Composition and Method for Inhibiting Herpesviridae Infections

Abstract

The present invention relates to a pharmaceutical composition when used for inhibiting a herpesviridae infection and/or providing relief from a herpesviridae infection in a subject. The composition includes an effective amount of an extract from a plant in the Asteraceae family.

Claims

1. A method of treating shingles in a subject, said method comprising topical application to a lesion and/or an affected area associated with the shingles an effective amount of a composition comprising a topically acceptable additive and a water soluble extract produced by macerating, grinding or crushing all or part of a plant in the Asteraceae family in an aqueous solvent and extracting the water soluble component, wherein the water soluble extract is not an extract from a plant in the sub-families Heliantheae and Asteroideae, or an extract from a plant in the genus Youngia, and thereby treating shingles in the subject.

2. The method according to claim 1, wherein the composition is formulated as a cream, a lotion, a paste, an ointment a gel or a spray.

3. The method according to claim 1, wherein the plant is selected from the group consisting of Chrysanthemum spp., Olearia spp., Brachycome spp., Arctotis hybrids; Celmisa spp. Dimorphotheca spp.; and a daisy referred to as white oxyeye, white daisy, paris daisy, dog daisy, goldens, moon-daisy, maudlin daisy, field daisy, dun daisy, butter daisy, horse daisy, China aster, bellis perennis, Leucanthemum vulgare, or Argyranthemum frutescens.

4. The method according to claim 1, wherein the plant is selected from the group consisting of Chrysanthemum frutescens, varieties referred to as “Marguerite daisy”, Ox-eye daisy (Chrysanthemum leucanthemum), Chrysanthemum×morifolium, Chrysanthemum parthenium, Chrysanthemum vulgare, Chrysanthemum anethifolium, Chrysanthemum indicum, Chrysanthemum balsamita, Olearia phlogopappa, Olearia microphylla, Olearia ramulosa, Brachycome multida, Brachycome iberidfolia, Celmisa incana, and Dimorphotheca aurantiaca.

5. A method of providing relief from shingles in a subject, said method comprising topical application to a lesion and/or affected area associated with the shingles an effective amount of a composition comprising a topically acceptable additive and a water soluble extract produced by macerating, grinding or crushing all or part of a plant in the Asteraceae family in an aqueous solvent and extracting the water soluble component, wherein the water soluble extract is not an extract from a plant in the sub-families Heliantheae and Asteroideae, or an extract from a plant in the genus Youngia., and thereby providing relief from the shingles in the subject.

6. The method according to claim 5, wherein the composition is formulated as a cream, a lotion, a paste, an ointment a gel or a spray.

7. The method according to claim 5, wherein the plant is selected from the group consisting of Chrysanthemum spp., Olearia spp., Brachycome spp., Arctotis hybrids; Celmisa spp. Dimorphotheca spp.; and a daisy referred to as white oxyeye, white daisy, paris daisy, dog daisy, goldens, moon-daisy, maudlin daisy, field daisy, dun daisy, butter daisy, horse daisy, China aster, bellis perennis, Leucanthemum vulgare, or Argyranthemum frutescens.

8. The method according to claim 5, wherein the plant is selected from the group consisting of Chrysanthemum frutescens, varieties referred to as “Marguerite daisy”, Ox-eye daisy (Chrysanthemum leucanthemum), Chrysanthemum×morifolium, Chrysanthemum parthenium, Chrysanthemum vulgare, Chrysanthemum anethifolium, Chrysanthemum indicum, Chrysanthemum balsamita, Olearia phlogopappa, Olearia microphylla, Olearia ramulosa, Brachycome multida, Brachycome iberidfolia, Celmisa incana, and Dimorphotheca aurantiaca.

9. The method according to claim 5, wherein the relief comprises analgesia without an anaesthetic or numbing effect.

Description

DESCRIPTION OF SPECIFIC EMBODIMENTS

[0106] Reference will now be made to experiments that embody the above general principles of the present invention. However, it is to be understood that the following description is not to limit the generality of the above description.

Example 1

Production of Plant Extract

[0107] An amount of marguerite daisy (Chysanthemun frutescens) was macerated in water in a macerator. All or part of the daisy plant was macerated. Typically, a single daisy plant was obtained and the stem, leaves and flowers macerated in water to produce a water soluble extract.

[0108] The extract may be used filtered or not-filtered.

