CN104337775A - Naproxen injection - Google Patents

Abstract

The invention discloses a preparation method for naproxen injection. The naproxen injection comprises the following components in parts by weight: 2 to 5 parts of naproxen, 1 to 5 parts of PVA (polyvinyl alcohol), 1 to 2 parts of lecithin , 0.5 to 1 part of sorbitan fatty acid, 0.5 to 1 part of polysorbate and 1 to 3 parts of PEG (polyethylene glycol). The naproxen injection is high in stability and solubility, and the preparation process is simple.

Description

A kind of naproxen injection

Technical field

The present invention relates to a kind of preparation method of naproxen injection.

Background technology

Naproxen has another name called (+)-Alpha-Methyl-6-methoxyl-2-naphthylacetic acid, is a kind of NSAID (non-steroidal anti-inflammatory drug), has the effect of antipyretic-antalgic antiinflammatory, can suppress the synthesis of prostaglandin and play anti-inflammatory and analgesic effect.For alleviating mild to moderate pain, as arthralgia, neuralgia, myalgia, migraine, headache, dysmenorrhea, toothache.This product is dissolved in methanol/ethanol, does not dissolve in water.

Summary of the invention

The invention provides a kind of preparation method of naproxen 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 naproxen 1-5 part; PVA1-5 part; PVP1-2 part; Lecithin 1-3 part; The smooth 0.5-1 part of fatty acid Pyrusussuriensis; Polysorbate 0.5-1 part; PEG1-3 part.Described PVA 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, PVA is 3-5 part.

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

As preferably, PVP is selected from PVP-4000 or PVP-6000.

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

(1) each component is taken by formula proportion;

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

(3) PVA, 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 naproxen

Naproxen 500g;

PVA400g；

PVP100g；

Lecithin 100g;

The smooth 2050g of fatty acid Pyrusussuriensis;

Polysorbate 40 50g;

PEG100g；

Naproxen, PVP 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 naproxen

Naproxen 300g;

PVA200g；

PVP300g；

Lecithin 200g

The smooth 8050g of fatty acid Pyrusussuriensis;

Polysorbate 40 50g;

PEG50g。

Naproxen, PVP 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 note injection naproxen

Naproxen 400g;

PVA100g；

PVP100g；

Lecithin 100g

The smooth 2050g of fatty acid Pyrusussuriensis;

Polyoxyethylene sorbitan monoleate 50g;

Glycerol 100g;

Naproxen, PVP 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 naproxen, measures with laser diffraction particle size instrument.The naproxen 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 naproxen is dissolved in water into the solution of every 1mL containing naproxen 1mg, with the centrifugation 15min of 6000r/min, gets supernatant 1mL, with dissolve with ethanol, measure the content of naproxen.

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 naproxen 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 naproxen injection, is characterized in that the parts by weight of component are:

Naproxen 1-5 part;

PVA1-5 part

PVP1-2 part;

Lecithin 1-3 part;

The smooth 0.5-1 part of fatty acid Pyrusussuriensis;

Polysorbate 0.5-1 part;

PEG1-3 part;

Described PVA 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 PVA 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 PVP is selected from PVP-4000 or PVP-6000.

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

(1) each component is taken by formula proportion;

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

(3) PVA, 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.