CA2174240A1 - Use of peniclorin for the treatment of posttherapeutic neuralgia - Google Patents
Use of peniclorin for the treatment of posttherapeutic neuralgiaInfo
- Publication number
- CA2174240A1 CA2174240A1 CA002174240A CA2174240A CA2174240A1 CA 2174240 A1 CA2174240 A1 CA 2174240A1 CA 002174240 A CA002174240 A CA 002174240A CA 2174240 A CA2174240 A CA 2174240A CA 2174240 A1 CA2174240 A1 CA 2174240A1
- Authority
- CA
- Canada
- Prior art keywords
- treatment
- acyclovir
- composition according
- patients
- phn
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Catching Or Destruction (AREA)
Abstract
The use of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing in the manufacture of a medicament for use in the treatment (including prophylaxis) of post-herpetic neuralgia (PHN).
Description
W 095/11027 2 ~ ~ ~ 2 ~ ~ PCT/GB94/02262 USE OF PENCICLORIN FOR THE TREATMENT OF POSTTHERAPEUTIC NEURALGIA
This invention relates to tre~tmPnt of post-herpetic neuralgia, and to the use ,~ of compounds in the preparation of a metlic~mellt for use in the treatment of such conditions.
r When used herein, 'treatment' inclu(~es prophylaxis as app.opliate.
EP-A-308065 (The Wellcome Foundation r.imited) discloses certain amino acid esters of the purine nucleo.~ide, acyclovir including the compound, 2-[2-amino-1,6-dihydro-6-oxo-9~-purin-9-yl)methoxy3ethyl L-valinate, valaciclovir, as having improved oral bioavailabilty as compared with the alanine and glycine esters of acyclovir, disclosed in EP-A-99493. The prupe,Lies of valaciclovir are reviewed in 'Drugs of the Future, 18, 619-628).
Post-herpetic neuralgia (PHN) is by far the most common complication of herpes zoster infection and is one of the most intractable pain disorders (Strommen et al, Pharmacotherapy. 1988:8:52-68). Patients who develop PHN suffer from a debilit~ting and often intractable pain which can persist for months or even years.
Although rare in patients under 50 years of age, the frequency of PHN rises steeply with increasing age.
There is currently no proven therapy for preventing PHN. The pain is due to injury of the nervous system and therefore seldom responds to analgesia used to treat pain associated with tissue damage. Hence, there is a need for therapy which alleviates or shortens the duration of post-herpetic neuralgia.
For many years, acyclovir given 800 mg five times daily for seven to ten days has been the only oral antiviral agent approved for treatment of acute herpes zoster.
Its effectiveness in lessening the acute signs and symptoms of herpes zoster has been established, but "the effects of acyclovir on postherpetic neuralgia are less clear cut."
(Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks, J. A
r~n(lQmi7Pd trial of acyclovir for 7 days or 21 days with and without prednisolone for tre~tment of acute herpes zoster. New Engl J Med. 1994;330:896-900.) Postherpetic nellr~lgi~ is a common severe complication of herpes zoster. In the largest acyclovir herpes zoster trial (McKPn-irick et al, Br Med J. 1989;298:431), no difference was shown between acyclovir and placebo in either the incidence or the duration of postherpetic neuralgia, despite enrolling only those patiPnr~ most at risk of developing postherpetic neuralgia (eg, elderly). However, in two smaller trials (Huff et al,Am J Med. 1988;85 (Suppl 2A):84-9; Morton and Thompson, NZ Med J.
1989;102:93-5) which enrolled both young and elderly patients in about equal proportions, some effects were seen during the first three months, but not during months 4 to 6. When one of these studies was re-analyzed (Huff et al J Med Virol.
This invention relates to tre~tmPnt of post-herpetic neuralgia, and to the use ,~ of compounds in the preparation of a metlic~mellt for use in the treatment of such conditions.
r When used herein, 'treatment' inclu(~es prophylaxis as app.opliate.
EP-A-308065 (The Wellcome Foundation r.imited) discloses certain amino acid esters of the purine nucleo.~ide, acyclovir including the compound, 2-[2-amino-1,6-dihydro-6-oxo-9~-purin-9-yl)methoxy3ethyl L-valinate, valaciclovir, as having improved oral bioavailabilty as compared with the alanine and glycine esters of acyclovir, disclosed in EP-A-99493. The prupe,Lies of valaciclovir are reviewed in 'Drugs of the Future, 18, 619-628).
Post-herpetic neuralgia (PHN) is by far the most common complication of herpes zoster infection and is one of the most intractable pain disorders (Strommen et al, Pharmacotherapy. 1988:8:52-68). Patients who develop PHN suffer from a debilit~ting and often intractable pain which can persist for months or even years.
Although rare in patients under 50 years of age, the frequency of PHN rises steeply with increasing age.
There is currently no proven therapy for preventing PHN. The pain is due to injury of the nervous system and therefore seldom responds to analgesia used to treat pain associated with tissue damage. Hence, there is a need for therapy which alleviates or shortens the duration of post-herpetic neuralgia.
For many years, acyclovir given 800 mg five times daily for seven to ten days has been the only oral antiviral agent approved for treatment of acute herpes zoster.
Its effectiveness in lessening the acute signs and symptoms of herpes zoster has been established, but "the effects of acyclovir on postherpetic neuralgia are less clear cut."
(Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks, J. A
r~n(lQmi7Pd trial of acyclovir for 7 days or 21 days with and without prednisolone for tre~tment of acute herpes zoster. New Engl J Med. 1994;330:896-900.) Postherpetic nellr~lgi~ is a common severe complication of herpes zoster. In the largest acyclovir herpes zoster trial (McKPn-irick et al, Br Med J. 1989;298:431), no difference was shown between acyclovir and placebo in either the incidence or the duration of postherpetic neuralgia, despite enrolling only those patiPnr~ most at risk of developing postherpetic neuralgia (eg, elderly). However, in two smaller trials (Huff et al,Am J Med. 1988;85 (Suppl 2A):84-9; Morton and Thompson, NZ Med J.
1989;102:93-5) which enrolled both young and elderly patients in about equal proportions, some effects were seen during the first three months, but not during months 4 to 6. When one of these studies was re-analyzed (Huff et al J Med Virol.
2 1 7 ~ 2 ~ Q PCT/GB94102262--1993;1(Suppl 1):93-6), a cignific~nt effect was seen on all zoster-associated pain (ie, contimulm of pain from enrollment into study until complete ces.C~tinn)~ but postherpetic neuralgia was not addressed.
Additionally, a recent study ev~lu~ting acyclovir ~minictPred for 7 or 21 days 5 with or without concomitant prednisolone for the tre~tmPnt of acute herpes zoster revealed that although acute pain was reduced in patients treated with concomitant predni.cQIQne or 21 days of acyclovir compared with those who had received 7 days of acyclovir tre~tm~nt alone, neither the frequency of zoster-associated pain nor the time to complete cess~tiQn of pain was affected by the 14 additional days of acyclovir tre~tmPnt or by concomitant prednisolone therapy (New Engl J Med. 1994;330:896-900). No information on the duration of postherpetic neuralgia was reported fromthat study. Also, as this study did not include a placebo control, no conclusion can be drawn regarding the effect of acyclovir on postherpetic neuralgia.
Beutner et al in 'Abstract. American Academy of Dermatology Annual Meeting, San Francisco, USA, 30 July - 4 August 1994' report efficacy of valaciclovir in zoster associated pain.
It has now been discovered that the above compounds are effective in reducing the duration of PHN when given to the patient during the acute infection.
Accordingly, the present invention provides a method of tre~tmPnt of PHN in 20 h~m~n.s, which method comprises the ~minictration to the human in need of such tre~tment, an effective amount of acyclovir or a biol,lt;.;ulsor, or a ph~rrn~reuti~lly acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing.
Examples of bioprecursors, pharmaceutically acceptable salts and derivatives are as described in the aforementioned European Patent references, the subject matter 25 of which are incorporated herein by reference.
A particular compound of interest is valaciclovir, the well-absorbed oral form of acyclovir (ACV).
The compound, in particular, acyclovir or valaciclovir, may be ~fiminictered by the oral route to hum~ns and may be compounded in the form of syrup, tablets or 30 c~rsulP When in the form of a tablet, any ph~rm~cellti~ ~l carrier suitable for formulating such solid compositions may be used, for example m~gnecit-m stearate, starch, lactose, glucose, rice, flour and chaL~c The compound may also be in the form of an ingestible capsule, for example of gelatin, to contain the compound, or in the form of a syrup, a solution or a s~spencion Suitable liquid ph~rm~t~eutic~l carriers 35 include ethyl alcohol, glycerine, saline and water to which flavouring or colouring agents may be added to form syrups. S~st~ined release form~ tions, for example tablets cont~ining an enteric coating, are also envisaged.
For parenteral ~rlministration~ fluid unit dose forms are prepared c~nt~inin Wo 95/11027 21 7 ~ 2~ o PcTlGs94lo2262 the compound and a sterile vehicle. The compound depending on the vehicle and the concelltr~tion, can be either suspended or dissolved. Parenteral solutions are norm~lly prepared by dissolving the compound in a vehicle and filter st~Prili~ing before filling into a suitable vial or ampoule and sP~iing- Advantageously, adjuvants 5 such as a local ~n~PsthP,tic7 plesel vatives and b"rr~ ;ng agents are also dissolved in the vehicle. To enh~nl~e the stability, the composition can be frozen after filling into the vial and the water removed under vacuum.
P~e~ l su~pen.cion.c are prepared in subst~nti~lly the same manner except that the compound is suspended in the vehicle instead of being dissolved and 10 sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
Advantageously, a surfactant or wetting agent is inclu ied in the composition tof~rilit~t~P uniform distribution of the compound of the invention.
As is common practice, the compositions will usually be accomp~niPd by written or printed directions for use in the medical treatment concerned.
An amount effective to treat the virus infection depends on the nature and severity of the infection and the weight of the m~mm~l A suitable dosage unit might contain from 50mg to lg of active ingredient, for example 800 mg in the case of acyclovir and 1000 mg in the case of valaciclovir.
Such doses may be ~mini~tpred up to 5 times a day, 5 times a day in the case of acyclovir and 2 or 3 times per day in the case of valaciclovir. The effective dose of compound is based on ~lminictration to an adult of 70kg body weight.
The treatment is preferably carried out as soon as possible after symptoms appear usually within 72 hours, preferably within 48 hours of rash onset and within 36 or 24 hours of rash onset if at all possible.
The tre~tment period is usually 7 days although it may be less or more than this, for example 5, 6, 10. 14, 21 days or for an indefinitP period.
The tre~tmPnt is particularly effective in the case of patients of greater than 50 years of age, and efficacy would be expected to be demon.ctr~ted further in patients greater than 60 years of age, especi~lly patients of greater than 70 years of age.
The present invention also provides the use of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosph~tP. ester and/or acyl deAvative of either of the foregoing, in the preparation of a mPt~ mPnt for use in the tre~tment of PHN.
Such tre~tmpnt may be carried out in the manner as hereinbefore descAbed.
The present invention further provides a ph~rm~ceutical composition for use in the tre~tme-nt of PHN, which compAses an effective amount of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyldeAvative of either of the foregoing, and a ph~rm~reuti~lly acceptable carAer. Such compositions may be prepared in the manner as hereinafter descAbed.
WO 95/11027 ~ 2 4 PCT/GB94/02262 --The following clinical data illustrate the invention.
~lin;~l Data S Patients >18 years of age with clinically (~i~gnosed uncomrlic~t~cl herpes zoster infection based on clinical judgment who gave written informed consent were eligible for study entry. Exclusion criteria insludecl patients with zoster rash that had been present for >72 hours; complications of herpes zoster (eg, ocular or visceral involvement, diccemin~ted zoster); presence of crusts at enrollment; patients with 10 other serious underlying disease (eg, immunoco~ ised and/or HIV-infect~d individuals); or pregnant or l?ct~ting females.
Patients were prohibited from receiving any concomitant antiviral or immunomodifying therapy and any topical me~lieation which would be applied to zoster lesions during the course of the study.
Patients were instructed to return to the clinic for lesion and pain evaluationseach of the seven therapy days and every day for the next seven days following therapy. Patients with lesions that were fully crusted by day 7 were ex~minPd every other day of the week following therapy. After day 14, weekly visits were required of all p~tip~nts until all lesions had lost their crusts. Patients were assessed for the presence of postherpetic neuralgia at monthly intervals following healing for an~litinn~l five months.
