31 results about "Timolol maleate" patented technology

Biodegradable polymeric microparticle compositions containing one or more active agents, especially those useful for treating or preventing or one or more diseases or disorders of the eye, and methods of making and using thereof, are described. The microsphere compositions release an effective amount of the one or more active agents for a period greater than 14 days in vivo, preferably greater than 60 days in vivo, more preferably up to 73 days in vivo, more preferably greater than 90 days in vivo, even more preferably over 100 days in vivo, and most preferably greater than 107 days in vivo. In a preferred embodiment, the microparticle compositions contain one or more active agents useful for managing elevated intraocular pressure (TOP) in the eye. In one embodiment, the microspheres are formed from polylactide-co-glycolide (“PLGA”); in another embodiment, the microspheres are formed from a blend PLGA and poly lactic acid (“PLA”). Relatively hydrophilic, and preferably carboxylated, polymeric materials such as PLGA are used for a drug such as timolol maleate, which is relatively water soluble, to increase drug loading. Higher molecular weight polymers, as well as the ratio of LA (which has a longer degradation time, up to one to two years) to GA (which has a short degradation time, as short as a few days to a week), are used to provide release over a longer period of time. The combination of drug loading and release rate, as well as the minimization of initial burst release, result in prolonged release of a higher amount of drug.

The invention relates to and belongs to a potentiometric chemical sensor, in particular to a timolol maleate potentiometric chemical sensor and a preparation method thereof. The preparation method comprises the following steps: (1) carrying out the chemical modification by the periodic scanning electro-polymerization method after pre-processing the surface of the matrix electrode to prepare the chemically modified electrode; (2) preparing a PVC-film sensitive solution by the conventional method with the solvent being tetrahydrofuran, and coating the modified electrode with the PVC sensitive film by the dip-coating method to prepare a chemical sensor (I); (3) preparing the molecularly imprinted polymer (Polymer A) of timolol maleate, and preparing the PVC film (Film II) containing Polymer A; and (4) compounding the Film II onto the PVC sensitive film of the chemical sensor I. The invention can effectively overcome the disadvantages of the existence of internal reference solution electrodes in the prior art, furthermore, the chemical sensor of the invention is significantly superior to the existing ion-selective electrodes in term of the selectivity of the drug (such as propranolol hydrochloride and the like) ions with the molecule with the structures, such as alcohol amine, imido and the like.

The invention provides timolol maleate (TM) eye gel and a preparation method thereof. One hundred grams of the eye gel comprises the following components by weight: 0.10-0.70g of TM, 0.10-2.0g of gel matrix, 0.2-5.0g of osmotic pressure regulator and the balance of water, wherein the gel matrix is a mixture of cellulose derivatives and carbopol and the weight ratio of cellulose derivatives to carbopol is 1:0.02-1, the cellulose derivatives comprise more than one of methylcellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose (HPMC) and carboxymethyl cellulose (CMC), and the carbopol comprises one of polyacrylic acid (PAA), polyacrylate or crosslinking polyacrylic resin. Patients with glaucoma and ocular hypertension use the controlled-release TM eye preparation once a day; and the prescription of the eye preparation is free of preservatives, thus lowering stimulation to eyes and improving medication safety if the gel is used for a long term.

The invention discloses a timolol maleate eye drop which does not contain bacteriostat and a preparation method thereof. The timolol maleate eye drop contains timolol maleate, pH regulator, isotonic agent, stabilizing agent, thickening agent, freshener, etc. The preparation method adopts antiseptic technique filling technology or heat pressing sterilizing technique, and the eye drop uses one-off individual package with single dose, so that the aseptic performance of the product is ensured, and the product is safer, more reliable, simpler, more convenient and sanitary.

The invention relates to timolol maleate cubic liquid crystal nanoparticle eye drops and a preparation method thereof. The imolol maleate cubic liquid crystal nanoparticle eye drops are mainly prepared from, by weight, 0.4-1.0 part of timolol maleate, 1.0-18.0 parts of liquid crystal material, 0.2-3.0 parts of surface active agent and 100 parts of water. The liquid crystal material is glycerol monoolein. The surface active agent is poloxamer. According to the timolol maleate cubic liquid crystal nanoparticle eye drops, the cornea infiltration capacity of timolol maleate can be remarkably improved, intra-ocular pressure can be remarkably and stably reduced, the retention time of a drug in the eyes can be prolonged, no preservative is added, and the problems that in the prior art, the retention time of timolol maleate eye drops in the eyes is short and irritation is caused by long-time use can be effectively solved.

The invention belongs to the field of preparations and relates to a timolol maleate pharmaceutical composition and a preparation method thereof. The timolol maleate pharmaceutical composition contains timolol maleate, Carbopol, triethanolamine, propylene glycol, ethylparaben and water. The pharmaceutical composition has the advantages of good biocompatibility, easiness in coating, no greasiness and the like, and the use compliance of a patient is greatly improved; the timolol maleate pharmaceutical composition can directly act on a focus of infection, and the local drug concentration is increased, so that the drug effect is furthest exerted, and the untoward effect of the whole body caused due to oral medication or intravenous medication is avoided; and the pharmaceutical composition is suitable for industrial large-scale production, is used for treating hemangioma and is particularly suitable for treating superficial type infantile hemangioma.

The invention discloses a gel agent for treating glaucoma and its preparing process which comprises Timolol Maleate, macromolecular material, glycerin, Ethylparabenum, Disodium Edetate, anti-oxidant agent, and distilled water, the preparation consists of steeping the macromolecular material into water, dissolving the Ethylparabenum with hot-water, charging Ethylparabenum solution, Timolol Maleate, glycerin, anti-oxidant agent, Disodium Edetate into macromolecular solution, agitating homogeneously.

The invention discloses an immediate type ophthalmic gelatin of timolol maleate and a preparation method thereof. 100 milliliters of the immediate type ophthalmic gelatin of timolol maleate contains 1 to 1.5 grams of the timolol maleate, 0.05 to 1 gram of preservative, 1.0 to 7.5 grams of permeation pressure conditioning agent and 30 to 150 grams of gelatin substrate. Remaining components are acid-base buffer regent and water for injection. The invention enriches the dosage forms of the timolol maleate by optimizing auxiliary materials and improving technology so that lag time in eyes is greatly prolonged and a curative effect is improved without adverse stimulus reaction.

The invention discloses a preparation method of timolol maleate sustained release microspheres. The preparation method comprises the following steps: by adopting an oil-in-oil technology, preparing an internal phase from timolol maleate, modified montmorillonite, acrylic resin, tween and a plasticizer and preparing an external phase from vegetable oil and span; carrying out ultrasonic treatment on an obtained oil-in-oil emulsion; then, electromagnetically stirring to evaporate the internal phase to obtain the timolol maleate sustained release microspheres. The grain diameter of the timolol maleate sustained release microspheres can be controlled in a range of 10 mu m, so that the demand of eye-drops preparations is met. The medicine encapsulation rate reaches up to 80-99%, and the in vitro releasing time can be prolonged to 10-12 hours. The timolol maleate sustained release microspheres prepared by the method serving as an ocular hypotensive agent can reduce intraocular discomfort and reduce the medication frequency, so that the purpose of reducing intraocular pressure for a long time by one-time delivery is realized.

The invention provides gel for infantile hemangioma and a preparation method of the gel, and belongs to the technical field of pharmaceutical preparations. The gel for infantile hemangioma consists ofpropranolol, timolol maleate, NVP-Gelbert alcohol maleate monoester copolymer, vaseline, liquid paraffin, glycerin monostearate, lauryl sodium sulfate, glycerinum, ethylparaben and water. The gel forhemangioma has the advantages of being easy to prepare, convenient to use, capable of taking effect fast, long in acting time, remarkable in treatment effect and the like, the acting time of the drugis prolonged through the NVP-Guerbet alcohol maleate monoester copolymer, the biocompatibility of the drug is improved, and the advantage of controlled release is achieved. The gel for hemangioma issuitable for industrial large-scale production and used for treating infantile hemangioma.

The invention discloses a method for separating a timolol compound and / or timolol maleate related impurities and application of the method. According to the method for separating the timolol compoundand / or the timolol maleate related impurities and the application of the method, a chromatographic column of which filler is silica gel bonded with quinine derivatives on the surface is applied to high performance liquid chromatography conditions to separate the timolol compound, a timolol maleate compound and the related impurities of timolol maleate. The method adopts a reversed-phase high-performance liquid phase system, the timolol compound and the related impurities of timolol maleate can be effectively separated, the accuracy is high, the sensitivity is high, and the method is environmentally friendly and can be used for quantitative detection of the timolol compound.

