CN1895284A - Gel for removing ocular by ice pearl and its preparation - Google Patents
Gel for removing ocular by ice pearl and its preparation Download PDFInfo
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- CN1895284A CN1895284A CNA2006100194337A CN200610019433A CN1895284A CN 1895284 A CN1895284 A CN 1895284A CN A2006100194337 A CNA2006100194337 A CN A2006100194337A CN 200610019433 A CN200610019433 A CN 200610019433A CN 1895284 A CN1895284 A CN 1895284A
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Abstract
A medical gel for preventing and treating cataract contains the hydrolytic liquid of pearl powder, borneol, Zn, beta-carotene, VE, gel matrix and pharmacologically acceptable carrier. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of disease of eye, exactly is a kind of gel for removing ocular by ice pearl preparation and preparation method thereof.
Background technology
Cataract be present blinding main diseases 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.
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.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 invention 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.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 objective of the invention is defective, a kind of gel for removing ocular by ice pearl preparation is provided at the existing product existence.It is a kind of eye-gel preparation of gel state, than ordinary eye drops, has that zest is little, intermiscibility good, keeps long, the more persistent characteristics of curative effect of medicine effective concentration time.
Another object of the present invention provides the preparation method of this gel for removing ocular by ice pearl preparation.
Gel for removing ocular by ice pearl preparation of the present invention comprises medicinal active ingredient Margarita layer powder hydrolysate, Borneolum Syntheticum, trace element zinc, beta-carotene, vitamin E, gel-type vehicle and medicine acceptable carrier.
Comprise in the eye-gel preparation of wherein per 1000 milliliters of finished products:
Margarita layer powder 10～1500g, zinc gluconate 0.01～100g, vitamin E 0.001～100g, beta-carotene 0.0001～10g, Borneolum Syntheticum 0.01～100g, gel-type vehicle 1～400g, medicine acceptable carrier 1～100g
Described gel-type vehicle is: one or more in carbomer, polyvinyl alcohol, hydroxypropyl emthylcellulose, polyacrylic acid, methylcellulose, hyaluronic acid sodium, the sodium alginate.
The carbomer of preferred 1～150g or the polyvinyl alcohol of 1～400g.The more preferably mixture of the polyvinyl alcohol of the carbomer of 100g and 300g.
Described medicine acceptable carrier is solubilizing agent, isoosmotic adjusting agent and pH regulator agent.
Described solubilizing agent is specially one or more in Tween 80, PEG400, Macrogol 600, poloxamer 188, polyvinyl pyrrolidone, the HP-, and its consumption is 0.01～30g.
Described isoosmotic adjusting agent is specially one or more in sodium chloride, glucose, glycerol, propylene glycol, mannitol or the sorbitol; The pH regulator agent is specially 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.The consumption of isoosmotic adjusting agent and pH regulator agent is those skilled in the art's a known technology.
Also contain 0.2～20g antiseptic in the described eye-gel preparation.
The preparation method of gel for removing ocular by ice pearl preparation of the present invention may further comprise the steps:
(1), Margarita layer powder added water be hydrolyzed, after the hydrolysis filtrate is concentrated, the antiseptic that adds 1/2 total amount is standby;
(2), in above-mentioned concentrated solution, add the zinc gluconate dissolving after, add the pH regulator agent again, isoosmotic adjusting agent obtains solution A;
(3), in addition get water for injection dissolving gel-type vehicle, stir rising temperature for dissolving down, get solution B; To go up two kinds of solution mixings of A, B, boil filtration; Get water for injection more in addition, add Borneolum Syntheticum, solubilizing agent, beta-carotene, vitamin E and stir, be added in the aforementioned filtrate, and leave standstill after adding the antiseptic of 1/2 total amount; Add the pH value regulator, regulating pH value is 4.5～9.0, and moisturizing is to the 800-980 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
Pharmacological action of the present invention is as follows:
Beta-carotene scalable DNA synthetic in crystal; Remove reactive oxygen free radical, the protection crystal exempts from oxidative damage.
Vitamin E has the snperoxiaized effect of prevention ester matter.It is by stoping peroxidating, the particularly formation of ester matter peroxide, and the protection cell membrane exempts from the damage of Oxidation.
