CN1839921A - Coryza-treating capsule and preparation process thereof - Google Patents

Abstract

The invention provides a capsule for treating rhinitis and a preparation method thereof, which is calculated according to weight components: Senecio 9696-2424, Selaginella 1616-404, Cassia 968-242, Ephedra 324-81, Notopterygium 64～8, Baizhi 64～8 and Chuanxiong 64～8 are extracted and prepared into medicinal powder, and then prepared by adding appropriate auxiliary materials; compared with the prior art, the present invention adopts a more scientific preparation process, and the prepared capsules The drug has the advantages of good disintegration effect, good drug dispersibility, complete absorption, etc., and can also regulate drug release, so that the drug gradually diffuses and dissolves into the gastrointestinal fluid, reduces the stimulation effect on the gastrointestinal mucosa, and has high bioavailability. Significant effect.

Description

Capsule for treating rhinitis and preparation method thereof

Technical field: The present invention relates to a capsule for treating rhinitis and a preparation method thereof, in particular to Qianbai Biyan Capsule and a preparation method thereof, belonging to the technical field of traditional Chinese medicine pharmacy.

Background technology: Acute and chronic rhinitis is a common disease, which greatly affects the facial features of the human body during the onset period. Chronic rhinitis includes: allergic rhinitis, paranasal sinusitis, atrophic rhinitis, upper frontal sinusitis, hypertrophic rhinitis, nasal polyps, etc. The clinical symptoms of the disease are different, and the harm is great. Patients are often prone to colds, sneezing, runny nose, itching, poor ventilation, bleeding, dryness, scabs, smelling, neurasthenia, headache, dizziness, and throat irritation. Swelling, arrhythmia, frequent yellow and thick nasal discharge, green nasal discharge, etc., and sinusitis alone can cause other diseases in addition to eye diseases, mainly including: 1. Intracranial complications; 2. , Osteomyelitis; 3, pharyngitis, tonsillitis, otitis media, bronchitis and other diseases. Visible above-mentioned disease brings great misery to rhinitis patient's work and life. The currently used Qianbai Biyan Tablet is a traditional sugar-coated tablet. Due to the simple process, the selected coating materials are conventional excipients, resulting in the disadvantages of drug disintegration exceeding the limit, poor dispersibility, incomplete absorption, and low bioavailability; In recent years, the research results of pharmacokinetics and pharmacodynamics have shown that Qianbai Biyan Tablets need to be taken orally three times, 3-4 tablets each time, and the blood concentration range for rhinitis is narrow (5-8mg/ml). Afterwards, the blood concentration is prone to "peak and valley" phenomenon, leading to side effects such as headache, nausea, vomiting, dizziness, insomnia, upper abdominal pain, fever, rapid heartbeat, cramps and allergies. In addition, the drug is easy to be released when it is transferred to the stomach and intestinal tract or accidentally retained in a certain part, which will cause irritation and affect the curative effect.

Invention content:

The object of the present invention is to: provide a kind of capsule for treating rhinitis and preparation method thereof, the present invention aims at the deficiency of existing Qianbai Biyan tablet preparation technology, has developed more scientific coating preparation process, the capsule prepared has It has the advantages of good disintegration effect, good drug dispersibility, complete absorption, etc., especially can regulate drug release, reduce stimulation to gastrointestinal mucosa, high bioavailability, and remarkable curative effect.

The present invention is constituted as follows: calculated according to weight components: it is made of Senecio 9696-2424, Selaginella 1616-404, Cassia 968-242, Ephedra 324-81, Notopterygium 64-8, Angelica dahurica 64-8 and Ligusticum chuanxiong 64-8 is extracted and prepared into medicinal powder, and then calculated by weight percentage, take mixed medicinal powder 50-85%, disintegrant 5-10%, glidant 0.5-10% and absorbent 0.5-10%, retarder It is prepared by adding 5-25% release coating material.

Specifically, it is calculated according to the weight components: it is prepared into a medicinal powder after extracting 4848g of Senecio, 808g of Selaginella, 484g of Cassia, 162g of Ephedra, 32g of Notopterygium, 16g of Angelica dahurica and 16g of Chuanxiong. It is prepared by mixing 68% of medicinal powder, 8% of disintegrating agent, 2% of glidant, 2% of absorbing agent and 20% of slow-release coating material.

The disintegrating agent is any one or two or more of pregelatinized starch PS, sodium carboxymethyl starch CMC-Na, low-substituted hydroxypropyl methylcellulose L-HPC, and cross-linked polyvinylpyrrolidone PPVP. mixture; the glidant is any one or a mixture of two or more of micronized silica gel, talcum powder, hydrated sodium silicate, Cab-O-sil, and magnesium stearate; the absorbent is light magnesium oxide, calcium bicarbonate, Any one of calcium carbonate or a mixture of two or more; slow-release coating materials are carnauba wax, corn gum, gelatin, ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose phthalate, Cellulose acetate phthalate, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose HPMC, hydroxymethyl cellulose, sodium hydroxymethyl cellulose, Any one or a mixture of two or more of polyvinylpyrrolidone and polyvinyl alcohol.

The preparation method of capsules for treating rhinitis is as follows: take notopterygium, chuanxiong, angelica dahurica, and ephedra net medicinal materials, pulverize them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put them in a steam sterilizing cabinet, Sterilize at 115°C for 30 minutes for later use; put Senecio, Selaginella, and Cassia officinalis into a multi-functional Chinese medicine extraction tank, add water 6-10 times the weight of the medicinal materials for the first time, and soak for 4-12 hours , decoct for 1 hour, add water 7-9 times the weight of the medicinal material for the second time, decoct for 1 hour, and control the decoction temperature at 95-100°C; combine the decocted liquid, inhale into a multi-effect energy-saving evaporation concentration device for concentration, The relative density reaches 1.21 to 1.25 at 80-85°C; the obtained extract is dried in a microwave vacuum oven, crushed and made into dry powder of extract of 80 to 100 mesh; the above powders are mixed, calculated by weight percentage, and 50-85% Mix the mixed medicine powder with 5-10% disintegrant for 30 minutes, then add 0.5-10% absorbent and 0.5-10% glidant, mix well, and set aside; take 5-25% slow-release coating material , dissolved in water and diluted to an appropriate concentration to be used as a binder, mixed with the medicinal powder to obtain master batches by a coating granulator, enlarged, polished, dried, granulated, and packed into capsules.

The more specific preparation method is as follows: take notopterygium, Chuanxiong, Baizhi, and ephedra net medicinal materials, crush them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put it in a steam sterilizing cabinet, and heat it at 115 ° C. Sterilize under conditions for 30 minutes for later use; put Senecio, Selaginella, and Cassia Cassiae into a multi-functional traditional Chinese medicine extraction tank, add water 10 times the weight of the medicinal materials for the first time, soak in warm for 6 hours, decoct for 1 hour, and Add water 8 times the weight of the medicinal materials twice, decoct for 1 hour, control the decoction temperature at 95-100°C, combine the decocted liquid, inhale into a multi-effect energy-saving evaporation concentration device, and concentrate until the relative density reaches 80-85°C 1.22; dry the obtained extract with a microwave vacuum drying oven, crush it to make 80-100 mesh dry extract powder; mix the above powders, calculate by weight percentage, take 68% of the mixed powder and 8% of the disintegrant carboxymethyl Sodium starch, mix for 30 minutes, then add 2% absorbent calcium bicarbonate and 2% glidant micropowder silica gel, mix well, set aside; take 20% ethyl cellulose and hydroxypropyl methyl cellulose mixture as Sustained-release coating material, dissolved in water and diluted to an appropriate concentration, used as a binder, and mixed with the drug powder to obtain master batches with a coating granulator, enlarged, polished, dried, granulated, and packed into capsules.

The described concentration process conditions are: steam pressure≤0.09Mpa, vacuum degree I effect is -0.01～-0.02Mpa, II effect is -0.03～-0.04Mpa, III effect is -0.05-～-0.06Mpa; temperature I effect 85-95°C, II effect 75-85°C, and III effect 65-75°C.

The microwave vacuum drying process conditions are as follows: the wavelength is 1mm-1m, and the frequency is 2450MHz. Under this condition, microwaves can penetrate deep into the extract, and if there is too much water, the heating temperature will be high and the friction will be severe, and it will not affect the active ingredients in Senecio, Selaginella, and Cassia. Under certain conditions, it can also sterilize the extract .

The coating and granulation process conditions are as follows: take the solution of the selected coating material as the binder, use the BJZ-1000 type coating and granulation machine to prepare the masterbatch of the mixed medicinal powder, and control the spraying speed at 30- 60r/min, the speed of the main engine is controlled at 80-150r/min, and the masterbatch is made into 40 mesh, and the masterbatch is dried for 1.5 hours, and the 24-40 mesh particles are screened out, and the remaining particles are crushed into 100 mesh fine powder for Start the mother; take 24-40 mesh particles and put them in BJZ-1000 type coating granulator, add coating solution and 100 mesh fine powder to enlarge, after the particles are enlarged to about 20 mesh, polish them; collect the enlarged particles and put them in PGL Dry in a type spray granulator, granulate, sieve out 16-24 mesh granules and pack them into capsules, and the rest of the granules continue to be crushed into 100 mesh powders for starting mother.

The more specific process conditions for coating and granulation are as follows: take the solution of the selected coating material as the binder, use the BJZ-1000 type coating and granulating machine to obtain the masterbatch of the mixed medicinal powder, and control the spraying speed at 50r /min, the speed of the main engine is controlled at 120r/min, and a 40-mesh masterbatch is made. The masterbatch is dried for 1.5 hours, and the 30-mesh particles are screened out. Put the target granules in BJZ-1000 coating granulator, add coating solution and 100 mesh fine powder to enlarge; after the granules are enlarged to about 20 mesh, polish them; collect the enlarged granules and dry them in PGL spray granulator , Whole grain, sieve out 20 mesh granules to pack into capsules, and the rest of the granules continue to be crushed into 100 mesh powder for starting mother.

Tablet is a traditional dosage form, which has stable quality, accurate dosage, convenient administration, high degree of mechanization, and low production cost, so it has become one of the most commonly used dosage forms at present. However, due to the pressure molding of the tablet, the disintegration is slow, the bioavailability is low, and the daily oral dose is large. After frequent administration, "peaks and valleys" are prone to occur, resulting in side effects such as headache, nausea, vomiting, dizziness, insomnia, and allergies. For this reason, the present invention adopts coating material to make coated pellet, after oral administration, disintegration speed is good, and medicine diffuses and dissolves gradually to gastrointestinal fluid, can reach the blood drug concentration of steady state.

In order to solve the above problems, the applicant has carried out an auxiliary material selection test and a pharmacodynamic test, as follows:

1. Since the present invention adopts a molding process different from that of the prior art, that is, the extracted medicinal powder is premixed with a disintegrant, and then mixed with a coating material, and the coating granulation process is adopted to make the drug into coated pellets. Realize the object of the present invention, we have carried out following selection to auxiliary material:

1. The way to add the disintegrant:

The present invention requires a suitable disintegration speed in order to exert a better drug effect. Since the disintegration agent is added in different ways, the disintegration effect is also different, so we use two methods of internal addition and external addition to examine the disintegration effect . The operation of the internal addition method referred to in the present invention is: firstly mix appropriate amount of medicinal powder with disintegrant, and then granulate together with the water dissolution of the slow-release coating material with a coating granulator. The operation of the external addition method is as follows: first mix an appropriate amount of sustained-release coating material with a disintegrant, dissolve it in water and dilute it to an appropriate concentration to be used as a binder, and then granulate it together with the drug powder with a coating granulator. The results of the comparison of the two methods are as follows:

