WO2000023058A2 - Use of an antianaerobic-bacterial or/and antiprotozoal agent (preferably metronidazole) in the manufacture of a medicament for the treatment of haemorrhoids - Google Patents

Abstract

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 e.g. metronidazole effective against micro-organisms present in the gut.

Description

METHOD OF TREATMENT

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. In this specification, 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. Fourth, the abundant 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. 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.

In one aspect, 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. In another aspect, 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. These include anti-bacterial agents, particularly bactericides, that are effective against anaerobic bacteria. Such antibacterial agents may also be effective against aerobic bacteria, though this is not necessary. Anti-protozoal agents include anti-amoebic agents such as amoebicides.

In principle, 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. Among such agents are 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.

These compounds may be administered by means which are conventional for other purposes; for example orally, or rectally by suppository or topically in the form of a cream or gel. Rates and frequency and duration of administration may also be as conventional for other purposes. For example metronidazole may be administered orally at a rate of 200 - 3000 mg per day for 1 day up to three months or more or until symptoms improve. Treatment of 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.

In another aspect 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. There is a rapid therapeutic response to systemic administration within a few days, and this has now been observed in five individuals. Specifically, these individuals took metronidazole orally at a rate of 400 mg three times per day for two to three weeks. While all five obtained relief, in one case maximum improvement was seen when ampicillin was taken as well as metronidazole.

Claims

1. 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.

2. The method of claim 1 , wherein the anti-anaerobic-bacterial or anti-protozoal agent is metronidazole.

3. The method of claim 1 or claim 2, wherein the anti-anaerobic-bacterial or anti-protozoal agent is administered orally.

4. The method of claim 1 or claims 2, wherein the anti-anaerobic-bacterial or anti-protozoal agent is administered topically.

5. The method of claim 4, wherein a healing agent is also administered.

6. The method of any one of ciaims 1 to 5, wherein an antibiotic effective against aerobic bacteria is also administered.

7. The method of any one of claims 1 to 6, wherein administration is continued until symptoms improve.

8. 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.

9. A composition for suppository or topical application for the treatment of haemorrhoids, comprising an effective concentration of at least one anti-aerobic-bacterial and/or anti-protozoal agent effective against micro-organisms present in the gut.

10. The composition of claim 9, wherein a healing agent is also present.