CN1895218A - Pyrrolechrisxi and its sodium-salt eye-gel preparation and its making method - Google Patents
Pyrrolechrisxi and its sodium-salt eye-gel preparation and its making method Download PDFInfo
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- CN1895218A CN1895218A CN 200610019432 CN200610019432A CN1895218A CN 1895218 A CN1895218 A CN 1895218A CN 200610019432 CN200610019432 CN 200610019432 CN 200610019432 A CN200610019432 A CN 200610019432A CN 1895218 A CN1895218 A CN 1895218A
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Abstract
An eye gel for preventing and treating hyperglycemic cataract is proportionally prepared from pirenoxine or its Na salt, gel matrix and pharmacologically acceptable carrier. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of eye medicinal, exactly is eye-gel preparation of a kind of pirenoxine and its sodium salt and preparation method thereof.
Background technology
The main diseases of the present blinding of cataract because of, according to WHO statistics, the blind person in the whole world 40% is because due to the cataract.The cataractous cause of disease does not still have definite conclusion at present, it is generally acknowledged: (1) excessive accepts radiation; (2) medicine or chemical poisoning; (3) metabolic disease is arranged.Cataract patient quickens crystalline protein set etc. all with crystalline intravital all biochemical changes as electrolyte balance imbalance, aminoacid, vitamin and reducing substances minimizing, the reduction of ATP concentration, the peroxidating of ester matter.Treat the cataractous following a few class that mainly is divided at present: the medicine that protein polymer forms after (1) prevention oxidation, as aspirin, catalin; (2) medicine of the various reactive oxygen free radical of elimination is as carotene, carotenoid; (3) increase reduced glutathion in the crystal, prevent crystalline protein-denatured medicine, as glutathion, taurine; (4) nutrient of anti-crystalline lens oxidative damage and inorganic salts are as vitamin, trace element; (5) aldose reductase inhibitor class medicine, as: sorbinil; (6) Chinese herbal medicine, Rehmanniae Bolus of Eight Ingredients, Margarita hydrolyzed solution etc.It is reported that said medicine is all just in different angles, treat cataract in various degree.But all do not become the cataractous specific drug of treatment.
Existing anti-cataract medicine is maximum with antioxidant, studies more having with trace element and regulates the relevant enzyme of antioxidation.Think about cataractous pathogenetic research recently: reactive oxygen free radical causes the ester matter peroxidating of texture, is that to induce cataractous fundamental cause, aldose reductase then be the key enzyme that causes sugared cataract.The present invention is based on above-mentioned mechanism and this ophthalmic preparation of developing.This ophthalmic preparation is intended to suppress the activity of aldose reductase by replenishing the crystal exogenous antioxidant and improving crystal endogenous antioxidative functional, reaches prevention and treats cataractous purpose.It has the advantage of antioxidation, aldose enzyme inhibitor and Chinese medicine concurrently.
Eye drop related to the present invention is the Bernetine Sodium eye drop, also have imported product pirenoxine suspendible eye drop, use confirmation through animal experiment, clinical trial and listing: with the ophthalmic preparation of pirenoxine as effective ingredient, can improve cataractous crystal muddiness, alleviate crystalline structural change, cataract is had significant curative effect.All the experimenter does not find that conjunctiva, cornea, anterior chamber, iris have ANOMALOUS VARIATIONS.But thereby there is certain zest, medicine short, the little curative effect of medication that influences of drug absorption of holdup time within the eye in this eye drop, and the number of times and the frequency of eye dripping are higher when therefore using, and brings very big inconvenience for patient's use.
Open day is that the application for a patent for invention of CN1106669A discloses " the cataractous eye drop of a kind of control " for August 16 nineteen ninety-five, publication number, this invention eye drop is used for cataractous treatment, confirm to improve cataractous crystal muddiness through animal experiment, clinical trial, alleviate crystalline structural change, cataract is had significant curative effect.But still there is above-mentioned defective in this invention.Therefore inventing a kind of novel formulation and novel drugs that can overcome the existing defective of above-mentioned eye drop is highly profitable.
