CN101703465A - Azithromycin injection and preparation method thereof - Google Patents
Azithromycin injection and preparation method thereof Download PDFInfo
- Publication number
- CN101703465A CN101703465A CN200910172751A CN200910172751A CN101703465A CN 101703465 A CN101703465 A CN 101703465A CN 200910172751 A CN200910172751 A CN 200910172751A CN 200910172751 A CN200910172751 A CN 200910172751A CN 101703465 A CN101703465 A CN 101703465A
- Authority
- CN
- China
- Prior art keywords
- injection
- azithromycin
- water
- mannitol
- citric acid
- 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
- 229940069981 azithromycin injection Drugs 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 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 61
- 229960004099 azithromycin Drugs 0.000 claims abstract description 60
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000002347 injection Methods 0.000 claims abstract description 21
- 239000007924 injection Substances 0.000 claims abstract description 21
- 229940090044 injection Drugs 0.000 claims abstract description 20
- 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 abstract description 19
- 229930195725 Mannitol Natural products 0.000 claims abstract description 19
- 239000000594 mannitol Substances 0.000 claims abstract description 19
- 235000010355 mannitol Nutrition 0.000 claims abstract description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000011265 semifinished product Substances 0.000 claims abstract description 14
- 238000003756 stirring Methods 0.000 claims abstract description 14
- 239000008215 water for injection Substances 0.000 claims abstract description 13
- 239000000243 solution Substances 0.000 claims abstract description 11
- 239000000725 suspension Substances 0.000 claims abstract description 10
- 230000003287 optical effect Effects 0.000 claims abstract description 9
- 238000004108 freeze drying Methods 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 23
- 239000003610 charcoal Substances 0.000 claims description 15
- 229940105082 medicinal charcoal Drugs 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 12
- 238000007689 inspection Methods 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000013505 freshwater Substances 0.000 claims description 11
- 238000005262 decarbonization Methods 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 5
- 238000002372 labelling Methods 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 5
- 238000012856 packing Methods 0.000 claims description 5
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 210000004907 gland Anatomy 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 4
- 239000012982 microporous membrane Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 abstract description 10
- 238000012360 testing method Methods 0.000 abstract description 5
- 238000010998 test method Methods 0.000 abstract description 2
- 238000009835 boiling Methods 0.000 abstract 1
- 239000012528 membrane Substances 0.000 abstract 1
- 238000001471 micro-filtration Methods 0.000 abstract 1
- 238000004806 packaging method and process Methods 0.000 abstract 1
- 238000000034 method Methods 0.000 description 12
- 230000003115 biocidal effect Effects 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000002775 capsule Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 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 6
- 229940079593 drug Drugs 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000711 polarimetry Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 208000029082 Pelvic Inflammatory Disease Diseases 0.000 description 3
- 206010035664 Pneumonia Diseases 0.000 description 3
- 229960003276 erythromycin Drugs 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 241000589248 Legionella Species 0.000 description 2
- 208000007764 Legionnaires' Disease Diseases 0.000 description 2
- 206010028116 Mucosal inflammation Diseases 0.000 description 2
- 201000010927 Mucositis Diseases 0.000 description 2
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000194103 Bacillus pumilus Species 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 241001647372 Chlamydia pneumoniae Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- MTBZIGHNGSTDJV-UHFFFAOYSA-N Ditalimfos Chemical compound C1=CC=C2C(=O)N(P(=S)(OCC)OCC)C(=O)C2=C1 MTBZIGHNGSTDJV-UHFFFAOYSA-N 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- 241000204048 Mycoplasma hominis Species 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 1
