IL41416A - Injectable oily peptide preparations and their manufactur - Google Patents
Injectable oily peptide preparations and their manufacturInfo
- Publication number
- IL41416A IL41416A IL41416A IL4141673A IL41416A IL 41416 A IL41416 A IL 41416A IL 41416 A IL41416 A IL 41416A IL 4141673 A IL4141673 A IL 4141673A IL 41416 A IL41416 A IL 41416A
- Authority
- IL
- Israel
- Prior art keywords
- preparations
- peptide
- contain
- process according
- usable salts
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims 41
- 108090000765 processed proteins & peptides Proteins 0.000 title claims 35
- 150000003839 salts Chemical class 0.000 claims 25
- 238000000034 method Methods 0.000 claims 22
- 235000001014 amino acid Nutrition 0.000 claims 18
- 150000001413 amino acids Chemical class 0.000 claims 18
- 235000014113 dietary fatty acids Nutrition 0.000 claims 16
- 229930195729 fatty acid Natural products 0.000 claims 16
- 239000000194 fatty acid Substances 0.000 claims 16
- -1 fatty acid salts Chemical class 0.000 claims 14
- 125000004432 carbon atom Chemical group C* 0.000 claims 9
- 102000004196 processed proteins & peptides Human genes 0.000 claims 9
- 159000000013 aluminium salts Chemical class 0.000 claims 7
- 229910000329 aluminium sulfate Inorganic materials 0.000 claims 7
- 150000004665 fatty acids Chemical class 0.000 claims 7
- 239000003921 oil Substances 0.000 claims 7
- 235000019198 oils Nutrition 0.000 claims 7
- 229920006395 saturated elastomer Polymers 0.000 claims 7
- 150000004671 saturated fatty acids Chemical class 0.000 claims 7
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims 7
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims 7
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims 6
- 239000002156 adsorbate Substances 0.000 claims 5
- 235000003441 saturated fatty acids Nutrition 0.000 claims 5
- 239000002253 acid Substances 0.000 claims 3
- 239000000813 peptide hormone Substances 0.000 claims 3
- 102000055006 Calcitonin Human genes 0.000 claims 2
- 108060001064 Calcitonin Proteins 0.000 claims 2
- 229930195711 D-Serine Natural products 0.000 claims 2
- 235000019483 Peanut oil Nutrition 0.000 claims 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 2
- 229910052782 aluminium Inorganic materials 0.000 claims 2
- 239000004411 aluminium Substances 0.000 claims 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000000312 peanut oil Substances 0.000 claims 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- 102400000739 Corticotropin Human genes 0.000 claims 1
- 101800000414 Corticotropin Proteins 0.000 claims 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- XMLNCADGRIEXPK-KUMOIWDRSA-M chembl2146143 Chemical compound [Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N+]2(C)C)C(=O)C(CO)C1=CC=CC=C1 XMLNCADGRIEXPK-KUMOIWDRSA-M 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 claims 1
- 125000005456 glyceride group Chemical group 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 150000004668 long chain fatty acids Chemical class 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
Classifications
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A61K38/35—Corticotropin [ACTH]
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH229972A CH574247A5 (en) | 1972-02-17 | 1972-02-17 | Oily, injectable peptide/aluminium alkanoate compsns - - with prolonged duration of activity |
| CH1782972 | 1972-12-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL41416A0 IL41416A0 (en) | 1973-03-30 |
| IL41416A true IL41416A (en) | 1976-03-31 |
Family
ID=25690055
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL41416A IL41416A (en) | 1972-02-17 | 1973-01-29 | Injectable oily peptide preparations and their manufactur |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US3869549A (cs) |
| JP (1) | JPS4892516A (cs) |
| AR (1) | AR197116A1 (cs) |
| AT (1) | AT335615B (cs) |
| AU (1) | AU472655B2 (cs) |
| BE (1) | BE795516A (cs) |
| CS (1) | CS172967B2 (cs) |
| DD (1) | DD102584A5 (cs) |
| DE (1) | DE2306075A1 (cs) |
| DK (1) | DK134098B (cs) |
| ES (1) | ES411655A1 (cs) |
| FR (1) | FR2181734B1 (cs) |
| GB (1) | GB1418408A (cs) |
| IE (1) | IE37151B1 (cs) |
| IL (1) | IL41416A (cs) |
| NL (1) | NL7300953A (cs) |
| PL (1) | PL90318B1 (cs) |
| SE (1) | SE7600435L (cs) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2254043C2 (de) * | 1972-11-04 | 1985-01-24 | Hoechst Ag, 6230 Frankfurt | LH-Releasing Hormon zur nasalen Applikation |
| DE2254061A1 (de) * | 1972-11-04 | 1974-05-16 | Hoechst Ag | Lh-releasing hormon zur nasalen applikation |
| JPS528375B2 (cs) * | 1973-07-02 | 1977-03-09 | ||
| GB1575343A (en) * | 1977-05-10 | 1980-09-17 | Ici Ltd | Method for preparing liposome compositions containing biologically active compounds |
| JPS55118415A (en) * | 1979-02-28 | 1980-09-11 | Pii Papahadojiyopo Dometoriosu | Method of encapsulating biologically active substance in lipoid cell |
| US4772466A (en) * | 1983-08-22 | 1988-09-20 | Syntex (U.S.A.) Inc. | Vaccines comprising polyoxypropylene-polyoxyethylene block polymer based adjuvants |
| US4770874A (en) * | 1983-08-22 | 1988-09-13 | Syntex (U.S.A.) Inc. | Polyoxypropylene-polyoxyethylene block polymer based adjuvants |
| US4933179A (en) * | 1983-08-22 | 1990-06-12 | Syntex (U.S.A.) Inc. | Feline leukemia virus antigen vaccines |
| US4606918A (en) * | 1983-08-22 | 1986-08-19 | Syntex (U.S.A.) Inc. | Polyoxypropylene-polyoxyethylene block polymer based adjuvants |
| US5086041A (en) * | 1984-10-04 | 1992-02-04 | Monsanto Company | Methods of using prolonged release somatotropin compositions |
| US5411951A (en) * | 1984-10-04 | 1995-05-02 | Monsanto Company | Prolonged release of biologically active somatotropin |
| US5474980A (en) * | 1984-10-04 | 1995-12-12 | Monsanto Company | Prolonged release of biologically active somatotropins |
| KR890002631B1 (ko) * | 1984-10-04 | 1989-07-21 | 몬산토 캄파니 | 생물학적으로 활성인 소마토트로핀을 지속적으로 유리하는 조성물 |
| DE3502099A1 (de) * | 1985-01-23 | 1986-08-07 | Dieter Prof. Dr. Dr. 5883 Kierspe Aderhold | Therapeutisches, peptid- und/oder aminosaeurehaltiges mittel |
| US4650854A (en) * | 1985-06-06 | 1987-03-17 | Usv Pharmaceutical Corporation | Amide analogs of calcitonin |
| US4804742A (en) * | 1985-06-06 | 1989-02-14 | Rorer Pharmaceutical Corporation | Amide analogs of calcitonin |
| US4775659A (en) * | 1985-08-19 | 1988-10-04 | Eli Lilly And Company | Injectable semi-solid formulations |
| IL79765A (en) * | 1985-08-23 | 1992-02-16 | Lilly Co Eli | Injectable sustained release formulations of bovine somatotropin |
| US5554372A (en) * | 1986-09-22 | 1996-09-10 | Emory University | Methods and vaccines comprising surface-active copolymers |
| US5179079A (en) * | 1986-12-16 | 1993-01-12 | Novo Nordisk A/S | Nasal formulation and intranasal administration therewith |
| US5635161A (en) * | 1995-06-07 | 1997-06-03 | Abbott Laboratories | Aerosol drug formulations containing vegetable oils |
| KR19990071255A (ko) | 1998-02-28 | 1999-09-15 | 성재갑 | 소마토트로핀과 비타민의 합제 조성물 |
| US7919109B2 (en) | 1999-02-08 | 2011-04-05 | Intarcia Therapeutics, Inc. | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicles |
| US7258869B1 (en) | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| WO2006097793A2 (en) * | 2004-04-15 | 2006-09-21 | Chiasma, Ltd. | Compositions capable of facilitating penetration across a biological barrier |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| GB0511269D0 (en) * | 2005-06-02 | 2005-07-13 | Creative Peptides Sweden Ab | Sustained release preparation of pro-insulin C-peptide |
| AU2007266475B2 (en) | 2006-05-30 | 2009-12-03 | Intarcia Therapeutics, Inc. | Two-piece, internal-channel osmotic delivery system flow modulator |
| NZ574524A (en) | 2006-08-09 | 2011-07-29 | Intarcia Therapeutics Inc | Piston assembly for positioning lumen of a reservoir for an osmotic delivery having a columnar body and a spring |
| IL290847B2 (en) | 2007-04-23 | 2024-11-01 | Intarcia Therapeutics Inc | Suspension formulations of insulinotropic peptides and uses thereof |
| US8968786B2 (en) | 2007-06-22 | 2015-03-03 | Board Of Regents, The University Of Texas System | Formation of stable submicron peptide or protein particles by thin film freezing |
