CN1569010A - Etimicin sulfate preparation and its preparing method - Google Patents
Etimicin sulfate preparation and its preparing method Download PDFInfo
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- CN1569010A CN1569010A CN 200410018196 CN200410018196A CN1569010A CN 1569010 A CN1569010 A CN 1569010A CN 200410018196 CN200410018196 CN 200410018196 CN 200410018196 A CN200410018196 A CN 200410018196A CN 1569010 A CN1569010 A CN 1569010A
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- acid
- etimicin sulfate
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- etimicin
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- 229950009953 etimicin Drugs 0.000 title claims abstract description 54
- OEBISAUVQBGQKC-ZIZSAZPJSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4-amino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]oxy-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](NC)[C@@](C)(O)CO1)O)NCC)[C@H]1O[C@H](CN)CC[C@H]1N OEBISAUVQBGQKC-ZIZSAZPJSA-N 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title abstract description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 41
- 239000002253 acid Substances 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 230000001954 sterilising effect Effects 0.000 claims abstract description 4
- 150000007513 acids Chemical class 0.000 claims abstract description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 33
- 239000000243 solution Substances 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000002347 injection Methods 0.000 claims description 21
- 239000007924 injection Substances 0.000 claims description 21
- 239000011780 sodium chloride Substances 0.000 claims description 16
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 14
- 239000000600 sorbitol Substances 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 238000005516 engineering process Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 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 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 230000003204 osmotic effect Effects 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 229920002799 BoPET Polymers 0.000 claims description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- 239000005041 Mylar™ Substances 0.000 claims description 3
- 238000003556 assay Methods 0.000 claims description 3
- 239000003610 charcoal Substances 0.000 claims description 3
- 230000008030 elimination Effects 0.000 claims description 3
- 238000003379 elimination reaction Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 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 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 239000001117 sulphuric acid Substances 0.000 claims description 2
- 235000011149 sulphuric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 230000003750 conditioning effect Effects 0.000 abstract 1
- VEGXETMJINRLTH-ALRICIOSSA-N etimicin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@H](O)[C@H]1O[C@@H]1[C@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N VEGXETMJINRLTH-ALRICIOSSA-N 0.000 abstract 1
- 238000004659 sterilization and disinfection Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 239000002932 luster Substances 0.000 description 6
- 239000008215 water for injection Substances 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
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- 239000007787 solid Substances 0.000 description 3
- 239000012085 test solution Substances 0.000 description 3
- 241000192125 Firmicutes Species 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 241000589291 Acinetobacter Species 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010063057 Cystitis noninfective Diseases 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000588770 Proteus mirabilis Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037597 Pyelonephritis acute Diseases 0.000 description 1
- 206010037601 Pyelonephritis chronic Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 201000001555 acute pyelonephritis Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
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- 238000013461 design Methods 0.000 description 1
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- 238000001647 drug administration Methods 0.000 description 1
- NZGMVSJQULXLHF-RAKCNUBFSA-N etimicin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](NC)[C@@](C)(O)CO1)O)NCC)[C@H]1O[C@H](CN)CC[C@H]1N NZGMVSJQULXLHF-RAKCNUBFSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000005308 flint glass Substances 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
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- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
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- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses etimicin sulfate preparation and its preparing method which comprises, charging acids or alkali as pH conditioning agent so as to increase the dissolving degree of the etimicin, charging right amount of isoosmotic adjustment agent, thus resulting the action of quick sterilization.
Description
Technical field
The invention belongs to pharmaceutical engineering, the medicine that relates to antibacterial is formed and preparation technology, relates in particular to Etimicin sulfate. medicine composition, preparation and preparation technology thereof.This drug mechanism is to suppress the normal protein synthesis of sensitive organism, and most of gram positive bacteria and gram negative bacteria are had good antibacterial action
Background technology
Etimicin sulfate. is a kind new medicine of China's development, has another name called antibiotic 89-07, likes big mycin, is semi-synthetic aminoglycoside antibiotics, has antibiotic spectrum width, low toxin.Be applicable to the various infection that its responsive escherichia coli, Cray Bai Shi pneumobacillus, Serratia genus, proteus mirabilis, Enterobacter, acinetobacter, Proteus, bloodthirsty hemophilus influenza, bacillus pyocyaneus and staphylococcus etc. are caused.Its mechanism of action is to suppress the normal protein synthesis of sensitive organism, and most of gram positive bacteria and gram negative bacteria are had good antibacterial action.Prove that through II, III clinical trial phase result its clinical effective rate is 87.2%～91.8%, bacteria clearance is 89.4%～91.7%, and it is less to ototoxicity.The pharmacokinetic result: healthy people is intravenous drip Etimicin sulfate. 100,150 and 200mg in 1 hour, and the average highest serum drug level when finishing of instiling is respectively 11.30,14.60 and 19.79mg/L; Eliminating the half-life is 1.5～1.9 hours.The output of original shape medicine, account for 80% of dosage in urinating in 24 hours.The protein binding rate of blood Chinese medicine is about 25%.Healthy people continuous 7 days, does not have tangible drug accumulation phenomenon with 12 hours interval administration every day 2 times.
