CN103040733B

CN103040733B - Pharmaceutical composition containing nalmefene hydrochloride compound

Info

Publication number: CN103040733B
Application number: CN201210302027.7A
Authority: CN
Inventors: 姚云
Original assignee: Individual
Current assignee: Luo Cheng
Priority date: 2012-07-12
Filing date: 2012-08-22
Publication date: 2014-02-26
Anticipated expiration: 2032-08-22
Also published as: CN103040733A

Abstract

The invention relates to a pharmaceutical composition containing a nalmefene hydrochloride compound. For every 1000 injections, the pharmaceutical composition comprises the following components: 100mg of nalmefene hydrochloride, 1-2g of Tween 80, 1-3g of EDTA (Ethylene Diamine Tetraacetic Acid) calcium, 1-2g of vitamin C, 1000ml of sodium hydrogencitrate and trisodium citrate buffer liquor with molar ratio of 1:4, and the balance of water for injection.

Description

A kind of pharmaceutical composition that contains nalmefene hydrochloride compound

Technical field

The present invention relates to injection preparation of a kind of nalmefene hydrochloride and preparation method thereof, belong to field of medicaments.

Background technology

Nalmefene (nalmefene) is a species specificity morphine receptor blocker, and structure is the naltrexone analog of 6 methylene, and this medicine is to synthesize for 1975, and in nineteen ninety-five listing, now gradually becomes the substitute products of naloxone.Compare with naloxone, nalmefene has the features such as long action time, route of administration is many, bioavailability is high, untoward reaction is little, clinical application is extensive, the symptoms such as the respiration inhibition having caused for antagonism opioid analgesics, calmness and hypotension, and be applied to the treatment of alcoholism and heroin dependence etc.

The nalmefene hydrochloride preparation having gone on the market is injection, belongs to injection liquid drugs injection, due to unstable under nalmefene hydrochloride room temperature, during storage for avoiding medicine variable color to need low temperature storage.Deposit pH value in process and easily fluctuate, need to add activated carbon decolorizing in production process, easily cause containing quantity not sufficient, product the invention provides prescription and the preparation method that a kind of Nalmefene hydrochloride injection is new, has overcome above-mentioned defect.

Summary of the invention

The invention provides a kind of pharmaceutical composition that contains nalmefene hydrochloride compound, is to take the injection liquid drugs injection preparation that nalmefene hydrochloride is active component, it is characterized in that, and every 1000 injections, it is composed as follows:

Nalmefene hydrochloride 100mg;

Tween 80 1-2g;

EDTA calcium 1-3g;

Vitamin C 1-2g;

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 1000ml of 1:4;

Water for injection adds to 2L.

Compositions of the present invention, most preferred formula is: every 1000 injections, it is composed as follows:

Nalmefene hydrochloride 100mg;

Tween 80 1g;

EDTA calcium 2g;

Vitamin C 1.5g;

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 1000ml of 1:4,

Water for injection adds to 2L.

Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is as follows: take DisodiumHydrogen Citrate 13g, trisodium citrate 60g is dissolved in the buffer solution that obtains pH value 7.0 in 1000ml water for injection.

Compositions of the present invention, its preparation method is as follows: first join DisodiumHydrogen Citrate and trisodium citrate buffer 1000ml, then get the nalmefene hydrochloride of above-mentioned amount, Tween 80, EDTA calcium, vitamin C adding citric acid buffer dissolves, and then uses water for injection standardize solution to 2000ml, and the filter membrane of via hole diameter molecular cut off 20000 filters, after clarity is qualified, fill, packing, obtains.

The present invention has used DisodiumHydrogen Citrate and trisodium citrate buffer to make the pH obtaining of the present invention remain on 6.9-7.1, and fluctuation range is minimum, guarantees its stability.

Adopt heavy dose of Tween 80 to play hydrotropy effect, use EDTA calcium and vitamin C to guarantee that it places at normal temperatures the long period and also can not change, guarantee its stability.

Compositions of the present invention, its formula obtains through screening, and screening process is as follows:

(1) strong illumination test:

The primary stability result of the test (30 day) of table 1 after strong illumination

?	Formula 1	Formula 2	Formula 3	Formula 4	Formula 5	Formula 6
							Medicament contg %	98.2	98.4	97.2	97.3	99.3	96.0

The formula of 1-6 injection of wherein filling a prescription is composed as follows:

Above evidence 5 stabilizing effects of filling a prescription are best.