The number of papules, vesicles, ulcers, and crusts within the primary dermatome was recorded as none, mild (<25 lesions), moderate (25-50 lesions), orsevere (>50 lesions). A specimen for viral culture was taken at baseline and daily thereafter while vesicles were present. Patients were asked to rate the intensity of their pain on a scale of none, mild, moderate, or severe.
Wo 95/11027 2 1 7 4 2 4 0 PcT/Gss4/02262--The effect of tre~tm~-nt on resoludon of pain following healing was assessed by de~lllfinillg the median dme to pain resoludon By 90 days after healing 60% of the p~ti~nts had lost pain. In patdents >50 years of age, median time to loss of pain following healing was 57 days.
S
Time to event Acyclovir (days) 800 m~*
Median 58 Ql 30 * Five tdmes daily by oral ~mini.ctration Time to event: Timepoints at which at least 25% (Q1), 50% (Median), or 75% (Q3) of the padents no longer had pain When the figures are compared with those for famciclovir (FCV) and placebo, the results were as follows:
The median tdmes to loss of pain following healing in a first study were compared with those seen in a second study for all padents and in patdents >50 years 15 of age, to con~ll-ing that the speed of pain resoludons were of the same order for famciclovir, and to establish the improvement of acyclovir (ACV) over placebo.
Study Group FCV FCV FCV Placebo ACV
250m~ 500m~ 750m~
first All S6 Sl 38 58 second All 63 61 119 first 250yrs S6 55 43 S7 second 250yrs 63 63 163
Additionally, a recent study ev~lu~ting acyclovir ~minictPred for 7 or 21 days 5 with or without concomitant prednisolone for the tre~tmPnt of acute herpes zoster revealed that although acute pain was reduced in patients treated with concomitant predni.cQIQne or 21 days of acyclovir compared with those who had received 7 days of acyclovir tre~tm~nt alone, neither the frequency of zoster-associated pain nor the time to complete cess~tiQn of pain was affected by the 14 additional days of acyclovir tre~tmPnt or by concomitant prednisolone therapy (New Engl J Med. 1994;330:896-900). No information on the duration of postherpetic neuralgia was reported fromthat study. Also, as this study did not include a placebo control, no conclusion can be drawn regarding the effect of acyclovir on postherpetic neuralgia.
Beutner et al in 'Abstract. American Academy of Dermatology Annual Meeting, San Francisco, USA, 30 July - 4 August 1994' report efficacy of valaciclovir in zoster associated pain.
It has now been discovered that the above compounds are effective in reducing the duration of PHN when given to the patient during the acute infection.
Accordingly, the present invention provides a method of tre~tmPnt of PHN in 20 h~m~n.s, which method comprises the ~minictration to the human in need of such tre~tment, an effective amount of acyclovir or a biol,lt;.;ulsor, or a ph~rrn~reuti~lly acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing.
Examples of bioprecursors, pharmaceutically acceptable salts and derivatives are as described in the aforementioned European Patent references, the subject matter 25 of which are incorporated herein by reference.
A particular compound of interest is valaciclovir, the well-absorbed oral form of acyclovir (ACV).
The compound, in particular, acyclovir or valaciclovir, may be ~fiminictered by the oral route to hum~ns and may be compounded in the form of syrup, tablets or 30 c~rsulP When in the form of a tablet, any ph~rm~cellti~ ~l carrier suitable for formulating such solid compositions may be used, for example m~gnecit-m stearate, starch, lactose, glucose, rice, flour and chaL~c The compound may also be in the form of an ingestible capsule, for example of gelatin, to contain the compound, or in the form of a syrup, a solution or a s~spencion Suitable liquid ph~rm~t~eutic~l carriers 35 include ethyl alcohol, glycerine, saline and water to which flavouring or colouring agents may be added to form syrups. S~st~ined release form~ tions, for example tablets cont~ining an enteric coating, are also envisaged.
For parenteral ~rlministration~ fluid unit dose forms are prepared c~nt~inin Wo 95/11027 21 7 ~ 2~ o PcTlGs94lo2262 the compound and a sterile vehicle. The compound depending on the vehicle and the concelltr~tion, can be either suspended or dissolved. Parenteral solutions are norm~lly prepared by dissolving the compound in a vehicle and filter st~Prili~ing before filling into a suitable vial or ampoule and sP~iing- Advantageously, adjuvants 5 such as a local ~n~PsthP,tic7 plesel vatives and b"rr~ ;ng agents are also dissolved in the vehicle. To enh~nl~e the stability, the composition can be frozen after filling into the vial and the water removed under vacuum.
P~e~ l su~pen.cion.c are prepared in subst~nti~lly the same manner except that the compound is suspended in the vehicle instead of being dissolved and 10 sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
Advantageously, a surfactant or wetting agent is inclu ied in the composition tof~rilit~t~P uniform distribution of the compound of the invention.
As is common practice, the compositions will usually be accomp~niPd by written or printed directions for use in the medical treatment concerned.
An amount effective to treat the virus infection depends on the nature and severity of the infection and the weight of the m~mm~l A suitable dosage unit might contain from 50mg to lg of active ingredient, for example 800 mg in the case of acyclovir and 1000 mg in the case of valaciclovir.
Such doses may be ~mini~tpred up to 5 times a day, 5 times a day in the case of acyclovir and 2 or 3 times per day in the case of valaciclovir. The effective dose of compound is based on ~lminictration to an adult of 70kg body weight.
The treatment is preferably carried out as soon as possible after symptoms appear usually within 72 hours, preferably within 48 hours of rash onset and within 36 or 24 hours of rash onset if at all possible.
The tre~tment period is usually 7 days although it may be less or more than this, for example 5, 6, 10. 14, 21 days or for an indefinitP period.
The tre~tmPnt is particularly effective in the case of patients of greater than 50 years of age, and efficacy would be expected to be demon.ctr~ted further in patients greater than 60 years of age, especi~lly patients of greater than 70 years of age.
The present invention also provides the use of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosph~tP. ester and/or acyl deAvative of either of the foregoing, in the preparation of a mPt~ mPnt for use in the tre~tment of PHN.
Such tre~tmpnt may be carried out in the manner as hereinbefore descAbed.
The present invention further provides a ph~rm~ceutical composition for use in the tre~tme-nt of PHN, which compAses an effective amount of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyldeAvative of either of the foregoing, and a ph~rm~reuti~lly acceptable carAer. Such compositions may be prepared in the manner as hereinafter descAbed.
WO 95/11027 ~ 2 4 PCT/GB94/02262 --The following clinical data illustrate the invention.
~lin;~l Data S Patients >18 years of age with clinically (~i~gnosed uncomrlic~t~cl herpes zoster infection based on clinical judgment who gave written informed consent were eligible for study entry. Exclusion criteria insludecl patients with zoster rash that had been present for >72 hours; complications of herpes zoster (eg, ocular or visceral involvement, diccemin~ted zoster); presence of crusts at enrollment; patients with 10 other serious underlying disease (eg, immunoco~ ised and/or HIV-infect~d individuals); or pregnant or l?ct~ting females.
Patients were prohibited from receiving any concomitant antiviral or immunomodifying therapy and any topical me~lieation which would be applied to zoster lesions during the course of the study.
Patients were instructed to return to the clinic for lesion and pain evaluationseach of the seven therapy days and every day for the next seven days following therapy. Patients with lesions that were fully crusted by day 7 were ex~minPd every other day of the week following therapy. After day 14, weekly visits were required of all p~tip~nts until all lesions had lost their crusts. Patients were assessed for the presence of postherpetic neuralgia at monthly intervals following healing for an~litinn~l five months.
The number of papules, vesicles, ulcers, and crusts within the primary dermatome was recorded as none, mild (<25 lesions), moderate (25-50 lesions), orsevere (>50 lesions). A specimen for viral culture was taken at baseline and daily thereafter while vesicles were present. Patients were asked to rate the intensity of their pain on a scale of none, mild, moderate, or severe.
Wo 95/11027 2 1 7 4 2 4 0 PcT/Gss4/02262--The effect of tre~tm~-nt on resoludon of pain following healing was assessed by de~lllfinillg the median dme to pain resoludon By 90 days after healing 60% of the p~ti~nts had lost pain. In patdents >50 years of age, median time to loss of pain following healing was 57 days.
S
Time to event Acyclovir (days) 800 m~*
Median 58 Ql 30 * Five tdmes daily by oral ~mini.ctration Time to event: Timepoints at which at least 25% (Q1), 50% (Median), or 75% (Q3) of the padents no longer had pain When the figures are compared with those for famciclovir (FCV) and placebo, the results were as follows:
The median tdmes to loss of pain following healing in a first study were compared with those seen in a second study for all padents and in patdents >50 years 15 of age, to con~ll-ing that the speed of pain resoludons were of the same order for famciclovir, and to establish the improvement of acyclovir (ACV) over placebo.
Study Group FCV FCV FCV Placebo ACV
250m~ 500m~ 750m~
first All S6 Sl 38 58 second All 63 61 119 first 250yrs S6 55 43 S7 second 250yrs 63 63 163
Claims (11)
1. A method for the treatment (including prophylaxis) of PHN in mammals, including humans, which method comprises administering to the mammal in need of such treatment an effective amount of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing.
2. The use of acyclovir or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing in the manufacture of a medicament for use in the treatment (including prophylaxis) of PHN.
3. A pharmaceutical composition for use in the treatment (including prophylaxis) of PHN, which comprises acyclovir, or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing, and a pharmaceutically acceptable carrier.
4. A method, use or composition according to claim 1, 2 or 3 wherein the treatment is within 72 hours of herpes zoster rash onset.
5. A method, use or composition according to claim 4 wherein the treatment is within 48 hours of rash onset.
6. A method, use or composition according to any one of claims 1 to 5 where the treatment period is 7 days.
7. A method, use or composition according to any one of claims 1 to 6 wherein the treatment is carried out on patients of greater than 50 years of age.
8. A method, use or composition according to claim 7 wherein the treatment is carried out on patients of greater than 60 years of age.
9. A method, use or composition according to claim 8 wherein the treatment is carried out on patients of greater than 70 years of age.
10. A method, use or composition according to any one of claims 1 to 9 wherein the Compound is acyclovir.
11. A method, use or composition according to any one of claims 1 to 9 wherein the Compound is valaciclovir.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9321394.0 | 1993-10-16 | ||
| GB939321394A GB9321394D0 (en) | 1993-10-16 | 1993-10-16 | Pharmaceuticals |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2174240A1 true CA2174240A1 (en) | 1995-04-27 |
Family
ID=10743678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002174240A Abandoned CA2174240A1 (en) | 1993-10-16 | 1994-10-14 | Use of peniclorin for the treatment of posttherapeutic neuralgia |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0723448A1 (en) |
| JP (1) | JPH09503779A (en) |
| AU (1) | AU7860394A (en) |
| BE (1) | BE1007586A3 (en) |
| CA (1) | CA2174240A1 (en) |
| FR (1) | FR2711061B1 (en) |
| GB (2) | GB9321394D0 (en) |
| WO (1) | WO1995011027A1 (en) |
| ZA (1) | ZA948065B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ508489A (en) * | 1998-07-09 | 2004-06-25 | Warner Lambert Co | Pharmaceutical composition containing GABA analogs and an antiviral agent to treat shingles |
-
1993
- 1993-10-16 GB GB939321394A patent/GB9321394D0/en active Pending
-
1994
- 1994-10-14 JP JP7511498A patent/JPH09503779A/en active Pending
- 1994-10-14 AU AU78603/94A patent/AU7860394A/en not_active Abandoned
- 1994-10-14 FR FR9412300A patent/FR2711061B1/en not_active Expired - Fee Related
- 1994-10-14 ZA ZA948065A patent/ZA948065B/en unknown
- 1994-10-14 EP EP94929608A patent/EP0723448A1/en not_active Withdrawn
- 1994-10-14 GB GB9420754A patent/GB2282759A/en not_active Withdrawn
- 1994-10-14 CA CA002174240A patent/CA2174240A1/en not_active Abandoned
- 1994-10-14 WO PCT/GB1994/002262 patent/WO1995011027A1/en not_active Application Discontinuation
- 1994-10-14 BE BE9400928A patent/BE1007586A3/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2711061B1 (en) | 1995-12-01 |
| WO1995011027A1 (en) | 1995-04-27 |
| GB2282759A (en) | 1995-04-19 |
| JPH09503779A (en) | 1997-04-15 |
| GB9420754D0 (en) | 1994-11-30 |
| ZA948065B (en) | 1996-04-10 |
| FR2711061A1 (en) | 1995-04-21 |
| BE1007586A3 (en) | 1995-08-16 |
| EP0723448A1 (en) | 1996-07-31 |
| AU7860394A (en) | 1995-05-08 |
| GB9321394D0 (en) | 1993-12-08 |
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