CN102380101B - A compound medicinal preparation containing pholcodine for treating common cold - Google Patents

Abstract

The invention relates to the field of medicines, in particular to a medicine preparation for treating colds and influenza. The pharmaceutical preparations include pholcodine, antipyretic and analgesic agents, and decongestants.

Description

A compound medicinal preparation containing pholcodine for treating common cold

This application is a divisional application of the application number 200910222919.4 and the title of the invention "a compound pharmaceutical preparation containing pholcodine for treating colds" submitted on November 13, 2009.

technical field

The invention relates to the field of pharmaceutical preparations, in particular to a compound pharmaceutical preparation containing pholcodine for treating colds.

Background technique

Influenza is a common respiratory disease caused by a variety of viruses, and has a high incidence rate. At present, the more practical treatment method is to relieve cold symptoms through the combination of antipyretic and analgesics, nasal decongestants, antihistamines and central cough suppressants--fever caused by colds, headache, sore limbs, sneezing , runny nose, stuffy nose, cough, etc.

Central antitussives have strong antitussive effect and have mild sedative and analgesic effects; antipyretic and analgesic drugs have antipyretic effect while relieving pain; decongestants can relieve nasal congestion symptoms and relieve cough; Amine medicines can relieve allergic symptoms such as sneezing in colds, and these medicines have the characteristics of drowsiness. If the preparations containing such medicines are taken at night, patients can have better sleep and relieve fatigue and other symptoms better.

At present, the central antitussive drugs that are widely used in the market are codeine phosphate and dextromethorphan hydrobromide: codeine phosphate has a relatively high degree of addiction, and there have been many abuse accidents in the market and have been criticized by the state. Strict control by the Food and Drug Administration; dextromethorphan hydrobromide has a good antitussive effect, but now there are more and more cases of adverse reactions, and there are also a large number of abuse incidents. The U.S. Food and Drug Administration always pays attention to the right Abuse of dextromethorphan and warnings not to abuse dextromethorphan. Pholcodine is also a central antitussive drug, which has a central antitussive effect similar to codeine phosphate, and also has sedative and analgesic effects, but its addiction is weaker than codeine phosphate, and newborns and children tolerate this drug . Moreover, the drug is absorbed quickly and eliminated slowly, which has a positive effect on reducing the number of times of taking the drug and ensuring safe drug use.

Patent CN200410040448.2 "Cold Medicine Composition for Treating Phlegmless Cough and Its Processing Method" is currently the only patent related to pholcodine in China. The patent uses pholcodine, pseudoephedrine hydrochloride, and chlorpheniramine maleate Sensitivity, 95% medicinal ethanol and purified water are prepared into medicaments. This patent can only be used for relieving cough and relieving asthma, but for fever caused by cold, headache, sore limbs, sneezing, runny nose, nasal congestion cannot be effectively relieved. Simultaneously owing to contain chlorpheniramine maleate, produce very strong side effect during daily use.

Contents of the invention

The object of the present invention is to provide a compound preparation using pholcodine as a central antitussive drug, which can effectively and rapidly treat colds and influenza.

The pharmaceutical preparation for treating cold and flu symptoms of the present invention is characterized in that the pharmaceutical preparation comprises: pholcodine, antipyretic analgesic and decongestant.

Antihistamines are also included in the pharmaceutical preparations of the invention.

Pharmaceutical preparation of the present invention, the preparation of its unit dose is composed as follows:

Pholcodine 1-60mg

Antipyretic analgesic 50-4000mg

Decongestants 5-400mg

or

The compound preparation of the present invention is divided into daily preparation and night preparation.

The daily preparation includes: pholcodine, antipyretic analgesic, and decongestant. Daily formulation for the relief of cold and flu symptoms during the day.

The nighttime preparations include: pholcodine, antipyretic analgesics, decongestants and antihistamines. The nighttime formulation can help improve sleep in addition to relieving cold and flu symptoms.

Daily preparation of the present invention, formula is composed as follows:

Pholcodine 1-60mg

Antipyretic analgesic 50-4000mg

Decongestants 5-400mg

The night preparation of the present invention has a formula as follows:

Wherein said antipyretic and analgesic drugs are selected from paracetamol, aspirin, ibuprofen or ketoprofen. Acetaminophen is preferred.

The decongestant is selected from: ephedrine, pseudoephedrine or pharmaceutically acceptable salts thereof. Pseudoephedrine hydrochloride is preferred.

The antihistamine is selected from the group consisting of diphenhydramine, chlorpheniramine, tripyramine, promethazine, loratadine, cetirizine or pharmaceutically acceptable salts thereof. Diphenhydramine hydrochloride is preferred.

The preferred daily preparation of the present invention, formula is as follows:

Pholcodine 1-60mg

Acetaminophen 50-4000mg

Pseudoephedrine hydrochloride 5-400mg.

The preferred night-use preparation of the present invention has a formula as follows:

The further preferred daily preparation of the present invention, formula composition is as follows:

Pholcodine 1-30mg

Acetaminophen 50-750mg

Pseudoephedrine hydrochloride 10-300mg.

The further preferred night-use preparation of the present invention, formula composition is as follows:

The particularly preferred daily preparation of the present invention, formula composition is as follows:

Pholcodine 1-15mg

Acetaminophen 50-650mg

Pseudoephedrine hydrochloride 1-50mg.

The particularly preferred night-use preparation of the present invention, formula composition is as follows:

The most preferred compound preparation of the present invention is in the embodiment.

One or more pharmaceutical additives can be added into the formula of the compound preparation of the present invention.

The pharmaceutical additives include but not limited to diluents, fillers, binders, adhesives, lubricants, glidants, disintegrants, surfactants, carrier solvents, plasticizers, diluents, buffers agents, antibacterial agents, preservatives, coloring agents, flavoring agents, stabilizers and other pharmaceutical additives known in the art.

Lubricants include, but are not limited to, magnesium stearate, calcium stearate, zinc stearate, powdered stearic acid, glyceryl monostearate, glyceryl palmitostearate, silica gel, magnesium silicate, silicon dioxide , titanium dioxide, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, nitrogenated vegetable oil, talc, macrogol and mineral oil.

Surfactants include, but are not limited to, sodium lauryl sulfate, sodium dioctyl sulfosuccinate, triethanolamine, polyoxyethylene sorbitan; excipients such as lactose, mannitol, glucose, fructose, xylose, Galactose, sucrose, maltose, xylitol, sorbitol, and chlorides, sulfates, and phosphates of potassium, sodium, and magnesium; gelling agents, such as colloidal clay; thickening agents, such as sodium alginate, effervescent mixtures and wetting agents such as lecithin, polysorbates or lauryl sulfates.

Colorants can be used to improve appearance, or to identify pharmaceutical compositions. Such as food coloring.

In embodiments where the pharmaceutical composition is compressed into a solid dosage form such as a tablet, a binder can help to hold the ingredients together. Binders include, but are not limited to, sugars such as sucrose, lactose, and glucose; complex syrups; soybean polysaccharides; gelatin; povidone; cellulose derivatives such as microcrystalline cellulose, hydroxypropylmethylcellulose, hydroxypropyl Acrylic acid and methacrylic acid copolymers; Carbomer; Polyvinylpolypyrrolidine; Polyethylene glycol; Syrups; alginates, such as alginic acid and sodium alginate; gums, such as acacia, guar and acacia; tragacanth; dextrins and maltodextrins; milk derivatives, such as whey; starches Such as pregelatinized starch and starch slurry; hydrogenated vegetable oil; magnesium aluminum silicate, and other conventional binders known to those skilled in the art. Typical, non-limiting fillers include sugar, lactose, gelatin, starch and silicon dioxide.

Glidants can improve the fluidity of non-compressed solid dosage forms, and can improve the accuracy of quantitative feeding. Glidants include, but are not limited to, silicon dioxide, silica gel, talc, magnesium trisilicate, magnesium or calcium stearate, micronized cellulose, starch and tricalcium phosphate.

Plasticizers include, but are not limited to, hydrophobic and/or hydrophilic plasticizers such as diethyl phthalate, butyl phthalate, diethyl sebacate, dibutyl sebacate, lemon Triethyl Citrate, Acetyl Triethyl Citrate, Acetyl Tributyl Citrate, Propylene Glycol, Castor Oil, Glyceryl Acetate, Polyethylene Glycol, Propylene Glycol, Glycerin and Sorbitol. Plasticizers are particularly useful in pharmaceutical compositions containing polymers and pharmaceutical compositions in soft capsules and film-coated tablets. Flavoring agents improve palatability, especially for chewable tablet or liquid dosage forms. Flavoring agents include, but are not limited to, maltitol, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid, ethyl maltitol, and tartaric acid. Sweeteners include, but are not limited to, sorbitol, saccharin, sodium saccharin, sucrose, aspartame, fructose, mannitol, and invert sugar.

Preservatives and/or stabilizers to improve shelf life include, but are not limited to, ethanol, sodium benzoate, butylated hydroxytoluene, butylated p-hydroxytoluene, and ethylenediaminetetraacetic acid.

Disintegrants can increase the dissolution rate of pharmaceutical compositions. Disintegrants include, but are not limited to, alginates (such as alginic acid and sodium alginate), calcium carboxymethylcellulose, sodium carboxymethylcellulose, colloidal silicon dioxide, croscarmellose sodium, crosslinked Povidone, polyvinylpolypyrrolidine, guar gum, magnesium aluminum silicate, methylcellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, starch, pregelatinized starch, sodium starch glycolate.

Diluents can increase the bulk of the dosage form, which can make the dosage form easier to handle. Typical diluents for solid dosage forms such as tablets and capsules include, but are not limited to, lactose, dextrose, sucrose, cellulose, starch, and calcium phosphate; olive oil and ethyl oleate for soft capsules; water and vegetable oils for dosage forms such as suspensions and emulsions. Other suitable diluents include, but are not limited to, sucrose, dextran, dextrin, maltodextrin, microcrystalline cellulose, micronized cellulose, powdered cellulose, pregelatinized starch, calcium phosphate dihydrate, soybean polysaccharide, gelatin , Silica, Calcium Sulfate, Calcium Carbonate, Magnesium Carbonate, Magnesium Oxide, Sorbitol, Mannitol, Kaolin, Polymethacrylate, Potassium Chloride, Sodium Chloride, and Talc.

In embodiments wherein the combination formulation is presented as a liquid dosage form, the pharmaceutical composition may comprise one or more solvents. Suitable solvents include, but are not limited to, water, alcohols (eg, ethanol and isopropanol), vegetable oils, polyethylene glycol, propylene glycol, and glycerin, or mixtures and combinations thereof.

According to the present invention, the compound preparation may contain a buffering agent. Buffering agents include, but are not limited to, lactic acid, citric acid, acetic acid, sodium lactate, sodium citrate, and sodium acetate.

Hydrophilic polymers suitable for sustained release formulations include: one or more natural or partially or fully synthetic hydrophilic gums, such as gum arabic, tragacanth; modified cellulosic substances, such as methylcellulose, Hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose; protein analogs such as agar, pectin, and alginates; other hydrophilic Hydrophilic polymers such as carbomer, gelatin, casein, zein, magnesium aluminum silicate, polysaccharides, modified starch derivatives and other hydrophilic polymers or combinations of such polymers known to those skilled in the art.

The compound preparation of the present invention can be made into any pharmaceutically acceptable dosage form, which is suitable for retarding the formulation and ensuring the release of the active compound in the manner of the present invention. Preferred dosage forms are: syrup, oral liquid, granule, suspension, drop, tablet, capsule, powder, chewable tablet, dispersible tablet, sustained-release tablet, sustained-release capsule, pellets, gel preparation, etc. These medication forms all achieve clinical effects through oral administration.

Another object of the present invention is to provide a preparation method of the compound preparation of the present invention.

The compound preparation of the present invention can be made into oral preparations, such as: oral liquids, syrups, granules, suspensions, drops, gel preparations and other oral liquid preparations, and the unit dose is the amount of the pharmaceutical composition per 1ml . Oral liquid preparations are prepared by dissolving and diluting, and then the liquid is subpackaged into, for example, a syrup with suitable additives and methods.

The preparations prepared by the method of dissolution and dilution according to the present invention are preferably carried out at an elevated temperature during the mixing of the ingredients, which may be from 25 to 100°C, preferably from 40 to 60°C. The components should remain in solution to achieve the benefits of the present invention, and the solution should be stable over time and under the conditions normally encountered in consumer use. For example, having stood at room temperature for a period of time, the solution remains clear and stable without precipitation of the active ingredient. Furthermore, the solution has been subjected to alternating freezing and room temperature conditions without crystallization of the active ingredient and remains clear and stable.

The compound preparation of the present invention can also be made into oral preparations of other dosage forms, such as: tablets, capsules, chewable tablets, dispersible tablets, sustained-release tablets, sustained-release capsules, and oral solid preparations such as micropills. The unit dose is each tablet, The amount of pharmaceutical composition contained in granules and bags.

Oral solid preparations are particularly advantageous in which the drug is manufactured by spraying and extrusion granulation techniques, and then compressed into, for example, tablets or subpackaged into, for example, capsules using suitable additives and methods. In a particularly preferred embodiment, the extrusion spheronization method is used to manufacture pharmaceutical preparations, the main processes of which are compounding, mixing and granulation, extrusion forming, centrifugal spheronization, sieving, and drying. In the embodiment, the purpose is achieved through professional equipment. Such as wet mixing granulator, extrusion machine, centrifugal spheronizer, etc.

The extrusion spheronization method is a newly established production method in recent years. The drug produced by the extrusion spheronization method is a pellet, which is different from the drug granules produced by the general extrusion method. The high drug loading is one of its major advantages. According to reports at home and abroad, the pellets made by the coating pot and the fluidized bed are used. The drug loading of pellets prepared by pelleting method or other methods is generally 20-50%, while the drug loading of pellets prepared by extrusion and spheronization technology can reach more than 80%. And it can be coated with moisture-proof and light-proof coating according to the needs of varieties. Those skilled in the art can fully understand that in order to produce products with desired characteristics, various parameters can be changed during the extrusion spheronization process, such as raw material particle size, moisture content, pellet size, extrusion speed, spheronization speed, spheronization time wait. The Examples section provides various examples of formulations according to the invention, which were prepared using extrusion spheronization.

The above parameters will be determined by the professional equipment used, the nature of the drug, and the production environment. In an embodiment, the particle size of the raw material may be 50 to 200 mesh, preferably 100 mesh. Moisture is determined because of the difference of packing material, selects capsule for use in the embodiment, because this kind diphenhydramine hydrochloride is hygroscopic seriously, so moisture is controlled below 3%. Often select the appropriate particle size of the pellets to increase the bulk density of the pellets and meet the loading requirements. The preferred particle size of the pellets is about 0.1mm to 1.5mm, especially preferably 0.5mm. Those skilled in the art can fully understand that the extrusion speed, spheronization speed, and spheronization time have a great influence on the quality of the drug, and the extrusion speed can be 10 to 200 rpm, preferably 55 rpm. The spheronization speed can be 100 to 2000 rpm, preferably 600 to 800 rpm, and the spheronization time can be 0.5 min to 3 min, preferably 2 min.

Those skilled in the art know that the above-mentioned parameters all depend on special production conditions (production environment, equipment type, material properties, material quantity, etc.), and it may be necessary to modify them so that the preparations obtained by extrusion or extrusion spheronization provide continuous , independent and stable release, and the aforementioned storage stability.

The compound preparation of the present invention is divided into daily preparation and night preparation.

The compound preparation of the present invention can be packaged individually for daily use, for night use alone or as a mixture of day and night preparations. Likewise, the combination preparations of the present invention may also contain or be accompanied by indicia that allow one to identify the combination preparations as products for the prescribed treatment. For example, in order to distinguish the mixed packaging of day-use and night-use preparations, the day-use and night-use preparations can be endowed with different colors or three-dimensional geometric configurations.

The compound preparation of the invention can effectively and rapidly treat colds and influenza, such as: fever, headache, soreness in limbs, sneezing, runny nose, nasal congestion, coughing, etc. caused by colds.

Compared with the prior art, the compound preparation of the present invention has synergistic effect, good therapeutic effect, quick effect, low drug resistance, high medicinal safety, few side effects, good stability, long value preservation period, convenient portability and low price , simple preparation and operation, suitable for large-scale production and the like.

Description of drawings

Fig. 1: the test curve chart of prescription 1 daily use preparation in embodiment 4

Fig. 2: the test graph of prescription 2 daily use preparations in embodiment 4

Fig. 3: the test curve graph of prescription 1 night use preparation in embodiment 4

Fig. 4: the test curve graph of prescription 2 night use preparations in embodiment 4

Detailed ways

The present invention is further illustrated by the following examples, but not as a limitation of the present invention.

Embodiment 1 utilizes the compound tablet that spray granulation method makes to contain different amounts

Table 1, compound tablet of the present invention form

Preparation

In a 100,000-class clean area

A crosses 100 mesh sieves with pholcodine, paracetamol, pseudoephedrine hydrochloride, diphenhydramine hydrochloride (night use);

B receives a small amount of starch for mixing, adds half of the prescription amount of Tween 80 and stirs to make an adhesive;

C takes the prescribed amount of povidone, adds purified water and Tween 80 and stirs to make an adhesive;

D paracetamol, pseudoephedrine hydrochloride, diphenhydramine hydrochloride (night use) and starch, sodium carboxymethyl starch are put into premixed boiling granulator;

E successively spray the adhesive and the adhesive into the boiling granulator with a peristaltic pump, and turn off the peristaltic pump after spraying. Dry, control moisture 3%;

D18 mesh granules, mixed with magnesium stearate, compressed into tablets.

Embodiment 2 utilizes the compound tablet that extrusion granulation method makes

Table 2, compound tablet of the present invention.

Preparation

In a 100,000-class clean area

A crosses 100 mesh sieves with pholcodine, paracetamol, pseudoephedrine hydrochloride, diphenhydramine hydrochloride (night use);

B takes the main ingredient and microcrystalline cellulose of prescription dosage, precrossed starch, PVPP, and mixes evenly;

C3% PVP solution for softening, 18# granulation, drying, moisture control 3%;

D18 mesh granules, mixed with magnesium stearate, compressed into tablets.

The compound syrup that embodiment 3 makes

Table 3, compound syrup of the present invention.

components daily preparations night preparation Acetaminophen 325g 325g Pholcodine 5 5g Pseudoephedrine Hydrochloride 30g 30g Diphenhydramine hydrochloride - 12.5g citric acid 0.8g 0.8g

sucrose some some Potassium sorbate 1.5g 1.5g ethanol Appropriate amount Appropriate amount artificial flavor 200μL 200μL Co-made 1000Ml 1000mL

Preparation:

In a 100,000-class clean area

A540g sucrose is dissolved in 200mL boiled water to make syrup, filter;

B takes by weighing the prescribed amount of pholcodine, and dissolves it in an appropriate amount of ethanol;

C takes prescription quantity paracetamol, pseudoephedrine hydrochloride, diphenhydramine hydrochloride (night use) and is dissolved in 50mL purified water;

D Mix the solution obtained in step A, step B and step C, add purified water to 1000mL, then add potassium sorbate, artificial essence, citric acid, filter to obtain syrup, check and pack.

Embodiment 4 utilizes the compound capsule that extrusion spheronization method makes

Table 4. Compound capsules of the present invention prepared by extrusion spheronization.

Preparation:

In a 100,000-class clean area

A Pass pholcodine, acetaminophen, pseudoephedrine hydrochloride and diphenhydramine hydrochloride through a 100-mesh sieve;

B Mix the prescribed amount of pholcodine, pseudoephedrine hydrochloride, diphenhydramine hydrochloride (night use), microcrystalline cellulose, and sodium carboxymethyl starch, and mix them evenly with acetaminophen in equal increments.

C Dissolve the prescribed amount of sodium lauryl sulfate in 5% PVPk30 solution to make wet soft material.

D is extruded at a speed of 45rpm through an extruder with a 0.5mm screen. After extrusion, it is quickly cast into pellets in a shot blasting machine, and then dried in a fluidized bed at 60-70°C, and sieved to 16-30 mesh The pellets in between, measure the water content, pack into capsules, and pack.

The release pattern of the compound capsule that embodiment 5 embodiment 4 makes

Apply the drug basket method of the Chinese Pharmacopoeia, use hydrochloric acid solution as the dissolution medium, paracetamol use spectrophotometry, pseudoephedrine hydrochloride, pholcodine and diphenhydramine hydrochloride use high performance liquid phase method, after 45 minutes to measure the concentration of active compounds freed. Tested the compound capsule in prescription 1 in embodiment 4, prescription 2. Figure 1, Figure 2, Figure 3, and Figure 4 are the test curves respectively.

Table 5. The release of different components over 45 minutes as measured by prescription 1 in Example 4

Table 6. Release of different components over 45 minutes as measured for formulation 2 in Example 4

The stability investigation situation of the compound capsule that embodiment 6 embodiment 4 makes

The drug basket method of the Chinese Pharmacopoeia was applied, with hydrochloric acid solution as the dissolution medium, paracetamol was used spectrophotometry, pseudoephedrine hydrochloride, pholcodine and diphenhydramine hydrochloride were used high performance liquid chromatography, and the active compounds were measured over 24 months release and content. Tested the compound capsule in prescription 1 in embodiment 4, prescription 2.

From the values shown in the table below, it is known that the release of components with different contents remains the same and stable.

Table 7. The release and content of different components measured over 24 months for the prescription 1 daily formulation in Example 4.

Table 8. The release and content of different components measured over 24 months for the prescription 1-night formulation in Example 4.

Table 9. The release and content of different components measured over 24 months for the prescription 2-day formulation in Example 4.

Table 10. The release and content of different components measured over 24 months for the prescription 1-night formulation in Example 4.

Embodiment 7, daily use of the present invention, night preparation

Daily use:

Pholcodine 1mg

Acetaminophen 50mg

Pseudoephedrine hydrochloride 1mg.

Night use preparation, the formula composition is as follows:

Embodiment 8, daily use of the present invention, night preparation

Daily use:

Pholcodine 1mg

Acetaminophen 50mg

Pseudoephedrine hydrochloride 1mg.

Night use preparation, the formula composition is as follows:

Embodiment 9, daily use of the present invention, night preparation

Daily use:

Pholcodine 1mg

Acetaminophen 50mg

Pseudoephedrine hydrochloride 10mg.

Night use preparation, the formula composition is as follows:

Embodiment 10, daily use of the present invention, night preparation

Daily use:

Pholcodine 30mg

Acetaminophen 750mg

Pseudoephedrine hydrochloride 300mg.

Night use preparation, the formula composition is as follows:

Embodiment 11, daily use of the present invention, night preparation

Daily use:

Pholcodine 1mg

Acetaminophen 50mg

Pseudoephedrine hydrochloride 5mg.

The preferred night-use preparation of the present invention has a formula as follows:

Embodiment 10, daily use of the present invention, night preparation

Daily use:

Pholcodine 60mg

Acetaminophen 4000mg

Pseudoephedrine hydrochloride 400mg.

Night use preparation, the formula composition is as follows:

Embodiment 11, daily use of the present invention, night preparation

Daily use:

Pholcodine 60mg

Aspirin 250mg 325mg

Ephedrine 15mg 30

Night use preparation, the formula composition is as follows:

Embodiment 12, daily use of the present invention, night preparation

Daily use:

Pholcodine 60mg

Ibuprofen 325mg

Ephedrine 30mg

Night use preparation, the formula composition is as follows:

Embodiment 13, daily use of the present invention, night preparation

Daily use:

Pholcodine 60mg

Ketoprofen 250mg

Ephedrine 15mg

Night use preparation, the formula composition is as follows:

Embodiment 14, daily use of the present invention, night use preparation

Daily use:

Pholcodine 60mg

Ketoprofen 325mg

Ephedrine 30mg

Night use preparation, the formula composition is as follows:

Embodiment 15, daily use of the present invention, night preparation

Daily use:

Pholcodine 60mg

Ketoprofen 325mg

Ephedrine 30mg

Night use preparation, the formula composition is as follows:

Embodiment 16, daily use of the present invention, night use preparation

Daily use:

Pholcodine 60mg

Ketoprofen 325mg

Ephedrine 30mg

Night use preparation, the formula composition is as follows:

Claims (2)

1. a preparation method of a pharmaceutical preparation for the treatment of cold and influenza symptoms, wherein the pharmaceutical preparation consists of:

The preparation method of described daily preparation is: In a 100,000-class clean area A will pass pholcodine, paracetamol, pseudoephedrine hydrochloride through 100 mesh sieves; B mixes the pholcodine, pseudoephedrine hydrochloride, microcrystalline cellulose, carboxymethyl starch sodium of prescription quantity, mixes evenly with acetaminophen by the method of increasing in equal amounts; C dissolve the sodium lauryl sulfate of prescription quantity in 5% PVPk30 solution and make wet soft material; D is extruded at a speed of 45rpm through an extruder with a 0.5mm screen. After extrusion, it is quickly cast into pellets in a shot blasting machine, and then dried in a fluidized bed at 60-70°C, and sieved to 16-30 mesh The pellets in between, measure the water content, pack into capsules, and pack them; The preparation method of described night preparation is: In a 100,000-class clean area A Pass pholcodine, acetaminophen, pseudoephedrine hydrochloride and diphenhydramine hydrochloride through a 100-mesh sieve; B mixes the pholcodine, pseudoephedrine hydrochloride, diphenhydramine hydrochloride, microcrystalline cellulose, carboxymethyl starch sodium of the prescribed amount evenly, and mixes evenly with acetaminophen by the method of increasing in equal amounts; C dissolve the sodium lauryl sulfate of prescription quantity in 5% PVPk30 solution and make wet soft material; D is extruded at a speed of 45rpm through an extruder with a 0.5mm screen. After extrusion, it is quickly cast into pellets in a shot blasting machine, and then dried in a fluidized bed at 60-70°C, and sieved to 16-30 mesh The pellets in between, measure the water content, pack into capsules, and pack. 2. a preparation method of a pharmaceutical preparation for the treatment of cold and influenza symptoms, wherein the pharmaceutical preparation consists of:

The preparation method of described daily preparation is: In a 100,000-class clean area A will pass pholcodine, paracetamol, pseudoephedrine hydrochloride through 100 mesh sieves; B mixes the pholcodine, pseudoephedrine hydrochloride, microcrystalline cellulose, carboxymethyl starch sodium of prescription quantity, mixes evenly with acetaminophen by the method of increasing in equal amounts; C dissolve the sodium lauryl sulfate of prescription quantity in 5% PVPk30 solution and make wet soft material; D is extruded at a speed of 45rpm through an extruder with a 0.5mm screen. After extrusion, it is quickly cast into pellets in a shot blasting machine, and then dried in a fluidized bed at 60-70°C, and sieved to 16-30 mesh The pellets in between, measure the water content, pack into capsules, and pack them; The preparation method of described night preparation is: In a 100,000-class clean area A Pass pholcodine, acetaminophen, pseudoephedrine hydrochloride and diphenhydramine hydrochloride through a 100-mesh sieve; B mixes the pholcodine, pseudoephedrine hydrochloride, diphenhydramine hydrochloride, microcrystalline cellulose, carboxymethyl starch sodium of the prescribed amount evenly, and mixes evenly with acetaminophen by the method of increasing in equal amounts; C dissolve the sodium lauryl sulfate of prescription quantity in 5% PVPk30 solution and make wet soft material; D is extruded at a speed of 45rpm through an extruder with a 0.5mm screen. After extrusion, it is quickly cast into pellets in a shot blasting machine, and then dried in a fluidized bed at 60-70°C, and sieved to 16-30 mesh The pellets in between, measure the water content, pack into capsules, and pack.

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