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003103 anti-anaerobic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 230000007849 functional defect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 229920005555 halobutyl Polymers 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 201000001371 inclusion conjunctivitis Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012473 microbial detection method Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000003448 neutrophilic effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 238000011170 pharmaceutical development Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 206010044325 trachoma Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an azithromycin injection, which comprises the following components by weight in 3000 ml injection: 250.0 g or 500.0 g of azithromycin, 1.0 g of citric acid, 120.0 g of mannitol, 18.0 g of medicinal carbon and the balance of water for injection. The preparation method comprises the following steps of: (1) adding the mannitol into the water for injection, heating for dissolving, adding the medicinal carbon, boiling for 30 minutes, decarburizing and filtrating; (2) preparing a suspension by adding the azithromycin to the water for injection; (3) after dissolving the citric acid, adding the dissolved citric acid into the azithromycin suspension for fully dissolving the azithromycin with the pH value controlled to be 5.7-5.9, adding the medicinal carbon, stirring, standing, decarburizing and filtrating; (4) adding the mannitole filtrate into the azithromycin solution with the pH value controlled to be 5.7-5.9, adding the water for injection till a prepared full dose, filtrating through microfiltration membranes with 0.45 micrometers and 0.22 micrometers; (5) measuring the content of a semi-finished product by adopting an optical rotation test method; (6) if the semi-finished product is tested to be qualified, transmitting the medicinal solution to a bottling department, wherein the bottled injection holding volume is 3 ml; (7) freeze-drying, totally pressing pistons, pressing covers, and light-inspecting, and if the semi-finished product is qualified after the quality test, label-sticking, packaging and obtaining the product.
Description
Technical field:
The present invention relates to a kind of injection and production method thereof, particularly relate to prescription of a kind of Azithromycin injection and preparation method thereof, belong to the biologic pharmacological science field.
Background technology:
Azithromycin is first 15 yuan of macrolide antibiotics, owing to inserted nitrogen-atoms in ring, also is referred to as lipid antibiotic in the azo-cycle.This distinctive molecular structure is given many important chemistry of azithromycin and pharmacological property just.Azithromycin has broad spectrum antibiotic activity.Azithromycin is except keeping the effect of erythromycin to gram positive bacteria, and to the part gram negative bacteria, anaerobe and intracellular pathogen also have good antibacterial activity, and this helps the treatment of mixed infection especially.Strong more than 4 times as azithromycin to hemophilus influenza and gonococcal specific activity erythromycin, active strong 2 times to legionella, to also effective by isolated helicobacter pylori in the duodenal ulcer patients intestinal mucosa, to other pathogenic microorganisms, better curative effect is also arranged as mycoplasma pneumoniae, trachoma clothing original paper etc.The azithromycin oral bioavailability is 37% only, makes injection and can improve bioavailability, and it is wide to distribute in the tissue concentration height, body, and more is applicable to critical patient's treatment.Azithromycin is eliminated in serum slowly, and the half-life reaches 46 hours, and only need be administered once every day, makes things convenient for doctor and patient's medication.Its metabolism mainly is that the original shape medicine is got rid of from the biliary tract secretion.In addition, azithromycin also has characteristics such as short treating period, absolute acid stability be good.
Because azithromycin is water insoluble, so numerous enterprises and research unit are arranged in the research of carrying out the azithromycin injection, but they become salt, double salt or organic salt to azithromycin, after water-soluble, make injection, process operation is loaded down with trivial details like this, time-consuming length, and the medicinal liquid for preparing has the embedding sterilization time limit, so stability is just relatively poor, is easy to generate side effect.
All the time, the production technology personnel of applicant company are actively seeking redress, and through secular arduous exploration, rely on pharmaceutical developments company of group company and part colleges and universities inside the province, have solved the technical barrier of this product, have obtained important breakthrough.
Summary of the invention:
Technical problem to be solved by this invention is: overcome the deficiencies in the prior art, a kind of preparation method of stable Azithromycin injection is provided, satisfy needs clinically.
The technical scheme that the present invention is taked for the technical solution problem is:
A kind of Azithromycin injection, in the injection of 3000ml, contain following each composition: the azithromycin of 250.0g, the citric acid of 1.0g, the mannitol of 120.0g, the medicinal charcoal of 18.0g, surplus is a fresh water for injection.
