PT94016A - Processo para a producao de inibidores de proteinases - Google Patents

Processo para a producao de inibidores de proteinases

Info

Publication number: PT94016A
Authority: PT; Portugal
Prior art keywords: peptide variants; trypsin inhibitor; inhibitory activity; production; protein inhibitors
Prior art date: 1989-05-13

Application number

PT94016A

Other languages

English (en)

Other versions

PT94016B (pt

Inventor

Hans Fritz

Wolfgang Gebhard

Rathindra Das

Original Assignee

Bayer Ag

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.)

1989-05-13

Filing date

1990-05-11

Publication date

1991-01-08

1990-05-11 Application filed by Bayer Ag filed Critical Bayer Ag

1991-01-08 Publication of PT94016A publication Critical patent/PT94016A/pt

1997-05-28 Publication of PT94016B publication Critical patent/PT94016B/pt

Links

238000000034 method Methods 0.000 title abstract 2
229940121649 protein inhibitor Drugs 0.000 title 1
239000012268 protein inhibitor Substances 0.000 title 1
108090000765 processed proteins & peptides Proteins 0.000 abstract 4
230000002401 inhibitory effect Effects 0.000 abstract 2
LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 abstract 1
241000894006 Bacteria Species 0.000 abstract 1
102000004173 Cathepsin G Human genes 0.000 abstract 1
108090000617 Cathepsin G Proteins 0.000 abstract 1
241000206602 Eukaryota Species 0.000 abstract 1
102000016387 Pancreatic elastase Human genes 0.000 abstract 1
108010067372 Pancreatic elastase Proteins 0.000 abstract 1
108090000113 Plasma Kallikrein Proteins 0.000 abstract 1
102100034869 Plasma kallikrein Human genes 0.000 abstract 1
102000012479 Serine Proteases Human genes 0.000 abstract 1
108010022999 Serine Proteases Proteins 0.000 abstract 1
229940122618 Trypsin inhibitor Drugs 0.000 abstract 1
101710162629 Trypsin inhibitor Proteins 0.000 abstract 1
238000010353 genetic engineering Methods 0.000 abstract 1
108010093564 inter-alpha-inhibitor Proteins 0.000 abstract 1
244000005700 microbiome Species 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
210000002966 serum Anatomy 0.000 abstract 1
239000002753 trypsin inhibitor Substances 0.000 abstract 1
108010088854 urinastatin Proteins 0.000 abstract 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
- C07K14/8114—Kunitz type inhibitors
- 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
- A61K38/55—Protease inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- 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
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Biomedical Technology (AREA)
Hematology (AREA)
Diabetes (AREA)
Zoology (AREA)
Urology & Nephrology (AREA)
Biotechnology (AREA)
General Engineering & Computer Science (AREA)
Wood Science & Technology (AREA)
Pulmonology (AREA)
Plant Pathology (AREA)
Dermatology (AREA)
Immunology (AREA)
Epidemiology (AREA)
Endocrinology (AREA)
Physics & Mathematics (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Reproductive Health (AREA)
Microbiology (AREA)

PT94016A 1989-05-13 1990-05-11 Processo para a producao de inibidores de proteinases PT94016B (pt)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE3915689		1989-05-13
DE4001244		1990-01-18

Publications (2)

Publication Number	Publication Date
PT94016A true PT94016A (pt)	1991-01-08
PT94016B PT94016B (pt)	1997-05-28

Family

ID=25880860

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PT94016A PT94016B (pt)	1989-05-13	1990-05-11	Processo para a producao de inibidores de proteinases

Country Status (17)

Country	Link
US (1)	US5407915A (pt)
EP (1)	EP0401508B1 (pt)
JP (2)	JP3126975B2 (pt)
KR (1)	KR0156246B1 (pt)
AT (1)	ATE114332T1 (pt)
AU (1)	AU623769B2 (pt)
CA (1)	CA2016627C (pt)
DE (1)	DE59007737D1 (pt)
DK (1)	DK0401508T3 (pt)
ES (1)	ES2066033T3 (pt)
GR (1)	GR3015124T3 (pt)
HU (1)	HU214985B (pt)
IE (1)	IE65710B1 (pt)
IL (1)	IL94349A (pt)
NZ (1)	NZ233635A (pt)
PH (1)	PH27530A (pt)
PT (1)	PT94016B (pt)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20060134087A1 (en) *	1988-09-02	2006-06-22	Dyax Corp.	ITI-D1 Kunitz domain mutants as hNE inhibitors
US5663143A (en) *	1988-09-02	1997-09-02	Dyax Corp.	Engineered human-derived kunitz domains that inhibit human neutrophil elastase
US7078383B2 (en) *	1988-09-02	2006-07-18	Dyax Corp.	ITI-D1 Kunitz domain mutants as HNE inhibitors
WO1992015605A2 (en) *	1991-03-01	1992-09-17	Protein Engineering Corporation	Inhibitors of human neutrophil elastase and human cathepsin g
CA2055425A1 (en) *	1990-11-13	1992-05-14	Hideaki Morishita	Polypeptide, dna fragment encoding the same and process for producing the same, and enzyme inhibition process, drug composition and methods of treating using the same
CA2082226A1 (en) *	1991-11-08	1993-05-09	Hideaki Morishita	Polypeptide, dna fragment encoding the same, drug composition containing the same and process for producing the same
IL104327A0 (en) *	1992-01-07	1993-05-13	Novo Nordisk As	Variant of human kunitz-type protease inhibitor
JP2769083B2 (ja) *	1993-02-22	1998-06-25	日清食品株式会社	エラスターゼ阻害活性を有する新規ペプチドおよびその製造方法
JP3570558B2 (ja) *	1993-05-01	2004-09-29	持田製薬株式会社	Ｄｎａ断片およびそれを含むベクター、該ベクターによって形質転換された形質転換体、該ベクターを用いる蛋白質の産生方法
US5650394A (en) *	1993-11-04	1997-07-22	Adeza Biomedical	Use of urinastatin-like compounds to prevent premature delivery
ATE529444T1 (de) *	1994-01-11	2011-11-15	Dyax Corp	Inhibitoren des humanplasmins, die sich von den kunitz domänen ableiten
US6057287A (en)	1994-01-11	2000-05-02	Dyax Corp.	Kallikrein-binding "Kunitz domain" proteins and analogues thereof
AU4868096A (en) *	1995-02-23	1996-09-11	Adeza Biomedical Corporation	Polypeptides derived from urinastatin having calcium channel blocking activity and their use to delay premature delivery
WO1997033996A2 (en) *	1996-03-11	1997-09-18	Bayer Corporation	Human bikunin
US20070140979A1 (en) *	1998-12-22	2007-06-21	Bayer Aktiengesellschaft	Method for accelerating the rate of mucociliary clearance
WO2000037099A2 (en) *	1998-12-22	2000-06-29	Bayer Aktiengesellschaft	Method for accelerating the rate of mucociliary clearance by using a kunitz-type serine protease inhibitor
US6660482B1 (en) *	2000-02-28	2003-12-09	Rhode Island Hospital	Inter-alpha-trypsin inhibitor as a marker for sepsis
KR20040004562A (ko) *	2001-03-27	2004-01-13	어웨어, 인크.	수신기 투과성 ｑ-모드
US7153829B2 (en)	2002-06-07	2006-12-26	Dyax Corp.	Kallikrein-inhibitor therapies
DK2311432T3 (en)	2002-06-07	2015-02-02	Dyax Corp	Modified Kunitz domain polypeptides and their use in reducing ischemia or the onset of a systemic inflammatory response associated with a surgical procedure
TR201900937T4 (tr)	2002-08-28	2019-02-21	Dyax Corp	Organların ve dokuların muhafaza edilmesine yönelik yöntem.
JP2007524348A (ja) *	2003-01-07	2007-08-30	ダイアックス、コープ	クニッツドメインライブラリー
US6989369B2 (en) *	2003-02-07	2006-01-24	Dyax Corp.	Kunitz domain peptides
US7235530B2 (en)	2004-09-27	2007-06-26	Dyax Corporation	Kallikrein inhibitors and anti-thrombolytic agents and uses thereof
US8637454B2 (en) *	2009-01-06	2014-01-28	Dyax Corp.	Treatment of mucositis with kallikrein inhibitors
ES2688093T3 (es)	2010-01-06	2018-10-30	Dyax Corp.	Proteínas de unión a calicreína plasmática
IL269565B2 (en)	2011-01-06	2024-06-01	Dyax Corp	Plasma kallikrein binding proteins
MA39347B2 (fr) *	2014-02-24	2020-05-29	Takeda Pharmaceuticals Co	Protéines de fusion d'uti
EP3122782A4 (en)	2014-03-27	2017-09-13	Dyax Corp.	Compositions and methods for treatment of diabetic macular edema
BR112018011622A2 (pt)	2015-12-11	2018-11-27	Dyax Corp	método para tratar ataque de angioedema hereditário (hae) ou reduzir a taxa de ataque de hae
CA3167336A1 (en)	2020-01-13	2021-07-22	Takeda Pharmaceutical Company Limited	Plasma kallikrein inhibitors and uses thereof for treating pediatric hereditary angioedema attack
BR112022017718A2 (pt)	2020-03-05	2022-11-16	Diamedica Usa Inc	Polipeptídeos de ulinastatina

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU560584B2 (en) *	1983-07-28	1987-04-09	Bayer Aktiengesellschaft	Homologues of aprotinin
US4711848A (en) *	1984-03-14	1987-12-08	Zymogenetics, Inc.	Site specific mutagenesis in alpha-1-antitrypsin
FR2599752B1 (fr) *	1986-06-10	1989-11-03	Transgene Sa	Variants de l'alpha1- antitrypsine utiles notamment comme inhibiteurs de la kallikreine
FR2601033B1 (fr) *	1986-07-02	1990-01-19	Transgene Sa	Variants de l'alpha-antitryspine humaine glycosylee et procede pour la preparation
EP0255011A3 (en) *	1986-07-29	1988-11-23	Miles Inc.	Human inter-alpha-trypsin inhibitor gene

1990
- 1990-05-01 ES ES90108284T patent/ES2066033T3/es not_active Expired - Lifetime
- 1990-05-01 DK DK90108284.2T patent/DK0401508T3/da active
- 1990-05-01 AT AT90108284T patent/ATE114332T1/de not_active IP Right Cessation
- 1990-05-01 EP EP90108284A patent/EP0401508B1/de not_active Expired - Lifetime
- 1990-05-01 DE DE59007737T patent/DE59007737D1/de not_active Expired - Fee Related
- 1990-05-02 PH PH40464A patent/PH27530A/en unknown
- 1990-05-10 IL IL94349A patent/IL94349A/en not_active IP Right Cessation
- 1990-05-10 NZ NZ233635A patent/NZ233635A/en unknown
- 1990-05-11 PT PT94016A patent/PT94016B/pt active IP Right Grant
- 1990-05-11 JP JP02120186A patent/JP3126975B2/ja not_active Expired - Fee Related
- 1990-05-11 HU HU903010A patent/HU214985B/hu not_active IP Right Cessation
- 1990-05-11 CA CA002016627A patent/CA2016627C/en not_active Expired - Fee Related
- 1990-05-11 IE IE171390A patent/IE65710B1/en not_active IP Right Cessation
- 1990-05-11 AU AU54970/90A patent/AU623769B2/en not_active Ceased
- 1990-05-12 KR KR1019900006865A patent/KR0156246B1/ko not_active Expired - Fee Related
1993
- 1993-03-05 US US08/027,602 patent/US5407915A/en not_active Expired - Fee Related
1995
- 1995-02-22 GR GR940403586T patent/GR3015124T3/el unknown
2000
- 2000-09-13 JP JP2000278172A patent/JP2001112492A/ja active Pending

