molding requirement of big specification drop pill in the existing drop pill technology of preparing of while, therefore can't prepare the above big specification drop pill of 100mg, as for surpassing 200 and even drop pill more than the 300mg, under existing processes and appointed condition, just can't realize more.
Yet Chinese medicine dosage form modern one big obstacle just is its prescription complexity, and dosage is big.In recent years the new product of Chinese medicine watered pill newly developed, drop pill etc., the single dose of many kinds is all more than 20.Need take 25 as FUFANG DANSHEN DIWAN, Qingkailing dripping pill need be taken 25 at every turn at every turn, and this takes to the patient and brings very big inconvenience.Especially gerontal patient, hands is trembled dim eyesight mostly, the number of their grain to go out tens pillers and puts mouth more smoothly into and swallow down by no means easy.
(Zhang Shanyu, Li Fenglong. the application of drop pill in Chinese medicine preparation. prolong limit medical college journal 1996,19 (1) P.59-62)
Large specification vessel freeing drip pill involved in the present invention, utilize publication number to be disclosed in the CN 1586454A patent of invention " a kind of dripper device of special use ", and we and Changzheng Tianmin High Science ﹠ Technology Co., Ltd., Beijing adopt the disclosed dripper device co-design of patent of the present invention, the big specification special drilling pill machine of producing, the traditional handicraft that overcome of success is only dripped the disadvantage of making by medicinal liquid gravity, simultaneously again to the kind of condensing agent, model, the carrying out of process conditions such as temperature reasonably tested, screening, success prepared the above large specification vessel freeing drip pill of 100mg, make and to utilize the drop pill technology of preparing that the Chinese medicine dosage form is improved and become possibility, brought more must the convenience also for taking of extensive patients.
1. large specification vessel freeing drip pill involved in the present invention; utilize surfactant to be substrate; make solid dispersion with the extract that contains 3 flavor active ingredient of Chinese herbs such as Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae; making medicine be molecule, colloid or microcrystalline state is scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine had wetting action; can make medicine molten microgranule or the solution of loosing into rapidly; thereby make the dissolving of medicine and absorb quickening; thereby improved bioavailability, brought into play efficient, quick-acting effects etc.
2. large specification vessel freeing drip pill involved in the present invention, contact promptly with saliva and to dissolve rapidly, and absorb by oral mucosa, not only rapid-action, and the influence of not taken food, promptly all can containing take after meal ante cibum, can not produce any residual harmful substance at gastric yet, thereby make that patient's medication is safer, also have medication convenience, characteristic of accurate simultaneously.
3. large specification vessel freeing drip pill involved in the present invention mixes the extract that contains active constituents of medicine mutually with molten matrix, splashes in the not miscible condensed fluid and makes.Therefore, the stability of drug height, not facile hydrolysis, oxidation, and the operation be under liquid state, to carry out, no dust pollution is not subject to the influence of crystal formation, thereby has guaranteed the quality of medicine, has increased stability.
4. production technology, the equipment of preparation drop pill are simple, easy to operate, the automaticity height, and labor intensity is low, the production efficiency height.Workshop does not have dust simultaneously, helps labor protection and environmental protection yet.
5. the production cost of preparation drop pill is usually with about 50% of other oral formulations of kind.
The specific embodiment
Now with several groups of specific embodiments, be described further with regard to the preparation method of large specification vessel freeing drip pill of the present invention.