The Azithromycin injection of another specification, in the injection of 3000ml, contain following each composition: the azithromycin of 500.0g, the citric acid of 1.0g, the mannitol of 120.0g, the medicinal charcoal of 18.0g, surplus is a fresh water for injection.
The content of azithromycin recited above calculates according to anhydride.
The preparation method of two kinds of Azithromycin injections recited above, its concrete steps are as follows:
1., mannitol is added in the fresh water for injection of dose volume 10%, heating is dissolved it fully, adds half medicinal charcoal of formula ratio, boils decarbonization filtering 30 minutes;
2., the azithromycin of formula ratio is added in the water for injection below 20 ℃ of dose volume 60%, make into suspension;
3., citric acid dissolving back is slowly added in the Azithromycin mix suspension liquid, the limit edged stirs, and azithromycin is dissolved fully with an amount of water for injection, strict control liquid PH value is 5.7～5.9, adds second half medicinal charcoal of formula ratio, stirs 10 minutes, left standstill decarbonization filtering 20 minutes;
4., mannitol filtrate is added in the azithromycin solution, the repetition measurement liquid PH value should add the injection water to preparing full dose 5.7～5.9, stirs, through 0.45 μ m, 0.22 μ m filtering with microporous membrane;
5., check that the visible foreign matters of medicinal liquid is qualified after, the censorship semi-finished product adopt the optical rotation detection method to measure half-finished content;
6., the inspection of semifinished product is qualified, and medicinal liquid is reached bottling department, fill injection loading amount is 3ml;
7., lyophilization, the total head plug, gland, lamp inspection, after quality inspection was qualified, labeling, packing promptly obtained Azithromycin injection.
The main innovate point of the present invention on production technology has with the lower part:
1, this product adopts citric acid and azithromycin salify, makes the freeze-drying prods azithromycin injection in an amount of excipient of adding through lyophilization, and its technology is a domestic initiation.This production technology has solved the characteristic that azithromycin is insoluble in water, and its dissolubility strengthened greatly, meets quality of production requirement.
2, the azithromycin injection semi-finished product adopt polarimetry to measure its semi-finished product content; changed the azithromycin injection method of the microbial detection method control of usefulness in process of production, this method is simple, and is quick; can in time instruct Workshop Production, adapt to needs of scale production.
The composition of raw materials of Azithromycin injection of the present invention such as following table:
1. fill a prescription:
| Name of material | 1000 consumptions (0.25g) | 1000 consumptions (0.5g) |
| Azithromycin (by anhydride) | ??250g | ??500g |
| Citric acid | ??1.0g | ??1.0g |
| Mannitol | ??120g | ??120g |
| Medicinal charcoal | ??18.0g | ??18.0g |
| Fresh water for injection | Add to 3000ml | Add to 3000ml |
2. supplementary material is supplied producer:
Semi-finished product content check innovation is reported as follows:
In order further to determine the half-finished feasibility of optical rotation detection method mensuration azithromycin injection injection, the applicant has carried out a large amount of contrast tests, and test method and apparatus are as follows:
(1), polarimetry is measured:
1, detects requirement according to polarimetry.Required key instrument is: the automatic polariscope of WZZ-2B.
2, reagent: the azithromycin raw material that Beijing Taiyang Pharmaceutical Co., Ltd. produces, lot number 030804,030922,031017.
3, method:
(1), the preparation of standard solution: decide azithromycin, citric acid, mannitol according to the accurate title of the ratio of producing recipe quantity 100%, add in an amount of water for injection, stir and make dissolving fully, make every milliliter of solution that contains azithromycin (pure) 0.25 gram.
(2), with the mensuration pipe of 2dm, the optical rotation of the accurate solution of mark is a;
(3), be a1 according to optical rotation with the method working sample;
4, calculate according to following formula: the content=a1/a*100% that measures liquid
(2), the antibiotic microorganism method is measured:
1, detect requirement according to the antibiotic microorganism method, required main instruments is:
The microorganism measuring instrument of tiring.