Example 2

Formulations Containing Plant Extract

[0109] (i) Cream Formulation

[0110] The extract produced from Example 1 was prepared as a non-ionic cream formulation for topical application as follows:

[0111] 10 ml of plant extract was combined with 100 grams of a cream containing 15% (v/v) cetomacrogol emulsifying wax, 10% liquid paraffin (w/v), 10% white soft paraffin (v/v), 0.1% (w/v) chlorocresol, 5% propylene glycol (v/v), in an aqueous base.

[0112] (ii) Spray Formulation

[0113] The extract produced from Example 1 was prepared in a spray formulation for application to the mucosal surfaces of the nose or throat as follows:

[0114] 10 ml of plant extract was combined with water to a total volume of 100 ml. The spray was then delivered by way of atomization. Alternatively, the spray formulation was formulated as 10% (v/v) plant extract, 0.5% sodium chloride (w/v), 5% propylene glycol (v/v) in an aqueous base.

[0115] (iii) Gel Formulation

[0116] The extract produced from Example 1 was prepared as a gel formulation for topical application as follows:

[0117] 10 ml of plant extract was combined with 100 ml of a gel formulation containing 25% (v/v) gelatin, 40% glycerol (v/v) in an aqueous base.

[0118] An alternative gel formulation may be prepared as follows: 10 ml of plant extract combined with 100 ml of a gel formulation containing 0.5% (w/v) sodium chloride, 5% (v/v) propylene glycol in an aqueous base.

Example 3

Treatment of Primary Herpetic Gingivostomatitis with Plant Extract

[0119] Case 1:

[0120] A 16 year old otherwise healthy male presented with a two day history of a febrile illness associated with lip blistering and oral ulceration. There was no history of a herpetic infection. The subject had treated his temperature with paracetamol, which had reduced the temperature from 39.7° C. to 37.9° C. He had been unable to eat for two days due to the severity of the pain.

[0121] On examination, a 3.5 cm area of blistering and erythema was present on the skin of the upper lip and on the vermillion of the lower lip. Intraorally, blisters were present on the floor of the mouth and the tonsillar regions of the soft palate.

[0122] The clinical findings were those of a primary herpetic gingivostomatitis. The expected time period for resolution of the symptoms of primary herpetic gingivostomatitis without treatment would be expected to be in the range from 10 to 28 days (Fitzpatrick T. B., et al. (1992) in “Colour atlas and synopsis of Clinical Dermatology” McGraw Inc. N.Y.).

[0123] The subject consented to be treated with the plant extract in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0124] The extract was applied 5 times a day with administration of paracetamol until the temperature normalised. The subject reported immediate pain relief when the cream was applied to the circum-oral blisters.

[0125] The subject was reviewed by telephone 12 hours later and reported a dramatic improvement and was now able to take foods. The subject also reported that the analgesic properties of the plant extract lasted 90 to 120 minutes and that pain relief was evident as soon as the extract was applied.

[0126] The subject was reviewed 24 hours later and reported a continued improvement in the size of the lesions and in the oral pain. The lip blister had reduced to 1 cm and the throat ulcers had almost disappeared. The tongue lesions were slower to respond as the subject had difficulty applying the extract.

[0127] The subject was reviewed at day 4 and reported a complete resolution 24 hours earlier. Clinically, some mild erythema was noted on the upper lip and no oral or throat lesions were present.

[0128] No adverse or hypersensitivity reactions were reported.

[0129] Case 2:

[0130] A 62 year old female presented with a seven day history of oral ulceration affecting the floor of the mouth. There was no history of prior herpetic infections. The subject reported an associated febrile illness and was unable to eat properly.

[0131] On examination, multiple areas of ulceration were present on the floor of the mouth and the ventrum of the tongue.

[0132] The clinical findings were those of a primary herpetic gingivostomatitis. The expected time period for resolution of the symptoms of primary herpetic gingivostomatitis is 10 to 14 days.

[0133] The subject consented to be treated with the plant extract. The plant extract was delivered in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0134] The extract was applied 5 times a day with administration of paracetamol until the temperature normalised.

[0135] At review 48 hours later the subject reported a 40% improvement in the appearance of the lesions and a 75-80% improvement in her symptoms.

[0136] The subject ceased treatment with the extract at the end of day 4 as she was asymptomatic and free of lesions. In the early stages, she reported that the analgesia lasted for 30 to 60 minutes and thus increased the frequency of application. After the first 24 hours the analgesia lasted 90 to 120 mins.

