93 results about "Tadalafil" patented technology

The present disclosure is directed to pharmaceutical compositions comprising a PDE V inhibitor and one or more pharmaceutical excipients or additives wherein the pharmaceutical compositions are in the form of liquid pharmaceutical compositions. The pharmaceutical compositions of the present disclosure are useful for the treatment of diseases or conditions which are treatable by administration of PDE V inhibitor drug such as pulmonary arterial hypertension, erectile dysfunction, etc.

The disclosure relates to compositions comprising a phentermine and a unicyclic aminoketone and methods of use thereof. The methods of use include inducing weight loss or reducing weight gain in a human subject. The unicyclic aminoketone may be diethylpropion or bupropion. In some embodiments, the compositions further include tadalafil or naltrexone.

The invention discloses a preparation method of tadalafil, which comprises the following steps: S1, taking sarcosine as a raw material, and carrying out carboxyl hydroxyl chlorination reaction under the action of thionyl chloride or oxalyl chloride to generate sarcosine chloride hydrochloride; s2, taking tryptophan methyl ester hydrochloride and piperonitrile as raw materials, and carrying out nitrile-amine condensation to generate an intermediate A; s3, taking the intermediate A as a raw material, and carrying out ring closing under the action of phosphorus oxychloride to generate an intermediate B; s4, reducing the intermediate B under the action of sodium borohydride to generate an intermediate C crude product, and purifying; and S5, carrying out an amide condensation reaction on the intermediate C and sarcosine chloride, carrying out amine ester exchange to generate a tadalafil crude product, and refining to obtain the tadalafil product. The tadalafil is synthesized with high yield, high specificity and selectivity, and the process route has the advantages of cheap and easily available raw materials, specific reaction, high product yield, safety and simplicity in operation, environmental friendliness, low equipment requirement, easiness in industrialization and the like.

The invention provides a pharmaceutical composition and application thereof in preparation of a compound preparation, and belongs to the field of medicines. The pharmaceutical composition comprises a potassium ion channel opener, a 5 alpha-reductase inhibitor and a phosphodiesterase 5 inhibitor. The pharmaceutical composition can synergistically promote treatment of androgen dependent diseases or prevention of complications, and by taking the pharmaceutical composition of minoxidil, finasteride and tadalafil as an example, the effects in a benign prostatic hyperplasia rat model and an androgenic alopecia mouse model are verified, which indicates that the minoxidil, finasteride and tadalafil have a synergistic interaction effect, and the pharmaceutical composition can be used for treating the androgen dependent diseases or preventing the complications. Good clinical application prospects are realized.

The present invention relates an improved process for the preparation of piperonal (2), which is useful as an intermediate for the preparation of Tadalafil of formula (1).

A phosphodiesterase type 5 inhibitor is used in the preparation of a medicament for resisting fibrotic diseases. Experiments in animal models of ischemia-reperfusion (UIRI)-induced renal fibrosis, unilateral ureteral obstruction (UUO)-caused kidney fibrosis and idiopathic pulmonary fibrosis show that a PDE5 inhibitor such as tadalafil, sildenafil and vardenafil can significantly inhibit the expression of multiple fibrosis iconic proteins such as fibronectin, collagen I, renal injury molecule-1, and α-skeletal muscle actin in UIRI and UUO renal fibrosis lesions, improves glomerulopathy, degree of renal tubular distension, renal interstitial collagen fiber deposition and inflammatory cell infiltration, reduces the fibrotic area within the lesion, and significantly inhibits the progression of renal fibrosis; and the PDE5 inhibitor can significantly improve smooth muscle proliferation and inflammatory cell infiltration in bronchioles and pulmonary arterioles of idiopathic pulmonary fibrosis lesion, improve damage condition of alveolar tissue, and significantly inhibit the progression of pulmonary fibrosis.

1. The name of the product of this design: packaging box (Gugo Tadalafil). 2. Purpose of this design product: used for packaging tadalafil medicine. 3. The design key points of this appearance design product are: the combination of product color, shape and pattern. 4. The picture or photo that best illustrates the key points of the design: main view. 5. The design for which protection is sought includes color.

