CN104000777B - A kind of levofloxacin preparation - Google Patents

Abstract

The present invention relates to a kind of levofloxacin hydrochloride sodium chloride injection, it is characterised in that its prescription comprises: 20 parts of levofloxacin hydrochlorides; 0.1-0.2 part 2-amino-3-tolyl acid 10-15 part citric acid; 10-15 part Glacial acetic acid; Sodium hydroxide and water for injection.

Description

A kind of levofloxacin preparation

Technical field

The present invention relates to the injection field of chemicals, it is specifically related to levofloxacin preparation technique field.

Background technology

Levofloxacin (LevofloxacinHydrochloride) is the left-handed optical activity L-type isomer of Ofloxacine USP 23, and its anti-microbial activity is about 2 times of Ofloxacine USP 23, has has a broad antifungal spectrum, a feature that anti-microbial effect is strong. To most of enterobacteriaceae lactobacteriaceae, as the gram-negative bacterias such as escherichia coli, Klebsiella, Serratia, proteus, Shigella, Salmonella, citrobacter, acinetobacter and Pseudomonas aeruginosa, hemophilus influenzae, gonococcus have stronger anti-microbial activity. The gram positive organisms such as part methicillin-sensitivity staphylococcus, streptococcus pneumoniae, micrococcus scarlatinae, Hemolytic streptococcus and legionella, mycoplasma, chlamydozoan also there are is good anti-microbial effect, but the effect of anerobe and faecalis is poor.

Traditional method preparing levofloxacin hydrochloride sodium chloride injection, due to the defect in technique, after such as usually all raw material weighing is good during its preparation injection, add in the lump in charging tank, stirring and dissolving, due to different supplementary material different solubilities, the composition that solubleness is not good cannot dissolve completely, cause active constituent content not enough, affect the validity of product, in addition, the using method of Medicinal Charcoal routine directly joins in liquid, due to its light weight, easily assemble and float on liquid surface, disperse uneven, have impact on its adsorption effect, and, it easily disperses, deal with improperly and can pollute clean area and air conditioning and cleaning system, in conventional technique, also may there is the selection of pH scope or regulate improper, filter abundant not, sterilization temperature and mode are improper etc., cause the levofloxacin hydrochloride sodium chloride injection color adopting traditional method to prepare dark, clarity is poor, particulate is many, less stable, thus cause Clinical practice effect & Safety not good. not easily preserve, and result of use is not good, cause result for the treatment of not good.

Summary of the invention

The present invention proposes the preparation method of a kind of levofloxacin hydrochloride sodium chloride injection, solves in prior art the problems such as levofloxacin hydrochloride sodium chloride injection color is dark, clarity is poor, particulate is many, less stable, Clinical practice effect & Safety are not good.

The technical scheme of the present invention is prescription:

Further, prescription is preferably:

On the other hand, the technical scheme of the present invention is prepared by following preparation method:

(1) take 2-amino-3-tolyl acid, Glacial acetic acid, citric acid by recipe quantity, and add 25-45 DEG C of water for injection stirring and dissolving, inject water to the 20% of preparation cumulative volume;

(2) join after taking levofloxacin hydrochloride predissolve by recipe quantity in solution prepared by (1) step, and inject water to the 50% of preparation cumulative volume, stirring and dissolving, obtain just mixed liquid;

(3) add in solution sodium hydroxide then adjust ph to 6.5-7.0; Add injection water to full amount;

(4) 0.22 ��m of filtering with microporous membrane, are filled in the infusion bottle of sterilizing in advance by filtrate;

(5) 121 DEG C of hot steam sterilizers 20-30 minute;

(6) filtrate carries out assay, pH value and visible foreign matters inspection;

(7) carry out plug filling, upper after passed examination, roll lid, sterilizing, lamp inspection, packaging.

Compared with prior art, the Gatifloxacin and sodium chloride injection that the present invention relates to and its preparation method have following advantage and marked improvement:

(1) the injection stability prepared is higher, safe and reliable. Citric Acid is joined in levofloxacin injection liquid by the present invention, surprisingly finding through accelerated test, no longer there is precipitate in injection liquid, achieves unexpected effect, it is relevant that this may be easier to complexation of metal ions with citric acid, improves the security of medication well.

(2) preparation technology of injection liquid of the present invention is simple, is applicable to big production requirement.

Specific embodiment

Embodiment 1:

(1) prescription:

(2) preparation technology: take 2-amino-3-tolyl acid, Glacial acetic acid, citric acid by recipe quantity, and add 35 DEG C of water for injection stirring and dissolving, injects water to the 20% of preparation cumulative volume; Join after taking levofloxacin hydrochloride predissolve by recipe quantity in solution prepared by (1) step, and inject water to the 50% of preparation cumulative volume, stirring and dissolving, obtain just mixed liquid; Add in solution sodium hydroxide then adjust ph to 6.5-7.0; Add injection water to full amount; 0.22 ��m of filtering with microporous membrane, is filled in the infusion bottle of sterilizing in advance by filtrate; 121 DEG C of hot steam sterilizers 20-30 minute; Filtrate carries out assay, pH value and visible foreign matters inspection; Carry out plug filling, upper after passed examination, roll lid, sterilizing, lamp inspection, packaging.

Embodiment 2:

(1) prescription:

(2) preparation technology: take 2-amino-3-tolyl acid, Glacial acetic acid, citric acid by recipe quantity, and add 35 DEG C of water for injection stirring and dissolving, injects water to the 20% of preparation cumulative volume; Join after taking levofloxacin hydrochloride predissolve by recipe quantity in solution prepared by (1) step, and inject water to the 50% of preparation cumulative volume, stirring and dissolving, obtain just mixed liquid; Add in solution sodium hydroxide then adjust ph to 6.5-7.0; Add injection water to full amount; 0.22 ��m of filtering with microporous membrane, is filled in the infusion bottle of sterilizing in advance by filtrate; 121 DEG C of hot steam sterilizers 20-30 minute; Filtrate carries out assay, pH value and visible foreign matters inspection; Carry out plug filling, upper after passed examination, roll lid, sterilizing, lamp inspection, packaging.

Embodiment 3: the visible foreign matters of levofloxacin hydrochloride injection liquid and assay

In order to verify the stability of levofloxacin hydrochloride injection liquid prepared by the present invention, the injection liquid that specification sheets embodiment 1 of the present invention prepared, contrast A (injection liquid that CN101693008 embodiment 1 prepares), contrast B (injection liquid that CN103479522 specific embodiment prepares) three carry out the comparison of visible foreign matters inspection, assay. Experimentation result is as follows:

1. visible foreign matters inspection. Extract each embodiment sample, under being placed in 40 DEG C of environment, carry out accelerating to investigate. The results are shown in Table 1.

2. assay. Chromatographic column Shim-packGLC-ODS post (4.6mm �� 150mm, 5 ��m); Moving phase 0.02mol/L potassium dihydrogen phosphate (is adjusted to pH4.0 with phosphoric acid)-acetonitrile (85:15, containing 2mmol/L Tetrabutylammonium bromide); Flow velocity 1.0ml/min; Determined wavelength 292nm; Sample size 20 �� l; Post temperature is room temperature. The results are shown in Table 2.

Embodiment sample visible foreign matters measurement result before and after table 1 accelerated test

Embodiment samples contg measurement result before and after table 2 accelerated test

Sample source	0 day result	40 DEG C are accelerated 15 days results	40 DEG C are accelerated 180 days results
				Embodiment 1	99.9%	99.9%	99.9%
Contrast A	99.9%	99.5%	94.0%
				Contrast B	99.9%	98.2%	91.5%

From the experimental result of table 1, table 2 it will be seen that embodiment of the present invention sample is through accelerating to investigate, have no visible foreign matters, optimal stability.

Claims (3)

1. a levofloxacin hydrochloride sodium chloride injection, is characterised in that its prescription is:

2. injection liquid according to claim 1, is characterised in that its prescription is:

3. prepare a method for levofloxacin hydrochloride injection liquid, comprise the following steps:

(1) take the 2-amino-3-tolyl acid of 0.1-0.2g, the Glacial acetic acid of 10-15ml, the citric acid of 10-15ml, and add 25-45 DEG C of water for injection stirring and dissolving, inject water to 200ml;

(2) join after taking the levofloxacin hydrochloride predissolve of 20g in solution prepared by (1) step, and inject water to 500ml, stirring and dissolving, obtain just mixed liquid;

(3) add in solution sodium hydroxide then adjust ph to 6.5-7.0; Add injection water to 1000ml;

(4) 0.22 ��m of filtering with microporous membrane, are filled in the infusion bottle of sterilizing in advance by filtrate;

(5) 121 DEG C of hot steam sterilizers 20-30 minute;

(6) filtrate carries out assay, pH value and visible foreign matters inspection;

(7) carry out plug filling, upper after passed examination, roll lid, sterilizing, lamp inspection, packaging.