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Treatment of endometriosis, angiogenesis and/or endometrial lesion growth

a technology of endometriosis and angiogenesis, applied in the field of treatment of endometriosis, can solve the problems of not being suitable for long-term therapy, not supporting pregnancy, and none of these treatments, so as to reduce the number of available er- receptors and reduce the proliferation of sncg-mediated cells

Inactive Publication Date: 2016-02-11
SYNG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes the use of substances called γ-synuclein inhibitors to treat medical conditions such as endometriosis and angiogenesis. These substances can reduce the growth of cells in these conditions by blocking a protein called SNCG. The patent also describes pharmaceutical compositions containing these substances and other compounds that can enhance their performance. These compositions may have improved absorption, distribution, and efficacy.

Problems solved by technology

Lancet 364: 9447: 1789-1799, 2004) however, it is challenging due to the lack of appropriate non-invasive tests and varying symptoms (Rawson J M. J. Reprod. Med. 36: 7: 513-515, 1991).
None of these treatments, however, are suitable for long term therapy due to adverse side effects and high recurrence rates.
In addition, these treatments often do not support pregnancy.

Method used

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  • Treatment of endometriosis, angiogenesis and/or endometrial lesion growth
  • Treatment of endometriosis, angiogenesis and/or endometrial lesion growth
  • Treatment of endometriosis, angiogenesis and/or endometrial lesion growth

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cell Culture

[0096]HUVECs (Cell Applications, San Diego, Calif., USA) obtained previously from umbilical cord veins were cultured and maintained in T75 flasks containing endothelial cell growth media (Cell Applications, San Diego, Calif., USA). Cells were incubated at 37° C. in a humidified chamber with 5% CO2. HUVECs used in assays were between the third and the seventh passage.

[0097]Luminal epithelial cells derived from endometrium adenocarcinomas (CRL-2923, ATCC, Manassas, Va., USA) were cultured and maintained in T75 flasks containing RPMI-1640 (Sigma Chemical Co., St. Louis, Mo., USA) with 5% fetal bovine serum (FBS, Sigma Chemical Co., St. Louis, Mo., USA) and 1% penicillin and streptomycin (Sigma Chemical Co., St. Louis, Mo., USA). These cells were also incubated at 37° C. in a humidified chamber with 5% CO2. Epithelial cells used for assays were between the second and the fourth passage.

example 2

ST011 Peptide Synthesis

[0098]Peptide was synthesized by solid phase synthesis with amino-terminal acetylation and carboxyl-terminal amidation to mimic the intact protein at a commercial facility. Peptide was purified by reverse phase HPLC using a C18 column (Vydac, Hesperia, Calif.) and lyophilized. The molecular mass of the peptide was verified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Fifty μL aliquots of 1.2 mM ST011 peptide in 10 mM sodium phosphate buffer pH 7.0 were stored at −20° C. until use.

example 3

Cell Proliferation Assay

[0099]HUVECs and epithelial cells were trypsinized, suspended in cultured medium and counted. Approximately 10,000 cells per well were seeded onto a 96 well plate. After allowing 24 hours for attachment in 37° C., the cells were treated with either 600 ng / mL, 300 ng / mL, 150 ng / mL, 5 ng / mL or 2.5 ng / mL of TAT-P12 using phosphate buffer saline (PBS, (Sigma Chemical Co., St. Louis, Mo., USA) as a control. The drug was suspended in RPMI. The plates were incubated in 37° C. for 24 or 48 hours after which 10 μL of WST-1(Roche, Laval, QC, Canada) was added to each well. The plate was then incubated in 37° C. for another 4 hours. The absorbance of the wells was measured at a wavelength of 490 nm or at 510 nm.

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Abstract

Synuclein-gamma (SNCG) inhibitors are useful for inhibiting or treating angiogenesis, endometriosis and / or endometrial lesion growth. They also potentiate efficacy of other hormonal agents in treating angiogenesis, endometriosis and / or endometrial lesion growth.

Description

FIELD OF THE INVENTION[0001]The present invention relates to pharmaceutical compositions and their use in treating endometriosis, angiogenesis and / or endometrial lesion growth.BACKGROUND OF THE INVENTION[0002]Endometriosis:[0003]The uterus is a hollow organ with three layers: outer serous layer, middle muscular myometrium and inner glandular endometrium (Aguilar et al. Hum. Reprod. Update 16: 6: 725-744, 2010). Endometriosis is an estrogen dependent inflammatory disease that is characterized by the growth of endometrium outside of the uterine cavity (Bulun S E. N. Engl. J. Med. 360: 3: 268-279, 2009). Endometrial lesions are found mainly on the peritoneum in the pelvic cavity and the ovaries but they are also found on the fallopian tube and the rectovaginal septum (Giudice et al. Lancet 364: 9447: 1789-1799, 2004). Common symptoms of endometriosis include chronic pain, dyspareunia, dysmennorhea and infertility (Giudice et al. Lancet 364: 9447: 1789-1799, 2004). Approximately 6-10% o...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/10A61K45/06
CPCA61K45/06A61K38/10C07K7/08A61P15/00
Inventor SINGH, VINAY, K.
Owner SYNG PHARMA
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