[0137] No adverse or hypersensitive reactions were reported.

[0138] Case 3:

[0139] A 31 year old female presented with a thirty hour history of an inability to eat and increasing swelling and burning of the upper lip, gingivae and anterior hard palate. She required paracetamol for pain relief. There was no history of herpetic infections.

[0140] On examination, extensive blisters and erythema were present on the right upper lip and erythema of the adjacent ginigivae and the anterior hard palate.

[0141] The clinical findings were those of a primary herpetic gingivostomatitis. The subject consented to be treated with the plant extract. The plant extract was delivered in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0142] The extract was applied 5 times a day.

[0143] At review by telephone 24 hours later, the subject reported that she was able to eat that morning (13 hours after the initial presentation) and was asymptomatic at 24 hours. No analgesics were required by the subject. The subject reported some tingling of the lip the following day and so recommenced the application of the extract and the tingling ceased after 3 applications (duration of episode 5 to 6 hours).

[0144] No adverse or hypersensitive reactions were reported.

[0145] A summary of the results is shown in Table 1.

TABLE-US-00001 TABLE 1 Summary of treatment of herpetic gingivostomatitis with plant extract Time to Age(yrs)/ Duration Complete Sex of Symptoms Febrile Relief of Pain Healing 16 Male 2 days yes 90-120 mins 3 days 62 Female 7 days yes 30-60 mins 4 days increasing to 90-120 mins after first day 31 Female 30 hours no 120 mins 1 day

[0146] As can be seen, based on this sample of subjects, the mean healing time was 2.7 days. This is significantly faster than the expected 10-28 days if the subjects were treated symptomatically or with acyclovir.

[0147] The subjects also reported significant pain management and amelioration of undesired sensations with the plant extract and were able to cease use of paracetamol once their temperature had normalised. No adverse or hypersensitivity reactions were reported.

Example 4

Treatment of Recurrent Herpes Labialis with Plant Extract

[0148] An open prospective trial was used to assess the efficacy of the plant extract in the treatment of recurrent herpes labialis. Eight otherwise healthy subjects suffering 37 episodes of the infection entered the study and were treated with the extract in a non-ionic cream that was applied to the lesions 5 times a day. The subjects were reviewed by telephone and in person at regular intervals. The extract was applied by the clinician at the initial examination and any adverse reaction noted.

[0149] Case 1:

[0150] A 65 year old male with controlled hypertension presented with a four day history of a cold sore on the lip that was stinging and burning. He had a history of recurrent herpes labialis that would normally heal in 7 to 10 days.

[0151] The subject consented to be treated with the plant extract in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0152] The cream was applied 5 times a day.

[0153] At review by telephone 24 hours later, the subject reported that the lesion had resolved after 12 hours of treatment.

[0154] No adverse or hypersensitive reactions were reported.

[0155] Case 2:

[0156] A 24 year old female presented with a 24 hour history of a stinging and burning sensation at the base of the nostril due to a current herpes labialis infection. The subject had a history of recurrent herpes labialis.

[0157] The subject consented to be treated with the plant extract in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0158] The cream was applied 5 times a day and the lesion resolved in 36 hours.

[0159] No adverse or hypersensitive reactions were reported.

[0160] Case 3:

[0161] A 20 year old female presented with a recurrent herpetic lesions on the lip that would usually take 7 days to resolve. The current blisters started 24 hours earlier after 2 hours of tingling. The lesions were sensitive and burning.

[0162] The subject consented to be treated with the plant extract in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0163] The cream was applied 5 times a day and the subject reported complete resolution of the lesion by 24 hours.

[0164] No adverse or hypersensitive reactions were reported.

[0165] Case 4:

[0166] A 28 year old female presented with a history of recurrent herpetic lip lesions. The lesions would usually heal in 7-10 days. The current lesion developed 36 hours and was stinging and burning.

[0167] The subject consented to be treated with the plant extract in a cream formulation. Upon treatment, the extract eased the discomfort so that “it felt normal”.

[0168] The cream was applied 5 times a day and the subject reported complete resolution of the lesion in 24 hours.

[0169] No adverse or hypersensitive reactions were reported.

[0170] Case 5:

[0171] A 30 year old female with a history of cold sores that would usually resolve in 7 to 10 days presented with a herpetic lesions that started 24 hours earlier and was localized to the lower left lip. The lesion was burning and was extremely sensitive when eating.