In recent years, researcher finds that macromolecule hydrogel substrate can increase medicine viscosity, prolong drug action time promotes drug absorption, can play similar artificial tears's effect simultaneously, alleviates malaise symptoms such as eye is dried, puckery, asthenopia.
Summary of the invention
The purpose of this invention is to provide a kind of eye-gel preparation that contains pirenoxine and its sodium salt and preparation method thereof.It is a kind of colourless flowing or the eye-gel preparation of semifluid gel state, compares with ordinary eye drops, and it can keep the drug level of long period, thereby improves the curative effect of medicine.
Technical scheme of the present invention is achieved in that it contains the pirenoxine of effective dose, gel-type vehicle and medicine acceptable carrier.Contain pirenoxine 0.001～10g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
Described gel-type vehicle is one or more the mixture in carbomer, polyvinyl alcohol, hydroxypropyl emthylcellulose, polyacrylic acid, methylcellulose, hyaluronic acid sodium, the sodium alginate, and consumption is 1.0～400g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
Preferred carbomer of described gel-type vehicle or polyvinyl alcohol.When selecting carbomer for use, its consumption is 1.0～150g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.When selecting polyvinyl alcohol for use, its consumption is 1.0～400g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
The preferred scheme of the present invention is the mixture of gel-type vehicle carbomer 10g and polyvinyl alcohol 300g.When selecting this scheme for use, the gel effect of formation is best.
Described medicine acceptable carrier is one or more the mixture in antioxidant, filler, solubilizing agent, wetting agent, lubricant, isoosmotic adjusting agent, antibacterial, metal chelating agent, the pH regulator agent, and its consumption is 1.0～450g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
Described for antioxidant be sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium formaldehyde sulphoxylate, sodium dithionite, the L-cysteine, L-lysine, the L-arginine, taurine, the L-glutathion, the L-methionine, the L-valine, the L-leucine, the L-isoleucine, the L-tryptophan, vitamin C and ester thereof, the D-arabo-ascorbic acid, vitamin E, thioglycerin, thiourea, 2 mercapto ethanol, dimercaptopropanol, BAL, 1-sulfo-sorbitol, TGA, thiosalicylic acid, dithiooxamide, in 6-methyl-2-deracil, fumaric acid, maleic acid, L-tartaric acid, pyrogallic acid and ester thereof, hydroquinone, oxine, para-aminophenol, the hydrochloric acid pyridoxamine, butylated hydroxyarisol, the mixture of one or more in the di-tert-butyl hydroxy-methylbenzene, its consumption is 0.1～100g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described solubilizing agent is one or more the mixture in Tween 80, PEG400, Macrogol 600, poloxamer 188, polyvinyl pyrrolidone, the HP-, and its consumption is 0.01～50g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described filler is one or more the mixture in sucrose or lactose, starch, microcrystalline Cellulose or dextrin, mannitol, sorbitol or the hydroxyl isomaltulose, and its consumption is 0.1～10g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described wetting agent is 50～90% ethanol waters, and its consumption is 0.1～15g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described lubricant is magnesium stearate or micropowder silica gel, and its consumption is 0.01～2g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described antibacterial is one or more the mixture in benzyl alcohol, chlorobutanol, thimerosal, hibitane, benzalkonium bromide, benzalkonium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate, the propylparaben, and its consumption is 0.01～30g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described isoosmotic adjusting agent is one or more the mixture in sodium chloride, glucose, glycerol, propylene glycol, mannitol or the sorbitol, and its consumption is 0.01～200g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.The complexing of metal ion agent is one or more in disodium EDTA (EDTA-2Na), EDTA calcium complex disodium salt (EDTA-NaCa), N-two (2-ethoxy) glycine.
Another technical scheme of the present invention is that its prescription is identical with technique scheme with the pirenoxine in the active component pirenoxine sodium salt replacement technique scheme.The kind of gel-type vehicle and medicine acceptable carrier is also identical with consumption.
The preparation method of the eye-gel preparation of pirenoxine of the present invention and its sodium salt may further comprise the steps:
(1), get water for injection dissolving with antibacterial, pH buffer system regulator, isoosmotic adjusting agent, complexing of metal ion agent, solubilizing agent dissolving after, stir, obtain A solution;
(2), pirenoxine raw material, antioxidant added dissolved in the solution of macromolecule hydrogel substrate, obtain B solution;
(3), mix two kinds of solution of above-mentioned A, B after; Re-adjustment pH is 3.0-7.5; Solution is used through the filtering water for injection of filter and is added to total amount by filtering with microporous membrane, makes eye-gel preparation.
When with the pirenoxine in the active component pirenoxine sodium salt replacement technique scheme, also can adopt the method preparation equally.
The preparation method of pirenoxine of the present invention and Bernetine Sodium eye-gel preparation also can realize by following steps:
(1), the pirenoxine sodium salt 80～120 mesh sieves excessively, antioxidant, pH buffer system regulator, macromolecule hydrogel host material and filler are crossed 60～100 mesh sieves;
(2), take by weighing the pirenoxine sodium salt of recipe quantity, the antioxidant of 70% recipe quantity, the pH buffer system regulator of 70% recipe quantity, the macromolecule hydrogel host material of 20% recipe quantity, adopt equivalent progressively increase method, fully mix homogeneously;
(3), take by weighing the filler of recipe quantity, adopt the equivalent method of progressively increasing it to be sneaked in the above-mentioned material mix homogeneously; With wetting agent system soft material, to cross 10～30 mesh sieves and granulate, the gained granule is 30～70 ℃ of dryings, and moisture Control is 1～3%; Dried particles is crossed 10～30 mesh sieve granulate;
(4), add the lubricant of recipe quantity, fully mix homogeneously; Content is measured in the intermediate check, calculates the heavy back of slice tabletting and gets tablet.
(5), in addition after getting water for injection and will remaining 30% antioxidant, 30% pH buffer system regulator, solubilizing agent, antibacterial, complexing of metal ion agent, isoosmotic adjusting agent dissolving, stir, obtain A solution; Obtain B solution after the macromolecule hydrogel host material dissolving with residue 80%; Above-mentioned two kinds of solution mix homogeneously, moisturizing to 950～1000 milliliter; Solution is used through the filtering water for injection of filter and is added to 1000 milliliters by filtering with microporous membrane, makes dedicated solvent.Tablet is dissolved in dedicated solvent, and jolting can form eye-gel preparation.
The present invention shows through the stability test that 40 ℃ of constant temperature quicken 10 days, 4500Lx illumination to quicken 10 days, gel stability of the present invention gone on the market more ordinary eye drops and suspendible eye drop, and stability has greatly improved.
The present invention can improve cataractous crystal muddiness, alleviates crystalline structural change, and cataract is had significant curative effect.Simultaneously macromolecule hydrogel substrate can increase medicine viscosity, prolong drug action time promotes drug absorption, can play similar artificial tears's effect simultaneously, alleviates malaise symptoms such as the eye that causes because of senescence is dried, puckery, asthenopia.
The specific embodiment
Following example will the present invention is further elaborated, but do not limit content of the present invention.
Embodiment 1
Bernetine Sodium 0.053g
Sodium pyrosulfite 15g
Carbopol 941 10g
Tween 80 2g
Benzalkonium chloride 1g
EDTA-2Na 1g
Borax 3g
Boric acid 8g
Glycerol 12g
Water for injection adds to 1000ml
Get water for injection dissolving Carbopol 941, stir rising temperature for dissolving down, get solution A; With benzalkonium chloride, boric acid, Borax, Tween 80, glycerol, the even solution B that gets of EDTA-2Na dissolving, put cold standby; The Bernetine Sodium, sodium pyrosulfite that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH value to the 950ml of total amount, and adding sodium hydroxide or dilute hydrochloric acid adjusting pH value in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 2
Bernetine Sodium 0.053g
L-arginine 15g
Acritamer 940 15g
Tween 80 2g
Benzalkonium bromide 1g
EDTA-2Na 1g
Sodium tartrate 2g
Triethanolamine 2g
Glucose 32g
Water for injection adds to 1000ml
Get water for injection dissolving Acritamer 940, stir rising temperature for dissolving down, get solution A; With benzalkonium bromide, Tween 80, glucose, EDTA-2Na, sodium tartrate, the even solution B that gets of triethanolamine dissolving, put cold standby; The Bernetine Sodium, L-arginine that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 3
Bernetine Sodium 0.053g
Vitamin C 10g
Polyvinyl alcohol 20g
PEG400 2g
EDTA-2Na 1g
Benzalkonium bromide 1g
Sodium citrate 3g
Sodium chloride 6.6g
Water for injection adds to 1000ml
Get the water for injection dissolve polyvinyl alcohol, stir rising temperature for dissolving down, get solution A; With benzalkonium bromide, PEG400, sodium chloride, EDTA-2Na, the even solution B that gets of sodium citrate dissolving, put cold standby; The Bernetine Sodium, vitamin C that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 4
Bernetine Sodium 0.053g
2 mercapto ethanol 5g
Hydroxypropyl emthylcellulose 15g
Tween 80 2g
EDTA-2Na 1g
Phenoxyethanol 3ml
Borax 3g
Boric acid 5g
Propylene glycol 12g
Water for injection adds to 1000ml
Get water for injection dissolving hydroxypropyl emthylcellulose, stir rising temperature for dissolving down, get solution A; With phenoxyethanol, Tween 80, propylene glycol, EDTA-2Na, Borax, the even solution B that gets of boric acid dissolving, put cold standby; The Bernetine Sodium, 2 mercapto ethanol that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 5
Pirenoxine 0.053g
Sodium formaldehyde sulphoxylate 0.5g
Propyl gallate 5g
Polyvinyl alcohol 10g
Poloxamer 188 2g
EDTA-2Na 1g
Benzalkonium bromide 1g
Sodium citrate 3g
Sodium chloride 6.4g
Water for injection adds to 1000ml
Get the water for injection dissolve polyvinyl alcohol, stir rising temperature for dissolving down, get solution A; With benzalkonium bromide, poloxamer 188, sodium chloride, the even solution B that gets of EDTA-2Na dissolving, put cold standby; The pirenoxine, sodium citrate, propyl gallate that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 6
The pastille tablet formulation:
Anhydrous Bernetine Sodium 0.53g
L-glutathion 30g
Taurine 35.0g
Boric acid 17.5g
Hydroxypropyl emthylcellulose 0.24g
50% ethanol 8ml
Sodium benzoate 0.3g
Make 1000
The dedicated solvent prescription:
Potassium chloride 1.6g
Sodium sulfite 2g
Tween 80 2g
Boric acid 12g
Borax 0.08g
Hydroxypropyl emthylcellulose 12g
EDTA-2Na 1g
Methyl parahydroxybenzoate 0.4g
Propyl p-hydroxybenzoate 0.2g
Add the injection water to 1000ml
Bernetine Sodium is crossed 80～120 mesh sieves, L-glutathion, taurine, boric acid, hydroxypropyl emthylcellulose are crossed 60～100 mesh sieves, take by weighing the recipe quantity Bernetine Sodium, the hydroxypropyl emthylcellulose of the L-glutathion after sieving, taurine, boric acid, 20% recipe quantity, adopt equivalent progressively increase method, fully mix homogeneously; With 50% ethanol system soft material, cross 10～30 mesh sieves and granulate drying; Dried particles is crossed 10～30 mesh sieve granulate, adds the sodium benzoate of recipe quantity, fully mix homogeneously; Content is measured in the intermediate check, calculates the heavy back of slice tabletting and gets tablet.Other gets water for injection and dissolves after sodium sulfite, boric acid, Borax, Tween 80, methyl parahydroxybenzoate, propyl p-hydroxybenzoate, EDTA-2Na, the potassium chloride dissolving, stirs; Hydroxypropyl emthylcellulose dissolving with residue 20%; Above-mentioned 2 kinds of solution mix homogeneously, moisturizing is to nearly full dose; Solution is used through the filtering water for injection of filter and is added to total amount by filtering with microporous membrane, makes dedicated solvent.Face with preceding tablet is dissolved in dedicated solvent, jolting can form eye-gel preparation.
Embodiment 7
Bernetine Sodium 0.001g
Sodium pyrosulfite 15g
Carbopol 941 10g
Tween 80 2g
Benzalkonium chloride 1g
EDTA-2Na 1g
Borax 3g
Boric acid 8g
Glycerol 12g
Water for injection adds to 1000ml
Get water for injection dissolving Carbopol 941, stir rising temperature for dissolving down, get solution A; With benzalkonium chloride, boric acid, Borax, Tween 80, glycerol, the even solution B that gets of EDTA-2Na dissolving, put cold standby; The Bernetine Sodium, sodium pyrosulfite that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 8
Bernetine Sodium 10g
L-arginine 15g
Acritamer 940 10g
Polyvinyl alcohol 300g
Tween 80 2g
Polyvinylpyrrolidone 2g
Polyethylene Glycol 10g
Benzalkonium bromide 1g
EDTA-2Na 1g
Sodium tartrate 2g
Triethanolamine 2g
Glucose 32g
Water for injection adds to 1000ml
Get water for injection dissolving Acritamer 940, polyvinyl alcohol, stir rising temperature for dissolving down, get solution A; With benzalkonium bromide, Tween 80, polyvinylpyrrolidone, Polyethylene Glycol, glucose, EDTA-2Na, sodium tartrate, the even solution B that gets of triethanolamine dissolving, put cold standby; The Bernetine Sodium, L-arginine that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 9
Bernetine Sodium 5g
Vitamin C 10g
Fumaric acid 10g
Butylated hydroxyarisol 2g
Polyvinyl alcohol 20g
PEG400 2g
EDTA-2Na 1g
Benzalkonium bromide 1g
Sodium citrate 3g
Sodium chloride 6.6g
Water for injection adds to 1000ml
Get the water for injection dissolve polyvinyl alcohol, stir rising temperature for dissolving down, get solution A; With benzalkonium bromide, PEG400, sodium chloride, EDTA-2Na, the even solution B that gets of sodium citrate dissolving, put cold standby; The Bernetine Sodium, vitamin C, butylated hydroxyarisol, fumaric acid that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 10
Bernetine Sodium 1g
2 mercapto ethanol 5g
Hydroxypropyl emthylcellulose 15g
Sodium alginate 5g
Tween 80 2g
EDTA-2Na 1g
Phenoxyethanol 3ml
Borax 3g
Boric acid 5g
Propylene glycol 12g
Water for injection adds to 1000ml
Get water for injection dissolving hydroxypropyl emthylcellulose, sodium alginate, stir rising temperature for dissolving down, get solution A; With phenoxyethanol, Tween 80, propylene glycol, EDTA-2Na, Borax, the even solution B that gets of boric acid dissolving, put cold standby; The Bernetine Sodium, 2 mercapto ethanol that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 11
Pirenoxine 0.1g
Sodium formaldehyde sulphoxylate 0.5g
Propyl gallate 5g
Polyvinyl alcohol 10g
Hyaluronic acid sodium 2g
Poloxamer 188 2g
EDTA-2Na 1g
Benzalkonium bromide 1g
Sodium citrate 3g
Sodium chloride 6.4g
Water for injection adds to 1000ml
Get water for injection dissolve polyvinyl alcohol, hyaluronic acid sodium, stir rising temperature for dissolving down, get solution A; With benzalkonium bromide, poloxamer 188, sodium chloride, the even solution B that gets of EDTA-2Na dissolving, put cold standby; The pirenoxine, sodium citrate, propyl gallate that takes by weighing recipe quantity adds in the solution A after the stirring and dissolving, solution C; Solution C adds in the solution B, mix homogeneously; Moisturizing is surveyed pH to 95% of total amount, and adding sodium hydroxide or dilute hydrochloric acid in case of necessity is 3.0-7.5; 0.45 μ m filtering with microporous membrane is used through the filterable water for injection of 0.45 μ m microporous filter membrane and added to full dose, stirs, high temperature sterilize 20～40min promptly gets gel for eye use.
Embodiment 12
The pastille tablet formulation:
Anhydrous Bernetine Sodium 2g
L-glutathion 30g
Vitamin C 10g
Taurine 35.0g
Boric acid 17.5g
Hydroxypropyl emthylcellulose 0.24g
50% ethanol 8ml
Sodium benzoate 0.3g
Make 1000
The dedicated solvent prescription:
Potassium chloride 1.6g
Sodium sulfite 2g
Tween 80 2g
Boric acid 12g
Borax 0.08g
Hydroxypropyl emthylcellulose 12g
EDTA-2Na 1g
Methyl parahydroxybenzoate 0.4g
Propyl p-hydroxybenzoate 0.2g
Add the injection water to 1000ml
Bernetine Sodium is crossed 80～120 mesh sieves, L-glutathion, taurine, boric acid, hydroxypropyl emthylcellulose are crossed 60～100 mesh sieves, take by weighing the recipe quantity Bernetine Sodium, the hydroxypropyl emthylcellulose of the L-glutathion after sieving, taurine, boric acid, 20% recipe quantity, adopt equivalent progressively increase method, fully mix homogeneously; With 50% ethanol system soft material, cross 10～30 mesh sieves and granulate drying; Dried particles is crossed 10～30 mesh sieve granulate, adds the sodium benzoate of recipe quantity, fully mix homogeneously; Content is measured in the intermediate check, calculates the heavy back of slice tabletting and gets tablet.Other gets water for injection and dissolves after sodium sulfite, boric acid, Borax, Tween 80, methyl parahydroxybenzoate, propyl p-hydroxybenzoate, EDTA-2Na, the potassium chloride dissolving, stirs; Hydroxypropyl emthylcellulose dissolving with residue 80%; Above-mentioned two kinds of solution mix homogeneously, moisturizing is to nearly full dose; Solution is used through the filtering water for injection of filter and is added to total amount by filtering with microporous membrane, makes dedicated solvent.Face with preceding tablet is dissolved in dedicated solvent, jolting can form eye-gel preparation.
Eye-gel preparation and listing product stability contrast test
Test specimen:
Prescription 1 eye-gel preparation self-control of the present invention
Prescription 6 eye-gel preparations self-control of the present invention
The BAINEITING DIYANYE Wuhan Yuanda Pharmaceutical Group Co.,Ltd of listing
The Ka Lin of listing-U suspendible eye drop Japan Santen Pharmaceutical Co. Ltd.
Detect index:
Detect according to the key index (outward appearance, pH, visible foreign matters, content, related substance) of 2005 editions requirements of Chinese Pharmacopoeia eye drop and eye-gel preparation.
Test method one:
Individual packaging is pasted the test specimen of respective labels and put into constant temperature reserved sample observing case, deposit for 40 ℃,, handle and detect relevant item according to 2005 editions requirements of Chinese Pharmacopoeia respectively at the 5th, 10 day taking-up sample.
The stability of the 10 days prescriptions of the present invention of 40 ℃ of heating and the product that goes on the market relatively
Stop eye drop test item 10 in embodiment 1 Ka Lin-U suspendible eye drop embodiment 6
0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days
Qualified qualified content (%) 99.4 98.4 97.6 99.7 97.6 96.2 99.2 98.9 98.4 99.4 98.5 97.8 related substances of qualified qualified pH 4.01 4.03 4.06 3.47 3.46 3.44 3.57 3.56 3.59 3.91 3.95 3.92 visible foreign matters of it outward appearance
1.10 2.62 4.10 1.59 4.07 6.26 0.93 1.01 1.12 1.23 1.49 1.64(％)
Test method two:
Individual packaging is pasted the test specimen of respective labels and put into illumination box, 4500lx deposits, and respectively at the 5th, 10 day taking-up sample, handles and detect relevant item according to 2005 editions requirements of Chinese Pharmacopoeia.
The stability of the 10 days prescriptions of the present invention of 500lx illumination and the product that goes on the market relatively
Embodiment 1 Ka Lin-U suspendible eye drop embodiment 6 BAINEITING DIYANYE test items
0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days qualified qualified content (%) 99.4 98.4 97.6 99.7 97.9 96.8 99.2 98.9 98.7 99.4 98.7 98.1 related substances of qualified qualified pH 4.01 4.05 4.08 3.47 3.46 3.44 3.57 3.56 3.58 3.91 3.95 3.92 visible foreign matters of outward appearance
1.10 2.37 3.62 1.59 3.98 5.43 0.93 1.02 1.07 1.23 1.44 1.66(％)
Annotate: the BAINEITING DIYANYE of embodiment 6 and listing all is before detecting tablet to be dropped into dedicated solvent.
The Ka Lin that conclusion: embodiment 1 correspondence is relatively gone on the market-U suspendible eye drop carries out in 40 ℃ of heating 10 days and 10 days the test of 4500lx illumination, and outward appearance, pH and clarity are all qualified.But content, related substance index can find out obviously that the present embodiment prescription is better than the product that goes on the market.
The embodiment 6 correspondences product BAINEITING DIYANYE of relatively going on the market, carried out 40 ℃ of heating 10 days and 10 days test of 4500lx illumination in, outward appearance, pH and clarity are all qualified.But content, related substance index also obviously are better than the product that goes on the market.
From totally relatively it seems, the embodiments of the invention prescription aspect content and related substance index, correspondence obviously be better than the multi-form product of liang kind.
Claims (10)
1, a kind of pirenoxine eye-gel preparation, it contains pirenoxine, gel-type vehicle and the medicine acceptable carrier of effective dose.
2, a kind of pirenoxine eye-gel preparation according to claim 1 is characterized in that: contain pirenoxine 0.001～10g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
3, a kind of pirenoxine eye-gel preparation according to claim 1, it is characterized in that: described gel-type vehicle is one or more the mixture in carbomer, polyvinyl alcohol, hydroxypropyl emthylcellulose, polyacrylic acid, methylcellulose, hyaluronic acid sodium, the sodium alginate, and consumption is 1.0～400g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
4, according to claim 1 or 3 described a kind of pirenoxine eye-gel preparations, it is characterized in that: described gel-type vehicle is a carbomer, and consumption is 1.0～150g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
5, a kind of according to claim 1 or 5 pirenoxine eye-gel preparation is characterized in that: described gel-type vehicle is a polyvinyl alcohol, and consumption is 1.0～400g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
6, a kind of pirenoxine eye-gel preparation according to claim 1, it is characterized in that: described medicine acceptable carrier is one or more the mixture in antioxidant, filler, solubilizing agent, wetting agent, lubricant, isoosmotic adjusting agent, antibacterial, metal chelating agent, the pH regulator agent, and consumption is 1.0～450g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
7, a kind of pirenoxine eye-gel preparation according to claim 6, it is characterized in that: described for antioxidant be sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, sodium formaldehyde sulphoxylate, sodium dithionite, the L-cysteine, L-lysine, the L-arginine, taurine, the L-glutathion, the L-methionine, the L-valine, the L-leucine, the L-isoleucine, the L-tryptophan, vitamin C and ester thereof, the D-arabo-ascorbic acid, vitamin E, thioglycerin, thiourea, 2 mercapto ethanol, dimercaptopropanol, BAL, 1-sulfo-sorbitol, TGA, thiosalicylic acid, dithiooxamide, in 6-methyl-2-deracil, fumaric acid, maleic acid, L-tartaric acid, pyrogallic acid and ester thereof, hydroquinone, oxine, para-aminophenol, the hydrochloric acid pyridoxamine, butylated hydroxyarisol, the mixture of one or more in the di-tert-butyl hydroxy-methylbenzene, its consumption is 0.1～100g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described solubilizing agent is one or more the mixture in Tween 80, PEG400, Macrogol 600, poloxamer 188, polyvinyl pyrrolidone, the HP-, and its consumption is 0.01～50g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described filler is one or more the mixture in sucrose or lactose, starch, microcrystalline Cellulose or dextrin, mannitol, sorbitol or the hydroxyl isomaltulose, and its consumption is 0.1～10g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described wetting agent is 50～90% ethanol waters, and its consumption is 0.1～15g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described lubricant is magnesium stearate or micropowder silica gel, and its consumption is 0.01～2g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described antibacterial is one or more the mixture in benzyl alcohol, chlorobutanol, thimerosal, hibitane, benzalkonium bromide, benzalkonium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate, the propylparaben, and its consumption is 0.01～30g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products; Described isoosmotic adjusting agent is one or more the mixture in sodium chloride, glucose, glycerol, propylene glycol, mannitol or the sorbitol, and its consumption is 0.01～200g in the pirenoxine eye-gel preparation of per 1000 milliliters of finished products.
8, a kind of Bernetine Sodium eye-gel preparation, it contains pirenoxine sodium salt, gel-type vehicle and the medicine acceptable carrier of effective dose.
9, the preparation method of a kind of pirenoxine and sodium salt eye-gel preparation, it may further comprise the steps:
(1), get water for injection dissolving with antibacterial, pH buffer system regulator, isoosmotic adjusting agent, complexing of metal ion agent, solubilizing agent dissolving after, stir, obtain A solution;
(2), pirenoxine sodium raw materials, antioxidant added dissolved in the solution of macromolecule hydrogel substrate, obtain B solution;
(3), mix two kinds of solution of above-mentioned A, B after; Re-adjustment pH is 3.0-7.5; Solution is used through the filtering water for injection of filter and is added to total amount by filtering with microporous membrane, makes eye-gel preparation.
10, the preparation method of a kind of Bernetine Sodium and sodium salt eye-gel preparation, it may further comprise the steps:
(1), the pirenoxine sodium salt 80～120 mesh sieves excessively, antioxidant, pH buffer system regulator, macromolecule hydrogel host material and filler are crossed 60～100 mesh sieves;
(2), take by weighing the pirenoxine sodium salt of recipe quantity, the antioxidant of 70% recipe quantity, the pH buffer system regulator of 70% recipe quantity, the macromolecule hydrogel host material of 20% recipe quantity, adopt equivalent progressively increase method, fully mix homogeneously;
(3), take by weighing the filler of recipe quantity, adopt the equivalent method of progressively increasing it to be sneaked in the above-mentioned material mix homogeneously; With wetting agent system soft material, to cross 10～30 mesh sieves and granulate, the gained granule is 30～70 ℃ of dryings, and moisture Control is 1～3%; Dried particles is crossed 10～30 mesh sieve granulate;
(4), add the lubricant of recipe quantity, fully mix homogeneously; Content is measured in the intermediate check, calculates the heavy back of slice tabletting and gets tablet.
(5), in addition after getting water for injection and will remaining 30% antioxidant, 30% pH buffer system regulator, solubilizing agent, antibacterial, complexing of metal ion agent, isoosmotic adjusting agent dissolving, stir, obtain A solution; Obtain B solution after the macromolecule hydrogel host material dissolving with residue 80%; Above-mentioned two kinds of solution mix homogeneously, moisturizing to 950～1000 milliliter; Solution is used through the filtering water for injection of filter and is added to 1000 milliliters by filtering with microporous membrane, makes dedicated solvent.Tablet is dissolved in dedicated solvent, and jolting can form eye-gel preparation.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101822677B (en) * | 2009-03-03 | 2012-05-30 | 吴文耀 | Eye drops for cataracts |
| CN104054704A (en) * | 2014-03-26 | 2014-09-24 | 中国人民解放军第三军医大学第一附属医院 | Hydroxypropyl-beta-cyclodextrin supermolecular inclusion complex of methylparaben, preparation method of inclusion complex and use method of inclusion complex |
| EP3310363A4 (en) * | 2015-06-18 | 2019-02-13 | Common Pharma, Inc | Antimicrobial formulations |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
-
2006
- 2006-06-22 CN CN 200610019432 patent/CN1895218A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101822677B (en) * | 2009-03-03 | 2012-05-30 | 吴文耀 | Eye drops for cataracts |
| CN104054704A (en) * | 2014-03-26 | 2014-09-24 | 中国人民解放军第三军医大学第一附属医院 | Hydroxypropyl-beta-cyclodextrin supermolecular inclusion complex of methylparaben, preparation method of inclusion complex and use method of inclusion complex |
| EP3310363A4 (en) * | 2015-06-18 | 2019-02-13 | Common Pharma, Inc | Antimicrobial formulations |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
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