CN105476976B - Pharmaceutical composition and its preparation method and application - Google Patents
Pharmaceutical composition and its preparation method and application Download PDFInfo
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- CN105476976B CN105476976B CN201510982014.2A CN201510982014A CN105476976B CN 105476976 B CN105476976 B CN 105476976B CN 201510982014 A CN201510982014 A CN 201510982014A CN 105476976 B CN105476976 B CN 105476976B
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- Prior art keywords
- seromycin
- pharmaceutical composition
- auxiliary material
- capsule
- mesh
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- 238000002360 preparation method Methods 0.000 title claims abstract description 74
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 58
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 claims abstract description 200
- 229940099992 seromycin Drugs 0.000 claims abstract description 200
- 239000000463 material Substances 0.000 claims abstract description 91
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 239000002775 capsule Substances 0.000 claims description 154
- 238000001035 drying Methods 0.000 claims description 64
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 63
- 239000000853 adhesive Substances 0.000 claims description 49
- 230000001070 adhesive effect Effects 0.000 claims description 49
- 108010010803 Gelatin Proteins 0.000 claims description 46
- 229920000159 gelatin Polymers 0.000 claims description 46
- 239000008273 gelatin Substances 0.000 claims description 46
- 235000019322 gelatine Nutrition 0.000 claims description 46
- 235000011852 gelatine desserts Nutrition 0.000 claims description 46
- 238000005469 granulation Methods 0.000 claims description 40
- 230000003179 granulation Effects 0.000 claims description 40
- 239000012530 fluid Substances 0.000 claims description 28
- 238000005550 wet granulation Methods 0.000 claims description 18
- 239000008187 granular material Substances 0.000 claims description 17
- 238000007908 dry granulation Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 11
- 208000008128 pulmonary tuberculosis Diseases 0.000 claims description 9
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 8
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 8
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229920002472 Starch Polymers 0.000 claims description 6
- 239000008107 starch Substances 0.000 claims description 6
- 235000019698 starch Nutrition 0.000 claims description 6
- 235000020985 whole grains Nutrition 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 3
- 229920001353 Dextrin Polymers 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 235000019425 dextrin Nutrition 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229950004422 hyetellose Drugs 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 abstract description 11
- 238000006731 degradation reaction Methods 0.000 abstract description 11
- 230000001133 acceleration Effects 0.000 abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 127
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 84
- 229920003081 Povidone K 30 Polymers 0.000 description 84
- 235000019441 ethanol Nutrition 0.000 description 56
- 238000002156 mixing Methods 0.000 description 52
- 238000004090 dissolution Methods 0.000 description 42
- 238000000034 method Methods 0.000 description 42
- 239000002245 particle Substances 0.000 description 37
- 239000000243 solution Substances 0.000 description 35
- 235000013339 cereals Nutrition 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- 239000011230 binding agent Substances 0.000 description 15
- 239000011122 softwood Substances 0.000 description 14
- 239000007921 spray Substances 0.000 description 14
- 238000005453 pelletization Methods 0.000 description 12
- 125000005909 ethyl alcohol group Chemical group 0.000 description 11
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 201000008827 tuberculosis Diseases 0.000 description 5
- -1 Calcium Phosphate, Dibasic Dihydrate Chemical class 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 3
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 239000003390 Chinese drug Substances 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001355 anti-mycobacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229960003350 isoniazid Drugs 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 201000003102 mental depression Diseases 0.000 description 1
- 239000002923 metal particle Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Inorganic Chemistry (AREA)
Abstract
The invention discloses a kind of pharmaceutical composition and its preparation method and application, which is made of seromycin and auxiliary material, the D of described pharmaceutical composition90Grain size is 75~380 μm, and the dosage of the auxiliary material accounts for the 9~45% of pharmaceutical composition gross mass.The stability of the pharmaceutical composition of the present invention has larger promotion, optimal example sealed storage 180 days, degradation amount of the percentage composition of preparation labelled amount under normal temperature condition (25 DEG C of temperature, humidity 60%) compared with prior art<0.5%, sealed storage 180 days, the degradation amount of the percentage composition of preparation labelled amount under acceleration environment (40 DEG C, humidity 75%)<4.0%.
Description
Technical field
The present invention relates to technical field of medicine, more particularly to a kind of pharmaceutical composition and preparation method thereof and answer
With.
Background technology
Pulmonary tuberculosis is a kind of disease influencing people's health in tuberculosis, with treating tuberculosis such as streptomysin and isoniazid
The appearance of medicine makes pulmonary tuberculosis become a kind of treatable disease.But the deficiency due to relevant knowledge and treatment
It 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 Organization
In the disease for needing priority control, pulmonary tuberculosis is only second to AIDS.China is the serious country of Pulmonary Tuberculosis, in addition with knot
The 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 to
The 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 circumfili
Propylhomoserin 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 bacillus
Disease.United States Patent (USP) US2014018349, World Intellectual Property Organization WIPO patent WO2008118785, European patent EP 2338482 and Europe
Continent patent EP0378134 discloses the treatment that seromycin can be used for mental disease, depression or Alzheimer disease.The U.S. is special
Sharp 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 bacillus
The 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 than
64 μm, the stability of preparation is poor, the sealed storage 40 days under acceleration environment (40 DEG C of temperature, humidity 75%), preparation mark
The 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 environment
It, 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 change
The stability of the mobility and preparation of kind capsule 's content, wherein the filler being added is mainly Calcium Phosphate, Dibasic Dihydrate, micro mist silicon
Glue and calcium stearate.The capsule increases Calcium Phosphate, Dibasic Dihydrate to improve the mobility of capsule 's content, but due to two hydrations
The 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 have
The 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 adding
Sealed 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 this
Side finds there are problems that content discoloration, reason may bring into interior with the metal particle in die wear in stability test
It 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 yet
It 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 composition90Grain
Diameter 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 bonding
The 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 drug
The 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 for
The 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 fiber
It is one or more of in element, ethyl cellulose, methylcellulose, sodium carboxymethylcellulose, hyetellose, dextrin；It is described to press
Property 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 are
Gelatin 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 material
Pharmaceutical composition；
Or, seromycin is mixed with auxiliary material by the mass percent, wet granulation, dry granulation or stream are then carried out
Change 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 ache
Using.
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 of
Quick-release class capsule containing seromycin.
Current seromycin preparation is mainly capsule, but the stability of its preparation is poor, in normal temperature condition (temperature 25
DEG 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 and
The safety used.
The present invention is by improving the grain size grain size of pharmaceutical composition (by improve) of auxiliary material and controlling pharmaceutical composition
The 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 seromycin
Mode, by the D of pharmaceutical composition90Size controlling at 75~380 μm, not only make capsule 's content have good mobility with
And lubricity, also improve the rate of release of preparation and the stability of preparation.Auxiliary material in prescription is mainly talcum powder, and viscous
Mixture 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 or
Hydroxypropyl 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 condition
Sealed 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 item
Sealed 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 circumfili
The 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 pH
1.2,15 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 is
Water, 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 added
Wet 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 place
The 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 seromycin
Fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.201%, disintegration time is 4 minutes in water, in pH
1.2,15 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 granulation
M), 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 added
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 will place
The 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 seromycin
Fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.015%, disintegration time is 4 minutes in water, in pH
1.2,15 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 is
Water, 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 added
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 will place
The 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 seromycin
Fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 2.183%, disintegration time is 4 minutes in water, in pH
1.2,15 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 granulation
M), 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 added
Wet 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 place
The 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 seromycin
Fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.627%, disintegration time is 4 minutes in water, in pH
1.2,15 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 second
Alcohol, 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 added
Sieve 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 will
The 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 seromycin
Lattice 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 pH
1.2,15 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 second
Alcohol, 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 added
Sieve 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 will
The 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 seromycin
Lattice 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 pH
1.2,15 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 molten
Agent 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 quantity
Talcum powder is placed in spray plus PVP K30 ethanol solution wet granular in fluid bed, and is done under fluidized state
It 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 every
The 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 pH
1.2,15 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 second
Alcohol, 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 prescription
The 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 sieve
Grain, 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 every
The 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 pH
1.2,15 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 second
Alcohol, 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 prescription
The 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 sieve
Grain, 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 every
The 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 pH
1.2,15 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 second
Alcohol, 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 prescription
The 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 sieve
Grain, 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 every
The 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 pH
1.2,15 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 second
Alcohol, 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 prescription
The 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 (grains
380 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 granulation
It 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 pH
1.2,15 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 is
Water, 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 added
Wet 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 prescription
The 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 seromycin
Fill No. 1 gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.558%, disintegration time is 4 minutes in water, in pH
1.2,15 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 is
Water, 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 wet
Particle 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 quantity
Seromycin sieve with 100 mesh sieve, then with the auxiliary materials and mixing after granulation, by the specification filling 1 of every capsule 250mg containing seromycin
Number gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 0.679%, disintegration time is 4 minutes in water, in pH
1.2,15 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 auxiliary
Material 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 quantity
Seromycin 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 seromycin
Gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.215%, disintegration time is 5 minutes in water, in pH
1.2,15 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 auxiliary
Material 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 quantity
Seromycin 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 seromycin
Gelatin hollow capsule.
Capsule prepared by the above method, loss on drying 1.153%, disintegration time is 5 minutes in water, in pH
1.2,15 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 auxiliary
Material 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 quantity
Propylhomoserin 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 seromycin
Capsules.
Capsule prepared by the above method, loss on drying 1.589%, disintegration time is 5 minutes in water, in pH
1.2,15 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 material
60 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, then
The 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 pH
1.2,15 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 material
60 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 60
Purpose 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 pH
1.2,15 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 material
60 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 purposes
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 1.122%, disintegration time is 12 minutes in water, in pH
1.2,15 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 material
60 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 40
Mesh 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 every
The 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 pH
1.2,15 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 material
60 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, add the PVP K30 ethanol solution configured, stir
Even 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 will
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieves with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 aqueous solution system be wet
Particle, 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 capsule
The 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 pH
1.2,15 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 material
60~80 mesh of grain, solvent are ethyl alcohol, and binder dosage accounts for total amount 3.0%, and adhesive is PVP K30, and gelatin is empty
The 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 mesh of grain, solvent are ethyl alcohol, and binder dosage accounts for total amount 3.0%, and adhesive is PVP K30, and gelatin is empty
The 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 mesh of grain, solvent is ethyl alcohol, and binder dosage accounts for total amount 3.0%, and adhesive is PVP K30, hydroxypropyl first
The 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 material
60~80 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 quantity
Seromycin sieve with 100 mesh sieve, then with talcum powder mixing, be placed in fluid bed spray plus PVP K30 ethanol solution
Wet 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 granulation
The 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 pH
1.2,15 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 bacillus
Drug in.It can also be applied to answer in the drug for preparing treatment mental disease, depression, Alzheimer disease or chronic ache
With.
Each technical characteristic of embodiment described above can be combined arbitrarily, to keep description succinct, not to above-mentioned reality
It 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 deposited
In 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 simultaneously
It 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 art
It 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 invention
Range.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (9)
1. a kind of pharmaceutical composition, which is characterized in that the pharmaceutical composition includes seromycin and auxiliary material, the pharmaceutical composition
The D of object90Grain size is 75~380 μm, and the dosage of the auxiliary material accounts for the 9~45% of pharmaceutical composition gross mass；
The auxiliary material includes talcum powder and adhesive and/or compressibility auxiliary material.
2. pharmaceutical composition according to claim 1, which is characterized in that it is total that the dosage of the talcum powder accounts for pharmaceutical composition
The 9~45% of amount, the dosage of described adhesive accounts for the 0~6% of pharmaceutical composition gross mass, and the dosage of the compressibility auxiliary material accounts for
The 0~16% of pharmaceutical composition gross mass.
3. pharmaceutical composition according to claim 1 or 2, which is characterized in that the auxiliary material includes talcum powder and adhesive,
The dosage of the talcum powder accounts for the 23~38% of pharmaceutical composition gross mass, and the dosage of described adhesive accounts for the total matter of pharmaceutical composition
The 0.05~2% of amount.
