CN101164619B - Pyritinol injection with special purpose solvent - Google Patents
Pyritinol injection with special purpose solvent Download PDFInfo
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- CN101164619B CN101164619B CN200610069510XA CN200610069510A CN101164619B CN 101164619 B CN101164619 B CN 101164619B CN 200610069510X A CN200610069510X A CN 200610069510XA CN 200610069510 A CN200610069510 A CN 200610069510A CN 101164619 B CN101164619 B CN 101164619B
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Abstract
The present invention belongs to the field of medicine technology, and discloses an injection preparation of pyritinol or its pharmaceutically-acceptable salt with matched special solvent. The injection preparation of pyritinol or its pharmaceutically-acceptable salt is a sterile powder or sterile strong solution which can be prepared or diluted into solution or suspension before clinical application, said sterile solution, emulsion or suspension can be injected into human body interior. The main component of said special solvent is an alkaline compound of alkali metal, it is one kind selected from sodium hydroxide, potassium of hydroxide, oxide of sodium or potassium, sodium carbonate, sodium hydrogen carbonate, potassium carbonate and potassium hydrogen carbonate or several kinds of them. The application of said matched special-purpose solvent can greatly reduce irritation of injection preparation of pyritinol or its pharmaceutically-acceptable salt to the blood vessel, can obviously raise tolerance of patient and safety of clinical application.
Description
1, technical field
The invention belongs to medical technical field, relate to a kind of the be furnished with pyritinol of special solvent or the injection of its pharmaceutically acceptable salt.
2, background technology
Pyritinol is the brain metabolism improving medicine, is vitamin B
6Derivant, can promote glucose and amino acid metabolism in the brain, improve the whole body assimilation, increase the carotid artery flow amount, improve cerebral blood flow, cerebral function improvement.Be applicable to the dizzy distending pain, insomnia, hypomnesis of cerebral trauma sequela, encephalitis and meningitis sequela etc., the improvement of absent minded, emotion changes clinically; Also be used for cerebral arteriosclerosis, senile dementia mental symptom etc.The chemistry of pyritinol is called 3,3-(dithio methylene) two (5-hydroxyls-6-methyl-pyridine methane), and structural formula is as follows:
The divalvon-D of listing is the pyritinol dihydrochloride monohydrate, has recorded version in 2005 " in the Chinese pharmacopoeia.The preparation of listing has sheet, capsule, liquid drugs injection, powder pin, sodium chloride injection and glucose injection, and its injection causes venous stimulation easily when clinical practice, limited its clinical application greatly.
3, summary of the invention
In order to solve the problem of the serious venous stimulation that the divalvon-D injection easily causes in clinical practice, the inventor is through number of research projects, be surprised to find the blood vessel irritation of alkali-metal alkali compounds can reduce the injection clinical application of pyritinol or its pharmaceutically acceptable salt greatly the time, significantly improve patient's the toleration and the safety of clinical use, medication is very convenient, can be used as the substitute of existing commercially available divalvon-D injection.
The present invention claimed a kind of the be furnished with pyritinol of special solvent or the injection of its pharmaceutically acceptable salt.
The injection of pyritinol of the present invention or its pharmaceutically acceptable salt faces with preceding preparation or is diluted to solution or the sterilized powder of suspension or aseptic concentrated solution for supplying, intravital sterile solution, emulsion or suspension be can inject, sterile powder for injection pin, injection freeze-dried powder, concentrated solution for injection, injection with small volume, high-capacity injection comprised.
Injectable sterile powder means that confession that medicine is made is faced with the suitable sterile solution of preceding usefulness and is mixed with settled solution or the evenly sterilized powder or the aseptic block of suspension; Available suitable solvent for injection preparation back injection, also available venous transfusion preparation posterior vein instils; Can make with solvent crystallization, spray drying method or freeze-drying etc.
Concentrated solution for injection means that confession that medicine is made faces the aseptic concentrated solution of using for intravenous drip with preceding dilution.
Injection means that the confession that medicine is made is injected into sterile solution type injection, emulsion-type injection or the suspension type injection of using in the body, can be used for intravenous injection or intravenous drip etc.; It indicates loading amount can be 0.5ml, 1ml, 2ml, 5ml, 10ml, 20ml, 50ml, 100ml, 200ml, 250ml, 500ml etc., be generally less than the injection with small volume that is called of 20ml, what be not less than 50ml is called high-capacity injection (the also title venous transfusion of using for intravenous drip).
The injection of pyritinol of the present invention or its pharmaceutically acceptable salt can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable additives in case of necessity.
The sterile powder for injection pin can make with solvent crystallization, spray drying method or freeze-drying, for direct packaging.
The Injectable sterile block can make with freeze-drying, can add suitable additives according to the character of medicine, and as excipient etc., usual excipients comprises mannitol, dextran, lactose, glucose, sucrose, maltose, xylitol, sorbitol etc.
When making injection, optional use solvent or non-aqueous solvent.The most frequently used aqueous solvent is a water for injection, also available 0.9% sodium chloride solution, 5% glucose solution or other suitable aqueous solutions; Non-aqueous solvent commonly used is a vegetable oil, is mainly the injection soybean oil, and other also have the aqueous solution of ethanol, propylene glycol, Polyethylene Glycol etc.During the preparation injection, can add suitable additives according to the character of medicine, as osmotic pressure regulator, pH value regulator, solubilizing agent, emulsifying agent, antioxidant, antibacterial, suspending agent etc.Osmotic pressure regulator commonly used comprises sodium chloride, glucose, potassium chloride, magnesium chloride, calcium chloride, sorbitol, glycerol etc., preferred sodium chloride or glucose; PH value regulator commonly used comprises acetic acid-sodium acetate, lactic acid, citric acid-sodium citrate, sodium bicarbonate-sodium carbonate, sodium hydrogen phosphate-sodium dihydrogen phosphate etc.; Solubilizing agent, emulsifying agent commonly used comprise polyoxyethylene sorbitan monoleate, propylene glycol, lecithin, polyoxyethylene castor oil, polyvidone etc.; Antioxidant commonly used has sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate etc.; Antibacterial commonly used is phenol, cresol, benzyl alcohol, chlorobutanol, hydroxypropyl butyl ester etc.; Suspending agent commonly used comprises methylcellulose, carboxymethyl cellulose, gelatin, pectin etc.
The main component of special solvent of the present invention is alkali-metal alkali compounds, is selected from: one or more in the oxide of sodium hydroxide, potassium hydroxide, sodium or potassium, sodium carbonate, sodium bicarbonate, potassium carbonate, the potassium bicarbonate.
When the active component of the injection of pyritinol of the present invention or its pharmaceutically acceptable salt is pyritinol, alkali-metal alkali compounds in the special solvent of being joined is selected from the oxide of sodium hydroxide, potassium hydroxide, sodium, in the oxide of potassium one or more, the mole of the metal ion in the wherein alkali-metal alkali compounds are at least 2 times of mole of pyritinol.Be preferably sodium hydroxide, its mole is at least 2 times of mole of pyritinol.
The active component of the injection of pyritinol of the present invention or its pharmaceutically acceptable salt is the pharmaceutically acceptable acid salt of pyritinol, when example hydrochloric acid salt, hydrobromate, sulfate, mesylate or benzene methanesulfonic acid salt, alkali-metal alkali compounds in the special solvent of being joined is selected from the oxide of sodium hydroxide, potassium hydroxide, sodium, in the oxide of potassium one or more, the mole of the metal ion in the wherein alkali-metal alkali compounds are at least 4 times of mole of pyritinol.
The active component of the injection of pyritinol of the present invention or its pharmaceutically acceptable salt is the pharmaceutically acceptable basic salt of pyritinol, during as sodium salt, potassium salt or natrium potassium salt, alkali-metal alkali compounds in the special solvent of being joined is selected from one or more in the oxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate of sodium hydroxide, potassium hydroxide, sodium or potassium, and the pH value of special solvent is not less than 7.
Special solvent of the present invention can adopt the conventional method production in the existing pharmaceutical field, except that adding above-mentioned alkali-metal alkali compounds, also can add suitable additives, as osmotic pressure regulator, pH value regulator, solubilizing agent, emulsifying agent, antioxidant, antibacterial, suspending agent etc.Osmotic pressure regulator commonly used comprises sodium chloride, glucose, potassium chloride, magnesium chloride, calcium chloride, sorbitol, glycerol etc., preferred sodium chloride or glucose; PH value regulator commonly used comprises acetic acid-sodium acetate, lactic acid, citric acid-sodium citrate, sodium bicarbonate-sodium carbonate, sodium hydrogen phosphate-sodium dihydrogen phosphate etc.; Solubilizing agent, emulsifying agent commonly used comprise polyoxyethylene sorbitan monoleate, propylene glycol, lecithin, polyoxyethylene castor oil, polyvidone etc.; Antioxidant commonly used has sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate etc.; Antibacterial commonly used is phenol, cresol, benzyl alcohol, chlorobutanol, hydroxypropyl butyl ester etc.; Suspending agent commonly used comprises methylcellulose, carboxymethyl cellulose, gelatin, pectin etc.
The application of the special solvent that the injection of the further claimed pyritinol of the present invention or its pharmaceutically acceptable salt is furnished with in the blood vessel irritation of the injection that reduces pyritinol or its pharmaceutically acceptable salt.Blood vessel irritation when the contained alkali-metal alkali compounds of the special solvent of being joined can reduce the injection clinical application of pyritinol or its pharmaceutically acceptable salt greatly, significantly improve patient's the toleration and the safety of clinical use, medication is very convenient.
Below example further specifies by experiment, used injection pyritinol 1,2,3 is referring to embodiment 1 preparation gained, used pyritinol hydrochloride for injection 1 is referring to embodiment 2 preparation gained, used pyritinol hydrochloride injection is referring to embodiment 3 preparation gained, used injection pyritinol sodium 1,2 is referring to embodiment 4 preparation gained, and used pyritinol sodium injection 1,2 is referring to embodiment 5 preparation gained.
Experimental example is of the present invention is furnished with the pyritinol of special solvent or the injection and the commercially available hydrochloric acid of its pharmaceutically acceptable salt
The pyritinol injection compares the vein irritating experiment of rabbit
Experiment purpose is observed of the present inventionly is furnished with the pyritinol of special solvent or the injection of its pharmaceutically acceptable salt has nonirritant to blood vessel.
Be subjected to the following specification of reagent thing that is subjected to of reagent thing all with pyritinol (C
16H
20N
2O
4S
2) meter, be self-control.
Injection pyritinol 1: specification 167mg, special solvent 10ml (containing sodium hydroxide 38mg);
Injection pyritinol 2: specification 167mg, special solvent 10ml (containing potassium hydroxide 53mg);
Injection pyritinol 3: specification 167mg, special solvent 10ml (containing sodium hydroxide 20mg, potassium hydroxide 25mg);
Pyritinol hydrochloride for injection 1: specification 167mg, special solvent 10ml (containing sodium hydroxide 75mg);
Pyritinol hydrochloride injection 1: specification 2ml:167mg, special solvent 10ml (containing sodium hydroxide 75mg);
Injection pyritinol sodium 1: specification 167mg, special solvent 10ml (containing sodium hydroxide 1mg);
Injection pyritinol sodium 2: specification 167mg, special solvent 10ml (containing sodium bicarbonate 2mg);
Pyritinol sodium injection 1: specification 2ml:167mg, special solvent 10ml (containing sodium hydroxide 1mg);
Pyritinol sodium injection 2: specification 2ml:167mg, special solvent 10ml (containing sodium bicarbonate 2mg).
Contrast medicine 5% glucose injection, Sanjiu Yimin Pharmaceutic Co., Ltd., Jinan produces, lot number: 0407160301;
Pyritinol hydrochloride injection, specification 2ml:0.2g, Tri-Lion Pharmaceutical Co., Ltd., Harbin.
The animal rabbit, body weight 2.0～2.5kg,
Dual-purpose, anti-medical Group Co.,Ltd provides by the Shandong, Shandong, the animal quality certification number: SCXK (Shandong) 20030006.
Dosage is provided with quiet of branch and quietly pushes away 2 kinds of route of administration.Quiet: 2 of commercially available pyritinol hydrochloride injections are diluted in the 250ml glucose injection; Injection pyritinol 1,2,3, pyritinol hydrochloride for injection 1, pyritinol hydrochloride injection 1, injection pyritinol sodium 1,2 is diluted in the 250ml glucose injection after each 2 of pyritinol sodium injections 1,2 dissolve with appended special solvent respectively; Each 12.5ml/kg (diluent).Quiet pushing away: pyritinol hydrochloride injection is diluted to 10ml with water for injection; Injection pyritinol 1,2,3, pyritinol hydrochloride for injection 1, pyritinol hydrochloride injection 1, injection pyritinol sodium 1,2, the appended special solvent dissolving of pyritinol sodium injection 1,2 usefulness; Each 0.5ml/kg.
Method is got 66 of healthy rabbits, is divided at random for reagent group and 5% glucose injection matched group, 3 every group.Before the administration rabbit is put in the fixed case, instil respectively, inject for reagent and 5% glucose injection by above-mentioned grouping in auricular vein, drip velocity be 1ml/min (20/min), the speed of injecting is slow, observe administration after the 24h injection site have or not hyperemia, edema, hemorrhage, downright bad.Successive administration 3 days, 24h does pathological examination getting the rabbit ear 10% formalin fixed away from the entad end of injection site 1cm after the last administration.The blood vessel of perusal agents area and surrounding tissue have or not hyperemia, edema, degeneration, scleroma and necrosis, relatively have or not significant difference with the position of 5% glucose injection; Originally, cut into slices then during pathologic finding away from the sampling of injection site 1cm place.
Experimental result and conclusion experimental result see Table 1 and 2.
5% glucose injection intravenous injection and intravenous drip group: the blood vessel of 6 rabbit perusal agents areas and surrounding tissue there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, epidermis does not have and thickens, subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis, the auricular vein endotheliocyte is arranged normal, do not find mural thrombus and cell infiltration in the tube chamber, the chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.
Table 1 is of the present invention is furnished with the perusal result of 24h and 3d after the injection of the pyritinol of special solvent or its pharmaceutically acceptable salt and the administration of commercially available pyritinol hydrochloride injection rabbit ear vein
Pyritinol hydrochloride injection intravenous injection group: when injecting beginning, 3 rabbit occur restless; After injecting, the visible capillary injection of perusal agents area, no hemorrhage, redden around the blood capillary, preliminary judgement has serious zest; Pathological examination results shows the vein blood vessel dilatation and congestion, and changes such as hyperemia, edema and inflammation appear in subcutaneous tissue and corium.
Injection pyritinol 1,2,3 intravenous injection groups: when injecting, restless phenomenon does not appear in 3 rabbit; The perusal agents area there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, and epidermis does not have and thickens, and subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis; The auricular vein endotheliocyte is arranged normal, does not find mural thrombus and cell infiltration in the tube chamber; The chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.With 5% glucose injection intravenous injection group there was no significant difference.
Pyritinol hydrochloride for injection 1 or pyritinol hydrochloride injection 1 intravenous injection group: when injecting, restless phenomenon does not appear in 3 rabbit; The perusal agents area there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, and epidermis does not have and thickens, and subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis; The auricular vein endotheliocyte is arranged normal, does not find mural thrombus and cell infiltration in the tube chamber; The chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.With 5% glucose injection intravenous injection group there was no significant difference.
Injection pyritinol sodium 1,2 or pyritinol sodium injection 1,2 intravenous injection groups: when injecting, restless phenomenon does not appear in 3 rabbit; The perusal agents area there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, and epidermis does not have and thickens, and subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis; The auricular vein endotheliocyte is arranged normal, does not find mural thrombus and cell infiltration in the tube chamber; The chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.With 5% glucose injection intravenous injection group there was no significant difference.
Table 1 is of the present invention is furnished with the perusal result (continuing) of 24h and 3d after the injection of the pyritinol of special solvent or its pharmaceutically acceptable salt and the administration of commercially available pyritinol hydrochloride injection rabbit ear vein
Pyritinol hydrochloride injection intravenous drip group: behind quiet of 3 rabbit, the visible blood capillary of perusal agents area is slightly congested, no hemorrhage, and preliminary judgement has zest; Pathological examination results shows changes such as the vein blood vessel dilatation and congestion occur.
Injection pyritinol 1,2,3 intravenous drip groups: the perusal agents area there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, and epidermis does not have and thickens, and subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis; The auricular vein endotheliocyte is arranged normal, does not find mural thrombus and cell infiltration in the tube chamber; The chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.With 5% glucose injection intravenous drip group there was no significant difference.
Pyritinol hydrochloride for injection 1 or pyritinol hydrochloride injection 1 intravenous drip group: the perusal agents area there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, and epidermis does not have and thickens, and subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis; The auricular vein endotheliocyte is arranged normal, does not find mural thrombus and cell infiltration in the tube chamber; The chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.With 5% glucose injection intravenous drip group there was no significant difference.
Injection pyritinol sodium 1,2 or pyritinol sodium injection 1,2 intravenous drip groups: the perusal agents area there is no hyperemia, edema, hemorrhage; Pathological examination results shows that vascular tissue's structure is normal, and epidermis does not have and thickens, and subcutaneous tissue and corium do not have hyperemia, edema, inflammation and necrosis; The auricular vein endotheliocyte is arranged normal, does not find mural thrombus and cell infiltration in the tube chamber; The chondrocyte marshalling of cartilaginous tissue is not seen changes such as degeneration, necrosis.With 5% glucose injection intravenous drip group there was no significant difference.
Table 2 pyritinol or the injection of its pharmaceutically acceptable salt and the pathological examination results after the administration of commercially available pyritinol hydrochloride injection rabbit ear vein of being furnished with special solvent of the present invention
Above-mentioned experimental result shows injection pyritinol 1,2,3, pyritinol hydrochloride for injection 1, pyritinol hydrochloride injection 1, injection pyritinol sodium 1,2, pyritinol sodium injection 1,2 and commercially available pyritinol hydrochloride injection relatively significantly reduce the venous zest, do not have zest substantially, the intravenously administrable blood vessel irritation that shows the injection of the pyritinol of being furnished with special solvent of the present invention or its pharmaceutically acceptable salt reduces greatly, is worth clinical application.
4, the specific embodiment
The specific embodiment by the following examples is described in further detail foregoing of the present invention.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.Adjuvant in following examples can be replaced with acceptable accessories, perhaps reduces, increases.
The preparation 1 of embodiment 1 injection pyritinol (aseptic powder)
The injection pyritinol
Prescription:
Preparation technology:
(1) will produce required antibiotic bottle and plug etc. cleans and aseptic process.
(2) pyritinol was pulverized 100 mesh sieves.
(3) the pyritinol branch is packed in the antibiotic bottle, lid is rolled in tamponade.
(4) finished product is examined entirely; The packing warehouse-in.
Special-purpose molten coal
Prescription 1:
Prescription 2:
Prescription 3:
Preparation technology:
(1) will produce required ampoule cleans and aseptic process;
(2) alkali-metal alkali compounds adds the water for injection of dosing amount 80%, stirring and dissolving;
(3) mend the standardize solution that adds to the full amount of water for injection, stir;
(4) add the needle-use activated carbon of dosing amount 0.03%, stirred filtering decarbonization 15 minutes;
(5) medicinal liquid is crossed 0.45 μ m microporous filter membrane fine straining;
(6) check the solution clarity;
(7) inspection of semifinished product;
(8) medicine liquid irrigation is enclosed in the flint glass ampoule;
(9) 100 degree flowing steam sterilizations 30 minutes;
(10) leak detection, lamp inspection;
(11) finished product is examined entirely, the packing warehouse-in.
The preparation 2 of embodiment 2 injection pyritinols (aseptic powder)
The injection pyritinol
Prescription:
Preparation technology: referring to embodiment 1.
Special-purpose molten coal
Prescription:
Preparation technology: referring to embodiment 1.
The preparation 1 of embodiment 3 pyritinol hydrochloride for injection (lyophilized powder)
Pyritinol hydrochloride for injection
Prescription:
Preparation technology:
(1) will produce used cillin bottle, plug and dosing with vessel, instrument and equipment etc. clear up, degerming, depyrogenation;
(2) take by weighing raw material and adjuvant by prescription;
(3) mannitol is added dosing amount 80% water for injection, stirring and dissolving; The needle-use activated carbon that adds dosing amount 0.05% then stirs 15min, filters, and takes off charcoal;
(4) in solution, add divalvon-D, stirring and dissolving;
(5) measure the also pH value of regulator solution;
(6) benefit adds to the full amount of water for injection standardize solution;
(7) medicinal liquid is checked clarity through the microporous filter membrane fine straining of 0.22 μ m;
(8) inspection of semifinished product;
(9) medicinal liquid is sub-packed in the cillin bottle, half tamponade;
(10) sample is put in the freeze dryer, adopted following freeze-dry process lyophilizing :-40 ℃ of pre-freezes 4 hours ,-30～0 ℃ of low-temperature vacuum drying 18 hours, 0～30 ℃ heated up dry 2 hours, 30 ℃ of freeze-day with constant temperature 2 hours.
(11) lyophilizing finishes tamponade, Zha Gai;
(12) finished product is examined entirely, the packing warehouse-in.
Special-purpose molten coal
Prescription 1:
Prescription 2:
Preparation technology: referring to embodiment 1.
The preparation 2 of embodiment 4 pyritinol hydrochloride for injection (lyophilized powder)
Pyritinol hydrochloride for injection
Prescription:
Preparation technology: referring to embodiment 3.
Special-purpose molten coal
Prescription:
Preparation technology: referring to embodiment 1.
The system of embodiment 5 pyritinol hydrochloride injections respectively
Pyritinol hydrochloride injection
Prescription:
Preparation technology:
(1) will produce with the ampoule dosing with vessel, instrument and equipment etc. clear up, degerming, depyrogenation;
(2) take by weighing raw material and adjuvant by prescription;
(3) get the water for injection that Polysorbate adds dosing amount 80%, stirring and dissolving; The needle-use activated carbon that adds dosing amount 0.05% stirs 15min, filters, and takes off charcoal;
(4) divalvon-D in solution, stirring and dissolving;
(5) measure the also pH value of regulator solution;
(6) benefit adds to the full amount of water for injection standardize solution;
(7) medicinal liquid is checked clarity through the microporous filter membrane fine straining of 0.22 μ m;
(8) inspection of semifinished product;
(9) medicinal liquid is loaded in the ampoule;
(10) 100 ℃ of flowing steam sterilization 30min;
(11) leak detection, lamp inspection;
(12) finished product is examined entirely, the packing warehouse-in.
Special-purpose molten coal
Prescription: referring to embodiment 3.
Preparation technology: referring to embodiment 1.
The system of embodiment 6 injection pyritinol sodium (lyophilized powder) each 1
Injection pyritinol sodium
Prescription:
Preparation technology: referring to embodiment 3.
Special-purpose molten coal
Prescription 1:
Prescription 2:
Prescription 3:
Preparation technology: referring to embodiment 1.
The preparation 2 of embodiment 7 injection pyritinol sodium (lyophilized powder)
Injection pyritinol sodium
Prescription:
Preparation technology: referring to embodiment 3.
Special-purpose molten coal
Prescription:
Preparation technology: referring to embodiment 1.
The preparation of embodiment 8 pyritinol sodium injections
The pyritinol sodium injection
Prescription:
Preparation technology: referring to embodiment 5.
Special-purpose molten coal
Prescription: referring to embodiment 7.
Preparation technology: referring to embodiment 1.
Claims (8)
1. be furnished with the pyritinol of special solvent or the injection of its pharmaceutically acceptable salt for one kind, it is characterized in that, the main component of described special solvent is alkali-metal alkali compounds, is selected from: one or more in the oxide of sodium hydroxide, potassium hydroxide, sodium or potassium, sodium carbonate, sodium bicarbonate, potassium carbonate, the potassium bicarbonate.
2. injection as claimed in claim 1, it is characterized in that, the injection of described pyritinol or its pharmaceutically acceptable salt can inject intravital sterile solution, emulsion or suspension for for facing with preceding preparation or being diluted to solution or the sterilized powder of suspension or aseptic concentrated solution.
3. injection as claimed in claim 2 is characterized in that, the injection of described pyritinol or its pharmaceutically acceptable salt is sterile powder for injection pin, concentrated solution for injection, injection with small volume, high-capacity injection.
4. as each described injection of claim 1～3, it is characterized in that, when active component is pyritinol, alkali-metal alkali compounds in the special solvent of being joined is selected from the oxide of sodium hydroxide, potassium hydroxide, sodium, in the oxide of potassium one or more, the mole of the metal ion in the wherein alkali-metal alkali compounds are at least 2 times of mole of pyritinol.
5. injection as claimed in claim 4 is characterized in that, when active component was pyritinol, the main component of the special solvent of being joined was a sodium hydroxide, and its mole is at least 2 times of mole of pyritinol.
6. as each described injection of claim 1～3, it is characterized in that, active component is the pharmaceutically acceptable acid salt of pyritinol, when being selected from hydrochlorate, hydrobromate, sulfate, mesylate or benzene methanesulfonic acid salt, alkali-metal alkali compounds in the special solvent of being joined is selected from the oxide of sodium hydroxide, potassium hydroxide, sodium, in the oxide of potassium one or more, the mole of the metal ion in the wherein alkali-metal alkali compounds are at least 4 times of mole of pyritinol.
7. as each described injection of claim 1～3, it is characterized in that, active component is the pharmaceutically acceptable basic salt of pyritinol, when being selected from sodium salt, potassium salt or natrium potassium salt, alkali-metal alkali compounds in the special solvent of being joined is selected from one or more in the oxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate of sodium hydroxide, potassium hydroxide, sodium or potassium, and the pH value of special solvent is not less than 7.
8. the application of special solvent as claimed in claim 1 in the medicine of the blood vessel irritation of the injection of preparation reduction pyritinol or its pharmaceutically acceptable salt.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610069510XA CN101164619B (en) | 2006-10-20 | 2006-10-20 | Pyritinol injection with special purpose solvent |
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|---|---|---|---|
| CN200610069510XA CN101164619B (en) | 2006-10-20 | 2006-10-20 | Pyritinol injection with special purpose solvent |
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| CN101164619B true CN101164619B (en) | 2011-05-18 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562007A (en) * | 2004-04-13 | 2005-01-12 | 金三九 | Pyrithioxine hydrochloride freeze-dried composition and its preparing method |
| CN1679565A (en) * | 2004-04-06 | 2005-10-12 | 王玫 | Injection of pyritinol hydrochloride and its preparation |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1679565A (en) * | 2004-04-06 | 2005-10-12 | 王玫 | Injection of pyritinol hydrochloride and its preparation |
| CN1562007A (en) * | 2004-04-13 | 2005-01-12 | 金三九 | Pyrithioxine hydrochloride freeze-dried composition and its preparing method |
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