CN1049337C - Concentrated aqueous solution of rotatory enzyme inhibitor - Google Patents
Concentrated aqueous solution of rotatory enzyme inhibitor Download PDFInfo
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- CN1049337C CN1049337C CN96116516A CN96116516A CN1049337C CN 1049337 C CN1049337 C CN 1049337C CN 96116516 A CN96116516 A CN 96116516A CN 96116516 A CN96116516 A CN 96116516A CN 1049337 C CN1049337 C CN 1049337C
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- acid
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- aqueous solution
- concentrated aqueous
- enzyme inhibitor
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Abstract
The present invention relates to a concentrated water solution of a gyrase inhibitor, which is mainly composed of an active compound gyrase inhibitor, water, acid which is allowed by physiology, and proper auxiliary materials of a medicinal formula. The present invention is characterized in that the active compound gyrase inhibitor is 6, 8-difluoride-1-(2-fluorine ethyl)-1, 4-dihydrogen-7-(4-methyl-1-piperazine)-4-oxygen-3-quinolinecarboxylic acid, and each milliliter of the concentrated water solution contains 0.02 to 0.2 gram of the active compounds. The acid is lactic acid or acetic acid, and the acid can enough dissolve the active compounds, and keeps the stability of the solution. The concentrated solution can be used for treating diseases of human bodies or animals after dilution.
Description
The present invention relates to a kind of concentrated aqueous solution, the reactive compound that wherein contains is a rotatory enzyme inhibitor.
Up to now, the preparation of quinolones rotatory enzyme inhibitor has DE3333719, DE3537761 patent, but 6,8-two fluoro-1-(2-fluoro ethyl)-1,4-dihydro-7-(4-methyl isophthalic acid-piperazine)-4-oxygen-3-quinoline carboxylic acid's preparation have only the bigger infusion solution of volume [concentration is the transfusion of the 50ml or the 100ml of 0.1%～0.4% (W/V)].Because volume is bigger, correspondingly increased the consumption of all kinds of solvents, adjuvant and packaging material, improved cost, and produce, transportation, storage have inconvenience more.Still do not have a kind of 2% concentration that surpasses at present, dosage form is 1～10ml ampoule or bottle, holds seance dosage (the spissated aqueous solution of injection for intravenous after 0.2～0.4g) the dilution.This is because this compound water soluble is lower, is difficult to make the gratifying concentrated aqueous solution that dilutes the high concentration of back injection for intravenous.
The object of the present invention is to provide a kind of concentrated aqueous solution of rotatory enzyme inhibitor of injection for intravenous of high concentration.
Technical scheme of the present invention is:
The present invention mainly is made up of acid and an amount of medicinal formula adjuvant that reactive compound rotatory enzyme inhibitor, water, physiology allow; Described reactive compound rotatory enzyme inhibitor is 6,8-two fluoro-1-(2-fluoro ethyl)-1,4-dihydro-7-(4-methyl isophthalic acid-piperazine)-4-oxygen-3-quinoline carboxylic acid, every milliliter of concentrated aqueous solution contains the described reactive compound of 0.02～0.2 gram, described acid is lactic acid or acetic acid, also can select from the mixed liquor of following acid or acid: hydrochloric acid, methanesulfonic acid, citric acid, propanoic acid, succinic acid, 1,3-propanedicarboxylic acid, fumaric acid, maleic acid, tartaric acid, glutamic acid, gluconic acid, glucuronic acid, galacturonic acid, ascorbic acid, phosphoric acid, nitric acid, malic acid, the L-aspartic acid.Described acid should be enough to make the reactive compound dissolving and make solution keep stable.
The present invention compared with prior art, patent DE3333719 has related to and the present invention's reactive compound ciprofloxacin inequality and the preparation of the Lactated intravenous fluid of ofloxacin, the pH value of the rota-enzyme restrainer of the reactive compound that the present invention relates to remains between 3.5～5.5, near the normal physiological PH value scope of human body (about pH value 7.4), acid-base balance influence to human body is little, and is also little to the zest of human body.The active substance that the present invention relates to has long biological half-life (8～12 hours), and only need be administered once every day, has and the same curative effect of medicine such as ofloxacin, has both reduced patient's amount of drug, has also alleviated the misery that patient causes because of injection.
Below by embodiment technical scheme of the present invention is further described:
Medicinal formula adjuvant described in the technical scheme mainly comprises: antioxidant, anti-photodissociation agent, chelating agent, PH regulator.Described antioxidant can be selected for use from sodium pyrosulfite, sodium sulfite, anhydrous sodium sulfite, anti-photodissociation agent can be selected for use from guanosine, inosine, L-cysteine, and chelating agent can be selected for use from disodiumedetate, calcio-disodium edetate.The PH regulator can be selected for use from sodium hydroxide solution, sodium carbonate liquor.Described medicinal formula adjuvant can also comprise cosolvent, and described cosolvent can be selected for use from following material: ethanol, propylene glycol, Polyethylene Glycol, glycerol, mannitol, fatty acid esters of sorbitan class (spans), polyethylene fatty acid esters of sorbitan class (Tweens), polyoxyethylene fatty acid ester class (wheat pool class), oxygen ethylene oxy acrylic polymers class (pluronic).Every milliliter of concentrated aqueous solution contains 0.02～0.2 gram reactive compound and described acetic acid or lactic acid, the consumption of acid is relevant with the reactive compound molar concentration, with respect to 1 mole of reactive compound, add 0.8～2.0 mole of acid, 1.0～1.6 moles better, need to prove that Suan amount has comprised dissociated and last dissociated acid here, with the pH value of above-mentioned PH regulator regulator solution.The pH value of concentrated solution is 3.5～4.5.The dosage form of described solution can prepare and is divided in ampoule bottle or the low capacity vial, and its bodge can be 1～10 milliliter, preferably 2～5 milliliters.Enumerate the prescription example of the concentrated aqueous solution of some reactive compounds that the present invention relates to below:
(1). fleroxacin 20.0g
Glacial acetic acid 16.7g
Disodiumedetate 0.2g
L-cysteine hydrochloride 0.5g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (2). fleroxacin 40.0g
Concentrated hydrochloric acid 19.2g
Tween 80 2.0g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (3). fleroxacin 60.0g
Lactic acid 18.3g
Concentrated hydrochloric acid is an amount of
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (4). fleroxacin 80.0g
Glacial acetic acid 12.0g
Succinic acid 1.2g
Anhydrous sodium sulfite 0.5g
Propylene glycol 100.0g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (5). fleroxacin 100.0g
Lactic acid 28.1g
L-cysteine hydrochloride 0.5g
Pluronic is an amount of
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (6). fleroxacin 100.0g
Concentrated hydrochloric acid 53.4g
Tween 80 2.0g
Sodium pyrosulfite 1.0g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (7). fleroxacin 100.0g
Glacial acetic acid 20.1g
Sodium pyrosulfite 2.0g
Mannitol 50.0g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (8). fleroxacin 200.0g
Glacial acetic acid 40.2g
Sodium pyrosulfite 4.0g
Mannitol 50.0g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (9). fleroxacin 200.0g
Concentrated hydrochloric acid 100.0g
Malonic acid 13.2g
L-cysteine hydrochloride 0.5g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml (10). fleroxacin 200.0g
Lactic acid 57.2g
Sodium chloride 0.5g
L-cysteine hydrochloride 0.5g
Pluronic 2.0g
10% sodium hydroxide solution is an amount of
Water for injection is an amount of
Total amount 1000.0ml
The preparation of aqueous solution of the present invention can be adopted the cold filter method of thermosol: reactive compound, acid, water for injection (or organic solvent) and suitable pharmaceutic adjuvant are heated to 40～60 ℃, be stirred to dissolving fully, add proper amount of active carbon, be incubated 1～4 hour, filter, filtrate is cooled to 5～10 ℃ with ice bath, leaves standstill 10～48 hours, is filtered to clear and bright once more.This technology can guarantee preparation storage-stable under 5 ℃～40 ℃ condition, is particularly conducive to and prevents sedimentary generation.
The concentrated aqueous solution of the reactive compound that the present invention relates to can be diluted in multiple venous transfusions such as sodium chloride injection, ringer's solution, glucose injection, Dextrose and Sodium Chloride Inj., metronidazole injection, formula mannitol injection liquid, adopt the method that instils or inject, also directly intramuscular injection is applied to the prevention and the treatment of human body or the multiple infection of animal body.
The concentrated aqueous solution of the reactive compound that the present invention relates to has has a broad antifungal spectrum, antibacterial activity is strong and toxicity is little characteristics.For Gram-positive and gram negative bacteria, especially enterobacteria belongs to all inhibitory action, more outstanding is to be responsive for drug-fast those antibacterials of multiple antimicrobial drug (as penicillin, cephamycin class, aminoglycosides, sulfonamides) to the concentrated aqueous solution of reactive compound of the present invention.Or various diseases that mixed infection cause simple by above-mentioned various pathogenic bacterium can reach prevention by the concentrated aqueous solution of reactive compound of the present invention, alleviate and the purpose of healing.
The concentrated aqueous solution of the reactive compound that the present invention relates to is effective especially for the inhibition of multiple microorganisms such as antibacterial, mycoplasma, chlamydia, antibacterial mechanisms is for suppressing the DNA gyrase in the synthetic system of DNA of bacteria, antibacterial action is an antibacterial type, thereby is specially adapted to human body or the part of animal body and the prevention and the treatment of systemic infection that these pathogenic microorganism cause.
For example: for being effective: gram-positive cocci such as staphylococcus and Streptococcus, Gram-negative coccus (gonococcus) and gram negative bacilli such as escherichia coli, pneumobacillus, hemophilus influenza, Citrobacter, Serratia, Proteus, bacillus pyocyaneus etc. by one or more parts that cause of following pathogenic bacterium or the prevention and the treatment of systemic infection.Antimicrobial spectrum also comprises anaerobe, Mycobacterium (tubercule bacillus), mycoplasma (multiple pathogenic microorganism such as mycoplasma hominis, mycoplasma pneumoniae, chlamydia.
