CN101036655A - Stable cefoperazone potassium clavulanatein medicine compound preparation - Google Patents

Stable cefoperazone potassium clavulanatein medicine compound preparation Download PDF

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CN101036655A
CN101036655A CN 200610034317 CN200610034317A CN101036655A CN 101036655 A CN101036655 A CN 101036655A CN 200610034317 CN200610034317 CN 200610034317 CN 200610034317 A CN200610034317 A CN 200610034317A CN 101036655 A CN101036655 A CN 101036655A
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cefoperazone
white powder
potassium
acid
clarification
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谭胜连
傅红燕
林宝儿
陈颖
唐润珊
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GUANGZHOU BAIYUNSHAN TIANXIN PHARMACEUTICAL CO Ltd
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GUANGZHOU BAIYUNSHAN TIANXIN PHARMACEUTICAL CO Ltd
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Abstract

The invention discloses a stable compound preparation of cefoperazone-piperacillin clavulanate drug, which is comprised by cefoperazone acid, piperacillin clavulanate and latent solvent, which weight ratio is 16~1:1:8.8~0.06. The latent solvent is preferred selected from sodium carbonate and sodium bicarbonate. Related substances content of the compound preparation, labelled content of the cefoperazone acid and the piperacillin clavulanate in the invention do not change much in influencing factor test, long-term sample tests and accelerated test in 40 DEG C. which accord with the standard of pharmacopoeia with stable product quality.

Description

Stable cefoperazone potassium clavulanatein medicine compound preparation
Technical field
The present invention relates to the drug compound preparation of cefoperazone, specifically relate to the stable cefoperazone for inj compound recipe injectable powder that clinical use has synergistic function.
Technical background
Because cephalo is sent the less stable of ketone sodium,, must preserve at the cold place of drying for guaranteeing that product is qualified before the deadline.And after being combined into compound recipe with clavulanate potassium, stability does not improve.This is the weak point of all compound preparations of cefoperazone sodium.
At present, cefoperazone acid is because its water-fast characteristic, generally use clinically.But, can draw cefoperazone acid ratio cefoperazone stable sodium by on the contrast test to cephalo piperazine keto acid and cefoperazone sodium.Because playing the main component of curative effect effect clinically is cefoperazone, therefore,, makes cefoperazone acid and cosolvent after share, reach the clinical efficacy of cefoperazone sodium, and meet the safety of clinical administration requirement by the effect of cosolvent to cephalo piperazine keto acid.
In addition, cosolvent commonly used clinically mainly is: natrium carbonicum calcinatum, arginine.The sodium bicarbonate aseptic powder is carried out aseptic mixed powder as medicine as cosolvent and cephalo-type or penicillins, does not see the relevant report of clinical use.But from the experiment of the study on the stability of cephalo piperazine keto acid and cosolvent, and the technological operation of mixed powder flow path is simple and feasible draws most preferably that cosolvent is: sodium bicarbonate.
Summary of the invention
At this weak point of cefoperazone sodium poor stability, the purpose of this invention is to provide the compositions of cefoperazone acid and clavulanate potassium and cosolvent, it preserves steady quality at room temperature, and clinical use dissolving is rapidly.
Technical solution of the present invention is: cefoperazone clavulanic acid drug compound preparation, it is characterized in that mainly forming by cefoperazone acid, clavulanate potassium and cosolvent, and three's weight ratio is: 16～1: 1: 8.8～0.06.
Described cosolvent is one or several a mixture of sodium carbonate, sodium bicarbonate, arginine, sodium hydroxide, sodium phosphate, sodium hydrogen phosphate.
Described cosolvent preferentially is selected from sodium carbonate, sodium bicarbonate, especially preferentially is selected from sodium bicarbonate.
Compound preparation of the present invention also comprises pharmaceutically useful stabilizing agent, as EDTA etc.
