Medical application of 11-ketoandrostenedione and 11-ketotestosterone

A ketoandrostenedione and ketotestosterone technology, which can be applied to medical preparations containing active ingredients, pharmaceutical formulations, antitumor drugs, etc., can solve the problem of inability to reduce the concentration of cortisol in the whole body, and achieve good resistance to hypogonadism. Effects of sexual dysfunction and/or infertility, accelerated metabolism, relief of symptoms of hypogonadism

Inactive Publication Date: 2013-10-09
HANGZHOU YIHAIXUAN BIOTECH
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the current inhibitors have less effect on inhibiting oxidase than inhibiting reductase, their disadvantages are: (1) it will inevitably offset part of the inhibitor's efficacy; (2) bidirectional inhibition of HSD11B1 can only prevent However, it cannot reduce the already elevated systemic cortisol concentration, and the already elevated cortisol level in the tissue will still maintain the inhibition of testosterone synthesis; the existing cortisol concentration needs to be activated by stimulating HSD11B1 oxidase Its conversion to inactive cortisone, especially due to high levels of circulating glucocorticoids, as in stress and Cushing's syndrome
[0012] US2007 / 0219172A1 (Selective testicular 11b-HSD inhibitors for the treatment of hypergonadism associated disorders and modulation of fertility” inventors: David J. Morris, Syed Abdul Latif, Matthew P. Hardy, Renshan Ge) discovered 11-ketoandrostene Diketone (11-keto-androstenedionem) and 11-keto-testosterone (11-keto-testosterone) new mechanism and new use, but only found their role in inhibiting HSD11B1, the application is also limited to hypergonadal related diseases Fertility and Modulation Therapy, and did not use them as HSD11B1 dual modulators

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Medical application of 11-ketoandrostenedione and 11-ketotestosterone
  • Medical application of 11-ketoandrostenedione and 11-ketotestosterone
  • Medical application of 11-ketoandrostenedione and 11-ketotestosterone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1: 11-ketotestosterone dually regulates HSD11B1 activity of rat Leydig cells in vitro

[0047] 1. HSD11B1 is an oxidoreductase with NADP+ / NADPH as coenzyme, mainly expressed in Leydig cells. The measurement of HSD11B1 activity in Leydig cells does not require the addition of NADP+ / NADPH. Compounds were measured with intact Leydig cells, reflecting compound penetration into cells.

[0048] 2. Isolation of Leydig cells from adult rat testes: The testes of 6 SD rats aged 90 days were used for the separation of Leydig cells from adult rats. The separation method was prepared according to the method reported by Salva, et al [Salva, A.; Klinefelter, G.R.; Hardy, M.P.J.Androl. 2001, 22, 665]. The purity of Leydig cells was determined according to the method reported by Payne et al [Payne. Endocrinology, 1980]. Leydig cells were 95% pure as assessed by histochemical staining for 3b-steroid dehydrogenase.

[0049] 3. Activity detection of HSD11B1 oxidation and reduct...

Embodiment 2

[0051] Example 2: 11-ketoandrogen dual regulation of human HSD11B1 activity in vitro

[0052] 1. Human HSD11B1 enzyme can be produced by HSD11B1 gene expression and COS1 cell line. The measurement of HSD11B1 activity in COS1 cells does not require the addition of NADP+ / NADPH. Compounds were measured with intact COS1 cells, reflecting compound penetration into cells.

[0053] 2. Human HSD11B1 enzyme comes from HSD11B1 gene expression: Human HSD11B1 gene was transfected into COS1 cell line and cultured in COS1 cell line: according to Ge et al (Ge et al 2000. J Androl. 21(2):303-10.) Human HSD11B1 gene transfected and cultured CHOP cell line.

[0054] 3. Activity detection of HSD11B1 oxidation and reduction in COS1 cell line: The activity detection of COS1 cell line HSD11B1 was carried out according to the method reported by Ge RS, et al. [Ge RS, et al. Endocrinology, 1997, 139 (9): 3787-95 ]. Using [3H]-cortisol as a substrate, the amount of cortisone produced was detected t...

Embodiment 3

[0056] Example 3: Mode of action of 11-ketoandrogen regulating HSD11B1 activity in vitro

[0057] 1. HSD11B1 is an oxidoreductase with NADP+ / NADPH as coenzyme, mainly expressed in hepatocytes. HSD11B1 activity in hepatocyte microsomes is affected by hexose phosphate dehydrogenase and so on. Hexose phosphate dehydrogenase uses hexose phosphate (G6P) as a substrate to generate NADPH to stimulate HSD11B1 reductase activity and reduce HSD11B1 oxidase activity. The measurement needs to add NADP+ or G6P.

[0058] 2. Rat hepatocyte microsomes were prepared according to the method reported by Ge RS, et al [Ge RS, et al. Endocrinology, 1997, 139(9):3787-95].

[0059] 3. Activity detection of HSD11B1 oxidation and reduction in rat hepatic microsomes: The activity detection of HSD11B1 in hepatic microsomes was carried out according to the method reported by Ge RS, et al. Endocrinology, 1997, 139 (9 ):3787-95]. Using [3H]-corticosterone as a substrate, the amount of 11-dehydrocorticos...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to medical application of 11-ketoandrostenedione and 11-ketotestosterone, in particular relates to application of a type I 11beta-hydroxysteroid dehydrogenase (11beta-hydroxysteroid dehydrogenase type I, HSD11B1) dual regulator, wherein dual regulation means that HSD11B1 reductase is inhibited while HSD11B1 oxidase is activated. The 11-ketoandrostenedione and the 11-ketotestosterone disclosed by the invention can be used for preparing androgen replacement treatment medicines, glucocorticoid hormonosis treatment medicines and hypogonadotropic hypogonadism dysfunction and / or sterility treatment medicines.

Description

technical field [0001] The present invention relates to the application of 11-ketoandrostenedione and 11-ketotestosterone as dual regulators of type I 11b-hydroxysteroid dehydrogenase (11b-hydroxysteroid dehydrogenase type I, HSD11B1) for the preparation of androgen replacement therapy drugs A medicine for treating hyperglucocorticoid hyperactivity and a medicine for treating hypogonadism, sexual dysfunction and / or infertility belong to the technical field of medicine. Background technique [0002] At present, there are about 500 million patients with significantly decreased sexual function in the world. According to the survey results of the sexual status of Chinese males conducted by the Sexual Medicine Professional Committee of the Chinese Society of Sexology, 9.7% of men over the age of 40 have experienced significant decline in sexual function. As men enter middle age, they may notice changes that cause less of a relative drop in testosterone that affects erections, ca...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5685A61P5/26A61P5/46A61P3/00A61P35/00A61P15/08
Inventor 葛仁山郭晶晶葛海芳
Owner HANGZHOU YIHAIXUAN BIOTECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap