IL216418A - Incalcitol for use in the treatment or prevention of vitamin-related diseases d - Google Patents
Incalcitol for use in the treatment or prevention of vitamin-related diseases dInfo
- Publication number
- IL216418A IL216418A IL216418A IL21641811A IL216418A IL 216418 A IL216418 A IL 216418A IL 216418 A IL216418 A IL 216418A IL 21641811 A IL21641811 A IL 21641811A IL 216418 A IL216418 A IL 216418A
- Authority
- IL
- Israel
- Prior art keywords
- inecalcitol
- treating
- associated disorders
- vitamin
- day
- Prior art date
Links
- BUDPDEVHCQIFNU-PUBYVPDWSA-N inecalcitol Chemical compound C1(/[C@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CC#CC(C)(C)O)C)=C/C=C1/C[C@@H](O)C[C@H](O)C1=C BUDPDEVHCQIFNU-PUBYVPDWSA-N 0.000 title abstract 2
- 229950003028 inecalcitol Drugs 0.000 title abstract 2
- 229940046008 vitamin d Drugs 0.000 title abstract 2
- 208000023275 Autoimmune disease Diseases 0.000 abstract 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 abstract 1
- 201000002980 Hyperparathyroidism Diseases 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 208000001132 Osteoporosis Diseases 0.000 abstract 1
- 201000004681 Psoriasis Diseases 0.000 abstract 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 abstract 1
- 229930003316 Vitamin D Natural products 0.000 abstract 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 201000006417 multiple sclerosis Diseases 0.000 abstract 1
- 208000005368 osteomalacia Diseases 0.000 abstract 1
- 208000007442 rickets Diseases 0.000 abstract 1
- 235000019166 vitamin D Nutrition 0.000 abstract 1
- 239000011710 vitamin D Substances 0.000 abstract 1
- 150000003710 vitamin D derivatives Chemical class 0.000 abstract 1
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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
- A61P5/20—Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of PTH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Reproductive Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Physiology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17990609P | 2009-05-20 | 2009-05-20 | |
| PCT/EP2010/056832 WO2010145903A1 (en) | 2009-05-20 | 2010-05-18 | New therapeutical uses of inecalcitol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL216418A0 IL216418A0 (en) | 2012-02-29 |
| IL216418A true IL216418A (en) | 2015-09-24 |
Family
ID=42308305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL216418A IL216418A (en) | 2009-05-20 | 2011-11-17 | Incalcitol for use in the treatment or prevention of vitamin-related diseases d |
Country Status (23)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2360145T3 (da) | 2010-01-26 | 2012-07-09 | Hybrigenics Sa | Hidtil ukendt fremgangsmåde til isomerisering af kondenserede bicykliske strukturer og fremstilling af D-vitaminanaloger, der omfatter disse |
| EP2407152A1 (en) * | 2010-07-15 | 2012-01-18 | Hybrigenics S.A. | Formulations of 14-epi-analogues of vitamin D |
| AU2011278346B2 (en) * | 2010-07-15 | 2016-04-07 | Hybrigenics Sa | New formulations of 14 - epi -analogues of vitamin D |
| US20120015913A1 (en) | 2010-07-15 | 2012-01-19 | Delansorne Remi | Formulations of 14-EPI-Analogues of Vitamin D |
| WO2015193480A1 (en) * | 2014-06-19 | 2015-12-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Composition comprising a combination of dna methylation inhibitor and a vitamin d receptor agonist for the treatment of drug resistant cancer or for the prevention of tumor relapse |
| SG11201809501PA (en) | 2016-06-06 | 2018-12-28 | Celgene Corp | Treatment of a hematologic malignancy with 2-(4-chlorophenyl)-n-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide |
| JP2020143008A (ja) * | 2019-03-05 | 2020-09-10 | 達也 楠堂 | 新規褐色脂肪細胞分化誘導剤 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU699200B2 (en) | 1993-07-09 | 1998-11-26 | Roger Bouillon | Novel structural analogues of vitamin D |
| US6242434B1 (en) * | 1997-08-08 | 2001-06-05 | Bone Care International, Inc. | 24-hydroxyvitamin D, analogs and uses thereof |
| GB0305332D0 (en) * | 2003-03-10 | 2003-04-09 | Leuven K U Res & Dev | Biological evaluation of novel vitamin D analogues |
| CA2580962A1 (en) * | 2004-09-24 | 2006-04-06 | Bioxell S.P.A. | 20-cycloalkyl,26,27-alkyl/haloalkyl vitamin d3 compounds and methods of use thereof |
-
2010
- 2010-05-18 NZ NZ596497A patent/NZ596497A/xx not_active IP Right Cessation
- 2010-05-18 EP EP10163156A patent/EP2263677B1/en active Active
- 2010-05-18 KR KR1020117030464A patent/KR101845320B1/ko not_active Expired - Fee Related
- 2010-05-18 AT AT10163156T patent/ATE505194T1/de active
- 2010-05-18 SI SI201030002T patent/SI2263677T1/sl unknown
- 2010-05-18 BR BRPI1009056-8A patent/BRPI1009056A2/pt not_active Application Discontinuation
- 2010-05-18 JP JP2012511265A patent/JP2012527424A/ja active Pending
- 2010-05-18 RU RU2011151854/15A patent/RU2571490C2/ru not_active IP Right Cessation
- 2010-05-18 SG SG2011085776A patent/SG176581A1/en unknown
- 2010-05-18 WO PCT/EP2010/056832 patent/WO2010145903A1/en not_active Ceased
- 2010-05-18 MX MX2011012330A patent/MX2011012330A/es active IP Right Grant
- 2010-05-18 CA CA2762458A patent/CA2762458C/en not_active Expired - Fee Related
- 2010-05-18 PT PT10163156T patent/PT2263677E/pt unknown
- 2010-05-18 UA UAA201113630A patent/UA105792C2/uk unknown
- 2010-05-18 AU AU2010261967A patent/AU2010261967B2/en not_active Ceased
- 2010-05-18 PL PL10163156T patent/PL2263677T3/pl unknown
- 2010-05-18 CN CN2010800222064A patent/CN102448466A/zh active Pending
- 2010-05-18 US US12/782,301 patent/US8481514B2/en not_active Expired - Fee Related
- 2010-05-18 ES ES10163156T patent/ES2363070T3/es active Active
- 2010-05-18 DE DE602010000019T patent/DE602010000019D1/de active Active
- 2010-05-18 DK DK10163156.2T patent/DK2263677T3/da active
-
2011
- 2011-06-09 HR HR20110433T patent/HRP20110433T1/hr unknown
- 2011-11-17 IL IL216418A patent/IL216418A/en not_active IP Right Cessation
-
2016
- 2016-06-09 JP JP2016115489A patent/JP2016179994A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL216418A0 (en) | 2012-02-29 |
| SI2263677T1 (sl) | 2011-07-29 |
| UA105792C2 (uk) | 2014-06-25 |
| EP2263677B1 (en) | 2011-04-13 |
| RU2011151854A (ru) | 2013-06-27 |
| RU2571490C2 (ru) | 2015-12-20 |
| JP2016179994A (ja) | 2016-10-13 |
| KR20120017075A (ko) | 2012-02-27 |
| EP2263677A1 (en) | 2010-12-22 |
| SG176581A1 (en) | 2012-01-30 |
| PL2263677T3 (pl) | 2011-09-30 |
| CN102448466A (zh) | 2012-05-09 |
| US20110015276A1 (en) | 2011-01-20 |
| DE602010000019D1 (de) | 2011-05-26 |
| JP2012527424A (ja) | 2012-11-08 |
| AU2010261967B2 (en) | 2016-03-03 |
| ES2363070T3 (es) | 2011-07-19 |
| WO2010145903A1 (en) | 2010-12-23 |
| MX2011012330A (es) | 2011-12-16 |
| ATE505194T1 (de) | 2011-04-15 |
| AU2010261967A1 (en) | 2011-12-08 |
| DK2263677T3 (da) | 2011-06-06 |
| CA2762458A1 (en) | 2010-12-23 |
| HRP20110433T1 (hr) | 2011-07-31 |
| US8481514B2 (en) | 2013-07-09 |
| NZ596497A (en) | 2013-05-31 |
| KR101845320B1 (ko) | 2018-04-04 |
| PT2263677E (pt) | 2011-06-01 |
| BRPI1009056A2 (pt) | 2020-06-02 |
| CA2762458C (en) | 2018-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IL216418A0 (en) | New therapeutical uses of inecalcitol | |
| CR20240003A (es) | Restos de administración terapéutica novedosos y usos de estos | |
| IL219857A0 (en) | Mitotic kinesin inhibitors, pharmaceutical compositions comprising them, uses thereof in the manufacture of a medicament for the treatment of disease or disorder in a human or animal that can be treated by inhibiting mitosis | |
| WO2006120682A3 (en) | Compositions and methods for treating hyperproliferative epidermal diseases | |
| MX2013013809A (es) | Dispositivos expandibles con revestimiento de una composicion de paclitaxel. | |
| MX2010004074A (es) | Combinacion 059. | |
| NO20071428L (no) | Kombinasjon inneholdende ZD6474 og Imatinib | |
| TN2012000062A1 (en) | Jak 2 inhibitors and their use for the treatment of myeloproliferative deseases and cancer | |
| WO2012018948A3 (en) | Combination therapy for the treatment of prostate carcinoma | |
| DOP2007000053A (es) | Compuestos de tetrahidropiridotienopirimidina y métodos para su empleo | |
| WO2010144721A3 (en) | Model systems and treatment regimes for treatment of neurological disease | |
| WO2010030781A3 (en) | Aromatic carboxylic acid derivatives for treatment and prophylaxis of gastrointestinal diseases including colon cancer | |
| NO20071426L (no) | Kreft kombinasjonsbehandling omfattende AZD2171 og Imatinib | |
| WO2006057884A3 (en) | 2α-METHYL AND 2ß-METHYL ANALOGS OF 19,26,27-TRINOR-(20S)-1α-HYDROXYVITAMIN D3 AND THEIR USES | |
| WO2012142615A3 (en) | Auranofin and auranofin analogs useful to treat proliferative disease and disorders | |
| SG158089A1 (en) | Antiangiogenesis therapy of autoimmune disease in patients who have failed prior therapy | |
| MX2009003241A (es) | Analogos de 2-metilen-(20r,25s)-19,27-dinor-(22e)-vitamina d. | |
| UY29161A1 (es) | Nuevos heterociclos | |
| WO2006057900A3 (en) | 17,20(z)-dehydro vitamin d analogs and their uses | |
| NO20076657L (no) | Kombinasjonsterapi av cancer med AZD2171 og gemcitabin | |
| NZ606678A (en) | Formulations of 14-epi-analogues of vitamin d | |
| WO2010065563A3 (en) | Apratoxin therapeutic agents: mechanism and methods of treatment | |
| MX2009002944A (es) | Analogos de 2-metilen-(20s,25s)-19,27-dinor-(22e)-vitamina d. | |
| WO2012153253A3 (en) | Aromatic compounds and metal complexes thereof | |
| SI1596879T1 (sl) | Uporaba spojine kahalalida za pripravo zdravila za zdravljenje luskavice |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |