CN102210690A - Fasudil hydrochloride injection composition and preparation method thereof - Google Patents
Fasudil hydrochloride injection composition and preparation method thereof Download PDFInfo
- Publication number
- CN102210690A CN102210690A CN2011101652437A CN201110165243A CN102210690A CN 102210690 A CN102210690 A CN 102210690A CN 2011101652437 A CN2011101652437 A CN 2011101652437A CN 201110165243 A CN201110165243 A CN 201110165243A CN 102210690 A CN102210690 A CN 102210690A
- Authority
- CN
- China
- Prior art keywords
- injection
- fasudic hydrochloride
- sodium chloride
- parts
- add
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a Fasudil hydrochloride injection composition and a preparation method thereof. The composition comprises Fasudil hydrochloride serving as a main medicine and 0.7-percent sodium chloride serving as an auxiliary material, wherein the pH value of the composition is 3.6 to 3.9. The preparation method of the composition comprises: adding water for injection into Fasudil hydrochloride and sodium chloride, regulating pH value by using hydrochloric acid, adding active carbon into the solution, adding water, stirring, filtering, filling and performing lamp detection to obtain the medicinal composition of the invention. The medicinal composition is less irritant, very stable and easy for storage and transport.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of Fasudic hydrochloride composition and method of making the same.
Background technology
Fasudic hydrochloride, chemical name are six hydrogen-1-(5-isoquinolinesulfonylcompounds)-1H-1,4-diazepine hydrochlorate, and molecular formula C14H17N3O2SHCl, molecular weight 327.83, structural formula is:
Be that a kind of kinases inhibitor is the intracellular calcium antagonist.A kind of preparation method of fasudil hydrochloride injection is disclosed among the Chinese patent CN1729985A, prepare hydrochloric fasudil, and the solution of sodium chloride, glucose, aminoacid or other pharmaceutically acceptable diluent, the adjusting pH value is 4.0-7.5, decolouring, sterilization.Disclose a kind of preparation method of freeze dry formulation of fasudil hydrochloride among the Chinese patent CN1729984A, made through lyophilization by the solution that contains pharmaceutically acceptable excipient such as Fasudic hydrochloride and mannitol, lactose, sodium chloride, glucose, glycine.The improvement method of the light stability of fasudil in a kind of water white transparency container or its esters is disclosed among the Chinese patent CN1929847A.There is the mass defect of less stable in the Fasudic hydrochloride injection of above-mentioned existing formulation preparation, is difficult to reach the standard-required of effect duration.
Summary of the invention
The object of the invention is to provide a kind of stable Fasudic hydrochloride compositions, and another purpose of the present invention is to provide Fasudic hydrochloride preparation of compositions method.
Said composition comprises the principal agent Fasudic hydrochloride, and adjuvant 0.7% sodium chloride, said composition pH value are 3.6～3.9.
The pH value of Fasudic hydrochloride compositions (3.6～3.9) makes stability of solution more excellent, shows that Fasudic hydrochloride analyte content is lower.
The said composition raw material consists of:
Fasudic hydrochloride 20～40 weight portions, preferred 25,30,35 weight portions;
0.1mol/L hydrochloric acid solution 30～80 parts by volume, preferred 35～70 parts by volume;
Water for injection is to the 1500-2500 parts by volume, preferred 1800,2000,2200 parts by volume;
1500-2500 parts by volume solution sodium chloride-containing 10.5～17.5 weight portions, preferred 1800 parts by volume solution sodium chloride-containing, 12.6 weight portions, 2000 parts by volume solution sodium chloride-containing, 14 weight portions, 2200 parts by volume solution sodium chloride-containing, 15.4 weight portions.
Preparation of drug combination method of the present invention comprises the steps:
Fasudic hydrochloride, 10.5～17.5 weight portion sodium chloride of preparation 20～40 weight portions, add water for injection, stirring makes dissolving, and pH to 3.6～3.9 with 0.1mol/L hydrochloric acid solution 30～80 parts by volume adjusting medicinal liquid add water for injection to 1500～2500 parts by volume; Add 0.3～2.5 weight portion needle-use activated carbon in gained solution, stirred 10～20 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, re-using aperture of filter material is 0.22 μ m fine straining, embedding, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Preparation of drug combination method of the present invention can be preferably as follows step:
Prepare Fasudic hydrochloride, the 12.6 weight portion sodium chloride of 25 weight portions, add water for injection, stir and make dissolving, the pH to 3.8 with 0.1mol/L hydrochloric acid solution 30～70 parts by volume adjusting medicinal liquid adds water for injection to 1800 parts by volume; Add 1.44 weight portion needle-use activated carbons in gained solution, stirred 15 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, re-using aperture of filter material is 0.22 μ m fine straining, embedding, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Preparation of drug combination method of the present invention can also be preferably as follows step:
Prepare Fasudic hydrochloride, the 15.4 weight portion sodium chloride of 35 weight portions, add water for injection, stir and make dissolving, the pH to 3.75 with 0.1mol/L hydrochloric acid solution 60 parts by volume adjusting medicinal liquid adds water for injection to 2200 parts by volume; Add 0.88 weight portion needle-use activated carbon in gained solution, stirred 15 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, re-using aperture of filter material is 0.22 μ m fine straining, embedding, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
The weight portion in the invention described above pharmaceutical composition and preparation method thereof and the pass of parts by volume are the relation of g/ml.
In the Chinese Pharmacopoeia about osmotic pressure: " during with pharmaceutical preparatioies such as liquid preparations, must pay close attention to its osmotic pressure at preparation injection, eye.Add the preparation of osmotic pressure regulator in the prescription, all should control its osmotic pressure molar density.”
In the pharmaceutical composition of the present invention, sodium chloride is osmotic pressure regulator, and its consumption is 0.7% o'clock, and the osmotic pressure of compositions is 260～320 mM osmotic pressuries (mOsmolkg-1), and this moment, infiltration was than should be 0.9～1.1.The sodium chloride of this consumption makes the zest of compositions less.
It is better stable that injection needs to verify that by low temperature or freezing-thawing test stability in its transportation or the use, the inventor find to contain the injection of osmotic pressure regulator sodium chloride in carrying out this test.
Find when studying at the said composition pH value, control its pH value, analyte content is reduced, pH value 3.6～3.9 o'clock said composition principal agent is the most stable, shows that 60 ℃ of fasudil analyte content of placing after March are low.
Experiment and embodiment are used to further specify but are not limited to the present invention below.
Experimental example one: measure the mM osmotic pressure experiment of pharmaceutical composition of the present invention (embodiment one preparation)
Prescription consists of:
| Prescription 1 | Prescription 2 ＊ | Prescription 3 | Prescription 4 | |
| Fasudic hydrochloride | 3.75g | 3.75g | 3.75g | 3.75g |
| Sodium chloride | 0 | 1.75g | 2.00g | 2.25g |
| 0.1mol/L hydrochloric acid solution | In right amount | In right amount | In right amount | In right amount |
| Water for injection | To 250.0ml | To 250.0ml | To 250.0ml | To 250.0ml |
| Make | 125 | 125 | 125 | 125 |
Annotate: * is the pharmaceutical composition of the present invention with embodiment one preparation.
Each prescription uses identical preparation method: Fasudic hydrochloride and solid adjuvant material add in an amount of water for injection, jolting makes dissolving, uses the 0.1mol/L hydrochloric acid solution to regulate pH to 3.6～3.9 of medicinal liquid, and medicinal liquid is accurately moved in the 250ml measuring bottle, add water for injection to scale, shake up, solution moves in the beaker, and using the aperture is the filter filtration fill of 0.22 μ m, every loading amount is 1.80～2.20ml (ampoule is through cleaning and sterilization), melt envelope, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection.The character of sample for reference and pH value, the mM osmotic pressure of working sample, the result is as follows.
| Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | |
| Character | Colourless clear liquid | Colourless clear liquid | Colourless clear liquid | Colourless clear liquid |
| PH value | 3.75 | 3.78 | 3.72 | 3.77 |
| The mM osmotic pressure | 69 | 293 | 322 | 358 |
| Osmotic pressure is judged | Hypotonic | Deng oozing | Slightly height oozes | Slightly height oozes |
The amount of calculating the isoosmotic adjusting agent sodium chloride that adds in the Fasudic hydrochloride compositions by the osmometry result is 0.7% o'clock, and this pharmaceutical composition is to wait to ooze.
Experimental example 2: freezing-thawing test
Prescription consists of:
Each prescription uses identical preparation method: Fasudic hydrochloride and solid adjuvant material add in an amount of water for injection, jolting makes dissolving, uses the 0.1mol/L hydrochloric acid solution to regulate pH to 3.6～3.9 of medicinal liquid, and medicinal liquid is accurately moved in the 250ml measuring bottle, add water for injection to scale, shake up, solution moves in the beaker, and using the aperture is the filter filtration fill of 0.22 μ m, every loading amount is 1.80～2.20ml (ampoule is through cleaning and sterilization), melt envelope, 121 ℃ of pressure sterilizings of sample 15 minutes, lamp inspection.
Sample is placed according to freezing-thawing test investigation condition, and concrete grammar is as follows:
Freezing-thawing test should comprise three circulations, and each circulation should be under-10～-20 ℃ of conditions 2 days, investigate 2 days then under 40 ℃ of acceleration environments, and sampling detects.
Check result is as follows:
Result of the test shows that pharmaceutical composition physical stability of the present invention is better, more can tolerate the variations in temperature of transportation and duration of storage.
Experimental example 3:
Experiment is done 2 groups altogether, and its sample is respectively pharmaceutical composition of the present invention (with experimental example 2) and the domestic preparation that gone on the market (with experimental example 2).
Get 3 of healthy qualified, the undamaged rabbit of ear edge for every group, by the body weight administration, when testing with sterile working's method injection this product 5ml/kg[; get 5 bottles of this product; add and test after 0.6mg/ml is dissolved in N.S to 50ml dilution respectively at the left side auricular vein]; the right side is with the N.S of method injection with volume, about the about 2ml/min of injection speed.Every day 1 time, injected altogether 3 days.48～96 hours and observation period finish back the 14th day before administration every day and after the last administration, observe injection site proximal part following tissue and blood vessel and have or not hyperemia, erythema, edema, 3 rabbit are divided 2 execution [96 hours (2) and observation period finish back the 14th day (1) after the last administration respectively] then, the rabbit ear edge of 0.5～5.0cm below the injection site proximal part is cut formaldehyde fixed with 10%.Two rabbit ears of every rabbit are done a pathological section respectively at 1.3cm, 2.6cm below the auricular vein entry point proximal part and 4.0cm place, observe to have or not significance irritant reaction such as endothelial injury, tissue degeneratiaon or necrosis.
The result is as follows:
Experimental result shows that pharmaceutical composition blood vessel irritation of the present invention is littler.
Experimental example 4:pH value screening experiment
| Prescription is formed: | |
| Fasudic hydrochloride | 30.0g |
| Sodium chloride | 14.0g |
| 0.1mol/L hydrochloric acid solution | In right amount |
| Water for injection | To 2000.0ml |
| Make | 1000 |
PH is respectively according to formulation: 3.5,3.55,3.6,3.75,3.9,4.0,4.1,4.5,4.9,5.0,5.1,5.5,6.0,6.5,7.0 and 7.5 sample, the pH value of sample uses the sodium hydroxide solution of 0.1mol/L hydrochloric acid solution and 0.1mol/L to regulate, medical filtration with each pH value in the experiment is filled in the brown curved neck easy breaking ampoule of 2ml, melt envelope, 121 ℃ of pressure sterilizings of sample 15 minutes.
Sample after the sterilization is placed March in 60 ℃, measures 60 ℃ of placements 0 month and March sample character, single impurity, total impurities and content, the result is as follows.
PH value is respectively 3.5,3.55,3.6,3.75,3.9,4.0,4.1,4.5,4.9,5.0,5.1,5.5,6.0,6.5,7.0 and 7.5 pharmaceutical composition character check result:
| The sample pH value | 0 month | Place March for 60 ℃ |
| 3.5 | Colourless clear liquid | Colourless clear liquid |
| 3.55 | Colourless clear liquid | Colourless clear liquid |
| 3.6 | Colourless clear liquid | Colourless clear liquid |
| 3.75 | Colourless clear liquid | Colourless clear liquid |
| 3.9 | Colourless clear liquid | Colourless clear liquid |
| 4.0 | Colourless clear liquid | Colourless clear liquid |
| 4.1 | Colourless clear liquid | Colourless clear liquid |
| 4.5 | Colourless clear liquid | Colourless clear liquid |
| 4.9 | Colourless clear liquid | Colourless clear liquid |
| 5.0 | Colourless clear liquid | Colourless clear liquid |
| 5.1 | Colourless clear liquid | Colourless clear liquid |
| 5.5 | Colourless clear liquid | Colourless clear liquid |
| 6.0 | Colourless clear liquid | Colourless clear liquid |
| 6.5 | Colourless clear liquid | Colourless clear liquid |
| 7.0 | Colourless clear liquid | Colourless clear liquid |
| 7.5 | Colourless clear liquid | Colourless clear liquid |
Single determination of foreign matter result:
| The sample pH value | 0 month | Place March for 60 ℃ | Increase |
| 3.5 | 0.03％ | 0.44％ | 0.41％ |
| 3.55 | 0.03％ | 0.14％ | 0.11％ |
| 3.6 | 0.03％ | 0.05％ | 0.02％ |
| 3.75 | 0.03％ | 0.06％ | 0.03％ |
| 3.9 | 0.03％ | 0.08％ | 0.05％ |
| 4.0 | 0.03％ | 0.11％ | 0.08％ |
| 4.1 | 0.03％ | 0.13％ | 0.10％ |
| 4.5 | 0.03％ | 0.17％ | 0.14％ |
| 4.9 | 0.03％ | 0.19％ | 0.16％ |
| 5.0 | 0.03％ | 0.21％ | 0.18％ |
| 5.1 | 0.03％ | 0.36％ | 0.33％ |
| 5.5 | 0.06％ | 1.28％ | 1.22％ |
| 6.0 | 0.07％ | 2.46％ | 2.39％ |
| 6.5 | 0.12％ | 3.79％ | 3.67％ |
| 7.0 | 0.20％ | 6.13％ | 5.93％ |
| 7.5 | 0.27％ | 9.65％ | 9.38％ |
The total impurities check result:
| The sample pH value | 0 month | Place March for 60 ℃ | Increase |
| 3.5 | 0.06％ | 0.77％ | 0.71％ |
| 3.55 | 0.07％ | 0.32％ | 0.25％ |
| 3.6 | 0.07％ | 0.12％ | 0.05％ |
| 3.75 | 0.07％ | 0.12％ | 0.05％ |
| 3.9 | 0.08％ | 0.16％ | 0.08％ |
| 4.0 | 0.08％ | 0.20％ | 0.12％ |
| 4.1 | 0.08％ | 0.26％ | 0.18％ |
| 4.5 | 0.08％ | 0.38％ | 0.30％ |
| 4.9 | 0.08％ | 0.43％ | 0.35％ |
| 5.0 | 0.09％ | 0.46％ | 0.37％ |
| 5.1 | 0.10％ | 0.90％ | 0.80％ |
| 5.5 | 0.16％ | 1.84％ | 1.68％ |
| 6.0 | 0.19％ | 3.33％ | 3.14％ |
| 6.5 | 0.28％ | 4.83％ | 4.55％ |
| 7.0 | 0.34％ | 7.15％ | 6.81％ |
| 7.5 | 0.46％ | 10.66％ | 10.20％ |
The content check result:
| The sample pH value | 0 month | Place March for 60 ℃ | Reduce |
| 3.5 | 99.32％ | 96.46％ | 2.86％ |
| 3.55 | 99.57％ | 97.37％ | 2.20％ |
| 3.6 | 99.64％ | 98.22％ | 1.42％ |
| 3.75 | 100.21％ | 98.72％ | 1.49％ |
| 3.9 | 99.58％ | 97.95％ | 1.63％ |
| 4.0 | 99.15％ | 97.24％ | 1.91％ |
| 4.1 | 99.70％ | 97.64％ | 2.06％ |
| 4.5 | 100.11％ | 97.87％ | 2.24％ |
| 4.9 | 99.26％ | 96.97％ | 2.29％ |
| 5.0 | 100.71％ | 98.37％ | 2.34％ |
| 5.1 | 99.04％ | 95.46％ | 3.58％ |
| 5.5 | 99.20％ | 94.02％ | 5.18％ |
| 6.0 | 99.37％ | 92.87％ | 6.50％ |
| 6.5 | 99.14％ | 91.74％ | 7.40％ |
| 7.0 | 99.25％ | 89.80％ | 9.45％ |
| 7.5 | 98.62％ | 86.32％ | 12.3％ |
By single impurity, total impurities and assay result as can be known, the pH of Fasudic hydrochloride compositions is better at 3.6～3.9 scope internal stabilities, places March for 60 ℃, single impurity and total impurities increase hardly, and the variation of content is very little, within 2%, also can ignore.
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment 1:
Fasudic hydrochloride, the 10.5g sodium chloride of preparation 20g add water for injection, stir and make dissolving, and the pH to 3.60 with 0.1mol/L hydrochloric acid solution 80ml regulates medicinal liquid adds water for injection to 1500ml; Add the 0.3g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 2:
Fasudic hydrochloride, the 12.6g sodium chloride of preparation 40g add water for injection, stir and make dissolving, and the pH to 3.90 with 0.1mol/L hydrochloric acid solution 30ml regulates medicinal liquid adds water for injection to 1800ml; Add the 2.5g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 3:
Fasudic hydrochloride, the 14g sodium chloride of preparation 30g add water for injection, stir and make dissolving, and the pH to 3.74 with 0.1mol/L hydrochloric acid solution 55ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 4:
Fasudic hydrochloride, the 12.6g sodium chloride of preparation 25g add water for injection, stir and make dissolving, and the pH to 3.85 with 0.1mol/L hydrochloric acid solution 35ml regulates medicinal liquid adds water for injection to 1800ml; Add the 0.9g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 5:
Fasudic hydrochloride, the 14g sodium chloride of preparation 35g add water for injection, stir and make dissolving, and the pH to 3.75 with 0.1mol/L hydrochloric acid solution 60ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.1g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 6:
Fasudic hydrochloride, the 14g sodium chloride of preparation 35g add water for injection, stir and make dissolving, and the pH to 3.70 with 0.1mol/L hydrochloric acid solution 70ml regulates medicinal liquid adds water for injection to 2000ml; Add the 0.4g needle-use activated carbon in gained solution, stirred 15 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 15 minutes lamp inspection of 121 ℃ of pressure sterilizings promptly get the present composition.
Embodiment 7:
Fasudic hydrochloride, the 14g sodium chloride of preparation 20g add water for injection, stir and make dissolving, and the pH to 3.80 with 0.1mol/L hydrochloric acid solution 30ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 8:
Fasudic hydrochloride, the 15.4g sodium chloride of preparation 40g add water for injection, stir and make dissolving, and the pH to 3.7 with 0.1mol/L hydrochloric acid solution 80ml regulates medicinal liquid adds water for injection to 2200ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 9:
Fasudic hydrochloride, the 14g sodium chloride of preparation 30g add water for injection, stir and make dissolving, and the pH to 3.8 with 0.1mol/L hydrochloric acid solution 30ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 10:
Fasudic hydrochloride, the 14g sodium chloride of preparation 30g add water for injection, stir and make dissolving, and the pH to 3.7 with 0.1mol/L hydrochloric acid solution 70ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 11:
Fasudic hydrochloride, the 17.5g sodium chloride of preparation 20g add water for injection, stir and make dissolving, and the pH to 3.8 with 0.1mol/L hydrochloric acid solution 30ml regulates medicinal liquid adds water for injection to 2500ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 12:
Fasudic hydrochloride, the 14g sodium chloride of preparation 30g add water for injection, stir and make dissolving, and the pH to 3.7 with 0.1mol/L hydrochloric acid solution 80ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Embodiment 13:
Fasudic hydrochloride, the 14g sodium chloride of preparation 40g add water for injection, stir and make dissolving, and the pH to 3.8 with 0.1mol/L hydrochloric acid solution 60ml regulates medicinal liquid adds water for injection to 2000ml; Add the 1.0g needle-use activated carbon in gained solution, stirred 15 minutes, gained solution use filter element aperture is that 1 μ m removes by filter active carbon, and re-using aperture of filter material is 0.22 μ m fine straining, embedding, and 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the present composition.
Claims (7)
1. Fasudic hydrochloride compositions, it is characterized by the said composition principal agent is Fasudic hydrochloride, accessory package sodium chloride-containing and hydrochloric acid, pH value are 3.6～3.9.
2. Fasudic hydrochloride compositions as claimed in claim 1 comprises 0.7% sodium chloride, and the osmotic pressure that it is characterized in that compositions is at 260～320 mM osmotic pressuries.
3. a Fasudic hydrochloride pharmaceutical composition is characterized in that said composition consists of: Fasudic hydrochloride 20～40 weight portions; Sodium chloride is 10.5～17.5 weight portions; 0.1mol/L hydrochloric acid solution 30～80 parts by volume; Water for injection to 1500～2500 parts by volume.
4. pharmaceutical composition as claimed in claim 1 is characterized in that above-mentioned Fasudic hydrochloride is 25,30 or 35 weight portions; Sodium chloride is 12.6,14 or 15.4 weight portions; 0.1mol/L hydrochloric acid solution is 35～70 parts by volume; Water for injection is 1800,2000 or 2200 parts by volume.
5. preparation of drug combination method as claimed in claim 1 or 2 is characterized in that this method comprises:
Fasudic hydrochloride, 10.5～17.5 weight portion sodium chloride of preparation 20～40 weight portions, add in 70%～90% water for injection, stirring makes dissolving, and pH to 3.6～3.9 with 0.1mol/L hydrochloric acid solution 30～80 parts by volume adjusting medicinal liquid add water for injection to 1500～2500 parts by volume; Add 0.3～2.5 weight portion needle-use activated carbon in gained solution, stirred 10～20 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, re-using aperture of filter material is 0.22 μ m fine straining, embedding, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the Fasudic hydrochloride compositions.
6. preparation of drug combination method as claimed in claim 3 is characterized in that this method comprises:
Prepare Fasudic hydrochloride, the 12.6 weight portion sodium chloride of 25 weight portions, add in 85% water for injection, stir and make dissolving, the pH to 3.8 with 0.1mol/L hydrochloric acid solution 30～70 parts by volume adjusting medicinal liquid adds water for injection to 1800 parts by volume; Add 1.44 weight portion needle-use activated carbons in gained solution, stirred 15 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, re-using aperture of filter material is 0.22 μ m fine straining, embedding, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the Fasudic hydrochloride compositions.
7. preparation of drug combination method as claimed in claim 3 is characterized in that this method comprises:
Prepare Fasudic hydrochloride, the 15.4 weight portion sodium chloride of 35 weight portions, add in 75% water for injection, stir and make dissolving, the pH to 3.75 with 0.1mol/L hydrochloric acid solution 60 parts by volume adjusting medicinal liquid adds water for injection to 2200 parts by volume; Add 0.88 weight portion needle-use activated carbon in gained solution, stirred 15 minutes, it is that 1 μ m removes by filter active carbon that gained solution uses the filter element aperture, re-using aperture of filter material is 0.22 μ m fine straining, embedding, 121 ℃ of pressure sterilizings 15 minutes, lamp inspection promptly gets the Fasudic hydrochloride compositions.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110165243A CN102210690B (en) | 2011-06-20 | 2011-06-20 | Fasudil hydrochloride injection composition and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110165243A CN102210690B (en) | 2011-06-20 | 2011-06-20 | Fasudil hydrochloride injection composition and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102210690A true CN102210690A (en) | 2011-10-12 |
| CN102210690B CN102210690B (en) | 2012-10-10 |
Family
ID=44742377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110165243A Expired - Fee Related CN102210690B (en) | 2011-06-20 | 2011-06-20 | Fasudil hydrochloride injection composition and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102210690B (en) |
Cited By (3)
| 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 |
| CN102697707A (en) * | 2012-04-17 | 2012-10-03 | 上海禾丰制药有限公司 | Fasudil hydrochloride injection and preparation method thereof |
| 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 |
Citations (6)
| 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 |
| CN1729984A (en) * | 2005-08-01 | 2006-02-08 | 吴良信 | Freeze dry formulation of fasudil hydrochloride and its preparation process |
| CN102008433A (en) * | 2010-12-01 | 2011-04-13 | 广东三信药业有限公司 | Fasudil salt injection for improving stability and preparation method thereof |
| CN102008487A (en) * | 2010-11-12 | 2011-04-13 | 天津红日药业股份有限公司 | Application of Fasudil in preparing drug for treating pulmonary hypertension by atomized inhalation |
| CN102028694A (en) * | 2010-11-12 | 2011-04-27 | 天津红日药业股份有限公司 | Application of Fasudil in preparing medicaments for treating glaucoma through ophthalmic drug delivery |
| CN102138894A (en) * | 2011-03-30 | 2011-08-03 | 奇方(天津)医药科技有限公司 | Stable large-capacity fasudil hydrochloride injection |
-
2011
- 2011-06-20 CN CN201110165243A patent/CN102210690B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1729984A (en) * | 2005-08-01 | 2006-02-08 | 吴良信 | Freeze dry formulation of fasudil hydrochloride and its preparation process |
| CN1729985A (en) * | 2005-08-02 | 2006-02-08 | 吴良信 | Fasudil hydrochloride injection and its preparation process |
| CN102008487A (en) * | 2010-11-12 | 2011-04-13 | 天津红日药业股份有限公司 | Application of Fasudil in preparing drug for treating pulmonary hypertension by atomized inhalation |
| CN102028694A (en) * | 2010-11-12 | 2011-04-27 | 天津红日药业股份有限公司 | Application of Fasudil in preparing medicaments for treating glaucoma through ophthalmic drug delivery |
| CN102008433A (en) * | 2010-12-01 | 2011-04-13 | 广东三信药业有限公司 | Fasudil salt injection for improving stability and preparation method thereof |
| CN102138894A (en) * | 2011-03-30 | 2011-08-03 | 奇方(天津)医药科技有限公司 | Stable large-capacity fasudil hydrochloride injection |
Cited By (4)
| 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 |
| CN102697707A (en) * | 2012-04-17 | 2012-10-03 | 上海禾丰制药有限公司 | Fasudil hydrochloride injection and preparation method thereof |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102210690B (en) | 2012-10-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102166360B (en) | Ibuprofen intravenously administrable preparation and preparation method thereof | |
| CN102302463B (en) | Lansoprazole lyophilized powder for injection and preparation method | |
| RU2694368C2 (en) | Solid pharmaceutical compositions containing biopterin derivatives, and methods of using such compositions | |
| CN102160852A (en) | Ibuprofen injection and preparation method thereof | |
| CN102210690B (en) | Fasudil hydrochloride injection composition and preparation method thereof | |
| TW202128210A (en) | A stable parenteral dosage form of cetrorelix acetate | |
| MX2012008516A (en) | Alpha-2 adrenergic agonist having long duration of intraocular pressure-lowering effect. | |
| CN101961311B (en) | 5alpha-androstane (alkyl)-3beta,5,6beta-triol injection and preparation method thereof | |
| CN102784382A (en) | Argatroban drug composition and preparation method and application of argatroban drug composition | |
| EP3984524A1 (en) | Ornidazole injection and s-ornidazole injection | |
| CN107198677A (en) | Progesterone suspension type long-acting injection and preparation method thereof and progesterone, which are suspended, injects powder pin | |
| CN104069063B (en) | Fasudic hydrochloride pharmaceutical composition and preparation method thereof | |
| CN102512379A (en) | Novel Echinocandin antifungal pharmaceutical composition and preparation method thereof | |
| CN102145162B (en) | Injection of medicine for treating premature delivery | |
| CN103520186B (en) | Pharmaceutical composition of a kind of fat-soluble vitamin for injection and preparation method thereof | |
| TW201440783A (en) | Pharmaceutical composition comprising micafungin or the salts thereof | |
| CN101795670A (en) | Liquid formulation of G-CSF | |
| CN101352441A (en) | Brimonidine tartrate in situ forming eye gel | |
| CN102302495A (en) | Tropisetron hydrochloride medicament composition for injection | |
| CN102526112B (en) | Sustained-release pearl clear-sighted eye drops and preparation method thereof | |
| CN103877578B (en) | Pharmaceutical naloxone hydrochloride composition for injection and preparation method of pharmaceutical naloxone hydrochloride composition | |
| CN102274194A (en) | Pharmaceutical composition containing tropisetron compound and preparation method thereof | |
| CN104922661A (en) | Pharmaceutical composition containing serelaxin and preparation method thereof | |
| ES2717299T3 (en) | A combination of dosage units for use in the treatment of premature labor | |
| CN114796104B (en) | Cyanomycin temperature-sensitive gel and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: HAINAN XIANTONG PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAINAN LIANGFANG MEDICINE CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 100012 Beijing city Chaoyang District Beiyuan No. 5 District four building three layer Research Institute Patentee after: HAINAN XIANTONG PHARMACEUTICAL CO., LTD. Address before: 100012 Beijing city Chaoyang District Beiyuan No. 5 District four building three layer Research Institute Patentee before: Hainan Liangfang Medicine Co., Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121010 Termination date: 20200620 |