Pantarhei Bioscience B.v.

Donesta Bioscience B.v.

Ares Trading S.a.

Evert Johannes Bunschoten

Herman Jan Tijmen Coelingh Bennink

Herman Jan Coelingh Bennink

Christian Franz Holinka

René Frank Van Der Linden

The present invention relates to a method of treating or preventing estrogen-sensitive tumours in a mammal, said method comprising the administration of a therapeutically effective amount of an estrogenic component to said mammal, wherein the estrogenic component is selected from the group consisting of: substances represented by the following formula in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. The estrogenic component according to the invention does not have undesirable proliferative effects on breast and/or endometrial tissue and displays sufficient estrogenicity to prevent that its administration will lead to hypoestrogenism and/or climacteric complaints. Other aspects of the invention relate to pharmaceutical compositions, drug delivery systems and kits comprising the aforementioned estrogenic component in combination with an estrogen suppressant.

Pharmaceutical composition comprising estetrol derivatives for use in cancer therapy

The present invention relates to a method of treating or preventing estrogen-suppressed tumors in a mammal, said method comprising the administration of a therapeutically effective amount of an estrogenic component to said mammal, wherein the estrogenic component is selected from the group consisting of: substances represented by the following formula in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. The estrogenic component according to the invention is particularly useful in the treatment or prevention of colorectal and prostate cancer and, unlike commonly used estrogens, does not simultaneously enhance the risk of estrogen-stimulated cancers such as breast cancer.

Pharmaceutical compositions comprising estetrol derivatives for use in cancer therapy

One aspect of the invention concerns a cosmetic method of treating human skin by delivering an estrogenic component to said skin. The method comprises applying to the skin a composition containing: (i) at least 5 &#x3bc;g/g of an estrogenic component selected from the group consisting of substances represented by the following formula (I) in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors; and (ii) a cosmetically acceptable vehicle. Other aspects of the invention relate to therapeutic methods of treating or preventing vaginal dryness or acne and a therapeutic method of promoting wound healing. Yet another aspect of the invention relates to a skin care composition comprising the aforementioned estrogenic component and a cosmetically acceptable vehicle.

Method of treating human skin and a skin care composition for use in such a method

The present invention relates to a method of treating or preventing estrogen-sensitive tumors in a mammal, said method comprising the administration of a therapeutically effective amount of an estrogenic component to said mammal, wherein the estrogenic component is selected from the group consisting of: substances represented by the following formula in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. The estrogenic component according to the invention does not have undesirable proliferative effects on breast and/or endometrial tissue and displays sufficient estrogenicity to prevent that its administration will lead to hypoestrogenism and/or climacteric complaints.

The present invention relates to a method of treating or preventing estrogen-suppressed tumors in a mammal, said method comprising the administration of a therapeutically effective amount of an estrogenic component to said mammal, wherein the estrogenic component is selected from the group consisting of: substances represented by the following formula (I) in which formula R, R, R, R, independently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. The estrogenic component according to the invention is particularly useful in the treatment or prevention of colorectal and prostate cancer and, unlike commonly used estrogens, does not simultaneously enhance the risk of estrogen-stimulated cancers such as breast cancer.

One aspect of the invention is concerned with a method of hormone replacement therapy, which method comprises administering to a person in need of such a therapy an effective amount of an estrogenic component selected from the group consisting of: substances represented by the formula in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alokxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; and no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method, and mixtures thereof; said composition containing virtually no progestogen or anti-progestin. Another aspect of the invention relates to a drug delivery system for enteral or parenteral administration that contains at least 1 &#x3bc;g of the aforementioned estrogenic component and virtually no progestogen or anti-progestin.

Pharmaceutical composition for use in hormone replacement therapy

One aspect of the present invention relates to a method of hormone replacement in mammals, which method comprises the oral administration of an estrogenic component and a progestogenic component to a mammal in an effective amount to prevent or treat symptoms of hypoestrogenism, wherein the estrogenic component is selected from the group consisting of substances represented by the above formula in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; and no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. Another aspect of the invention concerns a pharmaceutical kit comprising oral dosage units that contain the aforementioned estrogenic component and a progestogenic component as well as an androgenic component. 

Estrogenic compounds in combination with progestogenic compounds in hormone-replacement therapy

The invention relates to cosmetic methods of treating human skin. The method includes applying to the skin a composition containing an estrogenic component and a cosmetically acceptable vehicle. Other aspects of the invention relate to therapeutic methods of treating or preventing vaginal dryness or acne and a therapeutic method of promoting wound healing. Another aspect relates to a skin care composition comprising the aforementioned estrogenic component and a cosmetically acceptable vehicle.

The invention relates to pharmaceutical dosage units for oral, transmucosal or transdermal administration containing 15- or 16-substituted testosterone analogues, as well as to therapeutic methods that employ these testosterone analogues. More particularly, the invention is concerned with such pharmaceutical dosage units containing at least 10 &#x3bc;g of an androgenic steroid selected from the group consisting of 15-hydroxytestosterones, 16-hydroxytestosterones, precursors thereof and mixtures of these hydroxytestosterones and/or their precursors; and a pharmaceutically acceptable excipient. The term '15-hydroxytestosterones' encompasses both 15&#x3b1;-hydroxytestosterone (15&#x3b1;, 17&#x3b2;-dihydroxy-4-androsten-3-one) and 15&#x3b2;-hydroxytestosterone (15&#x3b2;, 17&#x3b2;-dihydroxy-4-androsten-3-one). Similarly, the term '16-hydroxytestosterones' encompasses both 16&#x3b1;-hydroxytestosterone hydroxytestosterone (16&#x3b1;, 17&#x3b2;-dihydroxy-4-androsten-3-one) and 16&#x3b2;-hydroxytestosterone (16&#x3b2;, 17&#x3b2;-dihydroxy-4-androsten-3-one). The androgenic steroids according to the invention are advantageously employed in e.g. a method of treating or preventing androgen deficiency or a method of hormonal contraception.

Pharmaceutical application of 15- or 16-substituted testosterone analogues

A method of treating or preventing an immune mediated disorder in a mammal, said method comprising the administration of a therapeutically effective amount of an estrogenic component to said mammal, wherein the estrogenic component is selected from the group consisting of: substances represented by the following formula: in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. Another aspect of the invention relates to a pharmaceutical formulation comprising the aforementioned estrogenic component, an immunotherapeutic agent and a pharmaceutically acceptable excipient.

Method of treating or preventing immune mediated disorders and pharmaceutical formulation for use therein

A method of contraception in mammalian females, which method comprises the parenteral or rectal administration of an estrogenic component and a progestogenic component to a female of childbearing capability in an amount effective to inhibit ovulation, wherein the estrogenic component is selected from the group consisting of substances represented by the following formula (1) in which R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; and no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. Another aspect of the invention concerns a drug delivery system for parenteral or rectal administration that contains the aforementioned estrogenic component and a progestogenic component, said drug delivery system being selected from the group consisting of suppositories, systems for intravaginal delivery, inhalers, nasal sprays and transdermal delivery systems.

Drug delivery system comprising a tetrahydroxylated estrogen for use in hormonal contraception

One aspect of the present invention is concerned with a method of controlled ovarian hyperstimulation in a mammalian female, said method comprising the co-administration to said female of &#x2014;a substance having follicle stimulating hormone activity (FSH substance) in an amount effective to stimulate multiple follicular development; &#x2014;gonadotropin releasing hormone (GnRH) antagonist in an amount equivalent to a daily subcutaneous dose of at least 0.5 mg ganirelix to prevent a premature LH-surge; and &#x2014;a LH substance in an amount effective to prevent or suppress symptoms of luteinising hormone (LH) deficiency resulting from the administration of the GnRH antagonist; followed by administering a meiosis and luteinisation inducing substance (ML substance) in an amount effective to stimulate resumption of meiosis and luteinisation, and wherein the LH substance is not obtained from the urine of human females. Another aspect of the to invention relates to a pharmaceutical kit for use in a method of controlled hyperstimulation, which kit comprises: &#x2014;at least one parenteral or oral dosage unit containing one or more FSH substances in an amount equivalent to a subcutaneous dose of 50-1500 I.U. FSH; &#x2014;at least one parenteral dosage unit containing one or more GnRH antagonists in an amount equivalent to a subcutaneous dose of 0.5-25 mg ganirelix; &#x2014;at least one parenteral dosage unit containing one or more LH substances in an amount equivalent to a subcutaneous dose of 50-3000 I.U. recombinant LH; wherein the LH substance is not obtained from the urine of human females.

Method of controlled ovarian hyperstimulation and pharmaceutical kit for use in such method

A method of contraception in mammalian females, which method comprises the oral administration of an estrogenic component and a progestogenic component to a female of childbearing capability in an amount effective to inhibit ovulation, wherein the estrogenic component is selected from the group consisting of substances represented by the following formula (1) in which R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; and no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors. Another aspect of the invention concerns a pharmaceutical kit comprising oral dosage units that contain the aforementioned estrogenic component and/or a progestogenic component.

Drug delivery system comprising a tetrahydroxilated estrogen for use in hormonal contraception

Disclosed is a method of increasing libido in a woman, said method comprising administering to said woman an effective amount of an estrogenic component selected from the group consisting of: substances represented by the following formula (I) in which formula R, R, R, Rindependently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R, R, Ris a hydroxyl group; no more than 3 of R, R, R, Rare hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method; and mixtures of one or more of the aforementioned substances and/or precursors.

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Heesch, Netherlands

Evert Johannes Bunschoten