The invention relates to a sustained-release suspension for treating glaucoma and a preparation method thereof, effectively solving the problem of low bioavailability in the prior art. According to the technical scheme, the sustained-release suspension comprises the following components in percentage by weight: 1.0-5.0 percent of timolol maleate, 1.0-5.0 percent of IRP-69 cation exchange resin, 0.1-10 percent of a micro-capsule coating material, 0.1-10 percent of plasticizer, 3-10 percent of impregnant, 0.1-20 percent of suspending agent, 0.1-10 percent of osmotic pressure regulator, 0.001-0.02 percent of preservative, 0.1-10 percent of pH regulator, 1.0-20 percent of sorbitan monooleate, 5-50 percent of liquid paraffin, 1.0-50 percent of micro-capsule coating material solvent, and 30-70 percent of super-pure water. The sustained-release suspension is safe in administration and definite in curative effect, does not have irritation, can remarkably improve the bioavailability of timolol maleate, and is an innovation in the field of medicine for treating glaucoma.

The invention discloses an ophthalmologic intraocular pressure reduction drug for external use. The drug takes timolol maleate as an active pharmaceutical ingredient; and the drug further comprises potassium sorbate, and the potassium sorbate is added according to the ratio that timolol maleate:potassium sorbate equals to 1:(0.1-5.0). The drug also takes tanshinone IIA as the active pharmaceutical ingredient, and the tanshinone IIA is added according to the ratio that timolol maleate:tanshinone IIA equals to 1:(0.1-5.0). The potassium sorbate-containing timolol maleate eye drops have a lasting medicinal effect, and the frequency for dropping the eye drops can be reduced.

The invention relates to timolol maleate cubic liquid crystal nanoparticle eye drops and a preparation method thereof. The imolol maleate cubic liquid crystal nanoparticle eye drops are mainly prepared from, by weight, 0.4-1.0 part of timolol maleate, 1.0-18.0 parts of liquid crystal material, 0.2-3.0 parts of surface active agent and 100 parts of water. The liquid crystal material is glycerol monoolein. The surface active agent is poloxamer. According to the timolol maleate cubic liquid crystal nanoparticle eye drops, the cornea infiltration capacity of timolol maleate can be remarkably improved, intra-ocular pressure can be remarkably and stably reduced, the retention time of a drug in the eyes can be prolonged, no preservative is added, and the problems that in the prior art, the retention time of timolol maleate eye drops in the eyes is short and irritation is caused by long-time use can be effectively solved.

The invention provides a timolol maleate liposome gel and a preparation method thereof. The gel is prepared from timolol maleate, a penetration enhancer, a humectant, a preservative, a liposome forming agent, a gel matrix, a pH regulator and medical purified water. The prepared timolol maleate liposome gel is uniform and delicate, suitable in viscosity and easy to spread, the drug release time is prolonged through the liposome technology, the concentration of the drug at the diseased region is kept, the gel is used for treating infantile hemangioma, drug administration is convenient, meanwhile, the first-pass effect of the liver is avoided, and meanwhile the gel is convenient to use, high in safety, simple in production process and good in application prospect.

The invention provides a hemangioma gel containing an amphiphilic polymer and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The invention provides a hemangioma gel containing an amphiphilic polymer, which is composed of propranolol or timolol maleate, NVP-maleic acid monodocosanol monoester copolymer, Tween-80 , sodium lauryl sulfate, propylene glycol, silicone oil, vaseline, chlorobutanol and purified water; the hemangioma gel has the characteristics of simple preparation, convenient use, quick onset, long acting time, and remarkable therapeutic effect. NVP ‑Docosanol monoester maleate copolymer increases the action time of the drug, improves the biocompatibility of the drug, has the advantages of slow and controlled release, and reduces the use of transdermal accelerators; the hemangioma coagulation agent of the present invention The glue is suitable for industrialized large-scale production and is used for treating infantile hemangioma.

