AU755502C - Immunostimulants - Google Patents

Immunostimulants

Info

Publication number
AU755502C
AU755502C AU34435/00A AU3443500A AU755502C AU 755502 C AU755502 C AU 755502C AU 34435/00 A AU34435/00 A AU 34435/00A AU 3443500 A AU3443500 A AU 3443500A AU 755502 C AU755502 C AU 755502C
Authority
AU
Australia
Prior art keywords
composition according
polycationic carbohydrate
polycationic
chitosan
carbohydrate
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
AU34435/00A
Other languages
English (en)
Other versions
AU3443500A (en
AU755502B2 (en
Inventor
Hazire Oya Alpar
Leslie William James Baillie
James Edward Eyles
Satyanarayana Somavarapu
Ethel Diane Williamson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
UK Secretary of State for Defence
Original Assignee
SECR DEFENCE
UK Secretary of State for Defence
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
Priority claimed from GBGB9906696.1A external-priority patent/GB9906696D0/en
Priority claimed from GBGB9906694.6A external-priority patent/GB9906694D0/en
Application filed by SECR DEFENCE, UK Secretary of State for Defence filed Critical SECR DEFENCE
Publication of AU3443500A publication Critical patent/AU3443500A/en
Application granted granted Critical
Publication of AU755502B2 publication Critical patent/AU755502B2/en
Publication of AU755502C publication Critical patent/AU755502C/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55583—Polysaccharides
    • 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
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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
    • A61K9/0043—Nose
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Virology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
AU34435/00A 1999-03-24 2000-03-23 Immunostimulants Ceased AU755502C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB9906696 1999-03-24
GBGB9906696.1A GB9906696D0 (en) 1999-03-24 1999-03-24 Vaccine composition
GB9906694 1999-03-24
GBGB9906694.6A GB9906694D0 (en) 1999-03-24 1999-03-24 Vaccine composition
PCT/GB2000/001118 WO2000056362A2 (en) 1999-03-24 2000-03-23 Polycationic carbohydrates as immunostimulants in vaccines

Publications (3)

Publication Number Publication Date
AU3443500A AU3443500A (en) 2000-10-09
AU755502B2 AU755502B2 (en) 2002-12-12
AU755502C true AU755502C (en) 2003-08-14

Family

ID=26315329

Family Applications (2)

Application Number Title Priority Date Filing Date
AU34435/00A Ceased AU755502C (en) 1999-03-24 2000-03-23 Immunostimulants
AU34424/00A Ceased AU762078B2 (en) 1999-03-24 2000-03-23 Vaccine composition

Family Applications After (1)

Application Number Title Priority Date Filing Date
AU34424/00A Ceased AU762078B2 (en) 1999-03-24 2000-03-23 Vaccine composition

Country Status (11)

Country Link
US (1) US20080057083A1 (https=)
EP (2) EP1163001A2 (https=)
JP (3) JP5124066B2 (https=)
AT (1) ATE403436T1 (https=)
AU (2) AU755502C (https=)
CA (2) CA2366908A1 (https=)
DE (1) DE60039754D1 (https=)
DK (1) DK1163002T3 (https=)
ES (1) ES2311451T3 (https=)
NZ (1) NZ514323A (https=)
WO (2) WO2000056362A2 (https=)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050181063A1 (en) * 2000-03-22 2005-08-18 Alpar Hazire O. Pharmaceutical composition for administration to mucosal surfaces
US7767197B2 (en) 2000-06-22 2010-08-03 Endo Pharmaceuticals Colorado LLC Delivery vehicle composition and methods for delivering antigens and other drugs
BR0111948A (pt) 2000-06-26 2004-08-24 Rxkinetix Inc Composição para entrega de fator de crescimento hematopoiético
WO2003005952A2 (en) * 2001-07-10 2003-01-23 Corixa Corporation Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres
EP1416916B1 (en) 2001-08-16 2007-10-17 Cmp Therapeutics Limited Chitin microparticles and their medical uses
US7850990B2 (en) 2001-10-03 2010-12-14 Celator Pharmaceuticals, Inc. Compositions for delivery of drug combinations
ES2272768T3 (es) * 2001-10-03 2007-05-01 Celator Pharmaceuticals Inc Composiciones para la administracion de combinaciones de farmacos.
CA2383259A1 (en) 2002-04-23 2003-10-23 Celator Technologies Inc. Synergistic compositions
GB0302218D0 (en) * 2003-01-30 2003-03-05 Chiron Sri Vaccine formulation & Mucosal delivery
GB0300885D0 (en) * 2003-01-15 2003-02-12 Secr Defence Pharmaceutical composition
JP2006516609A (ja) * 2003-01-30 2006-07-06 カイロン ソチエタ ア レスポンサビリタ リミタータ 粘膜髄膜炎菌性ワクチン
CA2514667C (en) * 2003-01-30 2013-01-08 Chiron Corporation Adjuvanted influenza vaccine
JP5557415B2 (ja) 2003-06-02 2014-07-23 ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド 吸着させたトキソイドおよび多糖類含有抗原を含む微粒子に基づく免疫原性組成物
JP4669665B2 (ja) * 2004-04-12 2011-04-13 正彦 阿部 細胞毒性のないポリカチオン修飾リポソームおよびその製造方法
GB0519871D0 (en) 2005-09-30 2005-11-09 Secr Defence Immunogenic agents
US8431160B2 (en) 2006-02-24 2013-04-30 Novartis Ag Microparticles containing biodegradable polymer and cationic polysaccharide for use in immunogenic compositions
WO2008041703A1 (en) * 2006-10-02 2008-04-10 Osaka University Adjuvant for influenza vaccine and influenza vaccine
JP5297009B2 (ja) * 2007-07-24 2013-09-25 大日精化工業株式会社 免疫アジュバント水溶液
MY148321A (en) * 2007-10-02 2013-03-29 Malaysian Palm Oil Board Mpob Vitamin e supplementation to tetanus toxoid
GB0721937D0 (en) 2007-11-08 2007-12-19 Secr Defence Rodenticide
CA2733147A1 (en) * 2008-08-06 2010-02-11 Novartis Ag Microparticles for use in immunogenic compositions
GB0900455D0 (en) 2009-01-13 2009-02-11 Secr Defence Vaccine
CN103747798B (zh) * 2011-05-18 2018-10-26 马特里瓦克斯公司 包含聚阳离子的蛋白质基质疫苗组合物
WO2012164480A1 (en) * 2011-05-30 2012-12-06 National Institute Of Immunology A vaccine composition capable of inducing memory antibody response from single point immunization
CN107200788B (zh) * 2017-05-11 2020-04-14 暨南大学 一种季鏻化壳聚糖及其作为疫苗免疫佐剂的应用
CN107899021A (zh) * 2017-11-06 2018-04-13 扬州大学 一种表面修饰s‑层蛋白的壳聚糖微球、制备及应用
KR102384808B1 (ko) * 2018-12-20 2022-04-08 주식회사 스킨메드 키토산으로 코팅된 나노 캡슐 및 이의 용도
EP3960203A1 (en) 2020-08-25 2022-03-02 Université de Liège Complexes for the delivery of proteinaceous agents

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996010421A1 (en) * 1994-10-04 1996-04-11 Medeva Holdings B.V. Vaccine compositions
WO1997020576A1 (en) * 1995-12-07 1997-06-12 Danbiosyst Uk Limited Vaccine compositions for intranasal administration comprising chitosan and use thereof

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3740421A (en) * 1966-09-19 1973-06-19 Basf Wyandotte Corp Polyoxyethylene-polyoxypropylene aqueous gels
GB1290141A (https=) * 1968-05-31 1972-09-20
FR2306684A1 (fr) * 1975-04-11 1976-11-05 Crinex Lab Nouvelle composition a action immunostimulante
US4606918A (en) * 1983-08-22 1986-08-19 Syntex (U.S.A.) Inc. Polyoxypropylene-polyoxyethylene block polymer based adjuvants
US6024983A (en) * 1986-10-24 2000-02-15 Southern Research Institute Composition for delivering bioactive agents for immune response and its preparation
ES2052685T3 (es) * 1987-03-17 1994-07-16 Akzo Nv Metodo para producir un adyuvante libre.
ATE115862T1 (de) * 1989-02-04 1995-01-15 Akzo Nobel Nv Tocole als impfstoffadjuvans.
US5562910A (en) * 1989-09-25 1996-10-08 University Of Utah Research Foundation Vaccine compositions and method for enhancing an immune response
US5126147A (en) * 1990-02-08 1992-06-30 Biosearch, Inc. Sustained release dosage form
DE4004430A1 (de) * 1990-02-09 1991-08-14 Schering Ag Aus polyaldehyden aufgebaute kontrastmittel
US5709860A (en) * 1991-07-25 1998-01-20 Idec Pharmaceuticals Corporation Induction of cytotoxic T-lymphocyte responses
US5292513A (en) * 1992-05-18 1994-03-08 Anthony G. Gristina Method for nonspecific cellular immune stimulation
EP0688205A1 (en) * 1993-03-11 1995-12-27 Secretech, Inc. Polymeric mucoadhesives in the delivery of immunogens at mucosal surfaces
US6913767B1 (en) * 1993-10-25 2005-07-05 Genentech, Inc. Compositions for microencapsulation of antigens for use as vaccines
US5643605A (en) * 1993-10-25 1997-07-01 Genentech, Inc. Methods and compositions for microencapsulation of adjuvants
US5902565A (en) * 1993-12-24 1999-05-11 Csl Limited Spray dried vaccine preparation comprising aluminium adsorbed immunogens
ATE252894T1 (de) * 1995-01-05 2003-11-15 Univ Michigan Oberflächen-modifizierte nanopartikel und verfahren für ihre herstellung und verwendung
DE69625802T2 (de) * 1995-03-13 2003-11-13 The Secretary Of State For Defence, Salisbury Impfstoffe gegen die pest
US6428771B1 (en) * 1995-05-15 2002-08-06 Pharmaceutical Discovery Corporation Method for drug delivery to the pulmonary system
DE19603649A1 (de) * 1996-02-01 1997-08-07 Werner Lubitz Rekombinante Expression von S-Layer-Proteinen
US6309623B1 (en) * 1997-09-29 2001-10-30 Inhale Therapeutic Systems, Inc. Stabilized preparations for use in metered dose inhalers
GB9810126D0 (https=) * 1998-05-13 1998-07-08 Glaxo Group Ltd
MXPA01004381A (es) * 1998-11-02 2005-09-08 Elan Corp Plc Composicion de multiparticulado de liberacion modificada.
US20030171258A1 (en) * 1999-03-24 2003-09-11 Alpar Hazire Oya Particle based vaccine composition
US20020103165A1 (en) * 2000-02-29 2002-08-01 Alliance Pharmaceutical Corp., Engineered spray-dried lipid-based microparticles for cellular targeting
US20050181063A1 (en) * 2000-03-22 2005-08-18 Alpar Hazire O. Pharmaceutical composition for administration to mucosal surfaces
GB0300885D0 (en) * 2003-01-15 2003-02-12 Secr Defence Pharmaceutical composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996010421A1 (en) * 1994-10-04 1996-04-11 Medeva Holdings B.V. Vaccine compositions
WO1997020576A1 (en) * 1995-12-07 1997-06-12 Danbiosyst Uk Limited Vaccine compositions for intranasal administration comprising chitosan and use thereof

Also Published As

Publication number Publication date
WO2000056361A3 (en) 2001-03-01
AU3443500A (en) 2000-10-09
ES2311451T3 (es) 2009-02-16
CA2366216C (en) 2012-10-23
CA2366908A1 (en) 2000-09-28
WO2000056361A2 (en) 2000-09-28
NZ514323A (en) 2003-03-28
DK1163002T3 (da) 2009-01-19
WO2000056362A2 (en) 2000-09-28
AU3442400A (en) 2000-10-09
CA2366216A1 (en) 2000-09-28
ATE403436T1 (de) 2008-08-15
EP1163001A2 (en) 2001-12-19
EP1163002B1 (en) 2008-08-06
JP5124066B2 (ja) 2013-01-23
EP1163002A2 (en) 2001-12-19
JP2012031186A (ja) 2012-02-16
AU762078B2 (en) 2003-06-19
AU755502B2 (en) 2002-12-12
US20080057083A1 (en) 2008-03-06
JP2002540076A (ja) 2002-11-26
WO2000056362A3 (en) 2001-02-01
DE60039754D1 (de) 2008-09-18
JP2002540077A (ja) 2002-11-26

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Legal Events

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DA2 Applications for amendment section 104

Free format text: THE NATURE OF THE PROPOSED AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 20030204

FGA Letters patent sealed or granted (standard patent)
DA3 Amendments made section 104

Free format text: THE NATURE OF THE AMENDMENT IS AS WAS NOTIFIED IN THE OFFICIAL JOURNAL DATED 20030306