CN118161576B - Preparation method of Chinese patent medicine granules for treating cold - Google Patents

Abstract

The application belongs to the technical field of pharmacy, and provides a preparation method of Chinese patent medicine granules for treating cold, which comprises the following steps: decocting herba Schizonepetae, herba Menthae, and folium Perillae with water to obtain volatile oil, decoction and residue; adding bupleuri radix, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodi, herba Violae, rhizoma Phragmitis, radix Puerariae and semen Armeniacae amarum into the residue, decocting with water, mixing the obtained filtrate with the decoction, and concentrating to obtain extract; granulating the extract, dextrin, arabinose and microcrystalline cellulose by using a one-step granulating method; further preparing the granules obtained by granulating and the volatile oil into Chinese patent medicine granules; wherein the mass ratio of the arabinose to the microcrystalline cellulose is (1-100): 1; the folium Perillae is one-sided purple and does not contain tender branch. The method of the application adopts arabinose and microcrystalline cellulose as auxiliary materials and adopts a one-step granulation method for granulation, which can improve the solubility and puerarin content of the granules, ensure the uniformity of the granules and enlarge applicable crowds.

Description

Preparation method of Chinese patent medicine granules for treating cold

Technical Field

The application belongs to the technical field of pharmacy, and particularly relates to a preparation method of Chinese patent medicine granules for treating cold.

Background

The common cold is a common and frequently encountered disease in clinic, and clinically manifested by symptoms such as fever, headache, sneeze, sore throat, weakness, ache, etc., and has high incidence rate and large drug demand.

The cold heat-clearing granule is a special medicine for treating diseases such as exogenous wind evil, has the effects of dispelling wind and cold, relieving exterior syndrome and clearing heat, is mainly used for treating wind-cold, and can obviously treat symptoms such as headache and fever, aversion to cold and body pain, nasal discharge and dry throat, and the like. The granule for treating common cold is prepared from eleven medicinal materials including perilla leaf, kudzuvine root, divaricate saposhnikovia root and the like by extracting and processing.

In the traditional preparation process of the cold and heat clearing granule, sucrose and dextrin are usually adopted as auxiliary materials for wet granulation. Therefore, the cold-clearing granules prepared by the traditional preparation method have the following problems: 1. the drying time is long, the heating time of the product is long, and the index components are low; 2. wet granulating to obtain granule with high hardness, and dissolving to obtain a small amount of Jiao Zhayang insoluble substances; 3. the auxiliary materials contain sucrose, so that the use is not suitable for diabetics.

Disclosure of Invention

Aiming at the problems existing in the prior art, the application provides a preparation method of Chinese patent medicine granules for treating cold.

In particular, the application relates to the following aspects:

1. A preparation method of Chinese patent medicine granules for treating cold, wherein the preparation method comprises the following steps:

decocting herba Schizonepetae, herba Menthae, and folium Perillae with water to obtain volatile oil, decoction and residue;

adding bupleuri radix, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodi, herba Violae, rhizoma Phragmitis, radix Puerariae and semen Armeniacae amarum into the residue, decocting with water, mixing the obtained filtrate with the decoction, and concentrating to obtain extract;

granulating the extract, dextrin, arabinose and microcrystalline cellulose by using a one-step granulating method;

further preparing the granules obtained by granulating and the volatile oil into Chinese patent medicine granules;

wherein the mass ratio of the arabinose to the microcrystalline cellulose is (1-100): 1;

the perilla leaf is purple-sided and does not contain a tender branch.

2. The production method according to item 1, wherein the mass ratio of arabinose to microcrystalline cellulose is (20-30): 1.

3. The preparation method according to item 1, wherein the mass ratio of the sum of arabinose and microcrystalline cellulose to the extract is (1-2): 2.

4. The preparation method according to item 1, wherein the mass ratio of dextrin to extract is 1:4.

5. The preparation method according to item 1, wherein the inlet air temperature is less than or equal to 115 ℃ and the outlet air temperature is less than or equal to 80 ℃ during one-step granulation, and the compressed air pressure is 0.4MPa.

6. The method according to item 1, wherein the extract has a relative density of 1.32 to 1.35 at 50 ℃.

7. The preparation method according to item 1, wherein the schizonepeta spike, peppermint and perilla leaf are decocted with water and extracted for 4 hours by adopting a heating reflux mode.

8. The preparation method of item 1, wherein adding radix bupleuri, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodonis, herba Violae, rhizoma Phragmitis, radix Puerariae, and semen Armeniacae amarum into the residue, and extracting with water for 1.5 hr for 2 times.

9. The preparation method according to item 1, wherein the Chinese patent drug particles are prepared from the following raw materials in parts by weight:

herba schizonepetae 200, peppermint 60, divaricate saposhnikovia root 100, bupleurum 100, perilla leaf 60, kudzuvine root 100, platycodon root 60, bitter apricot seed 80, dahurian angelica root 60, bunge corydalis herb 200 and reed rhizome 160.

Advantageous effects

According to the method, the arabinose and the microcrystalline cellulose are used for replacing sucrose to serve as auxiliary materials, and the one-step granulating method is used for granulating, so that the solubility and the puerarin content of the granules can be improved, the appearance and the uniformity of the granules can be ensured, and applicable crowds are enlarged. In addition, the method can ensure high total flavone content by selecting the dried medicinal materials which are purple and do not contain twigs from the purple perilla She Shanmian, and can further improve the oil yield in the step of the volatile oil.

The Chinese patent medicine particles prepared by the method can be melted completely within 1 minute at the highest speed, the puerarin content reaches 0.23%, and the oil yield of the perilla leaves can reach 1.2ml/100g. The method of the application improves the oil yield of the perilla leaves, the solubility of the Chinese patent medicine particles and the puerarin content, so that the drug effect of the Chinese patent medicine particles is improved compared with the existing cold and heat clearing particles, and the adverse effect is reduced.

Drawings

FIG. 1 is a photograph of purple perilla leaf;

FIG. 2 is a photograph of purple perilla leaf;

FIG. 3 is a photograph of a purple-purple-purple perilla leaf dry medicinal material without shoots;

FIG. 4 shows the purple perilla leaf and contains photographs of the dry medicinal material of the shoots;

FIG. 5 is a photograph of a purple-faced perilla leaf and a tender branch-containing dry medicinal material.

Detailed Description

The application will be further illustrated with reference to the following examples, which are to be understood as merely further illustrating and explaining the application and are not to be construed as limiting the application.

Unless defined otherwise, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the materials and methods are described herein below. In case of conflict, the present specification, including definitions therein, will control and materials, methods, and examples, will control and be in no way limiting. The application is further illustrated below in connection with specific examples, which are not intended to limit the scope of the application.

The application provides a preparation method of Chinese patent medicine granules for treating cold, which comprises the following steps:

Step 1: decocting herba Schizonepetae, herba Menthae, and folium Perillae with water to obtain volatile oil, decoction and residue;

step 2: adding bupleuri radix, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodi, herba Violae, rhizoma Phragmitis, radix Puerariae and semen Armeniacae amarum into the residue, decocting with water, mixing the obtained filtrate with the decoction, and concentrating to obtain extract;

Step 3: granulating the extract, dextrin, arabinose and microcrystalline cellulose by using a one-step granulating method;

step 4: and further preparing the granules obtained by granulating and the volatile oil into Chinese patent medicine granules.

In the step 1, the perilla leaves are dried medicinal materials which are purple on one side and do not contain twigs.

The folium Perillae medicinal material is described as dried leaf or leaf-carrying twig of Perillae herba of Labiatae according to classical books such as pharmacopoeia, chinese medicinal dictionary, and Chinese cortex Fraxini medicinal material, and has the shape of green upper surface, purple lower surface (i.e. Perilla She Shanmian purple as shown in figure 1) or purple both sides (i.e. purple both sides of folium Perillae as shown in figure 2). The sources of the perilla leaves are recorded in the Chinese medicine dictionary and are divided into 'perilla' and 'wild perilla'; in addition, according to the records of Chinese dao Di medicinal materials, purple perilla is firstly carried in Ming Yi Bie Lu (miscellaneous records of famous physicians), and Ben Cao Jing Ji Zhu (materia Medica concentrated injection) cloud: purple leaves, very fragrant smell, no purple smell, no common perilla, and many common perilla herb, the tea should be used.

The dried medicinal materials of the purple perilla She Shanmian and the purple perilla She Shuangmian can be formed by leaves only, namely, the dried medicinal materials do not contain the tender branches of the purple perilla, and can also be the leaves of the purple perilla containing the tender branches. The perilla leaves, which generally contain shoots, are taken from the end third of the perilla, and this part of the shoots and leaves are taken as a whole.

For example, fig. 3 shows a dried medicinal material of purple perilla She Shanmian without twigs, and it can be seen from the figure that the medicinal material only contains perilla leaves per se and does not contain perilla twigs. Fig. 4 shows a dried medicinal material containing the purple tender branch of the perilla She Shanmian, and the medicinal material can be seen to contain not only the perilla leaf per se but also the tender branch of the perilla. In the same way as described above, FIG. 5 shows the dried herbal material of purple double-sided purple of perilla leaf containing shoots.

According to the report of the literature, the content of the total flavonoids in the perilla leaves with single-sided purple can reach 7.49%, which is 31% higher than the content of the total flavonoids in the perilla leaves with other types by 5.69%, and is nearly doubled than the content of the total flavonoids in the perilla leaves with tender branches by 3.76%. The total flavone has antipyretic, antibacterial, antiemetic, antiinflammatory, antiallergic etc. activities, and is a key substance for treating and relieving common cold symptoms.

According to the preparation method disclosed by the application, for the perilla leaves which are raw material medicines, the perilla She Shanmian purple and dried medicines without twigs are selected, so that the high total flavone content can be ensured, and meanwhile, the oil yield of the perilla leaves in the step of volatile oil can be further improved.

In a specific embodiment, when the schizonepeta spike, the peppermint and the perilla leaf are decocted with water for extraction, a heating reflux mode is adopted for 4 hours. Specifically, water with the quantity of 10-20 times of that of the medicinal materials can be used for extraction, namely, the mass of the water is 10-20 times of that of the three medicinal materials including schizonepeta spike, peppermint and perilla leaf.

And (3) after the extraction in the step (1) is finished, obtaining volatile oil, decoction and dregs. Wherein the decoction is water solution obtained after distillation.

In step 2, radix bupleuri, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodonis, herba Violae, rhizoma Phragmitis, radix Puerariae, and semen Armeniacae amarum are added into the residues, and the decoction is carried out for 2 times for 1.5 hours each time. Compared with single decoction, 2 times of decoction and extraction can provide the utilization rate of the raw medicinal materials.

In a specific embodiment, the extract has a relative density of 1.32-1.35 at 50 ℃.

It will be understood by those skilled in the art that the step of concentrating to obtain an extract may be performed in multiple times, or may be performed in one time.

In step 3, arabinose and microcrystalline cellulose were used instead of sucrose and granulated using a one-step granulation method. The mass ratio of arabinose to microcrystalline cellulose is (1-100): 1, and may be 1:1、2:1、5:1、10:1、15:1、20:1、25:1、30:1、35:1、40:1、45:1、50:1、55:1、60:1、65:1、70:1、75:1、80:1、85:1、90:1、95:1、100:1, or any value between these values.

In a specific embodiment, the mass ratio of arabinose to microcrystalline cellulose is (10-50): 1.

In a specific embodiment, the mass ratio of arabinose to microcrystalline cellulose is (20-30): 1.

In the existing granulation process of Chinese patent medicine granules for treating cold, sucrose is generally required to be granulated by adopting a wet method, wherein the sucrose can be used as a flavoring agent and an adhesive. The Chinese patent medicine particles prepared by the method have long drying time and low index components such as puerarin caused by long heating time; wet granulating to obtain granule with high hardness, and dissolving to obtain a small amount of Jiao Zhayang insoluble substances; in addition, the auxiliary materials contain sucrose, so that the use of the medicine is not suitable for diabetics, and the applicable population of the medicine is limited.

According to the application, the arabinose is used for replacing sucrose as the flavoring agent, so that the rise of blood sugar caused by sucrose intake can be inhibited, and the applicable population of the medicine is expanded.

Further, the applicant has unexpectedly found that by compounding arabinose and microcrystalline cellulose in a certain mass ratio, the effects of the flavoring agent and the adhesive can be provided, the integrity and uniformity of the Chinese patent medicine particles are ensured, and the dissolution rate of the Chinese patent medicine particles is accelerated. And granulating by combining a one-step granulating method, the granulating time can be greatly reduced, so that the heating time of materials is shortened, and the content of main index components such as puerarin is improved.

The extract, dextrin and sucrose are granulated by a one-step granulating method, for example, the granulating can be performed in a boiling granulator.

In a specific embodiment, the one-step granulation is performed in a ebullated granulator.

In a specific embodiment, the inlet air temperature is less than or equal to 115 ℃ and the outlet air temperature is less than or equal to 80 ℃ during one-step granulation, and the compressed air pressure is 0.4MPa.

In a specific embodiment, the mass ratio of arabinose to extract is (1-2): 2, for example, may be 1:2, 1.2:2, 1.5:2, 1:8, 1:1, and any range between these values.

In a specific embodiment, the mass ratio of arabinose, microcrystalline cellulose and extract is 1:0.04:2.

In a specific embodiment, the mass ratio of dextrin to extract is 1:4.

In the step 4, the granules prepared in the step 3 and the volatile oil obtained in the step 1 are further prepared into a final product, namely Chinese patent medicine granules.

In a specific embodiment, the Chinese patent medicine particles are prepared from the following raw materials in parts by weight: herba schizonepetae 200, peppermint 60, divaricate saposhnikovia root 100, bupleurum 100, perilla leaf 60, kudzuvine root 100, platycodon root 60, bitter apricot seed 80, dahurian angelica root 60, bunge corydalis herb 200 and reed rhizome 160.

According to the method, the arabinose and the microcrystalline cellulose with certain mass ratio are used for replacing sucrose to serve as auxiliary materials, and a one-step granulating method is used for granulating, so that the integrity and the uniformity of the Chinese patent medicine granules can be ensured while the flavoring agent is provided, and the dissolution rate of the Chinese patent medicine granules is accelerated; the granulating time can be greatly reduced, so that the heating time of the material is shortened, and the content of main index components such as puerarin is improved; can enlarge the applicable crowd. In addition, the perilla She Shanmian purple and the dried medicinal materials without twigs are selected, so that the high total flavone content can be ensured, and the oil yield in the step of the volatile oil can be further improved.

Examples

The perilla leaves used in the following examples and comparative examples were purchased from Anhui Zheng and Tang decoction pieces of Chinese medicine Co., ltd.

Example 1

The prescription amounts are as follows:

200g of schizonepeta spike, 60g of peppermint, 100g of divaricate saposhnikovia root, 100g of Chinese thorowax root, 60g of perilla leaf (purple perilla She Shanmian and dry medicinal materials without twigs), 100g of kudzuvine root, 60g of platycodon root, 80g of bitter apricot seed, 60g of dahurian angelica root, 200g of bunge corydalis herb and 160g of reed rhizome.

Step 1

Weighing herba Schizonepetae, herba Menthae, and folium Perillae according to the amount, adding 4.8kg water, and heating and refluxing for 4 hr to obtain volatile oil. The distilled aqueous solution was collected in another vessel.

Step 2

Decocting the residue obtained in step 1 and the rest eight medicinal materials such as radix Saposhnikoviae with 11.8kg water for 2 times each for 1.5 hr, mixing decoctions, and filtering. The filtrate was combined with the aqueous solution collected in step 1. Concentrating the combined solution into an extract with the relative density of 1.32-1.35 (50 ℃).

Step 3

400.0G of extract is taken, 200.0g of L-arabinose, 100g of dextrin and 8.0g of microcrystalline cellulose are added for one-step granulation. Wherein the mass ratio of the extract to the L-arabinose to the dextrin to the microcrystalline cellulose is 1:0.5:0.25:0.02.

The specific process of one-step granulation is as follows: granulation was performed using a boiling granulator type FL-200. Adding auxiliary materials into a material cavity, pushing the auxiliary materials into a main machine, starting a fan, controlling the air inlet temperature to be less than or equal to 115 ℃ and the air outlet temperature to be less than or equal to 80 ℃ to mix the materials for 15 minutes and preheat the materials, simultaneously adding the extractum into a charging basket of an infusion vehicle, starting an infusion pump when the temperature of the materials in the container reaches 60-85 ℃, adjusting the pressure of compressed air to 0.4MPa, and adjusting and controlling the infusion quantity to start one-step granulation. And (5) screwing out the material cavity after the one-step granulation is finished, and preparing the granules.

Step 4

And adding the qualified particles subjected to moisture detection into an FS-0.6x1.5 square sieve, and storing the qualified particles, fine powder and large blocks separately. Adding the granule into square cone mixer, and diluting the volatile oil with 95% ethanol when half of the granule is added. Spraying the mixture into the particles, adding the other half of the particles, and mixing for 30 minutes to ensure uniform mixing until the particles are uniform and the color is consistent. And subpackaging the granules to obtain the Chinese patent medicine granules.

Examples 2 to 5

Examples 2-5 were identical to the total amount of arabinose and microcrystalline cellulose in example 1, i.e. the amounts of excipients ensuring that each example was identical to example 1, except that the mass ratio between the two was different. Wherein the mass ratio of arabinose to microcrystalline cellulose in example 2 is 10:1, the mass ratio of arabinose to microcrystalline cellulose in example 3 is 50:1, the mass ratio of arabinose to microcrystalline cellulose in example 4 is 1:1, and the mass ratio of arabinose to microcrystalline cellulose in example 5 is 100:1.

Comparative example 1

Comparative example 1 differs from example 1 only in that arabinose and microcrystalline cellulose were replaced with equal amounts of sucrose. Wherein the equivalent amount means that the mass of sucrose is equal to the sum of the mass of arabinose and microcrystalline cellulose.

Comparative example 2

Comparative example 2 differs from example 1 only in the manner of granulation. Comparative example 2 was wet granulated, and the specific granulation process was as follows: mixing sucrose and dextrin, pulverizing, adding the concentrated extract with the same ratio into a groove type mixer, and stirring to obtain soft material; starting a wet swing granulator, adding soft materials into the swing granulator to prepare wet granules, uniformly spreading the wet granules into a stainless steel material tray, sequentially filling the wet granules into a hot air circulation drying box according to the sequence from top to bottom, and starting a drying program to dry until the moisture of the granules meets the quality requirement. And after the drying is finished, collecting the particles, and finishing the particles, wherein the particle size of the particles is required to meet the quality requirement.

Comparative example 3

Comparative example 3 differs from example 1 in that the perilla leaf in step 1.1 is a dry medicinal material of the single purple leaf containing tender branch.

Comparative example 4

Comparative example 4 differs from example 1 in that the perilla leaf in step 1.1 is a dry medicinal material of the perilla leaf with purple double surfaces and without twigs.

Comparative example 5

Comparative example 5 differs from example 1 in that the perilla leaf in step 1.1 is a dry medicinal material of the purple double-sided purple containing tender branch of the perilla leaf.

The main process parameters of the above examples and comparative examples are shown in table 1.

TABLE 1

	Auxiliary material type	Mass ratio of arabinose to microcrystalline cellulose	Granulating mode	Perilla She Leixing
					Example 1	Arabinose, microcrystalline cellulose	25:1	One-step granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
Example 2	Arabinose, microcrystalline cellulose	10:1	One-step granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
					Example 3	Arabinose, microcrystalline cellulose	50:1	One-step granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
Example 4	Arabinose, microcrystalline cellulose	1:1	One-step granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
					Example 5	Arabinose, microcrystalline cellulose	100:1	One-step granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
Comparative example 1	Sucrose	/	One-step granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
					Comparative example 2	Arabinose, microcrystalline cellulose	25:1	Wet granulation	Perilla She Shanmian purple and tender branch-free dry medicinal material
Comparative example 3	Arabinose, microcrystalline cellulose	25:1	One-step granulation	Perilla She Shanmian purple and tender branch-containing dry medicinal material
					Comparative example 4	Arabinose, microcrystalline cellulose	25:1	One-step granulation	Perilla leaf double-sided purple and tender branch-free dry medicinal material
Comparative example 5	Arabinose, microcrystalline cellulose	25:1	One-step granulation	Perilla leaf dry medicinal material with purple surfaces and containing twigs

The Chinese patent medicine particles prepared in the examples and the comparative examples are detected.

1. Particle appearance detection

The color, particle size, etc. of the particles were observed.

The detection method comprises the following steps:

1.1 particle color: the appropriate amount of particles (about 100 g) was taken and placed in a clean white porcelain dish, and the color and state were observed under natural light.

1.2 Particle size measurement:

Instrument and appliance:

Standard medicine sieve No. one sieve (2000 [ mu ] m + -70 [ mu ] m,10 meshes), no. five sieves (180 [ mu ] m + -7 _., 6 [ mu ] m,80 meshes) and is provided with a sieve cover and a closed receiving container.

The analytical balance senses 10mg or 1mg.

The operation method comprises the following steps:

The method is used to determine the particle size or limit of a pharmaceutical formulation. The granule size measurement adopts a double screening method.

1.2.1A sieve was placed over a No. five sieve and a sealed receiving vessel was fitted under the No. five sieve.

1.2.2 Taking about 60g of the sample, weighing, placing in the upper layer of the standard medicine sieve, and covering the upper cover.

1.2.3 Sieving the content, keeping the horizontal state, reciprocating left and right, and tapping for 3 min while sieving.

1.2.4 Taking the granules and powder which can not pass through the first sieve and the fifth sieve, and weighing.

Recording and calculating:

each weighing data is recorded, and three significant digits are reserved.

The percentages were calculated based on the weighing of the particles and powders that failed the first sieve and that failed the fifth sieve.

Wherein, the particle size= (No. 1 sieve + No. 5 sieve)/test particle. Smaller particle size indicates more uniform particles.

2. Solubility detection

Detection method

Instrument and appliance: 250ml beaker and glass stirrer bar.

The checking method comprises the following steps:

About 12g of the sample was taken, 200ml of water (70 to 80 ℃ C.) was heated, stirred for 1 minute, and immediately observed. If all the materials are dissolved, stopping the operation, and recording the dissolution time for 1 minute; if the sample cannot be completely dissolved, 12g of the same sample is continuously taken, stirred for 2 minutes and immediately observed. In the above-described manner, the phenomenon (whether or not all melted) and the melting time (all melted) observed at each stirring time were recorded.

3. Puerarin content detection

Detection method

Chromatographic conditions and system applicability conditions: octadecyl silane bonds and silica gel are used as fillers; acetonitrile-water (11:89) as mobile phase; the detection wavelength was 250nm. The theoretical plate number is not lower than 4500 calculated according to puerarin peak.

Preparation of a control solution: taking a proper amount of puerarin reference substance, precisely weighing, adding 30% ethanol to prepare a solution containing 16 mug per 1 ml.

Preparation of test solution: taking the product with different loading amounts, grinding, taking about 0.8g, precisely weighing, placing into a conical flask with a plug, precisely adding 50ml of 30% ethanol, sealing, weighing, performing ultrasonic treatment (power 250w, frequency 33 KHz) for 20 minutes, cooling, weighing again, supplementing the lost weight with 30% ethanol, shaking, filtering, and taking subsequent filtrate.

Assay: respectively precisely sucking 10 μl of the reference substance solution and the sample solution, injecting into a liquid chromatograph, and measuring to obtain the final product.

4. Moisture detection

The detection method comprises the following steps:

Instrument and appliance:

The analytical balance senses 0.1mg.

Moisture meter (composed of three parts of a 500ml short neck round bottom flask, moisture measuring tube and straight condenser tube with an outer tube length of 40 cm). Before use, all instruments should be cleaned and dried in an oven. The instrument and device is shown in the fourth method of the four-part general rule 0800 limit check method 0832 moisture determination method of China pharmacopoeia 2015.

Electrothermal sheath (Adjustable temperature)

Antiknock articles (glass beads or ceramic chip fragments).

Reagent and reagent:

toluene: chemically pure.

The operation method comprises the following steps:

A proper amount of the sample (about 1-4 ml water content) was taken, precisely weighed, placed in a 500ml short-necked round bottom flask, about 200ml toluene was added, if necessary, a number of glass beads were added, the parts of the apparatus were connected, and toluene was added from the top of the condenser tube to the narrow part of the water-measuring tube filled with water.

A500 ml short-necked round bottom flask was placed in an electric mantle and heated slowly, and when toluene began to boil, the temperature was adjusted so that 2 drops per second were distilled off. When the water is completely distilled, i.e. the water quantity of the scale part of the measuring tube is not increased, the interior of the condensing tube is firstly washed by toluene, then the toluene attached to the tube wall is pushed down by a long brush or other suitable methods for saturated dipping of toluene, the distillation is continued for 5 minutes, and the cooling to the room temperature is carried out.

The dismounting device, such as water, is adhered to the pipe wall of the water measuring pipe, can be pushed down by copper wires dipped in toluene, and is placed to completely separate the water from the toluene (a small amount of methylene blue powder can be added to dye the water into blue for separation observation). The water content (%) of the test sample was calculated by detecting the water content.

And (3) calculating:

moisture% = actual measured moisture volume V (ml)/sample weight W (g) ×100%

And (3) notes:

toluene for measurement is first added with a small amount of water, shaken thoroughly, then left to stand, the water layer is separated and discarded, and distilled for use.

The sample for measuring the traditional Chinese medicine is generally crushed into particles or fragments with the diameter not exceeding 3 mm; the diameter and the length are below 3mm and can not be broken.

Notice that:

before using, the moisture meter should be cleaned until the inner wall is free from hanging water, and then dried or placed in an oven for low-temperature drying.

When the heating is stopped and the inner wall of the condensing tube is washed by toluene, the cooling is needed, and if the toluene is added immediately, the toluene is heated and boiled.

The method is characterized in that the method is directly measured by using chemically pure toluene, if necessary, a small amount of water can be added into the toluene, the toluene is placed after being fully shaken, the water layer is separated and discarded, and the toluene is distilled for use.

When the electric heating sleeve is used for heating, the heating temperature is controlled, so that the loss of water caused by overhigh temperature is prevented.

The scale portion of the moisture measuring tube should be calibrated to be acceptable.

The test results are shown in Table 2.

TABLE 2

	Granulating time length	Particle appearance and particle size	Solubility of	Puerarin content	Moisture content
						Example 1	8h36min	The particles are brown yellow and have the granularity of 1 percent.	All melted for 1 minute.	0.23%	2.9%
Example 2	9h50min	The particles are brown yellow and have the granularity of 3 percent.	And completely melted for 3 minutes.	0.19%	3.3%
						Example 3	11h15min	The particles are yellow-brown in color, and have a particle size: 6%.	All melted for 1 minute.	0.16%	4.5%
Example 4	9h22min	The particles are yellow-brown in color, and have a particle size: 5%.	And completely melted for 4 minutes.	0.18%	3.8%
						Example 5	10h56min	The particles are yellow-brown in color, and have a particle size: 8%.	All melted for 1 minute.	0.17%	4.9%
Comparative example 1	12h32min	The particles are brown yellow and have the granularity of 3 percent.	And completely melted for 5 minutes.	0.15%	3.3%
						Comparative example 2	21h35min	The particles were dark brown and had a particle size of 9%.	Melting (slight turbidity) for 6 minutes.	0.11%	3.7%
Comparative example 3	9h09min	The particles are brown yellow and have the granularity of 2 percent.	All melted for 1 minute.	0.21%	3.3%
						Comparative example 4	8h55min	The particles are brown yellow and have the granularity of 1 percent.	All melted for 1 minute.	0.22%	3.2%
Comparative example 5	9h02min	The particles are brown yellow and have the granularity of 2 percent.	All melted for 1 minute.	0.21%	3.4%

In addition, the applicant discovers through a large number of experiments that different perilla leaf medicinal materials have different oil yield. Oil yield was measured using the perilla leaves used in example 1 and comparative examples 3 to 5 as a test piece.

The oil yield detection method comprises the following steps:

1. The test sample for measurement is crushed and passed through No. 2-No. 3 sieve, and mixed uniformly.

2. Instrument device

2.1 A hard round bottom flask is used, a volatile oil tester is connected to the flask, and a reflux condenser is connected to the upper end of the volatile oil tester. All the parts are connected by a glass grinding port. The volatile oil tester should have a scale of 0.1 ml.

2.2 Branch pipe branching position of volatile oil tester in the device should be parallel to datum line.

2.3 The whole instrument should be thoroughly cleaned and checked for tightness of the joint to prevent escape of volatile oil.

3. Measurement method

100G of perilla leaf (about 0.5-1.0 ml of volatile oil) is weighed (accurate to 0.01 g) and placed in a flask. Adding 300-500 ml (or proper amount) of water and glass beads, shaking and mixing. Connect volatile oil tester and reflux condenser. Water was added from the upper end of the condenser tube to fill the scale portion of the volatile oil tester and overflowed into the flask. Heating to boiling in an electrothermal jacket or by other suitable method, and keeping micro boiling for about 2.5 hours. Stopping heating and standing for a while. The piston at the lower end of the measuring device is started to slowly release water until the upper end of the oil layer reaches the position 5mm above the scale 0 line. And (3) placing for more than 1 hour, starting the piston to enable the oil layer to descend until the upper end of the oil layer is just flush with the scale 0 line, and reading the volatile oil quantity.

The content (%) of volatile oil in the test sample is calculated according to the following formula:

4.1 taking test samples, attention should be paid to representative uniformity.

4.2 Should be heated slowly to boiling to prevent the volatile oil from overflowing and losing due to insufficient condensation.

4.3 When the volatile oil tester reads, the tangent point at the lowest part of the liquid level of the arc line should be read, and the eyes must be on the same level with the liquid level of the arc line.

The results of the oil yield obtained are shown in Table 3.

TABLE 3 Table 3

	Oil yield (ml/100 g)
		Example 1	1.20
Comparative example 3	0.72
		Comparative example 4	0.91
Comparative example 5	0.68

Test example:

clinical effect test of the Chinese patent medicine granule (abbreviated as the granule, hereinafter the same) prepared in the example 1 for treating wind-cold type common cold.

General data

All cases were from community outpatients for a total of 251. All patients have symptoms of headache, fever, aversion to cold, body pain, nasal discharge, cough, dry throat and other upper respiratory tract symptoms, and all meet the diagnosis standard of wind-cold type common cold in traditional Chinese medicine. All patients were randomly divided into test group (this granule), control group 1 (cold heat clearing granule) and control group 2 (cold heat clearing granule group). The test group had 83 cases (41 men and 42 women) and the age was 61.28 + -10.17; control group 1 had 84 cases (42 men and 42 women) and an age of 60.21.+ -. 9.69; control group 2 had 84 cases (42 men and 42 women) and was aged 60.75.+ -. 10.03. The data of the sex, age, course of disease and the like of three groups of patients are statistically processed, and the differences have no statistical significance (P is more than 0.05), so the three groups of patients have comparability. The study was approved by all patients and all signed informed consent.

Therapeutic method

Test group: the granule is orally taken, 12g each time, 2 times a day;

Control group 1: cold-clearing granules (produced by Shandong Sanjiu pharmaceutical Co., ltd.) of 12g each time and 2 times per day;

control group 2: the granule for treating common cold and clearing heat (produced by Tai Ji group Chongqing Chinese medicine two factories) is 12g each time and 2 times a day.

Three groups of patients were treated for 3 days.

Observation index

Observing the scores of all symptoms of headache, aversion to cold, body pain, nasal discharge, cough and dry throat of three groups of patients before and after treatment;

observing the clinical effective rate of three groups of patients;

three groups of adverse reaction occurrence rates were observed.

Therapeutic effect criterion

Disease efficacy criterion

Clinical recovery: the body temperature returns to normal within 3 days after the treatment, and the symptoms of the cold completely disappear.

The effect is shown: the body temperature is normal within 3 days after the treatment, and most symptoms of the cold disappear.

The method is effective: the body temperature is reduced within 3 days of treatment compared with the prior art, and the main symptom part of the common cold disappears.

Invalidation: the body temperature is not reduced or increased within 3 days of treatment, and the main symptoms of the cold are not improved.

Traditional Chinese medicine syndrome curative effect judgment standard

Clinical recovery: the clinical symptoms and signs disappear or disappear basically, and the integral of symptoms is reduced by 95 percent.

The effect is shown: the clinical symptoms and signs are obviously improved, and the integral of symptoms is reduced by more than 70 percent.

The method is effective: the clinical symptoms and signs are all improved, and the integral of symptoms is reduced by more than 30 percent.

Invalidation: the clinical symptoms and signs are not obviously improved or even aggravated, and the integral of symptoms is reduced by less than 30 percent.

Results

Comparison of the efficacy of three groups of patients

After treatment, the total effective rate of the disease treatment effect of the patients in the test group has certain advantages compared with the control group 1 and the control group 2, which shows that the test group is superior to the control group, and the details are shown in Table 4.

Table 4 disease efficacy comparison (examples) for three groups of patients

Comparison of the curative effects of three groups of Chinese traditional medicine syndromes

After treatment, the total effective rate of the traditional Chinese medicine symptoms of the patients in the test group has a slight advantage compared with the control group 1, and the advantages are obvious compared with the control group 2, which shows that the test group is superior to the control group, and the details are shown in Table 5.

Table 5 comparative curative effects of the Chinese medical science syndromes of three groups of patients (examples)

Three group patient symptom score comparison

Before treatment, the scores of the symptoms of the three groups of patients are compared, and the difference has no statistical significance (P > 0.05). After treatment, the patients in the test group had significantly lower scores for headache, aversion to cold, body pain, nasal discharge, cough, and dry throat than those in the control group 1, the control group 2, and the details are shown in Table 6.

Table 6 three groups of patient symptom score comparisons (mean.+ -. Standard deviation, score)

Comparison of adverse reactions in three groups

The test group has no adverse reaction patient; adverse reaction of control group 1 human; adverse reactions 3 persons in control group 2 are detailed in Table 7.

Table 7 comparison of adverse reaction rates of three groups of patients (examples)

Conclusion(s)

The results show that the test group has certain advantages compared with the control groups 1 and 2 in the aspects of disease treatment before and after treatment, syndrome treatment and symptom improvement, and no adverse reaction occurs during the treatment period of the test group, which indicates that the granule has obvious treatment effect on wind-cold type common cold, is safe and reliable, and is superior to the existing common cold heat-clearing granule on the market.

Claims (9)

1. A preparation method of Chinese patent medicine granules for treating cold, wherein the preparation method comprises the following steps:

decocting herba Schizonepetae, herba Menthae, and folium Perillae with water to obtain volatile oil, decoction and residue;

adding bupleuri radix, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodi, herba Violae, rhizoma Phragmitis, radix Puerariae and semen Armeniacae amarum into the residue, decocting with water, mixing the obtained filtrate with the decoction, and concentrating to obtain extract;

granulating the extract, dextrin, arabinose and microcrystalline cellulose by using a one-step granulating method;

further preparing the granules obtained by granulating and the volatile oil into Chinese patent medicine granules;

wherein the mass ratio of the arabinose to the microcrystalline cellulose is (1-100): 1;

the perilla leaf is purple-sided and does not contain a tender branch.

2. The process according to claim 1, wherein the mass ratio of arabinose to microcrystalline cellulose is (20-30): 1.

3. The preparation method according to claim 1, wherein the mass ratio of arabinose to extract is (1-2): 2.

4. The preparation method according to claim 1, wherein the mass ratio of the dextrin to the extract is 1:4.

5. The preparation method according to claim 1, wherein the inlet air temperature is less than or equal to 115 ℃ and the outlet air temperature is less than or equal to 80 ℃ during one-step granulation, and the compressed air pressure is 0.4MPa.

6. The method according to claim 1, wherein the extract has a relative density of 1.32 to 1.35 at 50 ℃.

7. The preparation method according to claim 1, wherein the schizonepeta spike, peppermint and perilla leaf are decocted with water to extract the schizonepeta spike, peppermint and perilla leaf by heating and refluxing for 4 hours.

8. The preparation method of claim 1, wherein adding radix bupleuri, radix Saposhnikoviae, radix Angelicae Dahuricae, radix Platycodonis, herba Violae, rhizoma Phragmitis, radix Puerariae, and semen Armeniacae amarum to the residue, and extracting with water for 1.5 hr for 2 times.

9. The preparation method of claim 1, wherein the Chinese patent medicine particles are prepared from the following raw medicines in parts by weight:

herba schizonepetae 200, peppermint 60, divaricate saposhnikovia root 100, bupleurum 100, perilla leaf 60, kudzuvine root 100, platycodon root 60, bitter apricot seed 80, dahurian angelica root 60, bunge corydalis herb 200 and reed rhizome 160.