2, reagent and material: the azithromycin raw material that Beijing Taiyang Pharmaceutical Co., Ltd. produces, lot number 030804,030922,031017.
A, strain: Bacillus pumilus;
B, culture medium: antibiotic calibrating culture medium (PH7.8～8.0);
C, buffer: Plondrel acid buffer (pH value 7.8);
D, condition of culture: 7 ℃ of temperature, 14～16 hours;
E, antibiotic concentration scope: 5～10KUL-1.
3, method: it is an amount of that precision is measured sample, add aquesterilisa and make the solution that contains azithromycin 1000 units among every 1ml, it is an amount of that other gets the azithromycin standard substance, add ethanol (every 10mg adds ethanol 4ml) dissolving, add water and make the solution that contains azithromycin 1000 units among every 1ml approximately, measure according to the method that the antibiotic microorganism calibrating is sent out under (two appendix XIA of Chinese Pharmacopoeia version in 2000) Zitromax prime implicant.1000 azithromycin units are equivalent to the C of 1mg
38H
72N
2O
12
(3), research process and data:
According to test requirements document, the sample to three lot numbers detects respectively, and the optical rotation of 100% sample is respectively:
| ??030804 | ??-6.250° |
| ??030922 | ??-6.380° |
| ??031017 | ??-6.090° |
The preparation of sample and labelling:
According to azithromycin injection production prescription, carry out the preparation of test specimen respectively, amount of preparation is three samples of each lot number, manufactures experimently with 95%, 100% and 105% of recipe quantity respectively, and lot number is respectively as following table:
| Feed intake | ??95％ | ??100％ | ??105％ |
| ??030804 | ??031101a | ??031101b | ??031101c |
| ??030922 | ??031102a | ??031102b | ??031102c |
| ??031017 | ??031103a | ??031103b | ??031103c |
Respectively same sample is measured according to two diverse ways respectively, each sample carries out three times respectively to be measured, and asks its meansigma methods as the last content of measuring, and specifically detects data such as following table:
Show by above-mentioned data and to utilize polarimetry to measure the half-finished content of azithromycin injection and utilize antibiotic microorganism method measurement result not have significant difference, meet statistics normal deviate scope, can correctly determine the half-finished content of azithromycin.
The various performances of the Azithromycin injection of producing with the present invention are as follows:
[nomenclature of drug] adopted name: azithromycin injection.
[composition] this product Main Ingredients and Appearance is an azithromycin.Adjuvant: citric acid, mannitol.
[character] this product is the loose block of white or off-white color.
[indication] this product is applicable to the caused following infection of responsive pathogenic strain: by the microbial community acquired pneumonia that need at first take the intravenous drip treatment of Chlamydia pneumoniae, hemophilus influenza, legionella pneumophilia, mucositis mora bacterium, mycoplasma pneumoniae, staphylococcus aureus or pneumonia streptococcus; The needs that caused by chlamydia trachomatis, Diplococcus gonorrhoeae, mycoplasma hominis are at first taked the pelvic inflammatory disease of intravenous drip treatment.
[specification] 0.25g (250,000 unit) 0.5g (500,000 unit)
[usage and dosage] fully dissolves this product with an amount of sterilized water for injection, is mixed with 0.1g/ml, joins in the sodium chloride injection or 5% glucose injection of 250ml or 500ml again, and final azithromycin concentration is 1.0～2.0mg/ml, intravenous drip then.Concentration is 1.0mg/ml, and the instillation time is 3 hours; Concentration is 2.0mg/ml, and the instillation time is 1 hour.
The treatment community acquired pneumonia: the 0.5g that is grown up a time, 1 time on the one, continuous use is 2 at least, and that continues uses azithromycin oral preparation 0.5g on the one instead, and 7～10 is a course of treatment.Transferring the oral medication time to should be definite according to the clinical treatment reaction by the doctor.
The treatment pelvic inflammatory disease: the 0.5g that is grown up a time, 1 time on the one, medication is used azithromycin oral preparation 0.25g on the one instead after 1 day or 2 days, and 7 is a course of treatment.Transferring the oral medication time to should be definite according to the clinical treatment reaction by the doctor.
