WO2009089534A2 - Compositions et procédés pour le traitement d'infections virales provoquées par un virus grippal - Google Patents

Compositions et procédés pour le traitement d'infections virales provoquées par un virus grippal Download PDF

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WO2009089534A2
WO2009089534A2 PCT/US2009/030753 US2009030753W WO2009089534A2 WO 2009089534 A2 WO2009089534 A2 WO 2009089534A2 US 2009030753 W US2009030753 W US 2009030753W WO 2009089534 A2 WO2009089534 A2 WO 2009089534A2
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oil
orange
pharmaceutical composition
hydrogen peroxide
composition
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PCT/US2009/030753
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English (en)
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WO2009089534A3 (fr
Inventor
Robert Bowker
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Knockout Technologies, Ltd.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/482—Cassia, e.g. golden shower tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Definitions

  • the present invention relates generally to compositions and methods that can be used for the treatment or prevention of infections caused by influenza viruses.
  • Influenza is a contagious infection caused by the influenza virus, classified in the orthomyxoviridae family.
  • influenza-type viruses which affect human beings: Influenza A, B and C.
  • Influenza A viruses have been isolated from many animal species, while the influenza B and C viruses have been found to infect mainly humans.
  • influenza infection It is estimated that millions of people in the United States get influenza each year. The majority of this population generally recovers in one to two weeks. In some cases, however, multiple complications can arise from an influenza infection, including death.
  • AIV Avian Influenza virus
  • Some existing medications for influenza virus include neuralminidase inhibitors (such as Zanamivir, Oseltamivir, etc.), ion channel blockers (such as Amantadine and rimantadine), and nucleotide medications (such as tribavirim, that is, ribavirin or virazole).
  • Ion channel blockers were considered as the best medications for prevention and treatment of influenza viruses.
  • each of these have shown limitations, including negative side effects and drug resistance.
  • the present invention is directed to methods and compositions for treatment or prevention of infections caused by influenza viruses, including Avian influenza virus strains HsN 1 and H 9 N 9 , and Swine influenza virus strain H 1 N 1 .
  • the invention provides pharmaceutical compositions comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier for use in treatment of influenza virus.
  • the pharmaceutical composition for use in treatment of influenza virus further comprises a non-ionic emulsifier (e.g. polysorbate 80).
  • the orange terpene oil is present in the composition from 5% to 40% v/v
  • the orange Valencia oil is present in the composition from 5 % to 40 % v/v
  • the non-ionic emulsifier is present in the composition from 5 % to 50 % v/v
  • the distilled or deionized H 2 O is present in the composition from 5 % to 80 % v/v
  • the hydrogen peroxide is present in the composition from 1.5 % to 8 % H 2 O 2 w/v
  • the composition comprises one half as much non-ionic emulsifier (e.g. polysorbate) by volume as the combined volume of orange Valencia oil and orange terpene oil.
  • the pharmaceutical composition comprises 5.25% H 2 O 2 (15% of a 35% hydrogen peroxide solution) 10% v/v orange terpene oil, 5% v/v orange Valencia oil, 10% v/v polysorbate 80, and 60% v/v distilled water.
  • the pharmaceutical composition further comprises an antioxidant preservative of H 2 O 2 such as oil of rosemary.
  • Methods for treating and/or preventing influenza virus infection in a patient comprise administering to said patient an effective amount of a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil and a pharmaceutically acceptable carrier.
  • the method comprises administering to said patient an effective amount of a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, a non-ionic emulsifier, and a pharmaceutically acceptable carrier.
  • the methods comprise administering a pharmaceutical composition comprising the non-ionic emulsifier polysorbate 80.
  • the methods comprise administering a pharmaceutical composition comprising 5 % to 40 % v/v orange terpene oil; 5 % to 40 % v/v orange Valencia oil; 5 % to 50 % v/v non-ionic emulsifier; 5 % to 80 % v/v distilled or deionized H 2 O; and 1.5 % to 8 % w/v hydrogen peroxide (H 2 O 2 ) and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition comprising 5 % to 40 % v/v orange terpene oil; 5 % to 40 % v/v orange Valencia oil; 5 % to 50 % v/v non-ionic emulsifier; 5 % to 80 % v/v distilled or deionized H 2 O; and 1.5 % to 8 % w/v hydrogen peroxide (H 2 O 2 ) and a pharmaceutically acceptable carrier.
  • the methods comprise administering a pharmaceutical composition comprising 5.25% w/v H 2 O 2 , 10% v/v orange terpene oil, 5% v/v orange Valencia oil, 10% v/v polysorbate 80, and 60% v/v distilled water and a pharmaceutically acceptable carrier.
  • composition in the methods of the invention can be administered orally, parenterally, intravenously, intramuscularly, transdermally, via buccal route, subcutaneously, or via suppository.
  • composition comprising an effective amount of hydrogen peroxide (H 2 O 2 ), orange terpene oil, and orange Valencia oil, for treating or preventing an influenza virus infection in a patient and a pharmaceutically acceptable carrier.
  • Figure 1 shows a table depicting the results of a Virucidal Efficacy Test as described in Example I.
  • the table indicates the measured titer of Avian Influenza Virus (strain HsN 1 ) after exposure of virus to a composition comprising 60% distilled water, 10% polysorbate 80, 5% orange Valencia oil, 10% orange terpene oil, and 15% of a 35% hydrogen peroxide solution (referred to as Citroxin). Results of exposure of strain HsN 1 to Occusyn O, Occusyn H and Occusyn are also depicted.
  • Methods for treating or preventing an influenza virus infection in a patient comprise administering an effective amount of a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier.
  • the method comprises administering an effective amount of a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, a non-ionic emulsifier, and a pharmaceutically acceptable carrier.
  • influenza refers to an RNA virus of the orthomyxoviridae family, including influenza A, influenza B, and influenza C, and mutants thereof.
  • Influenza viruses contemplated herein include those viruses that have two antigenic glycosylated enzymes on their surface: neuraminidase and hemagglutinin.
  • the term "patient,” as used herein, describes an organism, including humans, birds and mammals, to which treatment with the compositions according to the present invention is provided.
  • Mammalian species that benefit from the disclosed methods of treatment include, but are not limited to, apes, chimpanzees, orangutans, humans, monkeys; and domesticated animals (i.e., pets) such as dogs, cats, mice, rats, guinea pigs, and hamsters.
  • the pharmaceutical composition of the invention (a composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, a non-ionic emulsifier and a pharmaceutically acceptable carrier, or a composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier) can be concurrently administered with vaccinations, antiviral drugs, antitussives, mucolytics, and/or expectorants; antipyretics and analgesics; nasal decongestants.
  • a compound can be provided in admixture with the pharmaceutical composition of the invention, or separate pharmaceutical compositions can be administered consecutively, simultaneously, or at different times.
  • the pharmaceutical composition according to the invention can be administered concurrently with, but not limited to, a vaccination, and/or antiviral medications such as neuralminidase inhibitors (e.g. Zanamivir, Oseltamivir, etc.), ion channel blockers (e.g. Amantadine and rimantadine), and nucleotide medications (e.g. tribavirim, ribavirin or virazole).
  • neuralminidase inhibitors e.g. Zanamivir, Oseltamivir, etc.
  • ion channel blockers e.g. Amantadine and rimantadine
  • nucleotide medications e.g. tribavirim, ribavirin or virazole.
  • symptoms associated with a influenza viral infection include, but are not limited to, fever, headache, exhaustion/fatigue, muscular aches, sore joints, irritated watering eyes, malaise, nausea and/or vomiting, shaking chills, chest pain, sneezing and respiratory symptoms (i.e., inflamed respiratory mucous membranes, substernal burning, nasal discharge, scratchy/sore throat, dry cough, loss of smell).
  • symptoms associated with an influenza virus infection can start within 24 to 48 hours after infection and can begin suddenly. Chills or a chilly sensation are often the first indication of influenza.
  • Fever is common during the first few days, and the temperature may rise to 103 0 F. In many instances, subjects feel sufficiently ill to remain in bed for days; subjects often experience aches and pains throughout the body, most pronounced in the back and legs.
  • the orange Valencia oil (CAS-No. 8008-57-9 and CAS-No. 8028- 48-6; EINECS Number 232-433-8; FEMA No., 2825, Tarrif No. 3301.12; FDA 182.2) is a cold pressed Valencia type oil having about 00.1% Citral (CAS-No. 5392-40-5), about 0.4% Linalool (CAS-No. 78-70-6), about 0.3% Decanal, and a maximum of about 95% Limonene (CAS-No. 5989-27-5).
  • Orange Valencia oil is a cold pressed oil obtained by expression from peels of partially ripened fruits. The color is a clear orange-yellow liquid (intensely yellow, orange or deep orange).
  • the odor is of fresh sweet orange peel.
  • Physical and chemical properties include a flash point of about 45°C, vapor pressure at 20 0 C of about 1 hPa; and a density at 20 0 C of about 0.84 g/cm ; solubility in water about 0 g/L; optical rotation of about +94°- +99°.
  • the orange valencial oil is the product "Orange Oil Brazil Valencia Type” from Polarome International, Inc. (200 Theodore Conrad Drive, Jersy City, NJ 07035) Article no. 40760.
  • the orange Valencia oil is the product "Oil Orange Valencia” from Ungerer & Company (4 Bridgewater Lane, Lincoln park New Jersey 07035).
  • the orange Valencia oil by gas chromatograph contains the following components in approximated percent: Alpha Pinene 0.49%; Sabinene 0.33%; Myrcene 2.08%; Limonene 95.00%; Octanol 0.04%; Linalool 0.53%; Decanal 0.32%; Citral 0.20%; Undeacanal 0.03%; Dodecanal 0.07%; Valencene 0.07%; and Beta-sinensal 0.03%.
  • Orange Valencia oil is derived from the Valencia type orange, which has higher aldehyde content than other cold pressed orange oils that are primarily of the Pera type.
  • range terpene oil refers to orange terpenes (CAS- No.68647-72-3; EINECS Number 232-433-8, FDA 21 CFR 182.20, FEMA No. 2633;2825) produced by a distillation of orange oil and subsequent fractionation (such as when producing folded oils), where the product is a clear colorless liquid with a characteristic citrus-like odor.
  • the "orange terpene oil” also known as “orange terpenes,” by gas chromatograph contain, in an approximated percent, Limonene 96 %, linalool (CAS-No. 5989-27-5), 0.03% and Decanal 0.02%.
  • the orange terpenes are different from orange oils, in that they only contain hydrocarbons, whereas the orange oils contain oxygenated hydrocarbons, that give the oil more flavor and odor.
  • Physical and chemical properties include a boiling point of about 160-250 0 C, a flash point of about 50 0 C (122°F), vapor pressure at 20 0 C of about 1.2 hPa; and a density at 20 0 C of about 0.85 g/cm 3 , solubility in water about 0.03 g/L; an optical rotation of about +96°- +105°.
  • the orange terpene oil is the product "Orange Terpenes" from Polarome International, Inc. (200 Theodore Conrad Drive, Jersy City, NJ 07035) Article no.
  • the orange terpene oil is the product "Orange Terpenes" from Ungerer & Company (4 Bridgewater Lane, Lincoln park New Jersey 07035).
  • the orange terpene oil by gas chromatograph contains the following components in approximated percent: Alpha Pinene 0.60%; Sabinene 0.32%; Myrcene 2.40%; Limonene 96.30%; Octanol 0.03%; Linalool 0.03%; Decanal 0.02%; Citral 0.02%; Undeacanal 0.00%; Dodecanal 0.00%; Valencene 0.00%; and Beta-sinensal 0.00%.
  • the methods of the invention for treating influenza virus infection in a patient, include administering to the patient an effective amount of a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, a non-ionic emulsifier and a pharmaceutically acceptable carrier, or an effective amount of a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition for use in methods of the invention is a composition that comprises 60% v/v distilled water, 10% v/v polysorbate 80, 5% v/v orange Valencia oil, 10% v/v orange terpene oil, and 15% v/v of a 35% wt.% hydrogen peroxide solution (equivalent to 5.35% of H 2 O 2 ).
  • the composition can be used at full strength or can be diluted with water. Dilutions can range from 1:1 to 1:10,000.
  • the composition an be formulated in a solid form.
  • the pharmaceutical composition further comprises oil of rosemary, e.g. CAS Number 8000-25-7, which can be obtained from Polarome International, Inc. (200 Theodore Conrad Drive, Jersey City, New Jersey 07035).
  • the pharmaceutical composition for use in methods of the invention is a composition that further comprises oreganum, cumin oil, cassia oil, lavender oil, tea tree oil, and olive oil.
  • the pharmaceutical composition for use in methods of the invention is a composition that comprises l%-10% oreganum, l%-10% cumin oil, l%-10% cassia oil, l%-10% lavender oil, l%-10% tea tree oil, and 40%-95% olive oil.
  • the pharmaceutical composition for use in methods of the invention further comprises 5% oreganum, 3.3% cumin oil, 3.3% cassia oil, 3.3% lavender oil, 1.65% tea tree oil, and 83.45% olive oil.
  • the pharmaceutical composition for use in methods of the invention comprises 10%- 90% by weight a mixture of a composition comprising 5 % to 40 % v/v orange terpene oil; 5 % to 40 % v/v orange Valencia oil; 5 % to 50 % v/v non-ionic emulsifier; 5 % to 80 % v/v distilled or deionized H 2 O; and 1.5 % to 8 % w/v hydrogen peroxide (H 2 O 2 ), 10%-90% by weight a mixture of a composition comprising l%-10% oreganum, l%-10% cumin oil, l%-10% cassia oil, l%-10% lavender oil, l%-10% tea tree oil, and 40%-95% olive oil, and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition for use in methods of the invention comprises 50% by weight a mixture of a composition comprising 5 % to 40 % v/v orange terpene oil; 5 % to 40 % v/v orange Valencia oil; 5 % to 50 % v/v non-ionic emulsifier; 5 % to 80 % v/v distilled or deionized H 2 O; and 1.5 % to 8 % w/v hydrogen peroxide (H 2 O 2 ); 50% by weight a mixture of a composition comprising l%-10% oreganum, l%-10% cumin oil, l%-10% cassia oil, l%-10% lavender oil, l%-10% tea tree oil, and 40%- 95% olive oil; and a pharmaceutically acceptable carrier.
  • the cassia oil may be replaced by cinnamon oil.
  • the composition may include a coenzyme such as biopterin and or an enzyme such as lipase
  • the components of the pharmaceutical composition can be obtained from any source.
  • food grade components are used.
  • the orange terpene oil and orange Valencia oil can be obtained from Polarome International, Inc. (200 Theodore Conrad Drive, Jersy City, New Jersey 07035) (Orange Terpenes, CAS Number 68647-72-3, EINECS Number 232-433-8; Orange Oil Valencias, CAS Number 8008-57-9, EINECS Number 232-433-8)) or from Ungerer & Company (4 Bridgewater Lane, Lincoln park New Jersey 07035) ; the polysorbate 80 can be obtained from Spectrum Chemicals (14422 South San Pedro Street, Gardena, California 90248) and the hydrogen peroxide from Solvay Chemicals Inc.
  • the orange Valencia oil can be derived from a cold press expression method which preserves viable anti-oxidants. In one embodiment, the orange Valencia oil has at least 1.4% aldehydes.
  • the orange Valencia oil (CAS-No. 8008-57-9; EINECS Number 232-433-8; FEMA No., 2825, Tarrif No. 3301.12) is a cold pressed brasil Valencia type oil having a maximum of about 00.1% Citral (CAS-No. 5392-40-5), a maximum of about 0.4% Linalool (CAS-No. 78-70-6) and a maximum of about 95% Limonene (CAS-No. 5989-27-5) (Polarome International, Inc. 200 Theodore Conrad Drive, Jersy City, NJ 07035).
  • Physical and chemical properties include a flash point of about 450 0 C, vapor pressure at 20 0 C of about 1 hPa; and a density at 20 0 C of about 0.84 g/cm 3 , solubility in water about 0 g/L.
  • the orange terpene oil is a cold pressed orange terpene oil (CAS-No.68647-72-3; EINECS Number 232-433-8, FDA 21 CFR 182.20, FEMA No. 2633; having a maximum of about 96% Limonene (CAS-No. 5989-27-5).
  • Poly and chemical properties include a boiling point of about 160-250 0 C, a flash point of about 50 0 C, vapor pressure at 20 0 C of about 1.2 hPa; and a density at 20 0 C of about 0.85 g/cm , solubility in water about 0.03 g/L.
  • any ionic emulsifier can be used in the pharmaceutical composition of the invention, including, but not limited to, alkyl polyethyleneoxy ethers, alkyl phenol polyethyleneoxy ethers, polyethyleneoxy amines, polyethyleneoxy fatty acids, and alkyl dimethyl amino oxides.
  • the composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, a non-ionic emulsifier, and distilled or deionized water (H 2 O) does not comprise an anionic surfactant or an amphoteric surfactant.
  • the non-ionic emulsifier of the pharmaceutical composition is polysorbate 80 (CAS Number 9005-65-6).
  • the term "effective amount,” as used herein, refers to the amount necessary to elicit the desired biological response.
  • the effective amount of a pharmaceutical composition is the amount necessary to treat/prevent influenza viral infections; treat/ameliorate symptoms associated with influenza viral infections; and/or prevent/delay/ameliorate the onset of complications associated with influenza viral infections.
  • the amelioration in symptom and/or complication severity may be a 5%, 10%, 15%, 20%, 25% 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% decrease in severity.
  • compositions suitable for use in the present invention include compositions wherein the active ingredients (hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil) are contained in a therapeutically effective amount.
  • the amount of composition administered will, of course, be dependent on the subject being treated, on the subject's weight, the severity of the affliction, the manner of administration and the judgment of the prescribing physician. Determination of an effective amount is well within the capability of those skilled in the art.
  • an efficacious or effective amount of a pharmaceutical composition that comprises hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier, and alternatively further comprising a non-ionic emulsifier, is determined by first administering a low dose of the composition and then incrementally increasing the administered dose or dosages until a desired effect of reduced viral titer is observed in the treated subject, with minimal or no toxic side effects.
  • the present invention is particularly applicable to treatment and/or prevention of influenza virus infections in both humans and non-human animals (e.g. birds and mammals).
  • Influenza virus infections to be treated include Influenza A, B and C viruses, including infections caused by various Avian Influenza strains, including viruses of subtype H 1 N 1 , HiN 2 , H 2 N 2 , H 3 N 2 , H 3 N 8 , H 5 Ni, H 5 N 3 , H 5 N 8 , H 5 N 9 , H 7 Ni, H 7 N 2 , H 7 N 3 , H 7 N 4 , H 7 N 7 , H 9 N 2 , AND Hi 0 N 7 .
  • the pharmaceutical composition for use in methods of the invention is administered to subjects (either human or animal) in order to treat and/or prevent a HsN 1 avian influenza virus infection.
  • compositions of the invention can be administered using a variety of routes of administration, and formulations include, for example, orally- administrable forms such as tablets, capsules or the like, or via parenteral, intravenous, intramuscular, transdermal, buccal, subcutaneous, suppository, or other route.
  • the pharmaceutical compositions are in unit dosage form, namely, in physically discrete units suitable as unitary dosages for human or animal consumption, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect in association with one or more pharmaceutically acceptable other ingredients, i.e., diluents or carrier.
  • compositions of the subject invention comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and alternatively further comprising a non-ionic emulsifier, can be formulated according to known methods for preparing pharmaceutically useful compositions.
  • Formulations are described in a number of sources, which are well known and readily available to those skilled in the art. For example, In Remington: The Science and Practice of Pharmacy, 21st Edition, 2005, University of the Sciences in Philadelphia (USIP), Lippincott, Williams & Wilkins.
  • compositions described herein can be manufactured in a manner that is known to those of skill in the art, i.e., by means of conventional mixing, dissolving, granulating, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.
  • the components are mixed together sequentially.
  • the components can added in sequence to distilled water in the following order: orange terpene oil, orange Valencia, then non-ionic emulsifier (e.g. polysorbate 80). While being mixed at moderate speed, hydrogen peroxide is then added and mixed for approximately five minutes.
  • the distilled water is kept between 90° and 100° Fahrenheit to facilitate the emulsification process.
  • Formulations suitable for parenteral administration include, for example, aqueous sterile injection solutions, which may contain antioxidants, buffers, bacteriostats, and solutes, which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions, which may include suspending agents and thickening agents.
  • the formulations may be presented in unit-dose or multi-dose containers, for example sealed ampoules and vials, and may be stored in a freeze dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections, prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powder, granules, tablets, etc. It should be understood that in addition to the ingredients particularly mentioned above, the formulations of the subject invention can include other agents conventional in the art having regard to the type of formulation in question.
  • the formulations comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a pharmaceutically acceptable carrier include those suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal, parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) administration as well as administration to the eye.
  • the formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Such methods include the step of bringing into association the hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, with the carrier which constitutes one or more accessory ingredients.
  • a non-ionic emulsifier is also used in the formulation.
  • the formulations can be prepared by uniformly and intimately bringing into association the hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and non-ionic emulsifier with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product.
  • the hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and non-ionic emulsifier can be provided in a formulation for use in a skin patch.
  • the hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, are formulated into solid, semi solid, liquid or gaseous forms, such as tablets, capsules, pills, powders, granules, gels, slurries, ointments, solutions, suppositories, injections, inhalants, and aerosols.
  • Pharmaceutically acceptable carriers or diluents for use in the pharmaceutical compositions for the invention include, but are not limited to, ethanol, dimethyl sulfoxide, glycerol, silica, alumina, starch, sorbitol, inositol, xylitol, D-xylose, mannitol, powdered cellulose and derivatives, gelatin, microcrystalline cellulose, talc, colloidal silicon dioxide, calcium carbonate, magnesium carbonate, calcium phosphate, calcium aluminum silicate, aluminum hydroxide, sodium starch phosphate, lecithin, liposomes, polymers (e.g. polyethylene glycols), and equivalent carriers and diluents.
