WO2012139262A1

WO2012139262A1 - Sustained-release preparation of compound methoxyphenamine

Info

Publication number: WO2012139262A1
Application number: PCT/CN2011/001460
Authority: WO
Inventors: 田武; 王诺; 郑礼亮
Original assignee: 赛乐医药科技(上海)有限公司
Priority date: 2011-04-13
Filing date: 2011-08-30
Publication date: 2012-10-18
Also published as: CN102210687B; CN102210687A

Abstract

A sustained-release preparation of compound methoxyphenamine, with methoxyphenamine or hydrochloride thereof, noscapine, aminophylline and chlorpheniramine maleate as active components, wherein a ratio of the active components to a sustained-release adjuvant is 1:0.03 to 1:30, and the sustained-release preparation is a sustained-release tablet, a sustained-release capsule or a sustained-release suspensoid.

Description

Compound sustained release preparation of methoxyphenamine

The present invention relates to a compound sustained release preparation containing a pharmaceutical ingredient which is carbamazepine or its hydrochloride, narcotine, aminophylline, chlorpheniramine maleate, and which can be sustainedly released for 12 to 24 hours. Background technique

Compound methoxyphenamine is an antiasthmatic drug for bronchial asthma and asthmatic bronchitis. Bisphenamine or its hydrochloride can inhibit bronchospasm and relieve cough during asthma attacks. Nacod is a peripheral cough suppressant that inhibits coughing. Aminophylline can also inhibit bronchospasm, inhibit swelling of the bronchial mucosa, relieve cough during asthma attacks, and make cough easily. Chlorpheniramine maleate has antihistaminic effects. The compatibility of this product can not only reduce the cough caused by inflammation of the throat and bronchus, but also relieve the cough during the onset of asthma, which is conducive to drainage. At present, the compound oxymatrine product is taken by oral administration of 2 capsules once a day, 3 times a day.

Chinese Patent 200410065967. 4 discloses a preparation method of oral solid preparation containing pentoxamine, narcotine, aminophylline, chlorpheniramine maleate, and the compound oxime product obtained by the method does not have The effect of sustained release. According to the existing method of taking medicines for commercial use, not only the dosage is large, but also the number of times taken is high, which is not conducive to ensuring that patients take medicine on time.

Based on the shortcomings of existing formulations, the present invention provides a formulation which provides sustained release of the active ingredient for 12 to 24 hours. Summary of the invention

SUMMARY OF THE INVENTION An object of the present invention is to provide a sustained-release solid preparation and a suspension preparation which are effective ingredients of methoxyphenamine, narcotine, aminophylline, and chlorpheniramine maleate.

The object of the present invention can be achieved by the following measures:

The active ingredients are methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate, slow release excipients, and other excipients. The sustained release effect of the present invention is derived from a sustained release adjuvant, and is suitable for the water-soluble polymer sustained-release excipient of the present invention: one or more natural or partially or fully synthetic water-soluble colloids such as gum arabic, tragacanth, xanthan gum , locust bean gum, guar gum or carrageenan, cellulose derivatives such as methyl cellulose, hydroxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxy Sulfhydryl cellulose, protein such as agar, gelatin, pectin, carrageenan and alginic acid, sodium alginate, other water-soluble polymer sustained-release excipients such as hypromethylene, acrylic resin, polyvinylpyrrolidone, polyethylpyrrolidone Copolymer, polyethylene Alcohol, polyethylhydrin, gel, casein, zein, high territories, magnesium aluminosilicates, polysaccharides, starch derivatives, and other water soluble polymeric materials well known in the art; high water insolubility Molecular slow release excipients: polyacrylic acid, acrylic resin, acrylic latex emulsion, cellulose acetate phthalate, polyvinyl acetate phthalate, ethyl cellulose, cellulose acetate, polylactic acid, polyglycolic acid, poly Lactic acid-polyglycolic acid copolymer, carnauba wax, stearic acid, sodium stearyl fumarate and other water insoluble polymeric materials well known in the art. It is characterized in that the sustained-release excipient is any one or any two or a mixture of two or more of the above.

