26 results about "Estetrol" patented technology

The present invention relates to a composition comprising an estetrol component and drospirenone for use in treating unscheduled bleeding and spotting in an adolescent female subject. The invention also encompasses associated uses and methods of contraception as well as improving health-related quality of life and alleviating menstrual symptoms in adolescent subjects.

The present invention relates to a process for preparing (15α,16α,17β)-Estra-1,3,5(10)-triene-3,15,16,17-tetrol, also known as Estetrol, having the formula shown below:

The present invention relates to a process for the preparation of a compound of formula (I), a stereoisomer, a salt, a hydrate or a solvate thereof, comprising the step of desulfinylation of a compound of formula (II) to produce compound of formula (I); wherein: R1 and R2 are as defined in the claims, wherein said desulfinylation step is performed by continuous flow process.

The present invention relates to a composition comprising an estetrol component for use in alleviating estrogen deficiency symptoms, including menopause-related symptoms, in subjects characterized by a certain degree of liver dysfunction.Compared with existing estrogen-based compositions intended to alleviate estrogen deficiency symptoms, the composition described herein exhibits favorable pharmacokinetic properties.Also described herein are the uses for the above and corresponding treatment methods.

The invention provides an orodispersible solid pharmaceutical dosage unit having a weight between 30 and 1,000 mg, said dosage unit consisting of:0.1-25 wt. % of estetrol particles containing at least 80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof; and75-99.9 wt. % of one or more pharmaceutically acceptable ingredients;the solid dosage unit comprising at least 100 μg of the estetrol component; and wherein the solid dosage unit can be obtained by a process comprising wet granulation of estetrol particles having a volume weighted average particle size of 2 μm to 50 μm.The solid dosage unit is easy to manufacture and perfectly suited for sublingual, buccal or sublabial administration.

The present invention proposes a process for preparing high-purity estetrol, which uses (17β)-3-(phenylmethoxy)-estra-1,3,5(10),15-tetraen-17-ol acetate as a raw material, introduces hydroxyl groups at positions 15 and 16 through a dihydroxylation reaction, protects the hydroxyl groups at positions 15 and 16 through a ketal reaction, separates isomers, and then sequentially removes the benzyl protecting group, the acyl group, and the ketal protecting group. Finally, the process is purified to obtain a compound of formula (I) #imgabs0#. The present invention uses a ketal method to protect the hydroxyl groups at positions 15 and 16, and then separates the isomers, thereby achieving a satisfactory isomer removal effect and refining yield. Moreover, the process is convenient, and the ketal reaction only requires the use of an organic ketone reagent and a catalytic amount of acid. The organic ketone reagent can be completely recovered and reused, and almost no waste is generated.

Described are combined oral contraceptive compositions with reduced cardiovascular effects and methods using them. In some embodiments, the methods relate to contraceptive methods or methods for treating dysmenorrhea with reduced cardiovascular effects, such as reduced venous thromboembolism (VTE) risk. The methods comprise administering to a female subject an effective amount of an estetrol component and a progestogenic component. The methods enjoy a favourable profile for thromboembolism compared to currently available methods which employs contraceptives from the so-called second, third or fourth generation.

The present invention relates to a pharmaceutical composition comprising estetrol and drospirenone for use in relieving pain associated with endometriosis in a patient. The pharmaceutical compositions described in the present invention are particularly effective in relieving pain associated with endometriosis in patients having high levels, frequencies and / or intensities of pain, e.g., measured by visual analog scale (VAS) scoring, and / or with other complications such as adenomyosis or hysteromyoma. Uses related to the above and corresponding methods of treatment are also described.

This invention relates to a treatment for female sexual arousal disorder (FSAD), related compositions, dosing units, and packaging units. Specifically, this invention relates to the use of a composition comprising about 14 mg to about 25 mg of estradiol for the treatment of FSAD. This composition has achieved beneficial effects in patients diagnosed with FSAD based on a self-report questionnaire.

The present invention provides an estetrol synthesis process, and relates to the technical field of steroid compound synthesis processes, and the method comprises the following steps: taking estrone as an initial raw material, firstly carrying out 3-site hydroxyl protection, and then carrying out an oxidative dehydrogenation reaction in the presence of a metal catalyst and in an oxygen atmosphere to prepare a key intermediate ketene, then 17-site carbonyl reduction, 17-site hydroxyl protection, 15, 16-site double bond dihydroxylation, 3-site protecting group removal and hydrolysis reaction are sequentially carried out, and finally the target product estetrol is obtained. The method adopts metal catalysis to directly oxidize to construct cycloenone, effectively avoids the problem of poor stability of partial intermediates in the prior art, has the advantages of simple process, short reaction steps, greenness, environmental protection and the like, and is suitable for industrial production.

The present invention relates to a process for the preparation of (15 [alpha], 16 [alpha], 17 [beta])-estra-1, 3, 5 (10)-triene-3, 15, 16, 17-tetrol monohydrate, also known as estetrol monohydrate, having the following formula (I).

The present invention relates to a combined oral contraceptive with a reduced risk for side effects, including a reduced risk for QT interval prolongation, a reduced risk for testosterone decrease and a reduced risk for elevated C-reactive protein levels when compared to other combined oral contraceptives. The estetrol / drospirenone combined oral contraceptive described herein shows favorable pharmacokinetics for the progestogenic component. Use of a specific estrogenic component in the combined oral contraceptive entails multiple benefits over currently available combined oral contraceptives.

The present invention relates to a composition comprising an estetrol component for use in the prevention and treatment of the symptoms of menopausal-related Alzheimer's disease. The compositions described herein exhibit advantageous properties compared to existing estrogen-based compositions intended to alleviate symptoms of estrogen deficiency. Methods of treatment comprising administration of the composition and related uses are also described.

The present disclosure relates to a crystallization process of (15α, 16α, 17β)-estra-1, 3,5(10)- triene-3,15,16,17-tetrol monohydrate (Estetrol monohydrate, Compound 1) Form 12. Compound 1

The invention provides an orodispersible solid pharmaceutical dosage unit having a weight between 30 and 1,000 mg, said dosage unit consisting of:0.1-25 wt. % of estetrol particles containing at least 80 wt. % of an estetrol component selected from estetrol, estetrol esters and combinations thereof; and75-99.9 wt. % of one or more pharmaceutically acceptable ingredients;the solid dosage unit comprising at least 100 μg of the estetrol component; and wherein the solid dosage unit can be obtained by a process comprising wet granulation of estetrol particles having a volume weighted average particle size of 2 μm to 50 μm.The solid dosage unit is easy to manufacture and perfectly suited for sublingual, buccal or sublabial administration.

The present invention relates to a hormone replacement therapy, to the associated compounds and to the associated packaging units, for alleviating menopause-associated symptoms which is based on the administration to a female mammal of an estetrol component at specified daily doses, optionally in combination with a progestogenic component.The therapy enjoys a statistically significant efficacy combined with a favourable profile for side effects compared to currently available methods for alleviating menopause-associated symptoms.

The present invention relates to a hormone replacement therapy, to the associated compounds and to the associated packaging units, for alleviating menopause-associated symptoms which is based on the administration to a female mammal of an estetrol component at specified daily doses, optionally in combination with a progestogenic component.The therapy enjoys a statistically significant efficacy combined with a favourable profile for side effects compared to currently available methods for alleviating menopause-associated symptoms.

The present invention relates to topical compositions comprising an estetrol component and the use of said compositions to deliver an effective amount of an estetrol component to the skin, particularly for wound healing. Optionally, the estetrol component may be comprised in a composition that further comprises ingredients that are favourable for wound healing. The invention relates in particular to compositions such as estetrol-comprising gels and in particular hydrogels, creams, and ointments. The compositions of the present invention have a beneficial effect on the wound healing process and patient recovery.

The present invention relates to a process for preparing (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrol monohydrate, also known as estetrol monohydrate, having formula (I). [Formula 1] JPEG2026503158000010.jpg2674

The present invention relates to a cosmetic or therapeutic treatment for preventing or treating skin aging and related effects, to the associated compositions for doing such and to the associated formulations or dosage units. The cosmetic and / or therapeutic effect is obtained by relying on an effective amount of an estetrol component.

The invention relates to the preparation of estetrol of formula (I), derivatives thereof protected at positions 3,15α, 16α, 17β of general formula (III), and 3-hydroxy derivatives thereof protected at positions 15α,16α,17β of general formula (IV), and to the intermediates of general formulas (III) and (IV) applicable to the process. Another aspect of the invention is the use of estetrol of formula (I) obtained by the process of the invention for the preparation of a pharmaceutical composition.

The present invention discloses a method for preparing high-purity estragen-1,3,5(10)-triene-3,15α,16α,17β-tetrol (abbreviated as estragen-1,3,5(10),15-tetraene) using 3-hydroxy-17β-hydroxy-estragen-1,3,5(10),15-tetraene as a raw material, and preparing estragen-1 through three steps of phenolic hydroxyl protection, asymmetric dihydroxylation, and hydrolysis. In the preparation method of the present invention, 3-hydroxy-17β-hydroxy-estragen-1,3,5(10),15-tetraene is used as a raw material, alkoxy-substituted benzoyl is used to protect the 3-hydroxyl group, potassium osmate is used to catalyze oxidation to perform an asymmetric dihydroxylation reaction, and di-α-hydroxy groups are introduced at the 15,16 positions. The preparation method does not require the use of expensive chemical reagents and catalysts, the dihydroxylation has high stereoselectivity, is easy to purify and separate, has mild reaction conditions, and is simple and convenient to operate, thereby achieving efficient preparation of high-purity estragen-1,3,5(10),15-tetraene (≥99.5%).

The present invention relates to a hormone replacement therapy, to the associated compounds and to the associated packaging units, for alleviating menopause-associated symptoms which is based on the administration to a female mammal of an estetrol component at specified daily doses, optionally in combination with a progestogenic component.The therapy enjoys a statistically significant efficacy combined with a favourable profile for side effects compared to currently available methods for alleviating menopause-associated symptoms.

The present invention relates to a process for producing crystalline estetrol monohydrate, and particularly a certain polymorphic form thereof, comprising the steps of dissolving estetrol in an aqueous mixture comprising an alcohol to obtain a solution; cooling the solution to a cooling temperature 2; optionally, stirring the cooled solution at the cooling temperature 2; further cooling the solution to a cooling temperature 3 to form a suspension, stirring the suspension at the cooling temperature 3; and isolating crystalline estetrol monohydrate from the suspension.

The present invention relates to a process for the production of (15α,16α,17β)-estra-1,3,5(10)-triene-3,15,16,17-tetrol monohydrate, also known as estetrol monohydrate, having the following formula:

The present invention relates to a process for preparing (15α,16α,17β)-estra-1,3,5(10)-triene- 3,15,16,17-tetrol monohydrate, also known as Estetrol monohydrate, having formula (I).