WO2007100525A2

WO2007100525A2 - Methods for the treatment of viral diseases

Info

Publication number: WO2007100525A2
Application number: PCT/US2007/004168
Authority: WO
Inventors: Ruben G. Fabunan
Original assignee: Fil-Am Tech Inc
Current assignee: Fil-Am Tech Inc
Priority date: 2006-02-27
Filing date: 2007-02-15
Publication date: 2007-09-07
Anticipated expiration: 2008-08-27
Also published as: WO2007100525A3

Abstract

SARS, Ebola, Marburg, West Nile, German Measles, Yellow Fever, Saint Louis Encephalitis, Japanese Encephalitis, California Encephalitis, Human T-cell Leukemia, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever are treated by IM injection of a mixture comprising a first ingredient selected from the group consisting of procaine, chloroprocaine, tetracaine, chlorotetracaine, bromoprocaine, proparacaine, fluoroprocaine and benzocaine, and a second ingredient selected from the group consisting of dexamethasone, flumethasone and betamethasone.

Description

Viral Treatment

Related Application

[01] The present application claims priority from and is a continuation-in-part of U.S. Provisional Patent Application 60/777,052 filed February 27, 2006.

Background of the Invention

[02] The present invention provides a method of treating various diseases caused by viruses. Such diseases include Severe Acute Respiratory Syndrome Pneumonia (SARS Coronavirus or SARS-CoV), Ebola Hemorrhagic Fever (Ebola Virus), Marburg Hemorrhagic Fever (Marburg Virus), West Nile Fever or Encephalitis (West Nile virus), German Measles (Rubella), Yellow Fever (Yellow Fever Virus), Saint Louis Encephalitis (Saint Louis Encephalitis Virus), Japanese Encephalitis (Japanese Encephalitis Virus), California Encephalitis (California Encephalitis Virus), Human T-cell Leukemia (HTLV-I), Newcastle Disease (Newcastle Disease Virus), respiratory tract infection and bronchitis (Respiratory Syncytial Virus), Lymphocytic Choriomeningitis (Lymphocytic Choriomeningitis Virus), Lassa

Hemorrhagic Fever (Lassa Virus), and Hanta Hemorrhagic Fever (Hantavirus). The present invention represents an ongoing effort to find effective treatments (either to cure or to ameliorate symptoms) against these diseases.

Summary of the Invention [03] SARS, Ebola, Marburg, West Nile, German Measles, Yellow Fever, Saint Louis

Encephalitis, Japanese Encephalitis, California Encephalitis, Human T-cell Leukemia, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever are treated by intramuscular (IM) injection of a composition comprising a first ingredient selected from the group consisting of procaine, chloroprocaine, tetracaine, chlorotetracaine, bromoprocaine, proparacaine, fluoroprocaine and benzocaine, and a second ingredient selected from the group consisting of dexamethasone, flumethasone and betamethasone. The treatment further comprises administration of an electrolyte solution such as Hydrite, PEDIALYTE, etc. In an embodiment, the hydration solution is about half a tablet of Hydrite in approximately 500 ml water. In addition, the patient is also treated by administration of an antipyretic, such as calpol, paracetamol, aspirin, acetaminophen, ibuprofen, etc.

Detailed Description of the Invention [04] The present invention is directed to the treatment of SARS, Ebola, Marburg, West

Nile, German Measles, Yellow Fever, Saint Louis Encephalitis, Japanese Encephalitis, California Encephalitis, Human T-cell Leukemia, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever by IM injection of a mixture comprising a first ingredient selected from the group consisting of procaine, chloroprocaine, tetracaine, chlorotetracaine, bromoprocaine, proparacaine, fmoroprocaine and benzocaine, and a second ingredient selected from the group consisting of dexamethasone, flumethasone and betamethasone. In the context of the present disclosure, the named ingredients also include therapeutically effective salts and hydrates, thereof. [05] The scope of the present invention includes variants of viruses that cause the above-referenced diseases. For example, the Hantavirus includes numerous variants, including the Hantaan virus, the Puumala virus, the SEO virus, the Dobrava virus, the Sin Nombre virus, etc. Conversely, some of the above-referenced diseases are variants of the same genus. For example West Nile Disease and Japanese encephalitis are caused by variants of the Flavivirus genus, which also includes the Murray Valley encephalitis virus. The present disclosure encompasses all variants of the specifically referenced diseases that are capable of being treated by the method described herein.

[06] The treatment further comprises administration of an electrolyte solution such as Hydrite, PEDIALYTE, etc. Electrolytes can be administered orally or intravenously. In addition, the patient is also treated by administration of an antipyretic, such as calpol, paracetamol, aspirin, acetaminophen, ibuprofen, etc.

[07] The term "therapeutically effective salts or hydrates," as use herein, represents those salts or hydrates which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like and correspond to a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well-known in the art. The salts can be prepared in-situ during the final isolation and purification of the compounds of the invention or separately by reacting the free base group with a suitable organic acid. Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphersulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methyl amine, dimethyl amine, trimethylamine, triethylamine, ethylamine and the like.

[08] Injectable mixtures of this invention comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), vegetable oils (such as olive oil), injectable organic esters (such as ethyl oleate) and suitable mixtures thereof. Proper fluidity may be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.

[09] These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin.

[10] The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use.

[HJ A SARS patient is IM injected with a 2 ml dose of a 9:1 mixture of chloroprocaine (20 mg/ml) and dexamethasone (4 mg/ml) mixture followed by a second dose 60 minutes later. In addition, the patient is treated with electrolyte solution (about 500 ml per day) and aspirin, as needed. The treatment is repeated a second day and a third day (each with a 90 minute interval).

[12] A West Nile infant patient is IM injected with a 1 ml dose of a mixture of procaine and betamethasone mixture followed by a second dose 60 minutes later. In addition, the patient is treated with electrolyte solution and paracetamol. The treatment is repeated a second and a third day.

[13] An Ebola patient is IM injected with a 2 ml dose of a 9:1 mixture of tetracaine (20 mg/ml) and flumethasone (4 mg/ml) mixture. In addition, the patient is treated with electrolyte solution. The treatment is repeated daily for four days.

[14] An elderly Human T-cell Leukemia patient is IM injected with a 2 ml dose of a mixture of chloroprocaine and flumethasone mixture. In addition, the patient is treated with oral electrolyte solution. The treatment is repeated daily for 30 days. Thereafter, a maintenance dose is provided once weekly.

[15] An adult Marburg patient is treated with between about 1 -10 ml IM injection of a mixture comprising between about 0.6-9.5 ml of about 0.5-13% chloroprocaine and between about 0.1-8.7 ml of about 4 mg/ml dexamethasone sodium phosphate. In another embodiment, an adult Marburg patient is treated with between about 0.1-10 ml IM injection of a mixture comprising between about 0.1 -9.9 ml of about 0.5- 11 % proparacaine and between about 0.1 -8.4 ml of about 2-10 mg/ml betamethasone. A further embodiment treats an adult Marburg patient with between about 1-10 ml IM injection of between about 0.1-9.6 ml of about 0.5-30% benzocaine and between about 0.1-7.9 ml of about 2-10 mg/ml dexamethasone. Yet another embodiment treats an adult Marburg patient with between about 1-10 ml IM injection of between about 0.4-9.6 ml of about 0.5-20% chlorotetracaine and between about 0.1-8.0 ml of about 2-10 mg/ml flumethasone. In yet another embodiment, an adult Marburg patient is treated with between about 1-10 ml IM injection of amixture comprising between about 0.1-8.5 ml of about 0.5-18% tetracaine and between about 0.01-7.7 ml of about 4 mg/ml dexamethasone. Yet another embodiment treats an adult Marburg patient with between about 1-10 ml IM injection of a mixture comprising between about 0.6-9.5 ml of about 0.5-13% fluoroprocaine and between about 0.1-8.7 ml of about 4 mg/ml dexamethasone sodium phosphate. In a further embodiment, the patient is further treated with an oral hydration solution during treatment.

[16] In a Lymphocytic Choriomeningitis treatment, two injections of between about 0.1-9.6 ml of about 0.5-30% benzocaine and between about 0.1-7.9 ml of about 2-10 mg/ml betamethasone are administered daily over an about 60-120 minute interval for between about 3- 5 days. As an example, an adult Lymphocytic Choriomeningitis patient may be treated with two about 2 ml doses at about 60-90 minute intervals for about 11-18 days. During the IM treatment, the patient is further treated with an oral hydration solution. A child may be treated with about 1 ml doses.

[17] A Newcastle Disease patient is treated with between about 1-10 ml IM injection of a mixture comprising between about 0.3-8.7 ml of about 1-12% bromoprocaine and between about 0.1-7.9 ml of about 2-10 mg/ml flumethasone. In another embodiment, an adult Newcastle Disease patient is treated with between about 1-10 ml IM injection of a mixture comprising between about 0.1-9.0ml of about 0.5-15% chloroprocaine and between about 0.1-8.4 ml of about 4 mg/ml dexamethasone. A further embodiment treats an adult Newcastle Disease patient with between about 1-10 ml IM injection of a mixture comprising between about 0.3-8.6 ml of about 0.5-14% tetracaine and between about 0.1-8.8 ml of about 2-10 mg/ml betamethasone.

Yet another embodiment treats an adult Newcastle Disease patient with between about 1-5 ml IM injection of a mixture comprising between about 0.2-8.9 ml of about 1-17% chloroprocaine and between about 0.1-7.8 ml of about 4 mg/ml betamethasone. In yet another embodiment, an adult Newcastle Disease patient is treated with between about 0.5-10 ml IM injection of a mixture comprising between about 0.2-7.9 ml of about 0.5-22% proparacaine and between about 0.01 -9.2 ml of about 4 mg/ml flumethasone. In another embodiment, an adult Newcastle Disease patient is treated with between about 1-10 ml IM injection of a mixture comprising between about 0.1- 9.0 ml of about 0.5-15% fluoroprocaine and between about 0.1-8.4 ml of about 4 mg/ml dexamethasone. During the IM treatment, the patient is further treated with an oral hydration solution. [18] In a Hanta Hemorrhagic Fever embodiment, one or two injections of chloroprocaine and dexamethasone are administered daily for between about 1-3 days. When two injections are made, they are administered over an about 60-120 minute interval. As an example, an adult Hanta Hemorrhagic Fever patient is treated with about two 2 ml doses at about 60-90 minute intervals for 1-5 days. The patient is further treated with an oral hydration solution (bottled water 500 ml mixed with Vi electrolyte tablet). A child may be treated with 1 ml doses.

[19] More generally, an adult Encephalitis patient is treated with between about 1-10 ml IM injection of a mixture comprising between about 0.2-7.9 ml of about 0.5-17% tetracaine and between about 0.1-8.5 ml of about 2-10 mg/ml flumethasone. In another embodiment, an adult Encephalitis patient is treated with between about 0.1-10 ml IM injection of a mixture comprising between about 0.1-8.8 ml of about 0.5-14% chloroprocaine and between about 0.1- 9.3 ml of about 4 mg/ml flumethasone. A further embodiment treats an adult Encephalitis patient with between about 1-10 ml IM injection of a mixture comprising between about 0.2-7.9 ml of about 1-15% bromoprocaine and between about 0.2-9.9 ml of about 4 mg/ml dexamethasone. Yet another embodiment treats an adult Encephalitis patient with between about 1-10 ml IM injection of a mixture comprising between about 0.1-9.2 ml of about 0.5-15% proparacaine and between about 0.3-9.6 ml of about 4 mg/ml betamethasone. In yet another embodiment, an adult Encephalitis patient is treated with between about 0.5-10 ml IM injection of a mixture comprising between about 0.1-9.4 ml of about 0.5-33% benzocaine and between about 0.1-8.1 ml of about 2-10 mg/ml betamethasone. A further embodiment treats an adult Encephalitis patient with between about 1-10 ml IM injection of a mixture comprising between about 0.2-7.9 ml of about 1-15% fluoroprocaine and between about 0.2-9.9 ml of about 4 mg/ml dexamethasone. In a further Encephalitis embodiment, the patient is further treated with an oral hydration solution during the treatment.

[20] In a Yellow Fever embodiment, two injections of between about 0.1-9.2 ml of about 0.5-15% proparacaine and between about 0.3-9.6 ml of about 4 mg/ml betamethasone are administered daily for between about 3-5 days. The two injections are administered over an about 60-90 minute interval. As an example, an adult is treated with two about 2 ml doses daily for 3-5 days. The patient is further treated with an oral hydration solution during the treatment. A child may be treated with 1 ml doses. [21] More generally, patients having any of SARS, Ebola, Marburg, West Nile,

German Measles, Yellow Fever, Saint Louis Encephalitis, Japanese Encephalitis, California Encephalitis, Human T-cell Leukemia, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever are treated with an IM injection of a mixture comprising between about 0.2-7.9 ml of about 0.5-17% a first ingredient select from the group consisting of procaine, chloroprocaine, tetracaine, chlorotetracaine, bromoprocaine, proparacaine, fluoroprocaine and benzocaine, and between about 0.1-8.5 ml of about 4 mg/ml of a second ingredient selected from the group consisting of dexamethasone, flumethasone and betamethasone. The treatment plans for SARS, Ebola, Marburg, West Nile, German Measles, Yellow Fever, Saint Louis Encephalitis, Japanese Encephalitis, California Encephalitis, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever generally involve two injections at about 60-120 minute intervals for between about 1-5 days. For Human T-cell Leukemia, the treatment plan is similar except for the 15-30 day treatment duration. In a further embodiment, the Human T-cell Leukemia patient is treated for 5 days, and then treated daily under lab testing until favorable results are found. The patients are further treated with an electrolyte solution during the treatment.

[22] Generally, for all treatments, children may be treated by IM injections of between about 0.5-7 ml of the above-described mixtures in the above-described time intervals. In particular embodiments, an adult is injected with about 2 ml of the mixture, while children under 13 are injected with about 1 ml of the mixture. The treatment interval for all treatments can vary, depending on virus, from once every 3 days up to 3-4 per day.

[23] In an embodiment, a composition according to the present invention is made by mixing 2% chloroprocaine and dexamethasone Sodium Phosphate. Around 30 mg of chloroprocaine in 1.5 ml of a 20 mg/ml solution is mixed with around 2 mg of dexamethasone in 0.5 ml of a 4 mg/ml solution. The total volume of 2 ml comprising the two mixed formulations are gently mixed and aseptically transferred into a sterile 2 ml syringe. Empirical observation indicated that treatment by chloroprocaine and dexamethasone took less time and produced improved results over procaine and dexamethasone. In an alternative embodiment, 3 ml is taken out of a 30 ml bottle of chloroprocaine (20 mg/ml). Then 3 ml of dexamethasone (4 mg/ml) is added into the above-recited chloroprocaine bottle. This provides a 9:1 mixture of chloroprocaine and dexamethasone. The bottle is gently mixed (shaken) and the solution is ready to be aseptically transferred into a sterile syringe for IM administration.

[24] Finally, all references, including any priority documents, cited herein are hereby incorporated by reference. While the present invention has been described in considerable detail, it will be obvious to those skilled in the art that alterations may be made in the device itself or in the procedure for using the device without departing from the concept and scope of the present invention as described in the following claims.

Claims

I claim:

1. A method of treating a patient suffering an ailment selected from the group consisting of SARS, Ebola, Marburg, West Nile, German Measles, Yellow Fever, Saint Louis Encephalitis, Japanese Encephalitis, California Encephalitis, Human T-cell Leukemia, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever comprising administering to the patient an IM injection of a mixture comprising chloroprocaine and dexamethasone.

2. The method according to claim 1, wherein the mixture is administered once every 3 days up to 4 times per day, and the patient is further treated by oral administration of electrolyte solution.

3. The method according to claim 2, wherein the patient is further treated by administration of an antipyretic selected from the group consisting of aspirin, calpol, paracetamol, acetaminophen and ibuprofen.

4. The method according to claim 3, wherein the mixture is administered twice daily at an interval of between about 60-120 minutes and 500 ml of electrolyte solution is orally administered daily during the treatment.

5. The method according to claim 1, wherein treatment is conducted over about 1-5 days.

6. The method according to claim 1, wherein the treatment is conducted over about 11- 18 days.

7. The method according to claim 1, wherein the mixture is an about 1-2 ml dose of a 9:1 mixture of 20 mg/ml chloroprocaine and 4 mg/ml dexamethasone.

8. A method of treating a patient suffering an ailment selected from the group consisting of SARS, Ebola, Marburg, West Nile, German Measles, Yellow Fever, Saint Louis Encephalitis, Japanese Encephalitis, California Encephalitis, Human T-cell Leukemia, Newcastle Disease, respiratory tract infection and bronchitis, Lymphocytic Choriomeningitis, Lassa Hemorrhagic Fever, and Hanta Hemorrhagic Fever comprising administering to the patient an IM injection of a mixture comprising a first ingredient selected from the group consisting of procaine, chloroprocaine, tetracaine, chlorotetracaine, bromoprocaine, proparacaine, fluoroprocaine and benzocaine, and a second ingredient selected from the group consisting of dexamethasone, flumethasone and betamethasone.

9. The method of claim 8, wherein the mixture is administered twice daily at an interval of between about 60-120 minutes, and the patient is further treated by daily oral administration of about 500 ml of electrolyte solution during the treatment.

10. The method according to claim 9, wherein the patient is further treated by administration of an antipyretic selected from the group consisting of aspirin, calpol, paracetamol, acetaminophen and ibuprofen.

11. The method according to claim 8, wherein the mixture is an about 0.5-10 ml dose of an about 0.1-9.9 ml of an about 0.3-33% of the first ingredient and 0.1-8.8 ml of an about 2-10 mg/ml of the second ingredient.

12. The method according to claim 8, wherein the mixture is an about 1.5-4 ml dose of an about 0.5-3.0 ml of an about 1.5-25% of the first ingredient and an about 1 -3.5 ml of an about 4 mg/ml of the second ingredient.

13. The method according to claim 8, wherein the mixture is administered at intervals of between once every three days to four times per day.

14. The method according to claim 8, wherein the disease is Ebola, the mixture is an about 1.5-4 ml dose of an about 0.5-3.0 ml of an about 1.5-25% of chloroprocaine and an about 1-3.5 ml of an about 4 mg/ml of dexamethasone.

15. The method of claim 14, wherein the mixture is administered at intervals of between once every three days to four times per day, and the patient is further treated by administration of electrolyte solution during the treatment.

16. The method according to claim 8, wherein the disease is SARS, the mixture is an about 1.5-4 ml dose of an about 0.5-3.0 ml of an about 1.5-25% of chloroprocaine and an about 1 -3.5 ml of an about 4 mg/ml of dexamethasone.

17. The method according to claim 8, wherein the disease is German Measles, the mixture is an about 1.5-4 ml dose of an about 0.5-3.0 ml of an about 1.5-25% of chloroprocaine and an about 1-3.5 ml of an about 4 mg/ml of dexamethasone.

18. The method according to claim 8, wherein the disease is Lassa Hemorrhagic Fever, the mixture is an about 1-2 ml dose of an about 9:1 mixture of an about 20 mg/ml of procaine and an about 4 mg/ml flumethasone.

19. The method according to claim 8, wherein the disease is bronchitis caused by Respiratory Syncytial Virus, the mixture is an about 1.5-4 ml dose of an about 0.5-3.0 ml of an about 1.5-25% of chloroprocaine and an about 1-3.5 ml of an about 4 mg/ml of betamethasone.

20. The method according to claim 8, wherein the disease is a respiratory tract infection caused by Respiratory Syncytial Virus, the mixture is an about 0.5-10 ml dose of an about 0.1- 9.9 ml of an about 0.3-33% of chloroprocaine and an about 1.0-8.8 ml of an about 2-10 mg/ml of dexamethasone.

21. The method according to claim 8, wherein the treatment is conducted over about 1-5 days.

22. The method according to claim 8, wherein the treatment is conducted over about 11- 18 days.