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Inhibitors of phosphodiesterases in infertility

A technology of inhibitors and preparations, applied in the field of reproductive biology and assisted reproductive technology, can solve the problems of low success rate

Inactive Publication Date: 2006-07-12
LAB SERONO SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, while animal experiments in vitro maturation (IVM) have emerged as an effective method for IVF oocyte generation, clinically human IVM has documented very low success rates

Method used

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  • Inhibitors of phosphodiesterases in infertility
  • Inhibitors of phosphodiesterases in infertility
  • Inhibitors of phosphodiesterases in infertility

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0157] Example 1: Ovulation induction with various PDE inhibitors combined with low-dose FSH

[0158] The experiment was carried out according to the above-mentioned in vivo rat follicle maturation test. In one experiment, ovaries were collected for histological analysis in the middle of the second day of treatment before the last injection. These rats received only 3 doses of FSH and test compound prior to sacrifice and organ harvesting. Count the total number of secondary follicles, including small follicles (mid-mature follicles with multilayered granulosa and first-order scattered vacuoles but no antral cavity) and antral follicles (those with antral enlargement and an outer diameter of approximately 500 microns or greater, With or without thickened granulocyte layer), evaluate secondary follicles. Antral follicles (≥500mcm) were also counted separately.

[0159] data analysis

[0160] The proportion of ovulating animals, the average number of ova present in the ampull...

Embodiment 2

[0193] Example 2: Various PDE inhibitors in combination with low-dose FSH induce cAMP

[0194] In addition to evaluating the resulting granulosa cells as described above, JC-410 porcine granulosa cells were used for the determination of cAMP in the cell lines. These cells were obtained from Dr. Jorge Chedrese (Sakatchewan University). Cells were maintained in DNEN / F12 supplemented with 5% newborn calf serum (Gibco) and 5 μg / ml insulin (Gibco). Stable cell lines were established by transfection of cDNAs for human LH and FSH receptors into cells using standard transfection techniques and selection with 300 [mu]g / ml Geneticin (Gibco). Cells were maintained in the same concentration of geneticin after selection. For cAMP assays, cells were seeded in 96-well plates at a density of 25,000 cells / well and assayed one day later. The next day, cells were stimulated for 1 hour with increasing amounts of inhibitor molecules in the presence or absence of 1 nM FSH as indicated. All comp...

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Abstract

The present invention is directed to methods of increasing oocyte production in a mammal. More specifically, the specification describes methods and compositions for inducing follicular maturation using a PDE inhibitor. The inhibitor may be used alone at high doses. Alternatively, the follicular maturation is achieved by combining a low dose of FSH with the PDE inhibitor treatment.

Description

[0001] This application asserts U.S. Provisional Patent Application No. 60 / 458,955, filed April 1, 2003, U.S. Provisional Patent Application No. 60 / 470,434, filed May 15, 2003, U.S. Provisional Patent Application No. 60 / 470,434, filed January 28, 2004 Priority to Application No. 60 / 540,301 and U.S. Provisional Patent Application No. 60 / 544,003, filed February 12, 2004, the contents of each of which are incorporated herein by reference. technical field [0002] The present invention relates generally to reproductive biology and assisted reproductive technologies (ART), such as controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). More specifically, the present invention relates to methods and compositions for inducing follicle maturation in vivo, including stimulating follicle maturation, using one or more phosphodiesterase inhibitors alone, or in combination with one or more gonadotropins, Such as ovulation induction (OI). In addition, the present invent...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/505A61K31/519
Inventor S・S・帕尔马S・D・麦肯纳S・J・阿金斯托A・艾斯克尔M・C・麦克纳米
Owner LAB SERONO SA
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