CN101564374A - Medicinal in situ forming eye gel - Google Patents
Medicinal in situ forming eye gel Download PDFInfo
- Publication number
- CN101564374A CN101564374A CNA200810105214XA CN200810105214A CN101564374A CN 101564374 A CN101564374 A CN 101564374A CN A200810105214X A CNA200810105214X A CN A200810105214XA CN 200810105214 A CN200810105214 A CN 200810105214A CN 101564374 A CN101564374 A CN 101564374A
- Authority
- CN
- China
- Prior art keywords
- eye
- gel
- add
- sodium
- hydrochloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a medicinal in situ forming eye gel preparation, and belongs to the field of pharmacy. Active ingredients of the preparation come from bulk medicaments of the medicament, gel base materials of the preparation mainly comprise Gellan gum which is 0.4 to 0.7 percent of the weight of a finished product. The technical proposal overcomes the defects of low bioavailability, inconvenient use, short detention time and the like of the prior eye preparation, and achieves the effects of reducing applied dosage, prolonging the detention time in the eyes, convenient use, accurate applied dosage and the like.
Description
Technical field
The present invention relates to a kind of medicinal in situ forming eye gel preparation, especially a kind of is the situ forming eye gel preparation of main gel base material with gellan gum, belongs to field of medicaments.
Background technology
In present ophthalmic preparation, eye drop as a kind of traditional dosage form have easy to use, compliance good, advantage such as cheap, but its medicine shortcoming that the holdup time is short within the eye, bioavailability is low makes its curative effect be subjected to very big influence.Studies show that: the volume of one after another drop of eye liquid is substantially between 25～50ul, if do not bat an eyelid, the ophthalmic medicine liquid volume is only at 30ul, if nictation then be reduced to 10ul, so the medicine major part of eye external is not to enter ocular tissue, but lose through nasolacrimal duct system and eyelid slit flow.According to tear kinetics, ophthalmic solution is very short in the holdup time on eye surface, absorbed medication amount only is the sub-fraction of dosage usually, even medicine at eyeball surface, because the dilution of nictation and tear, concentration medicine reduces, medicine ask minimizing as the time spent, so solution must repeat administration, could guarantee effective drug level, increase the action time of medicine, reach higher drug absorption degree, this just needs frequent dripping eyedrop, but frequent drug administration very easily causes the lasting damage of ocular tissue, use inconvenience, the patient also is difficult to adhere to.
Except that eye drop, the ophthalmic preparation on the market mainly also has Eye ointments, common gel for eye etc.Though Eye ointments can keep certain drug level for a long time, but general only application just before going to bed at night, because the patient is coated with the back influence of applying ointment and looks thing, do not see thing, and use at night, be coated with the back sleep of applying ointment, do not need eyes to look thing, this also is the shortcoming of Eye ointments, uses daytime extremely inconvenient; Common gel for eye can the long period be trapped in mucous membrane surface, improve the thing availability that looks unfamiliar, but the viscosity of this type of preparation is big, have shortcomings such as production technology operating difficulties, clinical using dosage are inaccurate.
Along with the continuous development of newtype drug adjuvant, a kind of new situ forming eye gel preparation begins to receive publicity.Instant gel is a kind of macromolecular solution agent, its formation mechanism is to utilize macromolecular material to stimulate the response of (physiological environment that the inside and outside is different such as pH, temperature, ion etc.) to external world, make high molecular polymer issue the reversible change of diffusing state estranged or conformation, finish by the conversion process of solution to gel at physiological condition.This type of dosage form has certain novelty: be in a liquid state in storage period, be semi-solid state after splashing into ophthalmic, not only can solve the problem that the common eye drops ophthalmic holdup time is short, bioavailability is not high, also overcome common gel for eye use high viscosity and lacked good spreadability, the uppity problem of dosage, its unique solution-gel conversion character make it have advantages such as preparation is simple, easy to use, strong with agents area especially mucosal tissue affinity, the holdup time is long concurrently.
Gellan gum (gellan gum) is a kind of Microbial exopolysaccharides, is the water-soluble polymer that generates by fermentation, is produced by U.S. Kelco company at first.Gellan gum has double-spiral structure, and its distinguishing feature is to form gel with monovalence or bivalent cation effect.In a single day gellan gum contacts the cation (Na+ of physiological concentration, K+, Ca2+), glucuronic acid in the structure is neutralized, cation mediated cohesion promptly takes place, produce solution-gel phase transformation, its gel ability is subjected to the influence of cation type, cation concn and himself concentration, bivalent cation promotes that than monovalent cation the ability of gellan gum gel is strong, and wherein Ca2+ is more effective than Mg2+; Bivalent cation makes gellan gum form the heat irreversible gel, and monovalent cation makes gellan gum form the thermal reversibility gel.When cation existed, the intensity of the gel that some gellan gum forms in pH4.0～8.0 changed with pH hardly.
How gellan gum being applied to ophthalmic preparation, is the emphasis of present ophthalmic remedy research.Therefore, solving the ins and outs of gellan gum in the preparation medicinal in situ forming eye gel, make it really become product, is the problem that at first will solve.
Summary of the invention
The purpose of this invention is to provide a kind of medicinal in situ forming eye gel preparation, particularly is the instant gel for eye of main gel base material with gellan gum, so that improve the result of use of product, convenient clinical use better meets needs of medical treatment.The base material of gel described in the present invention is meant the precursor substance of gel, when mixing with the water equal solvent and reaching certain gelling condition, just can become gel.
In conjunction with existing result of study, the present invention seeks to be achieved through the following technical solutions:
We combine medicine with instant gel base material gellan gum, the conventional adjuvant that is aided with ophthalmic preparation has again been made instant gel for eye.Used effective ingredient is selected from but is not limited to Gatifloxacin; pirenzepine hydrochloride; raceanisodamine; pilocarpine nitrate; isoproterenol; bunazosin; maleic acid Saimaa Luo Er; the husky tropane in a left side; latanoprost; Quwo prostatitis element; bimatoprost; timolol; brimonidine tartrate; betaxolol hydrochloride; carteolol hydrochloride; erythromycin; chloromycetin; ciprofloxacin; ciprofloxacin lactate; ofloxacin; levofloxacin; moxifloxacin hydrochloride; levofloxacin hydrochloride; macrodex; neo-houttuyninum; atropine sulfate; ribavirin; ftibamzone; tiopronin; ciclosporin; ganciclovir; vitamin A palmitate; azithromycin; clarithromycin; raceanisodamine; ketotifen fumarate; netilmicin sulfate; indomethacin; phacolin; Bernetine Sodium; glutathion; vitamin B12; vitamin B6; taurine; bendazac lysine; tranilast; metipranolol; doxycycline hyclate; troxerutin; dexamethasone sodium phosphate; polygynax; fluorometholone; allantoin; chondroitin sulfate; tropicamide; brimonidine; sodium cromoglicate; clonidine hydrochloride; tetracaine hydrochloride; prednisolone acetate; flurbiprofen sodium; ketotifen fumarate; norfloxacin; epalrestat; amosulalol; voriconazole; itraconazole; ammonia iodine peptide; isepamicin; pranoprofen; Bu Linzuo amine; sulphacetamide; chlortetracycline hydrochloride; trifluorothymidine; sodium chromoglicate; the left-handed bunolol of hydrochloric acid; mensiso; the toluenesulfonic acid tosufloxacin; betamethasone sodium phosphate; amlexanox; physostigmine salicylate; sulfadiazine; quadracycline; Naphazoline Chloridum; chlorphenamine maleate; tobramycin; gentamycin sulfate; lincomycin hydrochloride; oxymetazoline hydrochloride; ketorolac tromethamine; natamycin; Micronomicin Sulfate; Ciclosporin A; asparagic acid azithromycin; methylbromtropin; amikacin; fluconazol; ketoconazole; miconazole; econazole; diclofenac sodium; acyclovir; puerarin; zinc sulfate; zinc gluconate; Sodium Houttuyfonate; puerarin; chlorogenic acid; berberine hydrochloride; Borneolum Syntheticum; at least a in the Mentholum.
Specifically:
Gel is to be prepared into by medicine and suitable adjuvant, and in 100 parts of finished weights, used medicine is 0.01～2.5 part.Wherein, medicine soluble in water directly joins to dissolve in the water for injection and gets final product, and the little medicine of dissolubility then needs to dissolve with small amount of ethanol or other solvents earlier in water, slowly is added to the water again, fully stirs and makes dissolving.
In the preparation process of gel for eye, in order to guarantee the molding of preparation, except the conventional adjuvant of ophthalmic preparation, critical work is to select the gel base material that suits, adopts a kind of novel base material-gellan gum of transformation mutually among the present invention.Gellan gum is the ion-sensitive type adjuvant, and the preparation that makes for liquid, splashes into the cation (Na that runs into physiological concentration in the eye external
+, K
+, Ca
2+) gelling then takes place.The inventor is by great deal of experimental, and the result is that the amount of gel base material gellan gum is 0.4～0.7 part in 100 parts of finished weights; Further preferred, the consumption of gellan gum is 0.6 part.
In the preparation process of instant gel for eye, the inventor has tested again with in gellan gum and other base materials such as carbomer, hydroxypropyl emthylcellulose, poloxamer 407, poloxamer 188, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, methylcellulose, sodium alginate, the polyacrylic acid one or more and has carried out applied in any combination.So anyly carry out the behavior that applied in any combination prepares instant gel for eye with gellan gum and above-mentioned adjuvant and also all belong to protection scope of the present invention.
For molding and the steady quality that guarantees gel, also need to add the conventional adjuvant of a certain amount of ophthalmic preparation, i.e. pH regulator agent, isoosmotic adjusting agent, antibacterial and water.The used isoosmotic adjusting agent of inventor comprises at least a in glucose, boric acid, Borax, glycerol, propylene glycol, the mannitol, the pH regulator agent comprises at least a in hydrochloric acid, lactic acid, citric acid, glacial acetic acid, triethanolamine, boric acid, the Borax, and antibacterial comprises at least a in benzyl alcohol, chlorobutanol, benzalkonium chloride, benzalkonium bromide, phenoxyethanol, Metagin, second, the propyl ester.Through further test, the mixture of the inventor is preferred boric acid, Borax both can be brought into play the effect of pH regulator agent again as isoosmotic adjusting agent, can reduce the consumption of other adjuvants.
Instant gel for eye among the present invention need add isoosmotic adjusting agent and pH regulator agent, its addition and ratio with the pH value of regulating preparation reach 5～8, osmotic pressure reaches etc. ooze or near etc. ooze and be as the criterion; Add antibacterial, addition is enough to reach antibacterial purpose and is as the criterion.
The inventor finds in experimental study, and when the preparation medicinal in situ forming eye gel, the hyaluronate sodium that can also add the HYDROXYPROPYL BETA-CYCLODEXTRIN of 0～1 part polyoxyethylene sorbitan monoleate or 0～1 part or 0～1 part in 100 parts of finished products improves the state of preparation.After adding polyoxyethylene sorbitan monoleate or hyaluronate sodium, the supplementary product consumption of preparation reduces, and viscosity also reduces, the perfect preparation technology of preparation, after adding HYDROXYPROPYL BETA-CYCLODEXTRIN, the dissolubility of many slightly solubility compositions of part medicine improves, thereby has improved the bioavailability of preparation.
The inventor investigates through overtesting, determined following technology during the preparation of instant gel for eye: will add the gel base material in the water for injection, mixing adds isoosmotic adjusting agent, pH regulator agent, antibacterial etc., mixing again, adding is with the appropriate solvent dissolved drug, filter, add the injection water, filter to total amount, aseptic subpackaged, promptly.
Beneficial effect
Owing to contain Na in the tear
+, K
+And Ca
2+Etc. cation, gellan gum can form gel with these ionizations, eliminates from the cornea forefoot area thereby suppress medicine.Gellan gum has characteristics such as gel formation ability is strong, transparency is high, the acidproof heat-proof performance is good, is the gel base material of main component with it, is liquid in the preparation, good fluidity, bring convenience to preparation, become gel state, also possessed all advantages of gel and splash into ophthalmic.Thereby solved the defective of present ophthalmic preparation.
For effect of the present invention is described, embody the eye retentivity of instant gel for eye, the inventor has carried out following test:
Experiment one: Gatifloxacin instant gel for eye release in vitro degree is investigated
Test objective: investigate the release behaviour in vitro of Gatifloxacin instant gel for eye, and compare with eye drop.
Test material: Gatifloxacin instant gel for eye: get water for injection 800ml, add gellan gum 6g, stir, put in the boiling water bath, stir to clarify, add boric acid 12g, Borax 0.6g, ethyl hydroxybenzoate 0.8g, stir to clarify, be heated to 60 ℃, cross microporous filter membrane (0.8 μ m), stir and add Gatifloxacin 3g down, stir evenly, add the injection water, cross microporous filter membrane (0.22 μ m) to 1000ml, aseptic subpackaged, promptly.
Gatifloxacin eye drop (Kunming Laoboyuntang Pharmaceutical Co., Ltd. produces, and the dose contained with the Gatifloxacin instant gel for eye is identical)
Tianjin, island LC-2010A high performance liquid chromatograph
Tianjin, island CLASS-VP work station
Isotonic phosphate buffer liquid (contains NaH in the 1000ml solution
2PO
41.60g, Na
2HPO
47.58g NaCl 4.32g transfers pH to 7.40)
Test method: take by weighing each 3g of Gatifloxacin instant gel for eye and gatifloxacin eye drop, place bag filter respectively, (removing bubble in the bag) tightened with nylon wire in bag two, is fixed in the 250ml beaker, and release medium is isotonic phosphate buffer liquid 100ml, the bag upper edge is apart from liquid level 1cm, beaker places on the magnetic stirrer, and stirrer is about 2.5cm, temperature control (34 ± 1) ℃, the 5ml that takes a sample at regular intervals adds simultaneously with the fresh phosphate buffer of volume.
Measure the content (is testing index with the Gatifloxacin) of each sample of being got respectively with the HPLC method, represent with peak area.Calculate the diffusion release amount that adds up as follows:
C
i＝f(A
i)，Qn＝100Cn+5∑C
i(Q1＝100C
1 i，n＝1，2，3...)
(C
iBe drug level, A is for recording peak area, and Q is the drug accumulation burst size, and i, n are respectively the sampling number of times.)
Result of the test: Gatifloxacin instant gel for eye and gatifloxacin eye drop release in vitro curve are seen accompanying drawing 1.
Above-mentioned cumulative release curve is discharged equation model, and it has the one-level release rule as a result, and regression equation has good dependency.One-level release fit equation is: Log (Y
∝-Y)=-Kr * t/2.303+M.The release equation of Gatifloxacin gel for eye use of the present invention is: Log (Y
∝-Y)=-0.1814t+1.8524, correlation coefficient is 0.9968.
The result shows that the external drug release rate of gatifloxacin eye drop is very fast, and the 1h release reaches about 80%, enters plateau afterwards; And the Gatifloxacin instant gel for eye reaches about 80% in the 3h release, and drug release rate is mild, has slow release characteristic preferably.
Conclusion (of pressure testing): the Gatifloxacin instant gel for eye has slow release characteristic preferably.Improve medicine by the present invention and have feasibility in the bioavailability of eye.
Experiment two: foscarnet sodium instant gel for eye release in vitro degree is investigated
Test objective: investigate the release behaviour in vitro of foscarnet sodium instant gel for eye, and compare with eye drop.
Test material: foscarnet sodium instant gel for eye: get among gellan gum 5g and boric acid, the Borax adding water for injection 950ml, heated and boiled, be cooled to 80 ℃, add foscarnet sodium 5g, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 0.4g again, and add the injection water to 1000ml, and stirred 30 minutes, cross microporous filter membrane (0.22 μ m), aseptic subpackaged, promptly.
Foscarnet sodium eye drop (favorable to the people pharmaceutical factory of Jinting Pharmaceutical Co., Ltd. produces, and the dose contained with the foscarnet sodium instant gel for eye is identical)
Tianjin, island UV1100 spectrophotometer
Isotonic phosphate buffer liquid (contains NaH in the 1000ml solution
2PO
41.60g, Na
2HPO
47.58g NaCl 4.32g transfers pH to 7.40)
Test method: take by weighing foscarnet sodium instant gel for eye and each 3g of foscarnet sodium eye drop, place bag filter respectively, (removing bubble in the bag) tightened with nylon wire in bag two, is fixed in the 250ml beaker, and release medium is isotonic phosphate buffer liquid 100ml, the bag upper edge is apart from liquid level 1cm, beaker places on the magnetic stirrer, and stirrer is about 2.5cm, temperature control (34 ± 1) ℃, the 5ml that takes a sample at regular intervals adds simultaneously with the fresh phosphate buffer of volume.
Measure the content of the foscarnet sodium in each sample of being got respectively with the HPLC method.Calculate the diffusion release amount that adds up as follows:
C
i＝f(A
i)，Qn＝100Cn+5∑C
i(Q1＝100C
1?i，n＝1，2，3...)
(C
iBe drug level, A is for recording peak area, and Q is the drug accumulation burst size, and i, n are respectively the sampling number of times.)
Result of the test: foscarnet sodium instant gel for eye and foscarnet sodium eye drop release in vitro curve are seen accompanying drawing 2.
Above-mentioned cumulative release curve is discharged equation model, and it has the one-level release rule as a result, and regression equation has good dependency.One-level release fit equation is: Log (Y
∝-Y)=-Kr * t/2.303+M.The release equation of foscarnet sodium gel for eye use of the present invention is: Log (Y
∝-Y)=-0.1814t+1.8524, correlation coefficient is 0.9981.
The result shows that the external drug release rate of foscarnet sodium eye drop is very fast, and the 1.5h release reaches about 80%, enters plateau afterwards; And the foscarnet sodium instant gel for eye reaches about 80% in the 3.5h release, and drug release rate is mild, has slow release characteristic preferably.
Conclusion (of pressure testing): the foscarnet sodium instant gel for eye has slow release characteristic preferably.Improve medicine by the present invention and have feasibility in the bioavailability of eye.
Experiment three: ciprofloxacin lactate instant gel for eye release in vitro degree is investigated
Test objective: investigate the release behaviour in vitro of ciprofloxacin lactate instant gel for eye, and compare with eye drop.
Test material: ciprofloxacin lactate instant gel for eye: get among gellan gum 6g and boric acid, the Borax adding water for injection 800ml, heated and boiled, be cooled to 80 ℃, add ciprofloxacin lactate 3g, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 0.5g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 1000ml, aseptic subpackaged, promptly.
Ciprofloxacin lactate eye drop (the bright red eagle Pharmaceutical in Ningbo limited company produces, and the dose contained with the ciprofloxacin lactate instant gel for eye is identical)
Isotonic phosphate buffer liquid (contains NaH in the 1000ml solution
2PO
41.60g, Na
2HPO
47.58g NaCl 4.32g transfers pH to 7.40)
Test method: take by weighing ciprofloxacin lactate instant gel for eye and each 3g of ciprofloxacin lactate eye drop, place bag filter respectively, (removing bubble in the bag) tightened with nylon wire in bag two, is fixed in the 250ml beaker, and release medium is isotonic phosphate buffer liquid 100ml, the bag upper edge is apart from liquid level 1cm, beaker places on the magnetic stirrer, and stirrer is about 2.5cm, temperature control (34 ± 1) ℃, the 5ml that takes a sample at regular intervals adds simultaneously with the fresh phosphate buffer of volume.
Measure the content (is testing index with the ciprofloxacin) of the ciprofloxacin lactate in each sample of being got respectively with colorimetry.Calculate the diffusion release amount that adds up as follows:
C
i＝f(A
i)，Qn＝100Cn+5∑C
i(Q1＝100C
1 i，n＝1，2，3...)
(C
iBe drug level, A is for recording trap, and Q is the drug accumulation burst size, and i, n are respectively the sampling number of times.)
Result of the test: ciprofloxacin lactate instant gel for eye and ciprofloxacin lactate eye drop release in vitro curve are seen accompanying drawing 3.
Above-mentioned cumulative release curve is discharged equation model, and it has the one-level release rule as a result, and regression equation has good dependency.One-level release fit equation is: Log (Y
∝-Y)=-Kr * t/2.303+M.The release equation of ciprofloxacin lactate gel for eye use of the present invention is: Log (Y
∝-Y)=-0.1814t+1.8524, correlation coefficient is 0.9967.
The result shows that the external drug release rate of ciprofloxacin lactate eye drop is very fast, and the 1h release reaches about 80%, enters plateau afterwards; And the ciprofloxacin lactate instant gel for eye reaches about 80% in the 3h release, and drug release rate is mild, has slow release characteristic preferably.
Conclusion (of pressure testing): the ciprofloxacin lactate instant gel for eye has slow release characteristic preferably.Improve medicine by the present invention and have feasibility in the bioavailability of eye.
Test four: tobramycin instant gel for eye animal pharmacodynamics test is investigated
Test objective: to the pharmacodynamics test research of Bacteritic Keratitis in Rabbits
Test material: tobramycin instant gel for eye: get among gellan gum 5g and boric acid, the Borax adding water for injection 800ml, heated and boiled, be cooled to 80 ℃, add tobramycin 3g, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 0.3g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 1000ml, aseptic subpackaged, promptly.
