CN100402030C - Pharmaceutical composition containing amoxicillin and preparation method thereof - Google Patents
Pharmaceutical composition containing amoxicillin and preparation method thereof Download PDFInfo
- Publication number
- CN100402030C CN100402030C CNB2006100326406A CN200610032640A CN100402030C CN 100402030 C CN100402030 C CN 100402030C CN B2006100326406 A CNB2006100326406 A CN B2006100326406A CN 200610032640 A CN200610032640 A CN 200610032640A CN 100402030 C CN100402030 C CN 100402030C
- Authority
- CN
- China
- Prior art keywords
- amoxicillin
- pharmaceutical composition
- weight
- ascorbic acid
- adjuvant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 title claims abstract description 58
- 229960003022 amoxicillin Drugs 0.000 title claims abstract description 53
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 27
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 48
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims abstract description 21
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims abstract description 21
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims abstract description 21
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 20
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 20
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 15
- 239000007787 solid Substances 0.000 claims abstract description 8
- 239000002671 adjuvant Substances 0.000 claims description 17
- 238000005303 weighing Methods 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 238000003113 dilution method Methods 0.000 claims description 5
- 238000007908 dry granulation Methods 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 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 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 229920002261 Corn starch Polymers 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
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 229920000881 Modified starch Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 235000010980 cellulose Nutrition 0.000 claims description 2
- 239000008120 corn starch Substances 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 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 2
- -1 hydroxypropyl Chemical group 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000002398 materia medica Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 14
- 239000012535 impurity Substances 0.000 abstract description 10
- 239000008187 granular material Substances 0.000 abstract description 8
- 238000010790 dilution Methods 0.000 abstract description 2
- 239000012895 dilution Substances 0.000 abstract description 2
- 238000001035 drying Methods 0.000 abstract 1
- 238000005469 granulation Methods 0.000 abstract 1
- 230000003179 granulation Effects 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 13
- 229930182555 Penicillin Natural products 0.000 description 7
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 7
- 229940049954 penicillin Drugs 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 5
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 4
- 229920002307 Dextran Polymers 0.000 description 4
- 229930003268 Vitamin C Natural products 0.000 description 4
- 208000003455 anaphylaxis Diseases 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 235000019154 vitamin C Nutrition 0.000 description 4
- 239000011718 vitamin C Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010002198 Anaphylactic reaction Diseases 0.000 description 3
- 230000036783 anaphylactic response Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 150000002500 ions Chemical group 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 235000019890 Amylum Nutrition 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000005321 cobalt glass Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229940124585 oral penicillin Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- 150000003952 β-lactams Chemical class 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010013700 Drug hypersensitivity Diseases 0.000 description 1
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019345 Heat stroke Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 208000032514 Leukocytoclastic vasculitis Diseases 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000037386 Typhoid Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 201000010235 heart cancer Diseases 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 230000008558 metabolic pathway by substance Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- XKLJHFLUAHKGGU-UHFFFAOYSA-N nitrous amide Chemical class ON=N XKLJHFLUAHKGGU-UHFFFAOYSA-N 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 201000005354 penicillin allergy Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000011003 system suitability test Methods 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 229910021655 trace metal ion Inorganic materials 0.000 description 1
- 201000008297 typhoid fever Diseases 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a medicine composition which can improve the stability of an amoxycillin solid oral preparation and reduce the content of high polymer impurities. The present invention also relates to a method for preparing the medicine composition. The medicine composition containing amoxycillin is mainly composed of amoxycillin, ascorbic acid and disodium ethylenediamine tetraacetate, wherein the weight proportion of the amoxycillin to the ascorbic acid to the disodium ethylenediamine tetraacetate is 1:0.002:0.001 to 1:0.1:0.05. The method for preparing the medicine composition containing amoxycillin comprises the following steps: a given amount of amoxycillin is weighed, and 1/500 to 1/10 weight portions of ascorbic acid, 1/1000 to 1/20 weight portions of disodium ethylenediamine tetraacetate and 1/4 to 3/2 weight portions of auxiliary materials are added to the amoxycillin; the components are uniformly mixed by an equivalent dilution increasing method, and sieved with a sieve with 80 meshes; granulation is carried out by a drying method at a temperature of 15 DEG C to 30 DEG C; granules are pulverized and sieved by a sieve with 100 meshes.
