CN105125558A - Antibacterial cefotiam hydrochloride drug composition - Google Patents
Antibacterial cefotiam hydrochloride drug composition Download PDFInfo
- Publication number
- CN105125558A CN105125558A CN201510594228.2A CN201510594228A CN105125558A CN 105125558 A CN105125558 A CN 105125558A CN 201510594228 A CN201510594228 A CN 201510594228A CN 105125558 A CN105125558 A CN 105125558A
- Authority
- CN
- China
- Prior art keywords
- cefotiam hydrochloride
- cefotiam
- hydrochloride
- weight portion
- injection
- 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.)
- Withdrawn
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an antibacterial cefotiam hydrochloride drug composition, belongs to the technical field of medicines. The drug composition comprises cefotiam hydrochloride and arginine, wherein cefotiam hydrochloride is crystalline, and the X-ray powder diffraction pattern measured by Cu-K-alpha rays is shown in the figure 1 (in the description). The new crystalline form of cefotiam hydrochloride provided by the invention is different from the crystal structure in the prior art, by experimental verification, the purity of the crystalline compound is high, the fluidity is good, the stability is good, the polymer content is low, hygroscopicity is avoided, and the stability of solution is good after being left to stand for 4 h at room temperature, wherein the solution is obtained by compounding the prepared powder injection with 0.9% sodium chloride injection, 5% glucose injection, and 5% sodium chloride and dextrose injection.
Description
Technical field
The invention belongs to medical art, relate to a kind of antibacterials cefotiam hydrochloride compositions.
Background technology
Cefotiam hydrochloride is for apply cephalosporin more widely clinically, because it is in storage process, particularly under the condition of high temperature (> 50 DEG C), often there is degraded and polyreaction, thus cause active constituents of medicine content to reduce, color and luster is strengthened, and polymeric impurities content raises.In addition, cross the cefotiam hydrochloride of effect duration, because the resting period is long, also usually make active constituents of medicine content reduce, darken, polymer content is high especially, and during polymer content height, easily makes human body produce anaphylaxis.
Although prior art to some extent solves its purity problem, but through further studying discovery, because cefotiam hydrochloride is positioned in the process of depositing, particularly under the condition of high temperature (> 50 DEG C), often there is degraded and polyreaction, along with the prolongation of resting period, its high polymer content increases, and the risk making human body produce anaphylactic reaction increases, and prior art is by various mode, as prepared by crystal formation, substantially increase its safety.
But containing unstable beta-lactam nucleus in the structure of cefotiam hydrochloride, easy generation hydrolysis and rearrangement reaction, cause structural damage and lose antibacterial activity, some catabolite may produce anaphylaxis, and therefore the stability of this kind of antibiotic in transfusion should cause extensive attention.
But, document " cefotiam hydrochloridefor inj and the research of three kinds of infusion solutions compatibility stability " [Luo Xiaoru, Wei Liping, Deng. cefotiam hydrochloridefor inj and the research of three kinds of infusion solutions compatibility stability, PLA's Acta Pharmaceutica Sinica [J], 2013,29(4): 354-356] after the stability of cefotiam hydrochloridefor inj and 0.9% sodium chloride injection, 5% glucose injection and 5% Dextrose and Sodium Chloride Inj. compatibility is investigated, under its result shows room temperature condition, cefotiam hydrochloridefor inj is all unstable in above-mentioned 3 kinds of solution.And all unresolved described problem of the crystal compound of prior art.
And the mobility of cefotiam hydrochloride is also poor, make when preparing cefotiam hydrochloridefor inj and the mixing homogeneity of adjuvant poor.The invention provides a kind of cefotiam hydrochloride Anxin crystalline compounds being different from prior art, its purity is high, good fluidity, good stability, polymer content is low, moist without drawing, after the injectable powder made and 0.9% sodium chloride injection, 5% glucose injection, 5% Dextrose and Sodium Chloride Inj. compatibility, room temperature places the good stability of solution after 4h.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of antibacterials cefotiam hydrochloride compositions.
In order to complete object of the present invention, the technical scheme of employing is:
A kind of antibacterials cefotiam hydrochloride compositions, consisting of of described compositions: cefotiam hydrochloride 1 weight portion, arginine 0.01-0.03 weight portion; Described cefotiam hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, consisting of of described compositions: cefotiam hydrochloride 1 weight portion, arginine 0.02 weight portion.
Preferably, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take cefotiam hydrochloride crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
The preparation method of the cefotiam hydrochloride crystal in described compositions comprises the following steps:
Prepare the saturated alcoholic solution of cefotiam hydrochloride crude product of 30 DEG C, then the isobutanol of 8 times and the mixed solvent of petroleum ether that volume is saturated volumes of aqueous ethanol is added, described isobutanol, the volume ratio of petroleum ether are 2:1.5, after stirring, cooling limit, limit is stirred, cooling rate is 10 DEG C/h, mixing speed is 105 revs/min, add the ether that volume is the mixed solvent volume 2 times of isobutanol and petroleum ether simultaneously, stop after being cooled to 0 DEG C stirring, leave standstill growing the grain 3 hours, filter, after drying under reduced pressure, obtain cefotiam hydrochloride crystalline compounds.
The polymorphism of solid chemical is the natural phenomena that a kind of general material exists, this phenomenon refers to that a kind of solid chemical can exist 2 kinds or two or more crystal form state, be also called the polymorphic state of material, the polymorphic state of material is also referred to as " allomorphism " phenomenon.Although its chemical nature of allomorphous solid matter is identical, its physicochemical property may be different.For " allomorphism medicine " that physicochemical property is different, also can show the curative effect of different disease preventing and treating clinically, directly affect application and the clinical effectiveness of medicine.
Because cefotiam hydrochloride is positioned in the process of depositing, particularly under the condition of high temperature (> 50 DEG C), often there is degraded and polyreaction, along with the prolongation of resting period, its high polymer content increases, and the risk making human body produce anaphylactic reaction increases, and prior art is by various mode, as prepared by crystal formation, substantially increase its safety.
But containing unstable beta-lactam nucleus in the structure of cefotiam hydrochloride, easy generation hydrolysis and rearrangement reaction, cause structural damage and lose antibacterial activity, some catabolite may produce anaphylaxis, and therefore the stability of this kind of antibiotic in transfusion should cause extensive attention.
But, document " cefotiam hydrochloridefor inj and the research of three kinds of infusion solutions compatibility stability " [Luo Xiaoru, Wei Liping, Deng. cefotiam hydrochloridefor inj and the research of three kinds of infusion solutions compatibility stability, PLA's Acta Pharmaceutica Sinica [J], 2013,29(4): 354-356] after the stability of cefotiam hydrochloridefor inj and 0.9% sodium chloride injection, 5% glucose injection and 5% Dextrose and Sodium Chloride Inj. compatibility is investigated, under its result shows room temperature condition, cefotiam hydrochloridefor inj is all unstable in above-mentioned 3 kinds of solution.And all unresolved described problem of the crystal compound of prior art.
And the mobility of cefotiam hydrochloride is also poor, make when preparing cefotiam hydrochloridefor inj and the mixing homogeneity of adjuvant poor.The invention provides a kind of cefotiam hydrochloride Anxin crystalline compounds being different from prior art, its purity is high, good fluidity, good stability, polymer content is low, moist without drawing, after the injectable powder made and 0.9% sodium chloride injection, 5% glucose injection, 5% Dextrose and Sodium Chloride Inj. compatibility, room temperature places the good stability of solution after 4h.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the cefotiam hydrochloride crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of cefotiam hydrochloride crystal
Prepare the saturated alcoholic solution of cefotiam hydrochloride crude product of 30 DEG C, then the isobutanol of 8 times and the mixed solvent of petroleum ether that volume is saturated volumes of aqueous ethanol is added, described isobutanol, the volume ratio of petroleum ether are 2:1.5, after stirring, cooling limit, limit is stirred, cooling rate is 10 DEG C/h, mixing speed is 105 revs/min, add the ether that volume is the mixed solvent volume 2 times of isobutanol and petroleum ether simultaneously, stop after being cooled to 0 DEG C stirring, leave standstill growing the grain 3 hours, filter, after drying under reduced pressure, obtain cefotiam hydrochloride crystalline compounds.
As shown in Figure 1, its purity of high-performance liquid chromatogram determination is 99.9% to the X-ray powder diffraction pattern that the cefotiam hydrochloride crystal prepared uses the measurement of Cu-K alpha ray to obtain.
embodiment 2:the preparation of cefotiam hydrochloride compositions
Consist of: cefotiam hydrochloride crystal 1 weight portion prepared by the present invention, arginine 0.01 weight portion.
Preparation method is:
(1) take cefotiam hydrochloride crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 3:the preparation of cefotiam hydrochloride compositions
Consist of: cefotiam hydrochloride crystal 1 weight portion prepared by the present invention, arginine 0.02 weight portion.
Preparation method is:
(1) take cefotiam hydrochloride crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 4:the preparation of cefotiam hydrochloride compositions
Consist of: cefotiam hydrochloride crystal 1 weight portion prepared by the present invention, arginine 0.03 weight portion.
Preparation method is:
(1) take cefotiam hydrochloride crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
experimental example 1,fluidity test
The mobility of this experimental example to the cefotiam hydrochloride crystal that the embodiment of the present invention 1 obtains detects.
Method: according to the embodiment of the present invention 1 method continuous production 6 batches of cefotiam hydrochlorides (batch: 1,2,3,4,5 and 6), respectively from 6 batches of obtained cefotiam hydrochloride regulating the spleen and stomach samplings, adopt fixed funnel method, funnel is placed in the suitable height on graph paper, cefotiam hydrochloride crystal is freely flowed down from bell mouth, until the cone top formed contacts with bell mouth, measure hypotenuse and the horizontal angle (θ angle of repose) of cefotiam hydrochloride accumulation horizon.The results are shown in Table 1:
The fluidity test result of table 1 cefotiam hydrochloride
From the interpretation of table 1, the mobility of cefotiam hydrochloride crystal of the present invention is fine.
experimental example 2:influence factor tests
1, hot test
The cefotiam hydrochloride crystalline compounds that Example 1 prepares, simulation listing packaging, puts in sealing clean container, place 10 days at 40 ± 2 DEG C of temperature, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result of the test compared with 0 day.
2, high humility test
The cefotiam hydrochloride crystalline compounds that Example 1 prepares, simulation listing packaging, put in sealing clean container, place 10 days under the condition of 25 ± 2 DEG C of relative humiditys 90% ± 5%, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result of the test compared with 0 day.
3, strong illumination test
The cefotiam hydrochloride crystalline compounds that Example 1 prepares, simulation listing packaging, puts in sealing clean container, being placed in illumination is place 10 days under the condition of 4500lx, in the 5th day and sampling in the 10th day, detect by stability high spot reviews project, result compared with 0 day.The results are shown in Table 2
Table 2 influence factor result of the test
Result shows: the cefotiam hydrochloride crystalline compounds that the present invention prepares, and its stability is good, and under high temperature, high humidity, high light conditions, equal retention is stablized.
experimental example 3:acceleration study
The cefotiam hydrochloride crystalline compounds that Example 1 prepares, simulation listing packaging, put in sealing clean container, in 40 DEG C ± 2 DEG C, place 6 months under relative humidity 70% ± 5% condition, at duration of test respectively at 1,2,3,6 sampling at the end of month once, each stability high spot reviews project is tested.The results are shown in Table 3.
Table 3 accelerated test result
Result shows: the cefotiam hydrochloride crystalline compounds that the present invention prepares, known through accelerated test result, its good stability, and polymer content is low, and total assorted content is low.
experimental example 4:wettability test
1 instrument
PL203 electronic balance, LRH-250-S constant temperature and humidity incubator, HH-400SD testing chamber for medicine stability;
2 methods
Get the glass desicator (for ensureing that saline solution is saturated, excessive salt should be had bottom exsiccator to exist) that bottom fills salt supersaturated solution, the built-in weighing botle of exsiccator, places 48h to constant humidity in calorstat.Sample thief is about 2g, puts in weighing botle, accurately weighed, bottle cap is opened, puts into exsiccator top, put in 25 DEG C of constant temperature and humidity incubators or 20 DEG C of stability test casees by different temperatures requirement and preserve, operation repetitive 3 parts, weighs respectively at different time, calculates the hydroscopicity of different time.
Computing formula: hydroscopicity=(medicated powder weight after moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount × 100%.Result is as table 4:
Table 4 hygroscopicity test results
According to above-mentioned experiment, the hygroscopicity of cefotiam hydrochloride crystalline compounds prepared by the present invention is low, good stability.
experimental example 4:compatibility stability is tested
This experimental example has investigated the stability of different cefotiam hydrochloridefor inj and three kinds of infusion solutions compatibilities.
Sample:
Test specimen: the cefotiam hydrochloridefor inj that the embodiment of the present invention 2 is obtained;
Control sample 1: prepare cefotiam hydrochloridefor inj according to the prescription of invention formulation embodiment 2 and preparation method, difference is cefotiam hydrochloride used is according to the obtained cefotiam hydrochloride of the method for CN102659818A embodiment 1;
Control sample 2: prepare cefotiam hydrochloridefor inj according to the prescription of invention formulation embodiment 2 and preparation method, difference is cefotiam hydrochloride used is according to the obtained cefotiam hydrochloride of the method for CN103232477A embodiment 1;
Compatibility stability test method: according to " cefotiam hydrochloridefor inj and the research of three kinds of infusion solutions compatibility stability " [Luo Xiaoru, Wei Liping, Deng. cefotiam hydrochloridefor inj and the research of three kinds of infusion solutions compatibility stability, PLA's Acta Pharmaceutica Sinica [J], 2013, method 29(4): 354-356] has investigated test specimen, control sample 1 and control sample 2 and 0.9% sodium chloride injection, 5% glucose injection, the stability of 5% Dextrose and Sodium Chloride Inj. compatibility, adopt HPLC method, place 0 at ambient temperature, 1, 2, 4h, measure the change of each sample related substance and content.The results are shown in Table shown in 5 and table 6.
Table 5 cefotiam hydrochloride is positioned on assay result in different medium
Table 6 cefotiam hydrochloride is positioned on determination of related substances result in different medium
As can be seen from above-mentioned result of the test, control sample 1 and control sample 2 are along with the prolongation of standing time, and the main constituent content of each sample all declines, and total impurities significantly increases, impurity number also showed increased, show room temperature place 4h after solution all unstable; Compare with control sample 2 with control sample 1, cefotiam hydrochloridefor inj of the present invention is along with the prolongation of standing time, its main constituent content changes hardly, total impurities is without significant change, impurity number is also without significant change, show under the condition that prescription is identical with preparation method, after after the cefotiam hydrochloridefor inj adopting cefotiam hydrochloride trihydrate crystal of the present invention to obtain and 0.9% sodium chloride injection, 5% glucose injection, 5% Dextrose and Sodium Chloride Inj. compatibility, room temperature places 4h, solution has good stability.
The cefotiam hydrochloridefor inj obtained to other embodiments of the invention has also carried out above-mentioned test, and its result obtained is similar.
Claims (4)
1. an antibacterials cefotiam hydrochloride compositions, is characterized in that: described compositions consist of cefotiam hydrochloride 1 weight portion, arginine 0.01-0.03 weight portion; Described cefotiam hydrochloride is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. antibacterials cefotiam hydrochloride compositions according to claim 1, is characterized in that: described compositions consist of cefotiam hydrochloride 1 weight portion, arginine 0.02 weight portion.
