SE9404196D0 - New antithrombotic formulation - Google Patents

New antithrombotic formulation

Info

Publication number
SE9404196D0
SE9404196D0 SE9404196A SE9404196A SE9404196D0 SE 9404196 D0 SE9404196 D0 SE 9404196D0 SE 9404196 A SE9404196 A SE 9404196A SE 9404196 A SE9404196 A SE 9404196A SE 9404196 D0 SE9404196 D0 SE 9404196D0
Authority
SE
Sweden
Prior art keywords
formulation
pct
thromboembolism
sec
date
Prior art date
Application number
SE9404196A
Other languages
English (en)
Swedish (sv)
Inventor
Jan-Erik Loefroth
Anna-Lena Ungell
Original Assignee
Astra Ab
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 Astra Ab filed Critical Astra Ab
Priority to SE9404196A priority Critical patent/SE9404196D0/xx
Publication of SE9404196D0 publication Critical patent/SE9404196D0/xx
Priority to IL11615395A priority patent/IL116153A/xx
Priority to EP95940490A priority patent/EP0799052B1/fr
Priority to PT95940490T priority patent/PT799052E/pt
Priority to BR9509853A priority patent/BR9509853A/pt
Priority to CA002206459A priority patent/CA2206459A1/fr
Priority to PL95320692A priority patent/PL320692A1/xx
Priority to EE9700121A priority patent/EE03338B1/xx
Priority to HU9800503A priority patent/HU216631B/hu
Priority to CZ971470A priority patent/CZ147097A3/cs
Priority to AT95940490T priority patent/ATE208628T1/de
Priority to CN95196581A priority patent/CN1168635A/zh
Priority to DE69523943T priority patent/DE69523943T2/de
Priority to AU41915/96A priority patent/AU689994B2/en
Priority to US08/564,122 priority patent/US5795896A/en
Priority to JP8518675A priority patent/JPH10513438A/ja
Priority to DK95940490T priority patent/DK0799052T3/da
Priority to PCT/SE1995/001425 priority patent/WO1996016671A1/fr
Priority to ES95940490T priority patent/ES2168395T3/es
Priority to NZ297118A priority patent/NZ297118A/xx
Priority to SK617-97A priority patent/SK61797A3/sk
Priority to TR95/01517A priority patent/TR199501517A2/xx
Priority to ARP950100405A priority patent/AR002254A1/es
Priority to ZA9510242A priority patent/ZA9510242B/xx
Priority to IS4483A priority patent/IS4483A/is
Priority to MXPA/A/1997/003975A priority patent/MXPA97003975A/xx
Priority to NO972475A priority patent/NO972475L/no
Priority to FI972332A priority patent/FI972332A0/fi

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55Protease inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)
  • Cephalosporin Compounds (AREA)
SE9404196A 1994-12-02 1994-12-02 New antithrombotic formulation SE9404196D0 (sv)

Priority Applications (28)

Application Number Priority Date Filing Date Title
SE9404196A SE9404196D0 (sv) 1994-12-02 1994-12-02 New antithrombotic formulation
IL11615395A IL116153A (en) 1994-12-02 1995-11-27 Antithrombotic formulation and process for its manufacturing
SK617-97A SK61797A3 (en) 1994-12-02 1995-11-29 New antithrombotic formulation, process for its manufacturing, and use thereof
DE69523943T DE69523943T2 (de) 1994-12-02 1995-11-29 Neue antithrombotische formulierung, verfahren zur herstellung und gebrauch davon
JP8518675A JPH10513438A (ja) 1994-12-02 1995-11-29 新規な抗血栓症剤、その製造法およびその使用
BR9509853A BR9509853A (pt) 1994-12-02 1995-11-29 Formulação farmacêutica uso da mesma e processos para fabricar a mesma para tratar um paciente em necessidade de tratamento anti-trombótico para tratar tromboembolismo e para intensificar a absorção do composto terapeuticamente ativo
CA002206459A CA2206459A1 (fr) 1994-12-02 1995-11-29 Nouvelle formulation antithrombotique, son procede de production et son utilisation
PL95320692A PL320692A1 (en) 1994-12-02 1995-11-29 Novel anticoagulant, method of obtaining same and application thereof
EE9700121A EE03338B1 (et) 1994-12-02 1995-11-29 Tromboosivastane ravim, selle valmistamise protsess ja kasutamine
HU9800503A HU216631B (hu) 1994-12-02 1995-11-29 Trombózisellenes gyógyszerkészítmény és eljárás előállítására
CZ971470A CZ147097A3 (cs) 1994-12-02 1995-11-29 Nová antitrombotická formulace, způsob její výroby a její použití
AT95940490T ATE208628T1 (de) 1994-12-02 1995-11-29 Neue antithrombotische formulierung, verfahren zur herstellung und gebrauch davon
CN95196581A CN1168635A (zh) 1994-12-02 1995-11-29 新的抗血栓形成的制剂及制备方法和用途
EP95940490A EP0799052B1 (fr) 1994-12-02 1995-11-29 Nouvelle formulation antithrombotique, son procede de production et son utilisation
AU41915/96A AU689994B2 (en) 1994-12-02 1995-11-29 New antithrombotic formulation, process for its manufacturing, and use thereof
US08/564,122 US5795896A (en) 1994-12-02 1995-11-29 Antithrombotic formulation, process for its manufacturing, and use thereof
PT95940490T PT799052E (pt) 1994-12-02 1995-11-29 Nova formulacao antitrombotica, processo para a sua preparacao e sua utilizacao
DK95940490T DK0799052T3 (da) 1994-12-02 1995-11-29 Ny antihrombotisk formulering, fremgangsmåde til dens fremstilling og anvendelse deraf
PCT/SE1995/001425 WO1996016671A1 (fr) 1994-12-02 1995-11-29 Nouvelle formulation antithrombotique, son procede de production et son utilisation
ES95940490T ES2168395T3 (es) 1994-12-02 1995-11-29 Nueva formulacion antitrombotica, procedimiento para su preparacion y utilizacion de la misma.
NZ297118A NZ297118A (en) 1994-12-02 1995-11-29 Antithrombotic formulation; comprises thrombin inhibitor and one or more absorption enhancing agents
ARP950100405A AR002254A1 (es) 1994-12-02 1995-11-30 Formulacion antitrombotica y procedimiento para su manufactura
TR95/01517A TR199501517A2 (tr) 1994-12-02 1995-11-30 Yeni antitrombotik formül, bunun imal edilmesi icin proses, ve bunun kullanilmasi.
ZA9510242A ZA9510242B (en) 1994-12-02 1995-12-01 New antithrombotic formulation process for its manufacturing and use thereof
IS4483A IS4483A (is) 1994-12-02 1997-05-16 Nýtt segavarnarlyf, aðferð við framleiðslu þess og notkun
MXPA/A/1997/003975A MXPA97003975A (en) 1994-12-02 1997-05-29 New antitrombotic formulation, process for its manufacture and use of the mi
NO972475A NO972475L (no) 1994-12-02 1997-05-30 Ny antitrombotisk formulering, fremgangsmåte for dens fremstilling og anvendelse derav
FI972332A FI972332A0 (fi) 1994-12-02 1997-06-02 Verisuonitukoksia estävä uusi formulaatio, menetelmä sen valmistamiseksi ja sen käyttö

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
SE9404196A SE9404196D0 (sv) 1994-12-02 1994-12-02 New antithrombotic formulation

Publications (1)

Publication Number Publication Date
SE9404196D0 true SE9404196D0 (sv) 1994-12-02

Family

ID=20396207

Family Applications (1)

Application Number Title Priority Date Filing Date
SE9404196A SE9404196D0 (sv) 1994-12-02 1994-12-02 New antithrombotic formulation

Country Status (27)

Country Link
US (1) US5795896A (fr)
EP (1) EP0799052B1 (fr)
JP (1) JPH10513438A (fr)
CN (1) CN1168635A (fr)
AR (1) AR002254A1 (fr)
AT (1) ATE208628T1 (fr)
AU (1) AU689994B2 (fr)
BR (1) BR9509853A (fr)
CA (1) CA2206459A1 (fr)
CZ (1) CZ147097A3 (fr)
DE (1) DE69523943T2 (fr)
DK (1) DK0799052T3 (fr)
EE (1) EE03338B1 (fr)
ES (1) ES2168395T3 (fr)
FI (1) FI972332A0 (fr)
HU (1) HU216631B (fr)
IL (1) IL116153A (fr)
IS (1) IS4483A (fr)
NO (1) NO972475L (fr)
NZ (1) NZ297118A (fr)
PL (1) PL320692A1 (fr)
PT (1) PT799052E (fr)
SE (1) SE9404196D0 (fr)
SK (1) SK61797A3 (fr)
TR (1) TR199501517A2 (fr)
WO (1) WO1996016671A1 (fr)
ZA (1) ZA9510242B (fr)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6984627B1 (en) * 1993-06-03 2006-01-10 Astrazeneca Ab Peptide derivatives
SE9301916D0 (sv) * 1993-06-03 1993-06-03 Ab Astra New peptides derivatives
GB9526273D0 (en) * 1995-12-21 1996-02-21 Astra Ab New prodrugs
TWI238827B (en) * 1995-12-21 2005-09-01 Astrazeneca Ab Prodrugs of thrombin inhibitors
SE9602145D0 (sv) * 1996-05-31 1996-05-31 Astra Ab New improved formulation for treatment of thromboembolism
US6423334B1 (en) * 1997-10-01 2002-07-23 Elan Corporation, Plc Composition and method for enhancing transport across gastrointestinal tract cell layers
AR023510A1 (es) * 1999-04-21 2002-09-04 Astrazeneca Ab Un equipo de partes, formulacion farmaceutica y uso de un inhibidor de trombina.
AR023819A1 (es) * 1999-05-03 2002-09-04 Astrazeneca Ab FORMULACIoN FARMACEUTICA, KIT DE PARTES Y UTILIZACION DE DICHA FORMULACION
SE9902550D0 (sv) * 1999-07-02 1999-07-02 Astra Ab New crystalline forms
SE9904377D0 (sv) * 1999-12-01 1999-12-01 Astra Pharma Prod Pharmaceutical combinations
US6462021B1 (en) 2000-11-06 2002-10-08 Astrazeneca Ab Use of low molecular weight thrombin inhibitor
SE0101932D0 (sv) * 2001-05-31 2001-05-31 Astrazeneca Ab Pharmaceutical combinations
US6884768B2 (en) 2001-06-14 2005-04-26 Otsuka Pharmaceutical Co., Ltd. Medicinal compositions
SE0103590D0 (sv) * 2001-10-26 2001-10-26 Astrazeneca Ab New Combination
SE0203349D0 (sv) * 2002-11-12 2002-11-12 Astrazeneca Ab New use
DK1569912T3 (en) 2002-12-03 2015-06-29 Pharmacyclics Inc 2- (2-hydroxybiphenyl-3-yl) -1h-benzoimidazole-5-carboxamidine derivatives as factor VIIa inhibitors.
US7345093B2 (en) * 2004-04-27 2008-03-18 Formatech, Inc. Methods of enhancing solubility of compounds
US9895444B2 (en) 2004-08-25 2018-02-20 Aegis Therapeutics, Llc Compositions for drug administration
US20060046962A1 (en) * 2004-08-25 2006-03-02 Aegis Therapeutics Llc Absorption enhancers for drug administration
US20090047347A1 (en) * 2005-07-29 2009-02-19 Aegis Therapeutics, Inc. Compositions for Drug Administration
US20140162965A1 (en) 2004-08-25 2014-06-12 Aegis Therapeutics, Inc. Compositions for oral drug administration
US8268791B2 (en) * 2004-08-25 2012-09-18 Aegis Therapeutics, Llc. Alkylglycoside compositions for drug administration
US8226949B2 (en) 2006-06-23 2012-07-24 Aegis Therapeutics Llc Stabilizing alkylglycoside compositions and methods thereof
RU2354647C2 (ru) 2007-06-28 2009-05-10 Общество С Ограниченной Ответственностью "Бионика" Новые соединения, обладающие функцией ингибиторов тромбина, и фармацевтические композиции на их основе
ES2586032T3 (es) 2008-03-28 2016-10-11 Hale Biopharma Ventures, Llc Administración de composiciones de benzodiazepinas
US8541360B2 (en) * 2008-11-19 2013-09-24 Ben Venue Laboratories, Inc. Parenteral formulations comprising sugar-based esters and ethers
US8440631B2 (en) 2008-12-22 2013-05-14 Aegis Therapeutics, Llc Compositions for drug administration
US20100215730A1 (en) * 2009-02-20 2010-08-26 Intrepid Therapeutics, Inc. Compositions for Nasal Administration of Phenothiazines
WO2011038068A1 (fr) * 2009-09-23 2011-03-31 Formatech, Inc. Méthodes de préparation de liposomes
US10143652B2 (en) 2009-09-23 2018-12-04 Curirx Inc. Methods for the preparation of liposomes
US20110070294A1 (en) * 2009-09-23 2011-03-24 Javeri Indu Methods for the Administration of Drugs Using Liposomes
WO2012174158A2 (fr) 2011-06-14 2012-12-20 Hale Biopharma Ventures, Llc Administration de benzodiazépine
WO2019157099A1 (fr) 2018-02-06 2019-08-15 Aegis Therapeutics, Llc Formulations d'épinéphrine intranasale et méthodes de traitement d'une maladie

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU178398B (en) * 1979-06-12 1982-04-28 Gyogyszerkutato Intezet Process for producing new agmatine derivatives of activity against haemagglutination
US4568636A (en) * 1981-03-25 1986-02-04 Pentapharm Ag Tripeptide derivatives
US4395401A (en) * 1981-09-09 1983-07-26 Smithkline Beckman Corporation Renally active dipeptides
HU192646B (en) * 1984-12-21 1987-06-29 Gyogyszerkutato Intezet Process for preparing new n-alkyl-peptide aldehydes
ZA86746B (en) * 1985-02-04 1986-09-24 Merrell Dow Pharma Novel peptidase inhibitors
DE3505555A1 (de) * 1985-02-18 1986-09-11 Behringwerke Ag, 3550 Marburg Neue oligopeptidylargininolderivate und deren homologe, verfahren zu deren herstellung, deren verwendung und diese enthaltende mittel
PT84170B (pt) * 1986-01-24 1989-03-30 Sanofi Sa Processo para a preparacao de derivados n alfa-substituidos das n alfa-aril-sulfonilaminoacil d-amidinofenil-alaninamidas
DE3606480A1 (de) * 1986-02-28 1987-09-03 Behringwerke Ag Oligopeptidylnitrilderivate, diese enthaltende mittel, verfahren zu ihrer herstellung und ihre verwendung
US5187157A (en) * 1987-06-05 1993-02-16 Du Pont Merck Pharmaceutical Company Peptide boronic acid inhibitors of trypsin-like proteases
EP0362002B1 (fr) * 1988-09-01 1995-07-26 Merrell Dow Pharmaceuticals Inc. Inhibiteurs de protease HIV
ZA897515B (en) * 1988-10-07 1990-06-27 Merrell Dow Pharma Novel peptidase inhibitors
US5053392A (en) * 1989-12-01 1991-10-01 Rhone-Poulenc Rorer Pharmaceuticals Inc. Novel arginine, glycine, aspartic acid derivatives as platelet-aggregation inhibitors
US5110812A (en) * 1990-06-04 1992-05-05 Bristol-Myers Squibb Co. Azetidin-2-one derivatives as serine protease inhibitors
US5037819A (en) * 1990-06-04 1991-08-06 Bristol-Myers Squibb Company Azetidin-2-one derivatives as serine protease inhibitors
TW201303B (fr) * 1990-07-05 1993-03-01 Hoffmann La Roche
GB9017694D0 (en) * 1990-08-13 1990-09-26 Sandoz Ltd Improvements in or relating to organic chemistry
GB9019558D0 (en) * 1990-09-07 1990-10-24 Szelke Michael Enzyme inhibitors
IL99527A (en) * 1990-09-28 1997-08-14 Lilly Co Eli Tripeptide antithrombotic agents
GB9024129D0 (en) * 1990-11-06 1990-12-19 Thrombosis Research Trust Inhibitors and substrates of thrombin
EP0511347A1 (fr) * 1990-11-15 1992-11-04 Pentapharm A.G. Derives de la phenylalanine metasubstitues
DE4115468A1 (de) * 1991-05-11 1992-11-12 Behringwerke Ag Amidinophenylalaninderivate, verfahren zu deren herstellung, deren verwendung und diese enthaltende mittel als antikoagulantien
SE9102462D0 (sv) * 1991-08-28 1991-08-28 Astra Ab New isosteric peptides
NZ245039A (en) * 1991-11-12 1994-12-22 Lilly Co Eli N-phenylalanyl and n-phenylglycyl derivatives of the dipeptide of l-azetidine-2-carboxylic acid and l-arginine aldehyde; anti-blood clotting compositions
SE9103612D0 (sv) * 1991-12-04 1991-12-04 Astra Ab New peptide derivatives
SE9301916D0 (sv) * 1993-06-03 1993-06-03 Ab Astra New peptides derivatives

