CN100563628C - A kind of Bendalysine eye gel preparation and preparation method thereof - Google Patents
A kind of Bendalysine eye gel preparation and preparation method thereof Download PDFInfo
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- CN100563628C CN100563628C CNB2006100194341A CN200610019434A CN100563628C CN 100563628 C CN100563628 C CN 100563628C CN B2006100194341 A CNB2006100194341 A CN B2006100194341A CN 200610019434 A CN200610019434 A CN 200610019434A CN 100563628 C CN100563628 C CN 100563628C
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Abstract
The present invention relates to a kind of Bendalysine eye gel preparation, it contains bendazac lysine, gel-type vehicle and the medicine acceptable carrier of effective dose.This eye-gel preparation is an aldose reductase inhibitor, the crystalline lens aldose reductase there is inhibitory action, makes bendazac lysine enter ocular tissue and aqueous humor by local eye drip, and in crystalline lens, concentrate, thereby aldose reductase activity in the inhibition eyes reaches prevention and treats cataractous purpose; Compare with ordinary eye drops, this gel for eye has that zest is little, intermiscibility good, keeps long, the lasting more effectively characteristics of curative effect of medicine effective concentration time.
Description
Technical field
The present invention relates to a kind of eye medicinal, specifically a kind ofly be used for prevention and treat cataractous Bendalysine eye gel preparation and preparation method thereof.
Background technology
Cataract is topmost diseases causing blindness.World Health Organization (WHO) estimates, reaches 50% (1,700,000) because of cataract blinding person in the world.Along with human longevity prolongs, aging grows with each passing day, and by 2010, the person will be multiplied because of the cataract blinding.In China, estimate according to hygiene department, annual newborn cataract patient 400,000 examples, it occupies China's diseases causing blindness and gets the first.Calculate that according to national sampling survey correct defects of vision 0.3 cataract patient of national eyes is about 5,000,000 people, annually accumulate with newly-increased 400,000～1,200,000 routine cataract patients.At present, worldwide prevent and treat cataractous measure and still be the measure of mainly recovering lost eyesight with operation or implantable artificial crystal, be the cataract mature period opportunity but because of performing the operation preferably, therefore, patient need stand the torment of long cataract state of an illness development, and operation is subjected to the restriction of condition and equipment, and expense is also relatively more expensive, is difficult to solve the demand of the cataract patient that grows with each passing day.Therefore, the medical treatment cataract has important social benefit and economic benefit.
Bendazac lysine is an aldose reductase inhibitor, the crystalline lens aldose reductase there is inhibitory action, makes bendazac lysine enter ocular tissue and aqueous humor by local eye drip, and in crystalline lens, concentrate, thereby aldose reductase activity in the inhibition eyes reaches prevention and treats cataractous purpose.This product is to In vitro culture mice crystalline lens cataract model Wheat Protein; To rat sugar cataract model, the means such as ultrastructure by slit lamp photography is observed lenticular opacity degree and employing electron micrograph crystallin fiber prove prevention and therapeutical effect; The degeneration of the mice that heat is caused, rabbit, pig crystallin, test in vivo and in vitro all has protective effect, and is dependency with dosage; The rabbit cataractous lens that the X-ray is caused has protective effect; To 2, dissolving of the inner membrance of the cell membrane of the rabbit cataractous lens that the 4-dinitrophenol causes and endochylema run off protective effect are arranged; These show that all bendazac lysine has the anti-cataract effect.
The Benzydalysine eye drop that gone on the market relevant with this product exists certain zest, medicine, and holdup time number of times and frequency short, eye dripping is higher within the eye, and patient dependence is relatively poor, causes using wish to reduce.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.
Summary of the invention
The purpose of this invention is to provide a kind of eye-gel preparation that contains bendazac lysine and preparation method thereof.It is a kind of colourless flowing or the eye-gel preparation of semifluid gel state.It has solved zest, medicine holdup time weak point, the eye dripping number of times that exists in the existing eye drop and frequency is higher, the problem of curative effect of medication difference.
Technical scheme of the present invention is achieved in that it contains the bendazac lysine of effective dose, gel-type vehicle and medicine acceptable carrier.The bendazac lysine consumption is 0.05～5g in per 100 milliliters of gel preparations.
