JP2008543730A - Drugs and treatment for herpes simplex - Google Patents

Abstract

A drug for use in the treatment of viral infections such as herpes simplex, transported antegradely through the nervous system. Viruses such as herpes simplex exist in the dormant or latent state in the CNS neuronal cell body, but when reactivated by something happened, the body moves antegradely along the nerve cell axon. Carried to the surface, causing symptoms of infection. The normal form of herpes simplex infection is dormant or latent in the ganglia until reactivated by stress, premenstrual tension, or a range of other triggers. Herpes simplex virus (HSV) is typically carried along the nerve axon to the lips leading to symptoms such as herpes simplex. Herpes simplex infection can take a more severe form when the virus is carried along the nerve cells into the orbit. Therefore, HSV can cause symptoms such as corneal ulceration and have a powerful and serious impact on the patient's vision. The active ingredient of the drug is an alkaloid such as colchicine, vinblastine, vincristine, cytochalasin, or derivatives thereof.
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Description

Description of the invention

  The present invention relates to agents for use in the treatment of viral infections such as herpes simplex transmitted through the nervous system. The invention also relates to a method for treating such infections.

  Many viral diseases are transported through the body along the nervous system, and the virus utilizes the elongated form of most neurons. A typical nerve cell comprises a cell body and an elongated axon away from it, which can easily exceed the length of one third of a meter. Axons use chemical structures known as microtubules to carry chemicals both away from the cell body (antegrade) and toward the cell body (retrograde). The tip of the axon distal from each cell body may bind to the cell body of one or more additional neuronal cells.

  The virus may therefore be transported in a retrograde route along one or more axons from the site of infection until it reaches the central nervous system (CNS), spinal cord, and brain.

  Viruses such as herpes simplex may be asymptomatically dormant or latent in the CNS nerve cell body, but along with nerve cell axons if reactivated by something happening It is transported antegradely to the surface of the body, causing symptoms of infection. The usual forms of herpes simplex infection are dormant or latent in the ganglia until reactivated by stress, premenstrual tension, or a range of other triggers. Herpes simplex virus (HSV) is typically carried along nerve axons to body parts such as the eyes, nose, genitals, or most commonly lips, leading to symptoms like herpes simplex . Herpes simplex infection can take a more severe form when the virus is carried along the nerve cells into the orbit. Therefore, HSV can cause symptoms such as corneal ulceration and have a powerful and serious impact on the patient's vision.

  It is estimated that up to 95% of the UK population has antibodies to herpes simplex and is therefore estimated to be infected with latent asymptomatic HSV. A typical infection vector is thought to be lip contact transmission from relatives, usually occurring before the age of five. Asymptomatic carriers are infecting others and no method has been developed to avoid this.

  The current preferred treatment for herpes simplex infection is an agent such as acyclovir that inhibits viral replication. For herpes simplex, this is administered as a topical cream, whereas for corneal ulcers, a typical prescription is administration of acyclovir as an ointment 5 times daily. In each case, acyclovir (or equivalent) is administered only when a recurrence of HSV activity is ongoing (eg, acyclovir herpes simplex cream typically has a “tingling” in patients with the onset of herpes simplex. Only if it is warned). It is preferable to delay or stop HSV before reaching the surface of the body and before unpleasant and harmful symptoms begin to occur. However, in chronic cases, a 400 mg dose can be administered orally twice a day for a long period.

  Although the specification has been described primarily with respect to drug therapy for treating viral infections in the human body, very similar considerations apply to viral infections in animals. All references to humans should be understood to refer to animals as well, unless stated otherwise.

  It is an object of the present invention to provide a medicament for treating viral infections that are antegradely transported through the nervous system. It is also an object of the present invention to provide a method for treating such infections.

  According to a first aspect of the present invention there is provided the use of an alkaloid or griseofulvin in the manufacture of a medicament for use in the treatment of antegrade neurologically transported viral infections.

Conveniently, the alkaloid comprises an antimicrobial alkaloid.
The alkaloid may include colchicine, vinblastine, vincristine, cytochalasin, or derivatives thereof.

  In a preferred embodiment, the viral infection to be treated comprises a herpes infection, such as herpes simplex infection.

Preferably, the medicament is in an orally administrable form.
Preferably, the medicament can be administered in the form of a tablet, capsule, powder or granule.
Alternatively, the medicament comprises a liquid composition suitable for drinking.

The medicament may comprise a topically applicable composition.
Said medicaments may therefore include creams, ointments, salves, eye drops, nasal sprays and the like.
The medicament may comprise an injectable or injectable liquid composition.

  According to a second aspect of the present invention, there is provided a method for treating herpes simplex infection, comprising the step of administering a substance capable of interfering with or blocking antegrade axonal transport. Is done.

Preferably, the method comprises the step of administering the substance before symptoms of the infection develop.
Alternatively, the method comprises the step of administering the substance prophylactically.

  The method preferably comprises administering a composition containing an alkaloid, preferably an antimicrobial alkaloid such as colchicine, vinblastine or vincristine, or griseofulvin.

  Embodiments of the invention are illustrated in more detail by the following examples.

  The first example concerns a patient with a history of herpes simplex caused by a known trigger. This takes the form of a stressful event such as a test. Another common trigger is a weakened immune system as a result of other infections (eg, colds and hence “cold sore”. Herpes simplex as premenstrual syndrome) Some women suffer from regular seizures, while the exact trigger for each patient is different, but they are more likely to be recognized if they are at risk of recurrence.

  In current treatments, if herpes simplex is formed or if an early stage of their formation is observed (eg as a skin tingling sensation), an ointment containing 5% w / w acyclovir is applied topically In general, it is applied 5 times a day or less until herpes simplex subsides. Although the duration of symptoms can be shortened as a result, the patient still suffers from herpes zoster that is bothersome and possibly painful for several days.

  In a treatment embodying the present invention, it is preferable to administer colchicine orally, for example in the form of a tablet or capsule, when the patient recognizes that a trigger event likely to result in herpes simplex occurs or is likely to occur. . Instead of waiting for herpes simplex to appear, the patient takes one or more tablets containing colchicine.

  Alternatively, the patient may immediately apply a topical cream around the area where herpes simplex may occur, typically around the lips. This cream, together with colchicine, comprises the usual excipients and, optionally, an agent for promoting the absorption of colchicine through the patient's skin. Colchicine is thought to penetrate retrogradely along nerve axons toward the trigeminal ganglia that act as reservoirs for latent herpes simplex virus. When HSV is activated, by this stage it moves antegradely towards the surface of the skin, but colchicine is thought to slow or stop its progression along the axon. If HSV does not reach the skin surface, it will not cause herpes simplex.

  The second example relates to patients with a history of herpes simplex infection in and around the eyes. These can lead to corneal ulcers and temporary or permanent damage to the patient's vision. Also, such infections are usually the result of latent HSV in the trigeminal ganglion, reactivated by a recognizable trigger, and propagated antegradely down the nerve axon.

  Current treatment is for the development of symptoms in and around the eyes, by which time the patient's vision may already be at risk. Acyclovir in the form of an ointment is administered until the ulcer has healed (5 times a day).

  In the treatment embodying the invention, colchicine in the form of tablets is administered prior to onset at regular or triggered events. Alternatively, an ointment or eye drop containing a solution of colchicine is administered to the patient's eyes as soon as he notices that a triggering event is likely. As far as the first example is concerned, colchicine raises axons toward the trigeminal ganglion and penetrates retrogradely, preventing or stopping the progression of HSV towards the eye. Having little or no HSV reaching the eye prevents or significantly reduces ulcer formation. Conventional acyclovir ointment treatments are used for ulcers that still occur, but they are much less severe than other conditions, so a much shorter course of treatment is required to remove them Will.

Claims (12)

  Use of an alkaloid or griseofulvin in the manufacture of a medicament for use in the treatment of a virally transmitted virally and antegradely.   2. Use in the manufacture of a medicament according to claim 1, wherein the alkaloid comprises colchicine, vinblastine, vincristine, cytochalasin, or a derivative thereof.   Use of an alkaloid in the manufacture of a medicament according to claim 1 or 2, wherein the viral infection to be treated comprises a herpes infection such as herpes simplex infection.   4. Use according to any one of claims 1 to 3, wherein the medicament is in an orally administrable form.   5. Use according to claim 4, wherein the medicament is administrable in the form of tablets, capsules, powders or granules.   5. Use according to claim 4, wherein the medicament comprises a liquid composition suitable for drinking.   4. Use according to any one of claims 1 to 3, wherein the medicament comprises a locally applicable composition.   4. Use according to any one of claims 1 to 3, wherein the medicament comprises an injectable or injectable liquid composition.   A method for treating a herpes simplex infection comprising administering a substance capable of interfering with or blocking antegrade axonal transport.   10. The method according to claim 9, comprising administering the substance before symptoms of infection develop.   10. The method of claim 9, comprising the step of prophylactically administering the substance.   10. The method of claim 9, comprising administering a composition containing an alkaloid, preferably an antimicrobial alkaloid such as colchicine, vinblastine, or vincristine.