43 results about "Olopatadin" patented technology

The invention relates to a new dosage form of olopatadine in the technical field of medicines, in particular to the preparation and an application of olopatadine in-situ gel. The invention is characterized in that the preparation is a solution in a non-physiological state and is converted into gel in a physical state. Olopatadine temperature-sensitive gel is prepared by systematically investigating shaft materials and properly proportioning poloxamer 407 (F127 for short) and poloxamer 188 (F68 for short). Olopatadine pH-sensitive gel is prepared by adjusting the consumption of carbomer 980 and hydroxypropyl methyl cellulose (HPMC). The preparations can be applied through the eyes or nasal cavity, the residence time of the drug in the administration parts is greatly prolonged, bioavailability is increased, curative effect is improved, and the preparation has ideal application prospects.

The present invention relates to a stable fixed dose aqueous pharmaceutical composition (e.g., contained in a container) for nasal administration to a human, comprising mometasone or its salt, olopatadine or its salt. The composition may further include a hydrocolloid. The invention also relates to a process for preparing the pharmaceutical composition, and the use of the pharmaceutical composition in the treatment of rhinitis in a subject.

The present invention provides a novel polymorphic form of olopatadine hydrochloride ([(Z)-3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride), a selective histamine H1-receptor antagonist that is used for the treatment of ocular symptoms of seasonal allergic conjunctivitis. The present invention also provides novel methods for producing olopatadine on a large scale, and in a manner that is cost effective, provides a low level of impurities and eliminates the need to use the costly and dangerous base, butyllithium, which is used in prior art reactions for making olopatadine. The present invention further provides novel processes for carrying out a large scale production of 3-dimethylaminopropyltriphenylphosphonium bromide and its corresponding hydrobromide salt, which are employed in the production of olopatadine, and pharmaceutically acceptable salts of olopatadine.

The present invention relates to a method of treating allergic rhinitis in a subject (e.g., a pediatric human subject) in need thereof comprising nasally administering to the subject an effective amount of a fixed-dose pharmaceutical composition comprising mometasone or its salt and olopatadine or its salt.

The present invention relates to a stable fixed dose aqueous pharmaceutical composition (e.g., contained in a container) for nasal administration to a human, comprising mometasone or its salt, olopatadine or its salt. The composition may further include a hydrocolloid. The invention also relates to a process for preparing the pharmaceutical composition, and the use of the pharmaceutical composition in the treatment of rhinitis in a subject.

The present invention relates to a novel process for the preparation of olopatadine hydrochloride starting from an advanced intermediate.

The invention provides an improved preparation method of 4-(2-carboxybenzyloxy) phenylacetic acid. 6, 11-dihydro-11-oxo-dibenz (b, e) oxepin-2-acetic acid which is a raw material for producing the anti-allergic drug of olopatatadine can be obtained through a cyclization reaction of the 4-(2-carboxybenzyloxy) phenylacetic acid.

The invention discloses a novel method for preparing olopatadine hydrochloride. The method comprises the steps as follows: (1) high-activity zinc and 3-bromo-N,N-dimethylpropylamine form an organic zinc reagent (I); (2) the organic zinc reagent is eliminated after electrophilic substitution with isoxepac (II) to form olopatadine (III); (3) the olopatadine with higher purity is obtained through recrystalization of the olopatadine, wherein structural formulas of the organic zinc reagent (I), the isoxepac (II) and the olopatadine (III) are as follows.

The invention relates to a detection method of olopatadine hydrochloride and related substance thereof. The method comprises a step of using high performance liquid chromatography for detection, wherein liquid chromatographic conditions are as follows: an octyl silane bonded silica gel chromatographic column is used; a mobile phase A is aqueous solution containing 0.01%-1% ion pair reagent, 0.3%-1% monoamine and 0.001-0.1mol / L buffer salt, a mobile phase B is acetonitrile and / or methyl alcohol, and gradient eluting is executed; and a pH value of buffer solution is 2.5-3.5, and detection wavelength is 220nm-280nm. The detection method of the olopatadine hydrochloride and the related substance thereof provided by the invention can effectively separate the olopatadine hydrochloride and impurities thereof, improve accuracy of a detection result and reduce clinical medication risks.

