Pharmaceutical composition and its preparation method and applicationTechnical field
The present invention relates to technical field of medicine, more particularly to a kind of pharmaceutical composition and preparation method thereof and answerWith.
Background technology
Pulmonary tuberculosis is a kind of disease influencing people's health in tuberculosis, with treating tuberculosis such as streptomysin and isoniazidThe appearance of medicine makes pulmonary tuberculosis become a kind of treatable disease.But the deficiency due to relevant knowledge and treatmentIt is lack of standardization so that Mycobacterium tuberculosis drug-resistant is increasingly severe.
Pulmonary tuberculosis is a kind of stronger disease of infectiousness caused by tubercle bacillus.Three kinds determined in the World Health OrganizationIn the disease for needing priority control, pulmonary tuberculosis is only second to AIDS.China is the serious country of Pulmonary Tuberculosis, in addition with knotThe drug resistance of core bacillus, Chinese drug resistance patient are also being continuously increased.Therefore the drug for the treatment of pulmonery tuberculosis disease is developed, especially treating tuberculosis is resistance toThe drug of medicine is very necessary.
Although the effect of the anti-mycobacterium tuberculosis of seromycin is weaker than streptomysin, it is not likely to produce drug resistance.So circumfiliPropylhomoserin is mainly used for pulmonary tuberculosis caused by treating drug resistance tubercle bacillus.
Seromycin can be also used for treating some other diseases other than being used to infect caused by treating tubercle bacillusDisease.United States Patent (USP) US2014018349, World Intellectual Property Organization WIPO patent WO2008118785, European patent EP 2338482 and EuropeContinent patent EP0378134 discloses the treatment that seromycin can be used for mental disease, depression or Alzheimer disease.The U.S. is specialSharp US2014213621 discloses the treatment that seromycin can be used for chronic ache.
There is the granted listing of the product of seromycin in the U.S., Europe, Japan and China, draws for treating tubercle bacillusThe pulmonary tuberculosis risen.
The preparation of the existing seromycin to emerge is mainly quick-release class preparation, its composition grain size very little, D90Granularity is less than64 μm, the stability of preparation is poor, the sealed storage 40 days under acceleration environment (40 DEG C of temperature, humidity 75%), preparation markThe percentage composition of amount drops to 43.3% from 99.1%, and it is 56.3% to accelerate 40 days degradation amounts, sealed storage 180 under acceleration environmentIt, main ingredient almost all degradations.Sealed storage 180 days, preparation labelled amount under normal temperature condition (25 DEG C of temperature, humidity 60%)Percentage composition drop to 86.4% from 99.1%, 180 days degradation amounts of normal temperature condition are 12.8%.Since preparation is more unstable,Therefore the safety that therapeutic effect can be influenced and used.
Russ P RU2248205 is disclosed, and some fillers are added in seromycin and are filled in capsule, to changeThe stability of the mobility and preparation of kind capsule 's content, wherein the filler being added is mainly Calcium Phosphate, Dibasic Dihydrate, micro mist siliconGlue and calcium stearate.The capsule increases Calcium Phosphate, Dibasic Dihydrate to improve the mobility of capsule 's content, but due to two hydrationsThe frictional force of calcium phosphate is even resulted in powder and changed colour fast problem for a long time compared with die machine easy to wear.The patent does not haveThe detection numerical value of body shows the situation of its stability, and according to preparation made from the patent prescription, stability is still poor, is addingSealed storage 180 days under fast condition (40 DEG C of temperature, humidity 75%), the percentage composition of preparation labelled amount is dropped to from 99.3%65.4%, it is 34.1% to accelerate 180 days degradation amounts.The sealed storage 180 under the conditions of normal temperature condition (25 DEG C of temperature, humidity 60%)It, the percentage composition of preparation labelled amount drops to 94.8% from 99.3%, and 180 days degradation amounts of normal temperature condition are 4.5%.In addition at thisSide finds there are problems that content discoloration, reason may bring into interior with the metal particle in die wear in stability testIt is tolerant, and then keep active ingredient accelerated degradation related, which does not solve the problems, such as that such variety stability is bad, does not have yetIt is found the open patent for improving seromycin preparation stability.
Therefore, need to develop a kind of better seromycin preparation of stability currently on the market to meet the needs of clinical.
Invention content
Based on this, the object of the present invention is to provide a kind of pharmaceutical compositions of the good seromycin of stability.
Specific technical solution is as follows：
A kind of pharmaceutical composition, the pharmaceutical composition include seromycin and auxiliary material, the D of the pharmaceutical composition90GrainDiameter is 75~380 μm, and the dosage of the auxiliary material accounts for the 9~45% of pharmaceutical composition gross mass.
In wherein some embodiments, the auxiliary material includes talcum powder and adhesive and/or compressibility auxiliary material.
In wherein some embodiments, the dosage of the talcum powder accounts for the 9~45% of pharmaceutical composition total amount, the bondingThe dosage of agent accounts for the 0~6% of pharmaceutical composition gross mass, and the dosage of the compressibility auxiliary material accounts for the 0 of pharmaceutical composition gross mass~16%.
In wherein some embodiments, the auxiliary material includes talcum powder and adhesive, and the dosage of the talcum powder accounts for drugThe 23~38% of composition gross mass, the dosage of described adhesive account for the 0.05~2% of pharmaceutical composition gross mass.
In wherein some embodiments, the auxiliary material includes talcum powder and compressibility auxiliary material, and the dosage of the talcum powder accounts forThe dosage of the 23~38% of pharmaceutical composition gross mass, the compressibility auxiliary material accounts for the 8~14% of pharmaceutical composition gross mass.
In wherein some embodiments, described adhesive is selected from polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl fiberIt is one or more of in element, ethyl cellulose, methylcellulose, sodium carboxymethylcellulose, hyetellose, dextrin；It is described to pressProperty auxiliary material it is one or more of in lactose, starch, calcium monohydrogen phosphate, microcrystalline cellulose, mannitol, dextrin.
In wherein some embodiments, the dosage form of the pharmaceutical composition is capsule, and the Capsules of the capsule areGelatin hollow capsule or hydroxypropyl methylcellulose Capsules, the loss on drying of the Capsules<15.0%.
It is a further object of the present invention to provide the preparation methods of aforementioned pharmaceutical compositions.
Specific technical solution is as follows：
The preparation method of aforementioned pharmaceutical compositions, includes the following steps：
By D90Grain size is that 75~380 μm of seromycin is uniformly mixed by the mass percent to get described with auxiliary materialPharmaceutical composition；
Or, seromycin is mixed with auxiliary material by the mass percent, wet granulation, dry granulation or stream are then carried outChange bed granulation, dry, sieving whole grain is to get described pharmaceutical composition；
Or, auxiliary material is carried out wet granulation, dry granulation or fluidized bed granulation, dry, whole grain of being sieved obtains D90Grain size is 75~380 μm of granules of accessories, then with D90Grain size is that 75~380 μm of seromycin is mixed by the mass percent, i.e.,Obtain described pharmaceutical composition.
In wherein some embodiments, the loss on drying of described pharmaceutical composition is between 0.2~2%, D90Grain size is between 120~380 μm.
It is a further object of the present invention to provide the applications of aforementioned pharmaceutical compositions.
Specific technical solution is as follows：
Application of the aforementioned pharmaceutical compositions in preparing phthisical drug caused by treating tubercle bacillus.
Aforementioned pharmaceutical compositions are in the drug for preparing treatment mental disease, depression, Alzheimer disease or chronic acheUsing.
The principle of the present invention and advantage are as follows：
In view of the deficiencies of the prior art, the present invention provides a kind of pharmaceutical compositions of seromycin, specifically a kind ofQuick-release class capsule containing seromycin.
Current seromycin preparation is mainly capsule, but the stability of its preparation is poor, in normal temperature condition (temperature 25DEG C, humidity 60%) and acceleration environment (40 DEG C, humidity 75%) under preparation main ingredient degradation it is all very fast, the effect of influencing preparation andThe safety used.
The present invention is by improving the grain size grain size of pharmaceutical composition (by improve) of auxiliary material and controlling pharmaceutical compositionThe amount of loss on drying not only increases the speed of preparation release, and greatly improves the stability of preparation.
