CN1843372A - Pharmaceutical compositions separately constituted by ambroxol and two other antibacterials - Google Patents
Pharmaceutical compositions separately constituted by ambroxol and two other antibacterials Download PDFInfo
- Publication number
- CN1843372A CN1843372A CN 200610078751 CN200610078751A CN1843372A CN 1843372 A CN1843372 A CN 1843372A CN 200610078751 CN200610078751 CN 200610078751 CN 200610078751 A CN200610078751 A CN 200610078751A CN 1843372 A CN1843372 A CN 1843372A
- Authority
- CN
- China
- Prior art keywords
- ambroxol
- clindamycin
- azithromycin
- kinds
- hydrochloride
- 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.)
- Pending
Links
- 229960005174 ambroxol Drugs 0.000 title claims abstract description 60
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 title claims abstract description 52
- 229940088710 antibiotic agent Drugs 0.000 title claims description 12
- 230000000844 anti-bacterial effect Effects 0.000 title claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 229960004099 azithromycin Drugs 0.000 claims abstract description 25
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims abstract description 25
- 229960002227 clindamycin Drugs 0.000 claims abstract description 22
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims abstract description 22
- 238000002347 injection Methods 0.000 claims abstract description 17
- 239000007924 injection Substances 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 3
- 239000013078 crystal Substances 0.000 claims abstract description 3
- 239000007921 spray Substances 0.000 claims abstract description 3
- -1 ambroxol compound Chemical class 0.000 claims description 13
- 239000002547 new drug Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 4
- 229940085314 azithromycin 250 mg Drugs 0.000 claims description 3
- 229940048373 clindamycin 150 mg Drugs 0.000 claims description 3
- 229940005067 clindamycin 300 mg Drugs 0.000 claims description 3
- 229940003827 azithromycin 500 mg Drugs 0.000 claims description 2
- 229940030887 clindamycin 100 mg Drugs 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 5
- 229960000985 ambroxol hydrochloride Drugs 0.000 description 31
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 description 30
- 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 description 13
- 239000003814 drug Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 206010036790 Productive cough Diseases 0.000 description 9
- 229960003022 amoxicillin Drugs 0.000 description 9
- 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 description 9
- 239000008215 water for injection Substances 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 6
- 229930186147 Cephalosporin Natural products 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 229940124587 cephalosporin Drugs 0.000 description 6
- 150000001780 cephalosporins Chemical class 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229940099563 lactobionic acid Drugs 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 206010057190 Respiratory tract infections Diseases 0.000 description 5
- 229960001200 clindamycin hydrochloride Drugs 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 description 4
- 229920002307 Dextran Polymers 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 206010006451 bronchitis Diseases 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229960005224 roxithromycin Drugs 0.000 description 4
- 208000024794 sputum Diseases 0.000 description 4
- 210000003802 sputum Anatomy 0.000 description 4
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 3
- 206010011224 Cough Diseases 0.000 description 3
- 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 description 3
- 206010062717 Increased upper airway secretion Diseases 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- UFUVLHLTWXBHGZ-MGZQPHGTSA-N [(2r,3r,4s,5r,6r)-6-[(1s,2s)-2-chloro-1-[[(2s,4r)-1-methyl-4-propylpyrrolidine-2-carbonyl]amino]propyl]-4,5-dihydroxy-2-methylsulfanyloxan-3-yl] dihydrogen phosphate Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](OP(O)(O)=O)[C@@H](SC)O1 UFUVLHLTWXBHGZ-MGZQPHGTSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 229960002291 clindamycin phosphate Drugs 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000012982 microporous membrane Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 208000026435 phlegm Diseases 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 239000007919 dispersible tablet Substances 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 206010025482 malaise Diseases 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- KDLRVYVGXIQJDK-PSUNAQLJSA-N (2s,4r)-n-[(1s)-2-chloro-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide Chemical compound CN1C[C@H](CCC)C[C@H]1C(O)=N[C@H](C(C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-PSUNAQLJSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- NCFTXMQPRQZFMZ-WERGMSTESA-M Cefoperazone sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C([O-])=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 NCFTXMQPRQZFMZ-WERGMSTESA-M 0.000 description 1
- 201000006306 Cor pulmonale Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 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 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 208000004186 Pulmonary Heart Disease Diseases 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 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 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229960002417 cefoperazone sodium Drugs 0.000 description 1
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 1
- 229960002727 cefotaxime sodium Drugs 0.000 description 1
- JEEWDSDYUSEQML-ROMZVAKDSA-M ceftazidime sodium Chemical compound [Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C([O-])=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 JEEWDSDYUSEQML-ROMZVAKDSA-M 0.000 description 1
- 229960002940 ceftazidime sodium Drugs 0.000 description 1
- 229960000479 ceftriaxone sodium Drugs 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- FDRNWTJTHBSPMW-GNXCPKRQSA-L disodium;(6r,7r)-7-[[(2e)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-6-oxido-5-oxo-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)/C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C FDRNWTJTHBSPMW-GNXCPKRQSA-L 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000003453 lung abscess Diseases 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to two compound preparations of Azithromycin / Ambroxol and Clindamycin / Ambroxol, which comprise three components of Azithromycin, Clindamycin and Ambroxol with unlimited acid radicals and crystal shapes. The preparations can be made into the forms of oral liquids, sprays and injections.
