CN104352455A - Cefalexin injection - Google Patents

Abstract

The invention discloses a method for preparing a cefalexin injection. The injection contains the ingredients in parts by weight: 2-5 parts of cefalexin, 1-5 parts of PVC, 1-2 parts of ethyl cellulose, 1-3 parts of lecithin, 0.5-1 part of fatty acid sorbitan, 0.5-1 part of polysorbate and 1-3 parts of PEG. The injection is high in drug stability, good in solubility and simple in preparation process.

Description

A kind of cefalexin injection

Technical field

The present invention relates to a kind of animal-use drug, particularly relate to a kind of preparation method of cefalexin injection.

Background technology

Cefalexin chemical name is: (6R, 7R)-3-methyl-7-[(R)-2-amino-2-phenylacetylamino]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formic acid-hydrate.Cefalexin belongs to first generation cephalosporin, except Enterococcus, methicillin-resistant Staphylococci, and streptococcus pneumoniae, Hemolytic streptococcus, product or not produce the staphylococcic most of bacterial strain of penicillinase responsive to this product.This product has better antibacterial action to neisseria, but the sensitivity of hemophilus influenza to this product is poor; This product has certain antibacterial action to part escherichia coli, proteus mirabilis, salmonella and shigella dysenteriae.All the other enterobacteriaceae lactobacteriaceaes, acinetobacter calcoaceticus, Pseudomonas aeruginosa, bacteroides fragilis all present drug resistance to this product.Fusobacterium and Wei Rong coccus are generally responsive to this product, and anaerobism gram positive coccus is to this product medium sensitivity.Be applicable to the respiratory tract infection such as the acute tonsillitis caused by sensitive organism, angina, otitis media, sinusitis, bronchitis, pneumonia, urinary tract infection and skin soft-tissue infection etc.This product is dissolved in methanol/ethanol, does not dissolve in water.

Cefalexin is used for the treatment of animal body by the present invention.

Summary of the invention

The invention provides a kind of preparation method of cefalexin injection; This injection has the features such as solubility is good, good stability, and drug loading is high, safety of clinical trials is good, overcomes the deficiencies in the prior art part.

In injection, the ratio of each component is cefalexin 1-5 part; PVC1-5 part; Ethyl cellulose 1-2 part; Lecithin 1-3 part; The smooth 0.5-1 part of fatty acid Pyrusussuriensis; Polysorbate 0.5-1 part; PEG1-3 part.

Described PVC molecular weight is between 5000-20000.

As preferably, emulsifying agent is the mixture of the smooth and Polysorbate of fatty acid Pyrusussuriensis, and its ratio is than being 0.5:1-1:2.

As preferably, PVC is 3-5 part.

As preferably, fatty acid Pyrusussuriensis used is smooth is fatty acid Pyrusussuriensis smooth 80,40,20; Polysorbate is polyoxyethylene sorbitan monoleate, 40,20.

As preferably, ethyl cellulose is selected from ethyl cellulose-4000 or ethyl cellulose-6000.

The preparation method of above-mentioned injection cefalexin, comprises the steps:

(1) each component is taken by formula proportion;

(2) cefalexin and ethyl cellulose, lecithin add in water for injection successively, and stirring and dissolving obtains interior aqueous phase W1;

(3) PVC, fatty acid Pyrusussuriensis is smooth and Polysorbate is dissolved in volume ratio is in the dichloromethane/acetone of 3: 1, obtains oil phase;

(4) PEG adds in water for injection to be stirred to and dissolves completely, obtains outer aqueous phase W2;

(5) under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Slowly added in W2 by colostrum and stir 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of sodium chloride, ice bath stirs 4h volatile residue organic solvent, and collect microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.

Detailed description of the invention

Embodiment 1: a kind of injection cefalexin

Cefalexin 500g;

PVC400g；

Ethyl cellulose 100g;

Lecithin 100g;

The smooth 2050g of fatty acid Pyrusussuriensis;

Polysorbate 40 50g;

PEG100g；

Cefalexin, ethyl cellulose and lecithin are added successively in 1000mL water for injection, stirring and dissolving obtains interior aqueous phase W1; It is in the 1000mL dichloromethane/acetone of 3: 1 that smooth for fatty acid Pyrusussuriensis 20, polysorbate 40 are dissolved in volume ratio, obtains oil phase; PEG is added in water for injection to be stirred to and dissolve completely, obtain outer aqueous phase W2; Under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Colostrum is slowly added in W2 and stirs 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of 1000mL sodium chloride, ice bath stirs 4h volatile residue organic solvent, collects microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.

Embodiment 2: a kind of injection cefalexin

Cefalexin 300g;

PVC200g；

Ethyl cellulose 300g;

Lecithin 200g

The smooth 8050g of fatty acid Pyrusussuriensis;

Polysorbate 40 50g;

PEG50g。

Cefalexin, ethyl cellulose and lecithin are added successively in 1000mL water for injection, stirring and dissolving obtains interior aqueous phase W1; It is in the 1000mL dichloromethane/acetone of 3: 1 that smooth for fatty acid Pyrusussuriensis 20, polysorbate 40 are dissolved in volume ratio, obtains oil phase; PEG is added in water for injection to be stirred to and dissolve completely, obtain outer aqueous phase W2; Under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Colostrum is slowly added in W2 and stirs 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of 1000mL sodium chloride, ice bath stirs 4h volatile residue organic solvent, collects microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.

Embodiment 3: a kind of injection cefalexin

Cefalexin 400g;

PVC100g；

Ethyl cellulose 100g;

Lecithin 100g

The smooth 2050g of fatty acid Pyrusussuriensis;

Polyoxyethylene sorbitan monoleate 50g;

Glycerol 100g;

Cefalexin, ethyl cellulose and lecithin are added successively in 1000mL water for injection, stirring and dissolving obtains interior aqueous phase W1; It is in the 1000mL dichloromethane/acetone of 3: 1 that smooth for fatty acid Pyrusussuriensis 20, polysorbate 40 are dissolved in volume ratio, obtains oil phase; PEG is added in water for injection to be stirred to and dissolve completely, obtain outer aqueous phase W2; Under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Colostrum is slowly added in W2 and stirs 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of 1000mL sodium chloride, ice bath stirs 4h volatile residue organic solvent, collects microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.

Embodiment 4: droplet measurement

The injection of Example 1-3, is dissolved in water into the solution of every 1mL containing 1mg cefalexin, measures with laser diffraction particle size instrument.The cefalexin injection that acetonideexample 1-3 prepares is spherical shape, and even particle size distribution, whole particle diameter is between 300-550nm.

Embodiment 5: envelop rate detects

The injection of cefalexin is dissolved in water into the solution of every 1mL containing cefalexin 1mg, with the centrifugation 15min of 6000r/min, gets supernatant 1mL, with dissolve with ethanol, measure the content of cefalexin.

Dose in envelop rate=microsphere/(dose in the dose+medium in microsphere) × 100%

The envelop rate of injection prepared by embodiment 1-3, between 80%-90%.

Embodiment 6: dissolution velocity is investigated

Each two bottles of injection in random selecting embodiment 1-3, numbering 1-6, sample number into spectrum 7 after physical mixed, the cefalexin freeze-dried powder numbering 8 of having gone on the market, by the dissolving method of clinical application, inject 10mL water for injection respectively, eddy mixer jolts, completely clear and bright for index to dissolve, calculate dissolution velocity.

Experimental result shows that the dissolution velocity of injection of the present invention is obviously better than the injection of direct packaging.

Embodiment 7: study on the stability

The injection that the sample prepared by embodiment 1-3 and raw material directly mix subpackage is placed in high temperature 40 DEG C, lower 6 months of relative humidity 75% ± 5% condition respectively, carries out acceleration and investigates.

Claims (6)

1. a cefalexin injection, is characterized in that the parts by weight of component are:

Cefalexin 1-5 part;

PVC1-5 part;

Ethyl cellulose 1-2 part;

Lecithin 1-3 part;

The smooth 0.5-1 part of fatty acid Pyrusussuriensis;

Polysorbate 0.5-1 part;

PEG1-3 part;

Described PVC molecular weight is between 5000-20000.

2. pharmaceutical composition as claimed in claim 1, it is characterized in that described emulsifying agent is the mixture of the smooth and Polysorbate of fatty acid Pyrusussuriensis, its ratio is than being 0.5:1-1:2.

3. pharmaceutical composition as claimed in claim 1, is characterized in that PVC is 3-5 part.

4. pharmaceutical composition as claimed in claim 1, it is characterized in that fatty acid Pyrusussuriensis used smooth be fatty acid Pyrusussuriensis smooth 80,40,20; Polysorbate is polyoxyethylene sorbitan monoleate, 40,20.

5. pharmaceutical composition as claimed in claim 1, is characterized in that described ethyl cellulose is selected from ethyl cellulose-4000 or ethyl cellulose-6000.

6. the preparation method of injection cefalexin as described in claim arbitrary in claim 1-5, comprises the steps:

(1) each component is taken by formula proportion;

(2) cefalexin and ethyl cellulose, lecithin add in water for injection successively, and stirring and dissolving obtains interior aqueous phase W1;

(3) PVC, fatty acid Pyrusussuriensis is smooth and Polysorbate is dissolved in volume ratio is in the dichloromethane/acetone of 3: 1, obtains oil phase;

(4) PEG adds in water for injection to be stirred to and dissolves completely, obtains outer aqueous phase W2;

(5) under agitation slowly added in oil phase by W1, under ice bath, supersound process 20s obtains colostrum; Slowly added in W2 by colostrum and stir 10min and obtain emulsion, poured into by emulsion in the aqueous solution for injection of sodium chloride, ice bath stirs 4h volatile residue organic solvent, and collect microsphere by 0.45 μm of filtering with microporous membrane, water for injection washs 3 times, vacuum lyophilization.