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
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
  • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• • 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
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
• • 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
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/47—Quinolines; Isoquinolines
  • A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
• • 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
  • A61P31/20—Antivirals for DNA viruses
  • A61P31/22—Antivirals for DNA viruses for herpes viruses

Definitions

• the present invention relates to a medicament for use in the treatment of viral infections, such as herpes simplex, that are transmitted through the nervous system.
• the present invention also relates to a method of treatment for such infections.
• a number of viral diseases are transported through the body along the nervous system, the viruses taking advantage of the elongate form of most nerve cells.
• a typical nerve cell comprises a cell body and an elongate axon extending away therefrom, which may easily be over a third of a meter long.
• the axon transports chemicals both away from the cell body (anterograde) and towards the cell body (retrograde), using structures known as microtubules.
• a tip of the axon distal from the respective cell body may link to a cell body of one or more further nerve cells.
• Viruses may thus be transported from a site of infection along a retrograde pathway along one or more axons, until they reach the central nervous system (CNS), spinal cord and brain.
• Viruses such as herpes simplex, may lie asymptomatically dormant or latent in nerve cell bodies of the CNS, but when reactivated, by whatever cause, are transported anterogradely along nerve cell axons to a surface of the body, where symptoms of the infection arise.
• a common form of herpes simplex infection lies dormant or latent in the nerve ganglion until reactivated by stress, premenstrual tension or a range of other triggers.
• the herpes simplex virus typically travels along nerve axons to any part of the body, such as eyes, the nose, genitalia or most usually to the lips, where it leads to symptoms such as cold sores.
• Herpes simplex infections may also take a more serious form in which the virus travels along nerve cells to the area of the eye socket.
• HSV may cause symptoms such as ulceration of the cornea, with a potential serious effect on a patient's vision.
• the current preferred treatment for herpes simplex infection is a drug, such as acyclovir, which interferes with viral replication.
• acyclovir which interferes with viral replication.
• cold sores this is administered as a topical cream
• a typical prescription is administration of acyclovir, five times daily, as an ointment.
• acyclovir (or equivalent) is only administered once a recurrence of HSV activity is underway (e.g. acyclovir cold sore creams are typically to be administered only once a "tingle” has warned the patient of an incipient cold sore). It would be preferable to slow or stop the HSV before it reaches the surface of the body and begins to cause annoying or harmful symptoms.
• it may be administered orally as twice daily 400mg doses over long periods.
• an alkaloids or griseofulvin in the manufacture of a medicament for use in the treatment of anterograde neurally transported viral infections.
• the alkaloid comprises an antimitotic alkaloid.
• the alkaloid may comprise colchicine, vinblastine, vincristine, a cytochalasin or derivatives thereof.
• the viral infection to be treated comprises a herpes infection, such as a herpes simplex infection.
• the medicament is in an orally administrable form.
• the medicament is administrable in tablet, capsule, powder or granular form.
• the medicament comprises a drinkable liquid composition.
• the medicament may comprise a topically applicable composition.
• the medicament may then comprise a cream, ointment, salve, eye drops, nasal spray or the like.
• the medicament may comprise an injectable or infusible liquid composition.
• a method for treating a herpes simplex infection comprising the step of administering a substance capable of interfering with or blocking anterograde axonal transport.
• the method comprises the step of administering said substance prior to the onset of symptoms of the infection.
• the method comprises the step of administering said substance prophylactically.
• the method preferably comprises the step of administering a composition comprising an alkaloid, advantageously an antimitotic alkaloid, such as colchicine, vinblastine or vincristine, or griseofulvin.
• an alkaloid advantageously an antimitotic alkaloid, such as colchicine, vinblastine or vincristine, or griseofulvin.
• a first example concerns patients with a history of cold sores, brought on by a known trigger. This might for example take the form of a stressful event, such as an examination. Another common trigger is a weakened immune system as a result of another infection (for example, a cold, hence the name "cold sore"). Some women suffer regular attacks of cold sores as a premenstrual symptom. While the exact trigger(s) for each patient will vary, they are likely to recognise when they are at risk of a recurrence.
• an ointment containing 5% w / w acyclovir is applied topically, up to five times a day, until the cold sores subside.
• the duration of the episode may well be reduced as a result, but the patient still suffers unsightly and possibly painful cold sores for several days.
• colchicine In a treatment embodying the present invention, it is preferred to administer colchicine orally, for example in tablet or capsule form.
• some trigger event likely to bring on his or her cold sores, has taken place or is imminent. Rather than wait for a cold sore to appear, the patient takes one or more tablets containing colchicine.
• a topical cream to a likely site of the cold sores, typically around the lips.
• This cream comprises colchicine, together with conventional excipients, and optionally agents to encourage absorption of the colchicine through the patient's skin. It is believed that the colchicine then permeates retrogradely along the nerve axons towards the trigeminal ganglion that is acting as a reservoir for latent herpes simplex virus. If the HSV has been activated, it will by this stage be migrating anterogradely towards the skin surface, but the colchicine is believed to slow or even halt its progress along the axon. If the HSV does not reach the skin surface, it will not cause cold sores.
• a second example concerns patients with a history of herpes simplex infections in and around the eye. These can lead to corneal ulceration and temporary or permanent harm to the patient's sight. Again, such infections are usually the result of latent HSV in the trigerminal ganglion becoming reactivated by some recognisable trigger, and travelling anterogradely down the nerve axons.
• Acyclovir in the form of ointment is administered (five times daily) until the ulcers heal.
• colchicine in tablet form is administered prior to an outbreak, either regularly or on recognition of a trigger event.
• ointment or eye drops containing a solution of colchicine are administered to the patient's eyes, as soon as a likely trigger event is noticed.
• the colchicine permeates retrogradely up the axon towards the trigerminal ganglion and interferes with or halts the progress of HSV towards the eye. Little or no HSV reaches the eye, either preventing or significantly reducing the formation of ulcers.
• Conventional acyclovir ointment treatment may be used on any ulcers which do still occur, but since these are likely to be far less severe than would otherwise be the case, a much shorter course of treatment will be required to clear them up.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Virology (AREA)
• Biotechnology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Molecular Biology (AREA)
• Communicable Diseases (AREA)
• Oncology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Organic Chemistry (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Furan Compounds (AREA)
• Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2005
  • 2005-03-11 GB GBGB0505076.0A patent/GB0505076D0/en not_active Ceased
• 2006
  • 2006-03-10 EP EP06726355A patent/EP1861088A1/de not_active Withdrawn
  • 2006-03-10 WO PCT/GB2006/000845 patent/WO2006095178A1/en not_active Application Discontinuation
  • 2006-03-10 JP JP2008500267A patent/JP2008543730A/ja active Pending
  • 2006-03-10 CN CNA2006800118064A patent/CN101155581A/zh active Pending

Non-Patent Citations (1)

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