CN1954815A - Anti-tuberculosis compound medicine quick-slow double-release preparation and its preparation method - Google Patents
Anti-tuberculosis compound medicine quick-slow double-release preparation and its preparation method Download PDFInfo
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Abstract
A both fast-release and slow-release compound medicine for preventing and treating tuberculosis (TB) is prepared from rifampin and isoniazid. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of preparation research of tuberculosis quick-slow double-release compound medicine.Particularly relate to complex rifampin (isoniazid+rifampicin) is developed into the quick-slow double-release preparation.The invention still further relates to the preparation method of antitubercular agent complex rifampin quick-slow double-release preparation.
Background technology
When tuberculosis had become the first killer of current global infectious disease and the maximum cause of the death, WHO just announced to the whole world that the whole world was in the tuberculosis state of emergency in 1993; Be decided to be the World Tuberculosis Prevention and Cure Day annual March 24; China's Ministry of Public Health also rose to the former tuberculosis of classifying the Class C communicable disease control as the Class B management in 1996.As seen tuberculosis being controlled fast and effectively, is extremely urgent great task, and wherein the screening of tuberculosis class medicine and research and development attract people's attention especially.
Stop the popular effective control strategy of tuberculosis---DOTS (every dose under promptly under the direct face of medical worker is looked, obeying, thereby assurance patient rule is taken medicine, the control source of infection) being the most feasible way of saving the life of global tuberculosis patient, is the fundamental way of the controlling tuberculosis source of infection.This strategy has been proved to be the best-of-breed technology scheme of controlling tuberculosis, i.e. brachytherapy (DOTS) under the direct observation of world health organisation recommendations.Being 2HRZ/4HR (be preceding 2 months with isoniazid, rifampicin, pyrazinamide, back 4 months with isoniazid, rifampicin) to one of the people that just cures the disease therapeutic scheme commonly used in this scheme, is to adopt the administration of supervising and guiding of the therapy of compound recipe administration.But practical situation is some patient is being impossible get rid of oneself fully to take medicine in some cases, does not also just get rid of the angle of patient from economy or incident, only takes a kind of situation of medicine, so also just causes occurring easily drug resistance.Adopt fixedly compound formulation administration, the possibility that can avoid the patient only to take single medicine reduces chemical sproof generation.In order to improve the compliance of tuberculosis patient, the seventies, multiple antituberculotics was just made " compound recipe " preparation by the drugmaker of the U.S., " bigeminy " (rifampicin+isoniazid), " three " (rifampicin+isoniazid+pyrazinamide) tablet and capsule as the development of U.S. Merrell Dow company, use for many years in state's clinical treatment tuberculosis such as American and Britain, obtain good result; France began tuberculosis is carried out 6 months scheme of combination drug therapy in 1981, and thinking has outstanding behaviours on curative effect; The tuberculotherapy clinical studies show that ground such as East Africa, Singapore, Hong Kong, Taiwan and Hongkong are finished: the treatment of 6 months drug combinations can reach 98% expectorant negative conversion rate, cure rate and reach more than 95%, and rare recidivist: the Rifiter of Merrell Dow (Li Fute+isoniazid+pyrazinamide) and Rifinah (Li Fute+isoniazid) finish clinical verification in China, get permission to enter China market, clinical effectiveness is fine, proof 2HRZ/4HR therapeutic scheme also is fit to the tuberculosis patient of China fully, and wherein Rifiter has been selected in " national essential drugs new directory ".Antitubercular agent mostly is ordinary preparation both at home and abroad at present.Peak-paddy the wave phenomenon of the blood drug level that occurs when reducing the ordinary preparation administration, can reach rapid-action after making the complex rifampin administration, can keep the effective blood drug concentration of long period again, to reduce the purpose of untoward reaction, this seminar is studied the supplementary material prescription of " tuberculosis quick-slow double-release compound medicine ", this is a kind of new form of administration, part medicine is present in the preparation with immediate release component, another partly is present in the preparation with the slow release component, make said preparation can reach rapid-action, can keep the purpose of the effective blood drug concentration of long period again.Using this result of study to make oral solid formulation, is the continuity of our seminar's research work.
Summary of the invention
The object of the present invention is to provide a kind of anti-tuberculosis compound medicine quick-slow two release formulations and preparation method thereof.Be about to two kinds of antituberculotics complex rifampins (rifampicin+isoniazid) fixedly combination drug be developed into " speed one slow two releasing " novel form, and its preparation technology and beneficial effect are studied.
The present invention is achieved in that
Complex rifampin quick-slow double-release preparation is made up of by certain weight ratio active component Rimactazid and adjuvant, and its weight ratio is: 2: 1: 0.4～1.3.Wherein adjuvant is made up of framework material, disintegrating agent.
The prescription of each component of medicine of the present invention its ratio range by weight is:
2 parts of rifampicin
1 part of isoniazid
0.08～0.3 part of disintegrating agent
0.2～2 part of framework material
Each component of medicine of the present invention its proportion optimization scope by weight is:
2 parts of rifampicin
1 part of isoniazid
0.09～0.2 part of disintegrating agent
0.3～1.5 part of framework material
Each component of medicine of the present invention its proportion optimization scope by weight is:
2 parts of rifampicin
1 part of isoniazid
0.11～0.18 part of disintegrating agent
0.4～1.0 part of framework material
Each component of medicine of the present invention its best proportioning by weight is:
2 parts of rifampicin
1 part of isoniazid
0.13 part of disintegrating agent
0.52 part of framework material
The feature of selected various adjuvants is as follows in the above-mentioned prescription:
Framework material is the blocker as pharmaceutical preparation of the present invention, works to delay drug release.Framework material can be selected hydroxypropyl emthylcellulose for use. and framework material can use more than a kind or a kind simultaneously.
Disintegrating agent is the disintegrate that promotes preparation, to guarantee the rate of release of medicine.Disintegrating agent can be selected cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, microcrystalline Cellulose, carboxymethyl starch sodium, Naso for use
410H
2O, processing agar, starch and derivant thereof also comprise the disintegrating agent of mentioning on the various preparation books that disintegration is arranged.Disintegrating agent can use more than a kind or a kind simultaneously.
The preferred kind of the adjuvant of medicine of the present invention is:
Framework material: the different model of hydroxypropyl emthylcellulose
Disintegrating agent: polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose sodium.
The preparation method of medicine of the present invention is:
Preparation technology:
(1), takes by weighing Rimactazid, framework material, disintegrating agent respectively by said ratio;
(2), isoniazid and part framework material are put in the mixing channel, fully mix homogeneously is made into soft material with containing alcoholic acid wetting agent, the granulation of sieving, drying, granulate;
(3), the framework material of rifampicin, disintegrating agent and other part is put abundant mix homogeneously in the mixing channel;
(4), (2) gained granule is put abundant mix homogeneously in the mixing channel with (3) gained mixed material;
(5), molding, packing are promptly.
Above-mentioned (4) gained mixture also can be made into acceptable oral solid formulation on the pharmaceutics, for example: capsule, tablet, dry suspension, micropill.
The condition of above-mentioned preparation method is characterized in that:
Crude drug rifampicin and isoniazid are made rapid release and slow-releasing granules respectively, be mixed together again evenly.
The condition of above-mentioned preparation method is characterized in that:
The scope of framework material is 0.27～0.89 part in the technology (2); The scope of framework material is 0.03～0.11 part in the technology (3).
Above-mentioned preparation method (1) (2) (3) (4) (5) is characterized in that specifically:
(1), takes by weighing 2 parts of rifampicin, 1 part of isoniazid, 0.6 part of hydroxypropyl emthylcellulose E50LV, 0.14 part of polyvinylpolypyrrolidone respectively by the prescription proportioning;
(2), isoniazid and 0.47 part of hydroxypropyl emthylcellulose E50LV are put in the mixing channel, abundant mix homogeneously, the alcoholic solution with 60% is made into soft material, the granulation of 35 mesh sieves, 50～55 ℃ of dryings.With 35 mesh sieve granulate;
(3), the hydroxypropyl emthylcellulose E50L0 of rifampicin, polyvinylpolypyrrolidone and 0.13 part is put in the mixing channel fully mix homogeneously;
(4), (2) gained granule is put abundant mix homogeneously in the mixing channel with (3) gained mixed material;
(5), the fill capsule promptly.
Medicine pharmacy check of the present invention should meet following result: this product is orange red granule and powder to kermesinus and white mix homogeneously for the slow capsule 's content of speed, the burst size of every two kinds of main constituents should meet and reached 30%～80% of labelled amount at 0.5 hour, reached 50%～90% in 1 hour, all should reach more than 85% of labelled amount in 2 hours, 4 hours and 8 hours, and contain isoniazid and rifampicin and should be 90.0%～110.0% of labelled amount.
The beneficial effect of medicine preparation of the present invention is:
1, medicine preparation release in vitro degree test of the present invention shows that it can reach the effect of speed-slow release.(see Table 1, table 2, Fig. 1, Fig. 2 Fig. 3, Fig. 4), and the dissolution of ordinary preparation is more than 75% of labelled amount maximum stripping in 30 minutes just.
(Fig. 1, Fig. 2, Fig. 3, Fig. 4 see Figure of description)
Description of drawings: Fig. 1 is the releasing curve diagram of isoniazid in the medicine of the present invention
Fig. 2 is the releasing curve diagram of rifampicin in the medicine of the present invention
Fig. 3 is the releasing curve diagram of the isoniazid in medicine three batch samples of the present invention
Fig. 4 is the releasing curve diagram of the rifampicin in medicinal three batch samples of the present invention.
The cumulative release percentage result (%) of table 1 medicine preparation 050104 sample of the present invention
| Title | Time (h) | 1 | 2 | 3 | 4 | 5 | 6 | On average | RSD |
| The isoniazid | 0.5 1.0 1.5 2.0 3.0 4.0 6.0 8.0 10 12 16 20 24 | 77.10 90.47 93.89 96.02 94.81 93.65 94.29 92.07 99.11 92.37 95.62 96.23 96.91 | 73.62 91.67 96.89 103.83 97.95 97.42 98.14 96.82 95.10 98.38 97.38 96.24 95.49 | 78.40 93.43 96.43 95.46 90.27 90.63 88.53 94.19 89.88 90.80 92.01 93.60 89.89 | 60.93 87.71 95.40 98.65 97.67 97.37 97.45 99.43 95.73 95.00 96.73 91.63 96.46 | 63.70 91.65 96.18 95.87 95.26 93.36 93.97 98.32 96.06 91.49 90.27 90.55 90.66 | 41.24 73.68 87.71 90.73 90.42 89.81 93.54 89.72 91.36 87.63 92.15 90.18 87.40 | 65.83 88.10 94.42 96.76 94.40 93.71 94.32 95.09 94.54 92.61 94.03 93.07 92.82 | 21.26 8.30 3.65 4.46 3.58 3.44 3.63 3.96 3.57 3.99 3.11 2.93 4.29 |
| Rifampin | 0.5 1.0 1.5 2.0 3.0 4.0 6.0 8.0 10 12 16 20 24 | 50.41 79.97 87.52 93.47 97.89 97.17 94.19 91.22 90.15 88.25 85.27 82.85 79.99 | 42.78 71.90 88.09 95.62 97.80 96.18 94.55 92.29 89.74 88.25 84.84 82.02 78.86 | 51.61 78.68 93.91 96.39 90.26 89.81 87.78 87.43 85.98 85.08 81.70 82.14 76.02 | 31.65 63.77 79.29 88.77 96.22 95.54 91.65 90.67 88.90 88.08 84.88 78.72 78.49 | 36.32 73.19 88.57 94.04 94.27 91.68 89.94 88.35 85.90 85.19 81.90 79.98 76.20 | 15.47 46.14 68.98 82.40 91.38 89.64 88.65 85.53 85.45 82.99 80.12 77.20 73.98 | 38.04 68.94 84.39 91.78 94.64 93.34 91.13 89.25 87.69 86.31 83.12 80.49 77.26 | 35.52 18.23 10.53 5.79 3.44 3.60 3.11 2.88 2.44 2.56 2.59 2.77 2.89 |
The cumulative release percentage result (n=6) of table 2 medicine preparation three batch samples of the present invention
| Title | Release time (h) | Average accumulated burst size (%) | ||
| (lot number) 041229 | 0501031 | 050104 | ||
| The isoniazid | 0.5 1.0 1.5 2 3 4 6 8 10 12 16 20 24 | 67.26 88.08 94.57 96.76 96.12 96.35 94.93 95.34 91.69 91.62 90.50 90.10 90.56 | 70.26 90.90 95.45 94.66 93.55 92.27 92.45 91.15 89.00 88.64 88.90 87.32 87.85 | 65.83 88.10 94.42 96.76 94.40 93.71 94.32 95.09 94.54 92.61 94.03 93.07 92.82 |
| Rifampin | 0.5 1.0 1.5 2 3 4 6 8 10 12 16 20 24 | 36.96 67.65 84.06 91.14 94.12 93.04 90.99 89.43 87.94 86.24 83.47 84.49 83.08 | 42.02 76.37 90.12 94.59 94.44 93.16 90.42 89.38 87.48 86.23 83.63 83.04 80.65 | 38.04 68.94 84.39 91.78 94.64 93.34 91.13 89.25 87.69 86.31 83.12 80.49 77.26 |
2, improved quality standard: on the standard of former conventional capsule, increased related substance and release Measure. Related substance should reach: the quinoid rifampin is no more than 2.5%, N-oxidation rifampin and is no more than 2%, 3-The formyl Rifamycin Sodium is no more than 2.5%, and other impurity sum is no more than 2.5%; Releasing of every two kinds of principal components High-volume should meet 30%～80%, 1 hour of reaching labelled amount at 0.5 hour reach 50%～90%, 2 hours, 4 little The time and all should reach more than 85% of labelled amount in 8 hours. This product contains rifampin (C43H
58N
4O
12) and isoniazid (C6H
7N
3O) All should be 90.0%～110.0% of labelled amount.
3, medicine preparation animal pharmacokinetics test of the present invention shows, identical and guarantee in the situation of equal drug disposition uptake and blood concentration in dosage, medicine of the present invention has faster onset time than general formulation, and interior holdup time of longer body and steady state plasma concentration.
1. single-dose:
Experimental technique:
Get 12 of beagle dogs, be divided at random two groups by sex, 6 every group, male and female half and half. Early 8 on an empty stomach administrations, one group of every animal gives one of Drug Capsule of the present invention, and every animal gives together another group One of the conventional capsule of equal-specification, the unified feed in rear 4 hours of taking medicine. Adopt the binary cycle interior extrapolation method to test, The wash-out phase was 1 week.
Blood specimen collection: two groups of blood-sample withdrawal intervals all are after taking medicine: 0.5,1,1.5,2,3,4,6,8,10, 12,24,48hr. In dog forelimb cephalic vein blood sampling 3ml, liquaemin 70IU/mL anti-freezing, 3000r/min from Heart 10min separated plasma is in-20 ℃ of preservations.
The isoniazid determination of plasma concentration:
Chromatographic condition: Alltima C18 chromatographic column (4.6 * 25 0mm, 5 μ m), mobile phase is 0.02mol/L Potassium dihydrogen phosphate (PH4)-acetonitrile (50: 50), flow velocity 1ml/min detects wavelength 340nm, 40 ℃ of column temperatures.
Plasma sample is processed: get blood plasma 0.3ml and add 20% trichloroacetic acid 0.3ml, shake at the vortex oscillator Swung 1 minute, and in the centrifugal 10min of 10000r/min, got supernatant 0.3ml and add 1% cinnaldehydrum methanol solution 15ml after the vortex mixed, places 15min in room temperature, gets 20 μ l sample introductions, with the external standard method peak area quantification.
The rifampin determination of plasma concentration:
Chromatographic condition: Lichrospher 100 RP-8 (4 * 250mm, 5 μ m), mobile phase is acetonitrile-methyl alcohol The mixed liquor of-0.2mol/L potassium dihydrogen phosphate (311: 89: 630) (phosphoric acid is transferred PH4.8), flow velocity 1.5ml/ min. Detect wavelength 254nm, 37 ℃ of column temperatures.
Plasma sample is processed: gets blood plasma 0.2ml, adds acetonitrile 0.4ml, and after vortex vibrated about 1 minute, in Centrifugal 10 minutes of 10000r/min gets supernatant 20 μ l sample introductions, with the external standard method peak area quantification.
Experimental result:
Single-dose, compare pharmaceutical preparation group isoniazid of the present invention and ordinary preparation group isoniazid, MRT (0-t) Value prolongs, and the moving parameter differences of all the other medicines is little. Pharmaceutical preparation group rifampin of the present invention and ordinary preparation group rifampin Relatively Tmax obviously shortens, and MRT (0-t) is worth prolongation, Cmax, and AUC (0-t) does not have variation. As seen guaranteeing In equal drug disposition uptake and the situation of blood concentration, when pharmaceutical preparation of the present invention has faster onset Between, and the holdup time in the longer body. See Table 3.
Table 3, pharmaceutical preparation of the present invention and ordinary preparation pharmacokinetic parameter are relatively
(n=12, X ± SD) (single-dose)
| Group/parameter | T1/2 (h) | Ke (1/h) | AUC(0-t) (mg/L*h) | Tmax (h) | MRT(0-t) (h) | Cmax (mg/L) |
| The slow preparation group rifampin of the slow preparation group isoniazid of speed, ordinary preparation group isoniazid ordinary preparation group rifampin speed | 2.24± 0.45 2.36± 0.41 13.93± 1.96 13.84± 2.29 | 0.321± 0.067 0.303± 0.057 0.051± 0.010 0.051± 0.008 | 87.98± 47.29 82.13± 33.15 828.60± 358.17 838.06± 441.49 | 1.46± 0.40 1.45± 0.72 3.5± 0.87 2.83± 1.11 | 3.88± 0.61 4.04± 0.93 15.84± 1.81 16.32± 1.83 | 18.21± 6.63 17.21± 5.63 40.57± 13.49 41.28± 15.05 |
2. multiple dosing:
Experimental technique:
Get 12 of beale dogs, be divided at random two groups by sex, 6 every group, male and female half and half. 8 skies early The abdomen administration, one group of every animal gives one in medicine preparation of the present invention, and every animal of another group gives with equal-specification One of conventional capsule, the unified feed in rear 4 hours of taking medicine. And in the same administration of 24,48,72,96,120hr, Adopt the binary cycle interior extrapolation method to test, the wash-out phase was 2 weeks.
Blood specimen collection: two groups of blood-sample withdrawal intervals all are after taking medicine: 0.5,1,1.5,2,3,4,6,8,10, 12,24,48,72,96,20.5,121,121.5,122,123,124,126,128,130, 132,144,168,192hr. In dog forelimb cephalic vein blood sampling 3ml, liquaemin 70IU/mL anti-freezing, 3000r/min Centrifugal 10min separated plasma is in-20 ℃ of preservations.
The determination of plasma concentration method of isoniazid and rifampin is the same.
Experimental result:
The multiple dosing result shows: relatively its T1/2 value is basic identical for medicine preparation group of the present invention and ordinary preparation, It is also basic identical to absorb dose in the body, but medicine group RFP of the present invention and ordinary preparation group RFP relatively have faster Peak time (Tmax), coefficient of variation (DF) slightly reduces, the Cmax of two kinds of components (Cmax) is all carried to some extent Height, but steady state plasma concentration is basically identical. Show that medicine of the present invention behind multiple dosing, reaches steady state plasma concentration Situation under, can shorten the Tmax of RFP; But concerning INH, then prolonged Tmax, can make like this Originally peak time differ bigger two kinds of bulk drugs by the present invention after, can make the drug effect time more approaching, subtract Lacked the peak valley wave phenomenon. See Table 4.
Table 4 is respectively organized the moving parameter of medicine relatively (n=10, X ± SD) (multiple dosing)
| Group/parameter | T1/2 (h) | AUC(0-t) (mg/L*h) | Tmax (h) | DF | Cmax (mg/L) | Cav (mg/L) |
| The slow preparation group rifampin of the slow preparation group isoniazid of speed, ordinary preparation group isoniazid ordinary preparation group rifampin speed | 2.585± 0.601 2.336± 0.432 12.540 ±3.639 11.929 ±1.830 | 58.761± 9.210 56.167± 13.126 741.278± 337.326 756.8591± 298.965 | 1.5± 0289 1.786± 1.890 4.25± 3.059 2.875± 1.356 | 5.086± 0.872 5.529± 1.391 1.126± 0.235 1.092± 0.260 | 12.463± 0.965 13.506± 3.325 47.183± 12.035 48.595± 14.595 | 2.486± 0.395 2.446± 0.375 27.123 ±8.782 26.846 ±7.070 |
Specific embodiment:
Embodiment 1:
2 parts of rifampicin
1 part of isoniazid
0.1 part of polyvinylpolypyrrolidone
0.3 part of hydroxypropyl emthylcellulose E50LV
Take by weighing the hydroxypropyl emthylcellulose E50LV mix homogeneously of isoniazid and 0.27 part by proportioning, make soft material with 60% ethanol, 35 mesh sieve granulate, 50～50 ℃ of dryings, granulate, the mixed material mix homogeneously of the rifampicin cross-linking sodium carboxymethyl cellulose that granule and proportioning take by weighing, 0.03 part hydroxypropyl emthylcellulose E50LV, the fill capsule.
Example 2:
2 parts of rifampicin
1 part of isoniazid
0.13 part of cross-linking sodium carboxymethyl cellulose
0.52 part of hydroxypropyl emthylcellulose E50LV
Take by weighing the hydroxypropyl emthylcellulose E50LV mix homogeneously of isoniazid and 0.47 part by proportioning, make soft material with 60% ethanol, 35 mesh sieve granulate, 50～50 ℃ of dryings, granulate, the mixed material mix homogeneously of the rifampicin cross-linking sodium carboxymethyl cellulose that granule and proportioning take by weighing, 0.05 part hydroxypropyl emthylcellulose E50LV, the fill capsule.
Example 3:
2 parts of rifampicin
1 part of isoniazid
0.2 part of carboxymethyl starch sodium
0.8 part of hydroxypropyl emthylcellulose E50LV
Take by weighing the hydroxypropyl emthylcellulose E50LV ' and an amount of mix homogeneously of lactose of isoniazid and 0.72 part by proportioning, make soft material with 60% ethanol, 35 mesh sieve granulate, 50～50 ℃ of dryings, granulate, the mixed material mix homogeneously of the rifampicin cross-linking sodium carboxymethyl cellulose that granule and proportioning take by weighing, 0.09 part hydroxypropyl emthylcellulose E50LV, packing had both got dry suspension.
Embodiment: 4
2 parts of rifampicin
1 part of isoniazid
0.3 part of cross-linking sodium carboxymethyl cellulose
1 part of hydroxypropyl emthylcellulose E50LV
Take by weighing the hydroxypropyl emthylcellulose E50LV mix homogeneously of isoniazid and 0.89 part by proportioning, make soft material with 60% ethanol, 35 mesh sieve granulate, 50～50 ℃ of dryings, granulate, the mixed material mix homogeneously of the rifampicin cross-linking sodium carboxymethyl cellulose that granule and proportioning take by weighing, 0.11 part hydroxypropyl emthylcellulose E50LV, adding fluidizer and lubricant are an amount of, tabletting, both.
Claims (12)
1, a kind of anti-tuberculosis compound medicine quick-slow two release formulations is characterized in that said preparation is made up of by 2: 1: 0.4～1.3 weight ratio following raw medicaments in portion by weight Rimactazid and adjuvant.Wherein adjuvant is made up of framework material and disintegrating agent.And make with the method for being prepared as follows:
(1), takes by weighing Rimactazid, framework material, disintegrating agent by weight ratio respectively;
(2), isoniazid and part framework material are put in the mixing channel, fully mix homogeneously is made into soft material with containing alcoholic acid wetting agent, the granulation of sieving, drying, granulate;
(3), the framework material of rifampicin, disintegrating agent and other part is put abundant mix homogeneously in the mixing channel;
(4), (2) gained granule is put abundant mix homogeneously in the mixing channel with (3) gained mixed material;
(5), molding, packing are promptly.
2, preparation according to claim 1, it is characterized in that wherein proportioning raw materials by weight its ratio range be:
2 parts of rifampicin
1 part of isoniazid
0.08～0.3 part of disintegrating agent
0.2～2 part of framework material.
3, preparation according to claim 1, it is characterized in that wherein proportioning raw materials by weight its ratio range be:
2 parts of rifampicin
1 part of isoniazid
0.09～0.2 part of disintegrating agent
0.3～1.5 part of framework material.
4, preparation according to claim 1, it is characterized in that wherein proportioning raw materials by weight its ratio range be:
2 parts of rifampicin
1 part of isoniazid
0.11～0.18 part of disintegrating agent
0.4～1.0 part of framework material.
5, preparation according to claim 1, it is characterized in that wherein proportioning raw materials by weight its ratio range be:
2 parts of rifampicin
1 part of isoniazid
0.13 part of disintegrating agent
0.52 part of framework material.
6, according to the arbitrary described preparation of claim 1～5, it is characterized in that:
Crude drug rifampicin and isoniazid are made rapid release and slow-releasing granules respectively, be mixed together again evenly.
7, according to the arbitrary described preparation of claim 1～5, it is characterized in that:
The scope of framework material is 0.27～0.89 part in the technology (2); The scope of framework material is 0.03～0.11 part in the technology (3).
8, according to the arbitrary described preparation of claim 1～7, it is characterized in that: framework material can be selected the different model of hydroxypropyl emthylcellulose for use in the used adjuvant, can use more than a kind or a kind simultaneously; Disintegrating agent can be selected cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, microcrystalline Cellulose, carboxymethyl starch sodium, Naso for use
410H
2O, processing agar, starch and derivant thereof also comprise the disintegrating agent of mentioning on the various preparation books that disintegration is arranged.Disintegrating agent can use more than a kind or a kind simultaneously.
9, preparation according to claim 8 is characterized in that: used disintegrating agent can be selected for use: polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose sodium.
10, according to the described arbitrary preparation of claim 1～7, it is characterized in that: the dosage form of described preparation is: acceptable oral solid formulation on the pharmaceutics, for example: capsule, tablet, dry suspension, micropill.
11, according to the described preparation of claim 10, it is characterized in that: the dosage form of described preparation is: capsule.
12, according to the preparation method of the described preparation of claim 10, it is characterized in that:
(1), takes by weighing 2 parts of rifampicin, 1 part of isoniazid, 0.6 part of hydroxypropyl emthylcellulose E50LV, 0.14 part of polyvinylpolypyrrolidone respectively by the prescription proportioning;
(2), isoniazid and 0.47 part of hydroxypropyl emthylcellulose E50LV are put in the mixing channel, abundant mix homogeneously, the alcoholic solution with 60% is made into soft material, the granulation of 35 mesh sieves, 50～55 ℃ of dryings.With 35 mesh sieve granulate;
(3), the hydroxypropyl emthylcellulose E50LV of rifampicin, polyvinylpolypyrrolidone and 0.13 part is put in the mixing channel fully mix homogeneously;
(4), (2) gained granule is put abundant mix homogeneously in the mixing channel with (3) gained mixed material;
(5), the fill capsule promptly.
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|---|---|
| CN (1) | CN1954815A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274453A (en) * | 2013-07-02 | 2015-01-14 | 安徽贝克生物制药有限公司 | Bigeminal compound preparation of anti-tuberculosis medicines and preparation method thereof |
| CN105832671A (en) * | 2016-04-13 | 2016-08-10 | 中国药科大学 | Dry suspension for controlled-release of medicine and preparation method of dry suspension |
-
2005
- 2005-10-28 CN CN 200510118362 patent/CN1954815A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104274453A (en) * | 2013-07-02 | 2015-01-14 | 安徽贝克生物制药有限公司 | Bigeminal compound preparation of anti-tuberculosis medicines and preparation method thereof |
| CN105832671A (en) * | 2016-04-13 | 2016-08-10 | 中国药科大学 | Dry suspension for controlled-release of medicine and preparation method of dry suspension |
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