The pathogenic bacterium of listing above just are illustrated as an example, never are to only limit to this.Provide the example of the disease of some or mixed infections simple by above-mentioned pathogenic bacterium below: the multiple of human body catches, as pneumonia, chronic bronchitis, diffuse panbronchiolitis, bronchiectasis (during infection), the superinfection of chronic respiratory, pharyngolaryngitis, tonsillitis, acute bronchitis, pyelonephritis, cystitis, prostatitis, epididymis inflammation, urethritis, folliculitis, cellulitis, lymphatic vessel (knot) inflammation, hidradenitis, the skin ulcer cellulitis, Subcutaneous tumor, acne agminata, infectious sebaceous cyst, skin ulcer, furuncle and phyma disease, suppurative cellulites around the anus, intrauterine infection, uterus appendages inflammation, bartholinitis, mastitis, typhoid fever, cholecystitis, cholangitis, otitis media, the paranasal sinus inflammation, the eyelash inflammation, hordeolum, dacryocystisis, corneal ulcer, bacillary dysentery, enteritis, periodontal tissue's inflammation, surrounding inflammation of corona, the jaw inflammation.
The same with human body, effective too to the bacterial infection of other animal, be exemplified below:
Pig: escherichia coli diarrhoea, intestinal viral disease, septicemia, dysentery, salmonellosis.
Cattle: diarrhoea, septicemia, bronchopneumonia, salmonellosis, Pasteur bar disease, mycoplasma and genital infection.
Horse: bronchopneumonia, arthrosis, puerperium and puerperal infection and salmonellosis.
Certainly, go up and just enumerated the example of some diseases, the concentrated aqueous solution of the reactive compound that the present invention relates to can prevent with (or) disease for the treatment of also never only refers to these.
Claims (4)
1. the concentrated aqueous solution of a rotatory enzyme inhibitor mainly is made up of the sour and an amount of medicinal formula adjuvant that reactive compound rotatory enzyme inhibitor, water, physiology allow; It is characterized in that: described reactive compound rotatory enzyme inhibitor is 6,8-two fluoro-1-(2-fluoro ethyl)-1,4-dihydro-7-(4-methyl isophthalic acid-piperazine)-4-oxygen-3-quinoline carboxylic acid, every milliliter of concentrated aqueous solution contains the described reactive compound of 0.02～0.2 gram, described acid is lactic acid or acetic acid, and described acid should be enough to make the reactive compound dissolving and make solution keep stable.
2. the concentrated aqueous solution of rotatory enzyme inhibitor according to claim 1, it is characterized in that: the consumption of described lactic acid or acetic acid is relevant with the reactive compound molar concentration, with respect to 1 mole of reactive compound, adds 0.8～2.0 mole of acid.
3. the concentrated aqueous solution of rotatory enzyme inhibitor according to claim 2 is characterized in that: the consumption of acid adds 1.0～1.6 moles acid with respect to 1 mole of reactive compound in the described solution.
4. the concentrated aqueous solution of rotatory enzyme inhibitor according to claim 1, it is characterized in that: the pH value of this solution is 3.5～5.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96116516A CN1049337C (en) | 1996-09-23 | 1996-09-23 | Concentrated aqueous solution of rotatory enzyme inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96116516A CN1049337C (en) | 1996-09-23 | 1996-09-23 | Concentrated aqueous solution of rotatory enzyme inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1150901A CN1150901A (en) | 1997-06-04 |
| CN1049337C true CN1049337C (en) | 2000-02-16 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96116516A Expired - Lifetime CN1049337C (en) | 1996-09-23 | 1996-09-23 | Concentrated aqueous solution of rotatory enzyme inhibitor |
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| CN (1) | CN1049337C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103479569A (en) * | 2013-01-14 | 2014-01-01 | 四川喜亚动物药业有限公司 | Ciprofloxacin injection for animals and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991009616A1 (en) * | 1989-12-22 | 1991-07-11 | Yale University | Quinolone antibiotics encapsulated in lipid vesicles |
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1996
- 1996-09-23 CN CN96116516A patent/CN1049337C/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991009616A1 (en) * | 1989-12-22 | 1991-07-11 | Yale University | Quinolone antibiotics encapsulated in lipid vesicles |
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| Publication number | Publication date |
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| CN1150901A (en) | 1997-06-04 |
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Owner name: JIANGSU WUZHONG INDUSTRY CO.,LTD. Free format text: FORMER OWNER: SUZHOU CHANGZHENG PHARMACEUTICAL FACTORY Effective date: 20021101 |
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Effective date of registration: 20021101 Address after: Wuzhong District Bridge East Road Suzhou city Jiangsu province 215128 No. 388 Patentee after: Jiangsu Wuzhong industrial Limited by Share Ltd Address before: 215007 No. 9-3, inner outer gate, South Gate, Suzhou, Jiangsu Patentee before: Chngzheng Pharmaceutic Factory, Suzhou |
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