| EP2240155B1 (en) | 2008-02-13 | 2012-06-06 | Intarcia Therapeutics, Inc | Devices, formulations, and methods for delivery of multiple beneficial agents |
| PL2343982T3 (pl) | 2008-09-17 | 2017-10-31 | Chiasma Inc | Kompozycje farmaceutyczne i związane z nimi sposoby dostarczania |
| JP5711138B2 (ja) | 2008-11-16 | 2015-04-30 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | 高濃度の低粘度懸濁液 |
| RU2753280C2 (ru) | 2009-09-28 | 2021-08-12 | Интарсия Терапьютикс, Инк. | Быстрое достижение и/или прекращение существенной стабильной доставки лекарственного средства |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| EA201692083A1 (ru) | 2014-04-16 | 2017-03-31 | Вейкс-Фарма Гмбх | Фармацевтическая композиция для ветеринарии и ее применение |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| DK3253401T3 (da) | 2015-02-03 | 2025-05-19 | Amryt Endo Inc | Behandling af akromegali med oral octreotid |
| KR20240042548A (ko) | 2015-06-03 | 2024-04-02 | 인타르시아 세라퓨틱스 인코포레이티드 | 임플란트 배치 및 제거 시스템들 |
| CL2016000217A1 (es) * | 2016-01-27 | 2016-07-01 | Farmacologia En Aquacultura Veterinaria Fav S A | Nueva composición veterinaria inyectable para la sincronización del desove en peces |
| EP3733694A1 (en) | 2016-05-16 | 2020-11-04 | Intarcia Therapeutics, Inc | Glucagon-receptor selective polypeptides and methods of use thereof |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| WO2018129058A1 (en) | 2017-01-03 | 2018-07-12 | Intarcia Therapeutics, Inc. | Methods comprising continuous administration of a glp-1 receptor agonist and co-adminstration of a drug |
| US11141457B1 (en) | 2020-12-28 | 2021-10-12 | Amryt Endo, Inc. | Oral octreotide therapy and contraceptive methods |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE950676C (de) * | 1948-01-06 | 1956-10-11 | Bristol Lab Inc | Verfahren zur Herstellung eines injizierbaren Arzneimittels |
| DE920148C (de) * | 1951-03-31 | 1954-11-15 | Nyegaard & Co As | Verfahren zur Herstellung von Adrenocorticotrophin-Praeparaten mit verlaengerter Wirkungsdauer |
| US2944940A (en) * | 1956-01-16 | 1960-07-12 | Armour & Co | Adrenocorticotrophin and zinc composition |
| US2945783A (en) * | 1957-06-20 | 1960-07-19 | Reheis Company Inc | Aluminum protein antacid and process of making |
-
0
- BE BE795516D patent/BE795516A/xx unknown
-
1973
- 1973-01-23 NL NL7300953A patent/NL7300953A/xx unknown
- 1973-01-29 IL IL41416A patent/IL41416A/en unknown
- 1973-01-29 IE IE135/73A patent/IE37151B1/xx unknown
- 1973-02-05 US US329519A patent/US3869549A/en not_active Expired - Lifetime
- 1973-02-08 DE DE2306075A patent/DE2306075A1/de active Pending
- 1973-02-14 AR AR246593A patent/AR197116A1/es active
- 1973-02-15 AU AU52189/73A patent/AU472655B2/en not_active Expired
- 1973-02-15 CS CS1106A patent/CS172967B2/cs unknown
- 1973-02-15 FR FR7305303A patent/FR2181734B1/fr not_active Expired
- 1973-02-15 PL PL1973160769A patent/PL90318B1/pl unknown
- 1973-02-15 ES ES411655A patent/ES411655A1/es not_active Expired
- 1973-02-16 DK DK86073AA patent/DK134098B/da unknown
- 1973-02-16 GB GB773573A patent/GB1418408A/en not_active Expired
- 1973-02-16 DD DD168904A patent/DD102584A5/xx unknown
- 1973-02-16 AT AT140873A patent/AT335615B/de not_active IP Right Cessation
- 1973-02-17 JP JP48018908A patent/JPS4892516A/ja active Pending
-
1976
- 1976-01-16 SE SE7600435A patent/SE7600435L/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL90318B1 (cs) | 1977-01-31 |
| JPS4892516A (cs) | 1973-11-30 |
| AT335615B (de) | 1977-03-25 |
| DK134098C (cs) | 1977-02-21 |
| ATA140873A (de) | 1976-07-15 |
| GB1418408A (en) | 1975-12-17 |
| DE2306075A1 (de) | 1973-08-23 |
| FR2181734A1 (cs) | 1973-12-07 |
| AR197116A1 (es) | 1974-03-15 |
| ES411655A1 (es) | 1976-09-01 |
| AU5218973A (en) | 1974-08-15 |
| IE37151B1 (en) | 1977-05-11 |
| IL41416A0 (en) | 1973-03-30 |
| SE7600435L (sv) | 1976-01-16 |
| DD102584A5 (cs) | 1973-12-20 |
| DK134098B (da) | 1976-09-13 |
| NL7300953A (cs) | 1973-08-21 |
| CS172967B2 (cs) | 1977-01-28 |
| AU472655B2 (en) | 1976-06-03 |
| US3869549A (en) | 1975-03-04 |
| FR2181734B1 (cs) | 1975-10-10 |
| BE795516A (fr) | 1973-08-16 |
| IE37151L (en) | 1973-08-17 |
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