USE OF A HYMENOPTERA VENOM FOR THE MANUFACTURE OF A MEDICAMENT FOR TREATING DNA VIRUS INFECTIONS

Abstract: The present invention relates to the use of hymenoptera venom or proteinaceous or polypeptide components contained therein in the manufacture of a medicament for treating DNA virus infections, and to a method for the treatment of mammalian DNA virus infections which uses hymenoptera venom or proteinaceous or polypeptide components contained therein.

Description: Use o f a h ymenoptera venom for the manufacture of a me d icament for treating DNA virus infec ¬ tions. FIELD OP THE INVENTION The present invention relates to the use of a hymenoptera venom or a proteinaceous or polypeptide component contained therein in the manufacture of a medicament for treating DNA virus infections, and to a method for the treatment of DNA virus infections which uses a hymenoptera venom or a protein¬ aceous or polypeptide component contained therein. BACKGROUND OF THE INVENTION The use of venoms of various origin as components in medica¬ ments is of long standing. Dilute solutions of different hymenoptera venoms are used for injection in immune therapy for patients who are allergic to the stings of the insects. Also, dilute solutions of the venoms are used as allergens by application to the skin in testing for allergy. In recent time, bee venom has been used in the management of certain types of bronchial asthma (Kirusha VP et al., Ter. Arkh. 60 (1988), 81 - 84: Organisation and Results of Treatment Of Bronchial Asthma Patients in the District of Vologda) and in the management of syringomyelia and various related condi¬ tions (Ludyanskii EA, Zh. Nevropatol. Psikhiatr. 91 (1991), 102 - 03. Other diseases in which bee venom has been used or tested are multiple sclerosis, arthritis and diseases which influence the coagulation properties of the blood. Other hymenoptera venoms have been suggested for treatment and prophylaxis of gingivitis. WO 91/08753 (to Gesellschaft fur Strahlen- und Umweltforschung MBH) discloses the use of an agent comprising at least one hymenoptera venom or a compo¬ nent thereof in the treatment of retroviral infections, in particular HIV infection, in a mammal. US 4,822,608 (to Vespa Laboratories, Inc.) discloses the use of at least one hymenoptera venom or a component thereof in combination with an antibiotic agent in the treatment of mammalian infections, including bacterial, viral, and cancerous infections. Combating virus infections is important not only in mammals. Thus, in poultry breeding virus infections may impart con- siderable losses. One of the most promising agents for the treatment of virus infections caused i.a. by herpes simplex virus types 1 and 2 and varicella-zoster virus is known as acyclovir (Whitley RJ, et al., N Engl J ed 327 (1992), 782 - 89: Acyclovir: A Decade Later) . In herpes genitalis, oral or intravenous the¬ rapy with acyclovir which are considered more effective than topical application of acyclovir does not reduce the frequen¬ cy of recurrences. Although the indications for acyclovir therapy expand, the appearance of isolates resistant to acyclovir underscores the need for continued development of new agents with new mechanisms of action. Accordingly, one object of the present invention is to provide an improved medicament and method for the treatment of DNA virus infections, preferably in mammals and birds, more preferred in mammals, which is based on a hymenoptera venom or an active proteinaceous or polypeptide component contained therein or mixtures thereof. Another object of the invention is to provide such a medica¬ ment and a method wherein the hymenoptera venom or component thereof is selected from the group consisting essentially of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, active proteinaceous components of said venoms, active polypeptide components of said venoms, and mixtures thereof. SUMMARY OF THE INVENTION Surprisingly, it has turned out that when a dilute aqueous solution of a hymenoptera venom is applied topically to human skin afflicted by a DNA virus infection a reduction of pain, an accellerated recovery, and a reduction in the number of recurrences is achieved. Thus, in its broadest aspect the present invention relates to the use of a subtoxic amount of a hymenoptera venom or a proteinaceous or a polypeptide component contained therein or mixtures thereof in the manufacture of a medicament for treating DNA virus infections, preferably in mammals and birds, more preferred in mammals and to a method for the treatment of such DNA virus infections which comprises administering to an individual in need of such treatment a subtoxic amount of a hymenoptera venom or a proteinaceous or a polypeptide component contained therein or a mixture there¬ of. In one preferred embodiment, the present invention relates to the use of an agent selected from the group consisting essen- tially of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, active proteinaceous compo¬ nents of said venoms, active polypeptide components of said venoms, and mixtures thereof in the manufacture of a medica¬ ment for treating DNA virus infections. In another preferred embodiment, the present invention re¬ lates to the use of an agent selected from the group