WO2000023058A2 - Methode de traitement - Google Patents

Methode de traitement Download PDF

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Publication number
WO2000023058A2
WO2000023058A2 PCT/GB1999/003449 GB9903449W WO0023058A2 WO 2000023058 A2 WO2000023058 A2 WO 2000023058A2 GB 9903449 W GB9903449 W GB 9903449W WO 0023058 A2 WO0023058 A2 WO 0023058A2
Authority
WO
WIPO (PCT)
Prior art keywords
bacterial
haemorrhoids
anaerobic
agent
treatment
Prior art date
Application number
PCT/GB1999/003449
Other languages
English (en)
Other versions
WO2000023058A3 (fr
Inventor
Kartar Tirath Lalvani
Original Assignee
Vitabiotics 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
Application filed by Vitabiotics Limited filed Critical Vitabiotics Limited
Publication of WO2000023058A2 publication Critical patent/WO2000023058A2/fr
Publication of WO2000023058A3 publication Critical patent/WO2000023058A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • Haemorrhoidal veins are classified as internal and external.
  • Internal haemorrhoidal veins are a plexus of superior haemorrhoidal veins above the mucocutaneous junction of the anorectum which are covered by mucosa.
  • External haemorrhoidal veins are formed by the inferior haemorrhoidal plexus and occur below the mucocutaneous junction in the tissues beneath the anal epithelium of the anal canal and the skin of perianal region.
  • the two plexuses of internal and external haemorrhoidal veins anastomose and comprise the venous return of the lower rectum and anus.
  • Haemorrhoidal veins become enlarged (varicose dilation) and symptomatic primarily as a result of straining at defaecation and are associated with chronic constipation, low-fibre diet and also pregnancy.
  • the straining causes an increase in venous pressure in the haemorrhoidal plexuses which leads to distension of the veins and stasis of venous blood in the plexuses. This explains the earliest and most characteristic symptom of haemorrhoids which is bleeding associated with defaecation.
  • haemorrhoids the dysfunctional state of haemorrhoidal veins is referred to as haemorrhoids.
  • the invention concerns the treatment of haemorrhoids and all its complications which may include prolapse of internal haemorrhoids; thrombosis of external haemorrhoids; and anaemia secondary to chroning bleeding.
  • Haemorrhoids have traditionally been treated in various ways: softening the stool by providing a diet including more fibre and or more water; warm baths with salt; steroids for blood clotting; injection sclerotherapy; rubber band ligation; cryotherapy ; and formal haemorrhoidectomy.
  • This invention is based on the idea that bacterial or other infection is a major cause of unhealing haemorrhoids; and that treatment of the infection is an effective way of alleviating or removing the symptoms. It is proposed that the static venous blood in enlarged haemorrhoids is predisposed to bacterial or other infection for four important reasons. First, stasis and lack of normal blood flow prevent physical clearance of micro-organisms away from this submucosal site. Second, the venous stasis moreover inhibits the continued access to this site of fresh blood-borne cells and proteins that mediate host defence against bacteria. Third, the abundant colonic flora provide an enormous source of ongoing bacterial infection to the relatively static blood in the damaged haemorrhoidal plexuses.
  • colonic flora also provides an enormous source of protozoan parasites causing amoebic infections of these haemorrhoidal plexuses. Entry of micro-organisms to these plexuses is promoted particularly at the time of passing stool, whereupon there would be an opportunity for direct ingress of microorganisms across the stretched, damaged surface of the venous plexus as the stool passes the haemorrhoids on its passage out of the anorectum. Since 99% of colonic bacteria are anaerobic, it is most likely that anaerobic bacteria will predominate in haemorrhoids.
  • haemorrhoidal plexuses It is proposed that ongoing anaerobic bacterial and other infection of haemorrhoidal plexuses causes a vicious cycle wherein chronic low grade infection of enlarged symptomatic haemorrhoids prevents healing of the haemorrhoidal plexuses and the surrounding tissue, predisposing the haemorrhoidal veins to further infection.