Gel-type vehicle described in the described gel preparation is one or more the mixture in carbomer, polyvinyl alcohol, hydroxypropyl emthylcellulose, polyacrylic acid, methylcellulose, hyaluronic acid sodium, the sodium alginate, and its consumption is 0.1～40g in per 100 milliliters of gel preparations.
Preferred carbomer of gel-type vehicle in the preparation or polyvinyl alcohol, when selecting carbomer for use, consumption is 0.1～15g in per 100 milliliters of gel preparations; When selecting polyvinyl alcohol as macromolecule hydrogel substrate for use, consumption is 0.1～40g in per 100 milliliters of gel preparations.
Described medicine acceptable carrier is one or more in local analgesia agent, solubilizing agent, antibacterial, isoosmotic adjusting agent, the pH value regulator.
Described local analgesia agent is selected from one or more the mixture in benzyl alcohol, phenethanol, chlorobutanol, ethanol, propylene glycol, glycerol, magnesium chloride, magnesium sulfate, procaine hydrochloride, urethane, the lidocaine hydrochloride, and its consumption is 0.001～2g in per 100 milliliters of gel preparations.
Described solubilizing agent is one or more the mixture in Tween 80, PEG400, Macrogol 600, poloxamer 188, polyvinyl pyrrolidone, polyvidone, the HP-, and its consumption is 0.001～5g in per 100 milliliters of gel preparations.
Described antibacterial is selected from one or more the mixture in chlorocresol, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, chlorobutanol, phenoxyethanol, chlorhexidine, oradol, benzalkonium chloride, Benzethonium, the benzalkonium bromide, and its consumption is 0.01～2g in per 100 milliliters of gel preparations; Described isoosmotic adjusting agent is selected from one or more the mixture in sodium chloride, glucose, glycerol, propylene glycol, mannitol or the sorbitol; Described pH value regulator is selected from one or more in hydrochloric acid, sodium hydroxide, triethanolamine, citric acid, sodium citrate, tartaric acid, sodium tartrate, boric acid, Borax, glacial acetic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, the phosphoric acid, and its consumption is for to be adjusted to 4.5～9.0 consumption with pH value.
Preparation method of the present invention may further comprise the steps:
(1), get gel-type vehicle and add sterilized water for injection and stir, make its abundant swelling, it is standby to make blank gel A;
(2), bendazac lysine dissolved fully after, add the medicine acceptable carrier again, be stirred to dissolving fully, solution B;
(3), with B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0, use through the filterable water for injection of 0.45 μ m microporous filter membrane and add to 100 milliliters with the pH value regulator, stir, promptly get Bendalysine eye gel.
The present invention can make bendazac lysine enter ocular tissue and aqueous humor by local eye drip, and concentrates in crystalline lens, thereby suppresses aldose reductase activity performance anti-cataract effect in the eyes, reaches prevention and treats cataractous purpose; By Drug therapy, can delay the development of lenticular opacity at the initial stage of a disease, keep and improve patient's quality of life; The present invention has simultaneously that the gel zest is little, intermiscibility good, keeps long, the more persistent characteristics of curative effect of medicine effective concentration time.
Macromolecule hydrogel substrate among the present invention 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.Than ordinary eye drops, eye-gel preparation has that zest is little, intermiscibility good, keeps long, the more persistent characteristics of curative effect of medicine effective concentration time, and the local analgesia agent among the present invention can effectively reduce ordinary eye drops and one cross property burn feeling and zest to what the patient brought.
The present invention shows that through eye irritation test the present invention through eye dripping repeatedly, organizes equal nonirritant to lagophthalmos.The present invention is different from general cycloplegic, can not cause platycoria, and is unaffected on class to child, adolescents with learning, accepted use by them easily.
The specific embodiment
Following example will the present invention is further elaborated, but do not limit content of the present invention.