The present invention relates to a method of treating allergic rhinitis in a subject (e.g., a human) in need thereof comprising nasally administering to the subject an effective amount of a fixed-dose pharmaceutical composition comprising mometasone or its salt and olopatadine or its salt.

Disclosed is a method wherein (Z)-11-(3- dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2- acetic acid (general name: olopatadine) or an acid addition salt thereof, which is useful as a pharmaceutical product, is produced by processing a dibenzoxepin derivative represented by the formula [I] below with a dehydrating agent for obtaining a mixture of a dibenzoxepin derivative represented by the formula [II] below and a dibenzoxepin derivative represented by the formula [III] below, and then processing the thus-obtained mixture with an acid. In the formula [I], R1, R2 and R3 independently represent an alkyl group having 1-2 carbon atoms.) (In the formula [II], R1, R2 and R3 are as defined above.) (In the formula [III], R1, R2 and R3 are as defined above.

The invention relates to the field of pharmaceutical preparations, and discloses a compound preparation composition containing olopatadine and brimonidine for a nasal cavity and a preparation method of the compound preparation composition. The compound preparation composition for the nasal cavity is prepared from the following components in percentage by weight: 0.01 to 0.5 percent of olopatadine and 0.01 to 0.5 percent of brimonidine. According to the compound preparation composition, olopatadine and brimonidine are combined for use, the curative effect is remarkably improved compared with single-drug treatment, a good synergistic interaction effect is shown, multiple pharmacological effects are achieved through one-time drug administration, and drug use convenience and long-term treatment compliance are greatly improved.

The present invention relates to a stable fixed dose aqueous pharmaceutical composition (e.g., contained in a container) for nasal administration to a human, comprising mometasone or its salt, olopatadine or its salt. The composition may further include a hydrocolloid. The invention also relates to a process for preparing the pharmaceutical composition, and the use of the pharmaceutical composition in the treatment of rhinitis in a subject.

The invention provides an olopatadine solid composition and a preparation method thereof, and relates to the field of pharmaceutical preparations. The olopatadine solid composition comprises an inner core and a medicine carrying layer from inside to outside, an isolating layer is arranged between the inner core and the medicine carrying layer, and the isolating layer isolates the inner core and the medicine carrying layer and prevents the inner core and the medicine carrying layer from making contact with each other; the inner core is a sucrose pellet core; the medicine carrying layer comprises olopatadine or a pharmaceutically acceptable salt of the olopatadine. Compared with the original products on the market, the tablet is simple in structure and only comprises the inner core, the isolating layer and the medicine carrying layer, so that the types of prescription auxiliary materials are few, quality control is more facilitated, clinical medication safety is guaranteed, meanwhile, the stability of the tablet is equivalent to that of the original products on the market, and the tablet has a wider application prospect compared with the original products on the market. The olopatadine solid composition is simple in structure and few in types of auxiliary materials, so that the preparation method of the olopatadine solid composition is simpler, more convenient and easier to operate, and industrial mass production is facilitated.

The present invention relates to a method of treating allergic rhinitis in a subject (e.g., a pediatric human subject) in need thereof comprising nasally administering to the subject an effective amount of a fixed-dose pharmaceutical composition comprising mometasone or its salt and olopatadine or its salt.

The invention discloses a medical application of olopatadine hydrochloride in treatment of primary liver cancer diseases, and discloses a novel medical application of olopatadine hydrochloride, the olopatadine hydrochloride has the capabilities of remarkably inhibiting proliferation of primary liver cancer cells and promoting apoptosis of the primary liver cancer cells, and the prepared medicine for treating the primary liver cancer has an obvious medical effect and relatively high safety. The invention belongs to the technical field of biological medicines, and relates to a novel medicine for treating primary liver cancer, which has extremely high clinical application value and medicine popularization potential, provides a novel effective medicine for treating primary liver cancer, has better clinical transformation potential and belongs to the technical field of biological medicines.