The present invention relates to a donepezil and tadalafil combination therapy for the prevention, treatment or amelioration of Alzheimer's disease or cognitive dysfunction. The combined administration of donepezil and tadalafil according to the present invention has an improvement effect on Alzheimer's disease or cognitive impairment superior to that of the individual administration of donepezil, and thus can be effectively used as a therapeutic or complexing agent or the like for Alzheimer's disease or cognitive impairment.

1. Name of the design product: Packaging box (Tadalafil tablets). 2. Use of the design product: For product packaging boxes. 3. Design key points of the design product: The combination of shape and pattern. 4. Picture or photograph that best shows the design key points: Front view.

The invention relates to the technical field of inspection and detection, in particular to a method for detecting tadalafil analogues. According to the method disclosed by the invention, the tadalafil impurity O, the EP impurity 1 and the impurity 82 in the sample are rapidly screened and quantitatively detected by adopting UPLC-MS / MS (Ultra Performance Liquid Chromatography-Mass Spectrometry). Extracting and purifying the sample by adopting a four-salt dispersion solid-phase extraction method; a C18 chromatographic column is adopted, 5-20 mM ammonium formate-acetonitrile is used as a mobile phase for gradient elution, and an MRM mode is combined for detection. A verification result of the method shows that the linear relation of target impurities is good, the quantitation limit of oral liquid is 0.02 mg / kg, the detection limit is as low as 0.007 mg / kg, the quantitation limit of a semi-solid preparation and a solid preparation is 0.05 mg / kg, the detection limit is as low as 0.02 mg / kg, and the average recovery rate reaches 80%-116% (RSDlt; 5.3%).

Disclosed herein are pharmaceutical compositions in the form of a suspension for oral delivery. Some embodiments provide a pharmaceutical composition in the form of a suspension for oral delivery comprising an active pharmaceutical ingredient; water, a suspending agent; a buffering agent; and one or more of a wetting agent and a binder / filler. In some embodiments, the active pharmaceutical ingredient is selected from quetiapine, sildenafil, tadalafil, cinacalcet, ticagrelor, mycophenolate, aprepitant, zonisamide, and primidone.

There is provided a pharmaceutical composition comprising, as active ingredients: 5 mg of tadalafil or a pharmaceutically acceptable salt thereof; and 0.5 mg of dutasteride or a pharmaceutically acceptable salt thereof, wherein the dissolution rate of tadalafil is 60-75% after 5 minutes and 80% or more after 30 minutes under dissolution conditions of a paddle speed of 50 rpm in 500 mL of a dissolution solution having a pH of 1.2 and containing 0.25% of SLS, and the dissolution rate of dutasteride is 50% or more after 15 minutes and 85% or more after 30 minutes under dissolution conditions of a paddle speed of 50 rpm in 500 mL of a dissolution solution containing water and 0.1% of SLS.

Provided is a pharmaceutical composition comprising as active ingredients: 5 mg of tadalafil or a pharmaceutically acceptable salt thereof; and 0.5 mg of dutasteride or a pharmaceutically acceptable salt thereof, wherein the dissolution rate of tadalafil under the dissolution conditions of a paddle rate of 50 rpm in 500 mL of a dissolution solution having a pH of 1.2 and containing 0.25% of SLS is 60-75% after 5 minutes and 80% or more after 30 minutes, and the dissolution rate of dutasteride under the dissolution conditions of a paddle rate of 50 rpm in 500 mL of a dissolution solution containing water and 0.1% of SLS is 50% or more after 15 minutes and 85% or more after 30 minutes.

The invention discloses a microneedle patch for treating male erectile dysfunction as well as preparation and application of the microneedle patch. The microneedle patch comprises a soluble matrix carrier and a needle-shaped array, wherein the needle-shaped array is formed by ED treatment medicines and is wrapped in the soluble matrix carrier; the matrix carrier comprises a polymer or polysaccharide with high mechanical strength, high biocompatibility and high water solubility; the ED treatment medicine is prepared from tadalafil, sildenafil and vardenafil; the micro-needle patch is used for rapidly delivering a drug for treating male erectile dysfunction in a percutaneous manner, and the effect of treating male erectile dysfunction is achieved.

The invention belongs to the technical field of analysis and detection, and discloses a method for detecting impurities in a tadalafil bulk drug and / or a tadalafil intermediate. The method for detecting the impurities in the tadalafil bulk drug and / or the tadalafil intermediate comprises the following steps: taking the tadalafil bulk drug and / or the tadalafil intermediate to be detected, and preparing a sample solution; taking an impurity standard substance, and preparing a standard sample solution; and detecting the impurities in the sample solution by adopting an ultra-high performance liquid chromatography-mass spectrometry method. According to the detection method, two N-nitroso genotoxic impurities and ten other process impurities in tadalafil raw materials and / or tadalafil intermediates can be determined at the same time, the specificity is high, the sensitivity is high, results of multiple different types of impurities can be obtained at the same time in one-time determination, the analysis efficiency is effectively improved, and the method is suitable for popularization and application. Powerful guarantee is provided for analyzing generation factors influencing impurities, effectively controlling medicine quality and guaranteeing medicine use safety.

The application discloses a preparation method of an amino tadalafil succinic acid derivative, and comprises the following steps: S1, synthesizing compound 1, i.e. 4-hydrazinyl-4-oxobutanoic acid, by reacting hydrazine with succinic anhydride; S2, synthesizing compound 3, i.e. the amino tadalafil succinic acid derivative, by carrying out a hydrazinolysis cyclization reaction of compound 2 with compound 1. In the amino tadalafil succinic acid derivative prepared by the application, the solubility of the amino tadalafil derivative is greatly improved by introducing succinic acid, and the drug administration mode is expanded; meanwhile, the existence of the carboxyl group as a reactive site can be used to derive other functional groups or to be connected with other active groups to form a synergistic active group, so that more possibilities are provided for preparing other related products based on the amino tadalafil derivative.

The present invention relates immediate-release tablet compositions comprising tadalafil, macitentan and one or more pharmaceutically acceptable excipients.

The invention discloses a tadalafil oral soluble film and a preparation method thereof. The oral soluble film comprises the following components in parts by weight on a dry basis; the pharmaceutical composition comprises 20-35 parts of a deep eutectic drug carrier, 50-65 parts of a film-forming matrix, 1-3 parts of a polymer anti-devitrification agent, 3-5 parts of a disintegration accelerator, 4-8 parts of a plasticizer and 3-6 parts of a flavoring agent. An amphiphilic natural deep eutectic solvent technology is adopted, choline chloride, dicarboxylic acid and a hydrophobic donor are used for constructing a ternary system according to a specific molar ratio, the hydrophobic donor remarkably improves the solubility of tadalafil through hydrophobic interaction, a strong hydrogen bond of the deep eutectic solvent inhibits drug crystallization, and a high-speed shearing micro-domain dispersion technology is combined, so that the solubility of tadalafil is remarkably improved. The high-efficiency solubilization of insoluble drugs, excellent anti-crystallization stability, rapid disintegration performance and good taste are realized, mucous membrane irritation of a traditional surfactant is avoided, and in-vivo absorption and patient compliance are expected to be improved.

1. Name of the product in this design: Packaging Box (Tadalafil Tablets). 2. Purpose of this design: for packaging pills or health products. 3. The key design feature of this product is its pattern. 4. The image or photograph that best illustrates the design's key features: the front view.

1. Name of the product of this design: Pharmaceutical packaging box (Ailijin Tadalafil tablets). 2. Purpose of this design product: This design product is used for packaging of medicines. 3. The key design point of this design product lies in the combination of shape and pattern. 4. The picture or photo that best illustrates the key points of the design: main view.

The invention discloses a method for determining related substances of cis-tetrahydrocarboline hydrochloride, an intermediate of tadalafil, which specifically adopts a diode array detector and uses 0.1% formic acid solution-acetonitrile as a mobile phase for gradient elution. Take an appropriate amount of cis-tetrahydrocarboline hydrochloride, add a solvent (water: acetonitrile 1:1) to prepare a solution containing 0.4 mg of cis-tetrahydrocarboline hydrochloride per 1 ml, as a test solution. Take the test solution and inject it into a liquid chromatograph, record the chromatogram, and process the chromatogram according to the area normalization method. The detection method of related substances of cis-tetrahydrocarboline hydrochloride, an intermediate of tadalafil, can quickly and accurately detect the situation of related substances of cis-tetrahydrocarboline hydrochloride. The operation is simple and the sensitivity is high, and the product quality can be well controlled.

1. The name of the product of this design: packaging box (coarse love tadalafil). 2. Purpose of this design product: used for packaging tadalafil medicine. 3. The design key points of this appearance design product are: the combination of product color, shape and pattern. 4. The picture or photo that best illustrates the key points of the design: main view. 5. The design for which protection is sought includes color.

1. The name of the design product: packaging box (Lei Cao tadalafil tablets). 2. The use of the design product: for product packaging. 3. The design points of the design product: in the combination of shape and pattern. 4. The picture or photo that best indicates the design points: perspective drawing.

The present disclosure relates to an injectable composition comprising tadalafil or a pharmaceutically acceptable salt thereof, a lipid, and a co-solvent. The injectable composition according to the present disclosure has the advantages of achieving a constant level of drug blood concentration over a long period of time, thereby reducing the number of drug administration, having excellent long-term safety due to absence of local tolerance and minimal side effects due to absence of initial rapid drug release, and providing high formulation stability.

1. The name of the design product: packaging box (sildenafil citrate tablet packaging). 2. The use of the design product: packaging box for packaging medicines. 3. The design features of the design product: the combination of shape and pattern. 4. The picture or photo that best indicates the design features: perspective view.

The invention discloses N-nitroso tadalafil and a synthesis method and application thereof, and the synthesis method comprises the following steps: adding tadalafil into a reaction container, then adding a solvent for dissolving, balancing the system at (-20) DEG C to (-2) DEG C for 8-16 minutes, adding a nitrosation reagent for sealed reaction, after the reaction is finished, extracting, drying, concentrating, and carrying out column chromatography to obtain the N-nitroso tadalafil. The target product N-nitroso tadalafil is obtained. The N-nitroso tadalafil synthesis method is simple and convenient in process, the obtained product is high in purity, a reliable standard substance can be provided for tadalafil product quality research and analysis method development and verification, and the method has good popularization value.

To provide an agent for the treatment of a patient suffering from pulmonary arterial hypertension (PAH).SOLUTION: An agent for initial triple combination therapy with macitentan, tadalafil, and selexipag for treating a patient having PAH, the agent containing macitentan, tadalafil, and selexipag, wherein the patient has, at initiation of the initial triple combination therapy, a resting mean pulmonary arterial pressure (mPAP) of about 25 mmHg or more, a mean pulmonary arterial wedge pressure (PAWP) of about 15 mmHg or less, and a pulmonary vascular resistance (PVR) of about 240 dyne sec / cm5 or more, and wherein the macitentan and the tadalafil are administered on day 1, and the selexipag is administered within 4 weeks.SELECTED DRAWING: None

The application relates to the technical field of organic synthesis, and discloses a method for preparing tadalafil or epi-tadalafil, which comprises the following steps: reacting N-(1,3-benzodioxol-5-methyl)-D-tryptophan methyl ester with Fomc-Ala-Cl to prepare compound IIa or compound IIb; and performing a deprotection / aminolysis reaction and a cyclization reaction on the compound IIa or the compound IIb in the presence of methylamine to prepare tadalafil or epi-tadalafil. Through the selection of a specific (Fomc-Ala-Cl) acylation reagent, the purity and / or yield of the compound IIa or the compound IIb are improved, so that the yield and / or purity of the tadalafil and / or epi-tadalafil are improved.

The present invention relates to a method for preparing a tadalafil impurity I, and belongs to the field of analytical chemistry. The method specifically relates to preparing a tadalafil impurity I by using a preparative liquid phase, characterized in that tadalafil, hydrogen peroxide and a reaction solvent are mixed, reacted to an end point, a crude product containing the tadalafil impurity I is obtained, and then an organic acid buffer-acetonitrile is used as a mobile phase, and a C18 filler is used as a preparative column for elution separation, and the tadalafil impurity I peak flow fraction is collected, and after removing the solvent, a high-purity tadalafil impurity I is obtained. The method of the present invention has simple steps, cheap and easily available raw materials, and high product purity.

Disclosed herein are pharmaceutical compositions in the form of a suspension for oral delivery. Some embodiments provide a pharmaceutical composition in the form of a suspension for oral delivery comprising an active pharmaceutical ingredient; water, a suspending agent; a buffering agent; and one or more of a wetting agent and a binder / filler. In some embodiments, the active pharmaceutical ingredient is selected from quetiapine, sildenafil, tadalafil, cinacalcet, ticagrelor, mycophenolate, aprepitant, zonisamide, and primidone.