CN101239037A - Acetylcysteine injection and preparation thereof - Google Patents
Acetylcysteine injection and preparation thereof Download PDFInfo
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- CN101239037A CN101239037A CNA200810085531XA CN200810085531A CN101239037A CN 101239037 A CN101239037 A CN 101239037A CN A200810085531X A CNA200810085531X A CN A200810085531XA CN 200810085531 A CN200810085531 A CN 200810085531A CN 101239037 A CN101239037 A CN 101239037A
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- acetylcysteine
- injection
- solution
- acetylcysteine injection
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- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 229940021715 acetylcysteine injection Drugs 0.000 title claims description 46
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims abstract description 63
- 229960004308 acetylcysteine Drugs 0.000 claims abstract description 51
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229960000281 trometamol Drugs 0.000 claims abstract description 8
- 239000000243 solution Substances 0.000 claims description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 238000002347 injection Methods 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 10
- 230000001681 protective effect Effects 0.000 claims description 10
- 229940090044 injection Drugs 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 239000003172 expectorant agent Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
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- 230000003078 antioxidant effect Effects 0.000 claims description 5
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- 230000008313 sensitization Effects 0.000 abstract description 6
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- 240000006409 Acacia auriculiformis Species 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
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- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
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- UIQKZVQFTHWEGC-FHNDMYTFSA-M sodium (2R)-2-acetamido-3-sulfanylpropanoic acid chloride Chemical compound [Na+].[Cl-].CC(=O)N[C@@H](CS)C(O)=O UIQKZVQFTHWEGC-FHNDMYTFSA-M 0.000 description 2
- ROBLTDOHDSGGDT-UHFFFAOYSA-M sodium;pentane-1-sulfonate Chemical compound [Na+].CCCCCS([O-])(=O)=O ROBLTDOHDSGGDT-UHFFFAOYSA-M 0.000 description 2
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- 239000008215 water for injection Substances 0.000 description 2
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- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to an acetylcysteine injecta, which contains tromethamine with stable dosage, further relating to the preparation method of the injecta. The acetylcysteine injecta of the invention has low sensitization and keeps stability and indissolubility after being sterilized under high temperature (115 DEG, 30 minutes) and stored for a long period and the PH value also can keep stability after being stored for a long period.
Description
Technical field
The present invention relates to a kind of Mucosolvin, in particular to a kind of acetylcysteine injection and preparation method thereof.
Background technology
Acetylcysteine (Acetylcysteine, N-acetyl group-3-sulfydryl third ammonia)
Be the precursor of reduced glutathion (GSH), belong to oxygen free radical scavenger in the body.The mechanism of its liver protection is still not fully aware of, may with keep or to recover glutathione level relevant.In addition, acetylcysteine also may be by improving hematodinamics and oxygen conveying capacity, expansion microcirculation performance liver protection.
The most of useful effect of acetylcysteine (NAC) comes from it to be had and reduces the extracellular cystine and be converted into the ability of cysteine, and can be used as the metabolic source of sulfydryl.Acetylcysteine can stimulate glutathion (GSH) synthetic, strengthens the activity of GSH-S-based transferase, promotes detoxifcation and to the direct effect of oxygen free radical reaction.Reach external evidence in the body and all point out, acetylcysteine can improve the biosynthesis of GSH in the cell.In cell culture experiments, acetylcysteine promotes the picked-up of cystine from the biosynthetic culture medium of GSH.In vivo, acetylcysteine can improve the level of GSH in the cell of erythrocyte, hepatocyte, lungs cell and replenish the consume that experimental GSH stores.
The GSH concentration that acetylcysteine is corrected the obstruction of biliary tract rat causes the important protective effect to the flowability of film and catalase, SOD2, multi-form GSH peroxidase.These effect prompting acetylcysteines may be a kind of active drugs of protecting the patients with biliary liver function.Acetylcysteine is demonstrating the synthetic support to GSH when GSH need increase.Show that acetylcysteine competence exertion under the state that GSH lacks promotes the synthetic effect of GSH.Acetylcysteine can also improve the concentration of single phosphoric acid cyclic guanosine under experiment condition.Harrison etc. have reported that acetylcysteine shows good hematodinamics activity by improving endogenous vasodilation nitric oxide level and increase sGC system activity when acute hepatic failure.Report acetylcysteines such as Nagasaki can be protected the GSH hepatic injury in when disappearance, and the integrity of liver can safeguard ischemia/reperfusion injury the time.This effect is as the biosynthetic substrate of GSH but bring into play as direct free radical scavenger, and directly to suppress the Kupffer cell activation relevant with it.There are some researches show that acetylcysteine can block apoptotic process.Its mechanism is that acetylcysteine can be removed the reactive oxygen intermediate that participates in the apoptotic signal transduction; Precursor as reduced form GSH provides anti-cell toxic effect; Can also disturb apoptosis the signal in downstream, back to occur.
The preparation of acetylcysteine is used more extensive clinically, and known have an expelling phlegm for arresting cough effect.Now also begin to be applied to treat various hepatic disease, particularly liver failure.
But acetylcysteine injection easily causes the body anaphylaxis in use, comprises skin pruritus, erythema etc.For this reason, this area is needed badly and is obtained the low acetylcysteine aqueous solution for injection of sensitization, and it is very big to prepare the low acetylcysteine injection difficulty of sensitization, is the difficult problem that pharmaceutical industry is demanded urgently capturing always.
Summary of the invention
The inventor is surprised to find that in development process, with the trometamol of consistent dose
Be added in the acetylcysteine solution, can obtain a kind of stable acetylcysteine injection, thereby successfully solved the problem that above-mentioned acetylcysteine injection easily causes allergic reaction.
Therefore, the invention provides the low acetylcysteine injection of a kind of sensitization, wherein contain the trometamol of consistent dose.
The present invention also provides the preparation method of above-mentioned acetylcysteine injection.Described method comprises the steps:
1) under logical nitrogen protective condition, preparation contains the aqueous solution of all the components except that acetylcysteine;
2) under logical nitrogen protective condition, prepare the mucolyticum aqueous acid, and transfer pH to 6-8 with sodium hydrate aqueous solution;
3) under logical nitrogen protective condition, solution and step 2 that step 1) is made) solution that makes mixes and transfers pH to 6-8, and filter, sterilize after the fill.
The specific embodiment
The invention provides the low acetylcysteine injection of a kind of sensitization, wherein contain the trometamol of consistent dose.
In a preferred embodiment of the invention, the concentration of trometamol in above-mentioned acetylcysteine injection is 0.01%-2.0% (W/V), with the stereometer of acetylcysteine injection.In a preferred embodiment, the concentration of trometamol in above-mentioned acetylcysteine injection is 0.05%-0.5% (W/V).
In a preferred embodiment of the invention, described acetylcysteine injection also comprises antioxidant and osmotic pressure regulator.
In a preferred embodiment of the invention, above-mentioned antioxidant can be selected from disodiumedetate, calcio-disodium edetate or its mixture, and their total concentration is preferably 0.001%-0.1% (W/V).
In a preferred embodiment of the invention, above-mentioned osmotic pressure regulator can be a sodium chloride, and its concentration is preferably 0.2-1.0% (W/V).
In a preferred embodiment of the invention, the mucolyticum acid concentration is 1%-50% (W/V) in the described acetylcysteine injection, in a preferred embodiment, the mucolyticum acid concentration is 1%-20% (W/V) in the described acetylcysteine injection.
In a preferred embodiment of the invention, the osmotic pressure of described acetylcysteine injection is 250-350mOsmol/kg, and pH is 6.0-8.0.Preferably, the total resultant of its related substance is no more than 5%, in the weight of acetylcysteine contained in this injection.
The definition of described " related substance " in the medicine stability test guideline of putting down in writing among two appendix XI of term as used in this specification " related substance " and Chinese Pharmacopoeia version in 2000 X is identical, is meant the catabolite of acetylcysteine and the material that other variations are produced.
The present invention also provides the preparation method of above-mentioned acetylcysteine injection.Described method comprises the steps:
1) under logical nitrogen protective condition, preparation contains the aqueous solution of all the components except that acetylcysteine;
2) under logical nitrogen protective condition, prepare the mucolyticum aqueous acid, and transfer pH to 6-8 with sodium hydrate aqueous solution;
3) under logical nitrogen protective condition, solution and step 2 that step 1) is made) solution that makes mixes and transfers pH to 6-8, and filter, sterilize after the fill.
Preferred sterilising conditions is the conventional sterilising conditions with regard to injection, for example, sterilizes 30 minutes down for 115 ℃.
Acetylcysteine sensitization in the acetylcysteine injection of the present invention is low, and still can keep stablizing after high temperature (115 ℃, 30 minutes) is sterilized back and long-term storage not decomposing, and it is stable that its pH value also can keep after long-term storage.
Acetylcysteine injection measuring method (acetylcysteine and its related substances assay method)
Measure the content of acetylcysteine and related substance in the acetylcysteine injection as follows, estimate with quality to injection.
The acetylcysteine assay:
Measure according to the high performance liquid chromatography of putting down in writing among two appendix V of Chinese Pharmacopoeia version in 2000 D.
The chromatography test condition:
With the octadecylsilane chemically bonded silica is filler, and it is mobile phase that 0.5% ammonium sulfate (1: 9) of methanol-0.02mol/L sodium pentanesulfonate is also regulated pH value to 2.0 with the 2mol/L hydrochloric acid solution; The detection wavelength is 205nm.Theoretical cam curve is calculated by the acetylcysteine peak should be not less than 2000.
Assay method:
It is an amount of that precision is measured acetylcysteine, adds mobile phase and make the solution that contains acetylcysteine 80 μ g among every 1ml, shakes up, and filters, and gets subsequent filtrate as need testing solution, accurately measures above-mentioned solution 20 μ l, injects chromatograph of liquid, the record chromatogram; Precision takes by weighing through the acetylcysteine reference substance of drying under reduced pressure to constant weight in addition, measures with method, gets the mucolyticum acid content by external standard method with calculated by peak area.
Related substance:
It is an amount of to get acetylcysteine, add the mobile phase dilution and make the solution (1) that contains acetylcysteine 2mg among the 1ml, it is an amount of to take by weighing acetylcysteine in addition respectively, adds mobile phase and makes the solution (2) that contains 2mg among every 1ml, and solution (2) room temperature is placed and become solution (3) in 2 hours.Get L-cysteine 20mg and L-cystine 20mg again, add 1mol/L hydrochloric acid solution 10ml dissolving.After adding acetylcysteine 40mg dissolving again, make with the mobile phase dilution immediately and contain the solution (4) that L-cysteine, L-cystine and acetylcysteine are respectively 10 μ g, 10 μ g and 20 μ g among every 1ml.Removing solution (3) should place 2 hours in room temperature, and other solution all should preparation temporarily before analysis.
High performance liquid chromatography according to two appendix VD of Chinese Pharmacopoeia version in 2000, with the octadecylsilane chemically bonded silica is filler, and it is mobile phase that 0.5% ammonium sulfate (1: 9) of methanol-0.02mol/L sodium pentanesulfonate is also regulated pH value to 2.0 with the 2mol/L hydrochloric acid solution; The detection wavelength is 205nm.Theoretical cam curve is calculated by the acetylcysteine peak should be not less than 2000.
Get each 20 μ l of above-mentioned solution (2) and (3) sample introduction respectively, the peak area of the diacetyl cystine that solution (3) is shown should be greater than corresponding peak on solution (2) chromatogram.Get solution (4) 20 μ l and inject chromatograph of liquid, regulate detection sensitivity, make the peak height of acetylcysteine chromatographic peak be about 20% of monitor full scale, the height of paddy should be less than 1/4 of acetylcysteine peak height between L-cysteine and L-cystine chromatographic peak.Accurately measure each 20 μ l of solution (1) and (4) sample introduction respectively again, the record chromatogram is to 3 times of acetylcysteine main constituent peak retention time.
Should be understood that, for those of ordinary skills, can be according to the above description for change of the present invention or conversion, and all these changes or conversion all should belong to the protection domain of claim.
By following examples the present invention is done further to specify, but be not intended to limit scope of the present invention.
Comparative example: the stability test of acetylcysteine solution
Extremely unstable when acetylcysteine solution is exposed in the air, easy oxidized decomposition produces impurity such as L-cystine, L-cysteine, diacetyl cystine.Measure acetylcysteine solution in the present embodiment and be exposed to the stable case in (oxygen) in the air.
1. determining instrument
Chromatograph: day island proper Tianjin LC-10AT;
UV-detector: SPD-10AVP;
Electronic analytical balance;
Chromatographic column: Agilent C18 5 μ, 4.6 * 250mm;
2. assay method
As mentioned before, measure according to the high performance liquid chromatography of putting down in writing among two appendix VD of Chinese Pharmacopoeia version in 2000.
3. experimental result
Table 1: the stability of acetylcysteine solution
By the result in the last table as can be seen, acetylcysteine solution was exposed in the air after 2 hours, and L-cysteine in the solution and diacetyl cystine raise obviously, showed this solution instability in air (oxygen), and is easily oxidized.
Embodiment 1: the preparation of acetylcysteine injection of the present invention
1. acetylcysteine injection prescription:
For checking the stability of acetylcysteine injection of the present invention, seven kinds of exemplary acetylcysteine injections have been prepared in the present embodiment.The prescription of these exemplary injection is as shown in table 2 below.
The prescription of the exemplary acetylcysteine injection of table 2
Annotate: sodium hydroxide is mixed with 20% and 5% solution respectively
2. the preparation of acetylcysteine injection
1) measures respectively by above-mentioned prescription and deserve to be called all the components except that acetylcysteine and sodium hydroxide solution in the table, it fully is dissolved in the water for injection, boil, (activated carbon dosage is 0.4% to activated carbon adsorption, and W/V), decarburization is filtered, make filtrate be cooled to 50-60 ℃, it is standby to continue logical nitrogen.
2) get 80 ℃ deoxygenated water (in advance logical nitrogen 30 minutes), take by weighing the mucolyticum acid starting material of respective amount in the above-mentioned prescription, dissolving is made into the concentrated solution of 20% (W/V); Get proper amount of sodium hydroxide and be made into 20% (W/V) sodium hydroxide solution, regulate the pH value of acetylcysteine concentrated solution to 6-8 with this sodium hydroxide solution.
3) under room temperature and the logical nitrogen state, with solution and the step 2 that makes in the step 1)) in the solution that makes mix, stir.
4) standardize solution and pH value are regulated
Add the capacity of water for injection, regulate pH value to 6-8 with 5% sodium hydroxide solution (W/V) to the prescription regulation.
5) filtration, fill
Use membrane filtration, fill, but fill becomes every bag or every bottle 100,250 or 500ml.
6) sterilization
Sterilising conditions: 115 ℃, 30 minutes.
Embodiment 2: the stability test of acetylcysteine injection of the present invention
The acetylcysteine injection product that makes among the embodiment 1 is placed container, placed six months down for 40 ℃, measure the stability of product, the results are shown in table 2.
Table 2: the accelerated test result of acetylcysteine injection
The result of last table shows: acetylcysteine injection of the present invention was through 6 months accelerated stability test, and its related substances is lower than 3%, and every index do not see significant change, and product is stable.
Embodiment 3: acetylcysteine injection of the present invention is to zest and the anaphylaxis of animal
Test
Present embodiment is by zoopery, investigated acetylcysteine sodium chloride injection intravenously administrable after, to the irritant reaction of blood vessel and surrounding tissue.
1. test material
No. 5 acetylcysteine sodium chloride injections of № of preparation among reagent: the embodiment 1, specification: 250ml/ bottle; Use 0.9% sodium chloride injection (lot number: in addition 2006121515) as negative control available from Huiyinbi Group (Jiangxi) Dongya Pharmaceutical Co., Ltd..
Experimental animal: 3 of male adult new zealand rabbits, body weight is respectively 2.8kg, 2.6kg, 2.4kg, and production licence number is provided by Zhejiang Province's Experimental Animal Center: SCXK (Zhejiang) 2003-0002.
2. test method
Get above-mentioned new zealand rabbit, fixing, auris dextra intravenous injection sample liquid (test group), injected dose is pressed new zealand rabbit body weight 10ml/kg, and injection speed is 2ml/min, at every turn at same position inserting needle, successive administration 3 days, 1 time/day.Same method, each rabbit left side ear injects 0.9% sodium chloride injection as negative control (matched group), and dosage and other injecting conditions are all with the auris dextra unanimity.After the last administration 16 hours, carotid artery sacrificed by exsanguination animal, get the left and right ear entry point of every rabbit precontract 1.5cm (near-end) and 3.0cm (far-end) auricular vein and surrounding tissue respectively, after being numbered, place 10% formalin solution fixing, do the pathology histological examination, observe the situations such as inflammatory reaction of auricular vein and surrounding tissue.
3. result
Perusal bilateral ear vein surrounding tissue does not all have phenomenons such as obvious edema, hyperemia.
The histopathological examination result is as follows:
Matched group:
No. 1 rabbit near-end: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, slightly thickens, the degeneration of vascular endothelial cell Mild edema, no thrombosis forms in the tube chamber, sees the moderate erythrocyte in the lumen of vessels.
No. 2 rabbit near-ends: accidental inflammatory cell infiltration around the blood vessel, blood vessel wall is complete, do not have obviously to thicken, the degeneration of vascular endothelial cell Mild edema, no thrombosis forms in the tube chamber, sees the minute quantity erythrocyte in the lumen of vessels.
No. 3 rabbit near-ends: be dispersed in inflammatory cell infiltration around the blood vessel, blood vessel wall is complete, does not have obviously to thicken, and vascular endothelial cell does not have the edema degeneration, and no thrombosis forms in the tube chamber, sees a small amount of erythrocyte in the lumen of vessels.
No. 1 rabbit far-end: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, slightly thickens, and vascular endothelial cell does not have the edema degeneration, and no thrombosis forms in the tube chamber, sees the moderate erythrocyte in the lumen of vessels.
No. 2 rabbit far-ends: accidental inflammatory cell infiltration around the blood vessel, blood vessel wall is complete, slightly thickens, the degeneration of vascular endothelial cell Mild edema, no thrombosis forms in the tube chamber, sees the moderate erythrocyte in the lumen of vessels.
No. 3 rabbit far-ends: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, do not have obviously to thicken, the degeneration of vascular endothelial cell Mild edema, no thrombosis forms in the tube chamber, sees a small amount of erythrocyte in the lumen of vessels.
The test group:
No. 1 rabbit near-end: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, do not have obviously to thicken, the degeneration of vascular endothelial cell Mild edema, no thrombosis forms in the tube chamber, sees a small amount of erythrocyte in the lumen of vessels.
No. 2 rabbit near-ends: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, does not have obviously to thicken, and vascular endothelial cell does not have the edema degeneration, and no thrombosis forms in the tube chamber, sees a small amount of erythrocyte in the lumen of vessels.
No. 3 rabbit near-ends: NIP cellular infiltration around the blood vessel, blood vessel wall is complete substantially, do not have obviously to thicken, the degeneration of vascular endothelial cell Mild edema, no thrombosis forms in the tube chamber, sees a small amount of erythrocyte in the lumen of vessels.
No. 1 rabbit far-end: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, slightly thickens, and vascular endothelial cell does not have the edema degeneration, and no thrombosis forms in the tube chamber, sees a small amount of erythrocyte in the lumen of vessels.
No. 2 rabbit far-ends: NIP cellular infiltration around the blood vessel, blood vessel wall is complete, and blood vessel endothelium has hypertrophy, and tube wall does not have obviously and thickens, and vascular endothelial cell does not have the edema degeneration, and a small amount of erythrocyte is seen in no thrombosis formation in the tube chamber in the lumen of vessels.
No. 3 rabbit far-ends: accidental inflammatory cell infiltration around the blood vessel, blood vessel wall is complete, slightly thickens, and vascular endothelial cell does not have the edema degeneration, and no thrombosis forms in the tube chamber, sees the moderate erythrocyte in the lumen of vessels.
By above-mentioned animal test results as can be seen, the zest of acetylcysteine injection of the present invention is little, does not have irritated reaction.
Claims (10)
1. an acetylcysteine injection is characterized in that, contains the trometamol of consistent dose in the described injection.
2. according to the acetylcysteine injection of claim 1, it is characterized in that the amount of described trometamol is 0.01%-2.0% (W/V), be preferably 0.05%-0.5% (W/V), with the stereometer of acetylcysteine injection.
3. according to the acetylcysteine injection of claim 1, it is characterized in that described injection also contains antioxidant and osmotic pressure regulator.
4. according to the acetylcysteine injection of claim 3, it is characterized in that described antioxidant is selected from disodiumedetate, calcio-disodium edetate or their mixture, the total concentration of described antioxidant is 0.001%-0.1% (W/V).
5. according to the acetylcysteine injection of claim 3, it is characterized in that described osmotic pressure regulator is a sodium chloride, its concentration is 0.2-1.0% (W/V).
6. according to the acetylcysteine injection of claim 1, it is characterized in that described mucolyticum acid concentration is 1%-50% (W/V), is preferably 1%-20% (W/V).
7. according to each acetylcysteine injection of claim 1-6, the osmotic pressure that it is characterized in that described acetylcysteine injection is 250-350mOsmol/kg, and pH is 6.0-8.0.
8. according to each acetylcysteine injection of claim 1-6, it is characterized in that its related substances is no more than 5% in the described acetylcysteine injection, in the weight of acetylcysteine contained in this injection.
9. according to the acetylcysteine injection of claim 7, it is characterized in that its related substances is no more than 5% in the described acetylcysteine injection.
10. preparation is according to each the method for acetylcysteine injection of claim 1-9, and described method comprises the steps:
1) under logical nitrogen protective condition, preparation contains the aqueous solution of all the components except that acetylcysteine;
2) under logical nitrogen protective condition, prepare the mucolyticum aqueous acid, and regulate pH value to 6-8 with sodium hydroxide solution;
3) under logical nitrogen protective condition, with step 1) and step 2) solution that makes mixes, and regulates pH value to 6-8, and filter, sterilize after the fill.
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| CN200810085531XA CN101239037B (en) | 2008-03-17 | 2008-03-17 | Acetylcysteine injection and preparation thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102514755A (en) * | 2011-11-04 | 2012-06-27 | 蚌埠丰原涂山制药有限公司 | Preparation method of xantinol nicotinate and sodium chloride injection packaged by using soft bag |
| CN114681397A (en) * | 2020-12-26 | 2022-07-01 | 四川汇宇制药股份有限公司 | Preparation method of acetylcysteine injection |
| US11413238B2 (en) | 2020-02-18 | 2022-08-16 | Endo Ventures Limited | N-acetylcysteine compositions and methods |
| CN115266963A (en) * | 2022-06-01 | 2022-11-01 | 北京诺康达医药科技股份有限公司 | Method for detecting cysteine and cystine in compound amino acid injection |
-
2008
- 2008-03-17 CN CN200810085531XA patent/CN101239037B/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102514755A (en) * | 2011-11-04 | 2012-06-27 | 蚌埠丰原涂山制药有限公司 | Preparation method of xantinol nicotinate and sodium chloride injection packaged by using soft bag |
| US11413238B2 (en) | 2020-02-18 | 2022-08-16 | Endo Ventures Limited | N-acetylcysteine compositions and methods |
| US11752097B2 (en) | 2020-02-18 | 2023-09-12 | Endo Ventures Limited | N-acetylcysteine compositions and methods |
| CN114681397A (en) * | 2020-12-26 | 2022-07-01 | 四川汇宇制药股份有限公司 | Preparation method of acetylcysteine injection |
| CN115266963A (en) * | 2022-06-01 | 2022-11-01 | 北京诺康达医药科技股份有限公司 | Method for detecting cysteine and cystine in compound amino acid injection |
| CN115266963B (en) * | 2022-06-01 | 2024-01-05 | 北京诺康达医药科技股份有限公司 | Method for detecting cysteine and cystine in compound amino acid injection |
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