Embodiment 1
Bendazac lysine 40g
Sodium dihydrogen phosphate 24.8g
Sodium hydrogen phosphate 133.6g
Sodium chloride 35.2g
Carbopol 941 80g
Benzalkonium chloride 0.4g
Tween 80 8ml
Lidocaine hydrochloride 5g
Water for injection adds to 8000ml
Make 1000
Get Carbopol 941 and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium chloride, lidocaine hydrochloride, tween 80 again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium chloride limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 2
Bendazac lysine 40g
Boric acid 100g
Borax 16g
Glycerol 30ml
Acritamer 940 100g
Benzalkonium bromide 0.4g
PEG400 (PEG400) 10ml
Ethanol 8ml
Water for injection adds to 8000ml
Make 1000
Get Acritamer 940 and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add boric acid, Borax, glycerol, ethanol, PEG400 (PEG400) again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium bromide limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 3
Bendazac lysine 40g
Boric acid 100g
Natrium carbonicum calcinatum 6g
Potassium chloride 50g
Polyvinyl alcohol 160g
Methyl hydroxybenzoate 0.2g
PEG600 (Macrogol 600) 8ml
Magnesium sulfate 3g
Water for injection adds to 8000ml
Make 1000
Get polyvinyl alcohol and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add boric acid, natrium carbonicum calcinatum, potassium chloride, magnesium sulfate, PEG600 (Macrogol 600) again, be stirred to dissolving fully; In above-mentioned solution, add methyl hydroxybenzoate limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 4
Bendazac lysine 40g
Sodium citrate 24g
Sodium chloride 50g
Hydroxypropyl emthylcellulose 120g
Ethyl hydroxybenzoate 0.2g
Tween 80 12ml
Magnesium chloride 3g
Water for injection adds to 8000ml
Make 1000
Get the sterilized water for injection of hydroxypropyl emthylcellulose adding more than 80 ℃ and stir, make its abundant swelling, be cooled to room temperature, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium citrate, sodium chloride, magnesium chloride, Tween 80 again, be stirred to dissolving fully; In above-mentioned solution, add ethyl hydroxybenzoate limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, stir into even gel with adding through the filterable water for injection of 0.45 μ m microporous filter membrane to full dose, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 5
Bendazac lysine 40g
Sodium tartrate 24g
Sodium chloride 50g
Polyvinyl alcohol 80g
Propylparaben 0.2g
Poloxamer 188 16g
Urethane 4g
Water for injection adds to 8000ml
Make 1000
Get polyvinyl alcohol and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium tartrate, sodium chloride, urethane, poloxamer 188 again, be stirred to dissolving fully; In above-mentioned solution, add propylparaben limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 6
Bendazac lysine 40g
Sodium alginate 32g
Sodium hydrogen phosphate 96g
Sodium dihydrogen phosphate 16g
Benzalkonium chloride 0.4g
PEG400 (PEG400) 16g
Lidocaine hydrochloride 5g
Water for injection adds to 8000ml
Make 1000
Get sodium alginate and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium hydrogen phosphate, sodium dihydrogen phosphate, lidocaine hydrochloride, PEG400 (PEG400) again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium chloride limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 7
Bendazac lysine 40g
Sodium dihydrogen phosphate 24.8g
Sodium hydrogen phosphate 133.6g
Sodium chloride 35.2g
Carbopol 941 80g
Sodium alginate 32g
Polyvinyl alcohol 30g
Hydroxypropyl emthylcellulose 50g
Benzalkonium chloride 0.4g
Propylparaben 0.4g
Polyvidone 10g
Tween 80 8ml
Lidocaine hydrochloride 5g
Water for injection adds to 8000ml
Make 1000
Get Carbopol 941, sodium alginate, polyvinyl alcohol, the stirring of hydroxypropyl emthylcellulose adding sterilized water for injection, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium dihydrogen phosphate, sodium hydrogen phosphate, sodium chloride, lidocaine hydrochloride, tween 80, polyvidone again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium chloride and propylparaben, the limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 8
Bendazac lysine 10g
Boric acid 100g
Borax 16g
Glycerol 30ml
Acritamer 940 50g
Polyacrylic acid 50g
Methylcellulose 100g
Benzalkonium bromide 0.4g
PEG400 (PEG400) 10ml
Ethanol 8ml
Water for injection adds to 8000ml
Make 1000