Margarita layer powder is that the shell of Margarita is the nearly internal layer of Concha Margaritifera.The ingredient that belongs to Concha Margaritifera.Also be the most medicable part in the Concha Margaritifera, nature and flavor are salty, cold, return liver, the heart two warps, and the traditional Chinese medical science thinks to have " removing nebula makes eye bright " " detoxifcation makes eye bright " " controlling the order skin " " controls cataracta tunica albuginea in the eye " and reach the effect of " removing toxic substances and promoting granulation ".Modern study shows and contains protein, calcium salt and various trace elements in the Margarita layer powder, wherein protein can be decomposed into polypeptide and a large amount of aminoacid through hydrolysis, as: aspartic acid, serine, glutamic acid, glycine, alanine, cysteine, valine, methionine, leucine, phenylalanine, lysine, it also contains various trace elements such as copper, ferrum.Its chemical constituent is almost similar to the Margarita decomposed solution.Modern medicine thinks that aminoacids complex can participate in ocular tissue's metabolism directly, collagen decomposition enzyme and the mucopolysaccharide catabolic enzyme that causes the crystal muddiness played inhibitory action, enzyme series to contained sulfydryl in the crystal has activation, suppress transparent soluble protein to the proteic transformation of insolubility, help crystal to strengthen transparency.
Borneolum Syntheticum nature and flavor suffering, hardship, be slightly cold, return liver, the heart, spleen channel, the function causing resuscitation with aromatic drugs, clearing away heat to alleviate pain has the removing nebula function of improving eyesight.Borneolum Syntheticum promotes the effect of other medicines angle of penetration envelope barrier in addition in opthalmological.
Zinc is the cofactor of multiple metalloenzyme, participates in the synthetic of plurality of enzymes, has the 26S Proteasome Structure and Function of keeping cell membrane, the effect that promotes growth promoter.Zinc content is abundant in the crystal, plays an important role in the crystal metabolism.Zinc participates in amphiblestroid conduction and metabolism, in the normal structure form that keeps retinal pigment epithelium, keeps the normal vision function aspects and plays an important role, and also participates in the metabolism of retinol.
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.
It is nutrition that eye-gel preparation of the present invention has the order of increasing, trace element supplement, additional crystal exogenous antioxidant, raising crystal endogenous antioxidative functional, inhibition aldose reductase activity, thus reach the prevention of cataract disease and the effect of treatment; Thickening agent among the present invention can increase medicine viscosity, prolong drug action time, promote drug absorption, increase curative effect of medication, can play similar artificial tears's effect simultaneously, malaise symptoms such as lacrimal secretion deficiency, the eye that alleviation age reason causes is dried, puckery, asthenopia.Than ordinary eye drops, eye-gel preparation itself has also that zest is little, intermiscibility good, keep the medicine effective concentration time long, curative effect is lasting more, the less characteristics of medication number of times.
The specific embodiment
Following example will the present invention is further elaborated, but do not limit content of the present invention.