Description
Technical field the present invention relates to pharmaceutical ambroxol and two kinds of two kinds of new drug compound preparations that the antibacterials difference makes up in proportion, by retrieval, should the related medical technical field of invention be domestic and international blank at present.
The background technology respiratory tract infection is a kind of commonly encountered diseases, frequently-occurring disease, and is all higher in domestic its incidence and mortality of world's model, and the trend of growth is arranged, and it also is one of key factor of China human mortality.According to statistics China more than 50 years old the bronchitis sickness rate of middle-aged and elderly people be about 15%～30%.Respiratory system disease often shows as cough, expectoration, or with breathing hard, pant etc., the breathing heavily of respiratory system disease, cough, expectorant, scorching four diseases is general common symptons, severe patient can concurrent emphysema, pulmonary heart disease etc., existence, reciprocal causation simultaneously often, therefore usually expectorant and antimicrobial drug share treatment clinically.
Ambroxol is the respiratory mucus regulator of a new generation, has the superior usefulness of eliminating the phlegm, and the synthetic and secretion of alveolar surfactant is had significant facilitation.Ambroxol now is widely used in the lung of respiratory tract abnormal secretion, the treatment of eliminating the phlegm of disease of bronchus, be applicable to acute and chronic respiratory tract disease, the thick sputum, the dys-expectoration that cause as acute and chronic bronchitis, bronchial asthma, bronchiectasis, pulmonary tuberculosis etc.External clinical research proof ambroxol can increase the concentration of many antibiotic in lung tissue such as amoxicillin, cefuroxime, erythromycin, doxycycline, so can increase the antibiotic curative effect of antibiotic respiratory tract, accelerates the elimination of symptom.Holy Martin's fort J.Peralta doctor of hospital with the patient of 23 routine acute episode of chronic bronchitis be divided at random two groups respectively singly with 500 milligrams of amoxicillin with share 500 milligrams of amoxicillin and add 30 milligrams of ambroxols.The result shows that ambroxol adds the improvement of amoxicillin group patient's cough, expectoration difficulty and purulent sputum than singly more Zao more obvious with the amoxicillin group, and the patient's sputum every day amount that adds with ambroxol obviously increases, ambroxol adds the 3rd, 6 days amount of expectoration of amoxicillin group patient obviously to be increased, treating the 3rd day ambroxol adds in amoxicillin group 80% patient's the sputum pathogenic bacterium and eliminates, and single with the pathogenic bacterium elimination of having only 31% in the group of amoxicillin, experimental result prompting ambroxol can strengthen the therapeutic effect of antibacterials such as amoxicillin.And the combination of antibacterials and ambroxol compound recipe can reach the effect for the treatment of both the principal and secondary aspects of a disease to respiratory tract infection, accelerates the elimination of symptom, and The combined is used and is more suitable for clinical needs.
The present compound oral administration preparation that existing amoxicillin, Roxithromycin are made with ambroxol hydrochloride respectively on the domestic and international market at respiratory tract infection, from control infection with eliminate the phlegm and set about, has effectively been treated various diseases due to the respiratory tract infection.But present go on the market be oral medication, bioavailability is relatively poor, onset is slow, and the more gastrointestinal side effect that occurs, be mainly that stomach is scorching hot, dyspepsia, occur feeling sick once in a while, vomiting etc.And amoxicillin, Roxithromycin since Time To Market early, be widely used, bacterial resistance is comparatively general, therefore prepare a kind of novel antibiotics and the ambroxol hydrochloride compound preparation has higher clinic value, particularly intravenously administrable antibacterials and ambroxol the combination compound injection, peak time is fast, the bioavailability height, and curative effect is faster more definite, being specially adapted to can not autonomous respiration, the patient with severe symptoms and the child of autonomous expectoration and the difficulty of taking medicine, and has good market prospect.
The domestic people of having proposes the assembled scheme of some cephalosporins medicines and ambroxol and proposes patent application at present, for example: a kind of compound medicinal formulation for the treatment of pneumonia infection disease and preparation method thereof (CN200410081382.1), compound ambroxol and cephalosporins preparation and application (CN200510005380.9) thereof, but the assembled scheme that it will be argued that cephalosporins medicine and ambroxol is feasible relatively poor when actual industrial production injection, and reason is:
1, ambroxol dissolves back PH5.0 with sterile water for injection, and can not mix greater than other solution of 6.3 with PH, because the pH value increase can cause producing ambroxol free alkali precipitation, and cephalosporin for injections class medicine is generally basic salt, liquor strength height when in cillin bottle, diluting before the powder pin uses, pH value is generally about 6.0～7.5, in person with 5ml: 15mg ambroxol solution splashes into 10% ceftazidime sodium respectively, ceftriaxone sodium, cefotaxime sodium newly disposes in the solution, all produce ambroxol free alkali precipitation in short time in various degree, therefore above drug regimen is produced injection influences stability of drug products.
2, existing cephalosporins medicine material is aseptic powder and all unstable in aqueous solution for a long time, and ambroxol then for the bacterium raw material is arranged, therefore can't prepare lyophilized powder or the injection that can regulate pH value in process of production.Must earlier ambroxol be prepared as and carry out pressed powder with the cephalosporins medicine behind the aseptic raw material and mix, and the unit dose of ambroxol is little, only be 15～30mg, both differ greatly at ratio, for example prepare cefoperazone sodium 1.5g and ambroxol 15mg combination preparation, be difficult to the accurate ratio of component in the control unit dose with aseptic raw material mixing method for filling.
I am through a large amount of drug screening and stability test, it is controlled to propose two kinds of qualities of production, can be used for the two kinds of antibacterials of industrialized great production and the assembled scheme of ambroxol, promptly azithromycin, clindamycin respectively with the drug regimen of ambroxol, its advantage is:
1, azithromycin, clindamycin are the antibacterials that have been able to extensive use since in recent years, determined curative effect in respiratory infection diseases such as pneumonia, pulmonary abscess, and untoward reaction is little, child, old person are not all had taboo, be better than the compound oral administration preparation that existing amoxicillin, Roxithromycin and ambroxol hydrochloride are made with the drug regimen curative effect of ambroxol.
2, azithromycin, clindamycin are more stable in aqueous solution, the present invention can regulate pH value, and accurate controlling content ratio in process of production, therefore but the various oral formulations of assembled scheme suitability for industrialized production of the present invention also can be produced various injections simultaneously, and product stability is very high.
Summary of the invention the present invention be intended to overcome Orally taken product onsets such as existing amoxicillin, Roxithromycin and ambroxol hydrochloride slowly, and the more shortcoming such as drug resistance that occurs, propose two kinds of new drug compound preparations that two kinds of antibacterials azithromycins, clindamycin make up in proportion with ambroxol respectively, filled up the market vacancy in this field.
1, prescription content:
The present invention is two kinds of new drug regimens that combined in proportion with ambroxol respectively by azithromycin, two kinds of antibacterials of clindamycin, and its portfolio ratio is:
Combination 1: azithromycin/ambroxol compound preparation, combine by azithromycin 50mg～500mg and ambroxol 5mg～90mg, but optimal proportion is azithromycin 125mg and ambroxol 15mg, azithromycin 250mg and ambroxol 15mg, azithromycin 500mg and ambroxol 30mg.