Preferably, the sustained release adjuvant is any one or any two or a mixture of two or more of the following:

(1) hydroxypropylmethylcellulose, (2) carboxymethylcellulose, (3) sodium carboxymethylcellulose, (4) hydroxypropylcellulose, (5) hydroxyethylcellulose, (6) Ethylcellulose, (7) polyvinylpyrrolidone, (8) polyvinylpyrrolidone copolymer, (9) sodium alginate, (10) cellulose acetate, (11) polyethylene glycol, (12) polyacrylic acid, ( 13) Acrylic resin, (14) cellulose acetate phthalate, (15) polyvinyl acetate phthalate, (16) polyvinyl alcohol, (17) gelatin, (18) gum arabic, (19) Carrageenan, (20) xanthan gum, (21) carnauba wax, ( ²² ) stearic acid, (23) sodium stearyl fumarate.

The weight ratio of the active ingredient to the sustained-release excipient in the present invention is between 1: 0.03 and 1:30, preferably between 1:0.05 and 1:16, more preferably between 1:0.08 and 1:10.

The filler in the present invention means any one or a mixture of microcrystalline cellulose, lactose, starch, pregelatinized starch, and calcium hydrogen citrate; and the lubricant means stearic acid or strontium stearate. Any one or a mixture of more than one of stearyl fumarate and silica.

The compound sustained release preparation of the present invention is a tablet, a capsule, or a suspension.

The preparation method of the tablet of the compound sustained-release preparation of the present invention is as follows:

Tablet preparation method one:

1. Mix the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) and slow-release excipients in a weight ratio of 1: 0.03 to 1: 30, and mix well;

2. Add appropriate amount of filler and lubricant to the above mixture and compress into tablets. Tablet preparation method 2:

2. Add an appropriate amount of solvent to the above mixture, stir into fine particles and dry; or extrude the mixture into a sheet; then pulverize the granules or flakes so that they can all pass the Chinese Pharmacopoeia No. 2 sieve ; 3. Add the dry granules from the previous step to the appropriate amount of filler and lubricant and compress into tablets. Tablet preparation method three:

1. Mix the active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) and mix well;

2. Dissolve the slow-release excipient in a suitable solvent to prepare a solution with a concentration of 1% to 30%;

3. adding the above-mentioned slow-release auxiliary solution to the above mixture to form wet granules; drying the wet granules; and pulverizing the dried granules so that they can all pass through the Chinese Pharmacopoeia No. 2 sieve;

4. Add the dry granules from the previous step to the appropriate amount of filler and lubricant and compress into tablets. Tablet preparation method four:

1. Mix the active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) with slow release excipients in a weight ratio of 1: 0.0 to 1: 30, stir well ;

2. The mixture is heated to a pellet; the granule or sheet is pulverized so that it can pass through the Chinese Pharmacopoeia No. 2 sieve;

3. Add the dry granules from the previous step to the appropriate amount of filler and lubricant and compress into tablets. Tablet preparation method five:

1. Mix the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) with an appropriate amount of filler and lubricant and compress into tablets;

2. Dissolve the slow-release excipient in a suitable solvent to prepare a solution with a concentration of 1% to 30%.

3. Pill the tablets prepared in the previous step with a 1% to 30% solution prepared in the previous step on a specific device. The weight ratio of the active ingredient to the sustained release excipient is between 1:03 and 1:30. Tablet preparation method six:

1. Dissolve the slow-release excipient in a suitable solvent to prepare a solution with a concentration of 1% to 30%.

2. The tablets obtained by the above methods 1 to 4 can be used at 1 °/. ~ 30% of the solution is coated on a specific device. The weight ratio of the active ingredient to the sustained release excipient is between 1:03 and 1:30. Tablet preparation method seven:

1. The active ingredients [methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate] and sustained release supplement Mix the hydroxypropyl ketone cellulose and xanthan gum in a weight ratio of 1: 0.03 to 1: 30 and mix well; or the active ingredients [曱 oxynamin, narcotine, aminophylline, horse And the sustained release hydroxypropyl ketone cellulose and sodium alginate are mixed and stirred evenly in a weight ratio of 1: 0.0 to 1: 30;