Gernebcin eye drops (Sichuan Fangxiang Medicine Limited Liability Company produces, and institute's content of dispersion is consistent with the tobramycin instant gel for eye)
Experimental animal and material: new zealand rabbit, the male and female dual-purpose, 2.2～2.8kg, totally 50 (provide the animal quality certification number: SCXK (Shandong) 20030004) by Shandong University's Experimental Animal Center;
Bacillus pyocyaneus (ACTT27853), concentration 1 * 10
6CFUml
-1
Staphylococcus aureus (ACTT25923), concentration 2.5 * 10
9CFUml
-1
Escherichia coli (ACTT25922), concentration 1.8 * 10
9CFUml
-1Get by the clinical separation of clinical laboratory of Hospital Attached to Shandong Chinese Medical Univ. Bacteriology Room.
Test method:
1, bacterial keratitis modelling: decide rabbit with rabbit seat clamping,, treat that its back of losing consciousness contains bacteria culture fluid with 1ml syringe extraction 0.1ml and (contains bacillus pyocyaneus 1 * 10 with 2～3 eye drips of 0.5% tetracaine
6CFU, staphylococcus aureus 2.5 * 10
9CFU or escherichia coli 1.8 * 10
9CFU) in the nearly central part of cornea is annotated people's cornea essential layer, make the white bacterial plaque that causes the about 2～3min of diameter, put into single cage respectively and raise treatment.
2, animal GP TH and medication: 50 of model rabbit are divided into the high, medium and low dosage group of tobramycin instant gel for eye (6 times/d of high dose administration, 1～2 droplet/time; Middle 4 times/d of dosed administration, 1～2 droplet/time; 2 times/d of low dosage administration, 1～2 droplet/time), Gernebcin eye drops group (8 times/d, 1～2 droplet/time) and blank group (giving 8 times/d of water for injection, 1～2 droplet/time).Begin medication with 12h after the modeling, schedule to last 5d, carry out dependent observation work every day.
3, observation index: the keratitis pathological changes is cured degree (perusal) and is begun behind cornea inoculated bacteria 6h, every day observed and recorded ordinary circumstance and empyema, redness, corneal clouding, the performance of ulcer isogonism film inflammation, and give rank scores:
0 minute (normally): no empyema, nothing redness, no cornea muddiness, no ulcer;
1 minute (slightly): cornea, do not have empyema, redness arranged, no cornea muddiness, no ulcer;
2 minutes (moderate): cornea has empyema, redness is arranged, no cornea muddiness, slight ulcer;
3 minutes (severe): cornea empyema redness, corneal clouding, ulcer.
Put to death animal on the 6th day in inoculation treatment back, get 10 corneas dos of side section HE and dye in inflammation such as microscopic examination corneal thickness, ulcer, cell infiltration, fibroblast proliferation performance scoring.10 corneas of opposite side are done 24h antibacterial culturing separation detection, staphylococcus aureus, bacillus pyocyaneus and escherichia coli counting contrast statistics.And with the statistical disposition of following pathogen negative conversion rate detection data.
Result of the test: rabbit with bacillus pyocyaneus, staphylococcus aureus, escherichia coli inoculation back grouping according to putting to death rabbit on the 6th day by scoring of ophthalmology illuminator perusal cornea inflammation and treatment back on the 5th day after the above-mentioned treatment, get the scoring of a side 10 corneas section HE dyeing microscopic examination cornea inflammation, two groups of 20 comprehensive statisticss see Table 1.Computing formula is as follows.
Cure rate (%)=(blank inflammation score value-respectively organize inflammation score value)/blank inflammation score value * 100%
The scorching result of the test table of table 1 tobramycin instant gel for eye treatment rabbit cornea
The result shows that to the curative effect of three kinds of pathogenic bacterium mixed infections of rabbit, the cure rate of three dosage groups of tobramycin instant gel for eye is higher, all is better than Gernebcin eye drops.Prompting tobramycin instant gel for eye is compared with Gernebcin eye drops has better therapeutic effect.
Description of drawings
Accompanying drawing 1: Gatifloxacin instant gel for eye and gatifloxacin eye drop release in vitro curve
Accompanying drawing 2: foscarnet sodium instant gel for eye and foscarnet sodium eye drop release in vitro curve
Accompanying drawing 3: ciprofloxacin lactate instant gel for eye and ciprofloxacin lactate eye drop release in vitro curve
The specific embodiment
Below further specify the present invention by specific embodiment, but following examples only are used to the present invention is described without limits to the present invention.
Embodiment one:
Prescription: Gatifloxacin 15g gellan gum 30g
Method for making: get water for injection 4000ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add boric acid 60g, Borax 3g, ethyl hydroxybenzoate 4g, stir to clarify, be heated to 60 ℃, cross microporous filter membrane (0.8 μ m), stir and add Gatifloxacin down, stir evenly, add the injection water, cross microporous filter membrane (0.22 μ m) to 5000ml, aseptic subpackaged, promptly.
Embodiment two:
Prescription: foscarnet sodium 15g gellan gum 18g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 2700ml, heated and boiled, be cooled to 80 ℃, add foscarnet sodium, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 1.5g again, and add the injection water to 3000ml, and stir evenly, cross microporous filter membrane (0.22 μ m), aseptic subpackaged, promptly.
Embodiment three:
Prescription: ciprofloxacin lactate 15ml gellan gum 30g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 4000ml, heated and boiled, be cooled to 80 ℃, add ciprofloxacin lactate, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 2.5g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 5000ml, aseptic subpackaged, promptly.
Embodiment four:
Prescription: tobramycin 6g gellan gum 10g carbomer 2g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 1600ml, heated and boiled is cooled to 80 ℃, add carbomer, fully dissolving adds tobramycin, is cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 0.8g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 2000ml, aseptic subpackaged, promptly.
Embodiment five:
Prescription: sodium cromoglicate 40g gellan gum 12g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 1600ml, heated and boiled, be cooled to 80 ℃, add sodium cromoglicate, be cooled to 60 ℃ while stirring, add methyl hydroxybenzoate 0.5g and propylparaben 0.5g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 2000ml, aseptic subpackaged, promptly.
Embodiment six:
Prescription: dexamethasone sodium phosphate 1g gellan gum 24g
Method for making: get water for injection 3200ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add polyoxyethylene sorbitan monoleate 4g, stir, add triethanolamine and glycerol, add ethyl hydroxybenzoate 2g, stir evenly, add dexamethasone sodium phosphate, add the injection water, cross microporous filter membrane (0.22 μ m) to 4000ml, aseptic subpackaged, promptly.
Embodiment seven:
Prescription: polygynax 10g gellan gum 14g
Method for making: get water for injection 1600ml, add gellan gum, chlorobutanol, put in the boiling water bath, stir to clarify, put coldly, add hyaluronate sodium 0.6g, swollen 12h stirs evenly, and adds boric acid, Borax, stir adding polygynax down, filter, add the injection water to 2000ml, cross microporous filter membrane (0.22 μ m), put cold, aseptic subpackaged, promptly.
Embodiment eight:
Prescription: tropicamide 2.5g gellan gum 4g
Method for making: get water for injection 900ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add triethanolamine and glycerol, add methyl hydroxybenzoate 0.4g and propylparaben 0.4g and polyoxyethylene sorbitan monoleate 1g, stir evenly, stir adding tropicamide down, cross microporous filter membrane, add the injection water to 1000ml, 120 ℃ of autoclavings 20 minutes are put cold, aseptic subpackaged, promptly.
Embodiment nine:
Prescription: acyclovir 5g gellan gum 30g
Method for making: get water for injection 4500ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add boric acid, Borax and propylene glycol, add ethyl hydroxybenzoate 2g and polyoxyethylene sorbitan monoleate 6g, stir evenly, add acyclovir, mixing, cross microporous filter membrane, add the injection water, cross microporous filter membrane (0.22 μ m) to 5000g, aseptic subpackaged, promptly.
Embodiment ten:
Prescription: cortisone acetate 10g gellan gum 10g
Method for making: get water for injection 1600ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add boric acid, Borax, add benzalkonium bromide 1g and hyaluronate sodium 10g, stir evenly, add cortisone acetate, add the injection water to 2000ml, cross microporous filter membrane, put cold, aseptic subpackaged, promptly.
Embodiment 11:
Prescription: ribavirin 5g gellan gum 30g
Method for making: get water for injection 4000ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add boric acid, Borax, add phenoxyethanol 2g, stir evenly, add ribavirin, stir evenly, add the injection water to 4000ml, cross microporous filter membrane, aseptic subpackaged, promptly.
Embodiment 12:
Prescription: acyclovir 2g gellan gum 8g methylcellulose 1.5g
Method for making: get water for injection 1800ml, add gellan gum, methylcellulose, stir, put in the boiling water bath, stir to clarify, add boric acid, Borax, add phenoxyethanol 2g, stir evenly, add acyclovir, stir evenly, add the injection water to 2000ml, cross microporous filter membrane, aseptic subpackaged, promptly.
Embodiment 12:
Prescription: sodium cromoglicate 20g gellan gum 7g
Method for making: get water for injection 900ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add boric acid, Borax, add phenoxyethanol 0.8g, stir evenly, add sodium cromoglicate, stir evenly, add the injection water to 1000ml, cross microporous filter membrane, aseptic subpackaged, promptly.
Embodiment 13:
Prescription: clonidine hydrochloride 5g gellan gum 12g
Method for making: get water for injection 1800ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add polyoxyethylene sorbitan monoleate 1.5g, stir, add triethanolamine and glycerol, add ethyl hydroxybenzoate 1g, stir evenly, add clonidine hydrochloride, add the injection water, cross microporous filter membrane (0.22 μ m) to 2000ml, aseptic subpackaged, promptly.
Embodiment 14:
Prescription: norfloxacin 9g gellan gum 18g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 2400ml, heated and boiled, be cooled to 80 ℃, add norfloxacin, be cooled to 60 ℃ while stirring, add methyl hydroxybenzoate 0.8g and propylparaben 0.8g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 3000ml, aseptic subpackaged, promptly.
Embodiment 15:
Prescription: foscarnet sodium 15g gellan gum 18g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 2700ml, heated and boiled, be cooled to 80 ℃, add foscarnet sodium, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 1.5g again, and add the injection water to 3000ml, and stir evenly, cross microporous filter membrane (0.22 μ m), aseptic subpackaged, promptly.
Embodiment 16:
Prescription: chloromycetin 5g gellan gum 10g
Method for making: get water for injection 1800ml, add gellan gum, chlorobutanol, put in the boiling water bath, stir to clarify, put coldly, add boric acid, Borax, stirring makes dissolving, adds HYDROXYPROPYL BETA-CYCLODEXTRIN 3g, mixing, stir and add chloromycetin down, filter, add the injection water, cross microporous filter membrane (0.22 μ m) to 2000ml, aseptic subpackaged, promptly.
Embodiment 17:
Prescription: tobramycin 6g dexamethasone 2g gellan gum 12g
Method for making: get among gellan gum and boric acid, the Borax adding water for injection 1600ml, heated and boiled, be cooled to 80 ℃, add tobramycin and dexamethasone, be cooled to 60 ℃ while stirring, add ethyl hydroxybenzoate 1g, stir evenly, and add the injection water, cross microporous filter membrane (0.22 μ m) to 2000ml, aseptic subpackaged, promptly.
Embodiment 18:
Prescription: taurine 10 g aminocaproic acid 10g Aspartic Acid 1.55g chlorphenamine maleate 0.1g gellan gum 6g
Method for making: get water for injection 900ml, add gellan gum, stir; put in the boiling water bath, stir to clarify, add boric acid, Borax; add benzalkonium bromide 0.6g and hyaluronate sodium 0.8g; stir evenly, add taurine, aminocaproic acid, Aspartic Acid, chlorphenamine maleate, stir and make dissolving; add the injection water to 1000ml; cross microporous filter membrane, aseptic subpackaged, promptly.
Embodiment 19:
Prescription: berberine hydrochloride 3g zinc sulfate 9g gellan gum 18g
Method for making: get water for injection 2700ml, add gellan gum, stir, put in the boiling water bath, stir to clarify, add boric acid 60g, add ethyl hydroxybenzoate 0.9g, stir evenly, add berberine hydrochloride and zinc sulfate, stir and make dissolving, add the injection water to 3000ml, cross microporous filter membrane, aseptic subpackaged, promptly.
Claims (10)
1, a kind of instant gel for eye is to be made by the conventional adjuvant of effective ingredient, gel base material and ophthalmic preparation, and the main component that it is characterized in that the gel base material is a gellan gum.
2, instant gel for eye according to claim 1 is characterized in that containing 0.4～0.7 part of gellan gum in 100 parts of finished weights.
3, instant gel for eye according to claim 2 is characterized in that containing 0.6 part of gellan gum in 100 parts of finished weights.
4; according to claim 1; 2 or 3 described instant gel for eye is characterized in that the effective ingredient of medicine mainly comes from following at least a crude drug: Gatifloxacin; pirenzepine hydrochloride; raceanisodamine; pilocarpine nitrate; isoproterenol; bunazosin; maleic acid Saimaa Luo Er; the husky tropane in a left side; latanoprost; Quwo prostatitis element; bimatoprost; timolol; brimonidine tartrate; betaxolol hydrochloride; carteolol hydrochloride; erythromycin; chloromycetin; ciprofloxacin; ciprofloxacin lactate; ofloxacin; levofloxacin; moxifloxacin hydrochloride; levofloxacin hydrochloride; macrodex; neo-houttuyninum; atropine sulfate; ribavirin; ftibamzone; tiopronin; ciclosporin; ganciclovir; vitamin A palmitate; azithromycin; clarithromycin; raceanisodamine; ketotifen fumarate; netilmicin sulfate; indomethacin; phacolin; Bernetine Sodium; glutathion; vitamin B12; vitamin B6; taurine; bendazac lysine; tranilast; metipranolol; doxycycline hyclate; troxerutin; dexamethasone sodium phosphate; polygynax; fluorometholone; allantoin; chondroitin sulfate; tropicamide; brimonidine; sodium cromoglicate; clonidine hydrochloride; tetracaine hydrochloride; prednisolone acetate; flurbiprofen sodium; ketotifen fumarate; norfloxacin; epalrestat; amosulalol; voriconazole; itraconazole; ammonia iodine peptide; isepamicin; pranoprofen; Bu Linzuo amine; sulphacetamide; chlortetracycline hydrochloride; trifluorothymidine; sodium chromoglicate; the left-handed bunolol of hydrochloric acid; mensiso; the toluenesulfonic acid tosufloxacin; betamethasone sodium phosphate; amlexanox; physostigmine salicylate; sulfadiazine; quadracycline; Naphazoline Chloridum; chlorphenamine maleate; tobramycin; gentamycin sulfate; lincomycin hydrochloride; oxymetazoline hydrochloride; ketorolac tromethamine; natamycin; Micronomicin Sulfate; Ciclosporin A; asparagic acid azithromycin; methylbromtropin; amikacin; fluconazol; ketoconazole; miconazole; econazole; diclofenac sodium; acyclovir; puerarin; zinc sulfate; zinc gluconate; Sodium Houttuyfonate; puerarin; chlorogenic acid; berberine hydrochloride; Borneolum Syntheticum; Mentholum.
5, instant gel for eye according to claim 4 is characterized in that can also containing in the gel base material in carbomer, hydroxypropyl emthylcellulose, poloxamer 407, poloxamer 188, sodium carboxymethyl cellulose, hydroxyethyl-cellulose, methylcellulose, the sodium alginate one or more.
6, instant gel for eye according to claim 4, the hyaluronate sodium that it is characterized in that can also adding the HYDROXYPROPYL BETA-CYCLODEXTRIN of 0～1 part polyoxyethylene sorbitan monoleate or 0～1 part or 0～1 part in 100 parts of finished products improves the state of preparation.
7, instant gel for eye according to claim 6 is characterized in that the conventional adjuvant of used ophthalmic preparation contains isoosmotic adjusting agent, pH regulator agent, antibacterial and water.
8, instant gel for eye according to claim 7, it is characterized in that isoosmotic adjusting agent is at least a in glucose, boric acid, Borax, glycerol, propylene glycol, the mannitol, the pH regulator agent is at least a in hydrochloric acid, citric acid, glacial acetic acid, triethanolamine, boric acid, the Borax, and antibacterial is at least a in benzyl alcohol, chlorobutanol, benzalkonium chloride, benzalkonium bromide, phenoxyethanol, Metagin, second, the propyl ester.
9, instant gel for eye according to claim 8, the addition that it is characterized in that the pH regulator agent to the pH value of preparation is to get final product in 5～8 o'clock, the addition of isoosmotic adjusting agent to the osmotic pressure of preparation for wait ooze or near etc. ooze and get final product, the addition of antibacterial then need reach antibacterial standard.
10, the method for preparing arbitrary described instant gel for eye in the claim 1 to 9, it is characterized in that: will add the gel base material in the water for injection, mixing adds isoosmotic adjusting agent, pH regulator agent, antibacterial etc., mixing again, adding is with the appropriate solvent dissolved drug, filter, add the injection water, filter to total amount, aseptic subpackaged, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810105214XA CN101564374A (en) | 2008-04-25 | 2008-04-25 | Medicinal in situ forming eye gel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA200810105214XA CN101564374A (en) | 2008-04-25 | 2008-04-25 | Medicinal in situ forming eye gel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101564374A true CN101564374A (en) | 2009-10-28 |
Family
ID=41280851
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA200810105214XA Pending CN101564374A (en) | 2008-04-25 | 2008-04-25 | Medicinal in situ forming eye gel |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101564374A (en) |
Cited By (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102727423A (en) * | 2012-06-20 | 2012-10-17 | 贵州大学 | Betaxolol hydrochloride ion-sensitive eye-use in-situ gel and preparation method thereof |
| CN102743760A (en) * | 2011-04-22 | 2012-10-24 | 天津金耀集团有限公司 | Bacteriostatic agent GellanGum-containing externally-used composite for eyes |
| CN102885768A (en) * | 2012-11-02 | 2013-01-23 | 江苏吉贝尔药业有限公司 | Pranoprofen in-situ gelling eye drop and preparation method thereof |
| CN102085203B (en) * | 2009-12-02 | 2013-01-30 | 沈阳兴齐眼药股份有限公司 | Ophthalmic preparation of levofloxacin and prednisolone acetate and preparation method thereof |
| CN102949331A (en) * | 2011-08-19 | 2013-03-06 | 苏州太湖美药业有限公司 | Preparation method of tobramycin ophthalmic in-situ gel eye-drops |
| CN103126981A (en) * | 2013-03-05 | 2013-06-05 | 宁夏康亚药业有限公司 | Foscarnet sodium eye drops and preparation method |
| CN103142462A (en) * | 2012-02-23 | 2013-06-12 | 四川大学 | Brinzolamide eye preparations, and preparation method and use thereof |
| CN103239390A (en) * | 2013-05-15 | 2013-08-14 | 中国人民解放军第三军医大学第二附属医院 | Tropicamide ophthalmic temperature-sensitive in-situ gel and preparation method thereof |
| US20140086975A1 (en) * | 2010-10-15 | 2014-03-27 | Rutgers, The State University Of New Jersey | Hydrogel formulation for dermal and ocular delivery |
| CN103720641A (en) * | 2013-11-25 | 2014-04-16 | 中国中医科学院中药研究所 | Taurine-containing ophthalmic in-vivo gel preparation and preparation method thereof |
| CN103919717A (en) * | 2014-04-15 | 2014-07-16 | 天津中医药大学 | Brimonidine d-tartrate ophthalmic gel preparation as well as preparation method and application thereof |
| CN104039307A (en) * | 2011-04-22 | 2014-09-10 | 爱尔康研究有限公司 | Ophthalmic composition with a viscosity enhancement system having two different viscosity enhancing agents |
| CN104055729A (en) * | 2013-03-22 | 2014-09-24 | 上海现代药物制剂工程研究中心有限公司 | Azithromycin eye drops and preparation method thereof |
| CN104069118A (en) * | 2014-07-01 | 2014-10-01 | 四川兴科蓉药业有限责任公司 | Eye-drop and preparation method thereof |
| CN104721130A (en) * | 2013-02-21 | 2015-06-24 | 四川大学 | Brinzolamide clathrate compound preparation used for eyes and preparation method thereof |
| CN105106107A (en) * | 2015-09-16 | 2015-12-02 | 杭州谷歌医药开发有限公司 | Eye gellan gum in-situ gel made of bendazac lysine and preparing method of eye gellan gum in-situ gel |
| CN105232449A (en) * | 2015-10-30 | 2016-01-13 | 上海昊海生物科技股份有限公司 | Moxifloxacin hydrochloride sodium hyaluronate controlled-release nanogel and preparation method thereof |
| CN106619573A (en) * | 2016-12-27 | 2017-05-10 | 广州中大南沙科技创新产业园有限公司 | Timolol maleate cubic liquid crystal nanoparticle eye drops and preparation method thereof |
| CN107982212A (en) * | 2017-11-28 | 2018-05-04 | 杭州赫尔斯科技有限公司 | A kind of atropic category medicament slow release eye drops and preparation method thereof |
| WO2018126522A1 (en) * | 2017-01-05 | 2018-07-12 | 首都医科大学附属北京朝阳医院 | Injectable intraocular sustained-release antiviral drug and manufacturing method and application thereof |
| CN109010268A (en) * | 2018-09-28 | 2018-12-18 | 湖北远大天天明制药有限公司 | A kind of ophthalmic composition and preparation method thereof improving chloramphenicol stability |
| CN109106684A (en) * | 2018-09-04 | 2019-01-01 | 广州君博医药科技有限公司 | A kind of non-steroidal anti-inflammatory gel for eye use and preparation method thereof |
| CN109200053A (en) * | 2018-11-17 | 2019-01-15 | 王海玲 | A kind of anti-epileptic external drug and application thereof |
| CN109316445A (en) * | 2018-11-15 | 2019-02-12 | 塔里木大学 | It is a kind of for ox, the spray of sheep eye disease |
| CN109481434A (en) * | 2018-12-18 | 2019-03-19 | 湖北远大天天明制药有限公司 | Eye drops, and the preparation method and application thereof |
| CN109966245A (en) * | 2019-04-03 | 2019-07-05 | 浙江省医学科学院 | A kind of brimonidine tartrate gellan gum type situ-gel eye drops and preparation method |
| CN110200904A (en) * | 2019-05-27 | 2019-09-06 | 上海昊海生物科技股份有限公司 | A kind of drop intraocular pressure sustained release eye drop composition and preparation method thereof |
| CN111228034A (en) * | 2020-01-16 | 2020-06-05 | 贵州省人民医院 | Drug-loading controlled-release lacrimal duct embolus and preparation method thereof |
| CN111643448A (en) * | 2020-02-27 | 2020-09-11 | 江苏艾立康药业股份有限公司 | Moxifloxacin hydrochloride ophthalmic gel and preparation method thereof |
| CN112618480A (en) * | 2020-11-10 | 2021-04-09 | 南昌大学 | Preparation method of novel ocular drug delivery system |
| CN113786380A (en) * | 2021-09-18 | 2021-12-14 | 华北制药股份有限公司 | Pilocarpine nitrate ophthalmic gel and preparation method thereof |
| CN115487139A (en) * | 2022-09-13 | 2022-12-20 | 杭州医学院 | Puerarin gellan gum ionic in-situ gel eye drops and preparation method thereof |
| CN115998943A (en) * | 2022-12-20 | 2023-04-25 | 北京中医药大学 | Hydrogel for promoting skin wound healing and application thereof |
| CN116474154A (en) * | 2022-12-20 | 2023-07-25 | 北京中医药大学 | Hydrogel dressing band-aid for diabetes wound and application thereof |
| WO2024104313A1 (en) * | 2022-11-18 | 2024-05-23 | Govita Tech Limited | Composition for antiviral or oxidation pretreatment, preparation method and usage method thereof |
-
2008
- 2008-04-25 CN CNA200810105214XA patent/CN101564374A/en active Pending
Cited By (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9763968B2 (en) | 2004-12-22 | 2017-09-19 | Rutgers, The State University Of New Jersey | Hydrogel formulation for dermal and ocular delivery |
| CN102085203B (en) * | 2009-12-02 | 2013-01-30 | 沈阳兴齐眼药股份有限公司 | Ophthalmic preparation of levofloxacin and prednisolone acetate and preparation method thereof |
| US20140086975A1 (en) * | 2010-10-15 | 2014-03-27 | Rutgers, The State University Of New Jersey | Hydrogel formulation for dermal and ocular delivery |
| CN102743760A (en) * | 2011-04-22 | 2012-10-24 | 天津金耀集团有限公司 | Bacteriostatic agent GellanGum-containing externally-used composite for eyes |
| CN104039307A (en) * | 2011-04-22 | 2014-09-10 | 爱尔康研究有限公司 | Ophthalmic composition with a viscosity enhancement system having two different viscosity enhancing agents |
| CN102949331A (en) * | 2011-08-19 | 2013-03-06 | 苏州太湖美药业有限公司 | Preparation method of tobramycin ophthalmic in-situ gel eye-drops |
| CN103142462A (en) * | 2012-02-23 | 2013-06-12 | 四川大学 | Brinzolamide eye preparations, and preparation method and use thereof |
| CN103142462B (en) * | 2012-02-23 | 2016-05-11 | 四川大学 | Brinzolamide eye-drops preparations and its production and use |
| CN102727423A (en) * | 2012-06-20 | 2012-10-17 | 贵州大学 | Betaxolol hydrochloride ion-sensitive eye-use in-situ gel and preparation method thereof |
| CN102885768A (en) * | 2012-11-02 | 2013-01-23 | 江苏吉贝尔药业有限公司 | Pranoprofen in-situ gelling eye drop and preparation method thereof |
| CN104721130A (en) * | 2013-02-21 | 2015-06-24 | 四川大学 | Brinzolamide clathrate compound preparation used for eyes and preparation method thereof |
| CN104721130B (en) * | 2013-02-21 | 2018-02-13 | 四川大学 | A kind of brinzolamide inclusion compound eye-drops preparations and preparation method thereof |
| CN103126981A (en) * | 2013-03-05 | 2013-06-05 | 宁夏康亚药业有限公司 | Foscarnet sodium eye drops and preparation method |
| CN104055729A (en) * | 2013-03-22 | 2014-09-24 | 上海现代药物制剂工程研究中心有限公司 | Azithromycin eye drops and preparation method thereof |
| CN103239390B (en) * | 2013-05-15 | 2014-08-06 | 中国人民解放军第三军医大学第二附属医院 | Tropicamide ophthalmic temperature-sensitive in-situ gel and preparation method thereof |
| CN103239390A (en) * | 2013-05-15 | 2013-08-14 | 中国人民解放军第三军医大学第二附属医院 | Tropicamide ophthalmic temperature-sensitive in-situ gel and preparation method thereof |
| CN103720641A (en) * | 2013-11-25 | 2014-04-16 | 中国中医科学院中药研究所 | Taurine-containing ophthalmic in-vivo gel preparation and preparation method thereof |
| CN103919717A (en) * | 2014-04-15 | 2014-07-16 | 天津中医药大学 | Brimonidine d-tartrate ophthalmic gel preparation as well as preparation method and application thereof |
| CN104069118A (en) * | 2014-07-01 | 2014-10-01 | 四川兴科蓉药业有限责任公司 | Eye-drop and preparation method thereof |
| CN104069118B (en) * | 2014-07-01 | 2016-08-24 | 武汉五景药业有限公司 | Eye drop and preparation method thereof |
| CN105106107A (en) * | 2015-09-16 | 2015-12-02 | 杭州谷歌医药开发有限公司 | Eye gellan gum in-situ gel made of bendazac lysine and preparing method of eye gellan gum in-situ gel |
| CN105232449A (en) * | 2015-10-30 | 2016-01-13 | 上海昊海生物科技股份有限公司 | Moxifloxacin hydrochloride sodium hyaluronate controlled-release nanogel and preparation method thereof |
| CN105232449B (en) * | 2015-10-30 | 2019-04-09 | 上海昊海生物科技股份有限公司 | Moxifloxacin hydrochloride Sodium Hyaluronate slow release nanometer gel and preparation method thereof |
| CN106619573A (en) * | 2016-12-27 | 2017-05-10 | 广州中大南沙科技创新产业园有限公司 | Timolol maleate cubic liquid crystal nanoparticle eye drops and preparation method thereof |
| WO2018126522A1 (en) * | 2017-01-05 | 2018-07-12 | 首都医科大学附属北京朝阳医院 | Injectable intraocular sustained-release antiviral drug and manufacturing method and application thereof |
| CN107982212A (en) * | 2017-11-28 | 2018-05-04 | 杭州赫尔斯科技有限公司 | A kind of atropic category medicament slow release eye drops and preparation method thereof |
| CN109106684A (en) * | 2018-09-04 | 2019-01-01 | 广州君博医药科技有限公司 | A kind of non-steroidal anti-inflammatory gel for eye use and preparation method thereof |
| CN109010268B (en) * | 2018-09-28 | 2020-07-10 | 湖北远大天天明制药有限公司 | Ophthalmic composition for improving stability of chloramphenicol and preparation method thereof |
| CN109010268A (en) * | 2018-09-28 | 2018-12-18 | 湖北远大天天明制药有限公司 | A kind of ophthalmic composition and preparation method thereof improving chloramphenicol stability |
| CN109316445A (en) * | 2018-11-15 | 2019-02-12 | 塔里木大学 | It is a kind of for ox, the spray of sheep eye disease |
| CN109200053A (en) * | 2018-11-17 | 2019-01-15 | 王海玲 | A kind of anti-epileptic external drug and application thereof |
| CN109481434A (en) * | 2018-12-18 | 2019-03-19 | 湖北远大天天明制药有限公司 | Eye drops, and the preparation method and application thereof |
| CN109481434B (en) * | 2018-12-18 | 2020-11-10 | 湖北远大天天明制药有限公司 | Eye drops, preparation method and application thereof |
| CN109966245A (en) * | 2019-04-03 | 2019-07-05 | 浙江省医学科学院 | A kind of brimonidine tartrate gellan gum type situ-gel eye drops and preparation method |
| CN110200904B (en) * | 2019-05-27 | 2021-07-23 | 上海昊海生物科技股份有限公司 | Intraocular pressure reducing sustained-release eye drop composition and preparation method thereof |
| CN110200904A (en) * | 2019-05-27 | 2019-09-06 | 上海昊海生物科技股份有限公司 | A kind of drop intraocular pressure sustained release eye drop composition and preparation method thereof |
| CN111228034A (en) * | 2020-01-16 | 2020-06-05 | 贵州省人民医院 | Drug-loading controlled-release lacrimal duct embolus and preparation method thereof |
| CN111643448A (en) * | 2020-02-27 | 2020-09-11 | 江苏艾立康药业股份有限公司 | Moxifloxacin hydrochloride ophthalmic gel and preparation method thereof |
| CN112618480A (en) * | 2020-11-10 | 2021-04-09 | 南昌大学 | Preparation method of novel ocular drug delivery system |
| CN112618480B (en) * | 2020-11-10 | 2022-07-12 | 南昌大学 | Preparation method of eye drug delivery system |
| CN113786380A (en) * | 2021-09-18 | 2021-12-14 | 华北制药股份有限公司 | Pilocarpine nitrate ophthalmic gel and preparation method thereof |
| CN115487139A (en) * | 2022-09-13 | 2022-12-20 | 杭州医学院 | Puerarin gellan gum ionic in-situ gel eye drops and preparation method thereof |
| CN115487139B (en) * | 2022-09-13 | 2023-10-27 | 杭州医学院 | Puerarin gellan gum ionic in-situ gel eye drops and preparation method thereof |
| WO2024104313A1 (en) * | 2022-11-18 | 2024-05-23 | Govita Tech Limited | Composition for antiviral or oxidation pretreatment, preparation method and usage method thereof |
| CN115998943A (en) * | 2022-12-20 | 2023-04-25 | 北京中医药大学 | Hydrogel for promoting skin wound healing and application thereof |
| CN116474154A (en) * | 2022-12-20 | 2023-07-25 | 北京中医药大学 | Hydrogel dressing band-aid for diabetes wound and application thereof |
| CN116474154B (en) * | 2022-12-20 | 2024-05-14 | 北京中医药大学 | Hydrogel dressing band-aid for diabetes wound and application thereof |
| CN115998943B (en) * | 2022-12-20 | 2024-05-24 | 北京中医药大学 | Hydrogel for promoting skin wound healing and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101564374A (en) | Medicinal in situ forming eye gel | |
| CN102078284B (en) | Gatifloxacin-containing gel for eyes and preparation method thereof | |
| CN1872026A (en) | New medicinal preparation for vagina | |
| CN102125516A (en) | Thermo-sensitive in-situ gel pharmaceutical composition | |
| TWI826685B (en) | Dissolvable polymeric eye inserts and method of using same | |
| Kesavan et al. | Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive gellan system | |
| CN107854424A (en) | A kind of azithromycin ocular in-situ gel and preparation method thereof | |
| CN102283799A (en) | Azithromycin gel eye drops and preparation process thereof | |
| CN109260146A (en) | Ophthalmic solution sodium in situ forming eye type gel eyedrop and preparation method | |
| Nanjwade et al. | Formulation and evaluation of micro hydrogel of Moxifloxacin hydrochloride | |
| CN104055729A (en) | Azithromycin eye drops and preparation method thereof | |
| WO2024045973A1 (en) | Use of dehydroepiandrosterone in preparation of medicament for preventing and treating ocular myopia, dosage form thereof, and preparation method therefor | |
| Jothi et al. | In-situ ophthalmic gels for the treatment of eye diseases | |
| CN108210450A (en) | Medicine-releasing system and azithromycin eye-drops preparations and preparation method comprising its composition | |
| Bharath et al. | Development and evaluation of a pH triggered in situ ocular gel of brimonidine tartrate | |
| CN101579305A (en) | Ready-to-use puerarin ophthalmic gel | |
| Tambe et al. | Hot-melt extruded in situ gelling systems (MeltDrops Technology): Formulation development, in silico modelling and in vivo studies | |
| CN102008488B (en) | Triamcinolone acetonide ophthalmic preparation and preparation method thereof | |
| CN101579357A (en) | Ready-to-use fel ursi ophthalmic gel | |
| CN101579358A (en) | Ready-to-use traditional Chinese medicine ophthalmic gel | |
| CN103720641A (en) | Taurine-containing ophthalmic in-vivo gel preparation and preparation method thereof | |
| Deshpande et al. | Formulation and Development pH induced in-situ gelling system of an anti infective drug for sustained ocular drug delivery | |
| CN107296791A (en) | A kind of azithromycin micro emulsion eye drops | |
| CN101579498A (en) | Ready-to-use zedoary turmeric oil ophthalmic gel | |
| CN101579403A (en) | Ready-to-use Dactylicapnos scandens ophthalmic gel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20091028 |