CN1768794B - Chinese medicinal preparation for treating respiratory diseases and its preparing process - Google Patents
Chinese medicinal preparation for treating respiratory diseases and its preparing process Download PDFInfo
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- CN1768794B CN1768794B CN 200510200601 CN200510200601A CN1768794B CN 1768794 B CN1768794 B CN 1768794B CN 200510200601 CN200510200601 CN 200510200601 CN 200510200601 A CN200510200601 A CN 200510200601A CN 1768794 B CN1768794 B CN 1768794B
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Abstract
The invention provides a Chinese medicinal preparation for treating respiratory tract system diseases and its preparing process, wherein the preparation is prepared from luckiness straw, poppy capsule, ardisia japonica and saxifrage.
Description
Technical field: the present invention is a kind of Chinese medicine preparation for the treatment of respiratory tract system disease and preparation method thereof, belongs to technical field of Chinese medicine.
Technical background: the cough that respiratory tract system disease such as flu cause, bronchitis etc. all are common diseases, traditional Therapeutic Method mostly is antibiotic therapy, the life-time service antibiotic, can make the patient that drug resistance takes place and easily cause double infection, prevent and treat purpose in order to reach, a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; The application number of submitting to as the applicant is: it is exactly to develop for treating this type of disease that 02134071.X, name are called " a kind of medicine for the treatment of the respiratory tract system disease that flu causes ", but, the extractum hygroscopicity of the capsule product of discovery preparation is very strong in the research that continues, make that the capsule hygroscopicity is stronger, storage for a long time is perishable, unstable product quality.And the disclosed dosage form kind of this application is abundant inadequately, is suitable for crowd's narrow range, and bioavailability, the medicine stability of conventional dosage forms are undesirable, and the problem that especially bioavailability of effective ingredient is not high is badly in need of solving; In view of such circumstances, improve the thing that dosage form has just become people to be badly in need of solving.
Summary of the invention: the objective of the invention is to: a kind of Chinese medicine preparation for the treatment of respiratory tract system disease and preparation method thereof is provided; The present invention is directed to prior art, the micropill that provides, dispersible tablet, disintegrative are good, and the bioavailability height is particularly suitable for infant, old people and swallow tablet or the inconvenient patient of capsule take; Soft capsule preparation provided by the invention forms drug blockage in soft gel coat, solved medicine and met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, can play the effect that increases stability, improves bioavailability; Granule good mouthfeel provided by the invention does not need disintegrate, absorbs soon taking convenience.
The present invention constitutes like this: according to listed as parts by weight, it is to be made into 24～45 parts of Herba Reineckeae Carneaes, 16～30 parts of Pericarpium Papaveriss, 12～23 parts of Herba Ardisiae Japonicaes, 12～23 parts of Herba Saxifragaes, 12～23 parts of Folium Eriobotryaes and 4～8 parts of Cortex Mori and appropriate amount of auxiliary materials: injection, powder pin, freeze-dried powder, tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill comprises micropill, concentrated pill, the watered pill, powder, drop pill, slow releasing preparation, controlled release preparation, gel, oral liquid, soft extract, extractum and membrane reach pharmaceutically all acceptable dosage forms.
Say accurately: calculate by weight: be made into tablet, soft capsule, granule, dispersible tablet, pellet, drop pill or oral liquid with Herba Reineckeae Carneae 30g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 15g, Folium Eriobotryae 15g and Cortex Mori 5g and appropriate amount of auxiliary materials.
The preparation method of the Chinese medicine preparation of treatment respiratory tract system disease: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae and Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, survey relative density when filtrate is concentrated into 40 ℃ and be 1.20～1.25 clear paste, spray drying adopts conventional method to make different preparations with an amount of adjuvant respectively then together.
Tablet in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying adds starch 30g, carboxymethyl starch sodium 15g, mixing again,, make the micropill of particle diameter, or particle diameter is less than the microcapsule of 2mm less than 2mm, drying, granulate, tabletting, coating, promptly.
Soft capsule in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity＜40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, thousand dry relative humiditys should be lower than 40%, and drying time is at 24～48 hours, promptly.
Granule in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Add 2～2.5% aspartames and 25g dextrin,, mixing is granulated, promptly.
Dispersible tablet in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get polyvinylpolypyrrolidone 3.5g and lemon yellow 1.5g, mixing, get 3/5 with the extract powder mix homogeneously, K30 anhydrous alcohol solution with 1.5% is made binding agent, 40 order system material, granulate, and the mixed powder 2g of residue 2/5PPVP and lemon yellow mixing is added in the particle that makes, tabletting, promptly.
Pellet in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, add 20g starch, with 65% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.2, the coating pan rotating speed is 40r/min, capping selects ball, promptly
Drop pill in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, survey relative density when filtrate is concentrated into 40 ℃ and be 1.20～1.25 clear paste, spray drying, mixing, extract powder; Get the extract powder portion, two parts of PEG4000 and polyoxyethylene monostearate S-40 portion, mix homogeneously fuses in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix 80 ℃ of ointment temperature, liquid coolant height 70cm, promptly.
Oral liquid in the described preparation prepares like this: get Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae, Cortex Mori Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing adds distilled water, 2.5g aspartame, sterilization, promptly.
