CN102266343A - Fasudil hydrochloride pharmaceutical composition for injection - Google Patents
Fasudil hydrochloride pharmaceutical composition for injection Download PDFInfo
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- CN102266343A CN102266343A CN2011102605217A CN201110260521A CN102266343A CN 102266343 A CN102266343 A CN 102266343A CN 2011102605217 A CN2011102605217 A CN 2011102605217A CN 201110260521 A CN201110260521 A CN 201110260521A CN 102266343 A CN102266343 A CN 102266343A
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Abstract
The invention discloses a fasudil hydrochloride pharmaceutical composition for injection. Each injection comprises fasudil hydrochloride 15-60 mg, cysteine hydrochloride 13.05-15.95 mg, and sodium chloride 0.2-0.8 mg. The preparation method of the injection comprises the following steps: preparing prescription dose of water for injection (55-65 DEG C) 90%, adding prescription dose of cysteine hydrochloride, and stirring to dissolve; adding prescription dose of fasudil hydrochloride, stirring to dissolve, adding prescription dose of sodium chloride, and stirring to dissolve; measuring initial pH value, and adjusting the pH value in a range of 5.5-6.5 with 4% sodium hydroxide solution and 10% cysteine hydrochloride solution; adding medicinal carbon, and stirring; performing suction filtering, supplementing water for injection to full quantity, and mixing uniformly; carrying out fine filtration; filling; sterilizing; performing lamp testing; and warehousing to obtain finished products. The fasudil hydrochloride pharmaceutical composition disclosed by the invention has the advantages of good light stability, no crystallization, and good clarity and stability. The fasudil hydrochloride pharmaceutical composition has more distinct advantages for increasing product yield, reducing cost, realizing industrialization and being better applied in clinics.
Description
Technical field
The present invention relates to the medicine in the field of medicaments, especially relate to a kind of stablely, can not produce crystallization, Fasudic hydrochloride pharmaceutical composition of the injection of good stability and preparation method thereof light.
Background technology
In the last few years, the subarachnoid hemorrhage that causes after cerebrovascular accident such as the aneurysm rupture was known by the clinicist.The most common and the severe complications of subarachnoid hemorrhage is a cerebral vasospasm, it is disabled or lethal main cause is the delayed cerebral ischemia that arteriospasm causes, nearly half patient betide hemorrhage after, if do not treat, neurological deficit or dead incidence rate are up to 20%.Though its potential danger of cerebral vasospasm is very big, unclear fully as yet to the mechanism of its morbidity, be commonly referred to be the coefficient result of multiple reason.So present treatment measure mainly is the treatment of carrying out at the possible pathogenesis of the cerebral vasospasm that causes behind the SAH.In the present existing Drug therapy, NO related drugs and ET antagonist class medicine all are not widely used in clinical, still are in conceptual phase; And because the inflammatory reaction behind the SAH is not clear and definite as yet, so the clinical efficacy of anti-inflammatory treatment is still unclear; Calcium antagonist class medicine is the blood vessel dilating microcirculation improvement effectively, thus use clinically at most.
At present using maximum calcium antagonists clinically is nimodipine, and the problem of its existence is not strong to cerebrovascular selectivity, in the cerebrovascular while of diastole systemic blood pressure is reduced.And Fasudic hydrochloride optionally acts on cerebrovascular, and it does not have influence to systemic blood pressure, and especially the calcium channel to cardiac muscle does not have effect, has avoided relevant side effect.Evidence, the vasodilatory effect of Fasudic hydrochloride is better than other calcium ion antagonists such as nimodipine, verapamil, and the Fasudic hydrochloride effect do not rely on extracellular Ca2+, but Ca2+ in the antagonism born of the same parents is different from conventional cell film calcium channel blocker fully.Clinical trial proves that the Fasudic hydrochloride toleration is good, and untoward reaction mostly is slightly, one cross property.It is water-soluble, and injection is solvent with water fully, has avoided the discomfort reaction of organic solvent (as ethanol and Polyethylene Glycol etc.).Fasudic hydrochloride is easy to use, can inject in 0.5 hour and finish, and nimodipine needs at least 12 hours.
Fasudic hydrochloride, English name: Fasudil, its structural formula is:
Molecular formula: C
14H
17N
3O
2SHCl
Molecular weight: 327.83
Character: this product is white or off-white color crystalline powder.Odorless, mildly bitter flavor; Have draw moist.This product is easily molten in water, in methanol, dissolves, and slightly soluble in ethanol, almost insoluble in chloroform or ether.Be that a kind of kinases inhibitor is the intracellular calcium antagonist, it is a kind of medicine for the treatment of ischemic encephalopathy, Fasudic hydrochloride can suppress terminal stage myosin light chain (MLC) phosphorylation of vascular smooth muscle contraction and the generation of free radical by suppressing the Rho kinases, make the vascular smooth muscle relaxation of spasm, reach the effect of blood vessel dilating.Fasudil hydrochloride injection is developed by Japanese Asahi Kasei Pharma Corp, and go on the market in Japan June nineteen ninety-five, and go on the market in China August calendar year 2001, trade name: Yi Lilu.The river prestige) and SHANXI POWERDONE PHARMACEUTICAL.,LTD's fasudil hydrochloride injection list marketing of being produced China's food and medicine Surveillance Authority fasudil hydrochloride injection of ratifying Tianjin Chasesun Pharmaceutical Co., Ltd respectively and produced on March 17th, 2004 and on May 7th, 2010 (trade name: then.Be mainly used in and improve and the cerebral vasospasm of prevention subarachnoid hemorrhage postoperative and the symptoms of cerebral ischemia that thereupon causes.
Application number is 200510089011.2 disclosure of the Invention a kind of fasudil hydrochloride injection and preparation method thereof, the hydrochloric fasudil of the fasudil hydrochloride injection of this patent disclosure, and the aqueous solution of sodium chloride, glucose, aminoacid or other pharmaceutically acceptable diluent.Fasudic hydrochloride content is 0.01% ~ 0.2% (percentage by weight), and pharmaceutically acceptable amount of diluent is 0.5% ~ 50%.When using sodium chloride, its content is 0.9% ~ 5%, and when using glucose, its content is 5% ~ 20%, and when using aminoacid, its content is 0.5% ~ 30%.Be bulk capacity injection, the cost height, quality controllability is poor, is unfavorable for transportation, storage.
Application number is that 200510130096.4 invention relates to a kind of Fasudic hydrochloride oral formulation, particularly a kind of oral drug preparation of Fasudic hydrochloride of the improvement that is used for the ischemic cerebrovascular symptom that cerebral vasospasm after subarachnoid hemorrhage etc. causes, preferably tablet, capsule and granule.
The freeze drying injection of application number a kind of fasudil hydrochloride that has been 200510136032.5 disclosure of the Invention and hydrate, the freeze drying injection that contains at least a composition of fasudil hydrochloride and hydrate thereof, this dosage form cost height, fabrication cycle is long, production environment requires high, has high input.Clinical use also will be redissolved operation, for clinical practice brings certain risk.
Application number is to provide the not good container of the visual property distinguished of special blocking light content of a kind of employing for 200580008301.8 invention, to the preparation that contains fasudil that has good stability of light, and provide a kind of said preparation that improves to the stability of light and to its method of preserving.The pH of the present invention by making the fasudil aqueous solution that is filled in the water white transparency container is below 5.5, can obtain the preparation that contains fasudil that has good stability to light, in addition, can also provide improve the fasudil aqueous solution to light stability and to its method of preserving.
Application number is 200610044980.0 to disclose six hydrogen-1-(5-sulfonyl isoquinolin)-1H-1; 4-diaza is the hydrate of the pharmaceutical salts of fasudil; especially the semihydrate of fasudil nitrate, sulfate, hydrobromate, mesylate, and preparation method thereof and be used for the treatment of and/or prevent purposes in the medicine of cardiovascular and cerebrovascular disease in preparation.
Application number is 200910016702.8 to disclose hydrochloric acid Fasudil liposome injection and new application the thereof, and its injection mainly is by 1 part of the Fasudic hydrochloride of weight portion meter, phosphatidase 12-20 part, cholesterol 0.5-10 part, polyoxyethylene sorbitan monoleate 1-8 part component.Also can be used for simultaneously smelting and treat vertebral artery type of cervical spondylosis.The polyoxyethylene sorbitan monoleate there be limited evidence currently of is applied to be added as adjuvant in the injection, because of certain haemolysis and skin irritation are arranged clinically.
The fasudil hydrochloride injection that prior art is produced all has very strict requirement to the requirement of storage, lucifuge, all has inconvenience in use, preservation and transportation.
The inventor is through studying for a long period of time, the unexpected discovery used special adjuvant, the Fasudic hydrochloride pharmaceutical composition of special process preparation, light resistance is good, be difficult for separating out, good stability has not only successfully solved the problem of the poor stability of Fasudic hydrochloride, reduce production costs, easy to implement, can realize industrialization, remarkable in economical benefits.
Summary of the invention
First purpose of the present invention is to provide a kind of Fasudic hydrochloride pharmaceutical composition of injection, this fasudil hydrochloride injection is stable to light, can long-living crystallization, good stability, to improving product yield, reduce cost, realize industrialization, better application has more obvious advantage in clinical.
Second purpose of the present invention is to provide the Fasudic hydrochloride preparation of drug combination method of injection of the present invention, and this method is simple, prepared Fasudic hydrochloride pharmaceutical composition, stable to light, can not produce crystallization, clarity is good, good stability.
For realizing first purpose of the present invention, the present invention adopts following technical scheme:
A kind of Fasudic hydrochloride pharmaceutical composition of injection, per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 15-60g
Sodium chloride 13.05-15.95g
Cysteine hydrochloride 0.2-0.8g
Water for injection adds to 2L.
Preferably, per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30-60g
Sodium chloride 14.5-15.95g
Cysteine hydrochloride 0.4-0.8g
Water for injection adds to 2L.
More preferably, per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30g
Sodium chloride 14.5g
Cysteine hydrochloride 0.4g
Water for injection adds to 2L.
Fasudic hydrochloride pharmaceutical composition of the present invention is to adopt following method preparation:
Get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal, stir; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Among the present invention, the consumption of described medicinal charcoal is 0.05-0.1%.
Among the present invention, described stirring is to stir 30 minutes down at 55-65 ℃.
Among the present invention, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes, is preferably 121 ℃ of pressure sterilizings 15 minutes.
For realizing second purpose of the present invention, the present invention adopts following technical scheme:
Fasudic hydrochloride preparation of drug combination method of the present invention, wherein, this method comprises the steps:
Get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal, stir; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
According to aforesaid preparation method, wherein, the consumption of described medicinal charcoal is 0.05-0.1%.
According to aforesaid preparation method, wherein, described stirring is to stir 30 minutes down at 55-65 ℃.
According to aforesaid preparation method, wherein, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes, is preferably 121 ℃ of pressure sterilizings 15 minutes.
Below to the more detailed elaboration of the present invention:
One aspect of the present invention provides a kind of Fasudic hydrochloride pharmaceutical composition of injection, per 1000 described Fasudic hydrochloride pharmaceutical compositions, and its prescription consists of:
Fasudic hydrochloride 15-60g
Sodium chloride 13.05-15.95g
Cysteine hydrochloride 0.2-0.8g
Water for injection adds to 2L.
Traditional fasudil hydrochloride injection, photostability is poor, and easily degraded is separated out, and quality can't guarantee.
Among the present invention, in stability study process to fasudil hydrochloride injection light, a certain amount of cysteine hydrochloride is selected in discovery for use, behind the pH value of elder generation's regulator solution, dissolve Fasudic hydrochloride again, add a certain proportion of sodium chloride, can effectively improve the stability of said preparation light, also make it be difficult for separating out, the related substance no change.Through the screening of tens of times test recipes and the summary of test data, optimized its recipe quantity, not only solved the problem of photostability difference, and made the product clarity good, constant product quality.
The Fasudic hydrochloride pharmaceutical composition of a kind of injection of the present invention, per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 15-60g
Sodium chloride 13.05-15.95g
Cysteine hydrochloride 0.2-0.8g
Water for injection adds to 2L.
Preferably, per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30-60g
Sodium chloride 14.5-15.95g
Cysteine hydrochloride 0.4-0.8g
Water for injection adds to 2L.
More preferably, per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30g
Sodium chloride 14.5g
Cysteine hydrochloride 0.4g
Water for injection adds to 2L.
The inventor finds through great deal of experimental, when the Fasudic hydrochloride pharmaceutical composition of counting is above-mentioned when more apolegamy side being arranged, and described injection the best in quality, stable best.
Another aspect of the present invention provides the preparation method of fasudil hydrochloride injection of the present invention, and this method is simple, and prepared fasudil hydrochloride injection is stable to light, can not separate out, and clarity is good, good stability.
Preparation method provided by the present invention comprises: get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal, stir; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
The fasudil hydrochloride injection that makes according to the inventive method proves that through industrial amplification production machine study on the stability product is stable, and through pharmacology, toxicological test, solution is non-stimulated to blood vessel, does not have irritated reaction, does not also have haemolysis, and human body is not had injury.
In the preparation method of the present invention, the consumption of described medicinal charcoal is 0.05-0.1%.
In the preparation method of the present invention, described stirring is to stir 30 minutes down at 55-65 ℃.
Add an amount of medicinal charcoal and can improve the clarity of solution, can adsorb thermal source, pigment again, medicinal charcoal there is no absorption to Fasudic hydrochloride, the inventor adopts UV-VIS spectrophotometry to measure the content of Fasudic hydrochloride, investigated the influence to Fasudic hydrochloride content in the injection of medicinal charcoal, temperature, adsorption time.The result shows, the medicinal charcoal consumption is at 0.05-0.1%, and adsorption time is at 30 minutes, and adsorption temp is at 55-65 ℃, best results.
In the preparation method of the present invention, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes, is preferably 121 ℃ of pressure sterilizings 15 minutes.
Product of the present invention is the sterile water solution of Fasudic hydrochloride, and sterilising conditions is very crucial, should reach sterilization effect, can not destroy solution again, and the inventor investigates sterilising conditions, sees test example 4 for details.The result shows, at 121 ℃ of pressure sterilizing 15-20 minutes, and wherein 121 ℃ of pressure sterilizings 15 minutes, best results.
Compared with prior art, the present invention has following advantage:
1) new Fasudic hydrochloride compositions provided by the present invention has thoroughly solved the stability problem of Fasudic hydrochloride to light.
2) fasudil hydrochloride injection provided by the present invention is for the market risk of the yield that improves this product, reduction product, and better application has very big help in clinical treatment.
3) new Fasudic hydrochloride compositions provided by the present invention proves constant product quality, through pharmacology, toxicological test through industrialized great production and study on the stability, solution is non-stimulated to blood vessel, do not have irritated reaction, do not have haemolysis yet, human body is not had injury.
4) new Fasudic hydrochloride preparation of compositions method provided by the present invention, this method is simple, and prepared fasudil hydrochloride injection is stable to light, can not separate out, and clarity is good, good stability.
The specific embodiment
Below in conjunction with embodiment the present invention is described in further detail
Embodiment 1
Per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30g
Sodium chloride 14.5g
Cysteine hydrochloride 0.4g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Embodiment 2
Per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 15g
Sodium chloride 14.5g
Cysteine hydrochloride 0.2g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Embodiment 3
Per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 60g
Sodium chloride 18g
Cysteine hydrochloride 0.8g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Embodiment 4
Per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30g
Sodium chloride 13.05g
Cysteine hydrochloride 0.4g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Embodiment 5
Per 1000 described Fasudic hydrochloride pharmaceutical compositions, its prescription consists of:
Fasudic hydrochloride 30g
Sodium chloride 15.95g
Cysteine hydrochloride 0.4g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Comparing embodiment 1
Fasudic hydrochloride 30g
Sodium chloride 18g
Water for injection adds to 2L.
Preparation technology: get recipe quantity water for injection 90%, temperature adds Fasudic hydrochloride, the sodium chloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal 0.05%, stir, placed 30 minutes; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; 121 ℃ of pressure sterilizings 15 minutes; Lamp inspection; Warehouse-in; Promptly get fasudil hydrochloride injection.
Test example 1
This test example is used to investigate the stability of solution of prescription and clarity, crystallization and the sedimentary situation that influences of cysteine hydrochloride recipe quantity and solution.
Prescription is formed
The 1-that will write out a prescription prescription 5 places the illumination 24 hours of 4500LX ± 500LX, respectively at 0 day, 10 days its character, pH value and related substance is checked.The results are shown in following table:
Above result of the test shows, adding a certain amount of cysteine hydrochloride in the prescription has certain effect to solution fast light, and related substance does not have obvious increase, and pH is stable.
Test example 2
This test example is to investigate the stability of Fasudic hydrochloride compositions provided by the present invention.
The accelerated test of fasudil hydrochloride injection
Method according to the embodiment of the invention 1 prepares three batches of fasudil hydrochloride injections (lot number is respectively HK1101001, HK1101002, HK1101003) according to commercially available back, at 40 ℃ ± 2 ℃, the condition of RH75% ± 5% was placed 6 months, during this time respectively at sampling in the 1st, 2,3,6 month, detect according to stable inspection item, and compare with 0 day data.
1, investigation project
High spot reviews: character, pH value, visible foreign matters, osmotic pressure molar density, related substance and content.
2, test data sees the following form
Above conclusion (of pressure testing) is as can be seen: this product is placed 6 months every detection indexs and was compared no significant difference with 0 month under long term test and accelerated test condition, stability is measured.
Test example 3
This test example is to investigate the influence to Fasudic hydrochloride content in the injection of medicinal charcoal consumption, temperature, adsorption time.
The preparation of 1 Fasudic hydrochloride sample solution: precision takes by weighing Fasudic hydrochloride 70g and places the 5000ml volumetric flask, and the dilute with water scale shakes up, and measures content, as reserve liquid.
The influence that 2 different time different amounts medicinal charcoal adsorb Fasudic hydrochloride: get reserve liquid 100ml25 part respectively, per 5 parts is one group, add medicinal charcoal 0,0.05,0.1,0.15,0.2g respectively, in 60 ℃ of thermostat water baths, worked overtime 15,20,25,30,35 minutes respectively for 5 parts in every group, be cooled to room temperature, get subsequent filtrate and measure trap, calculate content, the results are shown in Table according to containing under the quantifier:
Medicinal charcoal different amounts and different influences of stirring you to Fasudic hydrochloride content
As can be seen, the consumption of medicinal charcoal was greater than 0.15 o'clock from the table, and the content of Fasudic hydrochloride obviously descends, and adsorption time is long more, and it is obvious more that content descends, and therefore the medicinal charcoal consumption is 0.05 in preparation process, and adsorption time was at 30 minutes.
Test example 4
This test example is to investigate under the sterilising conditions temperature to the influence of fasudil hydrochloride injection content:
This product is the sterile water solution of Fasudic hydrochloride, sterilising conditions is very crucial, should reach sterilization effect, can not destroy solution again, the inventor investigates sterilising conditions, behind the Fasudic hydrochloride solution by prescription preparation certain volume, be packaged in the ampoule bottle respectively at 115 ℃ 30 minutes, 121 ℃ 20 minutes, 121 ℃ 15 minutes
,121 ℃ of sterilizations in 20 minutes, observe in the solution of sterilization back drug content following table as a result:
Sterilising conditions is to the influence of fasudil hydrochloride injection content
From above test as can be seen: the sterilising temp condition is little to this product influence, select 121 ℃ 15 minutes, F0〉12, reach sterilization effect, solution content is not almost had influence.
Comparative test example 1 and embodiment 1 were placed the illumination of 4500LX ± 500LX, 60 ℃ ± 2 ℃ pyritous calorstats respectively 10 days, its character, pH value and related substance are checked respectively at 0 day, 10 days.The results are shown in following table:
Comparative test example 1
According to result of the test as can be known, embodiment 1 and comparative example 1 placed 10 days in the illumination of 4500LX ± 500LX, 60 ℃ ± 2 ℃ pyritous calorstats, embodiment 1 is under different condition, each checks that item has no significant change, the comparative example is all comparatively responsive to light, heat, related substance is defective, and pH obviously descends.
Claims (6)
1. the Fasudic hydrochloride pharmaceutical composition of an injection is characterized in that, per 1000 described Fasudic hydrochloride pharmaceutical compositions, and its prescription consists of:
Fasudic hydrochloride 15-60g
Sodium chloride 13.05-15.95g
Cysteine hydrochloride 0.2-0.8g
Water for injection adds to 2L.
2. the described Fasudic hydrochloride preparation of drug combination of claim 1 method is characterized in that, this method comprises the steps:
Get recipe quantity water for injection 90%, temperature adds the cysteine hydrochloride of recipe quantity, after the stirring and dissolving at 55-65 ℃; The Fasudic hydrochloride that adds recipe quantity, be stirred to dissolving after, in solution, add the sodium chloride of recipe quantity again, be stirred to dissolving fully; Record original ph,, regulate the pH value scope at 5.5-6.5 with 4% sodium hydroxide solution and 10% CYSTEAMINE HCL acid solution according to original ph; To adding medicinal charcoal, stir; Sucking filtration replenishes water for injection to full dose, mix homogeneously; Fine straining; Fill; Sterilization; Lamp inspection; Warehouse-in; Get product.
3. preparation method according to claim 2 is characterized in that, the consumption of described medicinal charcoal is 0.05-0.1%.
4. preparation method according to claim 2 is characterized in that, described stirring is to stir 30 minutes down at 55-65 ℃.
5. preparation method according to claim 2 is characterized in that, described sterilization is at 121 ℃ of pressure sterilizing 15-20 minutes.
6. preparation method according to claim 5 is characterized in that, described sterilization is 121 ℃ of pressure sterilizings 15 minutes.
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| CN102525897A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Injection solution of fasudil hydrochloride composition and preparation method thereof |
| CN103083323A (en) * | 2013-02-21 | 2013-05-08 | 中国医学科学院阜外心血管病医院 | Application of fasudil hydrochloride in preparation of medicament for promoting in-vivo survival and repair of mesenchymal stem cells and preparation of fasudil hydrochloride |
| CN103222953A (en) * | 2013-05-03 | 2013-07-31 | 成都苑东药业有限公司 | Fasudil hydrochloride injection composition and its preparation method |
| CN110507608A (en) * | 2019-10-08 | 2019-11-29 | 四川太平洋药业有限责任公司 | A kind of fasudil hydrochloride injection preparation process |
| CN110755373A (en) * | 2019-11-18 | 2020-02-07 | 扬子江药业集团广州海瑞药业有限公司 | Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1729985A (en) * | 2005-08-02 | 2006-02-08 | 吴良信 | Fasudil hydrochloride injection and its preparation process |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1729985A (en) * | 2005-08-02 | 2006-02-08 | 吴良信 | Fasudil hydrochloride injection and its preparation process |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525897A (en) * | 2012-01-17 | 2012-07-04 | 山东罗欣药业股份有限公司 | Injection solution of fasudil hydrochloride composition and preparation method thereof |
| CN102525897B (en) * | 2012-01-17 | 2013-04-10 | 山东罗欣药业股份有限公司 | Injection solution of fasudil hydrochloride composition and preparation method thereof |
| CN103083323A (en) * | 2013-02-21 | 2013-05-08 | 中国医学科学院阜外心血管病医院 | Application of fasudil hydrochloride in preparation of medicament for promoting in-vivo survival and repair of mesenchymal stem cells and preparation of fasudil hydrochloride |
| CN103222953A (en) * | 2013-05-03 | 2013-07-31 | 成都苑东药业有限公司 | Fasudil hydrochloride injection composition and its preparation method |
| CN110507608A (en) * | 2019-10-08 | 2019-11-29 | 四川太平洋药业有限责任公司 | A kind of fasudil hydrochloride injection preparation process |
| CN110755373A (en) * | 2019-11-18 | 2020-02-07 | 扬子江药业集团广州海瑞药业有限公司 | Fasudil hydrochloride injection pharmaceutical composition and preparation method thereof |
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