4. pharmaceutical composition according to claim 1 or 2, which is characterized in that the auxiliary material includes talcum powder and compressibility
Auxiliary material, the dosage of the talcum powder account for the 23~38% of pharmaceutical composition gross mass, and the dosage of the compressibility auxiliary material accounts for drug
The 8~14% of composition gross mass.
5. pharmaceutical composition according to claim 1 or 2, which is characterized in that described adhesive is selected from polyvinylpyrrolidine
Ketone, hydroxypropyl methylcellulose, hydroxypropylcellulose, ethyl cellulose, methylcellulose, sodium carboxymethylcellulose, hyetellose, paste
It is one or more of in essence；The compressibility auxiliary material is in lactose, starch, calcium monohydrogen phosphate, microcrystalline cellulose, mannitol, dextrin
It is one or more of.
6. pharmaceutical composition according to claim 1 or 2, which is characterized in that the dosage form of the pharmaceutical composition is capsule,
The Capsules of the capsule are gelatin hollow capsule or hydroxypropyl methylcellulose Capsules, and the dry of the Capsules loses
Weight<15.0%.
7. the preparation method of claim 1~6 any one of them pharmaceutical composition, which is characterized in that include the following steps：
By D90Grain size is that 75~380 μm of seromycin is uniformly mixed by the mass percent to get the drug with auxiliary material
Composition；
Or, seromycin is mixed with auxiliary material by the mass percent, wet granulation, dry granulation or fluid bed are then carried out
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 be 75~
380 μm of granules of accessories, then with D90Grain size be 75~380 μm seromycin by the mass percent mixed to get
Described pharmaceutical composition.
8. preparation method according to claim 7, which is characterized in that the loss on drying of described pharmaceutical composition is between 0.2
Between~2%, D90Grain size is between 120~380 μm.
9. claim 1~6 any one of them pharmaceutical composition is preparing pulmonary tuberculosis caused by treating tubercle bacillus, spirit
Application in the drug of disease, depression, Alzheimer disease or chronic ache.
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| PCT/CN2015/100130 WO2017107242A1 (en) | 2015-12-22 | 2015-12-31 | Pharmaceutical composition, preparation method and application thereof |
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| CN107320471B (en) * | 2017-08-08 | 2020-10-09 | 湖南慧泽生物医药科技有限公司 | Cycloserine pharmaceutical composition for treating tuberculosis and application thereof |
| CN107308147B (en) * | 2017-08-08 | 2020-09-18 | 新乡医学院第一附属医院 | Use of aminomethylbenzoic acid composition in treating tuberculosis |
| US11291654B2 (en) * | 2018-09-13 | 2022-04-05 | Syneurx International (Taiwan) Corp. | Formulations of cycloserine compounds and applications thereof |
| US10485790B1 (en) * | 2018-09-13 | 2019-11-26 | Syneurx International (Taiwan) Corp. | Salts of cycloserine compounds and applications thereof |
| CN115177593B (en) * | 2022-08-08 | 2023-08-25 | 锦州奥鸿药业有限责任公司 | Glutamine granule and preparation method thereof |
| CN115944627A (en) * | 2023-01-13 | 2023-04-11 | 山西医科大学 | Pharmaceutical composition for treating breast cancer |
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| RU2248205C1 (en) * | 2003-09-18 | 2005-03-20 | Открытое акционерное общество "Щелковский витаминный завод" | Medicinal agent as gelatin capsule |
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| RU2248205C1 (en) * | 2003-09-18 | 2005-03-20 | Открытое акционерное общество "Щелковский витаминный завод" | Medicinal agent as gelatin capsule |
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| WO2008118785A2 (en) * | 2007-03-23 | 2008-10-02 | Tikvah Therapeutics | Methods for treating depression using immediate-impact treatments and d-cycloserine |
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| WO2017107242A1 (en) | 2017-06-29 |
| CN105476976A (en) | 2016-04-13 |
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