184 results about "Butylphthalide" patented technology

The invention discloses a preparation method of butylphthalide, which comprises the following steps: taking phthalic anhydride as a raw material; enabling the phthalic anhydride to carry out addition reaction with the Grignard reagent of butyl halide to obtain an intermediate of o-valeryl benzoic acid; and then, reducing by sodium borohydride, and carrying out acidic cyclization to obtain the butylphthalide. The phthalic anhydride and the butyl halide which are used as raw materials in the preparation method of the butylphthalide of the invention are commercial products, and the reaction raw materials can be obtained easily. Because the Grignard reaction, the sodium borohydride reduction and the acidic cyclization are classical reactions, the operation is simple, the industrialized production can be realized easily, the yield of the butylphthalide reaches 50-60%, and the purity of the butylphthalide reaches 97-98%.

The invention which relates to the medicinal field discloses an application of butylphthalide and derivatives thereof in the preparation of medicines for preventing and treating ALS (amyotrophic lateral sclerosis). Butylphthalide and the derivatives, which can delay the disease time of an SOD1-G93A transgenic mouse, prolong the lifetime of the mouse, reduce the degenerative change of spinal motorneurons, obviously increase the survival number of spinal anterior horn motor neurons of the mouse, reduce the electrophysiological abnormality of the transgenic mouse, obviously improve the action potential amplitude and the motion unit number of compound muscles, substantially inhibit the activation of astrocytes and microglial cells in the spinal cord of the mouse, and obviously reduce the expression level of iNOS and NF-kappaBp65, have good application prospects in the prevention and the treatment of the ALS.

The invention relates to an ester obtained by the reaction of 3-(3'-hydroxyl)-butylphthalide and acids, wherein, the acids can be acceptable inorganic acids or organic acids in pharmacy. Proved by testing, the efficacy of the ester is increased significantly. Part of the ester can go on reacting with the acids or alkalis to form salts in order to increase water solubility and prepare injection preparations; being proved by testing, the injection preparations have no muscle and vascular stimulation.

The invention relates to a drip pills of butylbenzene phthalein and its preparation method and it is characterized by comprising butylbenzene phthalein, base material, dispersing agent and coating materials. PEG4000, PEG6000, PEG20000 and poloxamer are selected as base materials. Dispersing agent is from lightweight aerosol and crospovidone. And coating materials are from hypromellose, hydroxypropyl cellulose, ethyl cellulose and Eudragit E30D.

The invention relates to a butylphthalide synthesis method. The method comprises the steps that methyl 2-formyl benzoic acid is adopted as a starting material, THF is adopted as a solvent to react with an n-butyl magnesium chloride Grignard reagent, and acid regulation is performed to prepare a butylphthalide product. The invention further relates to a technology for preparing high-purity butylphthalide. The obtained crude butylphthalide product is subjected to hydrolysis treatment by an alkaline substance, acid regulation is performed to separate out solids, and filtering is performed to obtain a butylphthalide midbody; the acid regulation and alkali regulation processes are executed repeatedly, and finally ring closure and decompression desolvation are performed to obtain high-purity butylphthalide. According to the synthesis method, low-flash diethyl ether is prevented from being adopted as a solvent, the purification technology is easy to implement, the reagent can be purchased in bulk easily, column chromatography product purification and reduced pressure distillation under high temperature and high vacuum degree are not needed, and industrial enlarged production is easy.

The invention relates to new use of 3-n-butylphthalide (abbreviated as butyl phthalide) and derivatives thereof, in particular to the use of the compounds in the preparation of the medicine for treating Parkinson disease. A mat model of hemiparkinsonian disease is built by using three-dimensional targeted injection of rotenone to perform a test, and the result of the test shows that the butyl phthalide and derivatives thereof can effectively improve symptoms aroused by Parkinson and have a nerve-protecting effect.

The invention provides a butylphthalide medicine active composition, which comprises the following ingredients: first ingredients: the butylphthalide content is higher than or equal to 98.0 percent; second ingredients: the second ingredients are one kind of materials or several kinds of materials selected from methylene phthalide, ethylene phthalide, propylene phthalide, butane phthalide, amylene phthalide, phthalide, methyl phthalide, ethyl phthalide, propyl phthalide and amyl phthalide, in addition, the content of the second ingredients is higher than 0 but is lower than or equal to 2.0 percent, when the second ingredients comprise any one kind of materials from methylene phthalide, ethylene phthalide, propylene phthalide, butane phthalide and amylene phthalide, the content of any one kind of included ingredients does not exceed 0.5 percent, and when the second ingredients comprise any one kind of materials from phthalide, methyl phthalide, ethyl phthalide, propyl phthalide and amyl phthalide, the content of any one kind of included ingredients does not exceed 1.0 percent. The quality of the medicine active composition is stable, and the clinic curative effect and the medication safety of the butylphthalide preparation can be ensured.

The invention provides a preparation method of high-purity butylphthalide. The preparation method comprises the following steps: A. adding a crude product of rac-3-n-butylphthalide to a reaction flask and reducing the pressure until the system vacuum degree is 1-2mbar; raising the temperature and collecting a 130-140 DEG C fraction, thus obtaining a rac-3-n-butylphthalide fraction; B. adding the rac-3-n-butylphthalide fraction and methanol to the reaction flask, stirring to dissolve the materials, adding a methanol solution of inorganic base, heating till reflux reaction, carrying out filtration, removing methanol through concentration, adding dichloromethane, stirring the materials to precipitate solids, and carrying out filtration and drying, thus obtaining 1-hydroxypentyl-2-benzoate; and C. adding 1-hydroxypentyl-2-benzoate to water, stirring to dissolve 1-hydroxypentyl-2-benzoate, then adding the solution to a reaction flask with a hydrochloric acid solution, stirring to react at a temperature of 35-45 DEG C, standing for layering, washing an oil phase with a sodium bicarbonate solution and water in sequence, and carrying out drying and filtration, thus obtaining the pure product of rac-3-n-butylphthalide.

The present invention relates to the field of pharmaceutical chemistry and therapeutics, and particularly relates to an optically active butylphthalide open-ring derivative as shown in the general formula I or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, preparation methods thereof, pharmaceutical compositions containing the compounds, and medical application thereof, especially application in medicines for prevention and treatment of cardiovascular and cerebrovascular and improvement of heart and brain circulatory disturbance, antiplatelet aggregation medicines, antithrombotic medicines, anti-ischemic medicines, anti-dementia medicines, anti-atherosclerotic medicines, and medicines for anti-diabetes and complications thereof. Pharmacological experimental results show that the compounds have good anti-platelet aggregation activity, anti-thrombotic activity, anti-ischemic activity and neuroprotective effects, and are clinically useful for the preparation of medicines for preventing or treating diseases associated with platelet aggregation.

The invention discloses a penicillium vulpinum fungi strain and a method for preparing levo 7-hydroxyl butylphthalide ((S)-(-)-butyl-7-hydroxyl phthalide) employing the fungi strain. The fungi strain disclosed by the invention is a penicillium vulpinum fungi strain NCC3421 (penicillium vulpinum) and is preserved at the China General Microbiological Culture Collection Center (CGMCC for short); and the preservation number is CGMCC No.9094. Under the culture condition provided by the method, the fermentation unit of the levo 7-hydroxyl butylphthalide reaches over 1600mg/L; the fermented product is relatively single in components, and easy to separate and purify, and can be applied to industrialized production of the levo 7-hydroxyl butylphthalide.

The invention relates to a microemulsion transdermal gel agent of butylphthalide or a derivative thereof, and a preparation method thereof, and belongs to the technical field of medicaments. The technical scheme is that: the microemulsion transdermal gel agent is prepared mainly from the following ingredients in part by weight: 1 to 5 parts of oil phase, 1 to 5 parts of emulsifying agent, 0.1 to 1 part of auxiliary emulsifying agent, 1.5 to 15 parts of purified water and 0.003 to 0.5 part of transdermal accelerator. Compared with a comparison example, the microemulsion transdermal gel agent of the butylphthalide or the derivative thereof almost does not influence the microemulsion appearance and granular size under the conditions of centrifugation and high temperature, and is a dynamic and thermodynamic stable system. An in vitro transdermal performance test proves that the microemulsion transdermal gel agent of the butylphthalide or the derivative thereof has good transdermal absorbability. In conclusion, the microemulsion transdermal gel agent of the butylphthalide or the derivative thereof has the simple preparation method, does not need the procedures of high-speed cutting or homogenizing and the like, has small product granular size, and contributes to industrialization.

The invention relates to the fields of pharmaceutical chemistry and pharmaceutical therapeutics, and more particularly to an optically active ring-opening butylphthalide-telmisartan heterocomplex or a pharmaceutically acceptable salt or ester thereof, preparation methods thereof, pharmaceutical compositions containing the compounds, and pharmaceutical application of the pharmaceutical compositions, particularly application in prevention and treatment of neuroinflammation-related diseases, including ischemic stroke, alzheimer's disease, brain trauma, Parkinson's disease, multiple sclerosis and depression.

The invention provides a compound air cleaning agent and a preparing method and application thereof. The compound air cleaning agent is formed by compounding multiple components of thyme essential oil, tea tree essential oil, castanea mollissima flower extracting solution, peony root and skin extracting solution, vine tea extracting solution, gardenia essential oil, osmanthus fragrans essential oil, costustoot essential oil, may lily of the valley alcohol, nerol, citric acid, 2-isopentyloxy allyl acetate, alcohol, assistant, 4-hydroxy-3-butylphthalide and deionized water. The air cleaning agent has the advantages of better sterilizing, mosquito repelling and aroma enhancing performances due to proper selecting of component and proportion and the coordinated action among the components, less using amount, long time effectiveness, and is more saved and fast in the aspect of life and use of people.

The invention provides a butylphthalide sublingual preparation. The butylphthalid sublingual preparation contains butylphthalide, lauric acid polyethylene glycol glyceride, an excipient, an adsorbent and a lubricating agent. A butylphthalide solid dispersion prepared by taking lauric acid polyethylene glycol glyceride as a carrier can be quickly dissolved in vitro, and a sample is prepared by adopting a hot melting extrusion method, so that drug loading capacity is high and sample stability is good.

The invention relates to a butylphthalide- and edaravone-containing compound injection and a preparation method thereof. The injection of every 100 ml contains 25-50 mg of active ingredient butylphthalide, 12.5-50 mg of edaravone, as well as absolute ethyl alcohol, hydroxypropyl-beta-cyclodextrin, an osmotic pressure regulator, an antioxidant and the like. With the adoption of the butylphthalide- and edaravone-containing compound injection, the administration dosage is greatly lowered, the burden of liver metabolism is reduced, and the incidence rate of liver adverse reactions is lowered. According to determination, with the adoption of the butylphthalide- and edaravone-containing compound injection, the administration dosage of the edaravone can be reduced by at least 20%, besides, the compound injection has a better curative effect, and the incidence rate of the liver adverse reactions is also remarkably lowered.

The present invention relates to a novel drug delivery and release system, i.e. Self-emulsifying Drug Delivery System (SEDDS), of butylphthalide, to a preparation process thereof, and to a use thereof in a pharmaceutical formulation. The drug delivery system comprises as essential ingredients 1% to 65% of butylphthalide and 10% to 65% of a emulsifying agent, together with various excipients as required depending on the desired dosage forms. The present invention significantly increases the contact area between butylphthalide and the mucous membrane of the gastrointestinal tract, and therefore improves the absorptivity of the drug.

The invention discloses a preparation containing a ligustilide type component and a preparation method thereof. The ligustilide type component comprises the following components by weight percent: ligustilide 14%-42%, sedanolide 3%-20%, butylidenephthalide 0.1%-5%, butylphthalide 0.1%-3%, senkyunolide-H 0.2%-3%, senkyunolide-I 0.4%-5%, levistilide A 0.5%-1.5%, and riligustilide 0.4%-1.2%. The preparation method prevents the ligustilide type component from being destroyed by the wet distillation method and the solvent extraction method, and the quality of the ligustilide type component is more ensured without solvent residue. The preparation containing the ligustilide type component is safe and controllable on the effective part. Drop pills and sublingual tablets containing the ligustilide type component can avoid the defects of the oral preparation after administration such as liver first pass effect and gastrointestinal reaction, and an injection containing the ligustilide type component can also avoid the possible situations during using the injections such as acute poisoning reaction and allergic reaction. The preparation containing the ligustilide type component is safer and more effective, and has good economic benefit and social benefit.

The invention belongs to the technical field of pharmaceutical chemistry and particularly relates to medical use of 7-hydroxy-butylphthalide in preparation of drugs for preventing and/or treating cardiac and cerebral vascular diseases.

The invention relates to a microencapsulated butylphthalide medicine composition, a preparation method and applications. Butylphthalide is microencapsulated to raise the solubility of butylphthalide, prevent volatilization, develop required solid preparations and liquid preparations clinically and give play to therapeutical effects of butylphthalide better. The composition contains butylphthalide effective component with a mass percent of 1-55%. Butylphthalide is coated with natural or synthesized high polymer materials as capsule wall materials or carrier materials to form microencapsules. The composition can be prepared into various preparations of powder, capsules, chewable tablets, buried tablets, buccal tablets, other oral compressed tablets, injection, liquid suspension, lotion, powder-injection, coating preparations, thin film preparations and the like.

The invention relates to stability-improved butylphthalide oral freeze-dried powder which is characterized by being prepared from the following raw and auxiliary materials by a freeze-drying method: butylphthalide and 4-methylbutyrolactone modified sulfobutyl beta-cyclodextrin sodium, the 4-methylbutyrolactone modified sulfobutyl-beta-cyclodextrin sodium has the following simple structural formula: the butylphthalide oral freeze-dried powder provided by the invention overcomes the defects of capsule preparations and injections, and the freeze-dried powder is liquid after being redissolved, so that the freeze-dried powder is easier for patients to take. Besides, the plasma peak reaching time of butylphthalide capsules is 60-80 min, after the butylphthalide oral freeze-dried powder is redissolved, the peak reaching time of oral liquid is less than 30 min, and the butylphthalide oral freeze-dried powder can take effect quickly after being taken and has important significance for rescuing cerebral apoplexy patients. Meanwhile, the butylphthalide oral freeze-dried powder has good stability, and can keep good purity, solubility and bioavailability of butylphthalide after being stored for 10 days under the conditions of 25 DEG C and 40RH%.

The invention relates to a butylphthalide controlled release preparation and a preparation method thereof. Drugs can be uniformly released at a constant speed, and release of liquid drugs from the controlled release preparation in a liquid form is achieved.

The present invention relates to the inclusion complexes of butylphthalide, which is D,L-mixed or levorotatory, with cyclodextrin or cyclodextrin derivatives, to a process for their preparation and the use thereof. In the invention, the butylphthalide is complexed with cyclodextrin or cyclodextrin derivatives, preferably with hydroxypropyl-β-cyclodextrin, in order to increase the water-solubility of butylphthalide, develop clinical solid or liquid formulations and improve the therapeutic effect of butylphthalide. The inclusion complex, in which the molar ratio of butylphthalide to cyclodextrin or cyclodextrin derivatives is in the range of 1:1-10, can be used to prepare infusion, injection, injectable powder, liquids for oral administration, syrup, tablets, granules, dispersible tablets and others.

The invention relates to the field of medicine, particularly to a medicine composition comprising butylphthalide and cosolvent, and aims to adopt a novel cosolvent to improve the water solubility of butylphthalide, develop clinically required solid, semisolid or liquid preparations of butylphthalide, and better exert the therapeutical effect of butylphthalide. The composition can be used for preparing a plurality of dosage forms such as tablets, capsules, ointment, cream, gel, transfusion, aqueous acupuncture, powder for injection, oral liquid and the like. Compared with the prior art, the medicine composition realizes better safety and improvement on the water solubility of butylphthalide.

The present invention provides an analysis detection method for concurrently determining butylphthalide and relates substances thereof. According to the analysis detection method, through a high performance liquid chromatograph, an octadecylsilane bonded silica gel is adopted as a filler, a 0.2% phosphate buffer liquid and acetonitrile are adopted as a mobile phase to carry out gradient elution, and the detection wavelength is 226-230 nm. According to the present invention, the analysis method has characteristics of good specificity, high sensitivity, good accuracy and good durability, wherein the separation degrees of each absorption peak are more than or equal to 7.

The invention provides novel medical application of butylphthalide, i.e. the application of the butylphthalide in the preparation of a medicament for treating the bronchial asthma. The experimental research on the spasmolysis of the butylphthalide on the isolated tracheal smooth muscle of a guinea pig and the influence of the butylphthalide on the incubation period of asthma of the guinea pig shows that the butylphthalide in the concentration range of 3.68*10-6 to 3.68*10-4g/mL has obvious spasmolysis on the tracheal smooth muscle of the guinea pig in the isolated spasticity caused by 5*10-6g/mL of acetylcholine or histamine. On the basis of continuously applying the butylphthalide to the guinea pig which is sensitive for the acetylcholine and the histamine for 10 days, a mixture of the acetylcholine and the histamine is atomized and sucked and the incubation period of asthma is observed. A result shows that 30 mg/kg and 90 mg/kg of butylphthalide has an effect of relieving the tracheospasm of the guinea pig, which is caused by the acetylcholine and the histamine. Therefore, the butylphthalide has a treatment effect on the asthma guinea pig and the treatment effect of the butylphthalide on the asthma guinea pig is related to the effect of inhibiting Ca2+ inner flow and expanded tracheal smooth muscle of the butylphthalide.