Combination 2: clindamycin/ambroxol compound preparation, combine by clindamycin 100mg～4800mg and ambroxol 5～90mg, but optimal proportion is clindamycin 150mg and ambroxol 15mg, clindamycin 300mg and ambroxol 15mg, clindamycin 600mg and ambroxol 30mg, clindamycin 900mg and ambroxol 15mg.
More than azithromycin, clindamycin, three kinds of components of ambroxol in two kinds of drug regimens, all do not limit acid group salt root and crystal form, can be prepared into oral formulations, spray, injection etc. respectively according to market demand and various processes.
In the specific embodiment, content of the present invention is further set forth below:
Specific embodiment the present invention can be illustrated with the following examples
Embodiment 1 azithromycin/ambroxol hydrochloride dispersible tablet, every contains azithromycin effective ingredient 250mg, ambroxol hydrochloride effective ingredient 30mg, prepares 1000 altogether.
Azithromycin 250g (to tire)
Ambroxol hydrochloride 30g (to tire)
Pharmaceutic adjuvant is an amount of
Make 1000
Preparation method: earlier take by weighing azithromycin, ambroxol hydrochloride in above prescription ratio precision, it is an amount of to take by weighing lactose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone, with medicine and adjuvant mix homogeneously; Dropwise 5 % polyvinylpyrrolidone K30 ethanol liquid system soft material is crossed 18 orders～24 mesh sieves and is granulated, and wet granular carries out drying under 50 ℃～80 ℃ conditions; Use 18 orders～24 mesh sieve granulate then, add magnesium stearate and micropowder silica gel mixing, tabletting promptly gets required azithromycin/ambroxol hydrochloride dispersible tablet.
Embodiment 2 lactobionic acid azithromycins/ambroxol hydrochloride freeze-dried powder injection, every bottle contains lactobionic acid azithromycin 250mg, and ambroxol hydrochloride 15mg prepares 1000 altogether.
Lactobionic acid azithromycin 250g (to tire)
Ambroxol hydrochloride 15g (to tire)
Mannitol 10g
Water for injection is an amount of
Make 1000 bottles
Preparation method: precision takes by weighing lactobionic acid azithromycin 250g, ambroxol hydrochloride 15g, mannitol 10g, earlier lactobionic acid azithromycin, mannitol are added in the water for injection, stirring down, the adding sodium sulfite makes material dissolution and transfers pH4.5～5.5, add ambroxol hydrochloride then to above solution, stirring and dissolving adds the water for injection full dose to 1000ml.The injection-use activated carbon of adding 0.3%, stirred 15-30 minute, the filtering active carbon, medicinal liquid is again through 0.45 μ m and 0.22 μ m filtering with microporous membrane, gained filtrate accurately is filled in the cillin bottle by every 10ml, place freezer dryer, being cooled to-25 ℃～-30 ℃ kept after 2 hours, be cooled to-40 ℃～-45 ℃ again, open vacuum, slowly be warming up to-5 ℃～0 ℃ sublimation drying, stop drying less than 1% to moisture, lyophilization is finished, and the gland packing promptly gets 1000 of lactobionic acid azithromycin for injections/ambroxol hydrochloride freeze-dried powder injections.
Embodiment 3 Clindamycin Hydrochlorides/ambroxol hydrochloride granule, every bag of 3g, wherein hydrochloric clindamycin 150mg, ambroxol hydrochloride 15mg prepare 1000 bags altogether.
Clindamycin Hydrochloride 150g (to tire)
Ambroxol hydrochloride 15g (to tire)
Pharmaceutic adjuvant is an amount of
Make 1000 bags
Preparation method: precision takes by weighing Clindamycin Hydrochloride 150g, ambroxol hydrochloride 15g.Add sucrose, pharmaceutic adjuvants such as dextrin are granulated, drying, and granulate, mixing by every bag of 3g accurate measurement packing, is promptly made 1000 bags of the Clindamycin Hydrochlorides of every bag of 3g/ambroxol hydrochloride granule.