The D of the pharmaceutical composition of the present invention90Grain size is between 75~380 μm, and loss on drying is between 0.2~2%.
The pharmaceutical composition of the present invention combines granulation with auxiliary material by the way that auxiliary material is added in seromycin, or by seromycinMode, by the D of pharmaceutical composition90Size controlling at 75~380 μm, not only make capsule 's content have good mobility withAnd lubricity, also improve the rate of release of preparation and the stability of preparation.Auxiliary material in prescription is mainly talcum powder, and viscousMixture and/or compressibility auxiliary material.
The dosage form of the pharmaceutical composition of the present invention is capsule, the Capsules of the capsule be gelatin hollow capsule orHydroxypropyl methylcellulose Capsules, the loss on drying of the Capsules<15.0%.
The stability of the pharmaceutical composition of the present invention has larger promotion compared with prior art, and optimal example is in normal temperature conditionSealed storage 180 days, the degradation amount of the percentage composition of preparation labelled amount under (25 DEG C of temperature, humidity 60%)<0.5%, accelerate itemSealed storage 180 days, the degradation amount of the percentage composition of preparation labelled amount under part (40 DEG C, humidity 75%)<4.0%.
Specific implementation mode
The present invention is further elaborated by the following examples.
Comparative example 1
Seromycin accounts for total amount 90.9%, seromycin content 99.713%, 325 mesh of talcum powder (44 μm of grain size).
Prescription：
Preparation method：
Take the seromycin of recipe quantity cross 200 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.769%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 1.
Comparative example 2
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 325 mesh of talcum powder.
Prescription：
Preparation method：
Take the seromycin of recipe quantity cross 200 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.521%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 1.
Comparative example 3
Seromycin accounts for total amount 55.6%, seromycin content 99.713%, 325 mesh of talcum powder.
Prescription：
Preparation method：
Take the seromycin of recipe quantity cross 200 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.672%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 1.
Comparative example 4
Seromycin accounts for total amount 64.1%, seromycin content 99.668%, 325 mesh of talcum powder.
Prescription：
Preparation method：
Take the seromycin of recipe quantity cross 200 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.530%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 1.
Table 1
Embodiment 5
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 200 mesh of talcum powder (75 μm of grain size).
Prescription：
Preparation method：
Take the seromycin of recipe quantity cross 200 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.496%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 2.
Embodiment 6
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 200 mesh of talcum powder.
Prescription：
Preparation method：
Take the seromycin of recipe quantity to sieve with 100 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.583%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 2.
Embodiment 7
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 100 mesh of talcum powder (150 μm of grain size).
Prescription：
Preparation method：
Take the seromycin of recipe quantity to sieve with 100 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.578%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 2.
Embodiment 8
Seromycin accounts for total amount 64.1%, seromycin content 99.619%, 100 mesh of talcum powder.
Prescription：
Preparation method：
Take the seromycin of recipe quantity to sieve with 100 mesh sieve, afterwards with the talcum powder mixing of recipe quantity, by every capsule ammonia containing circumfiliThe specification of sour 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.544%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 2.
Table 2
Embodiment 9
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 100 mesh of auxiliary material of wet granulation, and solvent isWater, adhesive account for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and PVP K30 mixing, suitable water softwood, 40 mesh of rear mistake sieve is addedWet granular processed is placed at 60 DEG C dry 2h, the particle after drying is sieved with 100 mesh sieve whole grain, the granules of accessories after must pelletizing.It will placeThe seromycin just measured sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the specification of every capsule 250mg containing seromycinFill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.201%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 10
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material (250 μ of grain size of wet granulationM), solvent is water, and adhesive accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and PVP K30 mixing, suitable water softwood, 40 mesh of rear mistake sieve is addedWet granular processed is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, the granules of accessories after must pelletizing.It will placeThe seromycin just measured sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the specification of every capsule 250mg containing seromycinFill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.015%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 11
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, and solvent isWater, adhesive account for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and PVP K30 mixing, suitable water softwood, 40 mesh of rear mistake sieve is addedWet granular processed is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, the granules of accessories after must pelletizing.It will placeThe seromycin just measured sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the specification of every capsule 250mg containing seromycinFill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 2.183%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 12
Seromycin accounts for total amount 90.9%, seromycin content 99.713%, 40 mesh of auxiliary material (380 μ of grain size of wet granulationM), solvent is water, and adhesive accounts for total amount 0.25%, and adhesive is PVP K30.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and PVP K30 mixing, suitable water softwood, 20 mesh of rear mistake sieve is addedWet granular processed is placed at 60 DEG C dry 2h, the particle after drying is crossed 40 mesh sieves, the granules of accessories after must pelletizing.It will placeThe seromycin just measured sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the specification of every capsule 250mg containing seromycinFill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.627%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 13
Seromycin accounts for total amount 64.1%, and seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, solvent is secondAlcohol, adhesive account for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and PVP K30 mixing, suitable ethyl alcohol softwood, 40 mesh of rear mistake is addedSieve wet granular processed is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, the granules of accessories after must pelletizing.It willThe seromycin of recipe quantity sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the rule of every capsule 250mg containing seromycinLattice fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.756%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 14
Seromycin accounts for total amount 55.6%, and seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, solvent is secondAlcohol, adhesive account for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and PVP K30 mixing, suitable ethyl alcohol softwood, 40 mesh of rear mistake is addedSieve wet granular processed is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, the granules of accessories after must pelletizing.It willThe seromycin of recipe quantity sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the rule of every capsule 250mg containing seromycinLattice fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.701%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 15
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, and 60~80 mesh of auxiliary material of fluidized bed granulation is moltenAgent is ethyl alcohol, and adhesive accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to PVP K30 ethanol solution, by recipe quantityTalcum powder is placed in spray plus PVP K30 ethanol solution wet granular in fluid bed, and is done under fluidized stateIt is dry, cross 60 mesh to 80 mesh sieves, by the seromycin of recipe quantity sieve with 100 mesh sieve afterwards with the auxiliary materials and mixing after granulation, then by everyThe specification of grain capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.723%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 16
Seromycin accounts for total amount 64.1%, and seromycin content 99.474%, 60 mesh of auxiliary material of wet granulation, solvent is secondAlcohol, adhesive account for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to PVP K30 ethanol solution, adds prescriptionThe talcum powder softwood of amount, 40 mesh of rear mistake sieve wet granular processed, are placed at 60 DEG C dry 2h, and it is whole that the particle after drying is crossed 60 mesh sieveGrain, the granules of accessories after must pelletizing.The seromycin of recipe quantity is sieved with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by everyThe specification of capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.635%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 17
Seromycin accounts for total amount 64.1%, and seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, solvent is secondAlcohol, adhesive account for total amount 0.1%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to PVP K30 ethanol solution, adds prescriptionThe talcum powder softwood of amount, 40 mesh of rear mistake sieve wet granular processed, are placed at 60 DEG C dry 2h, and it is whole that the particle after drying is crossed 60 mesh sieveGrain, the granules of accessories after must pelletizing.The seromycin of recipe quantity is sieved with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by everyThe specification of capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.697%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 18
Seromycin accounts for total amount 64.1%, and seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, solvent is secondAlcohol, adhesive account for total amount 3%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to PVP K30 ethanol solution, adds prescriptionThe talcum powder softwood of amount, 40 mesh of rear mistake sieve wet granular processed, are placed at 60 DEG C dry 2h, and it is whole that the particle after drying is crossed 60 mesh sieveGrain, the granules of accessories after must pelletizing.The seromycin of recipe quantity is sieved with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by everyThe specification of capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.640%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 19
Seromycin accounts for total amount 64.1%, and seromycin content 99.713%, 40 mesh of auxiliary material of wet granulation, solvent is secondAlcohol, adhesive account for total amount 6%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to PVP K30 ethanol solution, adds prescriptionThe talcum powder softwood of amount, 20 mesh of rear mistake sieve wet granular processed, are placed at 60 DEG C dry 2h, the particle after drying is crossed 40 mesh (grains380 μm of diameter) sieve, the granules of accessories after must pelletizing.The seromycin of recipe quantity is sieved with 100 mesh sieve, then mixed with the auxiliary material after granulationIt is even, fill No. 1 gelatin hollow capsule by the specification of every capsule 250mg containing seromycin.
Capsule prepared by the above method, loss on drying 0.814%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 20
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, and solvent isWater, adhesive account for total amount 1.0%, and adhesive is hydroxypropyl methylcellulose E5.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and hydroxypropyl methylcellulose E5 mixings, suitable water softwood, 40 mesh of rear mistake sieve system is addedWet granular is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, the granules of accessories after must pelletizing.By prescriptionThe seromycin of amount sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, filled out by the specification of every capsule 250mg containing seromycinFill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.558%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Embodiment 21
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material of wet granulation, and solvent isWater, adhesive account for total amount 1.0%, and adhesive is hydroxypropylcellulose MF.
Prescription：
Preparation method：
By the talcum powder of recipe quantity and hydroxypropylcellulose MF mixings, suitable water softwood is added, 40 mesh of rear mistake sieve system is wetParticle is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, the granules of accessories after must pelletizing.By recipe quantitySeromycin sieve with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the specification filling 1 of every capsule 250mg containing seromycinNumber gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.679%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 3.
Table 3
Embodiment 22
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material of dry granulation, and compressibility is auxiliaryMaterial dosage accounts for total amount 10%, and compressibility auxiliary material is Lactis Anhydrous.
Prescription：
Preparation method：
By dry granulation after the talcum powder of recipe quantity and Lactis Anhydrous mixing, the granules of accessories of 60 mesh is made.By recipe quantitySeromycin sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, fill No. 1 by the specification of every capsule 250mg containing seromycinGelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.215%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 4.
Embodiment 23
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material of dry granulation, and compressibility is auxiliaryMaterial dosage accounts for total amount 16%, and compressibility auxiliary material is Lactis Anhydrous.
Prescription：
Preparation method：
By dry granulation after the talcum powder of recipe quantity and Lactis Anhydrous mixing, the granules of accessories of 60 mesh is made.By recipe quantitySeromycin sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, fill No. 1 by the specification of every capsule 250mg containing seromycinGelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.153%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 4.
Embodiment 24
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, 60 mesh of auxiliary material of dry granulation, and compressibility is auxiliaryMaterial dosage accounts for total amount 10%, and compressibility auxiliary material is starch.
Prescription：
Preparation method：
By dry granulation after the talcum powder of recipe quantity and starch mixing, the granules of accessories of 60 mesh is made.By the circumfili of recipe quantityPropylhomoserin sieves with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, fill No. 1 gelatin by the specification of every capsule 250mg containing seromycinCapsules.
Capsule prepared by the above method, loss on drying 1.589%, disintegration time is 5 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 4.
Table 4
Embodiment 25
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin dry granulation together with auxiliary material60 mesh, compressibility supplementary product consumption account for total amount 0%.
Prescription：
Preparation method：
The seromycin of recipe quantity is sieved with 100 mesh sieve, then with dry granulation after talcum powder mixing, make 60 mesh particle, thenThe specification that particle after granulation is pressed to every capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.637%, disintegration time is 14 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are respectively less than 70%.
Stability data is shown in Table 5.
Embodiment 26
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin dry granulation together with auxiliary material60 mesh, compressibility supplementary product consumption account for total amount 10%, and compressibility auxiliary material is Lactis Anhydrous.
Prescription：
Preparation method：
The seromycin of recipe quantity is sieved with 100 mesh sieve, then with dry granulation after talcum powder and Lactis Anhydrous mixing, system 60Purpose particle, then the particle after granulation is pressed to the specification of every capsule 250mg containing seromycin and fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.985%, disintegration time is 9 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 85%.
Stability data is shown in Table 5.
Embodiment 27
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin dry granulation together with auxiliary material60 mesh, compressibility supplementary product consumption account for total amount 10%, and compressibility auxiliary material is starch.
Prescription：
Preparation method：
The seromycin of recipe quantity is sieved with 100 mesh sieve, then with dry granulation after talcum powder and starch mixing, make 60 purposesParticle, then the particle after granulation is pressed to the specification of every capsule 250mg containing seromycin and fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.122%, disintegration time is 12 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are respectively less than 85%.
Stability data is shown in Table 5.
Table 5
Embodiment 28
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin wet granulation together with auxiliary material60 mesh, solvent are ethyl alcohol, and binder dosage accounts for total amount 0%.
Prescription：
Preparation method：
The seromycin of recipe quantity is sieved with 100 mesh sieve, then be added suitable ethyl alcohol softwood after talcum powder mixing, cross 40Mesh sieves wet granular processed, is placed at 60 DEG C dry 2h, the particle after drying is crossed 60 mesh sieves, then by the particle after granulation by everyThe specification of grain capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.667%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 6.
Embodiment 29
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin wet granulation together with auxiliary material60 mesh, solvent are ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, add the PVP K30 ethanol solution configured, stirEven softwood processed sieves wet granular processed after 40 mesh, is placed at 60 DEG C dry 2h, then dry particle is crossed 60 mesh sieves, then willThe specification that particle after granulation presses every capsule 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.784%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 6.
Table 6
Embodiment 30 (preferred embodiment)
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.532%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 7.
Embodiment 31
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 6.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.661%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 7.
Embodiment 32
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is water, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the aqueous solution of PVP K30, by recipe quantitySeromycin sieves with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 aqueous solution system be wetParticle, and be dried under fluidized state, 60 mesh are crossed to 80 mesh sieves, then the particle after granulation is contained into ring by every capsuleThe specification of serine 250mg fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.620%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 7.
Embodiment 33
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent are ethyl alcohol, and binder dosage accounts for total amount 3.0%, and adhesive is PVP K30, and gelatin is emptyThe loss on drying of heart-soothing capsule is 13.6%.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.568%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 7.
Embodiment 34
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent are ethyl alcohol, and binder dosage accounts for total amount 3.0%, and adhesive is PVP K30, and gelatin is emptyThe loss on drying of heart-soothing capsule is 16.8%.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.699%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 7.
Embodiment 35 (preferred embodiment)
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 3.0%, and adhesive is PVP K30, hydroxypropyl firstThe loss on drying of cellulose hollow capsule is 2.2%.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 hydroxypropyl methylcellulose Capsules.
Capsule prepared by the above method, loss on drying 0.762%, disintegration time is 8 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 85%.
Stability data is shown in Table 7.
Table 7
Embodiment 36
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.676%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 8.
Embodiment 37
Seromycin accounts for total amount 64.1%, seromycin content 99.668%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.804%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 8.
Embodiment 38
Seromycin accounts for total amount 64.1%, seromycin content 99.619%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.758%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 8.
Embodiment 39
Seromycin accounts for total amount 64.1%, seromycin content 99.474%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.692%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 8.
Table 8
Embodiment 40
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.637%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 9.
Embodiment 41
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.741%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 9.
Embodiment 42
Seromycin accounts for total amount 64.1%, seromycin content 99.713%, seromycin fluid bed system together with auxiliary material60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 1.0%, and adhesive is PVP K30.
Prescription：
Preparation method：
The PVP K30 of recipe quantity is configured to the ethanol solution of PVP K30, by recipe quantitySeromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solutionWet granular processed, and be dried under fluidized state, it crosses 60 mesh and presses every capsule to 80 mesh sieves, then by the particle after granulationThe specification of the 250mg containing seromycin fills No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.608%, disintegration time is 4 minutes in water, in pH1.2,15 minutes dissolution rates in pH 4.0, pH 6.8 and water are all higher than 90%.
Stability data is shown in Table 9.
Table 9
The pharmaceutical composition that the embodiment of the present invention is prepared can be applied to pulmonary tuberculosis caused by preparing treatment tubercle bacillusDrug in.It can also be applied to answer in the drug for preparing treatment mental disease, depression, Alzheimer disease or chronic acheWith.
Each technical characteristic of embodiment described above can be combined arbitrarily, to keep description succinct, not to above-mentioned realityIt applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not depositedIn contradiction, it is all considered to be the range of this specification record.
Several embodiments of the invention above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneouslyIt cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the artIt says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the protection of the present inventionRange.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.