Process for the preparation of olopatadine (I), which comprises reacting a compound of formula (V) in the presence of a palladium catalyst to, provide a compound of formula (VI), wherein the acid protecting group is removed to provide the compound of formula (I) and if desired, transformation into its salts.

The present invention relates to an ophthalmic composition comprising pranoprofen and olopatadine and / or naphazoline. The invention also relates to a preparation method of the ophthalmic composition, which comprises the following steps: mixing the pranoprofen, the olopatadine and / or the naphazoline, the osmotic pressure regulator, the pH regulator, the metal ion chelating agent, the thickening agent, the preservative and the water for injection to obtain the ophthalmic composition. The invention also relates to an application of the ophthalmic composition in preparation of a medicine for treating ocular inflammation, and the ocular inflammation comprises external eye and / or anterior segment inflammation caused by gram-positive bacterium and / or gram-negative bacterium infection. When the ophthalmic composition provided by the invention is used as eye drops, the treatment effect on eye inflammation of a patient can be improved, and adverse effects of eye stimulation, conjunctival congestion, edema and the like after medication can be avoided, so that the medication compliance of the patient is improved, and the recovery time of the patient is shortened.

The present invention relates to a stable fixed dose aqueous pharmaceutical composition (e.g., contained in a container) for nasal administration to a human, comprising mometasone or its salt, olopatadine or its salt. The composition may further include a hydrocolloid. The invention also relates to a process for preparing the pharmaceutical composition, and the use of the pharmaceutical composition in the treatment of rhinitis in a subject.

The invention provides a method for detecting related substances of an olopatadine hydrochloride oral solution, which comprises the following steps: preparing a solvent, an auxiliary contrast solution, a test solution and the like, and carrying out separation detection by adopting a gradient elution procedure and a special chromatographic column, and chromatographic conditions comprise that a mobile phase A is a mixed solution of a supramolecular complex-phosphate buffer solution and acetonitrile in a specific ratio; the mobile phase B is phosphate buffer solution-acetonitrile; a zirconium-doped octyl silane bonded silica gel chromatographic column with the surface zirconium oxide loading capacity of 2.8-3.5 wt% and the pore diameter of 7-9 nm is used, and gradient elution is carried out. The method can be used for detecting related substances including impurities A, B, C, E and the like, the separation degree of each impurity is remarkably improved, the separation degree of a main component and each degraded impurity meets the requirements, and the method is good in system applicability and system precision, high in specificity, good in linear relation, high in accuracy and suitable for large-scale popularization and application, and the quantitation limit and the detection limit reach the standard. The related substances in the olopatadine hydrochloride oral solution can be accurately and reliably detected.

The invention provides a post-treatment purification method of olopatadine hydrochloride. The method comprises the steps of 1) washing a reaction liquid crude product with a sodium chloride solution to remove bromide ions so as to obtain an olopatadine hydrochloride salt-containing crude product; (2) dissolving the olopatadine hydrochloride salt-containing crude product prepared in the step (1) into a mixed solvent of dichloromethane, glacial acetic acid, acetic acid and alcohols, and carrying out desalting treatment so as to obtain an olopatadine hydrochloride crude product; and (3) recrystallizing the olopatadine hydrochloride crude product obtained in the step (2), wherein a solvent adopted for recrystallization is a mixed solvent of dimethyl sulfoxide and isopropyl ether. The target product olopatadine hydrochloride obtained through the method is extremely low in inorganic salt content, meanwhile, the preparation yield and the product purity of olopatadine hydrochloride are greatlyimproved, the production cost is reduced, and the method is suitable for industrial production.