Clinically be mainly used in respiratory tract infection: as acute bronchitis, acute episode of chronic bronchitis, community's pulmonary infection etc.; Urogenital infections: as acute pyelonephritis, cystitis, chronic pyelonephritis and chronic cystitis acute attack; And skin soft-tissue infection and other infection: as the infection in acute and chronic honeycomb group inflammation, wound, wound and operation puerperal etc.It is the active drug for the treatment of various infectious disease clinically.
The chemical structural formula of Etimicin sulfate. is as follows:
Molecular formula: C
21H
43N
5O
75/2H
2SO
4
Molecular weight: 722
Obtaining National Drug Administration's approval in 1997 produces.Domestic main production unit has Wuxi Shanhe Medicine Industry Co., Ltd, Changzhou FangYuan Pharmaceutical Co., Ltd and Hangzhou Aida Pharmaceutical Co., Ltd at present.Its preparation has Etimicin sulfate. injection and injection Etimicin sulfate., does not still have the transfusion specification at present.The Etimicin sulfate. injection of clinical use has two kinds of specifications of 1mL:5 ten thousand units and 2mL:10 ten thousand units, adopts intravenous drip.Inject again owing to need be dissolved in normal saline or the glucose solution during each the use, easily pollute., pollute for this reason, also be convenient clinical use on comprehensive document and market survey basis, the injection small-volume injection to be changed into two kinds of transfusions of 50mL:5 ten thousand units and 100mL:10 ten thousand units for reducing.
Summary of the invention
An object of the present invention is to provide a kind of pharmaceutical preparation isoosmotic with blood, that also keep the stable Etimicin sulfate. injection that can be used for intravenously administrable of medicine before the deadline.
Another object of the present invention provides the production technology of preparation Etimicin sulfate. injection, and this technology comprises:
(1) get the Etimicin sulfate. of recipe quantity, place solvent, dissolving adds active carbon and boiled 10 minutes, takes off charcoal with the buchner funnel sucking filtration, and (A) is standby for filtrate,
(2) get the isoosmotic adjusting agent of recipe quantity, place solvent, add the active carbon post-heating that stirs and boil, the elimination active carbon, (B) is standby for filtrate,
(3) two liquid mix homogeneously with pH regulator agent regulator solution pH, add solvent to full dose, and pH value, related substance and after the assay was approved are used the microporous filter membrane fine straining after measured, and fill adds mylar, jumps a queue, and rolls lid, and 115 ℃ of pressure sterilizings 30 minutes promptly.
The preparation technology of Etimicin sulfate. injection provided by the invention considers the tolerability of Human Physiology condition, and the pH value scope that is applied to intravenous injection or intravenous drip administration transfusion is between 3.5～9.0.Therefore, increase the dissolubility of Etimicin sulfate. by pH regulator agent such as acid or alkali, the pH of its final solution also should be controlled in this scope, the pH regulator agent comprises all kinds of acid or alkali, and wherein used acid comprises mineral acid (as: sulphuric acid, hydrochloric acid, phosphoric acid and according to Professional knowledge other mineral acids as can be known) and organic acid (as: acetic acid, lactic acid, methanesulfonic acid, citric acid, tartaric acid, maleic acid and according to Professional knowledge other organic acid as can be known).
These acid (comprising solid acid such as citric acid etc.) of variable concentrations are adopted in pH regulator agent of the present invention, can increase the stability of Etimicin sulfate. solution to some extent, the pH scope can be controlled between 1～5, and wherein preferred range is between 3.0～5.0, and most preferred scope is between 4.0～5.0.
Alkaline pH regulator of the present invention comprises all kinds of inorganic bases (as: sodium hydroxide, potassium hydroxide and according to Professional knowledge other inorganic bases as can be known) and organic base (as: triethanolamine and according to Professional knowledge other organic bases as can be known).
These alkali (comprising solid base such as sodium hydroxide etc.) of variable concentrations are adopted in pH regulator agent of the present invention, can increase the stability of Etimicin sulfate. solution to some extent, the pH scope can be controlled between 5～11, wherein preferred range is between 5.0～8.0, and most preferred scope is between 5.0～6.5.
The isoosmotic adjusting agent that the present invention selects for use comprises sodium chloride, glucose and sorbitol etc.
Another purpose of the present invention provides the medicine of Etimicin sulfate. injection to be formed, and this consists of:
Prescription 1:
Etimicin sulfate. (C
21H
43N
5O
7Meter) 100,000 units/100ml
Isoosmotic adjusting agent 1 5.48g/100ml
Or isoosmotic adjusting agent 2 0.9g/100ml
Solvent adds to 100ml
Prescription 2:
Etimicin sulfate. (C
21H
43N
5O
7Meter) 50,000 units/50ml
Isoosmotic adjusting agent 1 2.74g/50ml
Or isoosmotic adjusting agent 2 0.45g/50ml
Solvent adds to 50ml
Etimicin sulfate. injection provided by the invention, its Etimicin sulfate. dissolubility＞100,000 units/100ml in water; The osmotic pressure of solution equates with colloidal osmotic pressure.
The present invention has the following advantages: the Etimicin sulfate. injection that (1) provides can reach effective drug level (＞10 ten thousand units/100ml), play rapid bactericidal action; (2) medicinal liquid is stable in suitable pH scope; (3) add suitable isoosmotic adjusting agent after, still can reach enough drug solubilities, and medicine is stable before the deadline, to satisfy the needs of clinical application; (4) increase Etimicin sulfate. pharmaceutical preparation new varieties, enlarged clinical application range; (5) the production technology design is easy, reasonable, and production cost is low, and improves the quality of products.
The specific embodiment
The present invention is described further in conjunction with specific embodiments.
Example 1.
Get Etimicin sulfate. 100,000 units to the water for injection of about 80ml, dissolving, the acetic acid regulator solution pH of adding 5N, in the process that acetic acid adds, pH descends along with the amount that adds, and reduces to 1.0 the process from 5.02 at pH, medicinal liquid keeps achromatism and clarity, and no medicine is separated out.From above example as can be seen, regulate the pH value of medicinal liquid,, Etimicin sulfate. dissolubility in aqueous solution is not had influence, can satisfy target greater than 100,000 units/100ml when the pH of medicinal liquid control within the specific limits when (pH1.0～5.02) by acetic acid.
Example 2.
Select for use 10% lactic acid as the pH regulator agent, adopt and example 1 identical operations step, do not occur medicine equally and separate out phenomenon.
Example 3.
The hydrochloric acid of selecting 1N for use is as the pH regulator agent, and the operating procedure of identical and example 1 in pH1.0～5.02 scopes, does not have influence to the dissolubility of Etimicin sulfate. in water, can satisfy the target greater than 100,000 units/100ml.
Example 4.
Get Etimicin sulfate. 100,000 units and be dissolved in the water for injection of about 80ml, add sodium hydroxide test solution regulator solution pH, when the pH value of medicinal liquid is 11.03, have small amount of solid to separate out, continue to add sodium hydroxide test solution, the amount of solid of separating out does not have obvious increase.
Example 5.
Get and above-mentionedly use the dissolved Etimicin sulfate. solution of pH regulator agent such as acetic acid, lactic acid, hydrochloric acid and sodium hydroxide respectively (drug level is 100,000 units/100ml, pH value is respectively 4.06,5.25,6.52,8.01) and each two parts, every part is 100ml, add the sodium chloride of 0.9g and the sorbitol of 5.48g respectively and make isoosmotic adjusting agent, stirring at room makes dissolving, and puts in 0-5 ℃ the refrigerator, placing took a sample after 5,10 days checks, the results are shown in Table 1.
The adding of the different isoosmotic adjusting agent of table 1 is to the influence of various medicinal liquid solubility properties
The pH regulator agent adds behind the isoosmotic adjusting agent 0-5 ℃ of cold preservation 10 days
(dissolved substance is used) liquor strength medicinal liquid pH value sodium chloride sorbitol sodium chloride sorbitol
5N acetic acid 100,000 units/100ml 4.06++++
10% lactic acid, 100,000 units/100ml 5.25++++
1N hydrochloric acid 100,000 units/100ml 6.52++++
Sodium hydroxide test solution 100,000 units/100ml 8.01++++
Annotate: "+" expression is solvable, and "-" expression is not dissolved each other
By above-mentioned experimental result as can be known, can select for use acetic acid, lactic acid and hydrochloric acid etc. to do the pH regulator agent, select for use sorbitol and sodium chloride to make isoosmotic adjusting agent, make it to be suitable for intravenous injection or intravenous drip administration.This product belongs to aminoglycoside antibiotics, and unavailable glucose is as isoosmotic adjusting agent.
Example 6.
Prescription is formed
The supplementary material specification
50,000 units/bottle 100,000 unit/bottles
The Etimicin sulfate. 5,000,000 (C of unit
21H
43N
5O
7Meter) the 1000 ten thousand (C of unit
21H
43N
5O
7Meter)
Sorbitol 274g 548g
(or sodium chloride) 45g 90g
Water for injection adds to 5000ml 10000ml
Make 100 bottles 100 bottles altogether
Example 7. preparation technologies
Get the Etimicin sulfate. of recipe quantity, be scattered in an amount of hot fresh water for injection, make dissolving, add 0.03% active carbon and boiled 10 minutes, take off charcoal with the buchner funnel sucking filtration, filtrate for later use.
Sorbitol and the sodium chloride of getting recipe quantity drop in the hot water for injection, make into the concentrated solution of 40-50%, add the 0.1% needle-use activated carbon post-heating that stirs and boil about 15 minutes, with buchner funnel elimination active carbon, filtrate for later use.
Two liquid mix homogeneously add to the full amount of water for injection, and pH value, related substance and after the assay was approved after measured are with 0.22 μ m microporous filter membrane fine straining.Fill 100ml or 50ml infusion bottle add mylar, jump a queue, and roll lid, and 115 ℃ of pressure sterilizings 30 minutes promptly.
Influence factor's test of example 8. preparations
(1) exposure experiments to light
With placing under the medicine exposure experiments to light instrument, intensity of illumination 4500LX ± 500LX places and takes a sample to check after 5,10 days with embedding this product (lot number 1: isoosmotic adjusting agent is a sorbitol, lot number 2: isoosmotic adjusting agent is a sodium chloride) in the flint glass infusion bottle.The results are shown in Table 3,4.
Table 3. the exposure experiments to light ((lot number 1 of 4500LX ± 500LX); Specification: 100,000 units/100ml)
Time clarity pH value color and luster related substance Etimicin sulfate. sorbitol
(my god) (%) content (%) content (%)
0 qualified 4.82 colourless transparent solutions 6.37 104.1 99.5
5 qualified 4.87 colourless transparent solutions 6.24 104.3 99.4
10 qualified 4.81 colourless transparent solutions 6.29 103.4 99.4
Table 4. the exposure experiments to light ((lot number 2 of 4500LX ± 500LX); Specification: 100,000 units/100ml)
Time clarity pH value color and luster related substance Etimicin sulfate. sodium chloride
(my god) (%) content (%) content (%)
0 qualified 4.75 colourless transparent solutions 6.15 103.9 100.6
5 qualified 4.75 colourless transparent solutions 6.22 104.2 100.2
10 qualified 4.68 colourless transparent solutions 6.22 105.2 100.5
Result of the test shows that this product is stable to light.
(2) hot test
Embedding this product (lot number 1: isoosmotic adjusting agent is a sorbitol, lot number 2: isoosmotic adjusting agent is a sodium chloride) in colourless infusion bottle is placed 60 ℃ calorstat, and placing took a sample after 5,10 days checks.The results are shown in Table 5,6.
Table 5. hot test (60 ℃ of constant temperature) (lot number 1; Specification: 100,000 units/100ml)
Time clarity pH value color and luster related substance Etimicin sulfate. sorbitol
(my god) (%) content (%) content (%)
0 qualified 4.82 colourless transparent solutions 6.37 104.1 99.5
5 qualified 4.81 colourless transparent solutions 6.14 105.8 99.5
10 qualified 4.84 colourless transparent solutions 6.26 104.2 99.4
Table 6. hot test (60 ℃ of constant temperature) (lot number 2; Specification: 100,000 units/100ml)
Time clarity pH value color and luster related substance Etimicin sulfate. sodium chloride
(my god) (%) content (%) content (%)
0 qualified 4.75 colourless transparent solutions 6.15 103.9 100.6
5 qualified 4.72 colourless transparent solutions 6.11 107.3 100.4
10 qualified 4.74 colourless transparent solutions 6.15 106.7 100.5
Result of the test shows that related substance did not have significant change when this product was placed at high temperature, and other pH value, Etimicin sulfate., sodium chloride content do not have significant change, so this product is stable.
(3) cold preservation test
Embedding this product (lot number 1: isoosmotic adjusting agent is a sorbitol, lot number 2: isoosmotic adjusting agent is a sodium chloride) in colourless infusion bottle is placed 0-5 ℃ refrigerator, and placing took a sample after 5,10 days checks.The results are shown in Table 7,8.
Table 7. cold preservation test (0-5 ℃) (lot number 1; Specification: 100,000 units/100ml)
Time clarity pH value color and luster related substance Etimicin sulfate. sorbitol
(my god) (%) content (%) content (%)
0 qualified 4.82 colourless transparent solutions 6.37 104.1 99.5
5 qualified 4.86 colourless transparent solutions 6.28 104.9 99.8
10 qualified 4.79 colourless transparent solutions 6.13 102.2 99.5
Table 8. cold preservation test (0-5 ℃) (lot number 2; Specification: 100,000 units/100ml)
Time clarity pH value color and luster related substance Etimicin sulfate. sodium chloride
(my god) (%) content (%) content (%)
0 qualified 4.75 colourless transparent solutions 6.15 103.9 100.6
5 qualified 4.76 colourless transparent solutions 6.18 100.2 100.6
10 qualified 4.74 colourless transparent solutions 6.18 103.2 100.6
Result of the test shows, this product does not have medicine and separates out when low temperature is placed, and pH value, related substance and Etimicin sulfate., sodium chloride content do not have significant change, so this product is stable
The partial reference document that the present invention relates to:
1. national Bureau of Drugs Supervision standard [standard No.: WS-(X-030)-2002]
2. national Bureau of Drugs Supervision standard [standard No.: WS-(X-031)-2002]
3. " 2000 editions two ones of Chinese pharmacopoeia, 906～907 pages
4. " 2000 editions two ones of Chinese pharmacopoeia, 38 pages
Claims (10)
1. Etimicin sulfate. preparation, it is characterized in that: the dosage form of said preparation is an injection, and its medicine consists of
Prescription 1:
Etimicin sulfate. (C
21H
43N
5O
7Meter) 100,000 units/100ml
Isoosmotic adjusting agent 1 5.48g/100ml
Or isoosmotic adjusting agent 2 0.9g/100ml
Solvent adds to 100ml
Prescription 2:
Etimicin sulfate. (C
21H
43N
5O
7Meter) 50,000 units/50ml
Isoosmotic adjusting agent 1 2.74g/50ml
Or isoosmotic adjusting agent 2 0.45g/50ml
Solvent adds to 50ml
2. Etimicin sulfate. injection according to claim 1, the Etimicin sulfate. that the provides dissolubility＞100,000 units/100ml in water, the osmotic pressure of solution equates with colloidal osmotic pressure.
3. the preparation method of Etimicin sulfate. injection according to claim 1, technology comprises:
(1) get the Etimicin sulfate. of recipe quantity, place solvent, dissolving adds active carbon and boiled 10 minutes, takes off charcoal with the buchner funnel sucking filtration, and (A) is standby for filtrate,
(2) get the isoosmotic adjusting agent of recipe quantity, place solvent, add the active carbon post-heating that stirs and boil, the elimination active carbon, (B) is standby for filtrate,
(3) two liquid mix homogeneously with pH regulator agent regulator solution pH, add solvent to full dose, and pH value, related substance and after the assay was approved are used the microporous filter membrane fine straining after measured, and fill adds mylar, jumps a queue, and rolls lid, and 115 ℃ of pressure sterilizings 30 minutes promptly.
4. the preparation method of Etimicin sulfate. injection according to claim 3, the pH regulator agent comprises all kinds of acid or alkali.
5. according to the preparation method of claim 3 and 4 described Etimicin sulfate. injection, the pH regulator agent is regulated the pH value scope between 4.0～6.5.
6. according to the preparation method of claim 3 and 4 described Etimicin sulfate. injection, the used acid of pH regulator agent comprises mineral acid (as: sulphuric acid, hydrochloric acid, phosphoric acid and according to Professional knowledge other mineral acids as can be known) and organic acid (as: acetic acid, lactic acid, methanesulfonic acid, the acid of structure rafter, tartaric acid, maleic acid and according to Professional knowledge other organic acid as can be known).
7. according to the preparation method of claim 3 and 4 described Etimicin sulfate. injection, the used alkali of pH regulator agent comprises all kinds of inorganic bases (as: sodium hydroxide, potassium hydroxide and according to Professional knowledge other inorganic bases as can be known) and organic base (as: triethanolamine and according to Professional knowledge other organic bases as can be known).
8. according to the preparation method of claim 3 and 4 described Etimicin sulfate. injection, when adopting acid for adjusting pH, the pH scope can be controlled between 1～5, and wherein preferred range is between 3.0～5.0, and most preferred scope is between 4.0～5.0.
9. according to the preparation method of claim 3 and 4 described Etimicin sulfate. injection, when adopting alkali to regulate pH, the pH scope can be controlled between 5～11, and wherein preferred range is between 5.0～8.0, and most preferred scope is between 5.0～6.5.
10. according to the preparation method of claim 3 and 4 described Etimicin sulfate. injection, the isoosmotic adjusting agent of selecting for use comprises sodium chloride, glucose and sorbitol etc.
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|---|---|---|---|
| CN 200410018196 CN1569010A (en) | 2004-04-29 | 2004-04-29 | Etimicin sulfate preparation and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410018196 CN1569010A (en) | 2004-04-29 | 2004-04-29 | Etimicin sulfate preparation and its preparing method |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008025227A1 (en) * | 2006-08-25 | 2008-03-06 | Tianjin Hemay Bio-Tech Co. Ltd | The antibiotics composition comprising aminoglycoside antibiotics |
| CN102443026A (en) * | 2011-10-26 | 2012-05-09 | 无锡济民可信山禾药业股份有限公司 | Aminoglycoside compounds and extraction and separation method therefor |
| CN102512365A (en) * | 2011-12-21 | 2012-06-27 | 无锡济民可信山禾药业股份有限公司 | Etimicin sulfate micelle freeze-dried powder injection and its preparation method |
| CN102565208A (en) * | 2010-12-29 | 2012-07-11 | 江西济民可信集团有限公司 | Novel method for detecting etimicin sulfate |
| CN106727294A (en) * | 2016-12-23 | 2017-05-31 | 常州润诺生物科技有限公司 | A kind of oral formulations of Etimicin Sulfate and preparation method and application |
| CN111789827A (en) * | 2019-04-01 | 2020-10-20 | 北京盈科瑞创新药物研究有限公司 | Etomicin sulfate aerosol inhalation preparation and preparation method thereof |
| CN114146058A (en) * | 2020-09-07 | 2022-03-08 | 常州方圆制药有限公司 | Etimicin sulfate freeze-dried powder injection and preparation method thereof |
-
2004
- 2004-04-29 CN CN 200410018196 patent/CN1569010A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008025227A1 (en) * | 2006-08-25 | 2008-03-06 | Tianjin Hemay Bio-Tech Co. Ltd | The antibiotics composition comprising aminoglycoside antibiotics |
| JP2010501493A (en) * | 2006-08-25 | 2010-01-21 | 天津和美生物技▲術▼有限公司 | Antibiotic compound containing aminoglycoside antibiotics |
| CN102565208A (en) * | 2010-12-29 | 2012-07-11 | 江西济民可信集团有限公司 | Novel method for detecting etimicin sulfate |
| CN102565208B (en) * | 2010-12-29 | 2015-07-22 | 江西济民可信集团有限公司 | Novel method for detecting etimicin sulfate |
| CN102443026A (en) * | 2011-10-26 | 2012-05-09 | 无锡济民可信山禾药业股份有限公司 | Aminoglycoside compounds and extraction and separation method therefor |
| CN102443026B (en) * | 2011-10-26 | 2016-12-21 | 江西省药明扬海医药科技有限公司 | A kind of glucoside-containing component and extraction separation method thereof |
| CN102512365A (en) * | 2011-12-21 | 2012-06-27 | 无锡济民可信山禾药业股份有限公司 | Etimicin sulfate micelle freeze-dried powder injection and its preparation method |
| CN106727294A (en) * | 2016-12-23 | 2017-05-31 | 常州润诺生物科技有限公司 | A kind of oral formulations of Etimicin Sulfate and preparation method and application |
| CN111789827A (en) * | 2019-04-01 | 2020-10-20 | 北京盈科瑞创新药物研究有限公司 | Etomicin sulfate aerosol inhalation preparation and preparation method thereof |
| CN114146058A (en) * | 2020-09-07 | 2022-03-08 | 常州方圆制药有限公司 | Etimicin sulfate freeze-dried powder injection and preparation method thereof |
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