Embodiment 4 hydrochloride for injection clindamycin/ambroxol hydrochlorides, every hydrochloric clindamycin 300mg, ambroxol hydrochloride 15mg prepare 1000 altogether.
Clindamycin Hydrochloride 300g (to tire)
Ambroxol hydrochloride 15g (to tire)
Dextran 10 g
Water for injection is an amount of
Make 1000
Preparation method: precision takes by weighing Clindamycin Hydrochloride 300g, ambroxol hydrochloride 15g, Dextran 10 g, the hydrochloric acid crin is mould, dextran is added in the water for injection earlier, stirring down, the adding sodium bicarbonate makes material dissolution and transfers pH4.0～5.5, add ambroxol hydrochloride then to above solution, stirring and dissolving adds the water for injection full dose to 1000ml.The injection-use activated carbon of adding 0.3%, stirred 15-30 minute, the filtering active carbon, medicinal liquid is again through 0.45 μ m and 0.22 μ m filtering with microporous membrane, gained filtrate accurately is filled in the cillin bottle by every 10ml, place freezer dryer, being cooled to-25 ℃～-30 ℃ kept after 2 hours, be cooled to-40 ℃～-45 ℃ again, open vacuum, slowly be warming up to-5 ℃～0 ℃ sublimation drying, stop drying less than 1% to moisture, lyophilization is finished, and the gland packing promptly gets 1000 of hydrochloride for injection clindamycin/ambroxol hydrochloride freeze-dried powder injections.
Embodiment 5 clindamycin phosphates/ambroxol hydrochloride injection, every 5ml contains clindamycin phosphate 600mg, ambroxol hydrochloride 30mg, prepares 1000 altogether.
Clindamycin phosphate 600g (to tire)
Ambroxol hydrochloride 30g (to tire)
Water for injection is an amount of
Make 1000
Preparation method: precision takes by weighing clindamycin phosphate 600g, ambroxol hydrochloride 30g, the hydrochloric acid crin is mould, dextran is added in the water for injection earlier, stirring down, the adding sodium bicarbonate makes material dissolution and transfers pH4.0～5.5, add ambroxol hydrochloride then to above solution, stirring and dissolving adds the water for injection full dose to 500ml.The injection-use activated carbon of adding 0.3% stirred the filtering active carbon 15-30 minute, medicinal liquid is again through 0.45 μ m and 0.22 μ m filtering with microporous membrane, and filtrate accurately is filled to peace by every 5ml and cuts open in the bottle, seals, high temperature sterilize promptly gets 1000 of clindamycin phosphates/ambroxol hydrochloride injection.
The invention is not restricted to above example.
Claims (5)
1, the present invention relates to ambroxol and two kinds of two kinds of new drug compound preparations that antibacterials azithromycin, clindamycin make up respectively in proportion.
2, the described two kinds of new drug compound preparations of claim 1 are meant azithromycin/ambroxol compound preparation, clindamycin/ambroxol compound preparation.
3, the portfolio ratio of the described two kinds of new drug compound preparations of claim 1 is:
(1) azithromycin/ambroxol compound preparation: combine by azithromycin 50mg～500mg and ambroxol 5mg～90mg, but optimal proportion is azithromycin 125mg and ambroxol 15mg, azithromycin 250mg and ambroxol 15mg, azithromycin 500mg and ambroxol 30mg.
(2) clindamycin/ambroxol compound preparation: combine by clindamycin 100mg～4800mg and ambroxol 5～90mg, but optimal proportion is clindamycin 150mg and ambroxol 15mg, clindamycin 300mg and ambroxol 15mg, clindamycin 600mg and ambroxol 30mg, clindamycin 900mg and ambroxol 30mg.
4, azithromycin, clindamycin, three kinds of components of ambroxol in the described two kinds of new drug compound preparations of claim 1 all do not limit acid group, salt root and crystal form.