  • the hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and alternatively also a non-ionic emulsifier are provided in a formulation of a lipid-based particle delivery system, e.g. nano-lipidic particles (NLPs), as described in U.S. Patent Nos. 5,879,703 and 5,269,979, and in Australian Patent No. 6,77826, each of which are herein incorporated by reference. (See also Guzman et al., Infect Immun. 1993 February; 61(2): 573-579 and Brownlie et al. Microbial Pathogenesis Volume 14, Issue 2, February 1993, Pages 149-160, each herein incorporated by reference).
  • NLPs nano-lipidic particles
  • the composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and alternatively also a non-ionic emulsifier is prepared for delivery in a sustained-release, controlled release, extended-release, timed- release or delayed-release formulation, for example, in semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent.
  • H 2 O 2 hydrogen peroxide
  • orange terpene oil orange Valencia oil
  • a non-ionic emulsifier is prepared for delivery in a sustained-release, controlled release, extended-release, timed- release or delayed-release formulation, for example, in semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent.
  • sustained-release materials have been established and are well known by those skilled in the art.
  • Current extended-release formulations include film-coated tablets, multiparticulate or pellet systems, matrix technologies using hydrophilic or lipophilic materials and wax -based tablets with pore-forming excipients (See, for example, Huang, et al. DrugDev. Ind. Pharm. 29:79 (2003); Pearnchob, et al. Drug Dev. Ind. Pharm. 29:925 (2003); Maggi, et al. Eur. J. Pharm. Biopharm. 55:99 (2003); Khanvilkar, et al., DrugDev. Ind. Pharm.
  • sustained release delivery systems can, depending on their design, release the compounds over the course of hours or days, for instance, over 4, 6, 8, 10, 12, 16, 20, 24 hours or more.
  • sustained release formulations can be prepared using naturally-occurring or synthetic polymers, for instance, polymeric vinyl pyrrolidones, such as polyvinyl pyrrolidone (PVP); carboxyvinyl hydrophilic polymers; hydrophobic and/or hydrophilic hydrocolloids, such as methylcellulose, ethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose; and carboxypolymethylene.
  • the sustained or extended-release formulations can also be prepared using natural ingredients, such as minerals, including titanium dioxide, silicon dioxide, zinc oxide, and clay (See, U.S. Pat. No. 6,638,521 , herein incorporated by reference).
  • Exemplified extended release formulations that can be used for delivering the composition of the present invention include those described in U.S. Pat. Nos. 6,635,680; 6,624,200; 6,613,361 ; 6,613,358, 6,596,308; 6,589,563; 6,562,375; 6,548,084; 6,541,020; 6,537,579; 6,528,080 and 6,524,621, each of which is hereby incorporated herein by reference.
  • Controlled release formulations of particular interest include those described in U.S. Pat. Nos. 6,607,751 ; 6,599,529; 6,569,463; 6,565,883; 6,482,440; 6,403,597; 6,319,919; 6,150,354; 6,080,736; 5,672,356; 5,472,704; 5,445,829; 5,312,817 and 5,296,483, each of which is hereby incorporated herein by reference. Those skilled in the art will readily recognize other applicable sustained release formulations.
  • Control Release formulations suitable for use in the invention include incorporation of the active ingredients into self-assembled colloidal composite structures, colloidosomes, micron-sized hollow spheres with selectively permeable membranes that allow controlled release of the shell's contents (See Velev O. D., Furusawa K., and Nagayama K, Langmuir 12, p. 2374, 1996 and Dinsmore A. D. et al., Science, Vol. 298, p. 906, 2002, each herein incorporated by reference in their entirety) and the multicomponent delivery system developed by Salvona Technologies Inc. (Dayton, New Jersey 008-1523, USA) known as MultiSalTM (See, Shefer, A. and Shefer, S.
  • the system uses solid hydrophobic nanospheres composed of a blend of food-approved hydrophobic materials encapsulated in moisture- sensitive or pH-sensitive bioadhesive microspheres and generates nanospheres with a diameter of about 0.01-0.5 microns. Inactive ingredients such as flavors, cooling or heating agents, or sweeteners, can also be incorporated.
  • the nanospheres are then encapsulated in microspheres of about 20-00 microns in diameter.
  • the nanospheres are not individually coated by the moisture-sensitive microsphere matrix, but are homogeneously dispersed in it. When the microsphere encounters water, such as saliva, it dissolves, releasing the nanos-pheres and other ingredients.
  • Various ingredients can be incorporated into the hydrophobic nanosphere matrix, the water- sensitive microsphere matrix, or both matrices.
  • the active ingredients and sensory markers (flavors) encapsulated in the nanospheres can be the same as, or different from, those encapsulated in the microspheres.
  • the nanosphere surface can include a moisture- sensitive bioadhesive material, such as starch derivatives, natural polymers, natural gums, etc., making them capable of being bound to a biological membrane such as the oral cavity mucosa and retained on that membrane for an extended period of time.
  • the nanospheres can be localized and the target ingredient encapsulated within their structure to a particular region, or a specific site, thereby improving and enhancing the bioavailability of ingredients which have poor bioavailability by themselves, for example, these nanospheres have shown the ability to adhere to human epithelial cells, such as those in the oral cavity.
  • the hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and alternatively also a non-ionic emulsifier can be formulated as tablets, pills, capsules, emulsions, lipophilic and hydrophilic suspensions, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.
  • Pharmaceutical preparations for oral use can be obtained by lyophilizing and mixing the compounds with a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets.
  • the active ingredients can be incorporated into hydrophobic nanospheres.
  • Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl- cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP).
  • disintegrating agents can be added, such as a cross- linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.
  • compositions which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol.
  • the push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers.
  • the active compounds hydroogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil
  • suitable liquid paraffin or liquid polyethylene glycols.
  • stabilizers can be added. All formulations for oral administration should be in dosages suitable for such administration.
  • Dyestuffs or pigments can be added to the tablets for identification or to characterize different combinations of active compound doses.
  • composition of the present invention may also be formulated into a nasal aerosol or inhalant composition.
  • a nasal aerosol or inhalant composition may be prepared using well-known techniques.
  • suitable carriers may include the following ingredients: saline with one or more preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or conventional solubilizing or dispersion agents.
  • compositions for parenteral administration include aqueous solutions of the active compounds in water-soluble form.
  • suspensions of the active compounds can be prepared as appropriate oily injection suspensions.
  • Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes.
  • Aqueous injection suspensions can contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran.
  • the suspension can also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.
  • the active ingredient can be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.
  • the agents are formulated into ointments, creams, salves, powders and gels.
  • Systemic administration can also be by transmucosal or transdermal means.
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • the transdermal delivery agent can be, for example, DMSO, urea, l-methyl-2-pyrrolidone, oleic acid, or a terpene ⁇ e.g., 1- menthol, d-limonene, RS-(+/-)-beta-citronellol, geraniol).
  • Transdermal delivery systems can include, e.g., patches.
  • penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
  • Exemplified transdermal delivery formulations that can find use in the present invention include those described in U.S. Pat. Nos. 6,589,549; 6,544,548; 6,517,864; 6,512,010; 6,465,006; 6,379,696; 6,312,717 and 6,310,177, each of which are hereby incorporated herein by reference.
  • compositions can take the form of tablets or lozenges formulated in conventional manner.
  • the pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and alternatively also a non-ionic emulsifier, is delivered to a non-human animal in animal feed.
  • Dosage amount and interval can be adjusted individually to provide plasma levels of the active compounds (hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil) which are sufficient to maintain a therapeutic effect.
  • Therapeutically effective serum levels can be achieved by administering single daily doses, but efficacious multiple daily dose schedules are included in the invention. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration.
  • One having skill in the art will be able to optimize therapeutically effective local dosages without undue experimentation.
  • ком ⁇ онентs of the pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, orange Valencia oil, and a non-ionic emulsifier will depend on several factors, including without limitation, the selected route of administration, the age, weight and prognosis of the patient, the progression of the illness, etc.
  • An efficacious or effective amount of the composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, and orange Valencia oil can be determined by first administering a low dose of the composition and then incrementally increasing the administered dose or dosages until a desired effect of reduced viral titer is observed in the treated subject, with minimal or no toxic side effects.
  • Reduced viral titers can be monitored, by in vitro assays well known in the art, for example, a plaque reduction assay (PRA), cellular enzyme- linked immunosorbent assay (ELISA), ⁇ -galactosidase assay, and electron microscopy (EM).
  • PRA plaque reduction assay
  • ELISA cellular enzyme- linked immunosorbent assay
  • EM electron microscopy
  • the symptoms, caused by a viral infection, that may be treated, reduced, or at least partially prevented by this method of the present invention, may include one or more of headache, joint pain, fever, cough, sneezing, muscle ache, running nose, dry mouth, dizziness, and other symptoms related to influenza viral infection.
  • these symptoms include a lack of energy, decreased egg production, soft shelled eggs, a swelling of the head, eyelids, etc., nasal discharge, coughing or diarrhea.
  • the pharmaceutical composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, and orange Valencia oil is administered in an amount of from about 2 mg/kg to about 100 mg/kg active ingredient (hydrogen peroxide (H 2 O 2 ), orange terpene oil, and orange Valencia oil) per day, although the doses can be more or less, depending on the route of administration. For example, the doses can be less if the composition is administered intravenously.
  • the composition comprising hydrogen peroxide (H 2 O 2 ), orange terpene oil, and orange Valencia oil is administered in an amount of from about 20 mg active ingredient/kg to about 75 mg active ingredient/kg per day.
  • the composition is administered in an amount of about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 mg active ingredient /kg per day, or any integer within the range of .OOlmg-100 mg active ingredient/kg per day.
  • the pharmaceutical composition can be administered from about 1 to 6 times a day.
  • the hydrogen peroxide (H 2 O 2 ), orange terpene oil, and orange Valencia oil active ingredient is delivered as an oral pharmaceutical composition at a dosage ranging from 10 mg/kg body weight to 75 mg/kg body weight, delivered every six hours, or delivered four times per day.
  • the pharmaceutical composition is delivered as an oral pharmaceutical composition at a dosage ranging from 10 mg/kg body weight to 75 mg/kg body weight, delivered every six hours, or delivered four times per day.
  • the pharmaceutical composition further comprises oreganum, cumin oil, cassia oil, lavender oil, tea tree oil, and olive oil.
  • the pharmaceutical composition comprises l%-10% oreganum, l%-10% cumin oil, l%-10% cassia oil, l%-10% lavender oil, l%-10% tea tree oil, and 40%-95% olive oil.
  • the pharmaceutical composition further comprises 5% oreganum, 3.3% cumin oil, 3.3% cassia oil, 3.3% lavender oil, 1.65% tea tree oil, and 83.45% olive oil.
  • the pharmaceutical composition comprises 10%- 90% by weight a mixture of a composition comprising 5 % to 40 % v/v orange terpene oil; 5 % to 40 % v/v orange Valencia oil; 5 % to 50 % v/v non-ionic emulsifier; 5 % to 80 % v/v distilled or deionized H 2 O; and 1.5 % to 8 % w/v hydrogen peroxide (H 2 O 2 ), 10%-90% by weight a mixture of a composition comprising l%-10% oreganum, l%-10% cumin oil, l%-10% cassia oil, l%-10% lavender oil, l%-10% tea tree oil, and 40%-95% olive oil, and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition comprises 50% by weight a mixture of a composition comprising 5 % to 40 % v/v orange terpene oil; 5 % to 40 % v/v orange Valencia oil; 5 % to 50 % v/v non-ionic emulsifier; 5 % to 80 % v/v distilled or deionized H 2 O; and 1.5 % to 8 % w/v hydrogen peroxide (H 2 O 2 ); 50% by weight a mixture of a composition comprising l%-10% oreganum, l%-10% cumin oil, l%-10% cassia oil, 1%- 10% lavender oil, l%-10% tea tree oil, and 40%-95% olive oil; and a pharmaceutically acceptable carrier.
  • the cassia oil may be replaced by cinnamon oil.
  • the composition may include a coenzyme such as biopterin and or an enzyme such as lipase.
  • the oreganum contains 40% to 80% naturally occurring carvacrol.
  • Example I Virucidal Efficacy for H 5 Ni of the composition according to the Invention
  • a composition comprising 60% distilled water, 10% polysorbate 80, 5% orange Valencia oil, 10% orange terpene oil, and 15% of a 35% hydrogen peroxide solution (referred to as Citroxin in Figure 1) was tested against Avian Influenza Virus strain HsN 1 .
  • a toxicity test was performed by inoculation of egg using 1, 1:10, and 1:100 dilution of each composition. The highest concentration of compositions showing no lethal effect to chick embryos was chosen for embryo injection.
  • the composition was mixed with virus stock (10 8 ELDs 0 ZmI) for 10 minutes at room temperature. The mixture was then serially diluted, and inoculated into allantoic cavity of 9-12 days embryonated eggs.
  • Citroxin was tested against Avian Influenza Virus strain H 9 N 9 .
  • a toxicity test was performed by inoculation of eggs. The highest concentration of compositions showing no lethal effect to chick embryos was chosen for embryo injection.
  • the composition was mixed with virus stock for 10 minutes at room temperature. The mixture was then serially diluted, and inoculated into allantoic cavity of 9-12 days embryonated eggs. After 7 days of Incubation, the allantoic fluid was collected and a hemagglutination test performed to detect positive remaining infectious virus. Virus titers after neutralization were compared to control.
  • a composition CRS II comprising 50% by weight Citroxin plus 50% by weight a mixture of 5% oreganum, 3.3% cumin oil, 3.3% cassia oil, 3.3% lavender oil, 1.65% tea tree oil, and 83.45% olive oil was tested against Avian Influenza Virus strain H 9 Ng.
  • a toxicity test was performed by inoculation of eggs. The highest concentration of compositions showing no lethal effect to chick embryos was chosen for embryo injection.
  • the composition was mixed with virus stock for 10 minutes at room temperature. The mixture was then serially diluted, and inoculated into allantoic cavity of 9-12 days embryonated eggs. After 7 days of Incubation, the allantoic fluid was collected and a hemagglutination test performed to detect positive remaining infectious virus. Virus titers after neutralization were compared to control.
  • CRS II is toxic to erythrocytes. Pretreatment with 1:10 and 1:50 CRS II killed approximately 300 TCID 50 of AIV H 9 N 9 . Post treatment with 1:10 and 1:50 CRS II killed approximately 300 TCID 50 of AIV H 9 N 9 . Simultaneous treatment with 1:10 and 1:50 CRS II killed approximately 300 TCID 50 of AIV H 9 N 9 .
  • Citroxin was tested against Swine Influenza Virus (SIV) H 1 N 1 .
  • composition CRS II comprising 50% by weight Citroxin plus 50% by weight a mixture of 5% oreganum, 3.3% cumin oil, 3.3% cassia oil, 3.3% lavender oil, 1.65% tea tree oil, and 83.45% olive oil was tested against Swine Influenza Virus (SIV) H 1 N 1 .
  • CRS II is toxic to erythrocytes. Pretreatment with 1:10 CRS II killed approximately 10 5 TdD 50 of SIV H 1 N 1 . Post treatment with 1:10 CRS II resulted in inconclusive data. Simultaneous treatment with 1:10 and 1:50 CRS II killed approximately 10 4 TCID 50 Of SIV HiN 1 .
  • a strain of highly pathogenic SIV (A/Swine/Iowa/00239/2004 HlNl) will be used. This strain has previously been used in inoculation and vaccine evaluation studies (Vincent AL, Ma W, Lager KM, Janke BH, Webby RJ, Garcia-Sastre A, Richt JA. Efficacy of intranasal administration of a truncated NSl modified live influenza virus vaccine in swine. Vaccine. 2007 Nov 19;25(47):7999-8009. Epub 2007 Sep 29.; Vincent AL, Lager KM, Ma W, Lekcharoensuk P, Gramer MR, Loiacono C, Richt JA. Evaluation of hemagglutinin subtype 1 swine influenza viruses from the United States. Vet Microbiol. 2006 Dec 20;118(3-4):212-22. Epub 2006 Aug 1).
  • T2 Infected and non-treated Same as T1-T3 except no AVA will be given.
  • the difference in T1-T3 and T4 will indicate the efficacy of the AVA.
  • Each pig will be tagged with a unique number to identify the individual pig within the study. Tag numbers will be recorded and grouped by pen.
  • Pigs in groups T1-T4 will be sedated and virus will be given by intra-tracheal inoculation @ 2mL/pig on day 0 (4 weeks of age). Two pigs from each of the 6 groups will be euthanized at 3, 7, 10, and 14 dpi. Euthanized pigs will be subjected to post mortem (necropsy) examination to evaluate lung lesions/inflammation. Lung tissues will also be used for virus isolation and PCR. Fixed lung tissue will be characterized for histopathologic lesions.
  • Clinical signs will be monitored daily for up to 14 days. Clinical signs to be monitored are: lethargy, nasal discharge (moderate, severe), and dyspnea (moderate, thumping). Rectal temperatures will be taken daily from the time of inoculation until day 14; Normal temperature of pigs is up to 103.5F and >103.5 is febrile. We may also use a heat scan technique to develop a thermo-map of individual pigs at 24 hour intervals from day 0 to day 14 or until the temperatures stabilize for 3 consecutive days. The pigs will be weighed on days 3, 7, 10, and 14 to monitor weight loss/gain. Feed and water intake will be measured on a daily basis.
  • Nasal swabs will be collected on day 0 to show that prior to infection the pigs are negative for SIV; on day 3 to detect successful inoculation/infection; and on day 7, 10, and 14 to determine if the virus shedding has stopped or not by quantitating the virus present in swabs. Samples that are negative for virus isolation will be examined by RT-PCR to insure the validity of virus isolation data.
  • Fresh lungs will be used for quantitative virus isolation. Samples that are negative for virus isolation will be examined by RT-PCR.
  • Macroscopic pneumonia scores, microscopic pneumonia scores, lung tissue and nasal swab virus titers, will be analyzed using analysis of variance (ANOVA) with ap-value ⁇ 0.05 considered significant (JMP, SAS Institute, Cary, NC).
  • ANOVA analysis of variance
  • Response variables shown to have a significant effect by treatment group will be subjected to comparisons for all pairs using the Tukey-Kramer test. Pair- wise mean comparisons between treated and non-treated groups for virus titers will be made using the Student's t-test.

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Abstract

L'invention concerne des procédés et compositions pour le traitement ou la prévention d'infections provoquées par des virus grippaux comprenant la grippe A, la grippe B, la grippe C et leurs mutants. Les procédés de l'invention utilisent des compositions pharmaceutiques comprenant du peroxyde d'hydroxyde (H2O2), de l'huile de terpène orange, de l'huile de valence orange et un support pharmaceutiquement acceptable. Dans un mode de réalisation, la composition pharmaceutique comprend en outre un émulsifiant non ionique (par exemple, le polysorbate 80). Dans d'autres modes de réalisation, la composition comprend également de l'origan, de l'huile de cumin, de l'essence de cassis, de l'essence de lavande, de l'huile de Mélaleuca à feuilles alternes et de l'huile d'olive. Divers sous-types de virus grippaux peuvent être traités au moyen des matériaux et procédés de l'invention et comprennent, sans s'y limiter, les sous-types H1N1, H1N2, H2N2, H3N2, H3N8, H5N1, H5N3, H5N8, H5N9, H7N1, H7N7, H9N2, et H10N7 y compris les sous-types suivants couramment connus sous les noms « grippe espagnole », « grippe asiatique », « grippe de Hong Kong », « grippe aviaire », « grippe porcine », « grippe équine » et « grippe canine ».
PCT/US2009/030753 2008-01-10 2009-01-12 Compositions et procédés pour le traitement d'infections virales provoquées par un virus grippal WO2009089534A2 (fr)

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JP2013079219A (ja) * 2011-10-05 2013-05-02 Sit:Kk 口腔用組成物
US20130158127A1 (en) * 2011-12-14 2013-06-20 Jean-Christophe Sergere Tea tree oil derivatives
RU2527688C2 (ru) * 2010-02-27 2014-09-10 Общество С Ограниченной Ответственностью "Научно-Производственная Фирма "Материа Медика Холдинг" Способ лечения инфекционных заболеваний, вызванных вирусом гриппа с типом поверхностого антигена н1n1 и лекарственное средство для лечения инфекционных заболеваний, вызванных вирусом гриппа с типом поверхностного антигена н1n1
CN108220221A (zh) * 2017-12-22 2018-06-29 吉林冠界生物技术有限公司 一种全悬浮细胞培养重组禽流感亚型病毒的方法

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Cited By (4)

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Publication number Priority date Publication date Assignee Title
RU2527688C2 (ru) * 2010-02-27 2014-09-10 Общество С Ограниченной Ответственностью "Научно-Производственная Фирма "Материа Медика Холдинг" Способ лечения инфекционных заболеваний, вызванных вирусом гриппа с типом поверхностого антигена н1n1 и лекарственное средство для лечения инфекционных заболеваний, вызванных вирусом гриппа с типом поверхностного антигена н1n1
JP2013079219A (ja) * 2011-10-05 2013-05-02 Sit:Kk 口腔用組成物
US20130158127A1 (en) * 2011-12-14 2013-06-20 Jean-Christophe Sergere Tea tree oil derivatives
CN108220221A (zh) * 2017-12-22 2018-06-29 吉林冠界生物技术有限公司 一种全悬浮细胞培养重组禽流感亚型病毒的方法

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