The primary stability result of the test of table 2: embodiment 1 injection after strong illumination

The indices result of the Nalmefene hydrochloride injection sample of investigating embodiment 1 and having gone on the market

?	Embodiment 1 sample	The nalmefene hydrochloride sample having gone on the market
			Condition of storage	Room temperature	0-8℃

When room temperature is placed 10 days, embodiment 1 and the Nalmefene hydrochloride injection sample heavy metal of having gone on the market and impurity content are three batches, and result is as following table:

From test data, the three batches of injection heavy metals and the impurity content of embodiment 1 are less than the medicine having gone on the market.

Another group room temperature is placed 100 days, then detects three batches of heavy metal and impurity contents, and result is as following table:

From test data, the three batches of injection heavy metals and the impurity content of embodiment 1 are obviously less than the medicine having gone on the market.

Laboratory sample room temperature is placed 100 days in addition, and the fluctuation range of embodiment 1 solution pH value is 6.9-7.1, and the nalmefene hydrochloride having gone on the market is 6.7～7.4.

Storage-stable test

Embodiment 1 and the Nalmefene hydrochloride injection that gone on the market are preserved 18 months at normal temperatures, take impurity as investigating index, carry out long-time stability and investigate test.The results are shown in following table:

Different prescriptions long-time stability under room temperature storage condition

Minute	Embodiment 1	The Nalmefene hydrochloride injection having gone on the market
			0 month	0.82%	0.61%
June	1.18%	1.02%
			December	1.26%	1.46%
18 months	1.49%	1.89%

From table, the sample of the more commercially available formula preparation of the present invention is more stable, can under normal temperature, preserve 24 months, and product quality still meets the national drug standards, and matched group can only store 12 months.

To what buy on market of the present invention, contain nalmefene hydrochloride injection.Carried out the research of stability test, result shows that stability of the present invention is better than the product on market.

New hydrochloride for injection Nalmefene injection pharmaceutical composition provided by the invention, has good stability, and room temperature is placed, and invariant color does not stimulate during injection, better tolerance, and the multiple advantages such as easy to use, meets patient's needs greatly.

Specific implementation method

Embodiment 1

Nalmefene hydrochloride 100mg;

Tween 80 1g;

EDTA calcium 2g;

Vitamin C 1.5g,

Preparation method

(1) by recipe quantity, take supplementary material

(2) Tween 80, EDTA calcium, vitamin C being added to mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 1000ml of 1:4, stirring and dissolving.

(3) nalmefene hydrochloride of recipe quantity joins in solution, is stirred to dissolve completely.Add sterile water for injection to full dose, stir and make mix homogeneously.

(4) surveying solution pH value, is 7.0.

(5) with the microporous filter membrane fine straining of 0.2 μ m, check solution clarity.

(6) according to measurement result, with the volume of about 2ml by liquid medicine filling in the vial of XiLin.

(7) sample is put into the 18h of 35 ℃ of low-temperature vacuum dryings of 35 ℃ of pre-freeze 4h ， – of freeze dryer lyophilization ， –, 50 ℃ of intensifications are dried 4h again.

(8) lyophilizing finishes, and sample is jumped a queue, gland.

Embodiment 2

Nalmefene hydrochloride 100mg;

Tween 80 1g;

EDTA calcium 1g;

Vitamin C 1g,

Preparation method

With embodiment 1

Embodiment 3

Nalmefene hydrochloride 100mg;

Tween 80 1g

EDTA calcium 3g;

Catergen g,

Preparation method

With embodiment 1.

Claims

1. a pharmaceutical composition that contains nalmefene hydrochloride, is injection formulation, every 1000 injections, and each component is composed as follows:

Nalmefene hydrochloride 100mg;

Tween 80 1-2g;

EDTA calcium 1-3g;

Vitamin C 1-2g;

The preparation method of described compositions is as follows: first join DisodiumHydrogen Citrate and trisodium citrate buffer 1000ml, then get nalmefene hydrochloride, Tween 80, EDTA calcium, vitamin C adding citric acid disodium hydrogen and trisodium citrate buffer dissolve, with water for injection standardize solution to 2000ml, pH, is 7.0, and the filter membrane of via hole diameter molecular cut off 20000 filters, fill, obtains.

2. the pharmaceutical composition of claim 1, is characterized in that, every 1000 injections, and it is composed as follows:

Nalmefene hydrochloride 100mg;

Tween 80 1g;

EDTA calcium 2g;

Vitamin C 1.5g;

With water for injection standardize solution to 2000ml;

3. according to the preparation method of claim 1 pharmaceutical composition, it is characterized in that, by following composition, be processed into:

Nalmefene hydrochloride 100mg;

Tween 80 1-2g;

EDTA calcium 1-3g;

Vitamin C 1-2g;