Table 1 Examination of two adding methods of disintegrant investigation Addition Inner addition Dosage of disintegrant 15% 8% mixing time 50±10min 30±5min disintegration time 3-8 1-5 Adhesive effect easy to agglomerate Can be properly dispersed without caking Granulation effect Uneven particle size Uniform particle size

From the above table, it can be concluded that the amount of disintegrant used in the external addition method is more than that in the internal addition method, which will increase the dosage and production cost; the mixing time of the external addition method is more time-consuming than the internal addition method, and it will also increase the production cost; The disintegration time of the external addition method is longer than that of the internal addition method, which is not conducive to the efficacy of the preparation. In addition, the binding effect and granulation effect of the external addition method are not as good as the internal addition method. It can be seen that the present invention is suitable for internal addition, that is, an appropriate amount of drug powder is first mixed with a disintegrant, and then granulated with a coating granulator together with the water dissolution of the sustained-release coating material.

2. Selection of the type of disintegrant: Since the raw material is dry extract powder, it is easy to bond after moisture absorption, so it is considered to add a disintegrant. In this preparation, it is advisable that each capsule should be dissolved within 30 minutes. The result of the selection experiment: Accessories Disintegration mechanism price Dosage Disintegration time limit other comments Sodium Carboxymethyl Starch CMC-Na Expansion Low 5-10% 26 minutes Good disintegration effect, good dispersibility, suitable for hydrophobic and alkaline active ingredients polyethylene glycol capillary action middle 5-15% 34 minutes Improved formability and hardness, general disintegration effect Cross-linked PVP capillary action high 5-15% 29 minutes Good disintegration effect, promote dissolution, but strong hygroscopicity Pregelatinized Starch PS Expansion Low 5-15% 26 minutes Good disintegration effect, good dispersibility, promote dissolution Low Substituted Hydroxypropyl Methyl Cellulose L-HPC capillary action middle 5-15% 27 minutes Good disintegration effect, good dispersibility, and better effect when combined with PPVP Cross-linked polyvinylpyrrolidone PPVP capillary action middle 5-15% 26.5 minutes Good disintegration effect, good dispersibility, promote dissolution

According to the above comparison, we choose any one of pregelatinized starch, sodium carboxymethyl starch (CMC-Na), low-substituted hydroxypropyl methylcellulose (L-HPCC), cross-linked polyvinylpyrrolidone (PPVP) or A mixture of two or more acts as a disintegrant.

But consider from reducing preparation dosage and two aspects of price, carboxymethyl starch sodium consumption is less than other, cheap, so the present invention selects the carboxymethyl starch sodium of 8% amount as disintegrating agent.

3. Selection of other auxiliary materials (absorbent and glidant):

What the present invention adopts is whole powder granulation, especially in the process of coating pellets, the medicine powder feeding is not smooth, easily causes the accumulation of medicine powder in the coating pan, so it is considered to add a flow aid to improve the flow effect; at the same time because The coating solution and powder enter the coating pan continuously, and the coating solution will be continuously sprayed on the surface of the qualified pills, so it will bind other powders to increase the volume of the pills. In order to absorb the surface moisture in time, the coated pills will keep size, we consider adding absorbents.

Under the premise of considering fluidity and coating effect, the effects that different glidants and absorbents can achieve are as follows: Glidant absorbent evaluate name Dosage name Dosage fluidity Coating effect Micropowder silica gel 1-3% calcium bicarbonate 0.1-3% Good fluidity, uniform and dispersed flow rate Uniform size of pills, no sticking Micropowder silica gel 1-3% Light magnesium oxide 2-7% good liquidity Pills are uniform in size talcum powder 2-5% calcium bicarbonate 0.1-3% Uniform and dispersed flow rate Pills are uniform in size Sodium silicate hydrate 2-5% calcium carbonate 3-5% Uniform and dispersed flow rate Pills are uniform in size Magnesium stearate 3-5% calcium bicarbonate 0.1-3% good liquidity Pills are uniform in size Cab-O-sil 3-5% Light magnesium oxide 2-7% good liquidity Pills are uniform in size

It can be seen from the above table that when meeting the requirements of the present invention for fluidity and coating effect, the dosages of different glidants and absorbents are different, among which the dosage of micropowder silica gel and calcium bicarbonate is the least, and the effect achieved is also the best. . Therefore, under the premise of controlling the cost as much as possible and not increasing the dosage, we consider comprehensively and select 2% micropowder silica gel and 2% calcium bicarbonate as the flow aid and absorbent of the present invention respectively.

4. Selection of sustained-release coating materials: due to the different physical and chemical properties of drugs, the physical properties of the particles mixed with the coating materials, the appearance of pellets, and moisture absorption are also very different. In order to achieve the best effect, the The disintegration time, suspension or uniformity, and dissolution of the dispersed pellets were used as the investigation indicators, and the optimal dosage of the coating agent was screened by the uniform design method. At the same time, we follow the following three aspects for quality evaluation.

(1) Physical properties: processing phenomenon, appearance phenomenon, hardness, color, moisture, etc.

(2) Stability: change during storage, appearance (discoloration, deliquescence).

(3) In terms of drug efficacy: it can accelerate disintegration, dissolution and dissolution.

After the investigation of the above four aspects, we found that: choose carnauba wax, corn glue, gelatin, ethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, phthalate hydroxypropyl methyl cellulose , cellulose acetate phthalate, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, sodium hydroxymethyl cellulose, polyvinylpyrrolidone and polyvinyl alcohol Any one or a mixture of two or more as the coating auxiliary material of the present invention fully has the advantages of the above aspects. Below is the dissolution selection test of several auxiliary materials in the present invention: Coating material Dosage method the solution time Ethyl cellulose 0.5-25% blue method dilute hydrochloric acid solution 30 minutes

Hydroxypropylmethylcellulose 0.5-25% turn blue method dilute hydrochloric acid solution 29.5 minutes Polyvinylpyrrolidone 0.5-25% turn blue method Phosphate solution 30 minutes corn glue 0.5-25% turn blue method Aqueous solution 28 minutes Hydroxypropyl Methyl Cellulose Phthalate 0.5-25% Stirring method Hydrochloric acid solution 30 minutes Sodium Hydroxymethyl Cellulose 0.5-25% turn blue method Hydrochloric acid solution 28.5 minutes

As can be seen from the above test results, the dissolution rate is controlled within 30 minutes.

In addition, the coated pellets made of ethyl cellulose as the skeleton material and hydroxypropyl methyl cellulose, after oral administration, because ethyl cellulose is insoluble in the gastrointestinal tract and hydroxypropyl methyl cellulose gradually dissolves. There are intricate pores in the pellet, and the active ingredients of the drug slowly diffuse to the gastrointestinal fluid through the pores. By adjusting the dosage ratio of ethyl cellulose and hydroxypropyl methyl cellulose in the prescription, the in vitro dissolution rate test was carried out to screen out the best prescription. One dose (300mg) administration of the capsule of the present invention reaches the effective blood drug concentration in 3.5h, and can maintain the blood drug concentration above 12mg/ml to reach 23 hours; ml) is much wider. After multiple doses of administration, the effective blood drug concentration can be reached within 3 hours, and the steady state blood drug concentration of 12.78+0.45 mg/ml has been reached the next day, see the efficacy test of the present invention for details.

The present invention can solve the irritation problem caused by the release of the original tablet when it is shifted in the stomach and intestinal tract and accidentally retained in a certain part through the above technology. Compared with the original preparation, the preparation technology of the present invention is more advanced, conforms to the characteristics of modern pharmacy, has good disintegration, good dispersibility of drug components, complete absorption, high bioavailability and improved curative effect. And the appearance of the obtained granules is good, and the pellets formed by coating the sustained-release material can be directly used for filling capsules, which reduces preparation difficulties and facilitates medical needs, thereby achieving the purpose of the invention. The present invention also has other advantages: (1) It can overcome the difference in the transfer time of the gastrointestinal tract and the performance difference caused by the difference in irregular gastric emptying. (2) It can be distributed in the whole gastrointestinal tract, so that the drug can be absorbed, thereby improving the bioavailability. (3) The drug dose is dispersed in a large number of pellets, and part of the coating fails. As a result, the failure of the entire dose of the tablet does not occur. (4) The drug is uniformly dispersed in each pellet, and the stimulating effect on the gastrointestinal mucosa is reduced.

Above test shows, the selected auxiliary material of the present invention can realize expected effect, has reached the purpose of the invention.

2. Determining the plasma concentration of ranunculus in the preparation and calculating the corresponding metabolic parameters.

Methods HPLC method was used to determine the blood drug concentration at different times before and after administration.

Ranunculus in the capsule of the present invention is an effective ingredient of Senecio. In order to explore its mechanism of action and provide a basis for the present invention, we have established a ranunculusin high performance liquid chromatography (HPLC) assay method, measured the blood drug concentration at different times after the administration of white rabbits, and calculated the corresponding metabolic rate at the same time. parameter.

1 material

1.1 Medicine: capsules of the present invention, brown pellets.

1.2 Instruments HPLC-2010A/2010C High Performance Liquid Chromatography (Shimadzu products).

1.3 Animals Kunming female white rabbits, weighing 2.8-3.2kg, were provided by the Experimental Animal Institute of Guiyang Medical College (certificate number, Yidongzi No. 03-3001).

1.4 Reagents Acetonitrile is chromatographically pure, and other reagents are analytically pure.

2 methods

Sixty female Kunming white rabbits were used in the experiment, and they were randomly divided into 6 groups with 10 rabbits in each group. The medicine removes the capsule shell and takes it orally with small pills, filled with water. The dose was 250mg/kg, and blood was collected from ear veins in groups within 3 to 4.5 hours after administration. After the blood has clotted, it is centrifuged to get the serum. Take 200 μl of serum and add 400 μl of acetonitrile to precipitate protein. After centrifugation, take 100 μl of supernatant and inject directly. The chromatographic column is a C ₁₈ Ultrasphere semi-preparative column (5U, 10mm×250mm). Mobile phase: 20% acetonitrile-80% phosphate buffer (1/15mol H ₃ PO ₄ +1/15mol KH ₂ PO ₄ , pH=3), flow rate 2ml/min, detection wavelength 210nm. The plasma drug concentrations at different administration times were measured respectively.

3 Results (see Table 2)

Table 2 Determination of plasma concentration of ranunculus xanthin (ug/ml) Before administration (h) After administration (h) group 0.5 2 3 3.5 4 4.5 5 1 0 1.45 19.95 100.31 127.7 120.38 90.17 2 0 1.37 20.36 96.57 129.72 121.45 91.19 3 0 1.08 19.61 97.44 118.06 109.62 89.59 4 0 1.28 22.25 102.63 132.84 119.20 98.75 5 0 1.27 20.67 110.42 128.18 120.61 100.56 6 0 1.26 17.60 105.81 124.73 121.09 101.83

Table 2 is the serum drug concentration of ranunculusin in rabbits at different times after administration. The logC value of the logarithmic value logC of the administration time after 3 hours of administration and the corresponding serum drug concentration is used for regression analysis, and the equation Y=2.1447-0.8753×T is obtained, and the elimination system (Ke): -2.0133/h; elimination phase half-life (T1/2β) 3.5h; maximum plasma concentration (Cmax): 125.48μg/ml; time to peak plasma concentration (Tmax): 4h; apparent volume of distribution (Vd ): 3.29mg/L; Clearance (CL): 6.62L/(h·kg). Ranunculus in the system is well separated, retention time tR7.4～7.5min, drug content is linearly correlated with peak area, Y(μg)=0.0412+0.181/γA(peak area), γ=0.9999, minimum detection limit is 0.1μg . This method is for the determination of the free ranunculusin original drug in serum, and the possible reduction products cannot be detected. The drug is absorbed quickly, reaching the highest concentration 4 hours after administration, and maintaining a high concentration within 4.5 hours. The drug eliminates T1/2β in only 4.5 hours, only traces remain in 2 hours, and cannot be detected at all in 1 hour.