3. antibacterials cefotiam hydrochloride compositions according to claim 1 and 2, is characterized in that, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take cefotiam hydrochloride crystal and arginine in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
4. antibacterials cefotiam hydrochloride compositions according to claim 1, is characterized in that, the crystal preparation method of described cefotiam hydrochloride is:
Prepare the saturated alcoholic solution of cefotiam hydrochloride crude product of 30 DEG C, then the isobutanol of 8 times and the mixed solvent of petroleum ether that volume is saturated volumes of aqueous ethanol is added, described isobutanol, the volume ratio of petroleum ether are 2:1.5, after stirring, cooling limit, limit is stirred, cooling rate is 10 DEG C/h, mixing speed is 105 revs/min, add the ether that volume is the mixed solvent volume 2 times of isobutanol and petroleum ether simultaneously, stop after being cooled to 0 DEG C stirring, leave standstill growing the grain 3 hours, filter, after drying under reduced pressure, obtain cefotiam hydrochloride crystalline compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510594228.2A CN105125558A (en) | 2015-09-18 | 2015-09-18 | Antibacterial cefotiam hydrochloride drug composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510594228.2A CN105125558A (en) | 2015-09-18 | 2015-09-18 | Antibacterial cefotiam hydrochloride drug composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105125558A true CN105125558A (en) | 2015-12-09 |
Family
ID=54711381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510594228.2A Withdrawn CN105125558A (en) | 2015-09-18 | 2015-09-18 | Antibacterial cefotiam hydrochloride drug composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105125558A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769770A (en) * | 2016-05-12 | 2016-07-20 | 浙江永宁药业股份有限公司 | Cefotiam hydrochloride powder injection preparation for injection |
| CN107519172A (en) * | 2017-09-11 | 2017-12-29 | 浙江永宁药业股份有限公司 | A kind of cefotiam chloride organic base combination thing and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001083491A1 (en) * | 2000-04-28 | 2001-11-08 | Biochemie Gesellschaft M B H | Cephalosporin intermediates |
| CN102190667A (en) * | 2011-03-24 | 2011-09-21 | 海南灵康制药有限公司 | New method for purifying cefotiam hydrochloride |
| CN102659818A (en) * | 2012-04-19 | 2012-09-12 | 海南合瑞制药股份有限公司 | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound |
-
2015
- 2015-09-18 CN CN201510594228.2A patent/CN105125558A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001083491A1 (en) * | 2000-04-28 | 2001-11-08 | Biochemie Gesellschaft M B H | Cephalosporin intermediates |
| CN102190667A (en) * | 2011-03-24 | 2011-09-21 | 海南灵康制药有限公司 | New method for purifying cefotiam hydrochloride |
| CN102659818A (en) * | 2012-04-19 | 2012-09-12 | 海南合瑞制药股份有限公司 | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769770A (en) * | 2016-05-12 | 2016-07-20 | 浙江永宁药业股份有限公司 | Cefotiam hydrochloride powder injection preparation for injection |
| CN107519172A (en) * | 2017-09-11 | 2017-12-29 | 浙江永宁药业股份有限公司 | A kind of cefotiam chloride organic base combination thing and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105193819A (en) | Medicine cefotiam hydrochloride composition for treating bacterial infection | |
| CN105125558A (en) | Antibacterial cefotiam hydrochloride drug composition | |
| CN105085548A (en) | Pharmaceutical cefotiam composition for treating infectious diseases | |
| CN105055424A (en) | Anti-infective medicinal cefotiam hydrochloride composition | |
| CN105055406A (en) | Antibacterial drug aztreonam composition | |
| CN105055420A (en) | Medicine cefamandole nafate composition for treating bacterial infection | |
| CN103304604B (en) | Clindamycin phosphate compound and preparation method and pharmaceutical composition thereof | |
| CN106432274A (en) | Crystalline compound of drug ceftriaxone sodium for treating surgical operation infections | |
| CN105168223A (en) | Anti-bacterial medicine-ceftezole sodium composition | |
| CN104817523A (en) | Medicine ranitidine hydrochloride compound for treating stomach illness and preparation method of medicine ranitidine hydrochloride compound | |
| CN105055423A (en) | Medicine ceftezole sodium composition for curing infectious diseases | |
| CN105078999A (en) | Anti-infective medicine of cefamandole nafate composition | |
| CN105001215A (en) | Aztreonam compound serving as sterilization medicine and preparation method thereof | |
| CN113105478B (en) | Monascus sodium compound and crystal form, preparation method and preparation thereof | |
| CN105055419A (en) | Cefamandole nafate composition for the treatment of infectious diseases | |
| CN105193737A (en) | Medicinal tropisetron hydrochloride composition dry suspension for treating nausea and emesis | |
| CN105012310A (en) | Angiectasis medicine fasudil hydrochloride composition | |
| CN105030787A (en) | Ceftezole sodium composition serving as medicine for treating bacterial infection | |
| CN106432275A (en) | Method for preparing crystalline ceftriaxone sodium compound as drug for treating surgical infection | |
| CN103804396B (en) | A kind of cefepime hydrochloride compound prepared | |
| CN105012302A (en) | Tropisetron hydrochloride composition for vomit-stopping medicine | |
| CN105055442A (en) | Ranitidine hydrochloride composition for treating gastric diseases | |
| CN105055323A (en) | Anti-infective aztreonam composition | |
| CN104997785A (en) | Antibacterial drug-cefamandole nafate composition | |
| CN105055407A (en) | Medicine aztreonam composition for curing infectious diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20151209 |