Also Published As

Publication number Publication date
EP0799052A1 (fr) 1997-10-08
CN1168635A (zh) 1997-12-24
AU689994B2 (en) 1998-04-09
FI972332A (fi) 1997-06-02
HU216631B (hu) 1999-07-28
IS4483A (is) 1997-05-16
NO972475D0 (no) 1997-05-30
CZ147097A3 (cs) 1998-02-18
ATE208628T1 (de) 2001-11-15
FI972332A0 (fi) 1997-06-02
DE69523943D1 (de) 2001-12-20
WO1996016671A1 (fr) 1996-06-06
DE69523943T2 (de) 2002-06-27
IL116153A0 (en) 1996-01-31
NZ297118A (en) 1998-12-23
CA2206459A1 (fr) 1996-06-06
IL116153A (en) 1999-11-30
EE03338B1 (et) 2001-02-15
EP0799052B1 (fr) 2001-11-14
AU4191596A (en) 1996-06-19
AR002254A1 (es) 1998-03-11
ZA9510242B (en) 1996-06-03
PT799052E (pt) 2002-05-31
HUT77655A (hu) 1998-07-28
PL320692A1 (en) 1997-10-27
SK61797A3 (en) 1998-03-04
JPH10513438A (ja) 1998-12-22
TR199501517A2 (tr) 1996-07-21
US5795896A (en) 1998-08-18
DK0799052T3 (da) 2002-02-25
ES2168395T3 (es) 2002-06-16
MX9703975A (es) 1997-09-30
BR9509853A (pt) 1997-12-30
NO972475L (no) 1997-05-30

Similar Documents

Publication Publication Date Title
SE9404196D0 (sv) New antithrombotic formulation
DK0776202T3 (da) Liposomalt indkapslet taxol, dets fremstilling af dets anvendelse
DE69531457D1 (en) Sulfonamide
ES2128552T3 (es) Combinacion de un inhibidor de la biosintesis del colesterol y un inhibidor de la absorcion del colesterol beta-lactama.
UA32429C2 (uk) Засіб для лікування нетримання сечі
HU9700056D0 (en) New pharmaceutical composition for treating pains
EA200000994A1 (ru) Применение кабэрголина при лечении синдрома усталых ног
DE69116380D1 (de) Pharmazeutische zubereitung zur behandlung verlängerter gerinnungszeit
ES2059121T3 (es) Uso de agentes sensibilizantes de insulina para tratar la hipertension.
DE69932510D1 (de) Vaskularisierungsinhibitoren
DK0615751T3 (da) Anvendelse af tachykininantagonister til behandling af emesis
SE9603725D0 (sv) New teatment
ATE190843T1 (de) Zubereitungen zur behandlung von impotenz, die ein alpha-1 inhibitor und ein alpha-2 inhibitor enthalten
SE9402880D0 (sv) New peptide derivatives
DE69705110D1 (de) Topische pharmazeutische zusammensetzungen, welche heparin enthalten
DK0821588T3 (da) Levobupivacain og anvendelse heraf som et anæstetikum til gravide kvinder
DE69924483D1 (de) Kombinationstherapie zur behandlung von tumoren
DE69427116D1 (de) Verwendung von 4'-iodo - 4 - deoxydoxorubicin zur behandlung von amyloidosis
SE9602145D0 (sv) New improved formulation for treatment of thromboembolism
NO984196D0 (no) Fremgangsmåte for behandling av stoffmisbruk
SE9403861D0 (sv) Novel medicinal use
PT1313500E (pt) Associacoes de dalfopristina/quinupristina com o cefpirome
DE3776662D1 (de) Pharmazeutische zusammensetzungen zur behandlung von hyperproliferativer hautkrankheit.
UY26735A1 (es) Métodos y composiciones para tratar flavivirus y pestivirus