PH value with the control product during prescription of screening compound preparation is a standard, and pH value is low excessively, and cefoperazone dissolving not exclusively; PH value is too high, and the product solution color is obviously deepened, and influences product stability, is unfavorable for clinical practice simultaneously.Therefore add the amount of cosolvents such as sodium carbonate or sodium bicarbonate, cefoperazone is dissolved rapidly, can make its solution reach stable suitable pH value again, simultaneously, also will take into account the drug safety of product.General injection pH requires between 3～10, can not peracid or cross alkali, otherwise can cause the stimulation pain or the necrosis of local organization.Require pH between 4～9 for a large amount of intravenous fluids, otherwise after a large amount of intravenous injection the acid of causing, alkalotic danger are arranged.Guaranteeing safety, effectively, under stable, the quality controllable prerequisite of product, the scope of the pH value of this product is decided to be 5.5～7.5.
Obtain technical scheme of the present invention according to above-mentioned pH value scope screening pharmaceutical formulation:
Cefoperazone clavulanic acid drug compound preparation is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium bicarbonate is: 16～1: 1: 2.15～0.13.
Cefoperazone acid in the above-mentioned prescription: clavulanate potassium: the preferred weight ratio of sodium bicarbonate is: 16～4: 1: 2.15～0.52.
Further preferred weight ratio is: 16: 1: 2.15～2.09 or 8: 1: 1.11～1.04.
Preferred weight ratio is 16: 1: 2.12 or 8: 1: 1.07.
Above-mentioned cefoperazone clavulanic acid drug compound preparation, it is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium carbonate is: 16～1: 1: 1.6～0.08; Preferable range is 16～4: 1: 1.6～0.33; Further preferable range is 16: 1: 1.6～1.28 and 8: 1: 0.7～0.66; Preferred proportioning is 16: 1: 1.44 and 8: 1: 0.68.
Cosolvent also can be selected pharmaceuticals industries such as arginine, sodium hydroxide cosolvent commonly used for use in the technical solution of the present invention, and the prescription of selected above-mentioned its compound preparation of cosolvent is: cefoperazone acid: clavulanate potassium: arginic weight ratio is: 16～1: 1: 4.5～0.27; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium hydroxide is: 16～1: 1: 1.0～0.06; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium phosphate is: 16～1: 1: 6.8～0.4; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium hydrogen phosphate is: 16～1: 1: 8.8～0.5.
Above-mentioned compound preparation component is sterile preparation.Promptly under the sterile production environmental condition,,, prepare the injectable powder of loading amounts such as 0.5g, 0.75g, 1.0g, 1.5g, 2g, 2.125g, 2.25g, 2.5g and 3g by mechanical packing with degerming, fully mixed except that the aseptic component of thermal source.During clinical use, add injection water dissolved dilution and get final product.
To mix the powder pH value be feature to control in the preparation of above-mentioned compound preparation, and mixing powder dissolving back pH value is 5.5～7.5, and preferred pH value is 6.0～7.0.
Cefoperazone clavulanic acid drug compound preparation is characterized in that the preparation for a kind of parenterai administration, is preferably a kind of injection powder injection formulation.
The present invention also comprises the application of described cefoperazone clavulanic acid drug compound preparation in the medicine of preparation bacterial infection.
Preparating mechanism of the present invention is cosolvents such as cefoperazone acid-utilising sodium bicarbonate, with water-fast cefoperazone acid, can react rapidly in water with sodium bicarbonate, generates water-soluble cefoperazone sodium.
With the sodium bicarbonate is example, the relation of the addition of the sodium bicarbonate of cefoperazone compositions of the present invention, pH value, dissolution velocity:
1) addition of pH value and sodium bicarbonate is proportionate, and the amount that sodium bicarbonate adds is many more, and pH value is high more.
2) addition of dissolution time and pH, sodium bicarbonate is negative correlation, and the amount that sodium bicarbonate adds is many more, and pH value is high more, and the dissolving required time is just short more, helps more shortening the clinical pharmacy time.
3) addition of appearance luster and pH value, sodium bicarbonate is proportionate, and the amount that adds sodium bicarbonate is many more, and pH value is high more, and solution colour is dark more, illustrates that pH value is high more, and sample is just unstable more in aqueous solution.
Cefoperazone compositions of the present invention is respectively in cephalo piperazine keto acid: clavulanate potassium: the ratio of sodium bicarbonate is to feed intake in 16: 1: 2.12 and 8: 1: 1.07 to make the preparation of 2.125g specification (cefoperazone 2.0g+ clavulanic acid 0.125g) and 1.125g specification (cefoperazone 1.0g+ clavulanic acid 0.125g), carries out tests such as influence factor's test, accelerated test according to Chinese Pharmacopoeia and obtains following correction data:
Table 1 cefoperazone acid+clavulanate potassium+NaHCO 3Influence factor's testing data
Time Condition Character pH Clarity Color Related substance % Labelled amount %
Clavulanic acid Cefoperazone
0 day - White powder 6.43 ＜No. 0.5 ＜Y1 0.57 101.3 100.7
5 days Illumination White powder 6.51 ＜No. 0.5 ＜Y1 0.59 101.1 100.6
40℃ Off-white powder 6.55 ＜No. 0.5 ＜Y1 0.62 100.9 100.6
60℃ Off-white powder 6.44 ＜No. 0.5 ＜Y2 0.84 100.5 99.9
75％ Off-white powder 6.56 ＜No. 1 ＜Y3 0.75 100.7 100.2
10 days Illumination White powder 6.43 ＜No. 1 ＜Y1 0.63 100.8 100.5
40℃ Off-white powder 6.49 ＜No. 1 Y1 0.71 100.7 100.2
60℃ Off-white powder 6.58 ＜No. 1 Y2 1.23 100.3 99.5
75％ Off-white powder 6.55 ＜No. 1 Y3 1.09 100.4 99.7
Annotate: the specification of above-mentioned preparation is 2.125g (cefoperazone 2.0g+ clavulanic acid 0.125g).
Cefoperazone acid+clavulanate potassium+NaHCO 3Keep sample for a long time
Table 2 (25 ± 2 ℃, relative humidity 60% ± 10%) testing data
Lot number Standing time Character pH Clarity Color Related substance % Labelled amount %
Clavulanic acid Cefoperazone
Lot number 1 0 month White powder 6.55 Clarification ＜Y1 0.55 101.1 100.9
3 months Off-white powder 6.54 Clarification ＜Y2 0.63 100.9 100.4
6 months Off-white powder 6.73 Clarification Y2 1.08 100.5 99.7
9 months Off-white powder 6.68 Clarification ＜Y3 1.63 100.1 99.1
18 months Off-white powder 6.64 Clarification Y3 2.16 99.5 98.5
24 months Off-white powder 6.58 Clarification ＜Y4 2.83 98.9 97.8
Lot number 2 0 month White powder 6.42 Clarification ＜Y1 0.57 100.9 10.7
3 months Off-white powder 6.53 Clarification ＜Y2 0.66 100.8 100.3
6 months Off-white powder 6.55 Clarification Y2 1.11 100.4 99.5
9 months Off-white powder 6.53 Clarification ＜Y3 1.66 99.9 98.9
18 months Off-white powder 6.59 Clarification Y3 2.21 99.2 98.1
24 months Off-white powder 6.62 Clarification ＜Y4 2.89 98.3 97.4
Batch 0 month White powder 6.54 Clarification ＜Y1 0.52 101.2 100.8
Numbers 3 3 months Off-white powder 6.31 Clarification ＜Y2 0.61 101.0 100.8
6 months Off-white powder 6.44 Clarification Y2 1.01 100.6 99.7
9 months Off-white powder 6.57 Clarification ＜Y3 1.61 100.2 99.3
18 months Off-white powder 6.63 Clarification Y3 2.07 99.7 98.8
24 months Off-white powder 6.68 Clarification ＜Y4 2.79 99.1 98.0
Annotate: the specification of above-mentioned preparation is 2.125g (cefoperazone 2.0g+ clavulanic acid 0.125g).
Cefoperazone acid+clavulanate potassium+NaHCO 3
40 ℃ of accelerated tests of table 3 (40 ± 2 ℃, relative humidity 60% ± 5%) testing data
Lot number Standing time Character pH Clarity Color Related substance (%) Labelled amount %
Clavulanic acid Cefoperazone
Criticize 1 0 month White powder 6.54 Clarification ＜Y1 0.56 101.1 101.2
1 month Off-white powder 6.52 Clarification ＜Y2 0.85 100.7 100.4
2 months Off-white powder 6.48 Clarification Y2 1.13 100.3 99.7
3 months Off-white powder 6.55 Clarification ＜Y3 1.58 100.1 99.1
6 months Off-white powder 6.43 Clarification ＜Y4 2.01 100.0 98.3
Lot number 2 0 month White powder 6.54 Clarification ＜Y1 0.58 100.8 100.7
1 month Off-white powder 6.39 Clarification ＜Y2 0.94 100.6 100.2
2 months Off-white powder 6.54 Clarification Y2 1.17 100.2 99.7
3 months Off-white powder 6.62 Clarification ＜Y3 1.62 100.1 98.6
6 months Off-white powder 6.58 Clarification Y3 2.12 99.9 98.0
Lot number 3 0 month White powder 6.45 Clarification ＜Y1 0.54 101.2 100.9
1 month Off-white powder 6.55 Clarification ＜Y2 0.83 100.9 100.3
2 months Off-white powder 6.57 Clarification Y2 1.09 100.5 99.9
3 months Off-white powder 6.54 Clarification ＜Y3 1.35 100.3 99.1
6 months Off-white powder 6.61 Clarification ＜Y4 1.97 99.9 98.7
Annotate: the specification of above-mentioned preparation is 2.125g (cefoperazone 2.0g+ clavulanic acid 0.125g).
Table 4 cefoperazone acid+clavulanate potassium+NaHCO 3Influence factor's testing data
Time Condition Character pH Clarity Color Related substance % Labelled amount %
Clavulanic acid Cefoperazone
0 day - White powder 6.46 ＜No. 0.5 ＜Y1 0.53 100.9 101.5
5 days Illumination White powder 6.52 ＜No. 0.5 ＜Y1 0.58 100.8 101.0
40℃ Off-white powder 6.55 ＜No. 0.5 ＜Y1 0.61 100.6 100.9
60℃ Off-white powder 6.54 ＜No. 0.5 ＜Y2 0.83 100.3 100.2
RH75％ Off-white powder 6.59 ＜No. 1 ＜Y3 0.73 100.4 100.6
10 days Illumination White powder 6.45 ＜No. 1 ＜Y1 0.62 100.6 100.8
40℃ Off-white powder 6.49 ＜No. 1 Y1 0.73 100.3 100.5
60℃ Off-white powder 6.56 ＜No. 1 Y2 1.25 99.8 99.6
RH75％ Off-white powder 6.55 ＜No. 1 Y3 1.10 100.1 99.9
Annotate: the specification of above-mentioned preparation is 1.125g (cefoperazone 1.0g+ clavulanic acid 0.125g).
Cefoperazone acid+clavulanate potassium+NaHCO 3Keep sample for a long time
Table 5 (25 ± 2 ℃, relative humidity 60% ± 10%) testing data
Lot number Standing time Character pH Clarity Color Related substance % Labelled amount %
Clavulanic acid Cefoperazone
Lot number 1 0 month White powder 6.53 Clarification ＜Y1 0.53 100.9 101.2
3 months Off-white powder 6.54 Clarification ＜Y2 0.66 100.7 100.9
6 months Off-white powder 6.75 Clarification Y2 1.09 100.5 100.2
9 months Off-white powder 6.66 Clarification ＜Y3 1.68 100.1 99.6
18 months Off-white powder 6.64 Clarification Y3 2.18 99.8 98.8
24 months Off-white powder 6.72 Clarification ＜Y4 2.82 98.7 97.9
Lot number 2 0 month White powder 6.41 Clarification ＜Y1 0.55 100.9 100.9
3 months Off-white powder 6.55 Clarification ＜Y2 0.66 100.7 100.3
6 months Off-white powder 6.55 Clarification Y2 1.13 100.4 99.8
9 months Off-white powder 6.62 Clarification ＜Y3 1.71 99.8 98.9
18 months Off-white powder 6.59 Clarification Y3 2.20 99.5 98.5
24 months Off-white powder 6.62 Clarification ＜Y4 2.87 98.3 97.6
Lot number 3 0 month White powder 6.48 Clarification ＜Y1 0.58 101.1 101.3
3 months Off-white powder 6.56 Clarification ＜Y2 0.65 100.8 100.8
6 months Off-white powder 6.49 Clarification Y2 1.09 100.4 100.3
9 months Off-white powder 6.62 Clarification ＜Y3 1.67 100.1 99.5
18 months Off-white powder 6.66 Clarification Y3 2.17 99.7 98.8
24 months Off-white powder 6.68 Clarification ＜Y4 2.79 98.9 98.1
Annotate: the specification of above-mentioned preparation is 1.125g (cefoperazone 1.0g+ clavulanic acid 0.125g).
Cefoperazone acid+clavulanate potassium+NaHCO 3
40 ℃ of accelerated tests of table 6 (40 ± 2 ℃, relative humidity 60% ± 5%) testing data
Lot number Standing time Character pH Clarity Color Related substance (%) Labelled amount %
Clavulanic acid Cefoperazone
Lot number 1 0 month White powder 6.53 Clarification ＜Y1 0.55 100.9 101.1
1 month Off-white powder 6.52 Clarification ＜Y2 0.87 100.3 100.2
2 months Off-white powder 6.55 Clarification Y2 1.12 100.1 99.8
3 months Off-white powder 6.58 Clarification ＜Y3 1.55 99.9 98.8
6 months Off-white powder 6.56 Clarification ＜Y4 2.11 99.1 97.9
Lot number 2 0 month White powder 6.54 Clarification ＜Y1 0.58 100.8 100.9
1 month Off-white powder 6.48 Clarification ＜Y2 0.99 100.6 100.2
2 months Off-white powder 6.54 Clarification Y2 1.17 100.2 99.5
3 months Off-white powder 6.61 Clarification ＜Y3 1.66 100.1 98.3
6 months Off-white powder 6.57 Clarification Y3 2.15 99.9 98.0
Lot number 3 0 month White powder 6.45 Clarification ＜Y1 0.54 101.2 100.9
1 month Off-white powder 6.56 Clarification ＜Y2 0.86 100.9 100.4
2 months Off-white powder 6.53 Clarification Y2 1.09 100.5 99.9
3 months Off-white powder 6.49 Clarification ＜Y3 1.55 100.3 98.8
6 months Off-white powder 6.61 Clarification Y3 1.98 99.9 98.2
Annotate: the specification of above-mentioned preparation is 1.125g (cefoperazone 1.0g+ clavulanic acid 0.125g).
Can sum up from above-mentioned subordinate list, influence factor test, 25 ℃ keep sample for a long time and 40 ℃ of accelerated tests in, cefoperazone acid is with after the cosolvent sodium bicarbonate share by different proportionings, the compound preparation of forming with clavulanate potassium, its related substance all is less than 5.0%, indicates content all greater than 95%.Meet standards of pharmacopoeia at 25 ℃ of its sign content, related substances in two years that keep sample for a long time about cefoperazone sodium or its compound preparation.Prove that thus the compound preparation of cefoperazone acid+clavulanate potassium+cosolvent can keep steady quality in 2 years.
Specific embodiment
Be the specific embodiment of the invention below, but the present invention is not limited thereto.
The different proportionings of cefoperazone of the present invention acid and clavulanate potassium and cosolvent, and correlation circumstance (pH value, dissolution time, solution colour).
Figure A20061003431700101
Cefoperazone acid: clavulanate potassium: sodium bicarbonate: sodium hydroxide 16∶1∶1.04∶0.50 6.86 30S Be not deeper than yellow No. 2 colors
As seen from the above table: what dissolution time was the shortest is: sodium bicarbonate, sodium carbonate, sodium hydroxide.Medicine dissolution is fast more clinically, can shorten time of compounding more, is convenient to clinical practice.Therefore, analyze from the dissolution velocity of medicine, the stability and the drug safety each side of medicine: sodium bicarbonate is the best cosolvent of preparation cefoperazone for inj clavulanate potassium compound preparation.
Embodiment 1:
Cefoperazone acid is 16: 1 o'clock with the clavulanate potassium mass ratio, the proportioning of sodium carbonate and the pH value of hydrotropy:
Cefoperazone acid: sodium carbonate (mass ratio) PH value Appearance luster Dissolution time
16∶1.27 - - -
16∶1.28 5.52 Be not deeper than yellow No. 1 color 100S
16∶1.32 5.77 Be not deeper than yellow No. 1 color 100S
16∶1.33 5.84 Be not deeper than yellow No. 1 color 100S
16∶1.34 5.85 Be not deeper than yellow No. 1 color 90S
16∶1.38 6.01 Be not deeper than yellow No. 1 color 80S
16∶1.42 6.13 Be not deeper than yellow No. 1 color 75S
16∶1.43 6.45 Be equivalent to yellow No. 1 color 60S
16∶1.44 6.52 Be not deeper than yellow No. 2 colors 40S
16∶1.45 6.72 Be not deeper than yellow No. 2 colors 35S
16∶1.50 6.97 Be not deeper than yellow No. 2 colors 30S
16∶1.54 7.19 Be not deeper than yellow No. 2 colors 30S
16∶1.58 7.24 Be equivalent to yellow No. 2 colors 20S
16∶1.60 7.48 Be equivalent to yellow No. 2 colors ＜20S
16∶1.61 7.53 Be equivalent to yellow No. 2 colors ＜20S
As seen from the above table, press pH scope 5.5～7.5, cefoperazone acid: clavulanate potassium: the span of sodium carbonate: 16: 1: 1.28～1.60.Its color all is not more than yellow No. 3 colors, and dissolution time is not more than 100S.
Embodiment 2:
Cefoperazone acid is 16: 1 o'clock with the clavulanate potassium mass ratio, the proportioning of sodium bicarbonate and the pH value of hydrotropy:
Cefoperazone acid: sodium bicarbonate (mass ratio) PH value Appearance luster Dissolution time
16∶2.08 - - -
16∶2.09 5.58 Be not deeper than yellow No. 1 color 80S
16∶2.10 6.12 Be not deeper than yellow No. 1 color 60S
16∶2.11 6.22 Be not deeper than yellow No. 1 color 45S
16∶2.12 6.52 Be not deeper than yellow No. 2 colors 35S
16∶2.13 6.77 Be not deeper than yellow No. 2 colors 30S
16∶2.14 7.18 Be equivalent to yellow No. 2 colors 25S
16∶2.15 7.35 Be equivalent to yellow No. 2 colors 20S
16∶2.20 7.69 Be not deeper than yellow No. 3 colors ＜20S
As seen from the above table, press pH scope 5.5～7.5, cefoperazone acid: clavulanate potassium: the span of sodium bicarbonate: 16: 1: 2.15～2.09.Its color all is not deeper than yellow No. 3 colors, and dissolution time is not more than 80S.
Embodiment 3:
Cefoperazone acid is 8: 1 o'clock with the clavulanate potassium mass ratio, the proportioning of sodium carbonate and the pH value of hydrotropy:
Cefoperazone acid: sodium carbonate (mass ratio) PH value Appearance luster Dissolution time
8∶0.65 4.95 Be not deeper than yellow No. 1 color 80S
8∶0.66 5.63 Be not deeper than yellow No. 1 color 75S
8∶0.67 6.25 Be not deeper than yellow No. 1 color 70S
8∶0.68 6.52 Be not deeper than yellow No. 1 color 60S
8∶0.69 7.13 Be not deeper than yellow No. 1 color 50S
8∶0.70 7.39 Be equivalent to yellow No. 1 color 30S
8∶0.71 7.65 Be not deeper than yellow No. 2 colors 20S
As seen from the above table, press pH scope 5.5～7.5, cefoperazone acid: clavulanate potassium: the span of sodium carbonate: 8: 1: 0.70～0.66.Its color all is not more than yellow No. 2 colors, and dissolution time is not more than 80S.
Embodiment 4:
Cefoperazone acid is 8: 1 o'clock with the clavulanate potassium mass ratio, the proportioning of sodium bicarbonate and the pH value of hydrotropy:
Cefoperazone acid: sodium bicarbonate (mass ratio) PH value Appearance luster Dissolution time
8∶1.03 4.88 Be not deeper than yellow No. 1 color 100S
8∶1.04 5.78 Be not deeper than yellow No. 1 color 80S
8∶1.05 6.22 Be not deeper than yellow No. 1 color 60S
8∶1.06 6.38 Be not deeper than yellow No. 1 color 45S
8∶1.07 6.50 Be not deeper than yellow No. 1 color 35S
8∶1.08 6.77 Be not deeper than yellow No. 1 color 30S
8∶1.09 6.92 Be equivalent to yellow No. 1 color 30S
8∶1.10 7.23 Be equivalent to yellow No. 1 color 25S
8∶1.11 7.35 Be not deeper than yellow No. 2 colors 20S
8∶1.12 7.69 Be not deeper than yellow No. 2 colors ＜20S
As seen from the above table, press pH scope 5.5～7.5, cefoperazone acid: clavulanate potassium: the span of sodium bicarbonate: 8: 1: 1.11～1.04.Its color all is not deeper than yellow No. 2 colors, and dissolution time is not more than 100S.

Claims (10)

1, stable cefoperazone potassium clavulanatein medicine compound preparation is characterized in that mainly being made up of cefoperazone acid, clavulanate potassium and cosolvent, and three's weight ratio is: 16～1: 1: 8.8～0.06.
2, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 1 is characterized in that cosolvent is selected from one or several mixture of sodium carbonate, sodium bicarbonate, arginine, sodium hydroxide, sodium phosphate, sodium hydrogen phosphate.
3, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 2 is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium bicarbonate is 16～1: 1: 2.5～0.13; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium carbonate is: 16～1: 1: 1.6～0.08; Cefoperazone acid: clavulanate potassium: arginic weight ratio is: 16～1: 1: 4.5～0.27; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium hydroxide is: 16～1: 1: 1.0～0.06; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium phosphate is: 16～1: 1: 6.8～0.4; Cefoperazone acid: clavulanate potassium: the weight ratio of sodium hydrogen phosphate is: 16～1: 1: 8.8～0.5.
4, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 3 is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium bicarbonate is 16～4: 1: 2.15～0.52.
5, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 4 is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium bicarbonate is 16: 1: 2.15～2.09 or 8: 1: 1.11～1.04.
6, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 3 is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium carbonate is 16～4: 1: 1.6～0.33.
7, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 6 is characterized in that cefoperazone acid: clavulanate potassium: the weight ratio of sodium carbonate is 16: 1: 1.6～1.28 or 8: 1: 0.7～0.66.
8, the described cefoperazone potassium clavulanatein medicine compound preparation of one of claim 1～7 is characterized in that the pH scope of compound preparation is 5.5～7.5.
9, the described cefoperazone potassium clavulanatein medicine compound preparation of claim 8 is characterized in that the pH scope of compound preparation is 6.0～7.0.
10, the described cefoperazone potassium clavulanatein medicine compound preparation of one of claim 1～9 is characterized by a kind of injection.
CN 200610034317 2006-03-15 2006-03-15 Stable cefoperazone potassium clavulanatein medicine compound preparation Pending CN101036655A (en)

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