5, the dosage form of the described two kinds of new drug compound preparations of claim 1 does not limit, and can be prepared into oral formulations, spray, injection etc. respectively according to market demand and various processes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610078751 CN1843372A (en) | 2006-05-11 | 2006-05-11 | Pharmaceutical compositions separately constituted by ambroxol and two other antibacterials |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610078751 CN1843372A (en) | 2006-05-11 | 2006-05-11 | Pharmaceutical compositions separately constituted by ambroxol and two other antibacterials |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1843372A true CN1843372A (en) | 2006-10-11 |
Family
ID=37062358
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610078751 Pending CN1843372A (en) | 2006-05-11 | 2006-05-11 | Pharmaceutical compositions separately constituted by ambroxol and two other antibacterials |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1843372A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD4093B1 (en) * | 2004-05-03 | 2011-02-28 | Boehringer Ingelheim International Gmbh | Use of topical pharmaceutical composition containing ambroxol |
| EP2857012A4 (en) * | 2012-05-28 | 2015-11-25 | Hainan Wei Kang Pharmaceutical Qianshan Company Ltd | Compound ambroxol hydrochloride composition and preparation method therefor |
-
2006
- 2006-05-11 CN CN 200610078751 patent/CN1843372A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD4093B1 (en) * | 2004-05-03 | 2011-02-28 | Boehringer Ingelheim International Gmbh | Use of topical pharmaceutical composition containing ambroxol |
| EP2857012A4 (en) * | 2012-05-28 | 2015-11-25 | Hainan Wei Kang Pharmaceutical Qianshan Company Ltd | Compound ambroxol hydrochloride composition and preparation method therefor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3452018A2 (en) | Effervescent formulations comprising cefaclor and clavulanic acid as active agents | |
| KR101562608B1 (en) | Compound chemical medicine acting on respiratory disease, preparation process and use thereof | |
| CN101590043A (en) | A kind of compound preparation for the treatment of respiratory tract infection and preparation method thereof | |
| WO2008101428A1 (en) | Culture medium for lactobacillus acidophilus and streptococcus faecalis, composition comprising the same and preparation method thereof | |
| CN1843372A (en) | Pharmaceutical compositions separately constituted by ambroxol and two other antibacterials | |
| CN113546089A (en) | Application of 1-ethyl-3,7-dimethylxanthine in the preparation of medicine for treating pneumonia | |
| CN100574757C (en) | Composition of acetylcysteine or its salt and anti-infective drug | |
| CN100411621C (en) | Cefixime oral disintegration tablet and its preparation method | |
| CN1631371A (en) | Oral administered bitter free powder of macrolide antibiotic, its prescription and preparation process | |
| CN1951386A (en) | Medicinal combinations composed by meropenem with three kinds of sputum removing medicament respectively | |
| CN100553635C (en) | Contain the pharmaceutical composition and the application thereof of amoxicillin, ambroxol and beta lactamase restrainer | |
| CN101423516A (en) | Preparation of pidotimod sodium and medicinal use thereof | |
| CN1820749A (en) | Formula of amoxycillin sodium/ambroxo/ hydrochloride powder injection and its preparing method | |
| CN116036123A (en) | Compound montmorillonite particles for treating Helicobacter pylori infection and preparation method thereof | |
| CN101768156A (en) | Pidotimod arginine salt and preparation thereof | |
| CN1951387A (en) | Medicinal combinations composed by Imipenem, Cilastatin and three kinds of sputum removing medicament | |
| CN1951379A (en) | Medicinal combination composed by Fudosteine with nine kinds of antiseptic medicament respectively | |
| TW526062B (en) | Antimicrobial composition | |
| CN1729977A (en) | Freeze dry powdered injection of moxfloxacin or its salts and preparation process thereof | |
| CN113491668B (en) | Pharmaceutical composition preparation for injection and preparation method and application thereof | |
| CN1259904C (en) | Medicinal composition with sodium houttuy fonate and ambroxol hydrochloride | |
| CN101513409B (en) | Pharmaceutical composition of cephalexin | |
| CN1965851A (en) | Composition prepared by ambroxol and four kinds of antibacterials respectively | |
| CN1872055A (en) | Compound preparation of amoxicillin and ambroxol hydrochloride suitable to use for children, prescription and preparation method | |
| CN1857289A (en) | Dispersed compound tablet of glycyrrhizic acid and glycyrrhizinate and its preparing process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |