CN1739530A - Aspirin-Al-lysine for injection - Google Patents
Aspirin-Al-lysine for injection Download PDFInfo
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- CN1739530A CN1739530A CN 200510086400 CN200510086400A CN1739530A CN 1739530 A CN1739530 A CN 1739530A CN 200510086400 CN200510086400 CN 200510086400 CN 200510086400 A CN200510086400 A CN 200510086400A CN 1739530 A CN1739530 A CN 1739530A
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- aspirin
- lysine
- injection
- glycine
- aspisol
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Abstract
The present invention relates to one kind of aspirin-DL-lysine for injection, and the aspirin-DL-lysine for injection consists of aspirin-DL-lysine in 75-95 wt% and glycine in 4-25 wt%, with the optimal ratio between aspirin-DL-lysine and glycine being 90 wt% to 10 wt%. The present invention provides also the preparation process of the aspirin-DL-lysine for injection. The aspirin-DL-lysine for injection has raised storage stability, less generation of salicylic acid and less stimulation on muscles.
Description
One, technical field
The present invention relates to chemical pharmacy field, specifically, relate to a kind of more stable aspirin-Al-lysine for injection.
Two, background technology
Aspisol is the double salt of aspirin and lysine, is in a kind of novel antipyretic analgesic of the first-elected listing of the seventies by French Egic drugmaker as the derivant of aspirin.Because it is little, safe in utilization that it has toxic and side effects, no addiction, advantages such as good effect, be two, three grades of analgesic choice drugs of children's's antipyretic-antalgic and cancer patient, existing at home at present how tame pharmacy corporation production comprises enteric coated capsule, powder, injectable powder etc.Aspisol hydrolysis in vivo generates aspirin and lysine, and the then further hydrolysis of aspirin generates salicylic acid, thereby the mechanism of action of aspisol and aspirin is the same.But the aspirin-Al-lysine for injection of at present used clinically single composition has reduced drug effect owing to wet, heat, photo-labile, cause it to be decomposed into free salicylic acid with regard to part in storage period.Because free salicylic acid has strong zest and sensitization to human body, cause that zest and sensitization all increase after the medication, muscular death or severe allergic reaction appear when serious, even threat to life.So, still need the stability of aspirin-Al-lysine for injection is further improved, make it bring into play drug effect and reduction untoward reaction better.
Three, summary of the invention
(1), the technical problem that will solve
The purpose of this invention is to provide a kind of aspirin-Al-lysine for injection more stable when storing and preparation method thereof.
(2), technical scheme
Aspirin-Al-lysine for injection of the present invention is made up of aspisol and glycine, and the two proportioning is 75～96%: 5～25% by weight percentage, and optimum ratio is 85～92%: 8～15%, and best proportioning is 90%: 10%.
Glycine plays function of stabilizer in the present invention, and it can suppress the generation of catabolite free salicylic acid, thereby increases the stability of aspirin-Al-lysine for injection of the present invention in storage period.And the zest to muscle significantly alleviates.
When Aspisol decomposes, generate aspirin and lysine, aspirin further is decomposed into salicylic acid again.Because one of glycine and product lysine all belongs to aminoacid, all is a kind of amphoteric compound, their structure, chemical property all similar.According to the reversible principle of chemical reaction, the existence of glycine can suppress the generation of lysine, suppresses decomposition reaction exactly and takes place, and has also just suppressed salicylic generation.
Aspirin-Al-lysine for injection of the present invention prepares by following step:
A, take by weighing aseptic aspisol and glycine in proportion;
B, under aseptic condition above-mentioned raw materials is mixed, quantitative filling is in cillin bottle.Addition is 0.278g ± 7%, 0.556g ± 5% or 1.00g ± 5%, and controlling spice pH simultaneously is 4.5～6.5, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
Aspirin-Al-lysine for injection of the present invention is white crystals or crystalline powder, and content is greater than 98%, and pH is 4.5～6.5, the content of its free salicylic acid all≤1.5%, loss on drying≤0.10%.Undue toxicity, pyrogen, clarity all meet " national drug standards " (WS
1-XG-015-2001Z) related request.
(3), beneficial effect
Compare with the aspirin-Al-lysine for injection of clinical existing single composition, the stability of medicine of the present invention in storage period increases, and salicylic generation obviously descends by (adnexa), and the zest of muscle is significantly alleviated (adnexa)
Four, the specific embodiment
Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
With all sterilizations in 10000 grades of clean zones of plug, aluminium lid, glass tube vial, deposit standby in 100 grades of zones.Then,
A, in 100 grades of clean zones, take by weighing aspisol 500g and glycine 56g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 0.556g ± 5%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
Embodiment 2
A, in 100 grades of clean zones, take by weighing aspisol 750g and glycine 250g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 0.556g ± 5%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
All the other operations are with embodiment 1.
Embodiment 3
A, 100 grades the knot clean zones in, take by weighing aspisol 960g and glycine 40g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 0.278g ± 7%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
All the other operations are with embodiment 1.
Embodiment 4
A, in 100 grades of clean zones, take by weighing aspisol 900g and glycine 100g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 1.000g ± 5%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
All the other operations are with embodiment 1.
Embodiment 5
A, in 100 grades of clean zones, take by weighing aspisol 850g and glycine 150g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 1.000g ± 5%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
All the other operations are with embodiment 1.
Embodiment 6
A, in 100 grades of clean zones, take by weighing aspisol 920g and glycine 80g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 2.278g ± 7%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
All the other operations are with embodiment 1.
Embodiment 7
A, in 100 grades of clean zones, take by weighing aspisol 940g and glycine 60g, mixing in barrel-shaped mixing machine;
B, quantitatively add spice in cillin bottle with automatic filling machine, addition is 0.556g ± 5%, and control spice pH is 4.5～6.5 in stowing operation, moisture≤0.5%;
C, close plug, gland, packing after lamp inspection is qualified.
All the other operations are with embodiment 1.
Embodiment 8 stability tests
Test in a, the air at room temperature
Embodiment 1～4 gained aspirin-Al-lysine for injection sample is removed outer package, in air at room temperature, placed 10 days, respectively at sampling in the 1st, 3,5,10 day after the setting-out, investigate related item, the equal no change of all samples character is white crystalline powder, pH value is stable, is 5.6.Clarity, free salicylic acid content, the equal conformance with standard of steriling test (" national drug standards " WS
1-XG-015-2001Z, down together), content is all greater than 98.8%.
The investigation that keeps sample of b, room temperature
Get embodiment 1～4 gained sample, place in room temperature, respectively at sampling in 1,3,6,11 month after the setting-out, range of temperature is 13～29 ℃ therebetween, the RH excursion is 65～75%, investigates related item, the equal no change of all samples character, be white crystalline powder, pH value is stable, is 5.6.Clarity, free salicylic acid content, the equal conformance with standard of steriling test, content is all greater than 98.7%.
Embodiment 9 stable contrast tests
Reference substance: get aspisol 0.9g, aseptic embedding prepares 50 bottles altogether in glass tube vial.
Test sample: get embodiment 2 gained aspirin-Al-lysine for injection 1g, aseptic embedding prepares 50 bottles altogether in glass tube vial.
Glass tube vial is placed exsiccator top, and exsiccator is deployed constant humidity solution down, and exsiccator is put in the calorstat, and the condition of setting is 40 ℃, and RH is 75%, and related item is investigated in the sampling of the 0th, 1,2,3,4 weeks in accordance with the law after setting-out, the results are shown in Table 1.
The stable comparative test result of table 1
| Time (week) | Group | The investigation project | ||
| Content (%) | pH | Free salicylic acid content | ||
| 0 | The reference substance test sample | 99.9 99.9 | 5.45 5.45 | 0.46 0.46 |
| 1 | The reference substance test sample | 99.0 99.7 | 5.41 5.39 | 0.88 0.64 |
| 2 | The reference substance test sample | 98.7 99.0 | 5.24 5.34 | 1.17 0.84 |
| 3 | The reference substance test sample | 98.7 98.6 | 5.09 5.26 | 1.76 1.27 |
| 4 | The reference substance test sample | 97.7 98.6 | 4.92 5.18 | 2.29 1.47 |
According to data in the table as can be seen, because the adding of glycine, the decomposition of free salicylic acid obtains certain inhibition in the aspirin-Al-lysine for injection of the present invention, and promptly its stability in storage period strengthens.
The irritant test of 10 pairs of muscle of embodiment
(1), laboratory animal: 10 of adult healthy rabbit, the male and female dual-purpose, body weight 2.0～2.5kg is provided by China Medicine University's animal feeding room.
(2), medicine: the aspirin-Al-lysine for injection of commercially available single composition, be designated as reference substance, the 0.9g/ bottle, lot number: 920519, Bengbu institute of Pharmaceutical Research experiment pharmaceutical factory produces; The aspirin-Al-lysine for injection (aspisol+glycine) of the embodiment of the invention 1 gained is designated as test sample, the 1.0g/ bottle.Above medicine is provided by Gaoyou pharmaceutical factory, faces the time spent with the dissolving of 2ml sterile saline, and sterile saline is by Nanjing Xiaoying Pharmaceutical Factory production, lot number: 92072014.
(3), experimental technique and result: rabbit is divided into four groups at random.First and second organizes every group of 2 rabbit, injects reference substance and test sample respectively, is administered once; Third and fourth organizes every group of 3 rabbit, injects reference substance and test sample respectively, and be administered once every day, continuous seven days.All in injection site unhairing, sterilization, row is injected again before the per injection.The left back lower limb quadriceps femoris of all rabbit position injectable drug, right rear leg quadriceps femoris position injecting normal saline in contrast, the administration volume is 2ml.Observe the injection site behind the drug administration by injection every day and have or not red, swollen and caking, drug withdrawal is after two days, and blood-letting comes out to put to death animal, vertically cuts injection site muscle, observes the variation of injection site muscular tissue, and takes out the injection site surrounding tissue and carry out check pathological section.Carry out the stimulus intensity evaluation by muscular irritation reaction standards of grading (table 2), the results are shown in Table 3.
Table 2 muscular irritation reaction standards of grading
| Irritant reaction | Integration | |
| Negative reaction | Non-stimulated, promptly medicine-feeding part does not have any difference with contrast position muscle | 0 |
| Suspicious reaction | The hyperemia of medicine-feeding part muscular tissue, diameter is below 0.5cm | 1 |
| Mild reaction | The hyperemia of medicine-feeding part muscular tissue, diameter is below 1cm | 2 |
| The severe reaction | Medicine-feeding part muscular tissue redness, blue, gloss disappearance, visible downright bad point | 3 |
| Severe reaction | Medicine-feeding part muscular tissue redness, blue, gloss disappearance are about necrotic extent diameter 0.5cm | 4 |
| Utmost point severe reaction | Medicine-feeding part muscular tissue redness, blue, gloss disappear heavier, and have big loop dead | 5 |
Annotate: all average response progression can supply intramuscular injection 2 following persons, and the person answers retrial between 2～3
The perusal of table 3 pair muscle irritation
| Group | Medicine | Number of animals (only) | Administration time (my god) | The average response integration of muscular irritation | |
| The administration side | The normal saline side | ||||
| A | Reference substance | 2 | 1 | 1 | 0.2 |
| B | Test sample | 2 | 1 | 0.5 | 0 |
| C | Reference substance | 3 | 7 | 1.3 | 0.3 |
| D | Test sample | 3 | 7 | 0.6 | 0.3 |
Each group laboratory animal injection site surrounding tissue is carried out check pathological section, 22 of censorship specimen, the check pathological section result is as follows:
1,1 day group of injection:
Matched group is totally 2 examples, all visible focal myofibrosis, necrosis.
The test sample group is totally 2 examples, has 1 example focal myofibrosis, necrosis, another routine no abnormality seen to occur.
The normal saline group, no abnormality seen.
2,7 days groups of injection:
Matched group is totally 3 examples, reaches myofibrosis, necrosis between all visible special mess muscle bundle, and wherein 2 examples are heavier, visible a large amount of mononuclear cells and minority lymphocytic infiltration.
Test sample group 3 examples, only 1 example is seen focal myocyte's degeneration necrosis, surplus end is seen unusually.
The normal saline group, no abnormality seen.
By above result as seen: the reference substance group no matter organized in one day or seven days by administration, and injection back partial musculature degeneration necrosis response strength is bigger, and scope is also big.When clinical practice, may cause patient partial musculature pain after the injection.And the test sample group no matter administration one day or seven days groups all cause that than the aspisol injection local patholoic change degree and scope are for light.Experimental result shows that aspirin-Al-lysine for injection of the present invention is compared with commercially available single composition aspirin-Al-lysine for injection, and its zest to muscle significantly alleviates.
Claims (4)
1, a kind of aspirin-Al-lysine for injection, it is by 75～96% aspisol and 4～25% glycine are formed by weight percentage.
2, aspirin-Al-lysine for injection as claimed in claim 1 is characterized in that, the proportioning of aspisol and glycine is: 85～92%: 8～15%.
3, aspirin-Al-lysine for injection as claimed in claim 1 is characterized in that, the proportioning of aspisol and glycine is: 90%: 10%.
4, as the preparation method of each described aspirin-Al-lysine for injection of claim 1～3, may further comprise the steps:
A, take by weighing aseptic aspisol and glycine in proportion;
B, under aseptic condition above-mentioned raw materials is mixed, quantitative filling is in cillin bottle.Addition is 0.278g ± 7%, 0.556g ± 5% or 1.000g ± 5%, and controlling spice pH simultaneously is 4.5～6.5, moisture≤0.5%, and do not have the foreign body microgranule;
C, close plug, gland, packing after lamp inspection is qualified.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510086400 CN1739530A (en) | 2005-09-12 | 2005-09-12 | Aspirin-Al-lysine for injection |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510086400 CN1739530A (en) | 2005-09-12 | 2005-09-12 | Aspirin-Al-lysine for injection |
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| CN1739530A true CN1739530A (en) | 2006-03-01 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951846A (en) * | 2017-12-06 | 2018-04-24 | 海南皇隆制药股份有限公司 | A kind of aspirin-Al-lysine for injection freeze-dried powder and preparation method thereof |
| CN107982220A (en) * | 2017-12-06 | 2018-05-04 | 海南皇隆制药股份有限公司 | A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof |
| CN112305138A (en) * | 2020-10-28 | 2021-02-02 | 蚌埠丰原医药科技发展有限公司 | Method for simultaneously determining content of lysine and glycine |
| US11793748B1 (en) | 2019-04-05 | 2023-10-24 | Good Health, Llc | Pharmaceutical compositions of aspirin for parenteral administration |
-
2005
- 2005-09-12 CN CN 200510086400 patent/CN1739530A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107951846A (en) * | 2017-12-06 | 2018-04-24 | 海南皇隆制药股份有限公司 | A kind of aspirin-Al-lysine for injection freeze-dried powder and preparation method thereof |
| CN107982220A (en) * | 2017-12-06 | 2018-05-04 | 海南皇隆制药股份有限公司 | A kind of aspirin-Al-lysine for injection composition of anti-hydrolysis and preparation method thereof |
| US11793748B1 (en) | 2019-04-05 | 2023-10-24 | Good Health, Llc | Pharmaceutical compositions of aspirin for parenteral administration |
| CN112305138A (en) * | 2020-10-28 | 2021-02-02 | 蚌埠丰原医药科技发展有限公司 | Method for simultaneously determining content of lysine and glycine |
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