2. Add the appropriate amount of ethanol solution to the mixture obtained in the previous step, stir into fine particles and dry; pulverize and pass all the Chinese Pharmacopoeia No. 2 sieve;

3. Add the filler microcrystalline cellulose and the lubricant magnesium stearate to the granulated granules in the previous step and compress them into tablets. The preparation method of the capsule of the compound sustained-release preparation of the present invention is as follows:

Capsule preparation method one:

1. Mix the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) with slow release excipients in a weight ratio of 1: 0.03 to 1: 30, stir well ;

2. Add an appropriate amount of solvent to the above mixture, stir into fine particles and serve for drying; or extrude the above mixture into a sheet; then pulverize the granules or flakes so that they can all pass the Chinese Pharmacopoeia No. 2

3. Add the dry granules from the previous step to the appropriate amount of filler and lubricant and load into the capsule. Capsule preparation method 2:

1. Mix the active ingredients (oxyxazone, narcotine, aminophylline, chlorpheniramine maleate) with slow release excipients in a weight ratio of 1:0.3 to 1:30, and add Appropriate amount of filler, stir evenly;

2. Add an appropriate amount of solvent to the above mixture, stir it, and extrude it with a specific equipment to form pellets and dry;

3. Load the pellet from the previous step into the capsule. Preparation method of capsule preparation:

1. Dissolve the slow release excipient in a suitable solvent to a concentration of 1 ° /. ~ 30% solution

2. The pellets prepared by the above method 2 are coated on a specific device with the above 1% to 30% solution;

3. Fill the capsule with the coated pellets. Capsule preparation method four:

1. Dissolve or mix the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) Hang in a suitable solvent, add appropriate amount of binder, and mix well;

2. The solution or suspension prepared above is wrapped on the surface of a suitable size sugar pellet or microcrystalline cellulose pellet with a specific device to prepare a drug-coated pellet;

3. Dissolve the slow release auxiliary in a suitable solvent to prepare a solution with a concentration of 3% ~ 30%;

4. The drug-coated pellets prepared above are coated on a specific device with a 3% to 30% slow release adjuvant solution;

5. Pack the coated drug directly into the pellet, or add the appropriate amount of filler and lubricant to the capsule. Preparation method of capsule preparation:

1. The active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) and the slow release adjuvant polyethylene glycol and sodium alginate are in a weight ratio of 1: 0. 03 to 1 : Mix between 30, and add appropriate amount of filler microcrystalline cellulose, stir evenly;

2. Adding an appropriate amount of solvent to the mixture obtained in the previous step, stirring and hooking, preparing the pellets by an extrusion spheronizer and drying;

3. Fill the pellets obtained in the previous step into plastic bottles. Capsule preparation method six:

1. The active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) and the slow release adjuvant polyethylene glycol and sodium alginate are in a weight ratio of 1:0. 03 to 1 : Mix between 30, and add appropriate amount of filler microcrystalline cellulose, stir evenly;

2. Add an appropriate amount of solvent to the mixture obtained in the previous step, stir evenly, and prepare the pellets by an extrusion spheronizer and dry;

3. Dissolve the slow release auxiliary ethyl cellulose in a suitable solvent to prepare a solution having a concentration of 3 - 30%;

4. The pellet obtained in the step 2) is coated on the specific equipment by using the sustained-release auxiliary solution obtained in the step 3);

5. The coated pellets obtained in the previous step were filled into capsules. The preparation method of the suspension of the compound sustained-release preparation of the present invention is as follows:

Suspension preparation method one:

1. Mix the active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) with slow release excipients in a weight ratio of 1: 0.03 to 1: 30, stir well ; 2. Add an appropriate amount of solvent to the above mixture, stir into fine particles and dry; or extrude the mixture into a sheet; then pulverize the granules or flakes so that they can all pass the Chinese Pharmacopoeia No. 2 ;

3. Add the appropriate amount of filler and flavor to the dry granules of the previous step;

4. Add water to form a suspension before administration. Suspension preparation method 2:

3. Add the appropriate amount of filler and flavor to the pellets from the previous step;

4. Add water to form a suspension before administration. Suspension preparation method three:

1. Dissolve or mix the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) in a suitable solvent, add appropriate amount of binder, and mix well;

5. Add the coated drug-coated pellets to the appropriate amount of filler and flavoring agent; add water to stir to form a suspension. Suspension preparation method four:

1. The active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) and the slow release adjuvant ethyl cellulose, xanthan gum according to the weight ratio of 1: 0. 03 to 1 : mixing and adding microcrystalline cellulose between 30; adding appropriate amount of solvent to prepare granules;

2. Add appropriate amount of suspending ingredients, microcrystalline cellulose and sodium carboxymethyl cellulose, flavoring orange flavor and aspartame, to the granules obtained in the previous step, and mix well; 3. Add water to form a suspension before administration.

Through experiments, it has been found that the sustained release preparation of the compound of the present invention achieves a very good release effect by using the sustained release excipient, and the release degree is superior to the existing product, and meets the requirements of the national drug standard regarding the release degree. detailed description

The invention will now be described in further detail by way of specific examples, but not limited to the following examples: Example 1 : Compound tablets with sustained release up to 12 hours

Original excipient name Percent (%) Dose (mg) Methotrexate 11. 3 37. 5 Nacordine 6. 3 21 Aminophylline 22. 6 75 Chlorphenamine maleate 1. 8 6

Hydroxypropyl cellulose 36. 1 120

Xanthan gum 12. 0 40 microcrystalline cellulose 9. 0 30 magnesium stearate 0. 9 3 Preparation process:

According to the above formula amount, the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) are mixed with hydroxypropyl ketone cellulose and xanthan gum and stirred evenly; The ethanol solution is stirred into fine particles and dried; pulverized to pass all the Chinese Pharmacopoeia No. 2 sieve; the pulverized particles are added to the filler microcrystalline cellulose and the lubricant magnesium stearate, and pressed into tablets; : Compound tablets for extended release up to 24 hours

Original Excipient Name Percent (%) Dose (mg)

Methotrexate 10. 8 75 Nakodin 6. 1 42 Aminophylline 21. 6 150 Chlorpheniramine maleate 1. 7 12

Sodium alginate 21. 6 150 Hydroxypropyl cellulose 30. 3 21 0

Microcrystalline cellulose 7. 2 50 Magnesium stearate 0. 7 5 Preparation process:

According to the above formula amount, the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) are mixed with hydroxypropylmethylcellulose and sodium alginate and stirred; The ethanol solution is stirred into fine particles and dried; pulverized to pass all the Chinese Pharmacopoeia No. 2 sieve; the pulverized particles are added to the filler microcrystalline cellulose and the lubricant magnesium stearate, and pressed into tablets; 3: The percentage of the name of the compound capsules with a sustained release of up to 12 hours (%) The dose (mg) 曱那那 8 8. 5 37. 5 那可丁 4. 8 21 Ammonia tea city 17. 1 75 Malay Acid chlorpheniramine 1. 4 6

Sodium alginate 41. 0 180 Polyethylene glycol 9. 1 40 Microcrystalline cellulose 18. 2 80 Preparation process:

Mix and mix the active ingredients (曱氧那明, narcotine, aminophylline, chlorpheniramine maleate) with polyethylene glycol and sodium alginate and filler microcrystalline cellulose according to the above formula amount. Uniform; adding an appropriate amount of aqueous solution, using an extrusion spheronizer to make pellets having a diameter of about 1.0 mm and immersing them in a capsule; Example 4: Compound capsules with a sustained release of up to 24 hours

Percentage of raw material name (°/.) Dose (mg) 曱氧那明10. 6 75 那可丁 5. 9 42 Aminophylline 21. 2 150

Chlorpheniramine maleate 1. 7 12

Alginic acid 4 Within 19. 8 140 Polyethylene glycol 1 1. 3 80 Microcrystalline cellulose 22. 6 160 Ethyl cellulose

Preparation Process:

Mix and mix the active ingredients (methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate) with polyethylene glycol and sodium alginate and filler microcrystalline cellulose according to the above formula amount. Adding an appropriate amount of the aqueous solution, using an extrusion spheronizing machine to make pellets having a diameter of about 1.0 mm and drying; dissolving ethyl cellulose in water to prepare a solution having a solubility of about 10%, and using the pellets Solution coating; the coated pellets are filled into capsules. Example 5: Compound suspension with sustained release up to 12 hours

Original Excipient Name Percent (%) Dose ( mg )

Methotamine 1 1. 5 37. 5

Nakoding 6. 4 21

Ammonia Tea City 23. 0 75

Chlorpheniramine maleate 1. 8 6

Microcrystalline cellulose 20 65. 3 ethyl cellulose 19. 9 65 xanthan gum 1 1. 7 38

Microcrystalline cellulose and carboxy fluorene fiber 14. 7

4. 5

Vitamin sodium

Orange Flavors 0. 6 1. 8 Aspartame 0. 6 1. 8

Preparation Process:

The active ingredients (oxyxazone, narcotine, aminophylline, chlorpheniramine maleate) and the slow-release auxiliary ethylcellulose, xanthan gum and microcrystalline cellulose are added to the appropriate amount of solvent to form granules. Add the suspension ingredients microcrystalline cellulose and sodium carboxymethyl cellulose, flavoring orange flavor and aspartame, and mix well. Put in the bag, wear Add water to the mixture before use. The compound tablets obtained in Example 1 were tested for release of scars:

曱那那那那可氨氨氨氨马马马马马 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (

1 14. 3 20. 0 16. 7 18. 2

2 31. 5 39. 6 30. 9 36. 1

4 58. 1 63. 8 55. 1 60. 1

8 81. 7 88. 4 83. 2 85. 4

12 91. 0 100. 9 89. 7 98. 8 Meets the requirements for release of national drug standards. The test results of the compound tablets obtained in Example 2 were as follows:

曱那那那那可氨氨氨马马马马马马马马 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( (

2 18. 1 23. 4 17. 2 21. 5

4 32. 4 31. 8 33. 6 39. 9

8 45. 9 44. 0 42. 0 51. 1

12 63. 3 67. 5 60. 7 71. 2

18 86. 8 92. 7 81. 1 85. 3

24 99. 8 101 . 6 93. 9 95. 4 Meet the requirements of the national drug standards for release.

The other products of the present invention have been tested for release, and all meet the requirements for release of the national drug standard.

Claims

Rights request

1. A sustained-release preparation of a compound carbamazepine, comprising a sustained-release tablet, a sustained-release capsule and a sustained-release suspension, the active ingredient of which is oxynamine or its hydrochloride, narcotine, ammonia Theophylline, chlorpheniramine maleate, characterized in that the ratio of the active ingredient to the sustained release adjuvant is between 1: 0.03 and 1:30, and the sustained release of the controlled drug can be from 12 hours to 24 hours.

The sustained release preparation according to claim 1, wherein the sustained release adjuvant refers to: a water-soluble polymer sustained-release adjuvant: one or more natural or partially or fully synthetic water-soluble colloids such as gum arabic, jaundice Gum, xanthan gum, locust bean gum, guar gum or carrageenan, cellulose derivatives such as methyl cellulose, hydroxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, hydroxyethyl Cellulose, carboxymethyl cellulose, protein such as agar, gelatin, pectin, carrageenan and alginic acid, sodium alginate, other water-soluble polymer slow release adjuvants such as hypromethylene, acrylic resin, polyvinylpyrrolidone , polyvinylpyrrolidone copolymers, polyethylene glycols, polyvinyl alcohols, gels, casein, zein, high territories, magnesium aluminosilicates, polysaccharides, starch derivatives, and others well known in the art. Water-soluble polymer material; water-insoluble polymer slow-release auxiliary: polyacrylic acid, acrylic resin, acrylic acid latex emulsion, cellulose acetate phthalate, poly Vinyl acetate phthalate, ethyl cellulose, cellulose acetate, polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, carnauba wax, stearic acid, sodium stearyl fumarate and others A water-insoluble polymer material well known in the art is characterized in that the sustained-release excipient is any one or any two or a mixture of two or more of the above-listed excipients.

The sustained release preparation according to claim 1, wherein the sustained release tablet comprises phenoxygenamine or its hydrochloride, narcotine, aminophylline, chlorpheniramine maleate. , slow release excipients, fillers and lubricants.

The sustained release tablet according to claim 3, wherein the sustained release adjuvant refers to hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose. , hydroxyethyl cellulose, ethyl cellulose, polyvinylpyrrolidone, polyvinylpyrrolidone copolymer, sodium alginate, cellulose acetate, polyethylene glycol, polyacrylic acid, propionic acid resin, phthalic acid acetate Any one or one of cellulose, polyvinyl acetate phthalate, polyvinyl alcohol, gelatin, gum arabic, carrageenan, xanthan gum, carnauba wax, stearic acid, sodium stearyl fumarate a mixture of the above; the filler is any one or a mixture of microcrystalline cellulose, lactose, starch, pregelatinized starch, calcium hydrogen phosphate; the lubricant means stearic acid, magnesium stearate, Any one or a mixture of more than one of stearyl fumarate and silica.

The sustained release tablet according to any one of claims 1 to 4, wherein the preparation method is selected from any one of the following methods: Method 1, which comprises the following steps:

a) mixing the active ingredients methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate and slow release auxiliary materials in a weight ratio of 1:0. 03 to 1:30, and stirring uniformly;

b) adding an appropriate amount of a filler and a lubricant to the above mixture, and pressing into a tablet;

Method 2, which includes the following steps:

a) mixing the active ingredients oxynamine, narcotine, aminophylline, chlorpheniramine maleate and slow-release excipients in a weight ratio of 1:0. 03 to 1:30, and stirring uniformly;

b) adding an appropriate amount of solvent to the above mixture, stirring into fine particles and drying; or extruding the above mixture into a sheet; then pulverizing the granules or tablets so that they can all pass the Chinese Pharmacopoeia No. 2 sieve c) adding the dry granules of the previous step to the appropriate amount of filler and lubricant, and pressing into tablets;

Method 3, which includes the following steps:

a) mixing the active ingredients of oxynamin, narcotine, aminophylline, chlorpheniramine maleate and slow-release excipients in a weight ratio of 1:0. 03 to 1:30, and stirring uniformly;

d) dissolving the sustained-release excipient in a suitable solvent to prepare a solution having a concentration of 3% to 30%;

e) coating the pressed tablets on a specific device with the above 3% ~ 30% solution;

Method 4, which includes the following steps:

a) The active ingredients of oxynamin, narcotine, aminophylline, chlorpheniramine maleate and slow-release excipients are mixed in a weight ratio of 1:0.3 to 1:30, and an appropriate amount is added. Filler, stir evenly;

b) adding an appropriate amount of solvent to the above mixture, stirring uniformly, extruding and rolling with a specific equipment to form pellets and drying;

c) dissolving the sustained-release excipient in a suitable solvent to prepare a solution having a concentration of 3% to 30%;

d) The pellets prepared above are coated on a specific device with 3% to 30% of a slow release adjuvant solution; e) the coated pellets are added to an appropriate amount of filler and lubricant and compressed into tablets;

Method 5, which includes the following steps:

a) Dissolving or suspending the active ingredients oxynamine, narcotine, aminophylline, chlorpheniramine maleate in a suitable solvent, and adding an appropriate amount of binder, and stirring uniformly;

b) the solution or suspension prepared above is coated on the surface of a suitable size sugar pellet or microcrystalline cellulose pellet with a specific device to prepare a drug-coated pellet; c) dissolving the slow-release excipient in a suitable solvent to prepare a solution having a concentration of 3% to 30%;

d) The drug-coated pellets prepared above are coated on a specific device with a 3% to 30% slow release adjuvant solution;

e) compressing the coated drug-coated pellets into a tablet by adding an appropriate amount of a filler, a disintegrant, and a lubricant; and the method 6 includes the following steps:

a) The active ingredients of methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate and slow release adjuvant hydroxypropylmethylcellulose and xanthan gum according to the weight ratio of 1: 0. 03 to 1 : 30 mixed and stirred evenly; or the active ingredients of oxynamine, narcotine, aminophylline, chlorpheniramine maleate and slow-release excipient hydroxypropyl thioglycolate and sodium alginate according to the weight ratio Mix between 1 : 0.03 to 1: 30 and mix well;

b) adding an appropriate amount of ethanol solution to the mixture obtained in the previous step, stirring into fine particles and drying; pulverizing so that all can pass through the Chinese Pharmacopoeia No. 2 sieve;

c) Adding the filler microcrystalline cellulose and the lubricant magnesium stearate to the pulverized granules in the previous step, and pressing into tablets.

The sustained release preparation according to claim 1, wherein the sustained release capsule contains methoxyphenamine or a hydrochloride thereof, narcotine, aminophylline, and chlorpheniramine maleate. Sensitive, slow release excipients, fillers and lubricants.

The sustained release capsule according to claim 6, wherein the sustained release adjuvant refers to hydroxypropyl ketone cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl group. Cellulose, hydroxyethyl cellulose, ethyl cellulose, polyvinylpyrrolidone, polyvinylpyrrolidone copolymer, sodium alginate, cellulose acetate, polyethylene glycol, polyacrylic acid, acrylic resin, phthalic acid acetate Any one or a kind of polyvinyl acetate, polyvinyl alcohol, gelatin, gum arabic, carrageenan, xanthan gum, carnauba wax, stearic acid, sodium stearyl fumarate The above mixture; the filler refers to any one or a mixture of microcrystalline cellulose, lactose, starch, pregelatinized starch, and calcium hydrogen phosphate; the lubricant refers to stearic acid, magnesium stearate, Any one or a mixture of more than one of stearyl fumarate and silica.

The sustained-release gelatin preparation according to any one of claims 1 to 2, wherein the preparation method is selected from any one of the following methods:

Method 1, which comprises the following steps:

b) adding an appropriate amount of solvent to the above mixture, stirring into fine particles and drying; or extruding the above mixture into a sheet; then pulverizing the granules or tablets so that they can all pass the Chinese Pharmacopoeia No. 2 sieve c) adding the appropriate amount of filler and lubricant to the dried granules of the previous step; Method 2, comprising the steps of:

c) directly loading the pellets of the previous step, or adding a proper amount of filler and lubricant, and then loading the capsule; Method 3, which comprises the following steps:

a) mixing the active ingredients methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate and slow-release excipients in a weight ratio of 1: 0.0 to 1: 30, and adding an appropriate amount Filler, stir evenly;

b) adding an appropriate amount of solvent to the above mixture, stirring and hooking, extruding and rolling the pellets with a specific equipment to form pellets and drying;

d) The pellets prepared above are coated on a specific equipment with 3% ~ 30% slow release adjuvant solution; e) the coated pellets are directly or after adding appropriate amount of filler and lubricant嚢

Method 4, which includes the following steps:

a) dissolving or suspending the active ingredients methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate in a suitable solvent, adding an appropriate amount of binder, and stirring uniformly;

b) the solution or suspension prepared above is coated on the surface of a suitable size sugar pellet or microcrystalline cellulose pellet with a specific device to prepare a drug-coated pellet;

e) loading the coated drug-coated pellets directly, or adding the appropriate amount of filler and lubricant to the capsule; Method 5, which includes the following steps:

a) The active ingredients of oxynamin, narcotine, aminophylline, chlorpheniramine maleate and slow release adjuvant polyethylene glycol and sodium alginate according to the weight ratio of 1: 0. 03 to 1: 30 Mix between them, and add appropriate amount of filler microcrystalline cellulose, stir evenly;

b) adding an appropriate amount of solvent to the mixture obtained in the previous step, stirring and hooking, preparing the pellets by an extrusion spheronizer and drying;

c) loading the pellets obtained in the previous step into the capsule;

Method 6, which comprises the following steps: a) The active ingredients of methoxyphenamine, narcotine, aminophylline, chlorpheniramine maleate and slow release adjuvant polyethylene glycol and sodium alginate according to the weight ratio of 1: 0. 03 to 1: 30 Mix between them, and add appropriate amount of filler microcrystalline cellulose, stir evenly;

b) adding an appropriate amount of the solvent to the mixture obtained in the previous step, stirring uniformly, and forming the pellets by an extrusion spheronizer and drying;

c) dissolving the slow-release auxiliary ethyl cellulose in a suitable solvent to prepare a solution having a concentration of 3 - 30%; d) using the pellet obtained in step b) with the sustained-release auxiliary solution obtained in step c) Coating on the device;

e) The coated pellets obtained in the previous step were placed in a capsule.

The sustained release preparation according to claim 1, wherein the sustained release suspension contains methoxyphenamine or a hydrochloride thereof, narcotine, aminophylline, and chlorpheniramine maleate. Sensitive, slow release excipients, fillers and flavoring agents.

The sustained release suspension according to claim 9, wherein the sustained release adjuvant refers to hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, Hydroxyethyl cellulose, ethyl cellulose, polyvinylpyrrolidone, polyvinylpyrrolidone copolymer, sodium alginate, cellulose acetate, polyethylene glycol, polyacrylic acid, acrylic resin, cellulose acetate phthalate, polyacetic acid Any one or a mixture of ethylene phthalate, polyvinyl alcohol, gelatin, gum arabic, carrageenan, xanthan gum, carnauba wax, stearic acid, sodium stearyl fumarate; The filler refers to any one or a mixture of microcrystalline cellulose, lactose, starch, pregelatinized starch, and calcium hydrogen phosphate; the flavoring agent refers to orange flavor, aspartame, stevioside, and sucrose. Any one or more of the mixtures.

The sustained release suspension according to any one of claims 1 to 2, wherein the preparation method is selected from any one of the following methods:

Method 1, which comprises the following steps:

b) adding an appropriate amount of solvent to the above mixture, stirring into fine particles and drying; or extruding the above mixture into a sheet; then pulverizing the granules or tablets so that they can all pass the Chinese Pharmacopoeia No. 2 sieve c) adding the appropriate amount of filler and flavor to the dry granules of the previous step;

d) stirring with water to form a suspension before administration;

Method 2, which includes the following steps:

a) The active ingredients of oxynamin, narcotine, aminophylline, chlorpheniramine maleate and slow-release excipients are mixed in a weight ratio of 1:0.3 to 1:30, and an appropriate amount is added. Filler, stir evenly; b) adding an appropriate amount of solvent to the above mixture, stirring and hooking, extruding the pellets with a specific equipment to form pellets and drying;

c) adding the appropriate amount of filler and flavor to the pellet of the previous step;

d) stirring with water to form a suspension before administration;

Method 3, which includes the following steps:

e) adding the packaged drug-coated pellets to an appropriate amount of filler and flavoring agent;

f) stirring with water to form a suspension before administration;

Method 4, which includes the following steps:

a) The active ingredients of oxynamin, narcotine, aminophylline, chlorpheniramine maleate and slow release adjuvant ethyl cellulose, xanthan gum according to the weight ratio of 1: 0. 03 to 1: 30 Mixing and adding microcrystalline cellulose; adding an appropriate amount of solvent to form granules;

b) adding an appropriate amount of the suspension component microcrystalline cellulose and sodium carboxymethylcellulose, flavoring orange flavor and aspartame to the granules obtained in the previous step, and stirring uniformly;

c) Stirring with water before administration to form a suspension.