Also Published As

Publication number	Publication date
IL94349A0 (en)	1991-03-10
IL94349A (en)	1998-01-04
DE59007737D1 (de)	1995-01-05
EP0401508B1 (de)	1994-11-23
KR900017607A (ko)	1990-12-19
KR0156246B1 (ko)	1998-11-16
DK0401508T3 (da)	1995-05-15
PT94016B (pt)	1997-05-28
US5407915A (en)	1995-04-18
HU214985B (hu)	1998-08-28
ES2066033T3 (es)	1995-03-01
IE901713L (en)	1990-11-13
NZ233635A (en)	1991-12-23
AU623769B2 (en)	1992-05-21
ATE114332T1 (de)	1994-12-15
HU903010D0 (en)	1990-09-28
CA2016627C (en)	2000-08-22
CA2016627A1 (en)	1990-11-13
AU5497090A (en)	1990-11-15
JPH03255099A (ja)	1991-11-13
JP2001112492A (ja)	2001-04-24
EP0401508A2 (de)	1990-12-12
IE65710B1 (en)	1995-11-15
EP0401508A3 (de)	1991-03-27
PH27530A (en)	1993-08-18
GR3015124T3 (en)	1995-05-31
JP3126975B2 (ja)	2001-01-22

Legal Events

Date	Code	Title	Description
1997-05-30	FG3A	Patent granted, date of granting	Effective date: 19970218

Publication	Publication Date	Title
AU623769B2 (en)	1992-05-21	Proteinase inhibitors, process for the preparation thereof and medicaments containing these
Johnson et al.	1986	Cathepsin L inactivates alpha 1-proteinase inhibitor by cleavage in the reactive site region.
Potempa et al.	1986	The inactivation of human plasma alpha 1-proteinase inhibitor by proteinases from Staphylococcus aureus.
ATE226636T1 (de)	2002-11-15	Serpin-resistenter t-pa; mutanten; gene
WO1996035788A3 (en)	1996-12-12	Kunitz type protease inhibitors
MX9603775A (es)	1997-07-31	Proteinas inhibidoras del dominio de kunitz, derivadas del inhibidor del precursor de la beta-proteina amiloide de alzheimer.
MY116539A (en)	2004-02-28	New amino acid derivatives
TR200002940T2 (tr)	2001-02-21	Parazitlerin sebep olduğu hastalıkların papain süperfamilyasından sistein proteazların inhibisyonu yoluyla tedavisi
BR9815469A (pt)	2001-03-06	Inibidores de protease
AU6224790A (en)	1991-03-14	Proteins having anticoagulant properties
Rowan et al.	1990	Inhibition of cysteine proteinases by a protein inhibitor from potato
ATE92935T1 (de)	1993-08-15	Serinproteaseinhibitoren und isolierungsverfahren dazu.
NZ319474A (en)	2000-01-28	Guanidino protease inhibitors
Morgenstern et al.	1993	Isolation and characterization of an intracellular serine proteinase inhibitor from a monkey kidney epithelial cell line.
WO1999063090A3 (en)	2000-03-02	Protease inhibitor peptides
Braud et al.	2002	The stratagem utilized by the plasminogen activator from the snake Trimeresurus stejnegeri to escape serpins
Schoenberger et al.	1989	Limited proteolysis of Cl‐inhibitor by chymotrypsin‐like proteinases
Knäuper et al.	1991	Inactivation of human plasma C1‐inhibitor by human PMN leucocyte matrix metalloproteinases
HK1043534A1 (zh)	2002-09-20	蛋白酶抑制剂
Takahara et al.	1982	Mouse plasma trypsin inhibitors: Inhibitory spectrum of contrapsin and alpha-1-antitrypsin
Sulikowski et al.	2002	α1‐Proteinase inhibitor mutants with specificity for plasma kallikrein and C1s but not C1
Sasaki et al.	1990	Limited proteolysis of silkworm antitrypsin by several proteinases
Abe et al.	1989	Stoichiometry of the interaction of human plasma α1-proteinase inhibitor with subtilisin BPN'
Yusova et al.	0	Serpins' Reactive Sites Loops Mobility and Its Functional Value
Valueva et al.	1996	A novel human leukocyte elastase inhibitor from duck egg white