CN101744825A - Cefmenoxime hydrochloride preparation and preparation method - Google Patents

Abstract

The invention provides a cefmenoxime hydrochloride preparation used for injection, which is prepared from the mixture of sterile cefmenoxime hydrochloride and sterile sodium bicarbonate. Sterile cefmenoxime hydrochloride powder is mixed with sterile sodium bicarbonate powder which serves as cosolvent, and the proportion (based on cefmenoxime) of the cefmenoxime hydrochloride and the sodium bicarbonate by weight is 1: 0.15-1: 0.25, preferentially 1: 0.2, that means, 15% of sterile sodium bicarbonate powder (by weight) is added to per l gramme of sterile cefmenoxime hydrochloride powder (based on cefmenoxime). The mixture is blended to be even and then is packed in sterilized cylindroid vials according to labeled amounts through sterile-packing technique, then the cylindroid vials are blocked by tampons and capped, and finally the qualified cylindroid vials are packaged after full inspection. In this way, the cefmenoxime hydrochloride preparation used for injection can be prepared.

Description

A kind of Abbott 50192 preparation and preparation method

Technical field:

The present invention relates to a kind of Abbott 50192 preparation, particularly relate to the Abbott 50192 preparation that can be used for drug administration by injection that contains the cosolvent sodium bicarbonate.

Background technology:

Abbott 50192, chemical name: (6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyimino acetylamino]-3-[[1-methyl isophthalic acid H-tetrazolium-5-yl]-sulfur] methyl]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formates hydrochlorate (2: 1).

The semi-synthetic broad ectrum antibiotic that cefmenoxime hydrochloride in is the exploitation of Japanese Takede Chemical Industries Ltd, produce entered Chinese market in 1996.This medicine all has antibacterial action to Gram-negative and male aerobe and anaerobe.Antibacterial action to the escherichia coli in the gram negative bacteria, pneumobacillus is stronger slightly than cefotiam, and obviously be better than the cefazolin sodium of the first generation, the antibacterial action of Bacillus proteus, Citrobacter, influenza being bitten blood bacillus, Enterobacter, serratia marcesens is also more intense, and Bacteroides is also had very strong antibacterial action.Stronger to the micrococcus scarlatinae in the gram positive bacteria, pneumococcal antibacterial action.Peptococcus, Peptostreptococcus also there is the strong antibiotic effect.Stable to beta-lactamase.Quiet notes 1g, blood medicine peak value 99.4ug/ml, intramuscular injection 0.5g, blood medicine peak value is 10.8ug/ml, serum T _1/2Be about 1 hour.Metabolism hardly in vivo is mainly through renal excretion.Serum albumin combination rate 85%.This product is good to bile transport, and is higher at body fluid such as sputum, tonsil, cerebrospinal fluid, hydrothorax, peritoneal exudate, kidney, wall of urinary bladder, uterus, fallopian tube, ovary, pelvic cavity transudate, Cord blood, amniotic fluid and tissue distribution concentration.But transhipment seldom in milk.Be applicable to responsive microbial septicemia, meningitis, respiratory tract infection, empyema, liver and gallbladder infection, peritonitis, urinary tract infection, genital system infection and burn and surgical wound infection etc.This product is since the nineteen eighty-three listing, and clinical practice constantly enlarges, and sales volume rises year by year, and is written into state's latest edition pharmacopeia such as Japan and Korea S., U.S..

Its pharmacological action is as follows: 1. antibacterial action: cefmenoxime is a third generation cephalosporin, and Gram-negative and Gram-positive aerobe are had effect widely, and it act as bactericidal.Especially to escherichia coli, klebsiella, proteus mirabilis, gram negative bacilli such as hemophilus influenza have powerful antibacterial action.Gram-positive coccis such as Streptococcus, streptococcus pneumoniae also there is very strong antibacterial action.In addition anaerobe such as Gram-positive bacillus such as the positive Proteus of indole, intestinal Pseudomonas, citrobacter genus, Serratia and Bacteroides also there is splendid antimicrbial power.This product is stable to beta-lactamase, and beta-lactamase is produced bacterium also very strong antimicrbial power.

2. mechanism of action: hinder the synthetic of bacteria cell wall.It is because its pair cell adventitia has good permeability and stable and to penicillin-binding protein 1A to beta-lactamase that this product has strong antimicrbial power to gram negative bacteria, 1B, and 3 affinity is strong, thereby makes due to the cell wall mucopeptide crosslinked action is obstructed strongly.

At present, the cefmenoxime hydrochloride in that uses clinically makes as raw material is mixed with Abbott 50192 and natrium carbonicum calcinatum aseptic powder, and using method is that this product is dissolved in 0.9% sodium chloride injection or the glucose injection, carries out intravenous drip.

There are the following problems for the production of said preparation, storage and use:

1, Abbott 50192 is insoluble in water, could dissolve under the hydrotropy condition.And the cosolvent natrium carbonicum calcinatum at first forms hydrate on the surface in course of dissolution, causes the sodium carbonate course of dissolution slow, thereby influences the dissolving of Abbott 50192, makes the Abbott 50192 preparation poorly soluble, and dissolution time is long, is unfavorable for clinical use.And in long course of dissolution, impurity obviously increases, and makes adverse reaction rate height in clinical use, and the risk of clinical application is bigger.

2, by being investigated, the long-term and accelerated stability of the cefmenoxime hydrochloride in product that gone on the market finds, the poor stability of product, and color is obviously deepened in storage process, and related substance and polymer obviously increase, and content obviously descends.

Summary of the invention:

The novel formulation that the purpose of this invention is to provide problems such as a kind ofly can overcoming that existing cefmenoxime hydrochloride in is poorly soluble, impurity height such as poor stability, related substance and polymer, content are low, improve the dissolubility of product, guarantee product quality and product stability, ensure clinical drug safety.

And the alkalescence of sodium bicarbonate than sodium carbonate a little less than, course of dissolution also relaxes than sodium carbonate, be easier to combine with salt acid molecule in the Abbott 50192, make the course of dissolution of preparation even and rapid, and the pH value amplitude of variation is little in course of dissolution, impurity produces few, thereby has ensured the quality of product, has reduced the clinical application risk.

Therefore, determine through experimentation, cefmenoxime hydrochloride in of the present invention is that the mixed powder with Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder is the cefmenoxime hydrochloride in novel formulation of raw material, it has promptly guaranteed quality and the stability of product in production and storage process, make things convenient for clinical practice again, ensured the safety of medication.

Technical scheme:

The Abbott 50192 aseptic powder is mixed with cosolvent sodium bicarbonate aseptic powder, Abbott 50192 (pure) is 1: 0.15 to 1: 0.25 with the weight ratio of sodium bicarbonate, preferred proportion is 1: 0.2, and promptly 1 gram Abbott 50192 (pure) aseptic powder adds the sodium bicarbonate aseptic powder of 0.2 gram, behind the mix homogeneously, be loaded in the cillin bottle after the sterilization, lid is rolled in tamponade, full inspection, qualified back bag promptly obtains this product---cefmenoxime hydrochloride in.

The specific embodiment:

Embodiment 1

The prescription of cefmenoxime hydrochloride in:

Abbott 50192: 1000g (pure)

Sodium bicarbonate: 200g

????????????????????????????????

Make 1000

Preparation technology:

Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the recipe quantity weighing, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, examines qualified back packing entirely.

Check result sees Table 1.

Table 1

Project	Color	Clarity	PH value	Content %	Total impurities %
						The result	No. 2,＜yellow green	Clarification	??7.0	??95.1	??1.0

Test example 1 cefmenoxime hydrochloride in stability test

Product in 25 ℃ of placements, is carried out 24 months long-term stable experiment, investigate its stability, the result shows, this preparation stabilization.The results are shown in Table 2.

Table 2

Time	Color	Clarity	PH value	Content %	Total impurities %
						0 month	No. 2,＜yellow green	Clarification	??7.0	??95.1	??1.0
March	No. 3,＜yellow green	Clarification	??7.1	??95.0	??1.1
						June	No. 3,＜yellow green	Clarification	??7.1	??94.7	??1.2
December	No. 4,＜yellow green	Clarification	??7.2	??94.5	??1.4
						24 months	No. 4,＜yellow green	Clarification	??7.2	??94.0	??1.5

The room temperature stability test in 0.9% sodium chloride injection of test example 2 cefmenoxime hydrochloride in

With draw 0.9% sodium chloride injection 10ml dissolving of this product 1, solution is preserved down in room temperature (25 ℃), investigates its stability, and the result shows, and is stable in the solution at room temperature 2 hours.The results are shown in Table 3.

Table 3

Time	Color	Clarity	PH value	Content %	Total impurities %
						0 hour	No. 3,＜yellow green	Clarification	??7.1	??95.0	??1.1
1 hour	No. 3,＜yellow green	Clarification	??7.1	??94.5	??1.3
						2 hours	No. 4,＜yellow green	Clarification	??7.2	??94.0	??1.5
4 hours	No. 5,＜yellow green	Clarification	??7.2	??93.1	??1.6

Embodiment 2

The prescription of cefmenoxime hydrochloride in:

Abbott 50192: 1000g (pure)

Sodium bicarbonate: 150g

?????????????????????????????????

Make 1000

Preparation technology:

Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the recipe quantity weighing, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, examines qualified back packing entirely.

Check result sees Table 4.

Table 4

Project	Color	Clarity	PH value	Content %	Total impurities %
						The result	No. 2,＜yellow green	Clarification	??5.9	??95.0	??0.9

Embodiment 3

The prescription of cefmenoxime hydrochloride in:

Abbott 50192: 1000g (pure)

Sodium bicarbonate: 250g

????????????????????????????????

Make 1000

Preparation technology:

Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the recipe quantity weighing, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, examines qualified back packing entirely.

Check result sees Table 5.

Table 5

Project	Color	Clarity	PH value	Content %	Total impurities %
						The result	No. 5,＜yellow green	Clarification	??8.1	??93.8	??1.8

Embodiment 4

The prescription of cefmenoxime hydrochloride in:

Abbott 50192: 1000g (pure)

Sodium bicarbonate: 170g

???????????????????????????????

Make 1000

Preparation technology:

Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the recipe quantity weighing, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, examines qualified back packing entirely.

Check result sees Table 6.

Table 6

Project	Color	Clarity	PH value	Content %	Total impurities %
						The result	No. 3,＜yellow green	Clarification	??6.3	??94.8	??0.9

Embodiment 5

The prescription of cefmenoxime hydrochloride in:

Abbott 50192: 1000g (pure)

Sodium bicarbonate: 230g

????????????????????????????

Make 1000

Preparation technology:

Abbott 50192 aseptic powder and sodium bicarbonate aseptic powder are mixed after by the recipe quantity weighing, behind the mix homogeneously, be sub-packed in the cillin bottle of aseptic process, lid is rolled in tamponade, examines qualified back packing entirely.

Check result sees Table 7.

Table 7

Project	Color	Clarity	PH value	Content %	Total impurities %
						The result	No. 3,＜yellow green	Clarification	??7.4	??94.1	??1.3

Claims (4)

1. the Abbott 50192 preparation of a new injectable administration is that raw material makes with active ingredient Abbott 50192 and cosolvent carbonate.

2. Abbott 50192 novel formulation as claimed in claim 1, its cosolvent are sterile sodium bicarbonate.

3. Abbott 50192 novel formulation as claimed in claim 1, its active ingredient hydrochloric acid cefmenoxime (in cefmenoxime) is 1: 0.15 to 1: 0.25 with the weight ratio of sodium bicarbonate, preferred proportion is 1: 0.2.

4. the preparation method of novel formulation as claimed in claim 1, promptly 1 gram Abbott 50192 (in cefmenoxime) aseptic powder adds the sodium bicarbonate aseptic powder of 0.2 gram, be mixed, be loaded in the cillin bottle after the sterilization, tamponade, roll lid, examine qualified back packing entirely, promptly obtain product of the present invention---cefmenoxime hydrochloride in.