Get Acritamer 940, polyacrylic acid, the stirring of methylcellulose adding sterilized water for injection, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add boric acid, Borax, glycerol, ethanol, PEG400 (PEG400) again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium bromide limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 9
Bendazac lysine 400g
Boric acid 100g
Natrium carbonicum calcinatum 6g
Potassium chloride 50g
Polyvinyl alcohol 100g
Hyaluronic acid sodium 60g
Hydroxypropyl emthylcellulose sodium 60g
Methyl hydroxybenzoate 0.2g
PEG600 (Macrogol 600) 8ml
Magnesium sulfate 3g
Urethane 1g
Water for injection adds to 8000ml
Make 1000
Get polyvinyl alcohol, hyaluronic acid sodium, the stirring of hydroxypropyl emthylcellulose sodium adding sterilized water for injection, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add boric acid, natrium carbonicum calcinatum, potassium chloride, magnesium sulfate, urethane, PEG600 (Macrogol 600) again, be stirred to dissolving fully; In above-mentioned solution, add methyl hydroxybenzoate limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 10
Bendazac lysine 100g
Sodium citrate 24g
Sodium chloride 50g
Hydroxypropyl emthylcellulose 120g
Sodium alginate 80g
Ethyl hydroxybenzoate 0.2g
Tween 80 12ml
Magnesium chloride 3g
Water for injection adds to 8000ml
Make 1000
Get hydroxypropyl emthylcellulose, the sodium alginate adding sterilized water for injection stirring more than 80 ℃, make its abundant swelling, be cooled to room temperature, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium citrate, sodium chloride, magnesium chloride, Tween 80 again, be stirred to dissolving fully; In above-mentioned solution, add ethyl hydroxybenzoate limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, stir into even gel with adding through the filterable water for injection of 0.45 μ m microporous filter membrane to full dose, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 11
Bendazac lysine 100g
Sodium tartrate 24g
Sodium chloride 50g
Polyvinyl alcohol 80g
Propylparaben 0.2g
Poloxamer 188 16g
Urethane 4g
Water for injection adds to 8000ml
Make 1000
Get polyvinyl alcohol and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium tartrate, sodium chloride, urethane, poloxamer 188 again, be stirred to dissolving fully; In above-mentioned solution, add propylparaben limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 12
Bendazac lysine 40g
Sodium alginate 32g
Hyaluronic acid sodium 100g
Sodium hydrogen phosphate 96g
Sodium dihydrogen phosphate 16g
Benzalkonium chloride 0.4g
PEG400 (PEG400) 16g
Polyvinyl pyrrolidone 5g
Lidocaine hydrochloride 5g
Water for injection adds to 8000ml
Make 1000
Get sodium alginate and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium hydrogen phosphate, sodium dihydrogen phosphate, lidocaine hydrochloride, PEG400 (PEG400), polyvinyl pyrrolidone again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium chloride limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 13
Bendazac lysine 20g
Sodium tartrate 24g
Sodium chloride 50g
Polyvinyl alcohol 200g
Propylparaben 0.2g
Poloxamer 188 16g
HP-20g
Urethane 4g
Water for injection adds to 8000ml
Make 1000
Get polyvinyl alcohol and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium tartrate, sodium chloride, urethane, poloxamer 188, HP-again, be stirred to dissolving fully; In above-mentioned solution, add propylparaben limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Embodiment 14
Bendazac lysine 80g
Sodium alginate 120g
Sodium hydrogen phosphate 96g
Sodium dihydrogen phosphate 16g
Benzalkonium chloride 0.4g
PEG400 (PEG400) 160g
Lidocaine hydrochloride 5g
Water for injection adds to 8000ml
Make 1000
Get sodium alginate and add the sterilized water for injection stirring, make its abundant swelling, it is standby to make blank gel A; After bendazac lysine dissolved fully, add sodium hydrogen phosphate, sodium dihydrogen phosphate, lidocaine hydrochloride, PEG400 (PEG400) again, be stirred to dissolving fully; In above-mentioned solution, add benzalkonium chloride limit edged be stirred to dissolve fully solution B.With B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0 with the pH value regulator, with adding to full dose through the filterable water for injection of 0.45 μ m microporous filter membrane, stir, high temperature sterilize 20～40min promptly gets Bendalysine eye gel.
Eye-gel preparation and eye drop contrast test
One, stability relatively
Test specimen:
Prescription 1 eye-gel preparation specification: 8ml trial-production of the present invention
Prescription 2 eye-gel preparation specification: 8ml trial-production of the present invention
Prescription 3 eye-gel preparation specification: 8ml trial-production of the present invention
The Benzydalysine eye drop specification of listing: 8ml lot number: 050611
Manufacturer Zhejiang Pinghu pharmaceutical Co. Ltd
Detect index:
Require to measure eye drops and the drug content of gel for eye, the content of related substance according to Chinese Pharmacopoeia 2005 editions, the key index (outward appearance, pH value, visible foreign matters) to eye drop and eye-gel preparation detects simultaneously.
Test method one:
Test specimen is put into constant temperature reserved sample observing case, deposit for 60 ℃,, 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 60 ℃ of heating and the product that goes on the market relatively
Prescription 1 prescription 2 prescription 3 listing products of the present invention of the present invention of the present invention
Test item 0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days
Outward appearance is qualified qualified
PH value 6.93 6.98 6.94 7.02 6.99 6.98 6.89 6.95 6.92 7.15 7.09 7.04
Visible foreign matters is qualified qualified
Content (%) 99.8 99.5 99.4 98.7 98.5 98.5 98.9 98.8 98.6 99.6 99.2 98.8
Related substance (%) 0.30 0.32 0.48 0.28 0.35 0.43 0.32 0.39 0.45 0.45 0.56 0.64
Test method two:
Test specimen is put into illumination box, and 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 4500lx illumination and the product that goes on the market relatively
Prescription 1 prescription 2 prescription 3 listing products of the present invention of the present invention of the present invention
Test item 0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days 0 day 5 days 10 days
Outward appearance is qualified qualified
PH value 6.93 6.96 6.95 7.02 6.99 7.03 6.89 6.91 6.90 7.15 7.08 7.06
Visible foreign matters is qualified qualified
Content (%) 99.8 99.6 99.5 98.7 98.5 98.4 98.9 98.7 98.6 99.6 99.3 98.7
Related substance (%) 0.30 0.41 0.55 0.28 0.46 0.58 0.32 0.43 0.55 0.45 0.59 0.72
Conclusion: prescription of the present invention carries out in 60 ℃ of heating 10 days and 10 days the test of 4500lx illumination equally with the listing product, and outward appearance, content, pH value, related substance and clarity are all qualified.But the determination data of the total related substance of this prescription sample shows that prescription of the present invention is better than the eye drop that goes on the market in varying degrees.
Two, irritation test:
Test specimen:
Prescription 1 eye-gel preparation specification: 8ml trial-production of the present invention
Prescription 3 eye-gel preparation specification: 8ml trial-production of the present invention
The Benzydalysine eye drop specification of listing: 8ml lot number: 050611
Test objective: with listing product Benzydalysine eye drop is contrast, observes behind the animal eyes contact test sample irritant reaction situation to conjunctiva, cornea and iris.
Test method one: single eye drip zest: get 8 of healthy white rabbit, be divided into 2 groups, left eye is used prescription 1 of the present invention and prescription of the present invention 3 respectively; Right eye all adopts the contrast of listing product.2h, 6h, 24h, 48h, 72h and used fluorescent staining in 7 days before eye drip and behind the eye drip, slit lamp observation is to the irritant reaction of conjunctiva, cornea and iris.
Test method two: eye drip zest repeatedly: get 8 of healthy white rabbit, be divided into 2 groups, left eye is used prescription 1 of the present invention and prescription of the present invention 3 respectively; Right eye all adopts the contrast of listing product.Every day, eye drip was 5 times, and continuous 14 days, used fluorescent staining in 2,4,6,8,10,12,14 days before eye drip and behind the eye drip, slit lamp observation is to the irritant reaction of conjunctiva, cornea and iris.
Testing standard:
The score value result:
1. single-dose result of the test
2. multiple dosing result of the test
Conclusion: to testing result in score value, by statistics, prescription 1 of the present invention and 3, listing product are behind single-dose, equal nonirritant, but the score value of prescription 1 of the present invention is better than prescription 3 of the present invention, prescription of the present invention 3 score values are better than the product that goes on the market, and illustrates that prescription 1 of the present invention and 3 zests are all less than the eye drop that goes on the market.
Behind the multiple dosing, prescription 1 of the present invention, prescription of the present invention 3 and listing prescription zest all meet the requirements, but prescription 1 of the present invention, prescription of the present invention 3 zest after the zest behind the multiple dosing all is significantly less than the administration of listing product, and the holdup time obviously is longer than the eye drop of listing within the eye to can be observed prescription 1 of the present invention and 3 in the process of the test.
Claims (6)
1, a kind of Bendalysine eye gel preparation, it contains bendazac lysine, sodium alginate and the medicine acceptable carrier of effective dose, and wherein: the bendazac lysine consumption is that 0.05～5g, sodium alginate consumption are 0.1～40g in per 100 milliliters of gel preparations.
2, a kind of Bendalysine eye gel preparation according to claim 1 is characterized in that: described medicine acceptable carrier is one or more in local analgesia agent, solubilizing agent, antibacterial, isoosmotic adjusting agent, the pH value regulator.
3, a kind of Bendalysine eye gel preparation according to claim 2, it is characterized in that: described local analgesia agent is selected from one or more the mixture in benzyl alcohol, phenethanol, chlorobutanol, ethanol, propylene glycol, glycerol, magnesium chloride, magnesium sulfate, procaine hydrochloride, urethane, the lidocaine hydrochloride, and its consumption is 0.001～2g in per 100 milliliters of gel preparations.
4, a kind of Bendalysine eye gel preparation according to claim 2, it is characterized in that: described solubilizing agent is one or more the mixture in Tween 80, PEG400, Macrogol 600, poloxamer 188, polyvinyl pyrrolidone, polyvidone, the HP-, and its consumption is 0.001～5g in per 100 milliliters of gel preparations.
5, a kind of Bendalysine eye gel preparation according to claim 2, it is characterized in that: described antibacterial is selected from one or more the mixture in chlorocresol, methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, chlorobutanol, phenoxyethanol, chlorhexidine, oradol, benzalkonium chloride, Benzethonium, the benzalkonium bromide, and its consumption is 0.01～2g in per 100 milliliters of gel preparations; Described isoosmotic adjusting agent is selected from one or more the mixture in sodium chloride, glucose, glycerol, propylene glycol, mannitol or the sorbitol; Described pH value regulator is selected from one or more in hydrochloric acid, sodium hydroxide, triethanolamine, citric acid, sodium citrate, tartaric acid, sodium tartrate, boric acid, Borax, glacial acetic acid, sodium hydrogen phosphate, sodium dihydrogen phosphate, the phosphoric acid.
6, the preparation method of the described a kind of Bendalysine eye gel preparation of claim 1, it may further comprise the steps:
(1), get sodium alginate and add sterilized water for injection and stir, make its abundant swelling, it is standby to make blank gel A;
(2), bendazac lysine dissolved fully after, add the medicine acceptable carrier again, be stirred to dissolving fully, solution B;
(3), with B solution through 0.45 μ m filtering with microporous membrane, filtrate joined among the blank gel A stir, adjust pH value to 4.5～9.0, use through the filterable water for injection of 0.45 μ m microporous filter membrane and add to 100 milliliters with the pH value regulator, stir, promptly get Bendalysine eye gel.
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| RU2785343C1 (en) * | 2022-03-16 | 2022-12-06 | Общество с ограниченной ответственностью "ФАРМАЦЕЯ" | Veterinary hygienic eye lotion |
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| CN103735495B (en) * | 2014-01-23 | 2016-07-20 | 兆科药业（合肥）有限公司 | A kind of Ciclosporin eye gel and preparation method thereof |
| 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 |
| WO2016205574A1 (en) * | 2015-06-18 | 2016-12-22 | Common Pharma, Inc | Antimicrobial formulations |
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Non-Patent Citations (2)
| Title |
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| 复方氧氟沙星眼用凝胶剂的制备及质量控制. 吕竹芬.中国药师，第8卷第9期. 2005 |
| 复方氧氟沙星眼用凝胶剂的制备及质量控制. 吕竹芬.中国药师，第8卷第9期. 2005 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2785343C1 (en) * | 2022-03-16 | 2022-12-06 | Общество с ограниченной ответственностью "ФАРМАЦЕЯ" | Veterinary hygienic eye lotion |
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