  • this invention provides a method of treating a patient suffering from haemorrhoids, which method comprises administering to the patient at least one anti-anaerobic-bacterial and/or anti-protozoal agent effective against micro-organisms present in the gut.
  • the invention provides use of at least one anti-anaerobic- bacterial and/or anti-protozoal agent effective against micro-organisms present in the gut, in the preparation of a composition for administration to a patient suffering from haemorrhoids.
  • Micro-organisms present in the gut comprise bacteria, nearly all anaerobic bacteria and possibly protozoa, in particular those which cause amoebic infections.
  • the invention involves use of an agent that is effective to kill, or at least slow or halt the growth of, some or all of these micro-organisms.
  • anti-bacterial agents particularly bactericides, that are effective against anaerobic bacteria.
  • antibacterial agents may also be effective against aerobic bacteria, though this is not necessary.
  • Anti-protozoal agents include anti-amoebic agents such as amoebicides.
  • any anti-anaerobic-bacterial and/or anti-protozoal agents known to be effective against micro-organisms present in the gut can be used in this invention.
  • agents include compounds in the following groups: nitroimidazole and derivatives thereof; aromatic diamidines; dichloroacetamides; halogenated hydroxyquinolines; nitrofurans; and other compounds including emetine, mepacrine, atovaquone, and diclazuril.
  • Derivatives of nitroimidazole include albendazole; benznidazole; nimorazole; ornidazole; tenonitrozole; tinidazole; and particularly metronidazole which is preferred.
  • haemorrhoids in accordance with the invention may involve use of other agents in addition to the anti-anaerobic-bacterial and anti-protozoal agents noted above.
  • Ordinary antibacterial agents such as agents of the 4-quinoline group, penicillin, tetracyclines etc, effective against aerobic bacteria, may be used to combat secondary infection.
  • a luminal amoebicide such as diloxenide furoate or a halogenated hydroxyquinoline (e.g. clioquinal) may be used to eradicate any surviving organisms from the lumen or the large intestine to prevent relapse.
  • a healing agent to promote healing of the haemorrhoidal veins for example corticosteroids, zinc compounds, alantoin, some vitamins such as vitamin C and vitamin E, or pantothenic acid, may be provided e.g. in a suppository formula. These other agents may be administered, either together with the anti-anaerobic bacterial or anti-protozoal agents, or separately.
  • the invention provides a composition for suppository or topical application for the treatment of haemorrhoids, comprising an effective concentration of at least one anti-anaerobic- bacterial and/or anti-protozoal agent effective against micro-organisms present in the gut.
  • a healing agent may preferably be present in the composition.
  • Treatment with these agents will be expected to clear infection and thus permit healing of the haemorrhoids and the return to normal tissue architecture and local blood flow patterns.
  • the treatment will interrupt a cycle of chronic infection and impaired healing, and so will effect a lasting improvement with a much lower chance of recurrence than is seen with conventional treatments. Furthermore, the treatment will avoid the need for surgery in most cases with its attendant complications.
  • Clinical experience to date indicates anecdotally that these anti-anaerobic-bacterial and/or anti-protozoal agents do work in practice.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne une méthode de traitement des hémorrhoïdes. Cette méthode consiste à administer audit patient au moins un agent anti anaérobique-bactérien et/anti-protozoaire (métronidazole par exemple) efficace contre les microoranismes présents dans l'intestin.
PCT/GB1999/003449 1998-10-16 1999-10-18 Methode de traitement WO2000023058A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9822681.4 1998-10-16
GBGB9822681.4A GB9822681D0 (en) 1998-10-16 1998-10-16 Method of treatment

Publications (2)

Publication Number Publication Date
WO2000023058A2 true WO2000023058A2 (fr) 2000-04-27
WO2000023058A3 WO2000023058A3 (fr) 2000-07-06

Family

ID=10840749

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/003449 WO2000023058A2 (fr) 1998-10-16 1999-10-18 Methode de traitement

Country Status (2)

Country Link
GB (1) GB9822681D0 (fr)
WO (1) WO2000023058A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007065637A1 (fr) 2005-12-06 2007-06-14 Andreas Kern Antibiotiques s'administrant par voie orale destinés à traiter les douleurs hémorroïdaires

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0579435A1 (fr) * 1992-07-14 1994-01-19 CYCLOPS h.f. Complexation à l'amide de cyclodextrines
WO1994012164A1 (fr) * 1992-11-26 1994-06-09 The Wellcome Foundation Limited Combinaison d'atovaquone et de proguanil pour le traitement des infections par protozoaires
US5354866A (en) * 1989-05-23 1994-10-11 Abbott Laboratories Retroviral protease inhibiting compounds
WO1996003135A1 (fr) * 1994-07-25 1996-02-08 Milankovits Marton Compositions pharmaceutiques utilisables principalement comme ovule, renfermant plusieurs ingredients actifs differents
WO1998043644A1 (fr) * 1997-03-31 1998-10-08 David Granstrom Formulations et procedes de traitement et de prevention de la myelo-encephalite equine due a des protozoaires

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RO89526A2 (fr) * 1984-02-20 1986-05-30 Intreprinderea De Antibiotice,Ro Procede d'obtention d'un produit medicamenteu0 administrable par voierectale en infections avec germes anaerobes
JPH0692317B2 (ja) * 1990-08-06 1994-11-16 龍也 橋岡 肛門用外用薬剤
CN1097306A (zh) * 1993-07-12 1995-01-18 中国医科大学第二临床学院 复方抗炎栓剂

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5354866A (en) * 1989-05-23 1994-10-11 Abbott Laboratories Retroviral protease inhibiting compounds
EP0579435A1 (fr) * 1992-07-14 1994-01-19 CYCLOPS h.f. Complexation à l'amide de cyclodextrines
WO1994012164A1 (fr) * 1992-11-26 1994-06-09 The Wellcome Foundation Limited Combinaison d'atovaquone et de proguanil pour le traitement des infections par protozoaires
WO1996003135A1 (fr) * 1994-07-25 1996-02-08 Milankovits Marton Compositions pharmaceutiques utilisables principalement comme ovule, renfermant plusieurs ingredients actifs differents
WO1998043644A1 (fr) * 1997-03-31 1998-10-08 David Granstrom Formulations et procedes de traitement et de prevention de la myelo-encephalite equine due a des protozoaires

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BISWAS P: "Metronidazole in haemorrhoids" J INDIAN MED ASSOC, OCT 1 1968, 51 (7) P344-6, XP000885886 INDIA *
BROOK I. ET AL: "Aerobic and anaerobic microbiology of infected hemorrhoids" AMERICAN JOURNAL OF GASTROENTEROLOGY, 91/2 (333-335), XP000885600 United States *
CARAPETI EA ET AL: "Double-blind randomised controlled trial of effect of metronidazole on pain after day-case haemorrhoidectomy" LANCET, JAN 17 1998, 351 (9097) P169-72, XP000885602 ENGLAND *
DATABASE WPI Section Ch, Week 198701 Derwent Publications Ltd., London, GB; Class B03, AN 1987-005119 XP002135643 & RO 89 526 A (INTR ANTIBIOTICE), 30 May 1986 (1986-05-30) *
DATABASE WPI Section Ch, Week 199219 Derwent Publications Ltd., London, GB; Class B05, AN 1992-147958 XP002135646 & JP 04 091036 A (NIPPON KURIN GEJI K), 24 March 1992 (1992-03-24) *
DATABASE WPI Section Ch, Week 199719 Derwent Publications Ltd., London, GB; Class B03, AN 1997-204067 XP002135644 & CN 1 097 306 A (UNIV CHINA MEDICAL CLINICS COLLEGE NO 2), 18 January 1995 (1995-01-18) *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007065637A1 (fr) 2005-12-06 2007-06-14 Andreas Kern Antibiotiques s'administrant par voie orale destinés à traiter les douleurs hémorroïdaires

Also Published As

Publication number Publication date
WO2000023058A3 (fr) 2000-07-06
GB9822681D0 (en) 1998-12-09

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