[0172] The subject consented to be treated with the plant extract in a cream formulation. Upon treatment, the subject reported immediate pain relief. The pain relief was not by way of an anaesthetic or numbing effect.

[0173] The cream was applied 5 times a day. At review by telephone 24 hours later, she reported to be at least 70% better. The lesion resolved within 36 hours.

[0174] No adverse or hypersensitive reactions were reported.

[0175] Case 6:

[0176] A 40 year old female presented with a history of recurrent cold sores occurring twice a year and lasting 7 days. At presentation, she reported mild to moderate discomfort from her lip lesion that had been present for 24 hours.

[0177] The subject consented to be treated with the plant extract. Upon treatment, the lesion was 60-70% better at 24 hours and had resolved completely by 30 hours.

[0178] No adverse or hypersensitive reactions were reported.

[0179] Case 7:

[0180] A 50 year old healthy male presented with a 48 hour history of a cold sore on the lower lip. Such lesions would usually resolve within 10 days. The subject reported that the area was tender and sore.

[0181] The subject consented to be treated with the plant extract. Upon treatment, the subject reported that the extract immediately eased his symptoms so that it felt “normal”.

[0182] The cream was applied 5 times a day. At review 24 hours later, the subject reported that he was 50% better and the lesion had resolved completely in 36 hours.

[0183] No adverse or hypersensitive reactions were reported.

[0184] Case 8:

[0185] A 25 year old healthy female presented with a long history of recurrent herpes labialis that would last 7 to 10 days. Over the last three years, the subject had used the extract on 30 episodes of recurrent infection. On each occasion, the tingling and burning was immediately eased by the application of the extract.

[0186] The subject reported that if the lesion was treated as soon as it developed (i.e. within the first 24 hours), the lesion would resolve within 24 hours, but if there was a delay, it would last 36 to 48 hours.

[0187] No adverse or hypersensitive reactions were reported.

[0188] A summary of the results is shown in Table 2.

TABLE-US-00002 TABLE 2 Summary of results of treatment of herpes labialis with plant extract Time to Duration Complete Age(yrs)/Sex of Lesion Relief of Pain Healing 65 Male   4 days immediate 12 hours 20 Female   1 day immediate 24 hours 24 Female   1 day immediate 36 hours 28 Female 1.5 days immediate 12 hours 30 Female   1 day immediate 36 hours 40 Female   1 day immediate 30 hours 50 Male   2 days immediate 36 hours 25 Female 12 lesions @ 0.5 days immediate 12 hours 16 lesions @ 1 day immediate 24 hours  2 lesions @ 1.5 days immediate 36 hours

[0189] Seven subjects each suffered 1 episode of recurrent herpes labialis and the eighth suffered 30 episodes.

[0190] In each case the subjects reported immediate relief of pain on application of the extract. The mean duration of the herpetic lesion prior to treatment was 24 hours. No adverse or hypersensitivity reactions were reported. The mean time for complete healing was 21 hours.

[0191] Studies with acyclovir have stressed the importance of early treatment. Rabon et al. (1989) Oral Surg., Oral Med., Oral Path. 67:676-679 have reported that treatment commenced within 1 hour and achieved analgesia within 1-2 days. Complete healing under these conditions occurred in 7-8 days.

[0192] Thus the agent facilitated the resolution of herpes labialis lesions in 14% of the time for acyclovir, in a modified aqueous base, and in lesions that had been present for 24 hours and longer.

Example 5

Treatment of Recurrent Herpetic Oral Ulceration

[0193] The lesions associated with recurrent herpetic oral ulceration (stomatitis) commonly affect the attached gingivae, palate, tongue and buccal mucosa. Prodromal symptoms are rarely reported and the vesicles break soon after forming due to the frictional forces in the mouth. As such, the lesions are extremely painful and limit the ability of the subject to eat. The lesions usually heal in 7-10 days without scarring (Shafer W. G. et al. (1983) in “A textbook of oral pathology” WE Saunders. (Phil)).

[0194] An open prospective trial was used to assess the efficacy of the extract in the treatment of recurrent herpetic oral ulceration. Nine otherwise healthy subjects entered the study and were treated with the extract in a non-ionic cream that was applied to the lesions 5 times a day. Eight subjects had single episodes and the ninth subject had 2 episodes of herpetic ulceration. The subjects were reviewed by telephone and in person at regular intervals. The agent was applied by the clinician at the initial consultation and any adverse reactions were noted.

[0195] Case 1:

[0196] A 32 year old female presented with a 2 day history of pain on the tip of the tongue that had prevented her from eating. She reported a history of cold sores that would usually heal in 7-10 days. The clinical findings were those of herpetic ulceration.

[0197] The extract was applied and afforded her immediate relief. It was applied 5 times a day and at review by telephone 24 hours later, she reported a 70-80% improvement and she was now able to eat properly. At review, she reported that the lesions had completely resolved within 36 hours.

[0198] No adverse or hypersensitivity reactions were reported

[0199] Case 2:

[0200] An otherwise healthy 27 year old female presented in acute distress due to a 5 hour history of palatal ulceration. She reported a history of cold sores. The palatal ulcers affected the mucosa covering an exostosis. The clinical findings were those of herpetic ulceration.

[0201] The extract was applied and afforded her immediate relief. It was prescribed 5 times a day and the lesion resolved in 36 hours.

[0202] No adverse or hypersensitivity reactions were reported.

[0203] Case 3:

[0204] A healthy 18 year old female presented in acute distress due to her oral ulceration on the hard palate that had been present for 30 hours. She had been unable to eat due to the discomfort. She reported a history of herpes labialis in association with sunburn. The clinical findings were those of herpetic ulceration.

[0205] The extract was applied and afforded her immediate relief. The extract was prescribed 5 times a day and the lesions resolved over the following 48 hours.

[0206] No adverse or hypersensitivity reactions were reported.

[0207] Case 4:

[0208] A healthy 18 year old female with a history of herpes labialis presented with a 1 day history of ulceration on the tongue and adjacent lower lip. She reported a mild discomfort in the region, but felt that the symptoms were intensifying. The clinical findings were those of herpetic ulceration.

[0209] The agent was applied and afforded her immediate relief. It was prescribed 5 times a day and the lesions had resolved in 24 hours.

[0210] No adverse or hypersensitivity reactions were reported.

[0211] Case 5:

[0212] An 18 year old female presented in acute discomfort due to a 24 hour history of palatal ulceration behind the maxillary incisor teeth. She had been unable to eat in this region. She reported a history of cold sores that usually resolved in 10-12 days. The clinical findings were those of herpetic ulceration.

[0213] The extract was applied and afforded her immediate relief and she was able to eat more comfortably. The extract was applied 5 times a day and the lesions resolved completely in 36 hours.

[0214] No adverse or hypersensitivity reactions were reported.

[0215] Case 6:

[0216] A healthy 28 year old female with a history of recurrent herpetic lesions presented with a 1 day history of acute discomfort due to ulcers in her plate and adjacent buccal mucosa. She had been unable to eat due to the discomfort. The clinical findings were those of herpetic ulceration.

[0217] The extract was applied and afforded her immediate relief. Symptomatic relief was maintained provided the extract was reapplied 5 times a day as had been prescribed. She was able to normalize her diet and the lesions resolved in 36 hours.

[0218] No adverse or hypersensitivity reactions were reported.

[0219] Case 7:

[0220] A healthy 30 year old lady presented with a 10 hour history of pain on the hard palate and an inability to eat. She reported a history of cold sores that would resolve in 7-10 days. Clinically, an area of ulceration was present on the palatal vault. These findings were those of herpetic ulceration.

[0221] The extract was applied and afforded her immediate relief. The extract was applied 5 times a day and she reported to be free of pain provided the extract was used. The lesion resolved in 24 hours.

[0222] No adverse or hypersensitivity reactions were reported.

[0223] Case 8:

[0224] A 35 year old healthy female presented with a 5 hour history of painful upper and lower gums which prevented her from eating. She required panadeine for pain relief. She reported a history of herpetic infection. The clinical findings were those of a recurrent herpetic ulceration.

[0225] The agent was applied and afforded her immediate analgesia. The agent was applied 5 times a day and she reported to be 60% better at 24 hours. The lesions had completely resolved by 36 hours.

[0226] No adverse or hypersensitivity reactions were reported.

[0227] Case 9:

[0228] A 54 year old female who takes hormone replacement therapy reported a history of recurrent herpetic ulceration that could affect the palate and adjacent cheek mucosa. The lesions were extremely painful and would take at least 10 days to resolve. At presentation, she reported a 3 day history of pain and stinging in the right cheek mucosa.

[0229] On examination a herpetic ulcer was present on the right cheek mucosa and the anterior hard palate.

[0230] The agent was applied and afforded her immediate relief that lasted for 90 mins. She was reviewed by telephone 24 hours later and reported to be 80% better and the symptoms were controlled by the applications 5 times a day. She later reported that she was completely free of lesions and symptoms within 16 hours.

[0231] While on holidays, 2 months later she developed identical lesions (herpetic) that were present for 12 hours prior to the commencement of the agent.

[0232] The agent was applied and pain relief was immediate. The lesions resolved in 36 hours.

[0233] There were no adverse or hypersensitivity reactions.

[0234] A summary of the results is shown in Table 3.

TABLE-US-00003 TABLE 3 Summary of results of treatment of oral herpetic ulceration with plant extract Time to Duration Complete Age(yrs)/Sex of Symptoms Pain Relief Healing 32 Male 48 hours immediate 36 hours 27 Female  5 hours immediate 36 hours 18 Female 30 hours immediate 48 hours 18 Female 24 hours immediate 24 hours 18 Female 24 hours immediate 36 hours 28 Female 24 hours immediate 36 hours 30 Female 10 hours immediate 24 hours 35 Female  5 hours immediate 36 hours 54 Female 72 hours immediate 36 hours 12 hours immediate 36 hours

[0235] In each instance, the subjects reported immediate pain relief with the use of the extract. Treatment with the extract allowed them to improve their dietary intake.

[0236] The mean duration of symptoms prior to treatment was 25.4 hours and the mean duration of healing was 34.8 hours. No adverse or hypersensitivity reactions were reported.

[0237] The usual treatment for oral herpetic ulceration is a palliative local anaesthetic mouthwash. The lesions would usually heal in 7-10 days

[0238] Thus treatment with the extract results in healing of recurrent herpetic oral ulceration in 15-21% of the time that would normally be expected.

Example 6

Treatment of Herpetic Genital Infection

[0239] An open prospective trial was used to assess the efficacy of the agent in the treatment of recurrent genital herpetic infection. Two otherwise healthy subjects entered the study and were treated with the agent in a non-ionic cream that was applied 5 times a day. It was applied as soon as the lesion appeared.

[0240] Case 1:

[0241] A 35 year old female presented with a long history of recurrent genital herpetic infection that had in the past required prolonged courses of systemic acyclovir. Within 2 days of ceasing the medication, new lesions would develop.

[0242] The subject was prescribed the extract and was told to apply it 5 times a day as required. The subject reported that there was a significant decrease in both the duration and the frequency of the lesions while the agent was used. The results of treatment are shown in Table 4.

TABLE-US-00004 TABLE 4 Results of treatment of genital herpes with plant extract Time for lesions to Interval between Date of Onset resolve (days) attacks (days) Nov. 7, 1993 1 — Nov. 24, 1993 2 16 Jan. 11, 1994 2 46 Jan. 15, 1994 2  2 Feb. 3, 1994 1 17

[0243] No adverse or hypersensitivity reactions were reported.

[0244] Case 2:

[0245] A 40 year old female had a long history of recurrent genital herpetic infection that required prolonged courses of systemic acyclovir. Within 7 days of the cessation of the lesions, new lesions would develop.

[0246] The subject was prescribed the extract and told to apply it 5 times a day as required. The subject reported that there was a significant decrease in the frequency and the duration of the lesions while the agent was used. The results are shown in Table 5.

TABLE-US-00005 TABLE 5 Results of treatment of genital herpes with plant extract Time for lesions to Interval between Date of Onset resolve (days) attacks (days) Jan. 30, 1993 1 — Feb. 24, 1993 1 23 Mar. 13, 1994 1 19

[0247] No adverse or hypersensitivity reactions were reported.

[0248] Summary:

[0249] Both female subjects had been on prolonged courses of oral acyclovir and both experienced recurrence of the problem shortly after its cessation. Both subjects reported an increased interval between attacks when treated with the extract. No adverse or hypersensitivity reactions were reported.

[0250] There was a total of 8 attacks and the mean duration of healing was 1.3 days. This was significantly shorter than the 7.4 day healing rate observed in subjects treated with topical acyclovir (Corey et al. (1982) N. Engl. J. Med. 306:1313-1319) and the 5 day healing rate seen in subjects treated with oral acyclovir (Nilsen et al. (1982) Lancet ii:571-573).

[0251] Thus, when recurrent genital herpetic infection was treated with the extract, the healing time was 18% of that observed with topical acyclovir and 26% of the healing time of that seen with oral acyclovir.

Example 7

Treatment of Herpes Zoster

[0252] An open prospective trial was used to assess the efficacy of the extract in the treatment of herpes zoster. Two otherwise healthy subjects were treated with the extract. It was applied hourly for the first 24 hours and then 2 hourly. The clinical details are outlined below.

[0253] Case 1:

[0254] A 76 year old otherwise healthy male reported developing a transient tingling sensation on the scalp of his right forehead. At day 3 he noted a subtle erythematous localized rash in the right eyebrow. He arrived in Adelaide, South Australia on a holiday later in the week and the extent of the rash had extended.

[0255] He attended Flinders Medical Centre (SA) on the morning of day 6 and a diagnosis of herpes zoster was made. With the informed consent of the subject, he was treated with the extract in the form of a gel and it was applied hourly for the first 24 hours and then 5 times a day. The area was not washed until day 9.

[0256] At presentation, extensive areas of blistering were present on the right scalp that followed the distribution of the opthalmic division of the trigeminal nerve.

[0257] At review 1 hour later, a significant erythema was noted. The subject reported significant and immediate pain relief with each application of the extract. Occasional breakthrough pain occurred towards the end of the day and was controlled by panadeine. No new lesions were observed.

[0258] At 2.5 hours post initial application, initial crusting was observed and no new lesions were present.

[0259] The subject was reviewed by an ophthalmologist at FMC on 3 occasions as a uveitis developed and was treated with prednisolone drops. No viral ocular involvement occurred.

[0260] At review of day 4, the lesions showed evidence of increased healing and no new lesions were seen.

[0261] By day 7 the affected area was extremely dry and scaly and for this reason the extract was changed to a cream base and was applied 5 times a day.

[0262] At review on day 8, a further and significant improvement was noted. The subject was free of pain. The subject left the country the following day and continued with the extract until he ran out 6 days later.

[0263] At day 21 the lesion were almost completely healed.

[0264] No adverse or hypersensitivity reactions were reported.

[0265] Case 2:

[0266] A 93 year old lady with controlled hypertension (Renitec & Minipress) presented with a 7 day history of oral ulceration and blisters on the skin in keeping with herpes zoster affecting the right division of the trigeminal nerve. She was prescribed acyclovir tablets 5 days earlier and required both Digesic 4 hourly and MS Contin (morphine) 30 g 2 times a day for pain relief. The oral lesions were causing her significant distress and she was unable to eat anything but luke warm soup or yoghurt.

[0267] On examination, multiple local crusted lesions were present in the right preauricular and lip and chin region of the face. Intraorally extensive areas of ulceration were present on the right dorsum and lateral margin of the tongue.

[0268] The subject consented to being treated with the extract that afforded her significant and almost immediate pain relief (within 5 minutes). The relief lasted 60-90 minutes and the discomfort was largely controlled with the extract, applying it at ˜60-90 minute intervals for the first 24 hours and then 2 hourly.

[0269] At review 24 hours later, the lesions had reduced to such an extent that the LMO ceased the acyclovir and the extract was continued. She reported a need for analgesics at the end of the day and both Digesic and MS Contin were required. This represented a significant reduction in the intake of painkillers. She was also able to improve her dietary intake and was comfortably managing a wider range of foods.

[0270] At review on day 4, the viral lesions continued to improve and there was no evidence of rebound on withdrawal of the acyclovir. The subject was now managing a normal diet.

[0271] At review on day 5, there was a continued improvement but she still required Ms Contin at the end of the day for pain relief.

[0272] At review of day 7, there was a continued improvement, but her pain at the end of the day continued to be a management problem.

[0273] All lesions had completely resolved on day 9.

[0274] She experiences an ongoing problem of postherpetic neuralgia that was partially responsive to Ms Contin and topical capsaicin.

[0275] Summary:

[0276] In case 1, relief was achieved by and large with the extract alone and no new lesions developed after the commencement of the extract. Initial crusting was observed after 2.5 hours of treatment as compared with 2-3 days for initial crusting when subjects are treated with acyclovir (Esmann et al. (1982) Am. J. Med. 73(1A):320-325; Bean et al (1983) J. Antimicrob Chemo 12 (Sup B):123-127). The subject recovered far more rapidly than would have been expected if acyclovir was used.

[0277] In case 2, the degree of pain was far greater and the use of the agent allowed a significant reduction in the use of both digesic and Ms Contin. While a significant amount of scabbing extraorally had occurred with the use of acyclovir, intraorally ulceration and pain were still a significant problem at the time of commencement of the agent. All lesions responded within 24 hours of the use of the agent.

[0278] In conclusion, in both instances, the extract displayed a significant therapeutic benefit to these subjects with herpes zoster. Initial scabbing was observed in case 1 in 4% of the time expected with oral acyclovir.

Example 8

Treatment of Oral Hairy Leukoplakia

[0279] Oral hairy leukoplakia (OHL) presents as white corrugated lesions on the lateral and dorsal aspects of the tongue and may extend onto the buccal mucosae. It is thought to be due to an epithelial proliferation due to EBV.

[0280] A range of treatment options have been reported. Systemic acyclovir resulted in the resolution of OHL in 12/14 subjects after 20 days (Herbst et al. (1989) JAAD 12:753-756) and Resnick et al (1988) JAMA 259:374-388 reported a response of 5/6 after 10 days of oral acyclovir.

[0281] An open prospective trial was used to assess the efficacy of the extract in the treatment of Oral Hairy Leukoplakia. Three subjects entered the study and were prescribed the extract in a non-ionic cream 5 times a day. The clinician applied the extract in the surgery and no adverse reactions were noted. The clinical details are summarized below.

[0282] Case 1:

[0283] A 70 year old male reported a 6 month history of a roughened and tender lateral margin of his tongue. He was taking Aspirin, Lanoxin, Betaloc, Minipress and Deptran to control his cardiovascular disease and depression. He was otherwise well and was a non-smoker and a non-alcohol consumer.

[0284] On examination, corrugated white lesions were present on the lateral margins of the tongue and extended onto the dorsum.

[0285] The lesion was biopsied and the histopathology was characteristic of oral hairy leukoplakia, with EBV being demonstrated in the koilocytes (EM and EBV probe). He was HIV negative.

[0286] The subject was treated with the extract 5 times a day. At review 3 days later, the lesions had resolved.

[0287] No adverse or hypersensitivity reactions were reported

[0288] Case 2:

[0289] A 45 year old healthy male presented with a 3 week history of focal white patches on the anterior dorsum and lateral margins of the tongue. A biopsy was performed and the histopathology confirmed the clinical diagnosis of oral hairy leukoplakia.

[0290] The lesion was treated with the agent 5 times a day and the lesion resolved completely in 4 days.

[0291] No adverse or hypersensitivity reactions were reported.

[0292] Case 3:

[0293] A 36 year old male with cutaneous psoriasis and oral pemphigus vegetans presented. He developed sensitive corrugated white lesions on the lateral margins of his tongue after a course of topical corticosteroids for his oral pemphigus. These findings were those of biopsy proven oral hairy leukoplakia.

[0294] He was treated with the extract and the sensitivity and mild discomfort resolved immediately. It was applied 5 times a day and the lesions resolved in 3 days. No adverse or hypersensitivity reactions were reported.

[0295] Summary:

[0296] The 3 cases treated with the agent responded in a 3.3 day period (mean), which compares with a response time of at least 10-20 days with oral acyclovir (Herbst et al. (1989) JAAD 12:753-756) and Resnick et al (1988) JAMA 259:374-388).

[0297] Thus it was seen that OHL responded within 33% of the expected time with oral acyclovir.

Example 9

Overview of Treatment of Viral Infections with Extract

[0298] A summary of the results of the treatment of various viral infections with the plant extract are shown in Table 6.

TABLE-US-00006 TABLE 6 Summary of treatment of various viral infections with plant extract Number Healing Time with Expected healing Diagnosis of cases plant extract (mean) time Acyclovir Primary 3 2.7 10 days to Herpetic Stomatitis 4 weeks Recurrent 8 21 hours 7-8 days Herpes Labialis (37 episodes) Recurrent Herpetic 9 34.8 hours Unknown Oral Ulceration (10 episodes) Normal Healing 7-10 days Recurrent Genital 2 1.3 days 7.4 days topical Herpetic Infection (8 episodes) 5 days oral Herpes Zoster 2 2.5 hours with 2-3 days initial crusting initial crusting Oral Hairy 3 3.3 days 10-20 days-oral Leukoplakia

[0299] Finally, it will be appreciated that various modifications and variations of the described methods and compositions of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are apparent to those skilled in the art are intended to be within the scope of the present invention.