CN1768794B - Chinese medicinal preparation for treating respiratory diseases and its preparing process - Google Patents

Abstract

The present invention is a kind of traditional Chinese medicine preparation for treating respiratory system diseases and its preparation method. It is prepared from auspicious grass, poppy shell, dwarf tea, saxifrage, etc.; the product is suitable for respiratory system diseases, such as: cold-induced Cough, bronchitis, etc. have relatively good therapeutic effects; the preparation method provided is scientific and reasonable; the obtained product has stable quality, rich dosage forms, a wide range of applicable people, high bioavailability, and good drug stability.

Description

Traditional Chinese medicine preparation for treating respiratory system diseases and preparation method thereof

Technical field: The present invention relates to a traditional Chinese medicine preparation for treating respiratory system diseases and a preparation method thereof, belonging to the technical field of traditional Chinese medicine.

Technical background: Respiratory diseases such as cough and bronchitis caused by colds are common diseases. The traditional treatment methods are mostly antibiotic treatment. Long-term use of antibiotics can make patients resistant to drugs and easily cause double infection. In order to achieve the purpose of prevention and treatment, Many inventors and pharmaceutical companies have done a lot of research, and also provided some therapeutic products; the application number submitted by the applicant is: 02134071. Developed for the treatment of this type of disease, however, in the continuing research, it was found that the extract of the prepared capsule product had strong hygroscopicity, which made the capsule hygroscopicity stronger, perishable when stored for a long time, and the product quality was unstable. Moreover, the variety of dosage forms disclosed in this application is not rich enough, the scope of applicable population is narrow, the bioavailability and drug stability of traditional dosage forms are not ideal, especially the problem that the bioavailability of active ingredients is not high needs to be solved urgently; It has become something that people urgently need to solve.

Summary of the invention: The object of the present invention is to: provide a kind of traditional Chinese medicine preparation for the treatment of respiratory system diseases and its preparation method; The present invention aims at the prior art, and provides pellets, dispersible tablets, good disintegration, high bioavailability, especially It is suitable for infants, young children, the elderly, and patients who have difficulty swallowing tablets or capsules; the soft capsule preparation provided by the invention is made by sealing the drug in a soft rubber shell, which solves the problem of drug instability when exposed to heat and humidity, and can also cover up Drugs with bad taste and smell can increase stability and improve bioavailability; the granules provided by the invention have good taste, do not need to be disintegrated, are quick to absorb, and are convenient to take.

The present invention is constituted as follows: calculated according to parts by weight, it uses 24 to 45 parts of auspicious grass, 16 to 30 parts of poppy shell, 12 to 23 parts of short tea, 12 to 23 parts of saxifrage, and 12 to 23 parts of loquat leaves. 4 to 8 parts of Cortex Mori and appropriate amount of auxiliary materials are made into: injection, powder injection, freeze-dried powder injection, tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, including microcapsule Pills, concentrated pills, water pills, powders, dripping pills, sustained-release preparations, controlled-release preparations, gels, oral liquid preparations, decoctions, extracts and films, and all pharmaceutically acceptable dosage forms.

To be precise: Calculated by weight: 30g of auspicious grass, 20g of poppy shell, 15g of short tea, 15g of saxifrage, 15g of loquat leaves, 5g of mulberry bark and appropriate amount of auxiliary materials are used to make tablets, soft capsules, granules, Dispersible tablet, micropill, drop pill or oral liquid.

The preparation method of the traditional Chinese medicine preparation for the treatment of respiratory system diseases: take auspicious grass, poppy shell, short ground tea, saxifrage, loquat leaf and Morus alba, add water to decoct twice, each time for 2 hours, combine decoction and filter, Filtrate, concentrate the filtrate to 40°C, measure the clear paste with a relative density of 1.20-1.25, spray dry, and then prepare different preparations with appropriate amount of auxiliary materials by conventional methods.

The tablet in the preparation is prepared in this way: take the six medicinal materials of auspicious grass, poppy shell, dwarf tea, saxifrage, loquat leaf, and cortex mulberry, add water to decoct twice, each time for 2 hours, combine and decoct and filter, filter When the filtrate is concentrated to 40°C, the clear paste with a relative density of 1.20 to 1.25 is measured, spray-dried, then add 30g of starch and 15g of sodium carboxymethyl starch, mix well, and make pellets with a particle size of less than 2mm, or granules Microcapsules with a diameter of less than 2 mm are dried, granulated, compressed into tablets, and coated.

The soft capsules in the preparation are prepared in the following way: take auspicious grass, poppy shell, short tea, saxifrage, loquat leaves, and cortex Morus alba, add water to decoct twice, each time for 2 hours, and decoct and filter. Filter, when the filtrate is concentrated to 40 DEG C, measure the clear ointment with a relative density of 1.20 to 1.25, spray dry, and mix; add soybean oil according to the amount of drug: base amount=1: 1.2, and mix; the formula of the rubber is gelatin: glycerin : water: titanium dioxide = 100g: 45g: 100g: 2g, the batching and chemical glue conditions are: weigh the ingredients, put them into the chemical glue tank, gradually heat up to 65±5°C after cold soaking for 30 minutes, stir for 5 hours and simultaneously vacuumize and remove Air bubbles, after the rubber material is uniform, discharge the material, filter and put it into the rubber material barrel of the capsule machine; debug the pill press machine, control the temperature of the gelatin box at 65°C, the temperature control of the spray at 45°C, the speed of the rolling die at 2.0, and the thickness of the rubber skin at 0.8mm , indoor temperature 18-25°C, relative humidity <40%, press pellets; drying adopts two-step combination of rolling drying and tray drying, rolling drying for 2 hours, drying temperature 22°C, dry relative humidity should be lower than 40%, The drying time is 24-48 hours, that is to say.

The granules in the preparation are prepared in the following way: take auspicious grass, opium poppy shell, short ground tea, saxifrage, loquat leaves, and cortex Morus alba, add water to decoct twice, each time for 2 hours, combine and decoct, filter When the filtrate is concentrated to 40°C, the clear paste with a relative density of 1.20-1.25 is measured, spray-dried, and mixed; add 2-2.5% aspartame and 25g dextrin, mix, and granulate to obtain.

The dispersible tablet in the preparation is prepared in the following way: take auspicious grass, poppy shell, short ground tea, saxifrage, loquat leaf, and cortex Morus alba, add water to decoct twice, each time for 2 hours, combine and decoct and filter, Filtrate, concentrate the filtrate to 40°C, measure the clear paste with a relative density of 1.20-1.25, spray dry, and mix well; take 3.5g of crospovidone and 1.5g of lemon yellow, mix well, take 3/5 with the extract Mix the powder evenly, use 1.5% K30 absolute ethanol as a binder, prepare the material with 40 meshes, granulate, add 2 g of the remaining 2/5 PPVP and lemon yellow mixed powder to the prepared granules, and press into tablets. Instantly.

The micropills in the preparation are prepared in the following way: take the six medicinal materials of auspicious grass, poppy shell, dwarf tea, saxifrage, loquat leaves, and cortex mulberry, add water and decoct twice, each time for 2 hours, combine and decoct and filter, filter After the filtrate is concentrated to 40°C, the clear paste with a relative density of 1.20 to 1.25 is measured, spray-dried, and 20g of starch is added, and the soft material is made with 65% ethanol and 1.2% soybean oil, and the prepared soft material is pelletized with a pellet machine. The wet material is extruded through a 0.8mm sieve, the strip-shaped wet granules are cut and spheroidized, dried at 50-60°C, and passed through 16-20 mesh screened pellets or combined with the above four clear pastes, spray-dried, wet powder granulated and molded. The mold is placed in the coating pot and enlarged into pills, the ratio of medicine powder: water is 1:1.2, the speed of the coating pot is 40r/min, the surface is covered, and the pills are selected to obtain

The dripping pills in the preparation are prepared in the following way: take the six medicinal materials of auspicious grass, poppy shell, dwarf tea, saxifrage, loquat leaves, and cortex mulberry, add water to decoct twice, each time for 2 hours, combine and decoct, filter When the filtrate is concentrated to 40°C, the clear paste with a relative density of 1.20 to 1.25 is measured, spray-dried, and mixed to obtain an extract powder; take one part of the extract powder, two parts of PEG4000 and polyoxyethylene monostearate S -40 parts, mix evenly, melt on a water bath, stir well, drop into simethicone oil to form pellets, drop distance 5cm, drop diameter 2.5mm/2mm, temperature of mixed ointment 80°C, cooling liquid height 70cm, that is ready.

The oral liquid in the preparation is prepared in the following way: take auspicious grass, poppy shell, short tea, saxifrage, loquat leaf, and mulberry bark six medicinal materials, add water and decoct twice, each time for 2 hours, combine and decoct, filter When the filtrate is concentrated to 40°C, the clear paste with a relative density of 1.20 to 1.25 is measured, spray-dried, mixed with distilled water and 2.5g of aspartame, and sterilized to obtain the product.

In this prescription, auspicious grass, poppy shell, dwarf ground tea, saxifrage, loquat leaf and Morus alba are combined to moisten the lungs and relieve asthma, relieve cough and reduce phlegm; it is used for the treatment of cough, bronchitis and other diseases caused by colds.

Compared with the prior art, the micropills of the present invention have good disintegration and high bioavailability, and are especially suitable for the elderly and patients who have difficulty swallowing tablets or capsules; There are many ways, it can be swallowed, swallowed and sucked, which is far more convenient than other oral solid preparations. At the same time, the product can quickly disintegrate in water to form a uniformly dispersed aqueous solution within 3 minutes, which solves the problem of bioavailability of active ingredients. The problem is not high; the soft capsule of the present invention is formed by sealing the medicine in a soft rubber shell, which solves the problem of the instability of the medicine in case of heat and humidity, and can also cover up the bad taste and smell of the medicine, so as to increase the stability and improve the biological quality of the medicine. The effect of availability; the granules provided by the invention have good mouthfeel, fast absorption and high bioavailability.

The applicant found in the process of developing granules that the granules enter the body in a solution state, which reduces the disintegration process in the body compared with oral solid preparations, is beneficial to the absorption of this product, and greatly shortens the onset time, but the The product granules also have certain problems, which are strong hygroscopicity and bitter taste. The inventor of this patent intends to solve these two problems by adding flavoring agent and preferred adjuvant types. Considering that there may be diabetic patients in the applicable population, it is planned to prepare sugar-free granules, using high-efficiency sweeteners as flavoring agents, so that the overall consumption of excipients will be greatly reduced. At the same time, it is necessary to strictly screen the types of excipients and process parameters. , without increasing the amount of excipients, to solve the problem of excessive hygroscopicity of the original powder in the raw material medicine powder.

When developing dispersible tablets, the applicant found that the Pharmacopoeia stipulates that dispersible tablets must be completely disintegrated in water at 19°C to 21°C within 3 minutes, which also has higher requirements for suspensibility, bioavailability, and uniformity of dispersion. However, the present invention extracts The paste yield is very high, the viscosity is too high, and the hygroscopicity is too strong, which makes the selection requirements for the types and dosages of various auxiliary materials in the molding process prescription very strict. A slight deviation will lead to unqualified products. The diameter of the pellets is less than 2.5mm, which is similar to the nature of granules and has high bioavailability.

When the applicant is developing the product of the present invention, the biggest difficulty is that the extractum has strong hygroscopicity, poor fluidity, poor plasticity, is difficult to form and dissolves slowly. The soft capsule disintegrates quickly in the gastrointestinal tract, and the drug is quickly dispersed after the capsule shell is broken, so the drug releases and dissolves quickly, has a rapid effect, and has high bioavailability; the translucent soft capsule and better packaging materials can protect the drug from moisture Oxygen and light in the gas and air can improve the stability of unstable components; therefore, the stability of the soft capsule itself and the molding process directly affect the stability of the product, which is a very key technology.

In the process of developing drop pills, it was found that the commonly used matrix polyethylene glycol is formed by esterification, which is a surface-active water-soluble matrix (melting point is 46-51°C), and has poor solubility for insoluble drugs. , we add S-40 to change the properties of polyethylene glycols that do not have lipophilic structure and surface activity, which is beneficial to the absorption of drugs, but if the amount of S-40 is too high, it will lead to enhanced product hygroscopicity.

Experimental Example 1: Research on Molding Process

(1) Research on the molding process of granules:

During the development process, the applicant found that the biggest problem of the product being made into granules was strong hygroscopicity and bitter taste. Considering the applicable population, it is planned to prepare sugar-free granules, so the amount of excipients is relatively small, and the original powder of the extract contained in this product has strong hygroscopicity. Only strict screening and control can solve these problems.

(1) Types and dosage of excipients

① Choice of flavoring agent

Sweetener Function Comparison Table

Type Sucrose Aspartame Cyclamate

Sweetness 1 (comparison standard) 150-300 times 50 times

taste good good good metal taste

Price 1 (compared to standard) 80 times lower cost

Amount Unlimited Unlimited Amount Restricted,

Generally no more than 0.1%

Safety Good Good Good Good Better Better Low Cost

After comprehensive comparison, aspartame is selected as the flavoring agent of this product, and the required dosage is obtained through taste adjustment.

② Screening experiment: Take five parts of extract powder, one part without any auxiliary materials, and the other four parts were mixed with 0-1%, 1-2%, 2-2.5%, 2.5-3.5% aspartame, Add appropriate amount of boiled water and take it after brewing. After many people tasted it, the quality of the taste was judged. The results are shown in the table.

Aspartame dosage form

The results show that the taste is moderate when 2-2.5% aspartame is added.

(2) Hygroscopicity test Take two parts of extract powder, add dextrin to one part, mix well, put them in flat weighing bottles that have been weighed, accurately weigh them, and measure them at a temperature of 25°C and a relative humidity of 75%. Its moisture absorption, the results are shown in the table.

(2) Research on forming process of dispersible tablet:

The dispersible tablet can be rapidly disintegrated in water to form a uniform viscous suspension water dispersible tablet, which solves the disadvantages of poor disintegration and slow dissolution of the original dosage form. Disintegration, good suspension, high bioavailability, uniformity of dispersion.

① Screening of accessories

Prescription PPVP(g) K30(%) Disintegration time/s

                     

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

②Disintegration time limit inspection

Using the rotating basket method, lifting disintegration apparatus, take 6 tablets, and observe the situation of passing through the sieve. The higher the pass rate, the better the disintegration, which is more suitable for human body absorption.

Disintegration time limit (s)

Group 1 2 3 4 5 6

1 batch of tablets of the present invention 15 20 18 18 17 13

2 batches of tablets of the present invention 15 21 17 14 15 15

3 batches of tablets of the present invention 15 18 18 12 16 17

The results show that 3.5g of PPVP is mixed with lemon yellow, 3/5 is mixed with extract powder, and 1.5% K30 absolute ethanol is used as a binder, 40 mesh is prepared and granulated, and the remaining 2/5PPVP1 .4g of the mixed powder mixed with lemon yellow is added to the prepared granules, and compressed into tablets, and the obtained dispersible tablet product is easy to disintegrate.

(3) Research on pill forming process:

The diameter of the micropill is less than 2.5mm, which is similar to the nature of the granule and has high bioavailability. When the applicant is developing the product micropill of the present invention, the biggest difficulty is that it has strong hygroscopicity, poor fluidity, poor plasticity, and is difficult to form. The pellet manufacturing technology and auxiliary materials screened by the applicant make the product easy to disintegrate, have high bioavailability and good properties.

1. Extrusion-spheronization pellet making

① Selection of types and dosage of auxiliary materials

Hygroscopicity test Take two parts of the extract powder, add starch to one part, mix well, put them in flat weighing bottles that you have weighed, weigh them accurately, measure the moisture absorption at a temperature of 25 °C and a relative humidity of 75%, and the result is see table.

Hygroscopicity Test Results

The results show that it is reasonable and feasible to use starch as auxiliary material.

②Preparation of soft material Take extract fine powder, starch, soybean oil and ethanol in appropriate amount to make soft material by wet granulation method, so that it can be held into a ball, pinched to disperse, and set aside. The research focuses on the influence of ethanol concentration and soybean oil dosage on pill making, and the experimental results are shown in the table.

Investigation of ethanol concentration

test number ethanol concentration Making soft materials 1 70 % ethanol Soft materials are easy to bond 2 65 % ethanol Moderate soft material 3 50 % ethanol The viscosity of the soft material is not enough

Investigation on Soybean Oil Consumption

test number Soybean oil dosage Pill making situation 1 65% ethanol, 1% soybean oil The viscosity of the soft material is not enough to make pellets 2 65% ethanol, 1.2% soybean oil Moderate soft material, suitable for making pellets 3 65% ethanol, 1.5% soybean oil Soft materials are easy to bond and difficult to make pellets

The results show that it is ideal to use 65% ethanol and 1.2% soybean oil as the binder for granulation, otherwise it is difficult to form.

③The prepared soft material is made into pellets with pellets, the wet material is squeezed through a 0.8mm sieve, the strip-shaped wet pellets are cut and rounded, dried at 50-60°C, and passed through 16-20 mesh to screen the pellets.

2. Pan-made legal pills

Due to the wetting effect of water and the extrusion of the rotation of the coating pan, the powder is bound into pellets. Due to the high viscosity of this product, when making pellets, the speed of spraying water is fast and the speed of adding powder is slow, which will prolong the time of forming pellets and make them stick tightly, making them hard after drying, which is not conducive to the infiltration of water and affects the dissolution and drug dissolution. absorption and utilization.

serial number Coating pan speed (r/min) Dissolution time (min) Formability 1 30 6.63 Poor 2 40 7.82 better 3 50 12.55 harder 4 70 14.98 hard 5 100 15.99 hard

The results showed that 40r/min was the best value for the rotational speed of the coating pan.

(4) Research on the molding process of soft capsules:

The soft capsule disintegrates quickly in the gastrointestinal tract, and the drug is quickly dispersed after the capsule shell is broken, so the drug releases and dissolves quickly, has a rapid effect, and has high bioavailability; the translucent soft capsule and better packaging materials can protect the drug from moisture Oxygen and light in air and air can improve the stability of unstable components; therefore, the stability and molding process of capsules are very critical technologies.

1. Selection of types and dosage of excipients

① Dispersion medium (or matrix) is selected under the premise that the filling material and matrix can be mixed evenly, and the material can be smoothly conveyed and pelletized, and the amount of matrix should be reduced as much as possible. Through multiple tests, it is determined that the amount of drug (g): the amount of base (g) = 1: 1.2 is appropriate, and the experimental results are shown in the table.

Substrate dosage investigation

Drug amount (g): base amount (g) 1:1 1:1.2 1:1.5

Liquid quality High viscosity, poor fluidity Good viscosity, fluidity Poor viscosity, high fluidity

②The capsule shell formula is selected according to the ingredient ratio in the table below, put it into a 500ml suction filter bottle, melt in a water bath at 65°C, automatically stir the glue, and vacuumize at the same time, the vacuum degree is about 0.095Mpa, keep it for 1 hour after 5 hours, and filter Glue solution, take a part of the glue solution to measure viscosity and other properties, spread a part of the glue solution evenly on the iron plate into a thin layer (first put a layer of liquid paraffin on the bottom), place it on the next day to observe the rubber performance and then evaluate it. The results of the investigation are represented by "+++", "++", "+", "-" in order from good to bad, and the results are shown in the table.

Screening results of rubber ingredients

Formula Viscosity and Softness Softness and Elasticity Toughness Features Comprehensive Evaluation

(mpa·s)

1. Gelatin: glycerin: water 3.61 - - - + + Brittle, poor hardness

(100g: 35g: 100g)

2. Gelatin: Glycerin: Water 3.35 + ++ ++ +++ Toughness and film-forming properties are very good

(100g: 45g: 100g)

3. Gelatin: Glycerin: Water 3.57 + ++ ++ + + Good elasticity General

(100g:55g:100g)

4. Gelatin: Glycerin: Water 3.72 ++ ++ ++ + + Good elasticity, high viscosity Very good

(100g: 45g: 80g)

5. Gelatin: Glycerin: Water 3.11 +++ + - - Too soft Poor

(100g: 45g: 120g)

6. Gelatin: Glycerin: Sorbitol: Water 3.43 - + + ++ ++ Toughness is better

(100g: 35g: 5g: 100g)

7. Gelatin: Glycerin: Sorbitol: Water 3.46 + + + + + Good piercing performance Very good

(100g: 35g: 10g: 100g)

8. Gelatin: Glycerin: Sorbitol: Water 3.52 ++ + + + + Toughness is better

(100g: 45g: 5g: 100g)

9. Gelatin: Glycerin: Sorbitol: Water 3.47 ++ ++ ++ - Soft General

(100g: 45g: 10g: 100g)

10. Gelatin: Glycerin: Sorbitol: Water 3.62 + + ++ ++ Better toughness

(100g: 25g: 10g: 100g)

11. Gelatin: Glycerin: Sorbitol: Water 3.57 + ++ ++ + + Good piercing performance Very good

(100g: 35g: 20g: 100g)

12. Gelatin: Glycerin: Sorbitol: Water 3.36 ++ ++ ++ + 0.5mm or less

(100g: 55g: 5g: 90g) It is better if the rubber is easy to break

13. Gelatin: Glycerin: Sorbitol: Water The glue is too thick to melt

(84g: 28g: 28g: 20g)

14. Gelatin: Gum Arabic: Glycerin: Water 3.57 - - - + + The color is gray Poor

(100g: 25g: 35g: 100g)

15. Gelatin: Gum Arabic: Glycerin: Water 3.51 - + + + Poor

(85g: 15g: 45g: 100g)

16. Gelatin: Gum Arabic: Glycerin: 3.39 + + + ++ ++ 0.2～0.8mm rubber

Sorbitol: Water (85g: 15g: 60g: 10g: 60g) High tear strength Very good

17. Gelatin: Gum Arabic: Sorbet 3.68 + - - - Crunchy Poor

Alcohol: glycerin: water (50g: 150g: 10g: 60g: 55g)

18. Gelatin: Gum Arabic: Glycerin: 3.52 + + + + Brittle grayish in color General

Sorbitol: Water (85g: 15g: 45g: 10g: 110g)

19. Gelatin: Gum Arabic: Glycerin: 3.38 + + + - - 0.85mm or less

Sorbitol: water (85g: 15g: 60g: 10g: 90g) Poor rubber elasticity General

20. Gelatin: Gum Arabic: Glycerin: 3.35 + - - + + The color is grayish General

Sorbitol: Water (100g: 25g: 45g: 5g: 100g)

Through the above screening and comprehensive evaluation, considering the characteristics of the filling material, formula 2 is selected, namely gelatin 100g: glycerin 45g: water 100g.

③Selection of sunscreen

The transparent capsule shell is prone to instability, so a certain amount of opacifying agent needs to be added. After investigation, choosing titanium dioxide (titanium dioxide) as the sunscreen can achieve an effective sunscreen effect, and the quality is stable, and it will not chemically change with the glue and filling materials. The amount of gelatin: glycerin: water: titanium dioxide = 100g: 45g: 100g: 2g is appropriate after investigation, and has little effect on the quality of the rubber. The results are shown in the table.

Choice of sunscreen dosage

Dosage Ratio Comprehensive Evaluation

(Mpa·S)

Gelatin 100g: Glycerin 45g: Water 100g: Titanium Dioxide 0.5g Translucent 3.12 The dosage is not enough

Gelatin 100g: Glycerin 45g: Water 100g: Titanium Dioxide 1g Translucent 3.29 The dosage is not enough

Gelatin 100g: Glycerin 45g: Water 100g: Titanium Dioxide 2g Translucent 3.56 Good

100g of gelatin: 45g of glycerin: 100g of water: 3g of titanium dioxide opaque 3.82 relatively high viscosity

The quality is more stable after adding sunscreen to the capsule formula.

2. Inspection of molding process conditions

①Examination of crushed particle size of extract

Crush the extract, pass through sieves of 60 mesh, 80 mesh, 100 mesh, and 120 mesh respectively, and grind it evenly with a colloid mill according to the ratio of extract: matrix=1:1.2, observe the mixing situation, and the results are shown in the table.

Study on the crushing particle size of the extract

Granularity 60 mesh 80 mesh 100 mesh 120 mesh

Mixing situation Unable to mix, can mix, high-speed centrifugation can mix, high-speed centrifugation can mix, high-speed centrifugation

high speed centrifugation

(10000/min) (10000/min) (10000/min) (10000/min)

30min stratification 30min no stratification 30min no stratification 30min no stratification

It can be seen from the above table that if the extract is crushed to 80 mesh, it can be mixed evenly, so the crushing mesh of the extract is selected as 80 mesh.

② Filling material mixing laboratory takes the extract and crushes it through an 80-mesh sieve, adds soybean oil according to extract: matrix = 1: 1.2, mixes evenly with a colloid mill, vacuumizes to remove air bubbles, and sets aside.

③Inspection of batching gelatinization According to the above-mentioned preferred formula, namely gelatin: glycerin: water: titanium dioxide = 100g: 45g: 100g: 2g, the batching was weighed, and gelatinization was performed at different temperatures. The results are shown in the table.

Chemical gel temperature investigation

Temperature (℃) Curing Time (H) Rubber Quality

50 6 ok

60 5 ok

70 5 ok

80 5 ok

90 4 4 Harder

As indicated by the table, the most suitable temperature for curing gel is 60-70°C. Therefore, the conditions for batching chemical glue are: weigh the ingredients, put them into the chemical glue tank, gradually heat up to 65±5°C after cold soaking for 30 minutes, stir for 5 hours and vacuumize at the same time to remove air bubbles, discharge the material after the rubber is uniform, and filter Put it into the rubber barrel of the capsule machine.

④Pellet pressing: Send the heat-preserved rubber material barrel and the medicine material barrel at normal temperature to the top of the capsule machine, connect with the machine, and debug the pill pressing machine. The thickness of the rubber is 0.8mm, the indoor temperature is 18-25°C, and the relative humidity is less than 40%. After the pill press is debugged, adjust the content of the pill to 400mg/grain. During the pilling process, the loading is measured every half an hour.

⑤Drying: Shaped drying. The soft capsules extruded by the pellet machine are sent to the tumbler by the conveyor belt. The tumbler is turned while blowing cold air, and the shape is turned and dried for about 2 hours. Tray drying The capsules dried by the cold air in the tumbler are placed in a clean stainless steel tray, and moved to a drying room with a temperature of about 22°C and a relative humidity of less than 40% for 48 hours, and constantly turning, the water content of the capsules is measured below 10%. That is suitable for drying. Notes on drying: Drying adopts the combination of two steps of rolling drying and tray drying. The rolling drying is suitable for two hours. If the time is too long, the surface will not be smooth. The drying temperature is about 22°C, and the drying temperature is too low. If the time is too long, the drying time can be shortened by increasing the temperature, but it is easy to cause cracks on the surface of the capsule; the relative humidity of the drying should be lower than 40% after investigation, otherwise it is not easy to dry; the drying time is about 24-48 hours to control the moisture in the 10% or less is fine.

(5) Research on dripping pill forming process:

① Matrix screening

Comparison of the fusion of matrix and main drug

Prescription No. Prescription 1 Prescription 2 Prescription 3 Prescription 4 Prescription 5 Prescription 6 Prescription 7

Medication (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

Main drug and matrix Main drug energy and Main drug energy and Main drug energy and matrix fusion Main drug and base Main drug energy and Main drug energy and

Fusion status Matrix fusion Matrix fusion System fluidity is very good Quality fusion is poor Matrix fusion Matrix fusion

but system system flow - but system system flow

                                                                        

Dropping pill appearance - Poor roundness Smooth Smooth - Poor roundness -

Good roundness Good roundness - Trailing -

Dropping Pill Hardness - Small Hardness Better Hardness Better Hardness - Better Hardness -

Pill weight difference - 20% 8.0% 12.5% - 20% -

Dissolution time limit (min) - 7～8 4～5 9～10 - 6～8 -

The results show that the drop pills made by the composite matrix are dissolved faster, because the polyethylene glycol matrix is esterified, and it is a surface-active water-soluble matrix (melting point is 46 ~ 51 ° C), and S-40 has changed Polyethylene glycols do not have lipophilic structure and surface active properties, which improve the solubility of poorly soluble drugs and facilitate the absorption of drugs.

②Selection of drop distance, drop speed and temperature: the inner and outer diameter of the drop opening is fixed at 2.0mm~2.5mm. Evaluation index: The qualified rate of pill weight is within ±10% according to the weight difference requirement of Part One of the Pharmacopoeia of the People's Republic of China (2005 Edition).

Group Temperature/℃ Drop Distance/cm Coolant Height/cm Pill Weight Qualification Rate/%

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 that the optimal condition of the preparation drop pill of the present invention: be dropped in the simethicone oil and form a pill, the drop distance is 5cm and the drop diameter is 2.5mm/2mm, the temperature of the mixed ointment is 80°C, and the cooling liquid height is 70cm.

Experimental example 2, part of pharmacodynamics research

Bioavailability Comparison

SD rats, body weight 250-280g, half male and half male, were fasted overnight (without water), and administered intragastrically the next day at a dosage of 3.8g/kg. Cardiac blood was collected before administration and at 15min, 3omin, somin, somin, 2h, 3h, 4h and 8h after administration. Six rats were used for each blood sample point. Put the blood sample in a heparin anticoagulant tube, centrifuge at 3000r/min for 5min, separate the plasma, store it at 30°C, and store it until analysis. The high performance liquid chromatograph consists of M510 pump, U6K sample injector, M490 variable wavelength detector and 810 chromatographic data processing station (Waters, USA). The analytical column is μBondPakaC ₁₈ (0.45mm×25cm); the mobile phase is methanol: 0.03mol/L sodium acetate = 25:75; flow rate: 0.8.mL/min; detection wavelength: λ = 238nm. Codeine phosphate extraction in plasma: take 0.5mL plasma, add 5mL CHC ₁₃ , internal standard 50μl, place the test tube on a shaker inclined at 30° in the horizontal direction, shake and extract for 15min, centrifuge (3000r/min) for 10min, discard the water phase , Precisely pipette 4mL of the organic phase into a clean test tube, dry it in a water bath at 37°C, and dry it under N ₂ flow, redissolve the residue with 200μl mobile phase, and inject the sample for analysis.

Changes of Plasma Codeine Phosphate Concentration in Rats

(N=6) Time/h plasma codeine phosphate concentration/(mg·L ^-1 )

Dispersible tablets of the present invention Dropping pills of the present invention Micropills of the present invention Soft capsules of the present invention Granules of the present invention Capsules of the present invention Dropping pills 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 results show that the bioavailability of the product of the invention is greater than that of the capsules prepared by the prior art.

Experimental example 3, pharmacological action research:

1, the present invention causes the antitussive effect of guinea pig to citric acid

Principle: Citric acid is highly irritating. After spray inhalation, it stimulates the guinea pig's respiratory receptors and reflexively causes coughing.

Method: 150-200g guinea pigs, orally administered. The first group was given the present invention, the second group was given normal saline with the same volume, and the third group was given codeine (5 mg/kg). Half an hour later, spray sodium citrate solution at 0.2-0.5 atmospheric pressure for 10 seconds. One day before the experiment, the animals were screened, and those who did not cough within 120 seconds were not used. Record the incubation period of each guinea pig's cough respectively (the time from the end of spraying to the first cough is the incubation period). Record the experimental results, compare the administration group with the control group, and carry out statistical processing.

Results: The present invention can prolong the cough latency, and the reference values are shown in the table below.

Antitussive effect of the present invention (X±SD) (n=10)

group Dose (g/kg) Cough latency (s) Physiological saline codeine present invention 50ml5mg2.0 51.9±3.18144±2.14 ^** 295±18.13 ^**

According to the experimental data, the cough latency of the two groups of guinea pigs given codeine and the present invention was significantly longer than that of the normal saline group, p<0.05. Prompt that the drug has a strong cough-relieving effect.

2, the antiasthmatic effect of the present invention

Principle: This experiment uses histamine phosphate to create an asthma model to observe the anti-asthma effect of the present invention.

Method: A few juvenile guinea pigs weighing 150-200 g were preselected in the preparation room one day before the experiment, and placed in the spray box respectively, and sprayed with 1 mg/ml histamine phosphate and 1 ml into the device box at a pressure of 53.3-66.6 kPa (400-500 mmHg). After a certain incubation period after inhaling the above medicinal liquid, the animals will develop an asthmatic reaction. According to the procedure, the "asthmatic" reaction can be divided into four grades, grade I breathing acceleration, grade II dyspnea, grade III convulsions, and grade IV fall. Most animals have grade III or grade IV reactions within 90S; generally no more than 150S, those over 150S can be considered insensitive and should not be used. As soon as the animal convulsed, the door of the box was opened to take out the animal, and if necessary, artificial respiration was provided to prevent the animal from dying due to suffocation.

The next day, the preselected "asthma" guinea pigs were randomly divided into 3 groups, 10 in every group, group A was given 1.g/ml of the present invention 10g/kg, and group B was given 0.5g/ml of the present invention 10g/kg. Group C was fed with the same volume of normal saline, repeated administration once 15 minutes after administration, and 30 minutes after administration, put them into the spray device and sprayed histamine phosphate respectively under the same conditions when pre-selected. Record the time from the start of spraying to the onset of symptoms (based on convulsions and falls) as the incubation time, and it is considered effective if the incubation time is doubled. (see table below).

Antiasthmatic effect of the present invention (X±SD) (n=10)

group Dosage (10g/kg) Incubation period (S) Physiological saline present invention present invention Equivalent volume 2.0g/ml1.0g/ml 100331**289**

Results: The present invention can significantly prolong the latent period of asthma induction, compared with the control group, there is a significant difference, p<0.05. Prompt that the drug has a strong antiasthmatic effect.

Specific implementation methods:

Embodiment 1 of the present invention: preparation 1 of tablet

Take 24g of auspicious grass, 16g of poppy shell, 12g of short ground tea, 12g of saxifrage, 12g of loquat leaves, 4g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry, add 30g of starch and 15g of sodium carboxymethyl starch to make pellets with a particle size of less than 2mm, or microcapsules with a particle size of less than 2mm, and dry , granulate, compressed, and coated to obtain the tablet of the present invention. Oral, three times a day, 2 tablets each time.

Embodiment 2 of the present invention: preparation 2 of tablet

Take 45g of auspicious grass, 30g of poppy shell, 23g of short ground tea, 15g of saxifrage, 15g of loquat leaves, 5g of Morus alba, and decoct twice with water for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry, add 30g of starch and 15g of sodium carboxymethyl starch to make pellets with a particle size of less than 2mm, or microcapsules with a particle size of less than 2mm, and dry , granulate, compressed, and coated to obtain the tablet of the present invention.

Embodiment 3 of the present invention: preparation 3 of tablet

Take 30g of auspicious grass, 20g of poppy shell, 15g of short ground tea, 23g of saxifrage, 23g of loquat leaves, 8g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry, add 30g of starch and 15g of sodium carboxymethyl starch to make pellets with a particle size of less than 2mm, or microcapsules with a particle size of less than 2mm, and dry , granulate, compressed, and coated to obtain the tablet of the present invention.

Embodiment 4 of the present invention: preparation 1 of soft capsule

Take 24g of auspicious grass, 20g of poppy shell, 23g of short ground tea, 12g of saxifrage, 15g of loquat leaves, and 8g of mulberry bark. Add water and decoct twice for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When measuring relative density to 40 DEG C, be the clear ointment of 1.20～1.25, spray dry, mix; Add soybean oil by drug amount: base quantity=1: 1.2, mix; The formula of rubber is gelatin: glycerin: water: titanium dioxide= 100g: 45g: 100g: 2g, the batching and chemical conditions are as follows: weigh the ingredients, put them into the chemical tank, cold soak for 30 minutes, then gradually heat up to 65±5°C, stir for 5 hours and vacuumize at the same time to remove air bubbles. After uniformity, discharge the material, filter and put it into the rubber material barrel of the capsule machine; debug the pill press machine, control the temperature of the gelatin box at 65°C, the temperature control of the injection at 45°C, the speed of the rolling die at 2.0, the thickness of the rubber skin at 0.8mm, and the indoor temperature at 18～ 25 ℃, relative humidity is less than 40%, press pellets; drying adopts two-step combination of rolling drying and tray drying, rolling drying for 2 hours, drying temperature 22 ℃, dry relative humidity should be lower than 40%, drying time is 24 ~ 48 hours, that is. Take orally, three times a day, 2 capsules each time.

Embodiment 5 of the present invention: preparation 2 of soft capsule

Take 45g of auspicious grass, 16g of poppy shell, 15g of short ground tea, 23g of saxifrage, 12g of loquat leaves, 5g of Morus alba bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When measuring relative density to 40 DEG C, be the clear ointment of 1.20～1.25, spray dry, mix; Add soybean oil by drug amount: base quantity=1: 1.2, mix; The formula of rubber is gelatin: glycerin: water: titanium dioxide= 100g: 45g: 100g: 2g, the batching and chemical conditions are as follows: weigh the ingredients, put them into the chemical tank, cold soak for 30 minutes, then gradually heat up to 65±5°C, stir for 5 hours and vacuumize at the same time to remove air bubbles. After uniformity, discharge the material, filter and put it into the rubber material barrel of the capsule machine; debug the pill press machine, control the temperature of the gelatin box at 65°C, the temperature control of the injection at 45°C, the speed of the rolling die at 2.0, the thickness of the rubber skin at 0.8mm, and the indoor temperature at 18～ 25 ℃, relative humidity is less than 40%, press pellets; drying adopts two-step combination of rolling drying and tray drying, rolling drying for 2 hours, drying temperature 22 ℃, dry relative humidity should be lower than 40%, drying time is 24 ~ 48 hours, that is.

Embodiment 6 of the present invention: preparation 3 of soft capsule

Take 30g of auspicious grass, 30g of poppy shell, 12g of short ground tea, 15g of saxifrage, 23g of loquat leaves, 4g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When measuring relative density to 40 DEG C, be the clear ointment of 1.20～1.25, spray dry, mix; Add soybean oil by drug amount: base quantity=1: 1.2, mix; The formula of rubber is gelatin: glycerin: water: titanium dioxide= 100g: 45g: 100g: 2g, the batching and chemical conditions are as follows: weigh the ingredients, put them into the chemical tank, cold soak for 30 minutes, then gradually heat up to 65±5°C, stir for 5 hours and vacuumize at the same time to remove air bubbles. After uniformity, discharge the material, filter and put it into the rubber barrel of the capsule machine; debug the pellet machine, control the temperature of the gelatin box at 65°C, the temperature control of the injection at 45°C, the speed of the rolling die at 2.0, the thickness of the rubber skin at 0.8 mm, and the indoor temperature at 18～ 25 ℃, relative humidity is less than 40%, press pellets; drying adopts two-step combination of rolling drying and tray drying, rolling drying for 2 hours, drying temperature 22 ℃, dry relative humidity should be lower than 40%, drying time is 24 ~ 48 hours, that is.

Embodiment 7 of the present invention: granule preparation 1

Take 24g of auspicious grass, 16g of poppy shell, 15g of short ground tea, 15g of saxifrage, 23g of loquat leaves, 8g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry it, and mix it; add 2% aspartame and 25 g of dextrin, mix it, and granulate it.

Embodiment 8 of the present invention: granule preparation 2

Take 30g of auspicious grass, 20g of poppy shell, 23g of short ground tea, 23g of saxifrage, 12g of loquat leaf, 4g of Morus alba bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When the temperature reaches 40°C, measure the clear ointment with a relative density of 1.20 to 1.25, spray dry it, and mix it; add 2.5% aspartame and 25 g of dextrin, mix it, and granulate it.

Embodiment 9 of the present invention: preparation of granules 3

Take 45g of auspicious grass, 30g of poppy shell, 12g of short ground tea, 12g of saxifrage, 15g of loquat leaf, 5g of Morus alba bark, decoct twice with water, 2 hours each time, combine decoction and filter, and concentrate the filtrate to Measure the clear ointment with a relative density of 1.20 to 1.25 at 40°C, spray dry it, and mix it; add 2.25% aspartame and 25 g of dextrin, mix it, and granulate it.

Embodiment 10 of the present invention: Preparation 1 of dispersible tablet

Take 24g of auspicious grass, 30g of poppy shell, 23g of short ground tea, 23g of saxifrage, 23g of loquat leaves, and 8g of mulberry bark, decoct twice with water for 2 hours each time, combine and decoct, filter, and concentrate the filtrate At 40°C, measure the clear cream with a relative density of 1.20 to 1.25, spray dry it, and mix it; take 3.5 g of crospovidone and 1.5 g of lemon yellow and mix it evenly, take 3/5 and mix it with the extract powder, and use 1.5 % K30 absolute ethanol solution as binder, 40 mesh material preparation, granulation, the remaining 2/5 crospovidone and tartrazine mixed powder are added to the prepared granules, and compressed into tablets to obtain .

Embodiment 11 of the present invention: Preparation 2 of dispersible tablet

Take 45g of auspicious grass, 16g of poppy shell, 15g of short ground tea, 12g of saxifrage, 15g of loquat leaves, 8g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate At 40°C, measure the clear cream with a relative density of 1.20 to 1.25, spray dry it, and mix it; take 3.5 g of crospovidone and 1.5 g of lemon yellow and mix it evenly, take 3/5 and mix it with the extract powder, and use 1.5 % K30 absolute ethanol solution as binder, 40-mesh material preparation, granulation, the remaining 2/5 crospovidone and tartrazine mixed powder are added to the prepared granules, and compressed into tablets to obtain .

Embodiment 12 of the present invention: Preparation 3 of dispersible tablet

Take 30g of auspicious grass, 20g of poppy shell, 12g of short ground tea, 15g of saxifrage, 12g of loquat leaves, 5g of Morus alba bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate At 40°C, measure the clear cream with a relative density of 1.20 to 1.25, spray dry it, and mix it; take 3.5 g of crospovidone and 1.5 g of lemon yellow and mix it evenly, take 3/5 and mix it with the extract powder, and use 1.5 % K30 absolute ethanol solution as binder, 40-mesh material preparation, granulation, the remaining 2/5 crospovidone and tartrazine mixed powder are added to the prepared granules, and compressed into tablets to obtain .

Embodiment 13 of the present invention: pellet preparation 1

Take 45g of auspicious grass, 16g of poppy shell, 23g of short ground tea, 15g of saxifrage, 12g of loquat leaves, 5g of Morus alba bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20-1.25 at 40°C, spray dry, add 20g of starch, and use 65% ethanol and 1.2% soybean oil to make a soft material. The prepared soft material is pelletized with a pellet machine, and the wet material is extruded Pass through a 0.8mm sieve, cut and round the strip-shaped wet granules, dry and shape at 50-60°C, pass through 16-mesh screened pellets or combine the above four clear pastes, spray dry, granulate the wet powder and start the mold, and put the mold in the coating pan Internally amplify into pills, the ratio of powder: water is 1:1.2, the rotation speed of the coating pan is 40r/min, cover the surface, select the pills, and the product is ready.