Among the we, Herba Reineckeae Carneae, Pericarpium Papaveris, Herba Ardisiae Japonicae, Herba Saxifragae, Folium Eriobotryae and Cortex Mori compatibility, lung moistening and asthma relieving, relieving cough and resolving phlegm; Treatment of diseases such as the cough that causes, bronchitis are used to catch a cold.
Compared with prior art, micropill disintegrative of the present invention is good, and the bioavailability height is particularly suitable for the old people and swallow tablet or the inconvenient patient of capsule take; Medicine tablet formulation provided by the invention, the mode of taking is more, can swallow, buccal and sucking take, it is convenient to use more than other oral solid formulations, simultaneously, these product are met water can rapid disintegrate form homodisperse aqueous solution in 3 minutes, solved the not high problem of effective ingredient bioavailability; Soft capsule of the present invention is that drug blockage is formed in soft gel coat, has solved medicine and has met damp and hot problem of unstable, can also cover adverse drug taste, abnormal smells from the patient, plays the effect that increases stability, improves bioavailability; Granule provided by the invention, good mouthfeel absorbs soon the bioavailability height simultaneously.
The applicant finds in the process of development granule, granule enters in the body with solution state, compare with oral solid formulation, reduced disintegrating procedue in the body, help the absorption of this product, shortened onset time greatly, but also there is certain problem in this product granule, is exactly that hygroscopicity is strong, mouthfeel is bitter.The inventor herein intends solving this two problems by adding correctives with preferred supplementary product kind.Because consider among the crowd of being suitable for and have diabetics, draw up and be equipped with sugar-free granule, with high-potency sweetener as correctives, whole supplementary product consumption is reduced significantly, simultaneously, also need under the situation that does not increase supplementary product consumption, solve the strong excessively problem of former powder hygroscopicity that exists in the raw material medicated powder by the kind and the technological parameter of strict screening adjuvant.
The applicant finds when the development dispersible tablet, pharmacopeia regulation dispersible tablet must disintegrate fully in the 3min in 19 ℃～21 ℃ water, suspension ability, bioavailability, dispersed homogeneous degree etc. are also had higher requirements, and the paste-forming rate of extract of the present invention is very high, viscosity is excessive, hygroscopicity is strong excessively, make and select to require very strict the kind and the consumption of various adjuvants in the moulding process prescription, deviation is arranged slightly, will cause product defective.The diameter of micropill is less than 2.5mm, and class is in particle properties, the bioavailability height.
The applicant is when development product of the present invention, and maximum difficulty is exactly that the extractum hygroscopicity is strong and mobile poor, and poor plasticity is difficult to molding and molten diffusing slower.Soft capsule disintegrate in gastrointestinal tract is fast, and after softgel shell broke, medicine disperseed rapidly, so the drug release stripping is fast, produce effects is rapid, the bioavailability height; Semi-transparent soft capsule can protect medicine not to be subjected to the effect of oxygen, light in dampness and the air with packaging material preferably, thereby improves the stability of labile element; So the stability of soft capsule itself and moulding process directly influence the stability of product, be very crucial technology.
In the process of development drop pill, find, substrate polyethylene glycols commonly used is that esterification forms, be the surface-active water-soluble base of a kind of tool (fusing point is 46～51 ℃), dissolubility to insoluble drug is not good, we add S-40 change polyethylene glycols itself and do not have close ester structure and surface-active character, help the absorption of medicine, if but the consumption of S-40 is too high, and can cause product to draw moist enhancing.
Experimental example 1: Study on Forming
(1) granule Study on Forming:
The applicant finds that it is exactly that hygroscopicity is strong, mouthfeel is bitter that this product is made the greatest problem of granule in development process.Because consider the crowd of being suitable for, the sugar-free granule fully of drawing up is so supplementary product consumption is just fewer, and that this product contains the former powder hygroscopicity of extractum is very strong, supplementary product consumption can not be too much situation under, strictness screening and control that must be by adjuvant and process conditions just can address these problems.
(1) supplementary product kind and consumption thereof are investigated
1. correctives is selected
The function as sweeteners comparison sheet
Kind sucrose aspartame cyclamate
Doubly 50 times of sugariness 1 (standard of comparison) 150-300
Flavor matter has the metalloid flavor carefully
80 times of costs of price 1 (standard of comparison) are low
The unrestricted consumption of consumption is limited,
Generally be no more than 0.1%
Better cost is better low carefully in safety
Through relatively comprehensive, selected aspartame is made the correctives of this product, and institute's expense per os sense is debugged and got.
2. screening experiment: get five parts of extract powders, portion does not add any adjuvant, and four parts add 0～1%, 1～2% respectively in addition, 2～2.5%, 2.5～3.5% aspartame mixing adds an amount of boiled water and takes after mixing it with water, taste its flavor through many people, judge the quality of mouthfeel, it the results are shown in Table.
The aspartame scale
The result shows, adds 2～2.5% aspartames, and mouthfeel is moderate.
(2) wettability test is got two parts of extract powders, a dextrin that adds, and mixing is put respectively in the flat weighing bottle that oneself weighs, and accurately claims surely, is to measure its hygroscopic capacity under 75% condition at 25 ℃ of temperature, relative humidity, the results are shown in Table.
(2) dispersible tablet Study on Forming:
Dispersible tablet meet water rapidly disintegrate form the water dispersion tablet of uniform sticky suspension, it is poor to have solved former dosage form disintegrative, stripping is shortcoming slowly, and the dispersible tablet that the applicant makes is disintegrate fully in the 3min in 19 ℃ of-21 ℃ of water, and suspension ability is good, bioavailability is high, dispersed homogeneous degree.
1. adjuvant screening
Prescription PPVP (g) K30 (%) disintegration time/s
Add in adding
1 0.7 2.8 1.5 5.7
2 1.4 2.1 1.5 2.1
3 2.1 1.4 1.0 3.7
4 2.8 0.7 1.0 3.5
5 3.5 0 0.8 4.5
6 0 3.5 0?8 3.9
2. check disintegration
Adopting changes the basket method, and lift disintegration tester, tablet are got 6, observes the situation by screen cloth.Percent of pass height then disintegrative is good, more pleasant bulk absorption.
Disintegration (s)
Group 123456
1 batch 15 20 18 18 17 13 in tablet of the present invention
2 batches 15 21 17 14 15 15 in tablet of the present invention
3 batches 15 18 18 12 16 17 in tablet of the present invention
The result shows, get PPVP3.5g and lemon yellow mixing, get 3/5 with the extract powder mix homogeneously, K30 anhydrous alcohol solution with 1.5% is made binding agent, 40 order system material, granulate, the mixed powder of residue 2/5PPVP1.4g and lemon yellow mixing is added in the particle that makes, tabletting, and the dispersible tablet product that obtains is easy to disintegrate.
(3) pill Study on Forming:
The micropill diameter is less than 2.5mm, and class is in particle properties, the bioavailability height, and the applicant is when development product micropill of the present invention, and maximum difficulty is exactly that hygroscopicity is strong and mobile poor, and poor plasticity is difficult to molding.The micropill manufacturing technology and the adjuvant that adopt the applicant's screening to obtain make product be easy to disintegrate, and the bioavailability height is well-behaved.
1, extrudes-the spheronization pill
1. supplementary product kind and consumption are selected
Wettability test is got two parts of extract powders, a starch that adds, and mixing is put respectively in the flat weighing bottle that oneself weighs, and accurately claims surely, is to measure its hygroscopic capacity 75% time at 25 ℃ of temperature, relative humidity, the results are shown in Table.
The wettability test result
The result shows that it is rationally feasible to adopt starch to make adjuvant.
2. make soft material is got the extractum fine powder and starch, soybean oil and ethanol are made soft material with wet granulation process in right amount, make it to reach and hold agglomeratingly, that pinches can loose, standby.Research emphasis concentration of alcohol and soybean oil consumption influence pill, and experimental result sees Table.
Concentration of alcohol is investigated
| Tested number | Concentration of alcohol | System soft material situation | |
| 1 | 70 | % ethanol | Soft material easily bonds |
| 2 | 65 | % ethanol | Soft material is moderate |
| 3 | 50 | % ethanol | Soft material viscosity is not enough |
The soybean oil consumption is investigated
| Tested number | The soybean oil consumption | The pill situation |
| 1 | 65% ethanol, 1% soybean oil | Soft material viscosity is not enough, can't pill |
| 2 | 65% ethanol, 1.2% soybean oil | Soft material is moderate, suitable pill |
| 3 | 65% ethanol, 1.5% soybean oil | Soft material easily bonds, the pill difficulty |
The result as seen, it is more satisfactory to adopt 65% ethanol, 1.2% soybean oil to be that adhesive is granulated, otherwise is difficult to molding.
3. the soft material that makes of pill is with micropill mechanism ball, and wet feed pushed the 0.8mm sieve aperture, and the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 16～20 mesh sieves and selected ball.
2, general method for making pill
Because the extruding that the humidification of water and coating pan rotate makes medicated powder be bonded into ball.Because of this product viscosity is bigger, general when making ball, water spray is fast and to add medicated powder speed slow, causes that it is bonding closely the time that then prolongs into ball, makes dry back hard, is unfavorable for the infiltration of moisture and influences molten loosing and the absorbing of medicine.
| Numbering | Coating pan rotating speed (r/min) | The molten diffusing time (min) | Mouldability |
| 1 | 30 | ?6.63 | Relatively poor |
| 2 | 40 | ?7.82 | Better |
| 3 | 50 | ?12.55 | Harder |
| 4 | 70 | ?14.98 | Hard |
| 5 | 100 | ?15.99 | Hard |
The result shows that it is optimum that the coating pan rotating speed is selected 40r/min for use.
(4) soft capsule Study on Forming:
Soft capsule disintegrate in gastrointestinal tract is fast, and after softgel shell broke, medicine disperseed rapidly, so the drug release stripping is fast, produce effects is rapid, the bioavailability height; Semi-transparent soft capsule can protect medicine not to be subjected to the effect of oxygen, light in dampness and the air with packaging material preferably, thereby improves the stability of labile element; So capsular stability and moulding process are very crucial technology.
1, supplementary product kind and consumption are selected
1. disperse medium (or claiming substrate) is chosen in fill material and substrate energy mix homogeneously, and under the prerequisite of unobstructed defeated material of energy and pelleting, reduces substrates quantity as far as possible.By test of many times, determine medication amount (g): substrate amount (g)=be advisable at 1: 1.2, experimental result sees Table.
Substrates quantity is investigated
Medication amount (g): substrate amount (g) 1: 11: 1.2 1: 1.5
Big, the mobile difference viscosity of quality of liquid medicine viscosity, all good differences in viscosity of flowability are mobile big
2. capsule shells prescription screening according to the form below proportion scale is prepared burden, put into the 500ml bottle,suction, 65 ℃ of water-baths are dissolved, automatic stirringization glue, the while evacuation, about vacuum 0.095Mpa, insulation was placed 1 hour after 5 hours, filtered glue, get a part of glue and measure viscosity and other performance, part glue evenly is paved into skim (smear below earlier one deck liquid paraffin) on iron plate, be positioned over to observe the rubber performance next day and judge again, with the investigation result of each index by good to poorly using " +++" successively, " ++ ", "+",, "-" expression the results are shown in Table.
Rubber batching The selection result
Dispensing viscosity flexibility flexibility elasticity toughness characteristics overall merit
(mpa·s)
1. gelatin: glycerol: water 3.61--+crisp, poor firmly
(100g∶35g∶100g)
2. gelatin: glycerol: water 3.35+++ +++tough, film property is fine
(100g∶45g∶100g)
3. gelatin: glycerol: water 3.57++++good springiness is general
(100g∶55g∶100g)
4. gelatin: glycerol: water 3.72 ++ +++good springiness, viscosity are fine greatly
(100g∶45g∶80g)
5. gelatin: glycerol: water 3.11 ++++-too soft poor
(100g∶45g∶120g)
6. gelatin: glycerol: sorbitol: water 3.43-+++ tough better
(100g∶35g∶5g∶100g)
7. gelatin: glycerol: sorbitol: water 3.46+++to pierce through performance good fine
(100g∶35g∶10g∶100g)
8. gelatin: glycerol: sorbitol: water 3.52 ++++ tough better
(100g∶45g∶5g∶100g)
9. gelatin: glycerol: sorbitol: water 3.47 ++ ++-soft general
(100g∶45g∶10g∶100g)
10. gelatin: glycerol: sorbitol: water 3.62++ ++ tough better
(100g∶25g∶10g∶100g)
11. gelatin: glycerol: sorbitol: water 3.57++++to pierce through performance good fine
(100g∶35g∶20g∶100g)
12. gelatin: glycerol: sorbitol: water 3.36 ++ ++ below+the 0.5mm
(100g: 55g: 5g: 90g) rubber is easily broken better
13. gelatin: glycerol: sorbitol: glue liquid is too thick, can't change glue
(84g∶28g∶28g∶20g)
14. gelatin: arabic gum: glycerol: water 3.57--+ash is poor partially for color
(100g∶25g∶35g∶100g)
15. gelatin: arabic gum: glycerol: water 3.51-++ crisp poor
(85g∶15g∶45g∶100g)
16. gelatin: arabic gum: glycerol: 3.39++ ++ 0.2～0.8mm rubber
Sorbitol: (85g: 15g: 60g: 10g: 60g) tearing strength is fine greatly for water
17. gelatin: arabic gum: Pyrusussuriensis 3.68+--crisp poor
Alcohol: glycerol: water (50g: 150g: 10g: 60g: 55g)
18. gelatin: arabic gum: glycerol: 3.52+++ash is general partially for crisp color
Sorbitol: water (85g: 15g: 45g: 10g: 110g)
19. gelatin: arabic gum: glycerol: 3.38++-below the 0.85mm
Sorbitol: (85g: 15g: 60g: 10g: 90g) the rubber poor flexibility is general for water
20. gelatin: arabic gum: glycerol: 3.35+-+ash is general partially for color
Sorbitol: water (100g: 25g: 45g: 5g: 100g)
Through above screening, overall merit is considered the characteristics of fill material, and selecting prescription 2 is gelatin 100g: glycerol 45g: water 100g.
3. opacifier is selected
The transparent adhesive tape softgel shell easily causes instability, so need to add a certain amount of opacifier.Select titanium dioxide (titanium dioxide) to make opacifier through investigation and can reach effective shaded effect, and steady quality, not with rubber cement and fill material generation chemical change.Its consumption is through investigating with gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g is advisable, and little to the rubber quality influence, the results are shown in Table.
The opacifier consumption is selected
Usage ratio rubber transparency rubber cement viscosity overall merit
(Mpa·S)
Gelatin 100g: glycerol 45g: water 100g: translucent 3.12 consumptions of titanium dioxide 0.5g are not enough
Gelatin 100g: glycerol 45g: water 100g: translucent 3.29 consumptions of titanium dioxide 1g are not enough
Gelatin 100g: glycerol 45g: water 100g: titanium dioxide 2g translucent 3.56 is good
Gelatin 100g: glycerol 45g: water 100g: opaque 3.82 viscosity of titanium dioxide 3g are bigger
Quality is more stable after adding opacifier in the capsule formula.
2, molding technological condition is investigated
1. the extractum grinding particle size is investigated
Extractum is pulverized, crossed 60 orders, 80 orders, 100 orders, 120 mesh sieves respectively, press extractum: substrate=1: 1.2 is even through the colloid mill mill, and observation mixing situation the results are shown in Table.
The extractum grinding particle size is investigated
Granularity 60 orders 80 orders 100 orders 120 orders
The mixing situation can not mixing, can mixing, and high speed centrifugation can mixing, and high speed centrifugation can mixing, high speed centrifugation
High speed centrifugation
(10000/min) (10000/min) (10000/min) (10000/min)
The not stratified 30min of the not stratified 30min of 30min layering 30min is not stratified
As seen from the above table, extractum was pulverized 80 orders, and with regard to the energy mixing, therefore selecting extractum to pulverize the order number is 80 orders.
2. fill material combined experiments chamber is got extractum and was pulverized 80 mesh sieves, presses extractum: substrate=add soybean oil at 1: 1.2, use the colloid mill mixing, and evacuation removes bubble, and is standby.
3. the investigation of batchingization glue is a gelatin by aforementioned preferred prescription: glycerol: water: titanium dioxide=100g: 45g: 100g: the 2g weigh batching with different temperatures glue, the results are shown in Table.
Changing the glue temperature investigates
Temperature (℃) change glue time (H) rubber quality
50 6 is good
60 5 is good
70 5 is good
80 5 is good
90 4 is harder
By the table prompting, it is the most suitable with 60～70 ℃ to change the glue temperature.So batchingization adhesive tape part is: weigh batching, in the inputizations glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirs 5 hours also the while evacuation except that bubble, treat sizing material even after blowing, incapsulate after the filtration in the sizing material bucket of machine.
4. pelleting: the sizing material bucket and the spice bucket of room temperature of insulation are delivered to the capsule machine top, be connected, debug pellet press with machine, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity is less than 40%.Treat that it is the 400mg/ grain that ball content loading amount is regulated in pellet press debugging back.Survey loading amount once every half an hour in the pelleting process.
5. dry: the dry soft capsule through pellet press extrusions of typing is in conveyer belt is delivered to rotating cage, and rotating cage is blown a cold wind over while rotating, rotates about 2 hours of the drying of finalizing the design.Tray dried soft gelatin capsule of cold air drying in rotating cage is contained in clean rustless steel charging tray splendid attire, moves to about 22 ℃ of temperature, and airing is 48 hours in the hothouse of relative humidity below 40%, and constantly stirs, and surveys capsule moisture and is being dry suiting below 10%.The drying lime light: the dry typing drying of rolling that adopts combined with two steps of tray dried, and the typing of rolling is dry is advisable with two hours through investigation, and overlong time is then rough; Baking temperature is advisable about investigating with 22 ℃, and it is long that it's low drying time is past temperature, though increase in temperature can shorten drying time, easily produces Testudinis to capsule surface and splits; Dry relative humidity should be lower than 40% through investigating, otherwise is difficult for dry; Got final product below 10% with control moisture drying time about 24-48 hour.
(5) drop pill Study on Forming:
1. the screening of substrate
The fusion situation of substrate and principal agent relatively
Prescription number prescription 1 prescription 2 prescriptions 3 prescriptions 4 prescriptions 5 prescriptions 6 prescriptions 7
Medicine (g) 10 10 10 0 10 10 10
Macrogol 4000 (g) 30 20 20 20 10 10-
Polyethylene glycol 6000 (g)---20 30 35 40
S-40(g) - - 10 10 - - 10
The principal agent of principal agent and substrate can with principal agent can with principal agent can with substrate merge principal agent and basic principal agent can with principal agent can with
Fusion situation substrate merges the mobile fine matter of substrate fusion system and merges the fusion of relatively poor substrate fusion substrate
But system system stream-but system system stream
Do not have mobile moving property better-not have mobile moving property relatively poor
Drop pill outward appearance-roundness difference is smooth-and roundness is poor-
Hangover roundness good roundness is good-hangover-
The better hardness of the little hardness of drop pill hardness-hardness better-hardness better-
The ball method of double differences is different-20% 8.0% 12.5%-20%-
Dissolve scattered time limit (min)-7～8 4～5 9～10-6～8-
The result shows, the drop pill stripping that composite interstitial substance makes is very fast, because the esterification of polyethylene glycols substrate forms, it is a kind of surface-active water-soluble base (fusing point is 46～51 ℃) that has, S-40 has changed polyethylene glycols itself and has not had close ester structure and surface-active character, improve the dissolubility of insoluble drug, help the absorption of medicine.
2. drip distance, drip selection fast, temperature: the interior external diameter of drip is fixed as 2.0mm～2.5mm.Evaluation index: the heavy qualification rate of ball is by weight differential requirement of Pharmacopoeia of the People's Republic of China version in 2005: within ± 10%.
Group temperature/heavy qualification rate/the % of a ℃ distance/cm liquid coolant height/cm ball
1 90 4 50 85.7
2 90 5 60 4
3 90 8 70 84.0
4 80 4 60 90.3
5 80 5 70 95.7
6 80 8 50 91.0
7 70 4 70 92.7
8 70 5 50 89.8
9 70 8 60 85.8
The result shows, the optimum condition of preparation drop pill of the present invention: drip to become ball in dimethicone, drip apart from 5cm drip footpath 2.5mm/2mm, mix 80 ℃ of ointment temperature, liquid coolant height 70cm.
