CN102988304A - Medicinal composition containing lysine hydrochloride compound - Google Patents

Abstract

The invention relates to a medicinal composition containing a lysine hydrochloride compound, and in particular relates to freeze-dried injection of lysine hydrochloride and a preparation method thereof. Each 1,000 injections are prepared from the following components: 3,000g of lysine hydrochloride, 100 to 200g of mannitol, 1 to 3g of ethylene diamine tetraacetic acid (EDTA) calcium, 1 to 2g of vitamin C, and 2,000ml of buffer solution of disodium hydrogen citrate and trisodium citrate in a mole ratio of 1:4.

Description

A kind of pharmaceutical composition that contains the lysine hydrochloride chemical compound

Technical field

The present invention relates to freeze-dried powder of a kind of lysine hydrochloride and preparation method thereof, belong to field of medicaments.

Background technology

Lysine, English name: lysine is one of essential amino acid, in recent years, scientist finds, lysine be the important substance of control people bulk-growth to press down most important in the long element also be the most essential composition, people's nervus centralis and peripheral nervous system all played an important role.Now research shows that simultaneously lysine also bringing into play curative effect in treatment craniocerebral trauma, chronic brain tissue ischemia, Hypoxic disease, and its chemical structural formula is as follows:

The lysine hydrochloride injection that has gone on the market has the lyophilization injectable powder, soluble in water because of lysine hydrochloride, generally only use mannitol as filler in its prescription, but find in the practice, the problem of color jaundice is arranged after the existing medicament long storage time, need low temperature storage.Some product dissolution velocity in clinical use procedure is undesirable, causes and uses inconvenience, the invention provides a kind of new prescription and preparation method, and the medicament long storage time also can not turned to be yellow, and dissolution velocity is improved.

Summary of the invention

The invention provides a kind of pharmaceutical composition that contains the lysine hydrochloride chemical compound, is the injection freeze-dried pharmaceutical formulation take lysine hydrochloride as active component, and per 1000 injections are made by the component of following proportioning:

Lysine hydrochloride 3000g;

Mannitol 100-200g;

EDTA calcium 1-3g;

Vitamin C 1-2g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4.

Compositions of the present invention, most preferred prescription is: per 1000 injections, made by the component of following proportioning:

Lysine hydrochloride 3000g;

Mannitol 150g;

EDTA calcium 2g;

Vitamin C 1.5g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4,

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

Compositions of the present invention, its preparation method is as follows: prepare first DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml, then get lysine hydrochloride, mannitol, EDTA calcium, vitamin C adds mixed dissolution in DisodiumHydrogen Citrate and the trisodium citrate buffer, the filter membrane of via hole diameter molecular cut off 20000 filters, fill, half tamponade, lyophilization, and get final product.

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

Adopt High-dose Mannitol that the powder dissolution speed after the lyophilizing is accelerated, use EDTA calcium and vitamin C to guarantee that it places in use the long period and also can not change, guarantee its stability.

Compositions of the present invention, its prescription obtains through screening, and wherein most preferred prescription forms, referring to embodiment 1.Screening process is as follows:

Table 1: the prescription screening experiment take dissolution time as index

The above medicine of prescription, wiring solution-forming, the capacity of packing into are the 5ml ampulla, are prepared into lyophilized formulations with the method for embodiment 1, carry out again dissolution experiment.

Sample:

Each 10 bottles in the sample of each prescription, every bottle adds sodium chloride for injection solution 5ml, with hand moving.

The dissolving index:

Naked eyes are seen without floccule and are existed for whole dissolvings.

Table 2 is investigated embodiment 1 and the indices result of the lysine hydrochloride sample that gone on the market

	Embodiment 1 sample	The lysine hydrochloride sample that has gone on the market
			Mouldability	Good	Generally
Dissolubility	Good	Generally
			Water content	4.65%	4.86%
Condition of storage	Room temperature	4-8℃

As seen from table, embodiment 1 is better than reference substance.

Table 3 is investigated embodiment 1 and three batches in the lysine hydrochlorate for injection sample that gone on the market, detection heavy metal and impurity content:

From test data, the three batches of injection heavy metals and the impurity content of embodiment 1 are less than the medicine that has gone on the market.Another experimental group room temperature was placed 90 days, detected three batches of heavy metal and impurity contents, result such as following table again:

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

The laboratory sample room temperature was placed 60 days in addition, and the fluctuation range of embodiment 1 solution pH value is 6.9-7.1, and the lysine hydrochloride that has gone on the market is 6.7～7.4.

The dissolution velocity test:

Carry out the dissolution velocity test with the lyophilized injectable powder of the present invention of the method for the embodiment of the invention 1 preparation and the lysine hydrochloride lyophilized injectable powder that has gone on the market, result's demonstration, the product dissolution velocity of the embodiment of the invention 1 is higher than matched group.

The storage-stable test

Embodiment 1 and the lysine hydrochloride lyophilized injectable powder that gone on the market the lower storage of conventional refrigeration temperature (2 ~ 8 ℃) 18 months, take impurity as investigating index, are carried out long-time stability and investigate test.The results are shown in following table:

Different prescriptions long-time stability under 2 ~ 8 ℃ of holding conditions

Minute	Embodiment 1	The lysine hydrochloride lyophilized injectable powder that has gone on the market
			0 month	0.83%	0.79%
June	1.05%	1.18%
			December	1.25%	1.39%
18 months	1.48%	1.86%

The content of drug standard requirement impurity should be greater than 1.5%.By table as seen, the sample of the more commercially available formula preparation of the present invention is more stable, can be 2 ~ 8 ℃ of lower storages of conventional refrigeration temperature 18 months, and product quality still meets the national drug standards, and contrast can only store 12 months.

To the freeze dried injection that contains lysine hydrochloride of buying on the market of the present invention.Carried out the research of stability test, the result shows that stability of the present invention is better than the product on the market.

New lysine hydrochlorate for injection freeze-drying medicinal composition provided by the invention has good stability, and invariant color does not stimulate during injection, and better tolerance is dissolved the multiple advantages such as rapid, easy to use, satisfies greatly patient's needs.

Specific implementation method

By following specific embodiment the present invention is further detailed, but not as restriction.

Embodiment 1

Lysine hydrochloride 3000g;

Mannitol 150g;

Propylene glycol 1.5g

EDTA calcium 2g;

Vitamin C 1.5g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;

Preparation method

(1) takes by weighing supplementary material by recipe quantity

(2) with mannitol, propylene glycol, it is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4 that EDTA calcium, vitamin C add mol ratio, stirring and dissolving.

(3) lysine hydrochloride that adds recipe quantity joins in the solution, stirs to make dissolve complete.Stirring makes mix homogeneously.

(4) surveying the solution pH value, is 7.0.

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

(6) according to measurement result, with the volume about 2ml with 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 dry 4h again.

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

Embodiment 2

Lysine hydrochloride 3000g;

Mannitol 100g;

Propylene glycol 1.5g

EDTA calcium 1g;

Vitamin C 1g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;

Preparation method

With embodiment 1

Embodiment 3

Lysine hydrochloride 3000g;

Mannitol 200g;

Propylene glycol 1.5g

EDTA calcium 3g;

Vitamin C 2g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;

Preparation method

With embodiment 1.

Claims (3)

1. a pharmaceutical composition that contains lysine hydrochloride is freeze-dried pharmaceutical formulation, and per 1000 injections are made by the component of following proportioning:

Lysine hydrochloride 3000g;

Mannitol 100-200g;

EDTA calcium 1-3g;

Vitamin C 1-2g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;

The preparation method of described compositions is as follows: prepare first DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml, then get lysine hydrochloride, mannitol, EDTA calcium, vitamin C adds mixed dissolution in DisodiumHydrogen Citrate and the trisodium citrate buffer, and the filter membrane of via hole diameter molecular cut off 20000 filters, fill, half tamponade, lyophilization, and get final product.

2. the pharmaceutical composition of claim 1 is characterized in that, per 1000 injections are made by the component of following proportioning:

Lysine hydrochloride 3000g;

Mannitol 150g;

EDTA calcium 2g;

Vitamin C 1.5g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4,

Preparation method is as follows: prepare first DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml, then get lysine hydrochloride, mannitol, EDTA calcium, vitamin C adds mixed dissolution in DisodiumHydrogen Citrate and the trisodium citrate buffer, and the filter membrane of via hole diameter molecular cut off 20000 filters, fill, half tamponade, lyophilization, and get final product.

3. the preparation method of pharmaceutical composition according to claim 1 is characterized in that, is processed into by following composition: lysine hydrochloride 3000g;

Mannitol 100-200g;

EDTA calcium 1-3g;

Vitamin C 1-2g,

Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;

The preparation method of described compositions is as follows: prepare first DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml, then get lysine hydrochloride, mannitol, EDTA calcium, vitamin C adds mixed dissolution in DisodiumHydrogen Citrate and the trisodium citrate buffer, and the filter membrane of via hole diameter molecular cut off 20000 filters, fill, half tamponade, lyophilization, and get final product.