CN102988304B - Medicinal composition containing lysine hydrochloride compound - Google Patents
Medicinal composition containing lysine hydrochloride compound Download PDFInfo
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- CN102988304B CN102988304B CN201210303729.7A CN201210303729A CN102988304B CN 102988304 B CN102988304 B CN 102988304B CN 201210303729 A CN201210303729 A CN 201210303729A CN 102988304 B CN102988304 B CN 102988304B
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- lysine hydrochloride
- mannitol
- vitamin
- trisodium citrate
- disodiumhydrogen
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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
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 controlling people bulk-growth to press down most important in long element be also the most essential composition, nervus centralis and peripheral nervous system to people all play an important role.Now research shows that lysine also bringing into play curative effect in treatment craniocerebral trauma, chronic cerebral tissue ischemia, Hypoxic disease simultaneously, and its chemical structural formula is as follows:
The lysine hydrochloride injection having gone on the market has lyophilization injectable powder, soluble in water because of lysine hydrochloride, in its formula, generally only use mannitol as filler, but find in practice, the problem that has color jaundice after existing medicament long storage time, needs 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 medicament long storage time also can not be turned to be yellow, and makes dissolution velocity improve simultaneously.
Summary of the invention
The invention provides a kind of pharmaceutical composition that contains lysine hydrochloride compound, is the injection freeze-dried pharmaceutical formulation take lysine hydrochloride as active component, and every 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 formula is: every 1000 injections, by the component of following proportioning, made:
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 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 prepare DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml, then get lysine hydrochloride, mannitol, EDTA calcium, vitamin C adds mixed dissolution in DisodiumHydrogen Citrate and trisodium citrate buffer, the filter membrane of via hole diameter molecular cut off 20000 filters, fill, half tamponade, lyophilization, obtains.
The present invention has used DisodiumHydrogen Citrate and trisodium citrate buffer to make the solution pH value obtaining of the present invention remain on 6.9-7.1, and fluctuation range is minimum, guarantees its stability.
Adopt High-dose Mannitol that powder dissolution speed after 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 formula obtains through screening, and wherein most preferred formula composition, referring to embodiment 1.Screening process is as follows:
Table 1: the formula screening experiment take dissolution time as index
The more than medicine of formula, wiring solution-forming, packing capacity into is 5ml ampulla, with the method for embodiment 1, is prepared into lyophilized formulations, carries out dissolution experiment again.
Sample:
Each 10 bottles of the sample of each formula, every bottle adds sodium chloride for injection solution 5ml, with hand moving.
Dissolve index:
Naked eyes are seen without floccule and are existed for whole dissolvings.
Table 2, investigates the indices result of embodiment 1 and the lysine hydrochloride sample that gone on the market
| Embodiment 1 sample | The lysine hydrochloride sample having 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, the lysine hydrochlorate for injection sample that gone on the market, detects 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 having gone on the market.Another experimental group room temperature is placed 90 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 60 days in addition, and the fluctuation range of embodiment 1 solution pH value is 6.9-7.1, and the lysine hydrochloride having gone on the market is 6.7～7.4.
Dissolution velocity test:
The lyophilized injectable powder of the present invention of preparing by the method for the embodiment of the present invention 1 and the lysine hydrochloride lyophilized injectable powder having gone on the market carry out dissolution velocity test, result demonstration, and the product dissolution velocity of the embodiment of the present invention 1 is higher than matched group.
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 to 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 having 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% |
Drug standard requires the content of impurity should not be greater than 1.5%.From table, the sample of the more commercially available formula preparation of the present invention is more stable, can at 2 ~ 8 ℃ of conventional refrigeration temperature, preserve 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 market of the present invention.Carried out the research of stability test, result shows that stability of the present invention is better than the product on 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, meets 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) by recipe quantity, take supplementary material
(2), by 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 solution, is stirred to dissolve completely.Stirring makes 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 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 (1)
1. containing a pharmaceutical composition for lysine hydrochloride, is freeze-dried pharmaceutical formulation, and every 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: first prepare DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml, then get lysine hydrochloride, mannitol, EDTA calcium, vitamin C adds mixed dissolution in DisodiumHydrogen Citrate and trisodium citrate buffer, and the filter membrane of via hole diameter molecular cut off 20000 filters, fill, half tamponade, lyophilization, obtains.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210303729.7A CN102988304B (en) | 2012-07-12 | 2012-08-22 | Medicinal composition containing lysine hydrochloride compound |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210240257.5 | 2012-07-12 | ||
| CN201210240257 | 2012-07-12 | ||
| CN201210303729.7A CN102988304B (en) | 2012-07-12 | 2012-08-22 | Medicinal composition containing lysine hydrochloride compound |
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| Publication Number | Publication Date |
|---|---|
| CN102988304A CN102988304A (en) | 2013-03-27 |
| CN102988304B true CN102988304B (en) | 2014-04-16 |
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| CN201210303729.7A Active CN102988304B (en) | 2012-07-12 | 2012-08-22 | Medicinal composition containing lysine hydrochloride compound |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1631360A (en) * | 2003-12-23 | 2005-06-29 | 武汉佑德医药科技有限公司 | Freeze dried injection of lysine hydrochloride and its preparation process |
| CN1695606A (en) * | 2005-05-25 | 2005-11-16 | 冯东 | Technique for producing re-dissolvable lysine hydrochloride in use for injection |
| CN1754534A (en) * | 2004-09-29 | 2006-04-05 | 北京蓝贝望医药科技开发有限公司 | Lysine hydrochlorate for injection and its preparation method |
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2012
- 2012-08-22 CN CN201210303729.7A patent/CN102988304B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1631360A (en) * | 2003-12-23 | 2005-06-29 | 武汉佑德医药科技有限公司 | Freeze dried injection of lysine hydrochloride and its preparation process |
| CN1754534A (en) * | 2004-09-29 | 2006-04-05 | 北京蓝贝望医药科技开发有限公司 | Lysine hydrochlorate for injection and its preparation method |
| CN1695606A (en) * | 2005-05-25 | 2005-11-16 | 冯东 | Technique for producing re-dissolvable lysine hydrochloride in use for injection |
Non-Patent Citations (1)
| Title |
|---|
| 梁玉南.（二）抗氧剂.《医药商业药品质量管理》.中国医药科技出版社,1989, * |
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| CN102988304A (en) | 2013-03-27 |
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