WO2015092123A1 - Compositions comprenant glycérophosphoryléthanolamine - Google Patents

Compositions comprenant glycérophosphoryléthanolamine Download PDF

Info

Publication number
WO2015092123A1
WO2015092123A1 PCT/FI2014/050945 FI2014050945W WO2015092123A1 WO 2015092123 A1 WO2015092123 A1 WO 2015092123A1 FI 2014050945 W FI2014050945 W FI 2014050945W WO 2015092123 A1 WO2015092123 A1 WO 2015092123A1
Authority
WO
WIPO (PCT)
Prior art keywords
cancer cells
glycerophosphorylethanolamine
cancer
gpea
cells
Prior art date
Application number
PCT/FI2014/050945
Other languages
English (en)
Inventor
Simo Rasi
Original Assignee
Simo Rasi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Simo Rasi filed Critical Simo Rasi
Publication of WO2015092123A1 publication Critical patent/WO2015092123A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to anticancer agents.
  • the invention relates to glycerophosphorylethanolamine (GPEA) for use in treatment or prevention of cancer, and compositions including GPEA especially for decreasing risk of cancer caused by consumption of dairy products.
  • GPEA glycerophosphorylethanolamine
  • GPEA glycerophosphorylethanolamine
  • the present invention concern glycerophosphorylethanolamine for use in the treatment and/or prevention of cancer.
  • the present invention concerns pharmaceutical composition including GPEA.
  • Figures 1 -4 show the proliferation of a hormone dependent breast cancer cell line (MCF-7) as the function of GPEA concentration.
  • Estradiol (E2) concentration was 0, 1 .3 nM, 33.3 nM and 3333 nM, in Figs 1 -4, respectively.
  • Incubation time was 24 h.
  • Figure 6 shows the effect of GPEA on ERK phosphorylation in MCF-7 breast cancer cells (10 sec incubation.
  • MFI mean fluorescence intensity).
  • Figure 7 shows the proliferation of a hormone independent prostate cancer cell line (PC-3) as the function of GPEA concentration. Incubation time was 24 h. DETAILED DESCRIPTION OF THE INVENTION
  • the present invention concern glycerophosphorylethanolamine (GPEA) for use in the treatment and/or prevention of cancer.
  • the cancer is preferably breast, colon or prostate cancer, more preferably breast or prostate cancer, most preferably breast cancer.
  • the treatment and/or prevention is inhibition of cancer cell proliferation.
  • the cancer cells are preferably selected from breast cancer cells, colon cancer cells and prostate cancer cells, more preferably breast cancer cells and prostate cancer cells, most preferably breast cancer cells.
  • the breast cancer cells are hormone dependent breast cancer cells.
  • An exemplary hormone is oestrogen, in particular estradiol (E2).
  • Exemplary E2 dependent breast cancer cells are MCF-7 cells.
  • the prostate cancer cells are hormone independent prostate cancer cells. According to a particular embodiment the prostate cancer cells are independent to testosterone. According to an exemplary embodiment the prostate cancer cells are PC-3 cells.
  • the present invention concerns a pharmaceutical composition including GPEA.
  • GPEA can be used as such or as its pharmaceutically acceptable salt.
  • pharmaceutically acceptable salt is defined in the review article of Berge et al. [J. Pharm Sci, 66, 1977, 1 ]. Structure of GPEA is shown below.
  • GPEA may be administrated as such or in the form of suitable pharmaceutical composition, using conventional techniques and excipients.
  • An exemplary administration route is the oral route.
  • suitable pharmaceutical compositions include capsules, tablets, solutions, syrups, sachets and vials.
  • the required amount of the active compound may depend on the particular condition to be treated. Any kind of pharmaceutically acceptable solid or liquid carrier or excipient known to those skilled in the medicinal and pharmaceutical arts, may be used in the pharmaceutical preparation.
  • Amounts and regimens for the administration of the pharmaceutical compositions can be determined readily by those with ordinary skill in the clinical art of treating symptoms and disorders. Generally, the dosage depends on considerations such as age, gender and general health of the patient to be treated; kind of concurrent treatment, if any; frequency of the treatment and nature of the effect desired; duration of the symptoms; and other variables. A desired dose may be administered in one or more applications to obtain the desired results. If desired, the pharmaceutical compositions according to the present embodiments may be provided as unit dosage forms. Means and methods for formulating the present pharmaceutical preparations are known to persons skilled in the art, and may be manufactured in a manner which is in itself known, for example, by means of conventional mixing, granulating, dissolving, lyophilizing or similar processes.
  • the present invention concerns a composition, preferably an pharmaceutical composition including GPEA and one or more excipients, wherein the amount of GPEA in the composition is more than 3.5 mg/g, preferably at least 10 mg/g, most preferably at least 100 mg/g.
  • excipients are antiadherents (e.g. magnesium stearate), binders (e.g. saccharides such as sucrose, lactose, starches, cellulose, xylitol, sorbitol and maltitol, proteins such as gelatine, synthetic polymers such as polyvinylpyrrolidone and polyethylene glycol), coatings (e.g. hydroxypropyl methylcellulose), disintegrants (e.g.
  • crosslinked polyvinylpyrrolidone crosslinked sodium carboxymethyl cellulose and sodium starch glycolate
  • fillers e.g. plant cellulose, mannitol, sorbitol, calcium carbonate, and magnesium stearate
  • flavours e.g. mint, cherry, anise, peach, apricot, liquorice and vanilla
  • colours e.g. lubricants (e.g. talk, silica, stearin, magnesium stearate and stearic acid), glidants, sorbents, preservatives (e.g. antioxidants, cysteine, methionine, citric acid, sodium citrate, parabens), and sweeteners (e.g. syrups and sugars).
  • the composition includes freeze-dried colostrum, preferably freeze-dried bovine colostrum, added GPEA, and one or more excipient, wherein the composition includes more than 3.5 mg/g GPEA, preferably at least 10 mg/g GPEA, most preferably at least 100mg/g GPEA.
  • the composition includes freeze-dried bovine colostrum and 3-30% (by weight) added GPEA.
  • the composition is a 600 mg tablet that includes 200 mg freeze- dried bovine colostrum, and 20-200 mg added GPEA.
  • the composition is a 600 mg tablet that includes 200 mg freeze-dried bovine colostrum whey, and 20-200 mg added GPEA.
  • GPEA can be added to the composition during whey manufacturing process or afterwards.
  • An exemplary process for manufacture of bovine colostrum whey has been disclosed in Fl 103089.
  • GPEA is a physiological metabolite normally present in human body. It has been shown that as far as acute toxicology is concerned, oral route up to 3 g/kg does not cause either death of any symptomatology in mice, rats or rabbits [WO 88/07860]. It will be obvious to a person skilled in the art that, as the technology advances, the inventive concept can be implemented in various ways. The invention and its embodiments are not limited to the examples described below but may vary within the scope of the claims.
  • the effect of GPEA on oestrogen-induced intracellular signalling in MCF-7 cells The MCF-7 breast cancer cells were treated with 10 nM E2 and 2 ⁇ GPEA for three days in 24-well plates, 30 000 cells/well. The growth medium was changed to phenol red-free DMEM and the cells were incubated for another 24 h, rinsed with ice-cold PBS, solubilized in 200 ⁇ _ lysis buffer (containing a protease inhibitor), and the plates were frozen at -70 °C for kinase assays.
  • phosphorylated ERK and phosphorylated Src were quantified with commercial immunoassay kits (MILLIPLEX ® MAP: Cell Signalling Buffer and Detection Kit, Phospho Src (Tyr419) Magnetic Bead MAPmateTM ja 2-Plex Total/Phospho ERK Magnetic Bead Kit) and the samples were analysed by Luminex® 200TM analyser. Results are shown in Figures 5 and 6.
  • FIGS 2-4 show proliferation of breast cancer cells (MCF-7) in presence of various concentration of estradiol (E2) as the function of GPEA concentration.
  • E2 estradiol
  • Figure 1 the proliferation was also studied in the absence of E2 ( Figure 1 ).
  • the experiments were performed in the presence of 1 .3 nM, 33.3 nM and 3333 nM estradiol, respectively.
  • GPEA is able to inhibit proliferation of breast cancer cells promoted by E2.
  • Proliferation of MCF-7 cells is known to be promoted by oestrogens. Accordingly, GPEA is able to inhibit proliferation of breast cancer cells in the present of stimulant hormone that is also present in milk and other dairy products.
  • Src is a proto-oncogene encoding a tyrosine kinase expressed in most human tissues, including breast tissue. Its function in the cell is to promote other signals. Src is normally inactive while its activation has been observed in several cancers, including breast and colon cancers. There is also a correlation between elevated Src activity and the severity of the disease.
  • ERKs extracellular signal regulated kinase are intracellular signalling molecules activated by phosphorylation. They belong to MAPK (mitogen activated protein kinase) family and they exist in different forms, e.g. ERK1 (MAPK3) and ERK2 (MAPK1 ).
  • Figure 5 shows the effect of GPEA on E2-induced stimulation of Scr phosphorylation in MCF-7 breast cancer cells. As seen from Figure 5, oestrogen induces elevation of p-Src level ( Figure 5, middle). The effect of E2 is inhibited by GPEA ( Figure 5, right). Accordingly, GPEA prevents the E2-induced stimulation of Src activity in MCF-7 cells.
  • Figure 6 shows the effect on GPEA on ERK phosphorylation in MCF-7 breast cancer cells. According to this experiment, a clear inhibition of ERK phosphorylation is visible, indicating that GPEA prevents Src-activation and thereby, at least Src-mediated activation of ERK is prevented.
  • Figure 7 shows proliferation of prostate cancer cells (PC-3) as the function of GPEA concentration. As shown from the figure, GPEA is able to inhibit proliferation of prostate cancer cells. Further embodiments of the present invention are disclosed in the following numbered clauses
  • GPEA or its pharmaceutically acceptable salt and one or more excipients.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compositions comprenant glycérophosphoryléthanolamine (GPEA), utilisables dans le traitement et/ou la prévention du cancer.
PCT/FI2014/050945 2013-12-18 2014-12-03 Compositions comprenant glycérophosphoryléthanolamine WO2015092123A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FI20130377 2013-12-18
FI20130377 2013-12-18

Publications (1)

Publication Number Publication Date
WO2015092123A1 true WO2015092123A1 (fr) 2015-06-25

Family

ID=52232217

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI2014/050945 WO2015092123A1 (fr) 2013-12-18 2014-12-03 Compositions comprenant glycérophosphoryléthanolamine

Country Status (1)

Country Link
WO (1) WO2015092123A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1988007860A1 (fr) 1987-04-08 1988-10-20 Riace Establishment Compositions pharmaceutiques pour le traitement de syndromes cerebraux psycho-organiques
US5703062A (en) * 1995-12-07 1997-12-30 Clarion Pharmaceuticals Inc. N-het-substituted glycerophosphoethanolamines
US5707978A (en) * 1994-11-22 1998-01-13 Clarion Pharmaceuticals Inc. Heteroaryl-substituted deoxy glycero-phosphoethanolamines
FI103089B (fi) 1994-03-09 1999-04-30 Hi Col Oy Ternimaidon heraan perustuva ravintovalmiste ja menetelmä sen valmista miseksi
US20070065522A1 (en) * 2004-03-18 2007-03-22 Transave, Inc. Administration of high potency platinum compound formulations by inhalation
WO2008109432A2 (fr) * 2007-03-02 2008-09-12 The Board Of Regents Of The University Of Texas System Ciblage thérapeutique des interleukines utilisant l'arnsi dans des liposomes neutres
JP2009203191A (ja) * 2008-02-28 2009-09-10 Kose Corp 美白剤及び美白用皮膚外用剤

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1988007860A1 (fr) 1987-04-08 1988-10-20 Riace Establishment Compositions pharmaceutiques pour le traitement de syndromes cerebraux psycho-organiques
FI103089B (fi) 1994-03-09 1999-04-30 Hi Col Oy Ternimaidon heraan perustuva ravintovalmiste ja menetelmä sen valmista miseksi
US5707978A (en) * 1994-11-22 1998-01-13 Clarion Pharmaceuticals Inc. Heteroaryl-substituted deoxy glycero-phosphoethanolamines
US5703062A (en) * 1995-12-07 1997-12-30 Clarion Pharmaceuticals Inc. N-het-substituted glycerophosphoethanolamines
US20070065522A1 (en) * 2004-03-18 2007-03-22 Transave, Inc. Administration of high potency platinum compound formulations by inhalation
WO2008109432A2 (fr) * 2007-03-02 2008-09-12 The Board Of Regents Of The University Of Texas System Ciblage thérapeutique des interleukines utilisant l'arnsi dans des liposomes neutres
JP2009203191A (ja) * 2008-02-28 2009-09-10 Kose Corp 美白剤及び美白用皮膚外用剤

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BERGE ET AL., J. PHARM SCI, vol. 66, 1977, pages 1
BR. J. NUTRITION, vol. 84, 2000, pages 161 - 166
JI ET AL., BR J CANCER., 14 October 2014 (2014-10-14)
NEAL D. BARNARD, MILK CONSUMPTION AND PROSTATE CANCER, PHYSICIANS COMMITTEE FOR RESPONSIBLE MEDICINE

Similar Documents

Publication Publication Date Title
EP3782634B1 (fr) Compositions pour le traitement des symptômes des voies urinaires inférieures, de l'hyperplasie prostatique bénigne et de la dysfonction érectile et d'autres maladies ou symptômes
KR20120059207A (ko) 동충하초 추출물 또는 이로부터 분리된 코디세핀을 유효성분으로 하는 불면증 개선 및 치료용 약학 조성물
US20220249412A1 (en) Threonate Compounds and Methods of Use Thereof
JP2017507151A (ja) がんの治療のための併用療法としてのエリブリン及びｍＴＯＲ阻害剤の使用
JP5688467B2 (ja) 烏梅抽出物を含有する痴呆（認知症）予防または治療用組成物
JP2018517759A (ja) カルボプラチンを含む組成物及び用途
CN105579036B (zh) 用于改善膀胱尿道协同失调的药剂
TWI733026B (zh) 昭和草萃取物於治療乳癌之用途
CA2761384A1 (fr) Traitement du stress
US20210260146A1 (en) Compositions for preventing or treating diseases or disorders associated with neuro-inflammation, neuro-apoptosis, or neuro-oxidative damage and uses thereof
KR20220157313A (ko) 타우로데옥시콜린산 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 코로나바이러스감염증-19(covid-19) 치료용 조성물
Farah et al. The influence of khat on the in-vitro and in-vivo availability of tetracycline-HCl
WO2015092123A1 (fr) Compositions comprenant glycérophosphoryléthanolamine
KR102279105B1 (ko) 대추나무 뿌리 추출물을 포함하는 신장 질환의 예방 또는 치료용 조성물
AU2015360620A1 (en) Treatment of multiple sclerosis with combination of laquinimod and a statin
US20210161985A1 (en) Compositions for treating female sexual dysfunction
JP2016537428A (ja) エフェドラ・アラタ抽出物及びその使用方法
RU2784869C1 (ru) Чиаураниб для лечения мелкоклеточного рака легкого
TW201444561A (zh) 可治療癌症之藥學組合物
JP2008501785A (ja) 子宮腫瘍の治療用医薬の調製のための７−ｔ−ブトキシイミノメチルカンプトテシンの使用
KR101401002B1 (ko) Ｈｓ1792 또는 이의 약학적으로 허용되는 염을 포함하는 골량 저하 관련 질환의 예방 또는 치료용 약학 조성물 및 건강기능식품
TWI794847B (zh) 用於減少代謝症候群之組合物及其應用
TWI607752B (zh) 含4-乙醯基-安卓奎諾-b之組合物用於製備抑制卵巢癌細胞生長之藥物的用 途
JP2016088851A (ja) タウ蛋白質のリン酸化抑制用組成物
CN105816470A (zh) 20(R)-人参皂苷Rg3在制备缓解或/和治疗糖尿病药物或保健品中的应用及药物

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14820906

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 14820906

Country of ref document: EP

Kind code of ref document: A1