The invention discloses a method for determining impurities in timolol maleate. The method comprises the following steps: taking a timolol maleate sample homologous with a timolol maleate sample to be detected, and reacting to obtain a destroying solution containing an impurity X; the method comprises the following steps: taking a timolol maleate sample to be detected, and preparing a test solution by using a solvent; diluting the test solution as a contrast solution; respectively carrying out liquid chromatography detection on the destroyed solution, the test solution and the contrast solution so as to calculate the content of the impurity X in the to-be-detected sample. According to the method, impurities G, B, D, E, C and 5 can be directionally damaged, the interference impurity is small, the positioning of each impurity is not influenced, an impurity reference substance is not used, an ion pair reagent and a peak shape improver are removed from a chromatographic system, the loss of a chromatographic column is relatively small, the method can be simultaneously used for liquid chromatography and liquid chromatography-mass spectrometry detection, the qualitative analysis on the impurities can be conveniently carried out at the same time, and the detection accuracy is high. The economical efficiency and the universality of the method are improved.

The invention discloses a pharmaceutical composition consisting of latanoprost and timolol maleate, with weight percentages of 0.004-0.007% and 0.6-0.8% respectively. The invention also provides a compound preparation of the pharmaceutical composition, wherein the mass content of the timolol maleate is 0.6-0.8%, and the mass content of the latanoprost is 0.004-0.007%; and auxiliary materials include benzalkonium chloride or RH40 hydrogenated castor oil, sodium chloride, sodium dihydrogen phosphate, disodium hydrogen phosphate and purified water, with the pH of 5.0-6.5. The compound preparation can be used for treating glaucoma with small side effect, so that patient compliance is higher.

The invention discloses timolol maleate eye drops and a preparation process. The timolol maleate eye drops are prepared from the following raw materials in parts by weight: 10 to 12 parts of dispersion liquid C, 5 to 7 parts of timolol maleate nanoparticles, 20 to 30 parts of a water-based solvent, 4 to 6 parts of a buffering solution, 100 to 200 parts of a diluting agent and 0.01 to 0.03 part ofbenzalkonium chloride. The timolol maleate eye drops are prepared through the following steps: step 1, preparing the dispersion liquid C; step 2, adding the timolol maleate nanoparticles into the dispersion liquid C prepared by step 1 to prepare a nano mixed solution; and step 3, mixing a glucose solution with the mass percent of 8 percent and the nano mixed solution obtained by step 2, and carrying out vacuum freeze-drying for 8h to 10h; after freeze-drying is finished, adding a solid obtained by the freeze-drying into the buffering solution and the diluting agent; raising the temperature to80 DEG C, and keeping the heat for 30min; then cooling to 40 to 50 DEG C; adding the benzalkonium chloride and stirring and dissolving; filtering by a filter element; filling and sealing.

A method for treating choroidal neovascularization in a patient includes administrating as eye drops into the eye of the patient having choroidal neovascularization a therapeutically effective amount of an aqueous ophthalmic composition that is formulated for topical administration as eye drops. The aqueous ophthalmic composition consists essentially of Timolol Maleate at a concentration of about 0.1% to 0.5%, Dorzolamide at a concentration of about 0.5% to 2.5%, Prednisolone at a concentration of about 1.0% to 3.0%, Ketorolac Tromethamine at a concentration of about 0.4% to 1.2%, and sterile water at a concentration of at least about 90.0%.

The invention discloses timolol maleate gel eye drops. The timolol maleate gel eye drops are prepared from the following components in percentage by weight: 0.2 to 0.45 percent of timolol maleate, 3.2 to 4.4 percent of modified collagen, 3 to 4 percent of glycerol, 0.5 to 1.0 percent of medium-chain fatty glyceride, 0.4 to 0.6 percent of surfactant, 0.5 percent of polycarbophil and the balance of deionized water, the modified collagen is prepared by the following steps: dissolving chitosan and collagen in an acetic acid solution, shearing and stirring, carrying out ultraviolet irradiation, then adding alkali liquor for neutralization, washing with deionized water, and finally freeze-drying. The timolol maleate gel eye drops provided by the invention are better in slow release effect and longer in lasting period.

The invention discloses a preparation method of timolol maleate slow-release microspheres. The present invention adopts oil-in-oil technology, prepares inner phase with timolol maleate, modified montmorillonite, acrylic resin, Tween, and plasticizer, prepares outer phase with vegetable oil and Span, and the obtained oil-in-oil After the emulsion is ultrasonically treated, the internal phase is evaporated by electromagnetic stirring to obtain timolol maleate sustained-release microspheres, whose particle size can be controlled within the range of 10 μm, which meets the requirements of ophthalmic preparations. Its drug encapsulation rate is as high as 80-99%, and the release time in vitro can be extended to 10-12 hours. The timolol maleate sustained-release microspheres prepared by the method are used as an intraocular pressure-lowering drug, which can reduce discomfort in the eye, reduce the number of medications, and realize the purpose of lowering the intraocular pressure for a long time by one administration.

The invention discloses a timolol maleate external preparation and a preparation method thereof. The timolol maleate external preparation is prepared from the following components in percentage by mass: 4 to 8 weight percent of timolol maleate, 18 to 25 weight percent of polylactic acid, 3 to 8 weight percent of nanofiber, 10 to 15 weight percent of gel matrix, 4 to 10 weight percent of phospholipid, 1 to 2 weight percent of surfactant, 0.8 to 1.2 weight percent of water-retaining agent and the balance of deionized water. The invention provides the timolol maleate external preparation in a gel form, a thin film can be formed on the surface of the external preparation after the external preparation is smeared, the external preparation is slowly hardened into a soft sheet, timolol maleate is gradually and slowly released in the hardening process, and the hardening time is basically matched with the effective drug release time; the external preparation is not easy to erase by clothes and the like, is easy to tear off after being hardened, and is convenient to use.

The invention discloses a synthesis method of timolol maleate intermediates, which takes a cyclic compound as a dissolvent. The synthesis method is characterized in that the cyclic compound is taken as the dissolvent, and amine diol and benzaldehyde generates oxazole product by cyclization; and the timolol maleate intermediate is obtained after distillation, wherein the molar ratio of the cyclic compound as the dissolvent to the amine diol is 1:2-6.5. The invention adopts the cyclic compound as the dissolvent to replace a highly toxic benzene dissolvent so as to obtain high-quality and high-yield timolol maleate intermediates. The synthesis method of the invention has simple operation in industrial production, repeatedly recycled dissolvent, and environment protection, and is more favorable for large-scale industrial production.

The invention provides timolol maleate (TM) eye gel and a preparation method thereof. One hundred grams of the eye gel comprises the following components by weight: 0.10-0.70g of TM, 0.10-2.0g of gel matrix, 0.2-5.0g of osmotic pressure regulator and the balance of water, wherein the gel matrix is a mixture of cellulose derivatives and carbopol and the weight ratio of cellulose derivatives to carbopol is 1:0.02-1, the cellulose derivatives comprise more than one of methylcellulose, hydroxymethyl cellulose, hydroxypropyl methylcellulose (HPMC) and carboxymethyl cellulose (CMC), and the carbopol comprises one of polyacrylic acid (PAA), polyacrylate or crosslinking polyacrylic resin. Patients with glaucoma and ocular hypertension use the controlled-release TM eye preparation once a day; and the prescription of the eye preparation is free of preservatives, thus lowering stimulation to eyes and improving medication safety if the gel is used for a long term.

The invention relates to and belongs to a potentiometric chemical sensor, in particular to a timolol maleate potentiometric chemical sensor and a preparation method thereof. The preparation method comprises the following steps: (1) carrying out the chemical modification by the periodic scanning electro-polymerization method after pre-processing the surface of the matrix electrode to prepare the chemically modified electrode; (2) preparing a PVC-film sensitive solution by the conventional method with the solvent being tetrahydrofuran, and coating the modified electrode with the PVC sensitive film by the dip-coating method to prepare a chemical sensor (I); (3) preparing the molecularly imprinted polymer (Polymer A) of timolol maleate, and preparing the PVC film (Film II) containing Polymer A; and (4) compounding the Film II onto the PVC sensitive film of the chemical sensor I. The invention can effectively overcome the disadvantages of the existence of internal reference solution electrodes in the prior art, furthermore, the chemical sensor of the invention is significantly superior to the existing ion-selective electrodes in term of the selectivity of the drug (such as propranolol hydrochloride and the like) ions with the molecule with the structures, such as alcohol amine, imido and the like.

The present invention provides a preventive or therapeutic agent for glaucoma, which contains an angiotensin II antagonist and timolol maleate as active ingredients, and these active ingredients are used simultaneously, separately or sequentially, wherein the angiotensin II antagonist is A compound of the following general formula (I) or a pharmaceutically acceptable salt, ester or other derivative thereof, wherein R1 is as defined in the claims.