1. the preparation of drug extract: it is standby to make the dry powder that contains 3 flavor active ingredient of Chinese herbs such as Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae earlier according to [appendix 1];
2. substrate: Polyethylene Glycol
1000, Polyethylene Glycol
4000, Polyethylene Glycol
6000, Polyethylene Glycol
10000, Polyethylene Glycol
20000, span 40, polyoxyethylene stearate 40 esters, poloxamer, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac, polyoxyethylene stearate 40 esters+Polyethylene Glycol
4000, Polyethylene Glycol
1000+ Polyethylene Glycol
4000, carboxymethyl starch sodium+Polyethylene Glycol
4000, betacyclodextrin+Polyethylene Glycol
4000
3. proportioning: with g or kg is unit, by weight, and drug extract: substrate=1: 0.5～1: 5;
4. the volume with the dropping-pill machine head is set in 100mg, 200mg, 300mg, 400mg respectively;
5. according to the specification that sets, with reference to the label and the temperature of [appendix 2] selection and setting condensing agent, the process that provides according to [preparation method] 4～7 is prepared, and can obtain the large specification vessel freeing drip pill of different size.
[result of the test]
Test 1: the specification of setting pulse invigorating pill is 100mg, the dimethicone that adopts No. 100 is as condensing agent, dropping-pill machine head temperature is 75 ℃, the condensing agent upper temp is 20 ℃, bottom temp is 5 ℃, and the proportioning of drug extract and above-mentioned substrate was respectively 1: 0.5,1: 1,1: 4, was prepared according to the step of stipulating in the preparation method, single or complex carrier sees Table 1 as the experimental result of substrate with 17 kinds of differences respectively can to obtain three groups.
Test 2: the specification of setting pulse invigorating pill is 200mg, the dimethicone that adopts No. 200 is as condensing agent, dropping-pill machine head temperature is 75 ℃, the condensing agent upper temp is 25 ℃, bottom temp is 5 ℃, and the proportioning of drug extract and above-mentioned substrate was respectively 1: 0.5,1: 1,1: 4, was prepared according to the step of stipulating in the preparation method, single or complex carrier sees Table 2 as the experimental result of substrate with 17 kinds of differences respectively can to obtain three groups.
Test 3: the specification of setting pulse invigorating pill is 300mg, the dimethicone that adopts No. 300 is as condensing agent, dropping-pill machine head temperature is 75 ℃, the condensing agent upper temp is 30 ℃, bottom temp is 0 ℃, and the proportioning of drug extract and above-mentioned substrate was respectively 1: 0.5,1: 1,1: 4, was prepared according to the step of stipulating in the preparation method, single or complex carrier sees Table 3 as the experimental result of substrate with 17 kinds of differences respectively can to obtain three groups.
Test 4: the specification of setting pulse invigorating pill is 400mg, the dimethicone that adopts No. 500 is as condensing agent, dropping-pill machine head temperature is 75 ℃, the condensing agent upper temp is 35 ℃, bottom temp is-5 ℃, and the proportioning of drug extract and above-mentioned substrate was respectively 1: 0.5,1: 1.5,1: 4, was prepared according to the step of stipulating in the preparation method, single or complex carrier sees Table 4 as the experimental result of substrate with 17 kinds of differences respectively can to obtain three groups.
The partial reference data is as follows:
1. Du Guan China, Zhang Juntian. salvia-soluble effective ingredient---salvianolic acid progress. preclinical medicine and clinical 2000,20 (5) is P.10-14;
2. dagger-axe continues already, the Zhang Zhen mountain range. Rhizoma Chuanxiong pharmacological research and clinical practice new development. and 1994 the 14th the 10th phases of volume of Chinese combination of Chinese and Western medicine magazine;
3. the multitude sea is military, Chen Chaoyong. the curative effect of puerarin treatment ischemic cerebrovascular. and P.1035 clinical assembling rolled up for the 22nd phase in 2000 the 15th;
Table 1 100mg specification vessel freeing drip pill preparation experiment result
Condensing agent: No. 100 dimethicones, dropping-pill machine head temperature is 75 ℃, and the condensing agent upper temp is 20 ℃, and bottom temp is 5 ℃, drug extract: substrate=1: 0.5,1: 1,1: 4
Table 2 200mg specification vessel freeing drip pill preparation experiment result
Condensing agent: No. 200 dimethicones, dropping-pill machine head temperature is 75 ℃, and the condensing agent upper temp is 25 ℃, and bottom temp is 5 ℃, drug extract: substrate=1: 0.5,1: 1,1: 4
Table 3 300mg specification vessel freeing drip pill preparation experiment result
Condensing agent: No. 300 dimethicones, dropping-pill machine head temperature is 75 ℃, and the condensing agent upper temp is 28 ℃, and bottom temp is 0 ℃, drug extract: substrate=1: 0.5,1: 1,1: 4
Table 1 400mg specification vessel freeing drip pill preparation experiment result
Condensing agent: No. 500 dimethicones, dropping-pill machine head temperature is 75 ℃, and the condensing agent upper temp is 35 ℃, and bottom temp is-5 ℃, drug extract: substrate=1: 0.5,1: 1,1: 4
Claims (3)
- A ball great in/equal the large specification vessel freeing drip pill of 100mg, the pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease, with the extract that contains Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae 3 flavor active ingredient of Chinese herbs is raw material, be prepared from pharmaceutically suitable carrier as substrate, wherein:1.1 pulse invigorating pill as claimed in claim 1 is characterized in that the described extract that contains Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae 3 flavor active ingredient of Chinese herbs is made by following method: get Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong and the Radix Puerariae of equivalent, decoct with water secondary, 1.5 hours for the first time, 1 hour for the second time, collecting decoction filtered, it is 1.08 that filtrate is concentrated into relative density, filter while hot, it is 1.38～1.40 extractum that filtrate is concentrated into relative density, perhaps the direct spray-dried dry powder of making, that is, standby.1.2 substrate: Polyethylene Glycol 1000, Polyethylene Glycol 4000, Polyethylene Glycol 6000, Polyethylene Glycol 10000, Polyethylene Glycol 20000, span 40, polyoxyethylene stearate 40 esters, poloxamer, sodium lauryl sulphate, stearic acid, sodium stearate, glycerin gelatine, Lac, polyoxyethylene stearate 40 esters+Polyethylene Glycol 4000, Polyethylene Glycol 1000+ Polyethylene Glycol 4000, carboxymethyl starch sodium+Polyethylene Glycol 4000, betacyclodextrin+Polyethylene Glycol 40001.3 proportioning: with g or kg is unit, by weight, and drug extract: substrate=1: 1～1: 2.1.4, accurately take by weighing drug extract and substrate according to the given ratio of prescription, be placed on heating while stirring in the heating container, standby until the fused solution that obtains containing drug extract and substrate and/or emulsion and/or suspension;1.5 adopt big specification special drilling pill machine, the specification of pre-set required drop pill, and the temperature control system of adjustment drop pill machine, make the water dropper temperature heating of drop pill machine and remain on 50 ℃～90 ℃, the temperature cooling of condensing agent also forms the thermograde that decays gradually from top to bottom, upper temp is 15 ℃～35 ℃, and bottom temp is-5 ℃～10 ℃;1.6 when treating that the temperature of condensing agent in dropping-pill machine head and the condensation column is stable respectively and reaching desired state of temperature, to contain fused solution and/or the emulsion and/or the suspension of drug extract and substrate, place in the water dropper jar of drop pill machine, splash in the condensing agent, shrink molding, promptly.1.7 it is characterized in that: described condensing agent is the dimethicone greater than No. 100.
- 2. pulse invigorating pill as claimed in claim 1 is characterized in that: described substrate is Polyethylene Glycol 2000Or/and Polyethylene Glycol 4000Or/and Polyethylene Glycol 6000
- 3. any pulse invigorating pill as claimed in claim 1 or 2 is characterized in that: the mixed proportion of described drug extract and substrate is 1: 1～1: 2.
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| CN100348214C true CN100348214C (en) | 2007-11-14 |
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| 滴丸剂的研究进展 胡向青等.药学进展，第28卷第12期 2004 * |
| 部颁药品标准中药成方制剂第二十册 302页，卫生部药典委员会 1998 * |
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