Method of producing antibacterial solution

专利摘要:
This invention relates to the chemical and pharmaceutical industry, concerns a method for preparing an antibacterial solution solution. The purpose of the invention is to increase the stability to the sedimentation of the injection or infusional solution of the antibacterial agent. To do this, demineralized water is mixed with the lactic acid salt of the compound 1-cyclopropyl-6-fluoro-1,4-DIHIDRO-4-OXO-7- (1-piperazinyl) quinolone-3 carboxylic acid (compound A), add lactic acid (20-855%) per 1 mol of lactic acid salt or its hydrate and 2 M sodium hydroxide. Get a solution with a pH of 2.5-7. The resulting preparations are stored in ampoules at 5 ° C. After 1 month, a precipitated active substance is observed in ampules in a quantity of 1.5-4 mg. i w
公开号:SU1384187A3
申请号:SU843790651
申请日:1984-09-14
公开日:1988-03-23
发明作者:Гроэ Клаус；Ламменс Роберт
申请人:Байер Аг (Фирма)；
IPC主号:

专利说明:

SLE 00 4
00

|
c / 4
The invention relates to a chemical and pharmaceutical industry and concerns a method for preparing an antibacterial agent solution.
The purpose of the invention is to increase the stability to sedimentation of an injection or infusion solution of an antibacterial agent.
Example 1. A yul of demineralized water is mixed with 195.3 g of the acid-milk salt of the compound 1-cyclo-propyl-6-fluoro-1,4-DIHYDRO-4-OXO-7- (1-piperazinyl) -quinolon-3- carboxylic acid (hereinafter referred to as compound A), after which 216.7 g (478% per 1 mol of the milk acid salt) of lactic acid and 266 g of 2 M sodium hydroxide are successively added. A solution is obtained with a pH of 3.6, to which an additional 5 liters of demineralisation of torn water is added while mixing.
Example2. 0.1 l of demineralized water is mixed with 43 g of compound A, after which 87 ml (673% per 1 mol of compound A) of lactic acid and 2 M soda is added to pH 7.0. The resulting solution is mixed with another 0.1 liters of demineralized water. Example To 100 MP of demineralized water was added 1.28 g of the milk acid salt of the compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) quinolone-3- carboxylic acid (hereinafter compound B), then with stirring successively added 1.11 g (354% based on 1 mol of lactic acid salt) lactic acid, 1.85 g (501% per 1 mol of lactic acid salt) and 10 MP 2m sodium hydroxide until pH 2.5.
The percentages given in parentheses after the absolute amount of the acid, including lactic acid, are calculated per 1 mol of the lactic acid salt of the corresponding active substance or its hydrate. If nothing is indicated, the self-adjusting pH value is not adjustable. Example 4. Monolactate of Compound A
Molotic acid (90% by weight) 2 M sodium hydroxide (to adjust pH to 3.6) Mannitol Water
1.27 g
1.45 g (480%)
1.80 g 1.37 g To 100.0 ml
0
50
0
five
five
PRI and MER 5. Compound A Lactic acid (90 wt.%) Water
PRI and MER 6. Compound B Lactic acid (90 wt.%) Glucose. Water
PR and ME 7. 9-Fluoro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-2,3-dihydro-7H-pyrido-C1,2,3-deJ- 4-benzoxazine 6-carboxylic acid (compound B)
Lactic acid (90 wt.%) Water
PRI and MER 8. Compound A monolactate dihydrate. Lactic acid (90 wt.%) Water
PRI and MER 9. Connection
Lactic acid (90 masl) Water
Example 10. Compound A Lactic acid (90 wt.%) Water
Example 11. Compound B monolactate. Lactic acid (90 wt.%) Water
10.00 g
4.85 g (61%) up to 1000.0 MP
1.00 g
0.50 g (60%)
3.85 g
Up to 100.00 ml
5.00 g
2.20 g (59%) Up to 100.00 ml
69.0 g
24.2 g (160%) Up to 1000.0 ml
300.0 g
177.3 g (96%) Up to 6000.0 ml
200.0 g
75.0 g (24%) To 2000.0 ml
128.2 g
50.0 g (160%) Up to 1000.0 ml
0
five
Example 12
Compound B 100.0 g
Lactic acid
(90 wt.%)
Water
Example 13
Monolactate Compound A
Succinic acid
Water
44.4 g, (60%) Up to 1000.0 MP
1.30 g
0.71 g (199%)
Up to 100.00 ml





3.6.
1.27 g
0.60 g (207%)
Up to 100.00 ml 0
15
3.9.
1.27 g
0.56 g (185%)
1.45 g (501%) 20 Up to 100.00 ml.
25
3.7
1.00 g
0.86 g (185%)
1.12 g (502%) 30 Up to 100.00 ml.
3.8. 1.00 g
0.87 g (178%) 0.48 g (198%)
1.00 g
0.42 g (34%)
1.50 g (499%) up to 100.00 MP
3.8.
35
40
45
50
1.00 g
0.39 g (41%) 55
0.53 g (200% up to 100.00 MP
0
five
0
five
0
five
0
45
0
five
The pH is adjusted to 2 M with sodium hydroxide. Example 20. Compound B molnactate. Lactic acid (90 wt.%) Propionic acid. Water
Example 21 Compound B Lactic Acid (90% by Weight) Succinic Acid Water
2 M sodium liquor set the pH value. EXAMPLE 22 Compound A Lactic acid (90 wt.%) 1 M hydrochloric acid Water
Example 23: Compound A Lactic acid (90 wt.%) Water 1 M hydrochloric acid establishes a pK value of 4.0. EXAMPLE 24 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-OXO-7- (4-ethyl-1-piperazinsh1) - quinolone-3-carboxylic acid (compound D) Lactic acid (saturation 20%) Water
Example 25. Connection G. Lactic acid (saponification 20%) Benzyl alcohol Water
Example 26 Compound D Lactic acid (saponification 20%) Salt acid Water
3.9.
1.25 g
0.56 g (202%)
1.03 g (502%) up to 100.00 MP
1.00 g
1.39 g (401%) 0.64 g (196%) Up to 100.00 ml
3.7. 1.00 g 0.33 g (9%)
1.20 g (40%) up to 100.00 MP
1.00 g
0.41 g (36%) up to 100.00 MP
1.00 g
1.50 g Up to 100 ml
1, pO g
2.00 g 1.00 g Up to 100 ml
(59%)
1.00 g
1.50 g 0.66 g
(20%) (23%)
Up to 100 ml
Composition D Lactic acid (saponification 10%) Hydrochloric acid Water
Example 28. Connection


- -

15.00 g (20%)
1.30 g (32%) Up to 100 ml
5.00 g
10.00 g (59%) Up to 100 MP
1.00 g
1.78 g (27%) Up to 100 ml
108.3 mg
398 mg To 2
(41%)
g
Experience (proposed). The preparations of examples 1-31 are stored in ampoules at a temperature of 5 ° C for 6 months. No sediment of the active substance is observed.
ABOUT 2 (known). The preparations of examples 1-31, which, however, do not contain the corresponding acid, are stored in ampoules at a temperature. After 4 weeks already, a precipitate of the active substance in the amount of 1.5-4 mg is observed in all ampoules.
5 ° C.
0
five
0
Comparing the results of experiments 1 and 2 indicates the achievement of the objectives of the proposed method.
About Ps t 3 (comparative). Preparations consisting of 1 g of lactic acid salt of compounds A – D 18% based on 1 mol of lactic acid salt, lactic acid and water up to 100 MP are stored at a temperature of 5 ° C. In this case, after 4 weeks, the formation of a precipitate of compounds A – G is observed in an amount of 0.1-0.25 mg.
Thus, the goal of the proposed method is not achieved when using an acid in an amount of less than 20% based on the lactic acid salt.

权利要求:
Claims (1)
[1]
Invention Formula
The method of obtaining an antibacterial solution by mixing piperazine containing quinolone derivative of the general formula
25
soon
R,
soon
35
where X-N, C-H or C-F; Z is O or CHj;
Ri is RI hydrogen, methyl, ethyl;
cyclopropyl or ethyl; R is hydrogen, methyl or ethyl, in the form of a lactic acid salt with water at a pH of 2.5-7, characterized in that, in order to stabilize the solution by sedimentation, an acid is added to the lactic acid salt or its hydrate. selected from the group including lactic, succinic, methanesulfonic acid, hydrochloric or propionic, and the acid is used in an amount of 20-855% per 1 mol of the lactic acid salt or its hydrate.

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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DE19833333719|DE3333719A1|1983-09-17|1983-09-17|SOLUTIONS MILK ACID SALTS OF PIPERAZINYL CHINOLONIC AND PIPERAZINYL AZACHINOLONE CARBONIC ACIDS|

---