con¬ sisting essentially of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, active protein¬ aceous components of said venoms, active polypeptide compo- nents of said venoms, and mixtures thereof in the manufacture of a medicament for treating DNA virus infections, preferably in mammals and birds, more preferred in mammals. In another preferred embodiment, the present invention re¬ lates to the use of an agent selected from the group con¬ sisting essentially of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, active protein- aceous components of said venoms, active polypeptide com¬ ponents of said venoms, and mixtures thereof in the manufac¬ ture of a medicament for treating avian DNA virus infections. In another preferred embodiment, the present invention re¬ lates to the manufacture of a medicament for treating herpes virus infections. In another preferred embodiment, the present invention re¬ lates to the manufacture of a medicament for treating herpes simplex virus type 1 infections. In another preferred embodiment, the present invention re- lates to the manufacture of a medicament for treating herpes simplex virus type 2 infections. In another preferred embodiment, the present invention re¬ lates to the manufacture of a medicament for treating vari¬ cella infections. In another preferred embodiment, the present invention re¬ lates to the manufacture of a medicament for treating herpes zoster infections. In another preferred embodiment, the present invention re¬ lates to the manufacture of a medicament for treating cytome- galovirus infections. In another preferred embodiment, the present invention re¬ lates to the manufacture of a medicament for treating papil- loma virus infections. In another preferred embodiment, the present invention re¬ lates to a method for the treatment of DNA virus infections which comprises administering to an individual in need of such treatment a subtoxic amount of an agent selected from the group consisting of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, active protein¬ aceous components of said venoms, active polypeptide compo¬ nents of said venoms, and mixtures thereof. In another preferred embodiment, the present invention re- lates to a method for the treatment of herpes simplex type 1 infections. In another preferred embodiment, the present invention re¬ lates to a method for the treatment of herpes simplex type 2 infections. In another preferred embodiment, the present invention re¬ lates to a method for the treatment of varicella infections. In another preferred embodiment, the present invention re¬ lates to a method for the treatment of herpes zoster infec¬ tions. In another preferred embodiment, the present invention re¬ lates to a method for the treatment of cytomegalovirus infec¬ tions. In another preferred embodiment, the present invention re¬ lates to a method for the treatment of papilloma infections. DETAILED DESCRIPTION OF THE INVENTION The results reported in the examples indicate that the medi¬ cament and the method according to the present invention provides an improved therapy of DNA virus infections. A turn to the better is seen in three important parameters: the pain is reduced, healing is faster, and there are fewer recurren- cies. The daily dosage of the active agents of this invention is determined according to the condition of the individual to be treated by those skilled in the art. The amount of agent to be administered will depend i.a. on the specific agent in question, the condition to be treated, the particular mode of administration, and on the age, health, sex, bodyweight, and diet of the individual to be treated. Compositions for administering the active agents according to the invention may have either a local or a systemic effect. In such compositions, the active agents according to the invention may be combined with the carriers, adjuvants, and vehicles usually employed in the art. Solutions for topical application of an active agent according to the invention can be made in which water is the only solvent. Alternatively, the solvent can be a mixture of water and one or more pharmaceutically acceptable organic solvents. Other compositions suitable for topical application can be provided in the form of creams, ointments, gels, or powders. A systemic effect can be achieved by injection or infusion of sterile solutions of the active agents according to the invention the solutions being prepared according to the known art. Also, a systemic effect can be achieved by inhalation or by nasal administration of a powder or an aerosol containing the active agent. The present invention is further illustrated by the following examples which, however, are not to be construed as limiting the scope of protection. The features disclosed in the fore- going description and in the following examples may, both separately and in any combination thereof, be material for realising the invention in diverse forms thereof. EXAMPLE 1 Treatment of Herpes Labialis An open trial a was performed using wasp venom (from Vespula vulgaris, obtained from Allergologisk Laboratorium A/S, DK- 2970 Hørsholm, Denmark) . In the trial, the venom was used in the form of an aqueous solution which contained 120 μg/ml of the venom and 0.3 mg/ml of human albumin. 18 patients with recurrent herpes labialis were included in the the trial. The solution was applied topically on the day when the out¬ burst was observed and on the following day. The application was performed as follows: The whole afflicted area was moistened with the solution and allowed to dry. After 10 minutes, 20 minutes, and 30 minutes the afflicted area was again moistened with the solution and allowed to dry. It is estimated that approximately 0.01 ml of the solution was applied to each square centimeter of the afflicted area in each stage of the application. Before the trial, the time from the outburst- of symptoms un¬ til crust formation took place was seven days (median) . In the trial, the time until crust formation took place was two days (median) . Already a few hours after the first applica- tion of the solution the patients felt a reduction in pain. Before the trial, the patients had had an average of six episodes (a minimum of three, a maximum of ten) of herpes labialis per year. During a six month observation period fol¬ lowing the treatment the average number of recurrences was one (a minimum of zero, a maximum of three) . One patient had an outburst of herpes on the upper lip and simultaneously an outburst on the lower lip which looked very similar to the outburst on the upper lip. The solution was only applied to the upper lip where crust formation took place after two days. On the lower lip which was left un¬ treated crust formation only took place after five days. The results are reported in Table 1 Table 1 *) One patient was not followed. **) Medians are reported, figures in paranthesis are ranges. The above findings indicate that treatment with the solution containing vasp venom causes a faster healing of herpes labialis lesions and significantly reduces the number of recurrences. EXAMPLE 2 Treatment of Herpes Genitalis Three male patients with a history of herpes genitalis recurring at least six times per year were treated by topical application of the solution mentioned in Example 1 on the day of the outburst of a new episode and on the following day. The application was performed in four stages as described in Example l. The lesions had a faster healing than usual and less pain was experienced. After one year, two of the patients had had no recurrencies. One and a half year after the treatment the third patient had only had two recurrencies which were abortive episodes with formation of erythema but no crust formation.

Claims: CLAIMS 1. Use of an agent selected from the group con¬ sisting of a hymenoptera venom, an active proteinaceous or polypeptide component contained therein and mixtures thereof in the manufacture of a medicament for treating DNA virus infections. 2. Use according to claim 1 of an agent selected from the group consisting of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, an active proteinaceous or polypeptide component contained in said venoms, and a mixture thereof. 3. Use of an agent according to claim 1 in the manu¬ facture of a medicament for treating herpes virus infections. 4. Use of an agent according to claim 1 in the manu- facture of a medicament for treating herpes simplex virus type 1 infections. 5. Use of an agent according to claim 1 in the manu¬ facture of a medicament for treating herpes simplex virus type 2 infections. 6. Use of an agent according to claim 1 in the manu¬ facture of a medicament for treating varicella infections. 7. Use of an agent according to claim 1 in the manu¬ facture of a medicament for treating herpes zoster infec¬ tions. 8. Use of an agent according to claim 1 in the manu¬ facture of a medicament for treating cytomegalovirus infec¬ tions. 9. Use of an agent according to claim 1 in the manu¬ facture of a medicament for treating papilloma virus infec¬ tions. 10. A method for the treatment of DNA virus infec- 5 tions which comprises administering to an individual in need thereof a medicament comprising a subtoxic amount of an agent selected from the group consisting of a hymenoptera venom, an active proteinaceous or polypeptide component contained therein and a mixture thereof. 1011. A method according to claim 9 wherein the agent is selected from the group consisting of honey bee venom, bumble bee venom, yellow jacket venom, bald faced hornet venom, an active proteinaceous or polypeptide component con¬ tained in said venoms, and a mixture thereof. 1512. A method according to claim 9 for the treatment of herpes virus infections. 13. A method according to claim 9 for the treatment of herpes simplex type 1 virus infections. 14. A method according to claim 9 for the treatment 20 of herpes simplex type 2 virus infections. 15. A method according to claim 9 for the treatment of varicella virus infections. 16. A method according to claim 9 for the treatment of herpes zoster virus infections. 2517. A method according to claim 9 for the treatment of cytomegalovirus infections. 18. A method according to claim 9 for the treatment of papilloma virus infections.

Inventors: HANSEN MICHAEL, NIEBEN OLE GYRING, HANSEN, MICHAEL, NIEBEN, OLE, GYRING
Applicants: HANSEN MICHAEL, NIEBEN OLE GYRING, HANSEN, MICHAEL, NIEBEN, OLE, GYRING
Application year: 1993
Main classification: A61K35
IPC codes: A61K35, A61K38, A61P31