[untoward reaction]
1. this product common adverse reactions has:
(1) gastrointestinal reaction: diarrhoea, stomachache, loose stool, feel sick, vomiting etc.
(2) local response: injection site pain, local inflammation etc.
(3) dermoreaction: erythra, pruritus.
(4) other reactions: as sitophobia, vaginitis, stomatitis, dizziness or dyspnea etc.
2. this product also can cause following reaction:
(1) digestive system: strain bacterium disease, gastritis etc. are read in dyspepsia, flatulence, mucositis, oral cavity.
(2) nervous system: headache, drowsiness etc.
(3) anaphylaxis: bronchospasm etc.
(4) other reactions: parageusia etc.
(5) lab testing: serum aminotransferase, creatinine, lactic acid dehydrogenase, bilirubin and alkali phosphatase raise, and leukocyte, neutrophilic granulocyte and platelet count reduce.
[taboo] is to azithromycin, erythromycin or other any Macrocyclolactone lactone kind medicine allergy sufferers forbiddings
[points for attention] slight renal insufficiency patient (creatinine clearance rate＞40ml/ minute) need not make dose titration, but azithromycin is to than the non-avaible still of the use among the severe renal functional defect patient, should be prudent when using azithromycin for these patients.
Because liver and gall is the excretory main path of azithromycin, the careful usefulness of hepatic insufficiency person, serious hepatopath should not use.Regular follow-up liver function during the medication.
If anaphylaxis (as vasodilation, dermoreaction, Stevous-Jonson syndrome and the necrosis of toxicity epidermis etc.) takes place during the medication, drug withdrawal immediately, and take appropriate measures.
During the treatment,, should consider that pseudomembranous enterocolitis takes place if symptom of diarrhea appears in the patient.If diagnosis is established, should take the corresponding treatment measure, comprise and keep water, electrolyte balance, additional protein etc.
This product at every turn the time of instiling must not be less than 60 minutes, drip liquid concentration must not be higher than 2.0mg/ml.
If suspect the merging anaerobic infection, should share anti-anaerobic agent during the treatment pelvic inflammatory disease.
[storage] shading, airtight, preserve at the drying place.
[dosage form] lyophilized injectable powder.
[inner packaging material] hangs down borosilicate antibiotic bottle, halogenated butyl rubber plug.
[packing specification] 0.25g * 1/capsule * 300 capsules/case
0.25g * 2/capsule * 300 capsules/case
0.25g * 6/capsule * 120 capsules/case
0.5g * 1/capsule * 300 capsules/case
The specific embodiment:
Embodiment one: a kind of specification is 0.25g (250,000 a unit) Azithromycin injection, in the injection of 3000ml, contains following each composition: the azithromycin of 250.0g (anhydride), 1.0g citric acid, 120.0g mannitol, the medicinal charcoal of 18.0g, surplus is a fresh water for injection.
The preparation method of Azithromycin injection recited above, its concrete steps are as follows:
1., mannitol is added in the fresh water for injection of dose volume 10%, heating is dissolved it fully, adds half medicinal charcoal of formula ratio, boils decarbonization filtering 30 minutes;
2., the azithromycin of formula ratio is added in the water for injection below 20 ℃ of dose volume 60%, make into suspension;
3., citric acid dissolving back is slowly added in the Azithromycin mix suspension liquid, the limit edged stirs, and azithromycin is dissolved fully with an amount of water for injection, strict control liquid PH value is 5.7～5.9, adds second half medicinal charcoal of formula ratio, stirs 10 minutes, left standstill decarbonization filtering 20 minutes;
4., mannitol filtrate is added in the azithromycin solution, the repetition measurement liquid PH value should add the injection water to preparing full dose 5.7～5.9, stirs, through 0.45 μ m, 0.22 μ m filtering with microporous membrane;
5., check that the visible foreign matters of medicinal liquid is qualified after, the censorship semi-finished product adopt the optical rotation detection method to measure half-finished content;
6., the inspection of semifinished product is qualified, and medicinal liquid is reached bottling department, fill injection loading amount is 3ml;
7., lyophilization, the total head plug, gland, lamp inspection, after quality inspection was qualified, labeling, packing promptly obtained Azithromycin injection.
