WO2003006035A1 - Compositions antivomitives - Google Patents

Compositions antivomitives Download PDF

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Publication number
WO2003006035A1
WO2003006035A1 PCT/GB2002/003124 GB0203124W WO03006035A1 WO 2003006035 A1 WO2003006035 A1 WO 2003006035A1 GB 0203124 W GB0203124 W GB 0203124W WO 03006035 A1 WO03006035 A1 WO 03006035A1
Authority
WO
WIPO (PCT)
Prior art keywords
thl
mycobacterial
treatment
vaccae
emesis
Prior art date
Application number
PCT/GB2002/003124
Other languages
English (en)
Inventor
Graham Arthur William Rook
Christopher Alan Lowry
Stafford Louis Lightman
Original Assignee
Stanford Rook Limited
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 GB0116847A external-priority patent/GB0116847D0/en
Priority claimed from GB0117325A external-priority patent/GB0117325D0/en
Application filed by Stanford Rook Limited filed Critical Stanford Rook Limited
Publication of WO2003006035A1 publication Critical patent/WO2003006035A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • 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
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • 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

Definitions

  • Thl dominated immune responses are generated in an individual after pre-immunisation with an antigen, preferably a soluble antigen, in combination with a Thl adjuvant, or an agent which has both antigenic and Thl adjuvant activity.
  • an antigen preferably a soluble antigen
  • subsequent immunization may be performed using the antigen without the adjuvant, as described above.
  • a method of treatment of emesis may therefore include administering to a patient an effective amount of a first therapeutic composition comprising an antigen and a Thl adjuvant and subsequently administering to said patient an effective amount of a second therapeutic composition comprising said antigen.
  • Lectins and other Thl lymphocyte surface binding molecules such as antibodies may also be used as adjuvants in combination with particular antigens.
  • Such an adjuvant may be administered in vivo in an admixture or composition with an antigen according to a suitable immunisation schedule.
  • An agent which activates Thl lymphocytes non-specifically may be identified by administering the agent to a non-human mammal, such as a mouse, and determining an increase in levels of a cytokine associated with a Thl response, for example IL- 1, IL-2, IL-12 or IFN- ⁇ .
  • a cytokine associated with a Thl response for example IL- 1, IL-2, IL-12 or IFN- ⁇ .
  • Suitable mediators include IL-1, IL-2, IL-12 IL- 17, IL-18, IFN- ⁇ , lymphotoxin (TNF ⁇ ) , TNF ⁇ , prostaglandins, nitric oxide, urocortin (Bamberger et al J. Clin. Endocrinol . Metab. 83: 708-711), prolactin (Matera and Mori (2000) Ann. NY Acad. Sci. 917:505-513), opiates (Mousa et al (2001) J. Neuroimmunol . 115: 71-78), CGRP, bradykinnin, histamine, substance P (Blum et al (2000) Faseb J. 15: 950-957) and other neurokinins, NGF, BDNF (Barouch et al J. Neuroimmunol. 103:112-121) or somatostatin.
  • TNF ⁇ lymphotoxin
  • Another aspect of the present invention provides a method of treatment of emesis comprising triggering a peripheral sensory afferent by administering to a patient an effective amount of a therapeutic composition comprising a mediator of the Thl immune response as described herein.
  • M. vaccae cells may be disrupted prior to administration, for example by ultrasonication.
  • M. vaccae cells Prior to being killed and/or disrupted, M. vaccae cells may be grown on a suitable solid medium.
  • a modified Sauton's liquid medium may be preferred (Boyden et al . , (1955) J. Immunol. 75: 15), solidified with agar, preferably 1.3% agar. After aerobic incubation, generally at 32°C for 10 days, the organisms may be harvested, then weighed and suspended in diluent, ready for administration. Storage, if required before use, may be at 4°C.
  • a composition may be administered alone or in combination with other treatments, either simultaneously or sequentially dependent upon the condition to be treated.
  • Suitable formulations for administration via the gastrointestinal tract include capsules designed to release in the appropriate part of the gut .
  • a pharmaceutical composition suitable for oral administration may be in. tablet, capsule, powder or liquid form.
  • a tablet may include a solid carrier such as gelatin or an adjuvant.
  • Liquid pharmaceutical compositions generally include a liquid carrier such as water, petroleum, animal or vegetable oils, mineral oil or synthetic oil. Physiological saline solution, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol may be included.
  • Treatment with M. vaccae induces a predominantly Thl response which resulted in secretion of Interferon gamma (IFN ⁇ ), but not interleukin 4 (IL-4) .
  • IFN ⁇ Interferon gamma
  • IL-4 interleukin 4
  • a potent Thl dominated response to a protein that is not found within mycobacteria Keyhole limpet haemocyanin (KLH) ) can be evoked by treating with KLH mixed with the Thl-inducing cytokine, IL-12. This is based on the method of Wynn et al . (1995) Nature 376: 594-596, in which a Thl response was evoked with the Th2 antigen Schistosome ova by mixing with the Thl adjuvant IL-12.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Otolaryngology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Cette invention vise à combattre et/ou traiter les vomissements chez un individu à l'aide de compositions qui activent la réponse immunitaire des Th1, notamment des compositions qui comprennent une substance mycobactérienne. Ces compositions et leurs procédés d'utilisation sont également décrits.
PCT/GB2002/003124 2001-07-10 2002-07-08 Compositions antivomitives WO2003006035A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0116847A GB0116847D0 (en) 2001-07-10 2001-07-10 Therapeutic compositions
GB0116847.5 2001-07-10
GB0117325.1 2001-07-16
GB0117325A GB0117325D0 (en) 2001-07-16 2001-07-16 Therapeutic compositions

Publications (1)

Publication Number Publication Date
WO2003006035A1 true WO2003006035A1 (fr) 2003-01-23

Family

ID=26246296

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2002/003124 WO2003006035A1 (fr) 2001-07-10 2002-07-08 Compositions antivomitives

Country Status (1)

Country Link
WO (1) WO2003006035A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998044096A2 (fr) * 1997-03-28 1998-10-08 Cytoclonal Pharmaceutics, Inc. Vaccins recombines a base de mycobacteries

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998044096A2 (fr) * 1997-03-28 1998-10-08 Cytoclonal Pharmaceutics, Inc. Vaccins recombines a base de mycobacteries

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
O'BRIEN M E R ET AL: "A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma.", BRITISH JOURNAL OF CANCER, vol. 83, no. 7, October 2000 (2000-10-01), pages 853 - 857, XP001095848, ISSN: 0007-0920 *

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