4 Conclusion

Compared with the conventional auxiliary materials used in the commercially available Qianbai rhinitis tablets, the coating auxiliary materials used in the capsules of the present invention have fast absorption and fast metabolism in the body, and are not easy to accumulate. The drug is released evenly, the blood drug concentration is high and stable, and the frequency of taking the medicine is reduced to 2 times a day, 1-2 capsules each time. Compared with Qianbai Biyan Tablet, the daily dosage is significantly reduced.

Compared with the prior art, the present invention adopts a different molding process, that is, the extracted medicinal powder is premixed with a disintegrant, and then mixed with a coating material, and the drug is made into a coated pellet by using a coating granulation process. The prepared capsules have the advantages of good disintegration effect, good drug dispersibility, complete absorption, etc., and can also regulate drug release, so that the drug gradually diffuses and dissolves into the gastrointestinal fluid, reducing the stimulating effect on the gastrointestinal mucosa. The utilization is high and the curative effect is remarkable.

Detailed ways:

Example 1 of the present invention: Senecio 4848g, Selaginella 808g, Cassia 484g, Ephedra 162g, Notopterygium 32g, Angelica dahurica 16g and Ligusticum chuanxiong 16g are extracted and made into medicinal powder, and then calculated by weight percentage, take 68% mixed medicinal powder, 8% disintegrating agent (sodium starch glycolate), 2% glidant (micropowder silica gel), 2% absorbent (calcium bicarbonate), 20% sustained-release coating material (ethyl cellulose and hydroxypropyl methylcellulose mixture)

Preparation method: Take notopterygium, Chuanxiong, Baizhi, and ephedra net medicinal materials, crush them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put them in a steam sterilizing cabinet, and sterilize at 115°C Reserve for 30 minutes; put Senecio, Selaginella, and Cassia into a multi-functional Chinese medicine extraction tank, add water 10 times the weight of the medicinal materials for the first time, soak for 6 hours, decoct for 1 hour, and add 8 Water twice the weight of the medicinal materials, decocted for 1 hour, the decoction temperature was controlled at 95-100°C, combined the decocted liquid, inhaled into a multi-effect energy-saving evaporation and concentration device, and concentrated until the relative density reached 1.22 at 80-85°C; The extract is dried in a microwave vacuum drying oven, crushed and made into 80-100 mesh dry extract powder; the above powders are mixed, and the mixed powder and sodium carboxymethyl starch are taken according to the above weight percentage, and mixed for 30 minutes, then calcium bicarbonate and fine powder are added Silica gel, mixed well, ready for use; the mixture of ethyl cellulose and hydroxypropyl methyl cellulose is used as the slow-release coating material, dissolved in water and diluted to an appropriate concentration to be used as a binder, and the standby drug powder is prepared by a coating granulator Masterbatch, enlarged, polished, dried, granulated, encapsulated, ready to be obtained.

Among them, the coating and granulation process is as follows: take the solution of the selected coating material as the binder, and use the BJZ-1000 type coating and granulation machine to obtain the masterbatch of the mixed medicinal powder. The spraying speed is controlled at 50r/min. Control the rotation speed at 120r/min to make 40-mesh masterbatch, dry the masterbatch for 1.5 hours, sieve out 30-mesh particles, and crush the rest of the particles into 100-mesh fine powder for starting the masterbatch; take 30-mesh particles and put them in BJZ -Into the 1000-type coating granulator, add coating solution and 100 mesh fine powder to enlarge; after the particles are enlarged to about 20 mesh, polish them; collect the enlarged particles (dry matter quantity) and dry them in the PGL spray granulator , Whole grain, sieve out 20 mesh granules to pack into capsules, and the rest of the granules continue to be crushed into 100 mesh powder for starting mother. The concentration process conditions are: steam pressure ≤ 0.09Mpa, vacuum degree I effect is -0.01～-0.02Mpa, II effect is -0.03～-0.04Mpa, III effect is -0.05-～-0.06Mpa; temperature I effect is 85 ~95°C, II effect is 75~85°C, and III effect is 65~75°C. The microwave vacuum drying process conditions are as follows: the wavelength is 1mm ~ 1m, and the frequency is 2450MHz. This product is taken orally, 2 times a day, 1-2 capsules each time.

Example 2 of the present invention: Senecio 9696g, Selaginella 1616g, Cassia 968g, Ephedra 324g, Notopterygium 64g, Angelica dahurica 64g and Chuanxiong 64g are extracted to make medicinal powder, and then calculated by weight percentage, take 50% mixed medicinal powder, 9% disintegrant (pregelatinized starch), 8% glidant (hydrated sodium silicate), 8% absorbent (calcium carbonate), 25% sustained release coating material (polyvinylpyrrolidone and polyvinylpyrrolidone) vinyl alcohol)

Preparation method: Take notopterygium, Chuanxiong, Baizhi, and ephedra net medicinal materials, crush them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put them in a steam sterilizing cabinet, and sterilize at 115°C Reserve for 30 minutes; put Senecio, Selaginella, and Cassia into a multi-functional Chinese medicine extraction tank, add water 9 times the weight of the medicinal materials for the first time, soak for 12 hours, decoct for 1 hour, and add 9 times the weight for the second time Water twice the weight of the medicinal material, decoct for 1 hour, the decoction temperature is controlled at 95-100°C, the decocted liquid is combined, sucked into a multi-effect energy-saving evaporation concentration device, and concentrated until the relative density reaches 1.25 at 80-85°C; the obtained The extract is dried in a microwave vacuum drying oven, crushed and made into dry extract powder of 80-100 mesh; the above powders are mixed, and the mixed powder and pregelatinized starch are taken according to the above weight percentage, mixed for 30 minutes, and then calcium carbonate and hydrated silicic acid are added Sodium, mixed evenly, for later use; polyvinylpyrrolidone and polyvinyl alcohol are used as slow-release coating materials, dissolved in water and diluted to an appropriate concentration to be used as a binder, and the spare drug powder is prepared by a coating granulator to obtain master batches, enlarged, and polished , dried, whole grains, packed in capsules, ready to be obtained.

Among them, the coating and granulation process is: take the solution of the selected coating material as the binder, and use the BJZ-1000 type coating granulator to prepare the masterbatch of the mixed medicinal powder. The spraying speed is controlled at 60r/min. Control the rotation speed at 150r/min to make 40-mesh masterbatch, dry the masterbatch for 1.5 hours, sieve out 40-mesh particles, and crush the remaining particles into 100-mesh fine powder for starting mother; take 40-mesh particles and put them in BJZ -Into the 1000-type coating granulator, add coating solution and 100 mesh fine powder to enlarge; after the particles are enlarged to about 20 mesh, polish them; collect the enlarged particles (dry matter quantity) and dry them in the PGL spray granulator , granulate, sieve out 24 mesh granules and pack into capsules, and the rest of the granules continue to be crushed into 100 mesh powders for starting mother. Concentration process conditions and microwave vacuum drying process conditions are the same as in Example 1.

Example 3 of the present invention: Senecio 2424g, Selaginella 404g, Cassia 242g, Ephedra 81g, Notopterygium 8g, Angelica dahurica 8g and Ligusticum chuanxiong 8g are extracted and made into medicinal powder, and then calculated by weight percentage, take 85% mixed medicinal powder, 5% disintegrant (low substituted hydroxypropyl methylcellulose), 0.5% glidant (Cab-O-sil), 0.5% absorbent (light magnesia), 9% sustained release package Coating materials (carnauba wax, corn gum and gelatin)

Preparation method: Take notopterygium, Chuanxiong, Baizhi, and ephedra net medicinal materials, crush them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put them in a steam sterilizing cabinet, and sterilize at 115°C Reserve for 30 minutes; put Senecio, Selaginella, and Cassia into a multi-functional Chinese medicine extraction tank, add 6 times the weight of the medicinal materials in water for the first time, soak for 4 hours, decoct for 1 hour, and add 7 Water twice the weight of the medicinal materials, decoct for 1 hour, the decoction temperature is controlled at 95-100°C, the decocted liquid is combined, sucked into a multi-effect energy-saving evaporation and concentration device, and concentrated until the relative density reaches 1.21 at 80-85°C; The extract is dried in a microwave vacuum drying oven, crushed and made into 80-100 mesh dry extract powder; the above powders are mixed, and the mixed powder and low-substituted hydroxypropyl methylcellulose are mixed according to the above weight percentages, mixed for 30 minutes, and then added with light Magnesium oxide and Cab-O-sil, mixed well, for later use; carnauba wax, corn gum and gelatin were used as slow-release coating materials, dissolved in water and diluted to an appropriate concentration for use as a binder, and ready-made powder for coating The granulator takes the masterbatch, enlarges it, polishes it, dries it, granulates it, and packs it into capsules.

Among them, the coating and granulation process is as follows: take the solution of the selected coating material as the binder, and use the BJZ-1000 type coating granulator to prepare the masterbatch of the mixed medicinal powder. The spraying speed is controlled at 30r/min. The rotating speed is controlled at 80r/min to make 40-mesh masterbatch, and the masterbatch is dried for 1.5 hours, and the 24-mesh particles are screened out, and the remaining particles are crushed into 100-mesh fine powder for starting the masterbatch; take the 24-mesh granules and put them in BJZ -Into the 1000-type coating granulator, add coating solution and 100 mesh fine powder to enlarge; after the particles are enlarged to about 20 mesh, polish them; collect the enlarged particles (dry matter quantity) and dry them in the PGL spray granulator , Whole grain, sieve out 16 mesh granules and put them in capsules, and the rest of the granules continue to be crushed into 100 mesh powder for starting mother. Concentration process conditions and microwave vacuum drying process conditions are the same as in Example 1.

Example 4 of the present invention: Senecio 7272g, Selaginella 1212g, Cassia 726g, Ephedra 243g, Notopterygium 48g, Angelica 40g and Chuanxiong 40g are extracted and made into medicinal powder, and then calculated by weight percentage, take 65% mixed medicinal powder, 10% disintegrant (cross-linked polyvinylpyrrolidone), 10% glidant (talc powder), 10% absorbent (calcium bicarbonate), 5% sustained-release coating material (phthalic acid hydroxy Propyl methylcellulose and cellulose acetate phthalate)

Preparation method: Take notopterygium, Chuanxiong, Baizhi, and ephedra net medicinal materials, crush them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put them in a steam sterilizing cabinet, and sterilize at 115°C Reserve for 30 minutes; put Senecio, Selaginella, and Cassia into a multi-functional traditional Chinese medicine extraction tank, add water 8 times the weight of the medicinal materials for the first time, soak for 8 hours, decoct for 1 hour, add 8 Water twice the weight of the medicinal materials, decocted for 1 hour, the decoction temperature was controlled at 95-100°C, the decocted liquid was combined, sucked into a multi-effect energy-saving evaporation concentration device, and concentrated until the relative density reached 1.23 at 80-85°C; The extract is dried in a microwave vacuum oven, crushed and made into dry extract powder of 80-100 mesh; mix the above powders, take the mixed powder and cross-linked polyvinylpyrrolidone according to the above weight percentage, mix for 30 minutes, and then add calcium bicarbonate and talc Powder, mixed well, for later use; hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate are used as slow-release coating materials, dissolved in water and diluted to an appropriate concentration for use as a binder, for use as a spare medicine powder The coating granulator takes the masterbatch, enlarges it, polishes it, dries it, granulates it, and packs it into a capsule.

Among them, the coating and granulation process is as follows: take the solution of the selected coating material as the binder, and use the BJZ-1000 type coating granulator to prepare the masterbatch of the mixed medicinal powder. The spraying speed is controlled at 40r/min. The rotation speed is controlled at 100r/min to make a 40-mesh masterbatch, and the masterbatch is dried for 1.5 hours to screen out 36-mesh particles, and the remaining particles are crushed into 100-mesh fine powder for starting the masterbatch; take 36-mesh particles and put them in BJZ -Into the 1000-type coating granulator, add coating solution and 100 mesh fine powder to enlarge; after the particles are enlarged to about 20 mesh, polish them; collect the enlarged particles (dry matter quantity) and dry them in the PGL spray granulator , Whole grain, sieve out 18 mesh granules and put them in capsules, and the remaining granules continue to be crushed into 100 mesh powder for starting mother. Concentration process conditions and microwave vacuum drying process conditions are the same as in Example 1.

Example 5 of the present invention: Senecio 3636g, Selaginella 606g, Cassia 363g, Ephedra 121g, Notopterygium 20g, Angelica dahurica 12g and Ligusticum chuanxiong 12g are extracted and made into medicinal powder, and then calculated by weight percentage, take 75% mixed medicinal powder, 7% disintegrant (low-substituted hydroxypropyl methylcellulose and cross-linked polyvinylpyrrolidone), 4% glidant (magnesium stearate), 4% absorbent (calcium bicarbonate), 10% Sustained-release coating materials (hydroxymethylcellulose and sodium hydroxymethylcellulose)

Preparation method: Take notopterygium, Chuanxiong, Baizhi, and ephedra net medicinal materials, crush them with a universal grinder and pass through a 100-mesh sieve, pack the medicinal powder in a sterilizing car, put them in a steam sterilizing cabinet, and sterilize at 115°C Reserve for 30 minutes; put Senecio, Selaginella, and Cassia into a multi-functional Chinese medicine extraction tank, add 7 times the weight of the medicinal materials in water for the first time, warm soak for 10 hours, decoct for 1 hour, and add 9 Water twice the weight of the medicinal material, decoct for 1 hour, the decoction temperature is controlled at 95-100°C, the decocted liquid is combined, sucked into a multi-effect energy-saving evaporation and concentration device, and concentrated until the relative density reaches 1.24 at 80-85°C; The extract is dried in a microwave vacuum oven, crushed and made into 80-100 mesh dry extract powder; the above powders are mixed, and the mixed powder is mixed with low-substituted hydroxypropyl methylcellulose and cross-linked polyvinylpyrrolidone according to the above weight percentage. After 30 minutes, add calcium bicarbonate and magnesium stearate, mix well, and set aside; use hydroxymethylcellulose and sodium hydroxymethylcellulose as slow-release coating materials, dissolve them in water and dilute to an appropriate concentration for binding Preparation, standby medicinal powder, take the masterbatch with a coating granulator, enlarge, polish, dry, granulate, pack into capsules, that is to say.

Among them, the coating and granulation process is as follows: take the solution of the selected coating material as the binder, and use the BJZ-1000 type coating and granulation machine to obtain the masterbatch of the mixed medicinal powder. The spraying speed is controlled at 50r/min. Control the rotation speed at 130r/min to make 40-mesh masterbatch, dry the masterbatch for 1.5 hours, sieve out 32-mesh particles, and crush the remaining particles into 100-mesh fine powder for starting mother; take 32-mesh particles and put them in BJZ -Into the 1000-type coating granulator, add coating solution and 100 mesh fine powder to enlarge; after the particles are enlarged to about 20 mesh, polish them; collect the enlarged particles (dry matter quantity) and dry them in the PGL spray granulator , Whole grain, sieve out 22 mesh granules and pack into capsules, and the rest of the granules continue to be crushed into 100 mesh powder for starting mother. Concentration process conditions and microwave vacuum drying process conditions are the same as in Example 1.

Claims (9)

1. capsule for the treatment of rhinitis, it is characterized in that: calculate according to composition by weight: it is to be prepared into medicated powder after extracting with Herba Senecionis Scandentis 9696～2424, Herba Selaginellae 1616～404, Semen Cassiae 968～242, Herba Ephedrae 324～81, Rhizoma Et Radix Notopterygii 64～8, the Radix Angelicae Dahuricae 64～8 and Rhizoma Chuanxiong 64～8, count by weight percentage then, get mixed medicated powder 50～85%, disintegrating agent 5～10%, fluidizer 0.5～10% and absorbent 0.5～10%, sustained release coating material 5～25% is prepared from.

2. according to the capsule of the described treatment rhinitis of claim 1, it is characterized in that: calculate according to composition by weight: it is to be prepared into medicated powder after extracting with Herba Senecionis Scandentis 4848g, Herba Selaginellae 808g, Semen Cassiae 484g, Herba Ephedrae 162g, Rhizoma Et Radix Notopterygii 32g, Radix Angelicae Dahuricae 16g and Rhizoma Chuanxiong 16g, count by weight percentage then, get mixed medicated powder 68%, disintegrating agent 8%, fluidizer 2% and absorbent 2%, sustained release coating material 20% is prepared from.

3. according to the capsule of claim 1 or 2 described treatment rhinitis, it is characterized in that: described disintegrating agent is any one or a two or more mixture among pregelatinized Starch PS, carboxymethyl starch sodium CMC-Na, low substituted hydroxy-propyl methylcellulose L-HPC, the crospolyvinylpyrrolidone PPVP; Fluidizer is any one or a two or more mixture in micropowder silica gel, Pulvis Talci, hydrated silica gel acid sodium, Cab-O-sil, the magnesium stearate; Absorbent is any one or a two or more mixture in light magnesium oxide, calcium bicarbonate, the calcium carbonate; The sustained release coating material is any one or a two or more mixture in Brazil wax, corn gum, gelatin, ethyl cellulose, methylcellulose, Hydroxypropyl Methylcellulose Phathalate, cellulose acetate-phthalate, hydroxyethyl-cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose HPMC, hydroxy methocel, Carboxymethyl cellulose sodium, polyvinylpyrrolidone, the polyvinyl alcohol.

