266 results about "Tadalafil" patented technology

This invention relates to oral pharmaceutical compositions suitable for making pharmaceutical formulations for oral administration that provide for the rapid dissolution of the phosphodiesterase 5 inhibitor tadalafil. In particular, the pharmaceutical compositions comprise solid composites of tadalafil exhibiting high solubility and rate of dissolution. The invention further relates to methods of preparing these pharmaceutical formulations and the use of such pharmaceutical formulations for treating diseases associated with PDE5 inhibitors.

The invention discloses a preparation method of tadalafil. The concrete preparation method is used for successfully synthesizing tadalafil by taking L-tryptophan methyl ester hydrochloride as an initial raw material and utilizing the characteristics that an ortho-position of an ester group has the chiral inversion property under an alkaline condition, the reaction between ester group and Pictet-Spengler is reversible reaction, and the ester group is easily converted into a cis-form product with relatively small solubility, therefore, the preparation method is a brand new technology. The price of L-tryptophan methyl ester hydrochloride is only less than 1 / 5 of that of D-tryptophan methyl ester hydrochloride, so that the cost of the overall route is greatly lower than that of the prior art, and then the preparation method is suitable for industrial production.

A method of sexual enhancement in women includes the steps of identifying a woman requesting sexual enhancement, assuring that the woman's blood includes estradiol within a first predetermined range and testosterone within a second predetermined range, and thereafter administrating a drug selected from the group consisting of vardenafil hydrochloride and tadalafil prior to sexual activity. The selected drug may be loaded into a starch strip which is then applied to the woman's tongue. Sexual enhancement in women can also be achieved by transdermal or subcutaneous application of the steroid hormone DHEA.

Provided is a solid particulate tadalafil having a bimodal particle size distribution.

The invention relates to a preparing method of a phosphodiesterase 5 inhibitor tadalafil. D-methyl tryptophanate hydrochloride is adopted as an initial raw material, and is subjected to cyclization with heliotropin, N-acylation, aminolysis-cyclization, and other reactions to obtain a tadalafil crude product. The tadalafil crude product is recrystallized to obtain a tadalafil finished product. The method has characteristics of mild reaction conditions, short reaction time, high yield, good product stability and convenience for industrial production.

The present invention relates to a time-delayed sustained release pharmaceutical composition for oral administration, which comprises an immediate release phase and a prolonged sustained release phase, wherein said immediate release phase and prolonged sustained release phase respectively comprise dapoxetine therein as an active ingredient.; The pharmaceutical composition of the present invention comprises dapoxetine, which is an agent for treating premature ejaculation, in both the immediate release phase and the prolonged sustained release phase thereof, to thereby immediately exhibit the effectiveness of the pharmaceutical composition of the present invention in order to enable a patient to achieve sexual satisfaction during the early stage of administration, as well as to reduce side effects by means of the time-delayed sustained release of the prolonged sustained release phase during the early stage of administration and enable a continuous in vivo absorption of dapoxetines, to thereby lengthen the duration of the effectiveness of the pharmaceutical composition of the present invention.; Further, agents for treating erectile dysfunction, such as sildenafil, tadalifil or the like can be added to the immediate release phase so as to allow for a coincidence of the durations of the effectiveness of a premature ejaculation treatment agent and erectile dysfunction treatment agents, even though a half-life difference exists between the two types of treatment agents, thus maximizing patient satisfaction.

The invention belongs to the field of preparation of chemical raw medicaments, and more in particular relates to an improved preparation method for a phosphodiesterase 5 inhibitor tadalafil. A specific synthesis route is shown in the specification. The method comprises the following steps of performing Pictet-Spengler cyclization reaction and chloroacetyl chloride acylation on starting reactants (D-tryptophan methyl ester hydrochloride and piperonal) to obtain an intermediate product, directly performing subsequent reaction on the intermediate product without purification, preparing an intermediate 1-(1,3-benzodioxol-5-yl)-2-(chloracetyl)-2,3,4,9-tetrahydro-1H-pyridino-[3,4,-B]indol-3-thiophenate methyl by using a one-pot reaction method, performing column chromatography purification to obtain a single cis-isomer, and finally reacting the single cis-isomer with methylamine hydrochloride in the presence of an inorganic base to obtain the tadalafil.

The invention relates to a synthesis method for (6R, 12aR)-6-(1, 3-benzodioxane heterocyclas-5-base)-2-methyl-2, 3, 6, 7, 12, -12a-hexahydro pyrazinyl [1', 2':1, 6] pyridyl [3, 4-b] indole-1, 4-diketone in the technical field of the pharmaceutical engineering. With the D-methyl tryptophan and piperonal as raw materials, the cis-1, 3-disubstituted carboline intermediates are prepared and generated through the Pictet-Spengler cyclization and then the products called tadalafil are obtained through the acylation ammoniation of the 3-secondary amino group and the final MTX substitution and condensation close-loop. By adopting the acidic condition protic solvents in the invention, the trans-1, 3-disubstituted carboline intermediates generated through the Pictet-Spengler cyclization, which is a key step in the existing process, are converted into those with a cis-configuration, thus greatly enhancing the stereospecific configuration yield of the carboline intermediates so as to enhace the overal yield of the tadalafil with reaching the goal of optimizing and improving the synthesis process.

The present invention relates to methods of treating multidrug resistance in cancerous cells with phosphodiesterase (PDE) inhibitors, e.g., PDE5 inhibitors. More specifically, the invention relates to methods of treating multidrug resistance that arises, e.g., during administration of chemotherapeutic / antineoplastic (anticancer) agents for treatment of cancer, with a PDE5 inhibitor (e.g., sildenafil, vardenafil, and tadalafil). The invention also relates to methods of treating cancer, e.g., multidrug resistant cancer, using a PDE5 inhibitor in combination with an antineoplastic therapeutic agent. Further, the invention relates to pharmaceutical compositions for treating multidrug resistant cancers comprising a PDE5 inhibitor, or a combination of a PDE5 inhibitor and an antineoplastic agent.

The present invention relates an improved process for the preparation of tetrahydro-beta-carboline derivative of formula (V) which is useful as an intermediate for the preparation of Tadalafil of formula (I). Moreover, the present invention relates to the process for the preparation of Tadalafil of formula (I)

The invention discloses an immunoassay method for a nano-colloidal gold marker of tadalafil and analogs thereof. The determination method comprises the following steps: coupling oximate tadalafil with bovine serum albumin by adopting an activated ester method, synthesizing artificial immunity antigen which is used for immunizing animals, and preparing specific tadalafil and analogs thereof; in addition, coupling the oximate tadalafil with egg albumin to be used for construct an immunity detection method; separating, purifying and labeling the tadalafil and analogs thereof to the nano-colloidal gold, and then respectively curing the tadalafil and analogs detection antibodies thereof and goat-anti-rabbit IgG on a carrier, and adding a detection antigen into a detection solution. According to the method, the lowest detection limit of the tadalafil and analogs thereof legally added into health products and Chinese patent medicines is 10mu g / kg, and the fast detection can be completed within 5 minutes. The method is stable, fast and accurate, and suitable for one-step fast detection on legally added medicines.

The invention discloses an artificial antigen of tadalafil and analogues thereof, an antibody and an ELISA kit thereof. The kit comprises an enzyme label plate coated with a tadalafil antigen, a tadalafil antibody operating fluid, a horseradish peroxidase labelled secondary antibody, a tadalafil standard-substance operating fluid, a substrate liquid, a substrate buffer, a reaction stopping liquid and a condensation washing liquid. The invention also discloses a method for detecting tadalafil and analogues thereof in health-care food by utilizing the kit. The provided kit for detecting tadalafil and analogues thereof employs an indirect competitive enzyme-linked immunosorbent analysis technology, possesses the maximum detection scope of 0.12-7.45 ng / mL, the half-inhibitory concentration of 0.933 ng / ml, the detection limit of 0.095 ng / mL and the recovery rate of 83.0-119.2%, is low in detection limit, high in sensitivity, good in stability and low in cost, is extremely suitable for primary screening on a large amount of samples, and possesses practical significance on rapid detection on illegally-added tadalafil in health-care food.

The invention discloses a method for preparing Tadalafil crystal form A. The method is characterized in that the crystallization solvent is a binary mixed solvent of a C1-C4 alcohol and acetic acid or a ternary mixed solvent of a C1-C4 alcohol, acetic acid and water. The method has the characteristics that: a mixed solvent system is used, thus the dosage of the crystallization solvent can be greatly reduced, the drying process can be simplified and the corrosion of acidic materials to the equipment can be reduced.