Experimental example 2, pharmacodynamics part Study
Bioavailability relatively
The SD rat, body weight 250～280g, male and female half and half, fasting overnight (can't help water), next day gastric infusion, dosage is 3.8g/kg.15min before administration and after the administration, 3omin, somin, somin, 2h, 3h, the blood sampling of 4h and 8h heart., each blood sample point is with 6 rats.Blood sample is put the anticoagulant heparin pipe, the centrifugal 5min of 3000r/min, and separated plasma is put 30 ℃, is saved to analysis.High performance liquid chromatograph is by the M510 pump, the U6K injector, and M490 variable-wavelenght detector and 810 chromatographic data treating stations are formed (Waters, the U.S.).Analytical column is μ BondPakaC
18(0.45mm * 25cm); Mobile phase is methanol: 0.03mol/L sodium acetate=25: 75; Flow velocity: 0.8.mL/min; Detect wavelength: λ=238nm.Codeine phosphate extracts in the blood plasma: get 0.5mL blood plasma, add 5mLCHC
13, interior mark 50 μ l, test tube is done 30 ° and is favoured horizontal direction jolting device, and 15min is extracted in jolting, centrifugal (3000r/min) 10min, aqueous phase discarded, the accurate 4mL organic facies of drawing is in a clean tube, at 37 ℃ of water-baths, N
2Dry up under the air-flow, residue dissolves the sample introduction analysis again with 200 μ l mobile phases.
Rat plasma codeine phosphate concentration change
(N=6) time/h blood plasma codeine phosphate concentration/(mgL
-1)
Dispersible tablet of the present invention drop pill of the present invention micropill of the present invention soft capsule of the present invention granule of the present invention capsule of the present invention drop pill of the present invention
0 - - - - - - -
0.25 1.67±0.41 1.61±0.14 1.64±0.12 1.72±0.28 1.68±0.13 0.74±0.18 1.74±0.12
0.50 3.60±1.21 3.55±0.56 3.58±1.14 3.37±1.12 3.62±1.04 1.04±0.33 3.71±0.15
0.85 2.31±0.36 2.42±0.71 2.37±0.34 2.50±0.20 2.23±0.35 1.02±0.58 2.64±0.23
1.35 1.68±0.67 1.70±0.46 1.66±0.57 1.74±0.46 1.67±0.47 1.34±0.25 1.67±0.31
2.00 1.35±0.14 1.58±0.43 1.37±0.24 1.38±0.23 1.32±0.25 1.07±0.43 1.37±0.15
3.00 1.07±0.25 1.23±0.20 1.15±0.12 1.05±0.18 1.18±0.13 0.71±0.21 1.18±0.23
4.00 0.27±0.28 0.28±0.17 0.84±0.27 0.52±0.12 0.85±0.20 0.37±0.04 0.79±0.26
6.00 0.41±0.18 0.48±0.11 0.43±0.18 0.47±0.25 0.33±0.17 0.24±0.03 0.47±0.34
8.00 0.24±0.15 0.18±0.03 0.27±0.20 0.22±0.13 0.26±0.24 0.17±0.15 0.29±0.25
The result shows that the bioavailability of product of the present invention is greater than the capsule of prior art for preparing.
Experimental example 3, pharmacological research:
1, the present invention causes the antitussive action of Cavia porcellus to citric acid
Principle: the citric acid zest is stronger, after spraying sucks, stimulates Cavia porcellus respiratory tract sensor, causes cough reflectingly.
Method: 150～200g Cavia porcellus, oral administration.Give the present invention for first group, second group of co-content normal saline given codeine (5mg/kg) for the 3rd group.Spray into liquor sodii citratis with 0.2～0.5 atmospheric pressure after half an hour, spraying 10s.Tested preceding 1 day, animal is screened, need not as not coughing the person in the 120s.Write down respectively each guinea pig cough incubation period (from spraying finish to the time of cough for the first time be incubation period).The record experimental result, administration group and matched group relatively carry out statistical procedures.
The result: the present invention can prolong cough latent period, and reference value sees the following form.
Antitussive action of the present invention (X ± SD) (n=10)
| Group | Dosage (g/kg) | Cough latent period (s) |
| The present invention of normal saline codeine | 50ml 5mg 2.0 | ?51.9±3.18?144±2.14 **?295±18.13 ** |
Know by experimental data, give codeine and two groups of guinea pig cough incubation periods of the present invention obviously than normal saline group leader, p＜0.05.Point out this medicine that stronger antitussive action is arranged.
2, antiasthmatic effect of the present invention
Principle: this experiment utilizes histamine phosphate to cause asthmatic model, observes antiasthmatic effect of the present invention.
Method: test the previous day by some of preparation room preliminary election body weight 150～200g Cavia porcelluss childhood, put in the spray tank respectively, (400～500mmHg) pressure spray in the 1mg/ml histamine phosphate 1ml jetting device case with 53.3～66.6kPa, animal through certain incubation period, promptly produces asthma reaction after sucking above medicinal liquid, " asthma " reaction follow procedure can be divided into level Four, the I level is breathed and is quickened, II level dyspnea, the III level is twitched, and the IV level is fallen.Most animals at 90S with interior III level or the IV order reaction of occurring; Generally be no more than 150S, surpass 150S person and can think insensitive, will not select for use.Animal one is had a convulsion, and promptly draws back chamber door and takes out animal, is aided with the artificial respiration in case of necessity, in order to avoid animal dies because of being choked to death.
Next day, " asthma " Cavia porcellus with preliminary election was divided into 3 groups at random, every group 10, the first group is irritated stomach 1.g/ml 10g/kg of the present invention, the second group is irritated stomach 0.5g/ml 10g/kg of the present invention, third group of normal saline of irritating stomach with volume, after the administration 15min repeat administration once, 30min after the administration, the similarity condition when the putting into sprayer unit respectively histamine phosphate of spraying respectively by preliminary election.Record spraying begin to the time that symptom occurs (with twitch, falling is as the criterion) as latent time, prolong one times as latent time and think effective.(seeing the following form).
Antiasthmatic effect of the present invention (X ± SD) (n=10)
| Group | Dosage (10g/kg) | Incubation period (S) |
| Normal saline is of the present invention | Deng capacity 2.0g/ml 1.0g/ml | ?100?331**?289** |
The result: the present invention can obviously prolong to draw and breathes heavily incubation period, with matched group relatively, its significant difference is arranged, p＜0.05.Point out this medicine that stronger antiasthmatic effect is arranged.
Concrete embodiment:
Embodiments of the invention 1: the preparation 1 of tablet
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 12g, Herba Saxifragae 12g, Folium Eriobotryae 12g, Cortex Mori 4g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying adds starch 30g, carboxymethyl starch sodium 15g again, makes the micropill of particle diameter less than 2mm, or particle diameter is less than the microcapsule of 2mm, drying, granulate, tabletting, coating promptly gets tablet of the present invention.Oral, three times on the one, each 2.
Embodiments of the invention 2: the preparation 2 of tablet
Get Herba Reineckeae Carneae 45g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 15g, Folium Eriobotryae 15g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying adds starch 30g, carboxymethyl starch sodium 15g again, makes the micropill of particle diameter less than 2mm, or particle diameter is less than the microcapsule of 2mm, drying, granulate, tabletting, coating promptly gets tablet of the present invention.
Embodiments of the invention 3: the preparation 3 of tablet
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 23g, Folium Eriobotryae 23g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying adds starch 30g, carboxymethyl starch sodium 15g again, makes the micropill of particle diameter less than 2mm, or particle diameter is less than the microcapsule of 2mm, drying, granulate, tabletting, coating promptly gets tablet of the present invention.
Embodiments of the invention 4: preparation of soft capsule 1
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 12g, Folium Eriobotryae 15g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity is less than 40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, thousand dry relative humiditys should be lower than 40%, and drying time is at 24～48 hours, promptly.Oral, three times on the one, each 2.
Embodiments of the invention 5: preparation of soft capsule 2
Get Herba Reineckeae Carneae 45g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 23g, Folium Eriobotryae 12g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity is less than 40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, thousand dry relative humiditys should be lower than 40%, and drying time is at 24～48 hours, promptly.
Embodiments of the invention 6: preparation of soft capsule 3
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 12g, Herba Saxifragae 15g, Folium Eriobotryae 23g, Cortex Mori 4g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 65 ± 5 ℃ gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, mould rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8 mm, 18～25 ℃ of indoor temperatures, relative humidity is less than 40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, dry 2 hours of the typing of rolling, and 22 ℃ of baking temperatures, thousand dry relative humiditys should be lower than 40%, and drying time is at 24～48 hours, promptly.
Embodiments of the invention 7: granule preparation 1
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 15g, Folium Eriobotryae 23g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃,, spray drying, mixing; Add 2% aspartame and 25g dextrin, mixing is granulated, promptly.
Embodiments of the invention 8: granule preparation 2
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 23g, Folium Eriobotryae 12g, Cortex Mori 4g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Add 2.5% aspartame and 25g dextrin, mixing is granulated, promptly.
Embodiments of the invention 9: granule preparation 3
Get Herba Reineckeae Carneae 45g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 12g, Herba Saxifragae 12g, Folium Eriobotryae 15g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, the survey relative density was 1.20～1.25 clear paste when filtration filtrate was concentrated into 40 ℃, spray drying, mixing; Add 2.25% aspartame and 25g dextrin, mixing is granulated, promptly.
Embodiments of the invention 10: the preparation 1 of dispersible tablet
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 23g, Folium Eriobotryae 23g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get polyvinylpolypyrrolidone 3.5g and 1.5g lemon yellow mixing, get 3/5 with the extract powder mix homogeneously, make binding agent with 1.5% K30 anhydrous alcohol solution, 40 order system material, granulate, the mixed powder that remains 2/5 polyvinylpolypyrrolidone and lemon yellow mixing is added in the particle that makes, tabletting, promptly.
Embodiments of the invention 11: the preparation 2 of dispersible tablet
Get Herba Reineckeae Carneae 45g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 12g, Folium Eriobotryae 15g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get polyvinylpolypyrrolidone 3.5g and 1.5g lemon yellow mixing, get 3/5 with the extract powder mix homogeneously, make binding agent with 1.5% K30 anhydrous alcohol solution, 40 order system material, granulate, the mixed powder that remains 2/5 polyvinylpolypyrrolidone and lemon yellow mixing is added in the particle that makes, tabletting, promptly.
Embodiments of the invention 12: the preparation 3 of dispersible tablet
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 12g, Herba Saxifragae 15g, Folium Eriobotryae 12g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get polyvinylpolypyrrolidone 3.5g and 1.5g lemon yellow mixing, get 3/5 with the extract powder mix homogeneously, make binding agent with 1.5% K30 anhydrous alcohol solution, 40 order system material, granulate, the mixed powder that remains 2/5 polyvinylpolypyrrolidone and lemon yellow mixing is added in the particle that makes, tabletting, promptly.
Embodiments of the invention 13: pellet preparation 1
Get Herba Reineckeae Carneae 45g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 15g, Folium Eriobotryae 12g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, add 20g starch, with 65% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 16 mesh sieves and selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.2, the coating pan rotating speed is 40r/min, capping selects ball, promptly.
Embodiments of the invention 14: pellet preparation 2
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 23g, Folium Eriobotryae 12g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, add 20g starch, with 65% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 18 mesh sieves and selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.2, the coating pan rotating speed is 40r/min, capping selects ball, promptly.
Embodiments of the invention 15: pellet preparation 3
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 16g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 23g, Folium Eriobotryae 15g, Cortex Mori 4g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, add 20g starch, with 65% ethanol and 1.2% soybean oil system soft material, the soft material that makes micropill mechanism ball, wet feed pushed the 0.8mm sieve aperture, the wet grain of strip cuts off round as a ball, and 50～60 ℃ of drying and mouldings are crossed 20 mesh sieves and selected ball or merge above-mentioned four kinds of clear paste, spray drying, wet-milling granulation molding, mould placed add the great achievement ball in the coating pan, medicated powder: water is 1: 1.2, the coating pan rotating speed is 40r/min, capping selects ball, promptly.
Embodiments of the invention 16: drop pill preparation 1
Get Herba Reineckeae Carneae 45g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 23g, Herba Saxifragae 23g, Folium Eriobotryae 23g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get extract powder, two parts of Macrogol 4000s and polyoxyethylene monostearate S-40 portion, mix homogeneously fuses in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix 80 ℃ of ointment temperature, liquid coolant height 70cm, promptly.
Embodiments of the invention 17: drop pill preparation 2
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 15g, Folium Eriobotryae 15g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get extract powder, two parts of Macrogol 4000s and polyoxyethylene monostearate S-40 portion, mix homogeneously fuses in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix 80 ℃ of ointment temperature, liquid coolant height 70cm, promptly.
Embodiments of the invention 18: drop pill preparation 3
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 12g, Herba Saxifragae 23g, Folium Eriobotryae 12g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Get extract powder, two parts of Macrogol 4000s and polyoxyethylene monostearate S-40 portion, mix homogeneously fuses in the water-bath, stir evenly, drip and in dimethicone, to become ball, drip apart from 5cm drip footpath 2.5mm/2mm, mix 80 ℃ of ointment temperature, liquid coolant height 70cm, promptly.
Embodiments of the invention 19: the preparation 1 of oral liquid
Get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 30g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 23g, Folium Eriobotryae 15g, Cortex Mori 8g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Add distilled water, 2% aspartame, sterilization, promptly.
Embodiments of the invention 20: the preparation 2 of oral liquid
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 12g, Herba Saxifragae 15g, Folium Eriobotryae 12g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Add distilled water, 2.5% aspartame, sterilization, promptly.
Embodiments of the invention 21: the preparation 3 of oral liquid
Get Herba Reineckeae Carneae 24g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 23g, Folium Eriobotryae 23g, Cortex Mori 4g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Add distilled water, 2.3% aspartame, sterilization, promptly.
Claims (1)
1. relieving cough and asthma preparation of soft capsule method, it is characterized in that: get Herba Reineckeae Carneae 30g, Pericarpium Papaveris 20g, Herba Ardisiae Japonicae 15g, Herba Saxifragae 15g, Folium Eriobotryae 15g, Cortex Mori 5g Six-element medical material, decoct with water secondary, each 2 hours, merge and fry in shallow oil filter, filter, the survey relative density was 1.20～1.25 clear paste when filtrate was concentrated into 40 ℃, spray drying, mixing; Press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide: 100g: 45g: 100g: 2g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 5 ℃ of 65 scholars gradually after 30 minutes, stirred 5 hours and simultaneously evacuation remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, 45 ℃ of sprinkler body temperature controls, roll mould rotating speed 2.0, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity is less than 40%, pelleting: the dry typing drying of rolling that adopts combined with two steps of tray dried, the typing drying of rolling 2 hours, 22 ℃ of baking temperatures, dry relative humidity should be lower than 40%, drying time is at 24～48 hours, promptly.
Priority Applications (1)
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|---|---|---|---|
| CN 200510200601 CN1768794B (en) | 2005-10-12 | 2005-10-12 | Chinese medicinal preparation for treating respiratory diseases and its preparing process |
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|---|---|---|---|
| CN 200510200601 CN1768794B (en) | 2005-10-12 | 2005-10-12 | Chinese medicinal preparation for treating respiratory diseases and its preparing process |
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| CN111265610A (en) * | 2020-03-02 | 2020-06-12 | 贵州百灵企业集团制药股份有限公司 | Application of Keqing capsule in treating diseases caused by coronavirus infection |
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| Title |
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