Embodiment 1
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Carbopol 941 10g
Tween 80 2g
Benzalkonium chloride 1g
Borax 3g
Glycerol 15.5g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, the lasting stirring 48 hours, filtration also concentrates filtrate, and the benzalkonium chloride that adds recipe quantity 50% dissolves the even solution A that gets as antibacterial, puts cold standby; Other gets water for injection dissolving Carbopol 941, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add Borax, glycerol again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets water for injection, adds Borneolum Syntheticum, beta-carotene, vitamin E, Tween 80, stirs, dissolve solution D, standby; D solution is added C solution, and after adding remaining benzalkonium chloride, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH value be 4.5～9.0, moisturizing to 980 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
Embodiment 2
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Polyvinyl alcohol 20g
Tween 80 2g
Benzalkonium bromide 1g
Sodium citrate 3g
Sodium chloride 6.8g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, and the benzalkonium bromide that adds recipe quantity 50% dissolves the even solution A that gets as antibacterial, puts cold standby; Other gets the water for injection dissolve polyvinyl alcohol, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add sodium citrate, sodium chloride again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds Borneolum Syntheticum, beta-carotene, vitamin E, Tween 80, stirs, dissolve solution D, standby; D solution is added C solution, and after adding remaining benzalkonium bromide, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 950 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
Embodiment 3
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Acritamer 940 15g
Tween 80 2g
Benzalkonium bromide 1g
Triethanolamine 18g
Glucose 38g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, adds the benzalkonium bromide of recipe quantity 50%, dissolves the even solution A that gets, and puts cold standby; Other gets water for injection dissolving Acritamer 940, adds triethanolamine, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add glucose, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds Borneolum Syntheticum, beta-carotene, vitamin E, Tween 80, stirs, dissolve solution D, standby; D solution is added C solution, and after adding benzalkonium chloride, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 950 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.。
Embodiment 4
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Hydroxypropyl emthylcellulose 15g
Tween 80 2g
Phenoxyethanol 3ml
Borax 3g
Propylene glycol 12.4g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, adds the part phenoxyethanol, dissolves the even solution A that gets, and puts cold standby; Other gets water for injection dissolving hydroxypropyl emthylcellulose, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add Borax, sodium chloride again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds Borneolum Syntheticum, beta-carotene, vitamin E, Tween 80, stirs, dissolve solution D, standby; D solution is added C solution, and after adding remaining phenoxyethanol, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 900 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
Embodiment 5
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Polyvinyl alcohol 10g
Poloxamer 188 2g
Benzalkonium chloride 1g
Sodium tartrate 3g
Sodium chloride 6.2g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, adds the benzalkonium bromide of recipe quantity 50%, dissolves the even solution A that gets, and puts cold standby; Other gets the water for injection dissolve polyvinyl alcohol, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add sodium tartrate, sodium chloride again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds beta-carotene, vitamin E, Borneolum Syntheticum, poloxamer 188, stirs, dissolve solution D, standby; D solution is added C solution, and after adding remaining benzalkonium chloride, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 850 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
Embodiment 6
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Methylcellulose 40g
Sodium alginate 4g
PEG400 2g
Ethyl hydroxybenzoate 1g
Sodium hydrogen phosphate 12g
Sodium dihydrogen phosphate 2g
Glycerol 15.5g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, adds the ethyl hydroxybenzoate of recipe quantity 50%, dissolves the even solution A that gets, and puts cold standby; Other gets water for injection dissolving sodium alginate, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add sodium hydrogen phosphate, sodium dihydrogen phosphate, glycerol again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds beta-carotene, vitamin E, Borneolum Syntheticum, PEG400, methylcellulose, stirs, dissolve solution D, standby; D solution is added A solution, and after adding ethyl hydroxybenzoate, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 950 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.。
Embodiment 7
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
Methylcellulose 40g
PEG400 2g
Ethyl hydroxybenzoate 1g
Sodium hydrogen phosphate 12g
Sodium dihydrogen phosphate 2g
Glycerol 15.5g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, adds the ethyl hydroxybenzoate of recipe quantity 50%, dissolves the even solution A that gets, and puts cold standby; Other gets water for injection dissolving methylcellulose, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add sodium hydrogen phosphate, sodium dihydrogen phosphate, glycerol again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds beta-carotene, vitamin E, Borneolum Syntheticum, PEG400, stirs, dissolve solution D, standby; D solution is added A solution, and after adding remaining ethyl hydroxybenzoate, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 950 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
Embodiment 8
Margarita layer powder 350g
Zinc gluconate 4.18g
Beta-carotene 0.003g
Vitamin E 1g
Borneolum Syntheticum 0.6g
PEG400 200g
Acritamer 940 100g
Ethyl hydroxybenzoate 1g
Sodium hydrogen phosphate 12g
Sodium dihydrogen phosphate 2g
Glycerol 15.5g
Water for injection adds to 1000ml
Margarita layer powder is added the injection water, stir evenly, boil, continue to stir 48 hours, filter, filtrate is concentrated in right amount, adds the ethyl hydroxybenzoate of recipe quantity 50%, dissolves the even solution A that gets, and puts cold standby; Other gets water for injection dissolving Acritamer 940, stirs rising temperature for dissolving down, gets solution B; After adding the zinc gluconate dissolving in the solution A, add sodium hydrogen phosphate, sodium dihydrogen phosphate, glycerol again, after the stirring and dissolving, it is added in the solution B, and boil filtration, get solution C; Other gets an amount of water for injection, adds beta-carotene, vitamin E, Borneolum Syntheticum, PEG400, stirs, dissolve solution D, standby; D solution is added A solution, and after adding remaining ethyl hydroxybenzoate, leave standstill; Survey pH, adding sodium hydroxide or dilute hydrochloric acid in case of necessity, to regulate pH be 4.5～9.0, moisturizing to 950 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
The present invention and eye drop contrast test
One, stability relatively.
Test specimen:
Present embodiment 1 eye-gel preparation specification: 10ml trial-production
Present embodiment 2 eye-gel preparation specification: 10ml trial-production
Present embodiment 3 eye-gel preparation specification: 10ml trial-production
The precious removing nebula eye drop of the ice of listing specification: 10ml lot number: 050904
Sky, manufacturer Wuhan daybreak pharmaceutcal corporation, Ltd
Detect index:
Require to measure eye drops and the total nitrogen of gel for eye, the content of zinc gluconate according to Chinese Pharmacopoeia 2005 editions, the key index (outward appearance, pH, 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
Present embodiment 1 present embodiment 2 present embodiments 3 listing product test items
The 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 total nitrogen amount marks of qualified qualified pH 6.98 6.98 6.96 7.04 6.99 7.02 6.92 6.93 6.91 7.06 7.09 7.04 visible foreign matters of outward appearance
99.4 99.3 99.1 98.6 98.6 98.4 98.5 98.4 98.2 99.2 98.5 98.0 amount of showing (%) gluconic acids
99.8 99.8 99.7 99.6 99.5 99.5 99.2 99.1 99.1 99.7 99.6 99.6 zinc content (%)
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
Present embodiment 1 present embodiment 2 present embodiments 3 listing product test items
The 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 total nitrogen amount marks of qualified qualified pH 6.98 6.96 6.95 7.04 6.99 7.03 6.92 6.91 6.90 7.06 7.08 7.06 visible foreign matters of outward appearance
99.4 99.2 99.0 98.8 98.7 98.6 98.5 98.2 98.1 99.2 98.7 98.1 amount of showing (%) gluconic acids
99.8 99.8 99.7 99.6 99.6 99.5 99.2 99.2 99.2 99.7 99.7 98.6 zinc content (%)
Conclusion: the present embodiment prescription 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, related substance and clarity are all qualified.But the mensuration of total nitrogen indicates that present embodiment prescription result of the test obviously is better than the eye drop that goes on the market.
Two, irritation test:
Test specimen:
Present embodiment 1 eye-gel preparation specification: 10ml trial-production
Present embodiment 3 eye-gel preparation specification: 10ml trial-production
The precious removing nebula eye drop of the ice of listing specification: 10ml lot number: 050904
Sky, manufacturer Wuhan daybreak pharmaceutcal corporation, Ltd
Test objective: to ice precious removing nebula eye drop be contrast with the listing product, 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 present embodiment 1 and present embodiment 2 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 present embodiment 1 and present embodiment 2 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:
1. ocular tissue is to the evaluation criterion of eye drop irritant reaction degree
| Ocular tissue's irritative response | Score value |
| One, conjunctiva 1. hyperemia (comprise conjunctiva palpebrae, bulbar conjunctiva) (1) blood vessel is clear, color and luster pale red (2) blood vessel mild hyperaemia, be cerise (3) congestion of blood vessel and be aubergine, blood vessel is difficult for differentiating, smudgy not (4) diffusivity hyperemia is aubergine, the companion's no edema of ciliary congestion 2. edema (1) (2) Mild edema (comprising instant embrane) (3) are edema obviously, make eyelid and the eyelashes part is moist or adhesion (4) secretions makes whole eye district moist or adhere two with part ectropion (4) edema to a small amount of secretions (3) secretions of the no secretions of nearly semi-closed 3. secretions of eyelid (1) (2), cornea 1. epithelial damage degree (the painted observation of fluorescein) (1) epithelium nowhere dye or be dispersed in below 5 colored spots (2) epithelium colored spots more than 5 to below the 1/4 cornea area dye (3) and and dye area and surpass 1/4 to 1/2 cornea district (4) and and dye area to surpass 1/2 cornea district, 2. corneal clouding degree (1) corneas Clear ﹠ Transparent, do not have muddy (2) be dispersed in or diffusivity slightly muddy, as seen iris texture (3) cornea is translucent, iris is smudgy, reluctantly visible (4) cornea of pupil size is muddy fully, and iris is beyond recognition three, iris (1) iris texture is clear, aqueous humor transparent fully (2) iris mild hyperaemia, aqueous humor scintillation (+), slight ciliary congestion | 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 0 1 |
| (3) the congested aqueous humor scintillation of iris (++～+++), severe ciliary congestion, arroyo sign | 2 |
| (4) anterior chamber is oozed out or hemorrhage, iris local necrosis, and pupil is reactionless to light | 3 |
2. eye irritation evaluation criterion
| The stimulation degree | Integration | ||
| Zest moderate zest that nonirritant is slight | Conjunctiva 0～3＞1～3＞3～6 | Cornea 0～1＞1～2＞2～4 | Iris 0＞0～0.5＞0.5～1.5 |
| The severe zest | ＞6 | ＞4 | ＞1.5 |
The score value result:
1. single-dose result of the test
| Index is the time as a result | Conjunctival congestion | Chemosis | Corneal injury | Secretions | Iris | ||||||||||||||
| Epithelium | Turbidity | ||||||||||||||||||
| 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | ||
| Before the eye drip | 0 | 0 | 0 | 0 | 0 | 0 | 0.2 | 0.2 | 0.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Behind the eye drip | 2h | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.1 | 0.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 6h | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.1 | 0.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 24h | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.2 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 48h | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 72h | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.1 | 0.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 7 days | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
1. multiple dosing result of the test
| Index is the time as a result | Conjunctival congestion | Chemosis | Corneal injury | Secretions | Iris | ||||||||||||||
| Epithelium | Turbidity | ||||||||||||||||||
| 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | 1 | 2 | Right | ||
| Before the eye drip | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.1 | 0.4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| Behind the eye drip | 2 days | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 4 days | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 6 days | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 8 days | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 10 days | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 12 days | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.1 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
| 14 days | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0.2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Conclusion: to testing result in score value, by statistics after, present embodiment 1, present embodiment 2 and listing product are behind single-dose, all nonirritants, and present embodiment 1 and present embodiment 2 zests are all less than the eye drop of listing.But the score value of present embodiment 1 is better than the score value of present embodiment 2, embodiment 2 and is better than the product that goes on the market.
Behind the multiple dosing, present embodiment 1, present embodiment 2 and listing prescription zest all meet the requirements, but present embodiment 1, present embodiment 2 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 present embodiment 1 and present embodiment 2 in the process of the test.
Claims (10)
1, a kind of gel for removing ocular by ice pearl preparation, it comprises Margarita layer powder hydrolysate, Borneolum Syntheticum, trace element zinc, beta-carotene, vitamin E, gel-type vehicle and medicine acceptable carrier.
2, a kind of gel for removing ocular by ice pearl preparation according to claim 1, wherein said gel-type vehicle is: one or more in carbomer, polyvinyl alcohol, hydroxypropyl emthylcellulose, polyacrylic acid, methylcellulose, hyaluronic acid sodium, the sodium alginate.
3, according to a kind of gel for removing ocular by ice pearl preparation of claim 1 or 2, wherein said gel-type vehicle is the carbomer of 1～150g.
4, according to claim 1 or 2 described a kind of gel for removing ocular by ice pearl preparations, wherein said gel-type vehicle is the polyvinyl alcohol of 1～400g.
5, according to claim 1 or 2 described a kind of gel for removing ocular by ice pearl preparations, wherein said gel-type vehicle is the mixture of the polyvinyl alcohol of the carbomer of 100g and 300g.
6, a kind of gel for removing ocular by ice pearl preparation according to claim 1, wherein: described medicine acceptable carrier is solubilizing agent, isoosmotic adjusting agent and pH regulator agent.
7, a kind of gel for removing ocular by ice pearl preparation according to claim 6, wherein: described solubilizing agent is specially one or more in Tween 80, PEG400, Macrogol 600, poloxamer 188, polyvinyl pyrrolidone, the HP-, and its consumption is 0.01～30g.
8, a kind of gel for removing ocular by ice pearl preparation according to claim 6, wherein: described isoosmotic adjusting agent is specially one or more in sodium chloride, glucose, glycerol, propylene glycol, mannitol or the sorbitol; The pH regulator agent is specially one or more in hydrochloric acid, sodium hydroxide, triethanolamine, citric acid, sodium citrate, tartaric acid, sodium tartrate, boric acid, Borax, glacial acetic acid, phosphoric acid oxygen disodium, sodium dihydrogen phosphate, the phosphoric acid.
9, a kind of gel for removing ocular by ice pearl preparation according to claim 1 contains 0.2～20g antiseptic in the wherein said eye-gel preparation.
10, the preparation method of a kind of gel for removing ocular by ice pearl preparation of claim 1, it may further comprise the steps:
(1), Margarita layer powder added water be hydrolyzed, after the hydrolysis filtrate is concentrated, the antiseptic that adds 1/2 total amount is standby;
(2), in above-mentioned concentrated solution, add the zinc gluconate dissolving after, add the pH regulator agent again, isoosmotic adjusting agent obtains solution A;
(3), in addition get water for injection dissolving gel-type vehicle, stir rising temperature for dissolving down, get solution B; To go up two kinds of solution mixings of A, B, boil filtration; Get water for injection more in addition, add Borneolum Syntheticum, solubilizing agent, beta-carotene, vitamin E and stir, be added in the aforementioned filtrate, and leave standstill after adding the antiseptic of 1/2 total amount; Add the pH value regulator, regulating pH value is 4.5～9.0, and moisturizing is to the 800-980 milliliter, and solution is by filtering with microporous membrane, adds water filtration to 1000 from filter again and milliliter makes the gel for removing ocular by ice pearl preparation.
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| CNB2006100194337A CN100453086C (en) | 2006-06-22 | 2006-06-22 | Gel for removing ocular by ice pearl and its preparation |
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| CN101849898A (en) * | 2010-06-12 | 2010-10-06 | 马应龙药业集团股份有限公司 | Eye creams and preparation method thereof |
| CN101549067B (en) * | 2009-04-13 | 2011-11-02 | 俞寿良 | Chinese medicinal composition and uses thereof |
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| CN100423731C (en) * | 2004-01-01 | 2008-10-08 | 北海国发海洋生物产业股份有限公司 | Eye brightening eye washing liquid and its preparation method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101549067B (en) * | 2009-04-13 | 2011-11-02 | 俞寿良 | Chinese medicinal composition and uses thereof |
| US9278062B2 (en) | 2009-09-30 | 2016-03-08 | Rohto Pharmaceutical Co., Ltd. | Eye drops |
| CN101849898A (en) * | 2010-06-12 | 2010-10-06 | 马应龙药业集团股份有限公司 | Eye creams and preparation method thereof |
| CN101849898B (en) * | 2010-06-12 | 2012-01-04 | 马应龙药业集团股份有限公司 | Eye creams and preparation method thereof |
| CN102283797A (en) * | 2011-08-12 | 2011-12-21 | 马应龙药业集团股份有限公司 | Pouch-removing eye mask and preparation method thereof |
| CN103932975A (en) * | 2013-01-18 | 2014-07-23 | 江苏康倍得药业有限公司 | External use hydrogel composition and preparation thereof |
| CN105617350A (en) * | 2016-02-03 | 2016-06-01 | 王媛 | Extraction method of sheep sclera collagen, ophthalmic gel and preparation method thereof |
| CN112022799A (en) * | 2020-09-16 | 2020-12-04 | 上海昊海生物科技股份有限公司 | High-permeability local anesthetic gel and preparation method thereof |
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| CN100453086C (en) | 2009-01-21 |
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