4. treat the preparation method of the capsule of rhinitis according to claim 1, it is characterized in that: get Rhizoma Et Radix Notopterygii, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, the clean medical material of Herba Ephedrae, pulverize and cross 100 mesh sieves with Universalpulverizer, medicated powder is sub-packed in the vehicle of sterilization, put into vacuum sterilizer, under 115 ℃ of conditions the sterilization 30 minutes standby; In addition Herba Senecionis Scandentis, Herba Selaginellae, Semen Cassiae are dropped in the multipotency formula Chinese medicine extraction jar, add the water of 6-10 times of medical material weight for the first time, warm macerating 4-12 hour, decocted 1 hour, add the water of 7-9 times of medical material weight for the second time, decocted 1 hour, decoct temperature and be controlled at 95～100 ℃; Merge fried liquid, suck in the efficient energy-saving evaporation concentration device and concentrate, reach 1.21～1.25 to 80-85 ℃ of relative density; Gained extractum with microwave vacuum drying case drying, is made 80～100 purpose extract dry powder after the pulverizing; Above medicated powder mixes, and counts by weight percentage, and the mixed powder of getting 50-85% mixed 30 minutes with the disintegrating agent of 5-10%, added the absorbent of 0.5-10% and the fluidizer of 0.5-10% again, and mixing is standby; Get the sustained release coating material of 5-25%, with water dissolution and be diluted to debita spissitudo as binding agent, produce master batch with coating granulator, amplify, polish with mixed medicated powder, drying, granulate, encapsulated, promptly.

5. according to the preparation method of the capsule of the described treatment rhinitis of claim 4, it is characterized in that: get Rhizoma Et Radix Notopterygii, Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, the clean medical material of Herba Ephedrae, pulverize and cross 100 mesh sieves with Universalpulverizer, medicated powder is sub-packed in the vehicle of sterilization, put into vacuum sterilizer, under 115 ℃ of conditions the sterilization 30 minutes standby; Herba Senecionis Scandentis, Herba Selaginellae, Semen Cassiae are dropped in the multipotency formula Chinese medicine extraction jar in addition, the water that adds for the first time 10 times of medical material weight, warm macerating 6 hours, decocted 1 hour, and added the water of 8 times of medical material weight for the second time, decocted 1 hour, decoct temperature and be controlled at 95～100 ℃, merge fried liquid, suck and to advance type in the efficient energy-saving evaporation concentration device and concentrate, reach 1.22 to 80-85 ℃ of relative density; Gained extractum with microwave vacuum drying case drying, is made 80～100 purpose extract dry powder after the pulverizing; Above medicated powder mixes, and counts by weight percentage, and gets 68% mixed powder and 8% disintegrating agent carboxymethyl base Starch Sodium, mixes 30 minutes, adds 2% absorbent calcium bicarbonate and 2% fluidizer micropowder silica gel again, and mixing is standby; Get 20% ethyl cellulose and hydroxypropyl methylcellulose mixtures and make the sustained release coating material, with water dissolution and be diluted to debita spissitudo, produce master batch with coating granulator with mixed medicated powder as binding agent; amplify polishing, drying; granulate, encapsulated, promptly.

6. according to the preparation method of the capsule of claim 4 or 5 described treatment rhinitis, it is characterized in that: described concentration technology condition is: steam pressure≤0.09Mpa, vacuum I imitate to-0.01～-0.02Mpa, II imitate to-0.03～-0.04Mpa, III imitate for-0.05-～-0.06Mpa; It is 85～95 ℃ that temperature I is imitated, II is imitated is 75～85 ℃, III is imitated is 65～75 ℃.

7. according to the preparation method of the capsule of claim 4 or 5 described treatment rhinitis, it is characterized in that: described microwave vacuum drying process condition is: adopt wavelength 1mm～1m, frequency 2450MHz.

8. according to the preparation method of the capsule of claim 4 or 5 described treatment rhinitis, it is characterized in that: described coating granulating process condition is: the solution of getting selected coating material is made binding agent, mixed medicated powder is produced master batch with BJZ-1000 type coating granulator, spouting velocity is controlled at 30-60r/min, engine speed is controlled at 80-150r/min, make 40 purpose master batches, with master batch oven dry 1.5 hours, sift out 24-40 purpose granule, all the other size particles are ground into 100 order fine powders and have been used for female; Get 24-40 purpose granule and put in the BJZ-1000 type coating granulator, add coating solution and 100 order fine powders and amplify, after granule is amplified to about 20 orders, polishing; Granule after collect amplifying is put in the PGL type spray granulation machine dry, and granulate crosses that to sift out 16-24 order granule encapsulated, and all the other granules continue to be ground into 100 order powder and have been used for mother.

9. according to the preparation method of the capsule of the described treatment rhinitis of claim 8, it is characterized in that: the process conditions that coating is granulated are: the solution of getting selected coating material is made binding agent, mixed medicated powder is produced master batch with BJZ-1000 type coating granulator, spouting velocity is controlled at 50r/min, engine speed was controlled at 120r/min, makes 40 purpose master batches, with master batch oven dry 1.5 hours, sift out 30 purpose granules, all the other size particles are ground into 100 order fine powders and have been used for female; Get 30 purpose granules and put in the BJZ-1000 type coating granulator, add coating solution and 100 order fine powders and amplify; After granule is amplified to about 20 orders, polishing; Granule after collect amplifying is put in the PGL type spray granulation machine dry, and granulate crosses that to sift out 20 order granules encapsulated, and all the other granules continue to be ground into 100 order powder and have been used for mother.