Description
Technical field
The present invention relates to the pharmaceutical products field, particularly a kind of stability that improves the amoxicillin solid orally ingestible, the reduce pharmaceutical composition of high polymer impurity content and this preparation of drug combination method.
Background technology
The amoxicillin is the wide spectrum semisynthetic penicillin, belongs to the important kind in the beta-lactam antibiotic, is usually used in the treatment of respiratory tract, urinary tract and biliary tract infection and typhoid fever etc. due to the sensitive organism.Because the amoxicillin oral absorption is good, therefore, become the popular kind in the prescription drugs in the volume of production and marketing steady-state growth in the whole world, in the city and community hospital brought into play important effect.The folk prescription Wymox was once created 700,000,000 dollars brilliant achievement at world's medical market, be use in the present beta-lactam antibiotic extensively, achievement one of kind preferably.
Yet using the untoward reaction that penicillin caused is the focus that numerous medical personnel and patient pay close attention to all the time.The untoward reaction that penicillin medicine takes place mainly contains symptoms such as hemolytic anemia, leukopenia occur, cause serum syndrome, allergic angiitis etc., allergic dermatitis, whole body large tracts of land erythra occur, even show as consequences such as more serious anaphylactic shock, anaphylaxis death.Though oral penicillin is more light than the anaphylaxis of penicillin injection liquid,, occur causing that because of allergy takes place oral penicillin life danger even death also are possible owing to reasons such as individual variations.Penicillin is the small-molecule drug of being made up of beta-lactam and two rings of thiazole, and itself does not have antigenicity, can not directly cause anaphylaxis.Present research thinks that the anaphylactogen of penicillin allergy is a macromolecule impurity in the preparation.By wave spectrum and physico-chemical analysis, prove that these macromolecule impurities are the high molecular polymers that form after the beta-lactam class antibiotic degraded open loop.Reduce the general main content of making great efforts to control high polymer impurity from aspects such as raw material sources, preparation prescription, production environment, production equipment, preparation process, quality controls of method of amoxicillin high polymer impurity content at present.Simultaneously, because the unsettled lactam nucleus of amoxicillin molecule, be subject to nucleophilic, electrophilic reagent attack and degrade, preparation easy to change, the content problem such as fast that descends can occur in the shelf-life; For solving stability problem, formulation products is mainly taked methods such as tight tabletting, Cotton seeds and secluding air pack at present.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition that contains the amoxicillin, so that improve stability, the minimizing high polymer impurity content of amoxicillin solid orally ingestible.
Another object of the present invention is to provide a kind of method for preparing aforementioned pharmaceutical compositions.
The objective of the invention is to realize by the following technical solutions:
A kind of pharmaceutical composition that contains the amoxicillin, it mainly is made up of amoxicillin, ascorbic acid, disodium EDTA.
The weight ratio of above-mentioned each component is: the amoxicillin: ascorbic acid: disodium EDTA=1: 0.002: 0.001～1: 0.1: 0.05.
Described pharmaceutical composition also comprises adjuvant, and described adjuvant is selected the multiple use of uniting from microcrystalline Cellulose, Powderd cellulose, pregelatinized Starch, corn starch, citric acid, Pulvis Talci, stearic acid, calcium stearate, magnesium stearate, carboxymethylstach sodium, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, polyvidone, polyvinylpolypyrrolidone, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl emthylcellulose, lactose, mannitol, Macrogol 4000.
A kind ofly prepare the above-mentioned method that contains the amoxicillin pharmaceutical composition, may further comprise the steps:
Take by weighing a certain amount of amoxicillin, adding weight is the ascorbic acid of 1/500-1/10, the disodium EDTA of 1/1000-1/20 and the adjuvant of 1/4-3/2;
Adopt equivalent to increase progressively dilution method, cross 80 mesh sieves the said components mix homogeneously;
Dry granulation under 15 ℃-30 ℃ temperature;
Pulverized 100 mesh sieves.
In the said process, preferably add weight and be 1/50 ascorbic acid, 1/200 disodium EDTA and 4/5 adjuvant.
Ascorbic acid is that vitamin C has been widely used at field of medicaments, as treat hemorrhage, the infection of prevention filterable virus and antibacterial, and the enhance immunity systemic-function arranged, have antitumaous effect, help the formation that prevents nitroso-amines (carcinogen), treatment and preventing cold.Take vitamin C during the flu and help to get rid of toxin in the blood of human body, the course of disease of flu is shortened, disease alleviates.The function of its prevention filterable virus in preventing the infectious process of SARS, is proposed as main health care medicine.Vitamin C plays an important role in substance metabolism, promotes the effect that intercellular substance forms simultaneously in addition, and the normal function of keeping tissues such as bone, tooth, blood, muscle is played a very important role.Its major function comprises: help folic acid and mineral metabolism, ingestion of glucose and aminoacid; Improve the leukocyte function, improve immunity, preventing cold; Help skin and skeleton collagen protein to generate, keep bone density; Avoid arteriosclerosis, heart disease and cancer, allow acidify fat restore; Help the adrenal cortex secreting hormone, with counter pressure; Reduce bad cholesterol (LDL), improved cholesterol (HDL); The composition of blood coagulation is avoided in generation, to avoid apoplexy and heart disease; Medicine in the metabolism liver and food left drug, the tool function of detoxification; Increase the adaptive capacity of health, avoid heatstroke etc. variations in temperature.Ascorbic acid is as the treatment and the medicine of adjuvant treatment of diseases, be widely used in for a long time clinical, and frequent and other medicines use in conjunction.
Disodium EDTA is used as chelating agen in pharmaceutical preparation, they and alkaline-earth metal and heavy metal ion form stable water soluble complex (chelating agen).Ion in the chelate does not almost have the characteristic of dissociated ion.Disodium EDTA also is used as the antioxidant synergist, chelating can catalysis automatic oxidation reaction as trace metal ions such as copper, ferrum and manganese.It both can use separately also can unite usefulness with antioxidant, is usually used in stable vitamin C, hydrocortisone, epinephrine, folic acid, formaldehyde, natural gum and resin, hyaluronidase, hydrogen peroxide, oxytetracycline, penicillin, salicylic acid and unsaturated fatty acid.Because chelation, disodium EDTA has certain antibacterial activity, simultaneously, because it can prevent condensing of extracorporeal blood, also is used as anticoagulant and uses.
Because the pharmaceutical composition that contains the amoxicillin of the present invention comprises ascorbic acid and disodium EDTA makes the stability of Wymox significantly be strengthened raising; The high polymer impurity content obviously reduces.Preparation technology of the present invention in addition is simple, and amoxicillin pharmaceutical composition and other pharmaceutic adjuvant have the good compatibility, and easily preparation becomes various solid orally ingestibles, for Wymox production technology, packing and storage requirement provide preferred.
Following the present invention is contrast with existing Amoxicillin Capsules preparation, with the pharmaceutical composition that contains the amoxicillin of the present invention is test sample, carry out the series of stable test, content according to molecular exclusion chromatography (2005 editions two appendix VH of Chinese Pharmacopoeia) mensuration macromolecule impurity compares, analyzes the feasibility that proves technical scheme of the present invention with the result.
Accelerated test: this test is to carry out under acceleration environment, by quickening the chemistry or the physical change of medicine, inquires into its stability.Prepare three batches of the identical test samples (white solid) of quantity performance, under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, placed 6 months.Device therefor control temperature ± 2 ℃, relative humidity ± 5%.Take a sample respectively once at duration of test 1st month, 2 months, 3 months and 6 the end of month, detect the content of its high molecular polymer.Record chromatograph collection of illustrative plates, wherein 6 months chromatogram is seen attached Fig. 1 and 2.
Detection method:
1. chromatographic condition and system suitability test: with sephadex G-10 (40～120 μ m) is filler, glass column internal diameter 1.3～1.6cm, post height 30～40cm.With pH8.0 phosphate buffer (0.05mol/L sodium hydrogen phosphate-0.05mol/L sodium dihydrogen phosphate (95: 5)) is mobile phase A, is Mobile phase B with water, and flow velocity is per minute 1.5ml, and the detection wavelength is 254nm.Be mobile phase with mobile phase A, B, get 0.1mg/ml blue dextran 2000 solution 200 μ l and inject chromatograph of liquid that number of theoretical plate calculates by blue dextran 2000 peaks and all is not less than 700 respectively.Tailing factor all should be less than 2.0.Ratio two kinds of flow phase system Smalt Dextran 200 0 peak retention times should be between 0.93～1.07, and the ratio of the retention time at polymer peak and corresponding chromatographic system Smalt Dextran 200 0 peak all should be between 0.93～1.07 in contrast solution main peak and the need testing solution.Be mobile phase with the Mobile phase B in addition, precision is measured contrast solution 200 μ l, continuous sample introduction 5 times, and the relative standard deviation of peak area is not more than 5.0%.
2. the preparation of contrast solution: it is an amount of to get the penicillin reference substance, accurate claim fixed, be dissolved in water and quantitatively dilution make the solution that contains 0.2mg among every 1ml approximately.
3. algoscopy: get each about 0.2g of two kinds of samples, accurately claim surely, put in the 10ml measuring bottle, add 2% sodium carbonate liquor 4ml and make dissolving, be diluted with water to scale, shake up, precision is measured 200 μ l injecting chromatographs immediately, is mobile phase with the Mobile phase B, measures with method.With calculated by peak area, contain the amoxicillin polymer by external standard method in the amoxicillin.
High polymer assay result is shown in Fig. 3,4,5, and data show that the medicine stability of novel amoxicillin pharmaceutical composition significantly is superior to general Wymox, and macromolecule impurity content significantly reduces, and good reproducibility.
Conclusion (of pressure testing): ascorbic acid and disodium EDTA significantly strengthen the medicine stability of Wymox, the amoxicillin outward appearance of preparing is a white solid, quicken 6 months test solid appearance no changes, high molecular polymer content can be stabilized in below 0.05% before the deadline.
Description of drawings
Fig. 1 is the chromatogram of pharmaceutical composition accelerated tests of the present invention mensuration of high molecular polymer after 6 months;
Fig. 2 is the chromatogram of existing Amoxicillin Capsules preparation accelerated tests mensuration of high molecular polymer after 6 months;
Fig. 3-5 is the three batches of test samples and the reference substance high polymer assay result curve figure of accelerated test process pharmaceutical composition of the present invention.
The specific embodiment
Embodiment one
Take by weighing the 100g amoxicillin, 2.0g ascorbic acid, 0.5g disodium EDTA, 80g adjuvant; Adopt equivalent to increase progressively the dilution method mix homogeneously said components, and cross 80 mesh sieves; Dry granulation under 15 ℃-30 ℃ temperature; Pulverize 100 mesh sieves then and made pharmaceutical composition.The compositions 100g that gets it filled, adjuvant commonly used (diluent, lubricant etc. are as pre-paying starch, the stearate) mix homogeneously, the fill capsule that add 1%-20% promptly get capsule.
Embodiment two
Take by weighing the 100g amoxicillin, 0.2g ascorbic acid, 0.1g disodium EDTA, 25g adjuvant.Adopt equivalent to increase progressively the dilution method mix homogeneously said components, and cross 80 mesh sieves; Dry granulation under 15 ℃-30 ℃ temperature; Pulverize 100 mesh sieves then and made pharmaceutical composition.The compositions 100g that gets it filled adds adjuvant commonly used (disintegrating agent, adhesive, diluent, correctives, the lubricant etc. of 10%-50%.As: the plain sodium of carboxymethyl starch, polyvidone, amylum pregelatinisatum, aspartame, stearate), adopt marumerization to granulate.The granule that makes is crossed 16 mesh sieves earlier after 60 mesh sieve granulate, and the above part of following 60 mesh sieves of 16 mesh sieves is prepared granule.
Embodiment three
Take by weighing the 100g amoxicillin, 10g ascorbic acid, 5g disodium EDTA, 150g adjuvant.Adopt equivalent to increase progressively the dilution method mix homogeneously said components, and cross 80 mesh sieves; Dry granulation under 15 ℃-30 ℃ temperature; Pulverize 100 mesh sieves then and made pharmaceutical composition.The compositions 100g that gets it filled adds adjuvant commonly used (disintegrating agent, adhesive, diluent, correctives, the lubricant etc. of 10%-50%.As: the plain sodium of carboxymethyl starch, polyvidone, amylum pregelatinisatum, aspartame, stearate), adopt marumerization to granulate.The granule that makes is crossed 20 mesh sieve granulate.Tabletting promptly gets tablet.
In above-mentioned preparation process, before taking by weighing amoxicillin, ascorbic acid, disodium EDTA, all needed 100 mesh sieves; Needed 80 mesh sieves before taking by weighing adjuvant.
Claims (8)
1. pharmaceutical composition that contains the amoxicillin, it mainly is made up of amoxicillin, ascorbic acid, disodium EDTA.
2. a kind of pharmaceutical composition that contains the amoxicillin according to claim 1 is characterized in that the weight ratio of described each component is the amoxicillin: ascorbic acid: disodium EDTA=1: 0.002: 0.001～1: 0.1: 0.05.
3. a kind of pharmaceutical composition that contains the amoxicillin according to claim 1 and 2, it is characterized in that, described pharmaceutical composition also comprises adjuvant, and described adjuvant is from microcrystalline Cellulose, Powderd cellulose, pregelatinized Starch, corn starch, citric acid, Pulvis Talci, stearic acid, calcium stearate, magnesium stearate, carboxymethylstach sodium, sodium carboxymethyl cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethylcellulose calcium, polyvidone, polyvinylpolypyrrolidone, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl emthylcellulose, lactose, mannitol, select the multiple use of uniting in the Macrogol 4000.
4. a kind of pharmaceutical composition that contains the amoxicillin according to claim 3 is characterized in that the content of described adjuvant is the 1/4-3/2 of described amoxicillin content.
5. a kind of pharmaceutical composition that contains the amoxicillin according to claim 1 and 2 is characterized in that described pharmaceutical composition can be made into any solid orally ingestible on the materia medica.
6. one kind prepares any one described method that contains the amoxicillin pharmaceutical composition of claim 1-5, comprises following process:
Take by weighing a certain amount of amoxicillin, adding weight is the ascorbic acid of amoxicillin weight 1/500-1/10, and adding weight is that disodium EDTA and the adding weight of amoxicillin weight 1/1000-1/20 is the adjuvant of amoxicillin weight 1/4-3/2;
Adopt equivalent to increase progressively dilution method, cross 80 mesh sieves the said components mix homogeneously;
Dry granulation under 15 ℃-30 ℃ temperature;
Pulverized 100 mesh sieves.
7. preparation according to claim 6 contains the method for amoxicillin pharmaceutical composition, it is characterized in that, in the said process, adding weight is the ascorbic acid of amoxicillin weight 1/50, and adding weight is that the disodium EDTA and the adding weight of amoxicillin weight 1/200 is the adjuvant of amoxicillin weight 4/5.
8. preparation according to claim 6 contains the method for amoxicillin pharmaceutical composition, it is characterized in that, in above-mentioned preparation process, all needs 100 mesh sieves when taking by weighing amoxicillin, ascorbic acid, disodium EDTA; Needed 80 mesh sieves when taking by weighing adjuvant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100326406A CN100402030C (en) | 2006-01-05 | 2006-01-05 | Pharmaceutical composition containing amoxicillin and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100326406A CN100402030C (en) | 2006-01-05 | 2006-01-05 | Pharmaceutical composition containing amoxicillin and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1839832A CN1839832A (en) | 2006-10-04 |
| CN100402030C true CN100402030C (en) | 2008-07-16 |
Family
ID=37029137
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100326406A Active CN100402030C (en) | 2006-01-05 | 2006-01-05 | Pharmaceutical composition containing amoxicillin and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100402030C (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105168143B (en) * | 2015-10-08 | 2018-05-01 | 青岛康地恩动物药业有限公司 | A kind of Wymox and preparation method thereof |
| CN113304112B (en) * | 2021-05-26 | 2022-09-30 | 浙江耐司康药业有限公司 | Amoxicillin soluble powder and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5801153A (en) * | 1991-09-13 | 1998-09-01 | Badaway; Mohammed A. | Method of enhancing the antimicrobial properties of antibacterial antibiotics to massively control and prevent bacterial, fungal, and viral diseases in plants |
| CN1300208A (en) * | 1999-04-09 | 2001-06-20 | 牧岩生命工学研究所 | Icecream-type pharmaceutical formulation and process for preparing the same |
| WO2003068197A1 (en) * | 2002-02-12 | 2003-08-21 | Novartis Ag | Method for systemic drug delivery through the nail |
| WO2004066976A1 (en) * | 2003-01-28 | 2004-08-12 | Röhm GmbH & Co. KG | Method for producing an immediately decomposing oral form of administration which releases active ingredients |
-
2006
- 2006-01-05 CN CNB2006100326406A patent/CN100402030C/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5801153A (en) * | 1991-09-13 | 1998-09-01 | Badaway; Mohammed A. | Method of enhancing the antimicrobial properties of antibacterial antibiotics to massively control and prevent bacterial, fungal, and viral diseases in plants |
| CN1300208A (en) * | 1999-04-09 | 2001-06-20 | 牧岩生命工学研究所 | Icecream-type pharmaceutical formulation and process for preparing the same |
| WO2003068197A1 (en) * | 2002-02-12 | 2003-08-21 | Novartis Ag | Method for systemic drug delivery through the nail |
| WO2004066976A1 (en) * | 2003-01-28 | 2004-08-12 | Röhm GmbH & Co. KG | Method for producing an immediately decomposing oral form of administration which releases active ingredients |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1839832A (en) | 2006-10-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3383392B1 (en) | Dosing regimens for 2-hydroxy-6-((2-(1-isopropyl-1h-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde | |
| CN103181923B (en) | Pharmaceutical preparation comprising Repaglinide and preparation method thereof | |
| CN105943554A (en) | Capsule and powder formulations containing lanthanum compounds | |
| CN101167730B (en) | Compound betamethasone suspension injection | |
| CN101606913A (en) | Cefixime dispersible tablet and preparation method thereof | |
| CN108938626A (en) | A kind of good and highly-safe Carbazochrome sodium sulfonate pharmaceutical composition and its preparation method and application of stability | |
| EP2172206A1 (en) | The method for a sequoyitol-containing extract obtaining from the genus of trifolium, sobyean and ginkgo biloba and use thereof | |
| TWI747906B (en) | A new crystal form of dapagliflozin, its preparation method and use thereof | |
| CN101301455A (en) | Chinese medicine compound turmeric rhizome solid dispersion for treating hyperlipemia | |
| CN102349877A (en) | Hydroxychloroquine sulfate capsule, hydroxychloroquine sulfate dispersible tablet and application thereof | |
| CN109662950A (en) | A kind of pharmaceutical composition containing dapoxetine hydrochloride | |
| CN101219128A (en) | Dexibuprofen pharmaceutical composition with improved dissolving out capability and method for preparing the same | |
| CN100402030C (en) | Pharmaceutical composition containing amoxicillin and preparation method thereof | |
| CN100588399C (en) | A kind of temozolomide freeze-dried powder for injection and preparation method thereof | |
| CN101843596B (en) | Methadone hydrochloride dispersible tablet and preparation method thereof | |
| CN100496487C (en) | Mitiglinide preparation and preparing method | |
| CN102552210B (en) | Entecavir capsule and preparation method thereof | |
| CN101703481B (en) | Ribavirin lipid microsphere effervescent granules | |
| CN104688670B (en) | A kind of canagliflozin sustained release preparation and preparation method thereof | |
| CN103520186A (en) | Pharmaceutical composition comprising lipid-soluble vitamin for injection and preparation method of pharmaceutical composition | |
| CN104072400B (en) | Oxiracetam compound and pharmaceutical composition thereof | |
| CN102600149A (en) | Pharmaceutical composition for treating diabetes | |
| CN107184548B (en) | A kind of highly-safe L-ornidazole injection liquid and preparation method thereof | |
| CN102178709B (en) | Micropills of corylus heterophylla leaf extract and preparation method thereof | |
| CN111419820A (en) | Desloratadine citrate disodium capsule and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Zhuhai federal pharmaceutical Limited by Share Ltd Zhongshan branch Assignor: Zhuhai Lianbang Pharmaceutical Co., Ltd. Contract fulfillment period: 2008.8.8 to 2026.1.5 contract change Contract record no.: 2008440000222 Denomination of invention: Pharmaceutical composition containing amoxicillin and preparation method thereof Granted publication date: 20080716 License type: Exclusive license Record date: 2008.8.19 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENCE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.8.8 TO 2026.1.5 Name of requester: ZHUHAI FEDERATED PHARMACEUTICAL CO., LTD. ZHONGSH Effective date: 20080819 |