Embodiment 14 of the present invention: pellet preparation 2

Take 30g of auspicious grass, 16g of poppy shell, 15g of short ground tea, 23g of saxifrage, 12g of loquat leaves, and 8g of mulberry bark, decoct twice with water for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20-1.25 at 40°C, spray dry, add 20g of starch, and use 65% ethanol and 1.2% soybean oil to make a soft material. The prepared soft material is pelletized with a pellet machine, and the wet material is extruded Pass through a 0.8mm sieve, cut and round the strip-shaped wet granules, dry and shape at 50-60°C, pass through 18-mesh screened pellets or combine the above four clear pastes, spray dry, granulate the wet powder and release the mold, and put the mold in the coating pan Internally amplify into pills, the ratio of powder: water is 1:1.2, the rotation speed of the coating pan is 40r/min, cover the surface, select the pills, and the product is ready.

Embodiment 15 of the present invention: pellet preparation 3

Take 30g of auspicious grass, 16g of poppy shell, 23g of short ground tea, 23g of saxifrage, 15g of loquat leaves, 4g of mulberry bark and decoct twice with water for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20-1.25 at 40°C, spray dry, add 20g of starch, and use 65% ethanol and 1.2% soybean oil to make a soft material. The prepared soft material is pelletized with a pellet machine, and the wet material is extruded Pass through a 0.8mm sieve, cut and round the strip-shaped wet granules, dry and form at 50-60°C, pass through 20-mesh screened pellets or combine the above four clear pastes, spray dry, granulate the wet powder and release the mold, and put the mold in the coating pan Internally amplify into pills, the ratio of powder: water is 1:1.2, the rotation speed of the coating pan is 40r/min, cover the surface, select the pills, and the product is ready.

Embodiment 16 of the present invention: drop pill preparation 1

Take 45g of auspicious grass, 30g of poppy shell, 23g of short ground tea, 23g of saxifrage, 23g of loquat leaves, 8g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry, and mix well; take the extract powder, two parts of polyethylene glycol 4000 and one part of polyoxyethylene monostearate S-40, and mix well , melt on a water bath, stir well, drop into simethicone oil to form pellets, drop distance 5cm, drop diameter 2.5mm/2mm, mix ointment temperature 80°C, cooling liquid height 70cm, that is.

Embodiment 17 of the present invention: drop pill preparation 2

Take 30g of auspicious grass, 20g of poppy shell, 15g of short ground tea, 15g of saxifrage, 15g of loquat leaf, 5g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry, and mix well; take the extract powder, two parts of polyethylene glycol 4000 and one part of polyoxyethylene monostearate S-40, and mix well , melt on a water bath, stir well, drop into simethicone oil to form pellets, drop distance 5cm, drop diameter 2.5mm/2mm, mix ointment temperature 80°C, cooling liquid height 70cm, that is.

Embodiment 18 of the present invention: drop pill preparation 3

Take 24g of auspicious grass, 30g of poppy shell, 12g of short ground tea, 23g of saxifrage, 12g of loquat leaves, 8g of mulberry bark and decoct twice with water for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate Measure the clear paste with a relative density of 1.20 to 1.25 at 40°C, spray dry, and mix well; take the extract powder, two parts of polyethylene glycol 4000 and one part of polyoxyethylene monostearate S-40, and mix well , melt on a water bath, stir well, drop into simethicone oil to form pellets, drop distance 5cm, drop diameter 2.5mm/2mm, mix ointment temperature 80°C, cooling liquid height 70cm, that is.

Example 19 of the present invention: preparation of oral liquid preparation 1

Take 30g of auspicious grass, 30g of poppy shell, 15g of short ground tea, 23g of saxifrage, 15g of loquat leaves, and 8g of mulberry bark. Add water and decoct twice for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When the temperature reaches 40°C, the clear ointment with a relative density of 1.20-1.25 is measured, spray-dried, and mixed; add distilled water and 2% aspartame, and sterilize to obtain the product.

Example 20 of the present invention: preparation of oral liquid preparation 2

Take 24g of auspicious grass, 20g of poppy shell, 12g of short ground tea, 15g of saxifrage, 12g of loquat leaves, 5g of Morus alba, and decoct twice with water for 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When the temperature reaches 40°C, the clear ointment with a relative density of 1.20 to 1.25 is measured, spray-dried, and mixed; add distilled water and 2.5% aspartame, and sterilize to obtain the product.

Example 21 of the present invention: preparation of oral liquid preparation 3

Take 24g of auspicious grass, 20g of poppy shell, 15g of short ground tea, 23g of saxifrage, 23g of loquat leaves, 4g of mulberry bark, decoct twice with water, 2 hours each time, decoct and filter together, filter, and concentrate the filtrate When the temperature reaches 40°C, the clear ointment with a relative density of 1.20-1.25 is measured, spray-dried, and mixed; add distilled water and 2.3% aspartame, and sterilize to obtain the product.

Claims (1)

1. The preparation method of Zhike Pingchuan soft capsule is characterized in that: take 30g of auspicious grass, 20g of poppy shell, 15g of short tea, 15g of saxifrage, 15g of loquat leaf, 5g of Morus alba, and decoct twice , each 2 hours, combined decoction, filtered, and when the filtrate was concentrated to 40 ° C, the relative density was measured as a clear paste of 1.20 to 1.25, spray-dried, and mixed; add soybean oil by drug amount: base amount=1: 1.2, Mix evenly; the formula of rubber is gelatin: glycerol: water: titanium dioxide: 100g: 45g: 100g: 2g, the condition of batching chemical glue is: weigh batching, drop into chemical glue tank, after cold soaking for 30 minutes, gradually warming up to 65 ± 5 ℃, stirred for 5 hours and vacuumed to remove air bubbles at the same time, discharged after the rubber material was uniform, filtered and loaded into the rubber material barrel of the capsule machine; debugged the pill press machine, the temperature control of the gelatin box was 65 ℃, and the temperature control of the spray was 45 ℃ , rolling mold speed 2.0, rubber thickness 0.8mm, indoor temperature 18-25°C, relative humidity less than 40%, press pellets: drying adopts two-step combination of rolling shaping drying and tray drying, rolling shaping drying for 2 hours, drying temperature 22°C, The drying relative humidity should be lower than 40%, and the drying time should be 24-48 hours.