Embodiment two: a kind of specification is 0.5g (500,000 a unit) Azithromycin injection, in the injection of 3000ml, contains following each composition: the azithromycin of 500.0g, 1.0g citric acid, 120.0g mannitol, the medicinal charcoal of 18.0g, surplus is a fresh water for injection.
The preparation method of Azithromycin injection recited above, its concrete steps are as follows:
1., mannitol is added in the fresh water for injection of dose volume 10%, heating is dissolved it fully, adds half medicinal charcoal of formula ratio, boils decarbonization filtering 30 minutes;
2., the azithromycin of formula ratio is added in the water for injection below 20 ℃ of dose volume 60%, make into suspension;
3., citric acid dissolving back is slowly added in the Azithromycin mix suspension liquid, the limit edged stirs, and azithromycin is dissolved fully with an amount of water for injection, strict control liquid PH value is 5.7～5.9, adds second half medicinal charcoal of formula ratio, stirs 10 minutes, left standstill decarbonization filtering 20 minutes;
4., mannitol filtrate is added in the azithromycin solution, the repetition measurement liquid PH value should add the injection water to preparing full dose 5.7～5.9, stirs, through 0.45 μ m, 0.22 μ m filtering with microporous membrane;
5., check that the visible foreign matters of medicinal liquid is qualified after, the censorship semi-finished product adopt the optical rotation detection method to measure half-finished content;
6., the inspection of semifinished product is qualified, and medicinal liquid is reached bottling department, fill injection loading amount is 3ml;
7., lyophilization, the total head plug, gland, lamp inspection, after quality inspection was qualified, labeling, packing promptly obtained Azithromycin injection.
Claims (4)
1. Azithromycin injection is characterized in that: in the injection of 3000ml, contain following each composition: the azithromycin of 250.0g, and the citric acid of 1.0g, the mannitol of 120.0g, the medicinal charcoal of 18.0g, surplus is a fresh water for injection.
2. Azithromycin injection is characterized in that: in the injection of 3000ml, contain following each composition: the azithromycin of 500.0g, and the citric acid of 1.0g, the mannitol of 120.0g, the medicinal charcoal of 18.0g, surplus is a fresh water for injection.
3. Azithromycin injection according to claim 1 and 2 is characterized in that: the content of described azithromycin calculates according to anhydride.
4. the preparation method of an Azithromycin injection as claimed in claim 1 or 2, its concrete steps are as follows:
1., mannitol is added in the fresh water for injection of dose volume 10%, heating is dissolved it fully, adds half medicinal charcoal of formula ratio, boils decarbonization filtering 30 minutes;
2., the azithromycin of formula ratio is added in the water for injection below 20 ℃ of dose volume 60%, make into suspension;
3., citric acid dissolving back is slowly added in the Azithromycin mix suspension liquid, the limit edged stirs, and azithromycin is dissolved fully with an amount of water for injection, strict control liquid PH value is 5.7～5.9, adds second half medicinal charcoal of formula ratio, stirs 10 minutes, left standstill decarbonization filtering 20 minutes;
4., mannitol filtrate is added in the azithromycin solution, the repetition measurement liquid PH value should add the injection water to preparing full dose 5.7～5.9, stirs, through 0.45 μ m, 0.22 μ m filtering with microporous membrane;
5., check that the visible foreign matters of medicinal liquid is qualified after, the censorship semi-finished product adopt the optical rotation detection method to measure half-finished content;
6., the inspection of semifinished product is qualified, and medicinal liquid is reached bottling department, fill injection loading amount is 3ml;
