CN1634060A - Gelatin formulation of dextromethorphan hydrobromide and its preparing method - Google Patents
Gelatin formulation of dextromethorphan hydrobromide and its preparing method Download PDFInfo
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- CN1634060A CN1634060A CN 200410040849 CN200410040849A CN1634060A CN 1634060 A CN1634060 A CN 1634060A CN 200410040849 CN200410040849 CN 200410040849 CN 200410040849 A CN200410040849 A CN 200410040849A CN 1634060 A CN1634060 A CN 1634060A
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- Prior art keywords
- acetaminophen
- gel
- preparation
- dextromethorphan hydrobromide
- substrate
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- YQSHYGCCYVPRDI-UHFFFAOYSA-N (4-propan-2-ylphenyl)methanamine Chemical compound CC(C)C1=CC=C(CN)C=C1 YQSHYGCCYVPRDI-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 229960003782 dextromethorphan hydrobromide Drugs 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims abstract description 15
- 238000009472 formulation Methods 0.000 title claims abstract description 5
- 108010010803 Gelatin Proteins 0.000 title abstract description 8
- 239000008273 gelatin Substances 0.000 title abstract description 8
- 229920000159 gelatin Polymers 0.000 title abstract description 8
- 235000019322 gelatine Nutrition 0.000 title abstract description 8
- 235000011852 gelatine desserts Nutrition 0.000 title abstract description 8
- 238000000034 method Methods 0.000 title abstract description 4
- 239000000499 gel Substances 0.000 claims abstract description 50
- 238000002360 preparation method Methods 0.000 claims abstract description 35
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 claims abstract description 30
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 89
- 229960005489 paracetamol Drugs 0.000 claims description 48
- 238000003756 stirring Methods 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 239000000758 substrate Substances 0.000 claims description 22
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 17
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 claims description 17
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 claims description 17
- 241000596504 Tamarindus Species 0.000 claims description 12
- 235000004298 Tamarindus indica Nutrition 0.000 claims description 12
- 238000010521 absorption reaction Methods 0.000 claims description 12
- 239000000230 xanthan gum Substances 0.000 claims description 12
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- 238000009833 condensation Methods 0.000 claims description 8
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- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
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- 230000000694 effects Effects 0.000 abstract description 11
- 201000009240 nasopharyngitis Diseases 0.000 abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 1
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- 239000003814 drug Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
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- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
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- -1 acetaminophen compound Chemical class 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
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- 238000002474 experimental method Methods 0.000 description 6
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 4
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- 206010011224 Cough Diseases 0.000 description 2
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- LUEWUZLMQUOBSB-FSKGGBMCSA-N (2s,3s,4s,5s,6r)-2-[(2r,3s,4r,5r,6s)-6-[(2r,3s,4r,5s,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5s,6r)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O[C@@H]2[C@H](O[C@@H](OC3[C@H](O[C@@H](O)[C@@H](O)[C@H]3O)CO)[C@@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O LUEWUZLMQUOBSB-FSKGGBMCSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- 235000001206 Amorphophallus rivieri Nutrition 0.000 description 1
- 244000247812 Amorphophallus rivieri Species 0.000 description 1
- 208000031636 Body Temperature Changes Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
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- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229940086234 acetaminophen 300 mg Drugs 0.000 description 1
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- 239000000850 decongestant Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940050239 dextromethorphan hydrobromide 15 mg Drugs 0.000 description 1
- 229940055443 dextromethorphan hydrobromide 5 mg Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention provides a gelatin formulation of dextromethorphan hydrobromide and its preparing method, which is prepared from acetaminopher, chlorpheniramine maleate, d-pesudoephedrine hydrochloride, Dextromethorphan Hydrobromide and right amount of base material, The preparation is in the form of gel type oral form, the process for preparing the preparation is also disclosed. The children are willing to take the preparation, it has good effects for controlling children's virus infection of upper respiratory tract and treating children's common cold.
Description
Technical field: the present invention is a kind of acetaminophen Gel preparation and preparation method thereof, belongs to the technical field of medicine.
Technical background: flu also claims acute upper respiratory tract infection, is commonly encountered diseases and the frequently-occurring disease that influences human health.Cold virus has nearly 200 kinds, and children's is because health defensive enginery immaturity also, and a little less than the resistance against diseases, so that all must catch 6-7 time every year, Kai Fa children coryza medicine kind increases gradually in recent years, and dosage form is different; As: disclosed number of patent application is " 02110056 " in the Chinese patent communique, patent application, number of patent application that name is called " Rationed fenmameimin drops " are called the patent application of " U.S.A pounces on pseudo-numb dry suspension and processing technology " for " 00136032 ", name; They all are to be used for active drug that infantile common cold is prevented and treated; Wherein acetaminophen eases the pain by improving pain threshold, and by acting on the hypothalamus thermotaxic centre to reach the antipyretic effect, its antipyretic-antalgic effect is suitable with aspirin, but does not produce the side effect that aspirin may cause; Pseudoephedrine hydrochloride is a Decongestant, can eliminate nose hyperemia; Dextromethorphan hydrobromide is a cough medicine, can alleviate the cough symptom that common cold causes; Chlorphenamine maleate is a histamine antagonist, can alleviate stream grows, sneeze, shed tears and throat's allergic symptom such as itch, though product has good antipyretic-antalgic, antitussive, alleviates the congested curative effect of nasal mucosa, but be dosage form kind at the children characteristics, particularly for immature infant, need the head of a family with its pressure splash in the infant mouth, because the amount that splashes into is restive, so a patent application that is called " Rationed fenmameimin drops " has just been arranged in the prior art; But even now owing to be to force to splash into, has certain difficulty, displeased acceptance so infant uses.And existing listing product: the acetaminophen compound oral administration solution is a liquid preparation, can be said to be convenient though take, and has foregoing problems equally; Also exist packing, transportation, storage inconvenience, taking dose to be difficult for shortcomings such as accurately grasp; And acetaminophen stability is not good, the condition that needs PH5～7,45 ℃, otherwise facile hydrolysis becomes p-aminophenol, oxidation further takes place, and color is pulverize redness, brown gradually, becomes black at last, its water solublity also low (1: 70), oral absorption is subjected to the dosage form factor affecting, causes drug absorption slow, and blood drug level is low.Huge in view of child patient quantity in the real life, poor to the ability to accept of general formulation, the outward appearance of medicine, mouthfeel directly influence the application and the curative effect of medicine; And infantile common cold is a kind of commonly encountered diseases that has a strong impact on child health, the dosage form of selecting suitable prescription control children's upper respiratory tract viral infection and being suitable for child administration is setting about a little of research and development children coryza medicine, develop a kind of market prospect is wide, the child takes like a shot bioavailability height, strong drug action, divided dose accurately, the desirable novel form of being convenient to child administration is very necessary.
Summary of the invention: the objective of the invention is to: a kind of acetaminophen Gel preparation and preparation method thereof is provided; The present invention is directed to prior art, we are made fruit jelly or the soft sweet type gel isogel preparation that liked by the child, such dosage form children's extremely is ready to take, reduce the adult and advised the trouble of feeding, feeding by force, not only tasty, dosage is accurate, and therapeutical effect is good, has enriched the dosage form kind, and market prospect is very wide.
The present invention constitutes like this: calculate according to weight, it is made into fruit jelly or soft sweet type gel oral formulations by acetaminophen 300～350mg, chlorphenamine maleate 1～3mg, pseudoephedrine hydrochloride 20～40mg, dextromethorphan hydrobromide 5～15mg and an amount of substrate, and wherein: substrate can be animal glue, plant gum, microbiological gum, alginate jelly, chemical modification glue or compound gel.It can also be prepared into: injection comprises: injection, powder pin, freeze-dried powder, dispersible tablet, soft capsule, drop pill, slow releasing preparation.Acetaminophen Gel preparation of the present invention is semifluid or solid gel shape by the gel preparation that acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg and tamarind gum, the composite substrate of xanthan gum are prepared into.The preparation method of acetaminophen Gel preparation of the present invention is: acetaminophen, chlorphenamine maleate, pseudoephedrine hydrochloride, dextromethorphan hydrobromide are added to mix homogeneously in the substrate for preparing, after the sterilization promptly.
The preparation method of acetaminophen Gel preparation of the present invention is said so accurately: by mass percentage, tamarind gum with 0.5%, 0.1% xanthan gum, mixing is under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir then, be heated to 55 ℃, filter, transfer pH value 5.5, under condition of stirring, add acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride, mix homogeneously, join rapidly in the disinfecting container, seal, sterilization, be cooled to rapidly about 30 ℃, condensation, drying, promptly.
Compared with prior art, the application makes we fruit jelly or the soft sweet type gel that liked by the child, children's extremely is ready to take, reduce the adult and advised the trouble of feeding, feeding by force, tasty, dosage is accurate, for control children's upper respiratory tract viral infection, treatment children's's flu function well, bioavailability is good, enriched the dosage form kind, market prospect is very wide.
The applicant finds in development process, acetaminophen is stable under PH5～7, cryogenic condition, otherwise facile hydrolysis becomes p-aminophenol, oxidation can further take place, color is pulverize redness, brown gradually, become black at last, and most of substrate needs fusion at high temperature and not acidproof, so the acid resistance of gel-type vehicle, stability, melt temperature have played crucial effects to outward appearance, stability, the curative effect of product; And as a kind of novel form, the release of medicine, to absorb whether desirable, gel elastomer be key problem in technology problem of the present invention.
The applicant has carried out a series of experiments, adopt the composite substrate of 0.5% tamarind gum, 0.1% xanthan gum, control pH value 5.5,55 ℃ of heating-up temperatures, the product stability that makes, gel strength ideal, outward appearance is good, selects the supplementary product kind of preparation technology, use of pharmaceutical preparation provided by the invention and consumption, ratio etc.; Guarantee its science, reasonable, feasible; The preparation that obtains has effective therapeutic effect.
Experimental example 1: Study on Forming
(1) selection of pH value
Acetaminophen content (%) in the gel
PH value December in 0 month 6 months March
4.5 101.5 100.5 98.1 95.4
5.0 101.5 101.4 101.0 100.4
5.5 101.5 101.4 101.4 101.4
6.0 101.5 101.2 101.0 100.3
7.0 101.5 101.2 101.1 100.5
8.0 101.5 98.3 96.8 95.7
9.0 101.5 99.8 95.9 95.3
(2) selection of matrix species
Substrate pH value consumption % temperature ℃ gelling properties
40 colloidal sols not
Carrageenan 5.5 0.6 55 is colloidal sol not
70 colloidal sols, the gel instability
40 colloidal sols not
Gelatin 5.5 0.6 55 gels solidify, melting point is low
70 gels solidify, melting point is low
40 elasticity are poor slightly, can syneresis, and stable
Tamarind gum 5.5 0.6 55 elasticity are poor slightly, can syneresis, and stable
70 elasticity are poor slightly, can syneresis, and the medicine instability
40 elasticity are poor slightly, can syneresis, and medicine is stable
Xanthan gum 5.5 0.6 55 elasticity are poor slightly, can syneresis, and medicine is stable
70 elasticity are poor slightly, can syneresis, and the medicine instability
40 elasticity are poor slightly, are difficult for syneresis, and medicine is stable
Tamarind gum 5.5 0.6 55 good springiness are difficult for syneresis, and medicine is stable
+ xanthan gum 70 good springiness are difficult for syneresis, the medicine instability
(3) screening of substrate composition and consumption
Tamarind gum: xanthan gum consumption % mouthfeel
5: 1 0.4 difference of hardness, poor toughness, no bite
Hardness was moderate in 5: 1 0.6, and poor toughness has bite
Hardness was bigger in 5: 1 0.8, and toughness is relatively poor, no bite
4: 1 0.4 difference of hardness, tough good springiness has bite
4: 1 0.6 difference of hardness, tough elasticity has bite
4: 1 0.8 difference of hardness, tough elasticity is strong
Hardness was big in 6: 1 0.4, and tough elasticity is strong
Hardness was big in 6: 1 0.6, and tough elasticity is strong
Hardness was big in 6: 1 0.8, and tough elasticity is strong
The result shows: gelatin solidifies, melting point is low, and is not acidproof, and storage and preparation are all difficult; Carrageenan dissolves the temperature that needs more than 70 ℃ fully, and alkali condition is stable, but acetaminophen high temperature and alkali condition instability; The gel that xanthan gum, tamarind gum form in acid solution is solid, but elasticity is poor slightly under the cryogenic conditions; Xanthan gum can be dissolved in cold water, is used the elasticity that can improve gel with tamarind gum; The best composite condition of substrate is a tamarind gum: the part by weight of xanthan gum=5: 1, consumption is 0.6%.
Experimental example 2: preparation performance study
(1) preparation stability
Acetaminophen content (%) in the experimental condition gel
0d 1d 3d 5d 10d
40℃ 101.5 101.5 101.4 101.4 101.4
60℃ 101.5 101.5 101.5 101.4 101.3
80℃ 101.5 101.4 101.6 100.8 100.8
Relative humidity 75% 101.5 101.3 101.4 101.3 101.2
Relative humidity 92.5% 101.5 101.2 101.3 100.9 100.8
Illumination 101.5 101.4 101.2 101.3 100.7
Naturally place 101.5 101.4 101.5 101.5 104.7
The result shows: when preparing product, and control pH value 5.5,55 ℃ of heating-up temperatures have improved the preparation stability of acetaminophen.
(2) research of bioavailability
6 of rabbit, average weight (2.3 ± 0.85) kg is divided into two groups at random, 3 every group, fasting 24h gavages acetaminophen compound oral administration solution or gel of the present invention respectively, tests two groups of intersections for the second time, and twice experiment be a week at interval, take medicine the back respectively at 0.15,0.33,0.5,1,1.5,2,4,6,8h gets blood 3mL from auricular vein, centrifugal, separated plasma, the content of mensuration acetaminophen.
Blood drug level/mgL
-1
Time/h acetaminophen compound solution gel of the present invention
0.15 5.87±6.21 6.54±8.76
0.30 10.02±9.83 21.65±9.32
0.5 12.82±4.27 23.27±9.04
1 15.56±2.70 22.09±4.33
1.5 18.64±3.37 19.62±4.10
2 9.46±2.50 10.91±1.42
4 5.17±1.35 6.24±1.06
6 4.07±0.93 4.16±1.52
8 1.62±0.35 1.73±0.51
The result shows: the water solublity of acetaminophen low (1: 70), and oral absorption is subjected to the dosage form factor affecting, causes drug absorption slow, and blood drug level is low, and the bioavailability ideal of gel of the present invention, the product good effect.
Experimental example 3: pharmacodynamic experiment
(1) refrigeration function experiment
Get 30 of the healthy rabbits of body weight (2.5 ± 0.25) kg, be divided into 3 groups at random, 10 every group is the blank group with normal saline (NS), and the positive matched group of acetaminophen compound oral solution, gel of the present invention are experimental group.Use hydrargyrum anus temperature instrumentation amount man rabbit rectum normal body temperature 2 times earlier, 2 interval times are 30min.Getting its average is normal body temperature (T).Inject expired typhoid fever, the paratyphoid fever first and second triple vaccine 1.3ml/kg by auricular vein, treat (T0) behind about 1 ℃ of the fervescence beginning administration.The blank group irritates stomach for the 30ml normal saline.Oral administration solution group and gel group are all raised administration by 125mg/kg (calculating with the chlorphenamine maleate amount) mouthful, send down with the 30ml normal saline.Granule is dissolved in the 30ml normal saline with equivalent irritates stomach.Measure rectal temperature 1 time respectively at different time after the administration.
Comparison to rabbit body temperature change after the pyrogenicity
Group blank group positive controls experimental group
△T
0 0.98±0.18 1.02±0.35 1.00±0.23
△T
10 1.07±0.19 1.01±0.32 1.00±0.22
△T
20 1.13±0.22 0.95±0.37 0.86±0.24
△T
30 1.10±0.25 0.84±0.38 0.79±0.25
△T
15 1.24±0.23 0.81±0.36 0.73±0.21
△T
60 1.25±0.20 0.63±0.45 0.58±0.25
△T
90 1.26±0.25 0.44±0.43 0.32±0.24
△T
120 1.58±0.37 0.37±0.32 0.32±0.15
△T
150 1.89±0.34 0.40±0.34 0.35±0.16
△T
180 1.87±0.31 0.53±0.33 0.48±0.23
△T
240 1.88±0.35 0.71±0.28 0.65±0.26
(2) comparative experiments of analgesic activity
30 of the healthy Kunming kind white mice of body weight (20 ± 2) g are got in acetic acid twisting method experiment, are divided into 3 groups at random, 10 every group.The blank group is with 0.3ml/10g normal saline ig administration, and acetaminophen compound chewable tablet group is with granule suspendible ig administration, and gel group of the present invention is with solutions i g administration.Dosage is respectively 150mg/kg (in the chlorphenamine maleate amount).After treating ig administration 8min, immediately only, observe then and turn round the body number of times in the 10min to the glacial acetic acid solution 0.3ml/ of mouse peritoneal injection 0.7%.
Experimental result to the reaction of white mice acetic acid twisting
Group n turns round the body number of times
Blank group 10 31.6 ± 12.2
Chewable tablet group 10 14.7 ± 14.1
Gel group 10 13.4 ± 11.3
(3) to the effect of mice blood vessel
The influence of the swollen effect of mice auricular concha caused by dimethylbenzene xylene is chosen body weight for 30 of the Kunming mouses of (27 ± 3) g, be divided into 3 groups at random by the body weight equilibrium, 10 every group.Blank group ig normal saline 0.6ml/, acetaminophen compound solution group and gel component of the present invention, behind the ig administration 15min are put the dimethylbenzene of 0.05ml in mouse right ear not in 150mg/kg (with the chlorphenamine maleate amount).Taking off cervical vertebra behind the 2h and put to death, sweep away the identical left and right sides auricle of area with the card punch of diameter 7mm, weigh on analytical balance, is contrast with left ear, and the weight difference of calculating left and right sides auricle is auricular concha swelling degree.
To the bullate effect of mice auricular concha caused by dimethylbenzene xylene
Group n left and right sides ear weight difference mg
Blank group 10 31.2 ± 10.1
Solution group 10 24.5 ± 16.2
Gel group 10 23.4 ± 12.4
(4) to the influence of Cavia porcellus nasal mucosa sensitization
30 of healthy guinea pigs are chosen in the influence of grabbing nose and sneeze reaction to mucous membrane irritability due to the histamine, are divided into 3 groups at random by the body weight equilibrium, 10 every group.Blank group ig normal saline 3ml/, acetaminophen compound chewable tablet group and gel group of the present invention are respectively in 125mg/kg (with the chlorphenamine maleate amount) ig administration.The normal saline solution of clicking and entering 3% histamine hydrochloride for every Cavia porcellus nasal cavity immediately behind the administration 20min, two nasal cavity concurrent 0.03ml observe the sneeze in the 10min then and grab the nose number of times.
The Cavia porcellus that histamine is caused grabs the influence of nose and sneeze
Group n grabs nose number of times sneeze number of times
Blank group 10 21.0 ± 13.2 54.4 ± 6.5
Chewable tablet group 10 9.7 ± 13.1 12.0 ± 3.2
Gel group 10 8.6 ± 12.5 11.8 ± 4.6
The result shows: gel of the present invention is passable from analgesic, analgesia, antiinflammatory and antiallergic experimental result, is not less than pseudoephedrine hydrochloride oral administration solution and pseudoephedrine hydrochloride chewable tablet.
Concrete embodiment:
Embodiments of the invention 1:
Acetaminophen 300mg, chlorphenamine maleate 1mg, pseudoephedrine hydrochloride 20mg, dextromethorphan hydrobromide 5mg
By mass percentage, with 0.5% tamarind gum, 0.1% xanthan gum, mixing, under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir then, be heated to 55 ℃, filter, transfer pH value 5.5, under condition of stirring, add acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride, mix homogeneously joins rapidly in the disinfecting container, seals, sterilization, be cooled to about 30 ℃ condensation, drying rapidly, promptly get gel, this product oral, three times on the one, each 2 bags, every bag of 10g.
Embodiments of the invention 2:
Acetaminophen 350mg, chlorphenamine maleate 3mg, pseudoephedrine hydrochloride 40mg, dextromethorphan hydrobromide 15mg
By mass percentage, the methylcellulose with 1.5% is under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir, be heated to 55 ℃ then, filter, filter the back and adds acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride under condition of stirring, mix homogeneously joins rapidly in the disinfecting container, seal, sterilization is cooled to rapidly about 30 ℃, condensation, drying promptly gets gel.
Embodiments of the invention 3:
Acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg
Get chlorphenamine maleate, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, press medicine: substrate=1: 1.3, the mixed-matrix of adding soybean oil, soybean lecithin, heating and melting, mixing gets soft capsule content; The preparation of glue: with gelatin: glycerol: water=1: 0.3: 0.5, get gelatin and add an amount of distilled water and make its imbibition, glycerol and remaining water are put be heated to 70～80 ℃ in the glue pot in addition, mix homogeneously adds expansible gelatin and stirs, and makes it to dissolve into uniform glue, in 70 ℃ of insulations 1～2 hour, leave standstill, remove the come-up foam, filter with cloth bag, in encapsulating machine, be pressed into soft capsule, be pressed into soft capsule, put in the drum drying machine and finalize the design, whole ball, drying promptly gets soft capsule.
Embodiments of the invention 4:
Acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg
Get chlorphenamine maleate, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, splash into the ratio that adopts PEG6000 and PEG4000 and be in 3: 1 the mixed-matrix, the water dropper model adopts No. 2 water droppers, and coolant temperature is 18～22 ℃, promptly gets drop pill.
Embodiments of the invention 5:
Acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg
By mass percentage, the carrageenan with 0.9% is under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir, be heated to 55 ℃ then, filter, filter the back and adds acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride under condition of stirring, mix homogeneously joins rapidly in the disinfecting container, seal, sterilization is cooled to rapidly about 30 ℃, condensation, drying promptly gets gel.
Embodiments of the invention 6:
Acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg
By mass percentage, the gelatin with 0.9% is under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir, be heated to 55 ℃ then, filter, filter the back and adds acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride under condition of stirring, mix homogeneously joins rapidly in the disinfecting container, seal, sterilization is cooled to rapidly about 30 ℃, condensation, drying promptly gets gel.
Embodiments of the invention 7:
Acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg
By mass percentage, the polysaccharide that condenses with 1.2% is under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir, be heated to 55 ℃ then, filter, filter the back and adds acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride under condition of stirring, mix homogeneously joins rapidly in the disinfecting container, seal, sterilization is cooled to rapidly about 30 ℃, condensation, drying promptly gets gel.
Embodiments of the invention 8:
Acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg, dextromethorphan hydrobromide 10mg
By mass percentage, carrageenan with 1.0%, 0.2% Konjac glucomannan, mixing under stirring condition, is put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir, be heated to 55 ℃ then, filter, filter the back and adds acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride under condition of stirring, mix homogeneously joins rapidly in the disinfecting container, seal, sterilization is cooled to about 30 ℃ condensation rapidly, drying promptly gets gel.
Claims (5)
1, a kind of acetaminophen Gel preparation, it is characterized in that: calculate according to weight, it is made into fruit jelly or soft sweet type gel oral formulations by acetaminophen 300～350mg, chlorphenamine maleate 1～3mg, pseudoephedrine hydrochloride 20～40mg and dextromethorphan hydrobromide 5～15mg and an amount of substrate, and wherein: substrate can be animal glue, plant gum, microbiological gum, alginate jelly, chemical modification glue or compound gel.
2, according to the described acetaminophen Gel preparation of claim 1, it is characterized in that: it can also be prepared into: injection comprises: injection, powder pin, freeze-dried powder, dispersible tablet, soft capsule, drop pill or slow releasing preparation.
3, according to claim 1 or 2 described acetaminophen Gel preparations, it is characterized in that: it is prepared into the gel preparation that is semifluid or solid gel shape by acetaminophen 320mg, chlorphenamine maleate 2mg, pseudoephedrine hydrochloride 30mg and dextromethorphan hydrobromide 10mg and tamarind gum, the composite substrate of xanthan gum.
4, as the preparation method of acetaminophen Gel preparation as described in the claim 1～3 any, it is characterized in that: acetaminophen, chlorphenamine maleate, pseudoephedrine hydrochloride and dextromethorphan hydrobromide are added to mix homogeneously in the substrate for preparing, after the sterilization promptly.
5, preparation method according to the described acetaminophen Gel preparation of claim 4 is characterized in that: the gel in the described preparation prepares like this: by mass percentage, and the tamarind gum with 0.5%, 0.1% xanthan gum, mixing, under stirring condition, put into cold water, make it to disperse, soak 20～30min, make the abundant water absorption and swelling of substrate, stir then, be heated to 55 ℃, filter, transfer pH value 5.5, under condition of stirring, add acetaminophen, dextromethorphan hydrobromide, chlorphenamine maleate, pseudoephedrine hydrochloride, mix homogeneously joins rapidly in the disinfecting container, seal, sterilization is cooled to about 30 ℃ condensation rapidly, drying, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040849 CN1634060A (en) | 2004-10-11 | 2004-10-11 | Gelatin formulation of dextromethorphan hydrobromide and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410040849 CN1634060A (en) | 2004-10-11 | 2004-10-11 | Gelatin formulation of dextromethorphan hydrobromide and its preparing method |
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|---|---|
| CN1634060A true CN1634060A (en) | 2005-07-06 |
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| CN101596157A (en) * | 2008-06-04 | 2009-12-09 | 北京科信必成医药科技发展有限公司 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
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| CN103536527A (en) * | 2013-09-16 | 2014-01-29 | 南通丝乡丝绸有限公司 | Dextromethorphan hydrobromide injection and preparation method thereof |
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| CN101596157A (en) * | 2008-06-04 | 2009-12-09 | 北京科信必成医药科技发展有限公司 | The compound slow release preparation of a kind of pseudoephedrine, chlorphenamine and dextromethorphan |
| CN103110629A (en) * | 2013-02-19 | 2013-05-22 | 青岛正大海尔制药有限公司 | Compound phenol caplets dropping pills and preparation method thereof |
| CN103110631A (en) * | 2013-02-19 | 2013-05-22 | 青岛正大海尔制药有限公司 | Compound phenol caplets sustained release preparation and preparation method thereof |
| CN103110631B (en) * | 2013-02-19 | 2014-10-01 | 青岛正大海尔制药有限公司 | Compound phenol caplets sustained release preparation and preparation method thereof |
| CN103156850A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorpheniramine maleate slow-release capsule and preparation method thereof |
| CN103156851A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorpheniramine maleate slow-release particles and preparation method thereof |
| CN103156852A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorpheniramine maleate enteric capsule and preparation method thereof |
| CN103156852B (en) * | 2013-03-21 | 2014-07-23 | 青岛正大海尔制药有限公司 | Paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide and chlorpheniramine maleate enteric capsule and preparation method thereof |
| CN103156851B (en) * | 2013-03-21 | 2014-07-30 | 青岛正大海尔制药有限公司 | Pseudoephedrine hydrochloride slow-release particles and preparation method thereof |
| CN103156850B (en) * | 2013-03-21 | 2014-07-30 | 青岛正大海尔制药有限公司 | Dextromethorphan hydrobromide slow-release capsule and preparation method thereof |
| CN103536527A (en) * | 2013-09-16 | 2014-01-29 | 南通丝乡丝绸有限公司 | Dextromethorphan hydrobromide injection and preparation method thereof |
| CN104127371A (en) * | 2014-08-11 | 2014-11-05 | 大连大学 | Gel applicable to children |
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