This application relates to the field of pharmaceutical preparations, and discloses a compound preparation composition containing olopatadine and brimonidine for nasal use, and its preparation method. The compound preparation composition for nasal use comprises 0.01-0.5% olopatadine and 0.01-0.5% brimonidine by weight percentage. The compound preparation composition of this invention, with olopatadine and brimonidine used in combination, significantly improves efficacy compared to monotherapy, showing a good synergistic effect, and achieves multiple pharmacological effects with a single dose, greatly improving the convenience of medication and long-term treatment compliance.

The present invention provides an olopatadine composition, which comprises olopatadine, pyruvate and / or pyruvate, osmotic pressure regulator, metal ion complexing agent, preservative, pH regulator and purified water. The composition of the invention can improve the stability of the olopatadine, reduce the irritation to the nasal mucosa, accelerate the repair of the nasal mucosa, relieve nasal symptoms and improve the drug safety of the olopatadine.

The invention provides a simple and convenient method which is more suitable for industrial large-scale production and preparation of high-purity [3-(dimethylamine) propyl] triphenylphosphonium bromide hydrobromide. According to the preparation method, with triphenylphosphine and 1, 3-dibromopropane adopted as starting materials, reflux reaction is carried out in n-heptane to obtain (3-bromopropyl) triphenylphosphonium bromide; the obtained (3-bromopropyl) triphenylphosphonium bromide does not need to be separated, and directly reacts with a dimethylamine aqueous solution by means of a one-potmethod; after the reaction is finished, the n-heptane is concentrated, water in a system is taken out, so that a [3-(dimethylamine) propyl] triphenylphosphonium bromide hydrobromide crude product canbe obtained; and the crude product is thermally pulped with absolute ethyl alcohol, so that the high-purity [3-(dimethylamine) propyl] triphenylphosphonium bromide hydrobromide can be obtained.

The invention discloses a preparation method of E-olopatadine, which comprises the following steps: adding [3-(dimethylamino)propyl]triphenylphosphine bromide hydrobromide into a solvent, adding an n-pentane solution of tert-butyl lithium, carrying out heat preservation reaction for 0.5-2 hour, heating to 105-110 DEG C, dropwise adding a toluene solution of methyl 6, 11-dihydro-11-oxo-dibenzo(b, e)oxepine-2-acetate, heating to 105-110 DEG C, stirring for 2-5 hours at the temperature of 105-110 DEG C, then cooling to 0-15 DEG C, carrying out quenching reaction, adding concentrated hydrochloricacid to adjust the pH value to 6+ / -0.2, carrying out reduced pressure distillation to dryness to obtain a solid, enabling the solid to pass through a column to obtain an E-olopatadine methyl ester crude product, and carrying out purification. According to the preparation method of Eolopatadine provided by the invention, on the basis of the prior art, key steps are upgraded and transformed, so thatthe reaction steps can be reduced, and the loss is reduced.

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses an olopatadine oral rapidly disintegrating tablet composition and a preparation method thereof, the composition is composed of olopatadine, mannitol, a taste masking agent, a disintegrating agent, a flavoring agent, colloidal silica and magnesium stearate; the olopatadine tablet comprises the following components in percentage by weight: 1.0 to 10.0 percent of olopatadine, 30.0 to 90.0 percent of mannitol, 0.01 to 1.0 percent of taste masking agent, 0.01 to 1.0 percent of flavoring agent, 1.0 to 10.0 percent of disintegrating agent, 0.5 to 5.0 percent of colloidal silicon dioxide and 0.5 to 15.0 percent of magnesium stearate. The composition prepared by adopting the prescription can improve the stability of the medicine, the in-vitro dissolution curve is consistent with that of a reference preparation, the taste is good, and the smoothness of a patient can be improved in the taking process.

The present invention relates to a method of treating allergic rhinitis in a subject (e.g., a human) in need thereof comprising nasally administering to the subject an effective amount of a fixed-dose pharmaceutical composition comprising mometasone or its salt and olopatadine or its salt.