7., lyophilization, the total head plug, gland, lamp inspection, after quality inspection was qualified, labeling, packing promptly obtained Azithromycin injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910172751A CN101703465A (en) | 2009-11-27 | 2009-11-27 | Azithromycin injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910172751A CN101703465A (en) | 2009-11-27 | 2009-11-27 | Azithromycin injection and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101703465A true CN101703465A (en) | 2010-05-12 |
Family
ID=42373763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910172751A Pending CN101703465A (en) | 2009-11-27 | 2009-11-27 | Azithromycin injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101703465A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102429863A (en) * | 2011-11-29 | 2012-05-02 | 湖南科伦制药有限公司 | Azithromycin injection packaged by double-cavity bag and preparation method thereof |
| CN112629990A (en) * | 2021-01-24 | 2021-04-09 | 深圳博泰尔生物技术有限公司 | Azithromycin reference substance and preparation method thereof |
| US11779595B2 (en) * | 2017-02-02 | 2023-10-10 | Mcmaster University | Bicarbonate as a potentiator for antimicrobial agents |
-
2009
- 2009-11-27 CN CN200910172751A patent/CN101703465A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102429863A (en) * | 2011-11-29 | 2012-05-02 | 湖南科伦制药有限公司 | Azithromycin injection packaged by double-cavity bag and preparation method thereof |
| US11779595B2 (en) * | 2017-02-02 | 2023-10-10 | Mcmaster University | Bicarbonate as a potentiator for antimicrobial agents |
| CN112629990A (en) * | 2021-01-24 | 2021-04-09 | 深圳博泰尔生物技术有限公司 | Azithromycin reference substance and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mao et al. | Protective effects of natural and partially degraded konjac glucomannan on Bifidobacteria against antibiotic damage | |
| CN101411710A (en) | Pemetrexed disodium freeze-dried powder injection and preparation method thereof | |
| CN101836950A (en) | Moxifloxacin hydrochloride glucose injection and preparation method and use thereof | |
| KR20170007312A (en) | Microbiological growth media and methods of using the same | |
| CN101703465A (en) | Azithromycin injection and preparation method thereof | |
| CN113559013A (en) | Application of lithocholic acid compound in preparation of antibacterial product | |
| CN103494780B (en) | Gamithromycin composition lyophilized powder for injection and preparation method | |
| CN105213301B (en) | Netilmicin sulfate injection and its quality control method | |
| CN105147599B (en) | Netilmicin sulfate injection and preparation method | |
| CN103343157A (en) | Bacterial culture solution for detecting pathogenic bacteria in blood | |
| CN108157978A (en) | A kind of peptide composition of adjusting intestinal flora containing burdock polysaccharide and application | |
| CN104983710A (en) | Preparation method for plant capsule | |
| CN115838661B (en) | A kind of Lactobacillus plantarum Bianquejun 18, Lactobacillus plantarum preparation and application thereof | |
| CN102258521A (en) | Cefodizime sodium composition and preparation method thereof | |
| CN101618025B (en) | Veterinary doxycycline hydrochloride freeze-dried preparation and preparation method thereof | |
| CN101780052A (en) | Ceftizoxime sodium liposome injection | |
| CN101693010B (en) | Cefathiamidine prosoma liposome preparation | |
| CN102908312A (en) | Liquid combination for resisting hepatitis B viruses | |
| CN114129599A (en) | Application of silkworm chrysalis in the preparation of products for directional promotion of intestinal probiotics proliferation | |
| CN114164112A (en) | Microbial protection composition and preparation method and application thereof | |
| CN106821972B (en) | Moxifloxacin hydrochloride injection pharmaceutical composition and its preparation and quality control method | |
| CN1526396A (en) | New prepn form of cefmenoxime hydrochloride for injection | |
| CN1270723C (en) | Azithromycin injection and its preparation | |
| CN102058815B (en) | Application of Chinese cardamon oil to preparing medicament for treating bacterial infectious diseases | |
| CN102697788B (en) | Compound lactic acid levofloxacin oral liquid and preparation process 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 | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100512 |