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WO1998017264A1 - Composition et procede de traitement topique des infections a herpesvirus actives - Google Patents

Composition et procede de traitement topique des infections a herpesvirus actives Download PDF

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Publication number
WO1998017264A1
WO1998017264A1 PCT/US1997/019186 US9719186W WO9817264A1 WO 1998017264 A1 WO1998017264 A1 WO 1998017264A1 US 9719186 W US9719186 W US 9719186W WO 9817264 A1 WO9817264 A1 WO 9817264A1
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WO
WIPO (PCT)
Prior art keywords
herpesvirus
geranium oil
active
herpesviral
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1997/019186
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English (en)
Inventor
Frank L. Greenway
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nextech Enterprises International
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Nextech Enterprises International
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nextech Enterprises International filed Critical Nextech Enterprises International
Priority to AU49159/97A priority Critical patent/AU4915997A/en
Publication of WO1998017264A1 publication Critical patent/WO1998017264A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • 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)
    • 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

Definitions

  • This invention pertains to the treatment of active heipesviral infections through the topical administration of the compositions described and claimed herein.
  • the herpesvirus family is one of four viral families in which the virus contains double- stranded DNA.
  • Examples of herpesviruses include herpes simplex, herpes zoster, the Epstein-Barr virus, and cytomeglovirus.
  • Many herpes viruses are neurotropic; i.e., the virus remains latent in the neurons of sensory ganglia and periodically emerges to cause active skin or nerve infections.
  • Herpes simplex virus Type 1 (“HSV-1 ”) causes open lesions to develop generally on or around the mouth, labialis lesions, commonly called cold sores or fever blisters.
  • Herpes simplex virus Type 2 (“HSV-2”) causes lesions to develop generally on or around the anogenital region, genitalis lesions.
  • HSV-1 is also thought to cause Bell's palsy, an infection of the motor nerve to the face, the facial nerve. Bell's palsy results in a loss of motor function on one side of the face (unilateral paralysis). The most devastating symptom is the inability to close the eye. The eye often suffers from corneal drying, which can result in ulceration and threaten vision.
  • a related syndrome is Ramsey-Hunt syndrome, which is thought to be caused by herpes zoster virus.
  • SUBSTrrUTE SHEET (RULE 26) still frequently recur and then persist for several days.
  • Topical application of 5% acyclovir is also unsatisfactory for many patients.
  • acyclovir improves average healing time by only one day, from six to five days. No effect on recurrence of lesions is reported. See Van Vloten et ah , "Topical Acyclovir Therapy in Patients with Recurrent Orofacial Herpes Simplex Infections," Journal of Antimicrobial Chemotherapy, Vol. 12, Supplement B, pp. 89-93 (1983).
  • 5% acyclovir decreases average healing time to eight days from ten days.
  • the current recommended treatment for Bell's palsy is oral administration of both acyclovir and the corticosteroid prednisone. These drugs are reported to decrease the extent of the infection and to moderate the nerve damage. Neither directly affects the paralysis of the eye muscles.
  • the current recommended treatment to protect the eye is to wear dark glasses or an eye patch, and to keep the eye moist with drops or ointment. See Rakel, ed., Conn's Current Therapy: Latest Approved Methods of Treatment for the Practicing Physician, pp. 906-07 (1996).
  • Geranium oil has been used in perfumes and as a food additive since the 1800's. It is on the GRAS (Generally Regarded As Safe) list of the United States Food and Drug Administration. Geranium oil is extracted from plants of the family Geraniaceae, frequently by steam distillation of fresh plants. A variety of species of geranium plants exist throughout the world, with most having approximately the same chemical constituents in the extracted oil. "Geranium oil bourbon,” however, derived from Pelargonium graveolens Ait. from Reunion Island off the east African coast, has a unique composition, including a higher level of the semi-volatile alcohol citronellol than geranium oils derived from other species and varieties. U.S. Pat. No.
  • U.S. Pat. No. 5, 126,376, U.S. Pat. No. 5,086,076, and U.S. Pat. No. 4,983,637 describe a method of treating viral infections with terpenes that have been oxidized with ozone to produce "ozonides of terpenes. " Examples include oxidation products of limonene, citronellol, alpha-carotene, beta-carotene, vitamin A, linalool, linalyl acetate, squalene, and geraniol. U.S. Pat. No.
  • 5,260,313 describes a method to treat neuropathic pain resulting from postherpetic neuralgia with topical application of geranium oil bourbon; i.e., treating the pain that remains after an infection from a reactivation of a latent Herpes zoster viral infection (chicken pox).
  • U.S. Pat. No. 4,923,685 describes antimicrobial, flavored compositions for use as mouthwashes, and includes geranium oil in a list of possible aromatic, flavoring oils.
  • U.S. Pat. No. 4,832,947 describes a process to incorporate essential oils, such as geranium oil, into hair fibers of freshly permanent waved hair to remove bad odors and to change the consistency of the hair.
  • geranium oil preferably geranium oil bourbon
  • the novel geranium oil treatment can decrease the time of healing, decrease the frequency of recurrent lesions, and can prevent lesion formation when prodromal symptoms are noted.
  • geranium oil can decrease the extent of unilateral facial paralysis, allowing the eye to close.
  • geranium oil bourbon has been applied topically to active herpes lesions or to areas beginning to itch, signalling the beginning of an active herpes infection (prodromal symptoms).
  • Topical application of geranium oil bourbon to the lesions of herpes labialis or herpes genitalis accelerated healing by several days, decreased the frequency of recurrent lesions, and prevented lesion formation when prodromal symptoms were felt. These results were seen even with lesions resistant to high dose acyclovir.
  • Topical application of geranium oil bourbon to the facial nerve of patients afflicted with Bell's palsy decreased the unilateral paralysis typical of the disease, especially paralysis of the eye muscles.
  • Geranium oil bourbon has also been diluted with a cream or lip balm and applied to labialis lesions. At a concentration of 80% geranium oil bourbon, the lip balm was as effective as the undiluted oil. At a concentration of 9% , the cream was less effective on labialis lesions than undiluted oil, but still more effective than no treatment. Geranium oil bourbon may also be diluted with creams or balms containing compounds that are currently used to treat labialis lesions, e.g., acyclovir or allantoin.
  • Geranium oil bourbon has several advantages over prior methods for treating herpes simplex lesions.
  • the novel treatment can decrease healing times to as little as one day, substantially decrease frequency of recurrences, and can even prevent lesions if applied to an area with prodromal symptoms.
  • topical application of geranium oil decreases the extent of the paralysis in Bell's palsy, especially of the eye muscles.
  • a concentration or amount of geranium oil or citronellol is considered to be "therapeutically effective” if it accelerates lesion healing, decreases the frequency of recurrent lesions, prevents lesion formation when prodromal symptoms are noted, or decreases the extent of the paralysis due to Bell's palsy.
  • a 35-year-old female with culture-verified HSV-2 in her genital and anal areas was the subject for a single-patient trial.
  • the patient had a seven-year history of frequently recurring lesions.
  • the patient During the three-month period prior to initiating treatment with geranium oil and for three months following the initiation of that therapy, the patient kept daily records regarding her antiviral drug dosage and her symptoms.
  • acyclovir was taken orally at a dose between 600 mg and 2,000 mg per day, with an average dose of 964 mg per day. Even while taking the acyclovir, the patient experienced symptomatic HSV-2 infection thirty-nine of ninety-four days. Of those thirty- nine days, twenty-eight days included symptoms of open sores, and the remaining eleven days included the burning, itching, and stinging typical of the beginning and end of each outbreak.
  • topical geranium oil bourbon was applied and the vaginal lesions resolved in less than one day. She was not able to reach her rectal area well and the anal lesions took three days to heal after initiating the topical treatment.
  • Geranium oil bourbon is an effective topical treatment for HSV-2 infections. It decreases healing time by several days, decreases the frequency of recurrence, and prevents open lesions from developing when applied to an area with prodromal symptoms.
  • a 45-year-old female with frequently recurring fever blisters on the vermilion border of the lip was the subject of this single patient trial.
  • the fever blisters were typical of a HSV-1 infection, comprising of a grouped vesicular eruption on an erythematous base.
  • the patient had four episodes of fever blisters on the lip, each lasting six days, for a total of twenty-four out of thirty days with an active lip lesion.
  • the patient began the geranium oil treatment. She applied one drop of geranium oil bourbon on the first day of the onset of a fever blister on her lip. The sore healed in one day, and she experienced no recurrence in fifteen days of follow-up. Thus, out of seventeen days, she experienced only two days with an active lip lesion.
  • Geranium oil bourbon is effective in treating active infections of HSV-1. It decreases the healing time to as little as one day and decreases the frequency of recurrence. Treatment of Bell 's Palsy
  • Two patients with Bell's palsy used geranium oil bourbon to help alleviate paralysis on the affected side of the face, especially the inability to close the eye.
  • the first patient had suffered from Bell's palsy for two weeks and was unable to close her eye on the affected side.
  • Geranium oil bourbon was topically applied to the entire distribution of the facial nerve on the paralyzed side of her face. After three minutes she was able to close her eye on the affected side albeit with some effort.
  • Geranium oil bourbon proved effective in decreasing the facial paralysis, especially paralysis of the eye muscles.
  • a chapstick with 80% geranium oil bourbon in a stearic acid carrier was formulated.
  • a patient who had frequent cold sores that previously took an average of ten days to heal tested the chapstick.
  • Full strength geranium oil bourbon decreased the healing time to an average of three days, with a range of one to five days, from an average of ten days.
  • the 80% geranium oil bourbon in chapstick form gave a similar time for healing, an average of three days. The patient felt the chapstick was a superior delivery system for two reasons.
  • the chapstick kept the geranium oil in direct contact with the fever blister longer. Full strength geranium oil ran quickly off the lips. Second, the geranium oil in the chapstick was less fragrant than the pure geranium oil, which has a strong odor.
  • Triad cream is a cream base containing pyruvate and two fat soluble ingredients that may have some healing properties.
  • a cream was prepared of 9% geranium oil bourbon in triad base. (Higher concentrations resulted in separation of the geranium oil from this particular base, and destruction of the cream properties of the carrier.)
  • This geranium oil cream was tried by a patient with frequent cold sores that typically took an average of ten days to heal. This patient had previously used the full strength geranium oil, which reduced healing time to an average of three days.
  • the healing time was six to seven days. Although the cream was less fragrant than the full strength geranium oil, it was less effective in decreasing the time to heal.
  • the 9% geranium oil in triad base reduced healing time (from ten days to six or seven days), but was less effective than the full strength geranium oil.
  • Geranium oils especially oils derived from the genus Pelargonium, are comprised chiefly of two alcohols, geraniol and citronellol. The quantities and ratios of these two alcohols vary with variety and place of origin.
  • Oil of geranium Reunion (geranium oil bourbon), the most commercially-available oil, has a high citronellol content, 44 to 52% . See Guenther, "VI. Essential Oils of the Plant Family Geraniaceae, " in The
  • citronellol is the active ingredient effective against active heipesviral infections. Because it has been discovered that diluted geranium oil bourbon is therapeutically effective, other geranium oils of lower citronellol content are also expected to be effective.
  • examples of other geranium oils which may prove especially effective include geranium oil Madagascar (less than 45% citronellol), geranium oil Francen (26 to 40% citronellol), geranium oil provoke (45 % citronellol), geranium oil French (37 to 40% citronellol), geranium oil Spanish (32.9% citronellol), geranium oil Italian (26 to 40% citronellol), geranium oil Egyptian (50% citronellol), geranium oil Congo (34- 48% citronellol), and geranium oil Russian (64% citronellol).
  • Geranium oil or citronellol may be more effective when combined with other ingredients of known anti-herpesviral properties. While not limiting the scope of the invention, examples of other anti-herpesviral compounds which may prove especially effective in combination with either geranium oil or citronellol include acyclovir and allantoin.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne l'huile de géranium, et plus particulièrement, l'huile de géranium Bourbon permettant de traiter des infections à herpèsvirus actives. Dans des lésions labiales et génitales, le traitement à l'huile de géranium peut réduire le temps de cicatrisation, peut diminuer la fréquence des lésions récurrentes et peut empêcher la formation de lésions lorsqu'on note des symptômes avant-coureurs. Dans la paralysie de Bell, l'huile de géranium ralentit le développement de la paralysie faciale unilatérale, permettant de fermer les yeux.
PCT/US1997/019186 1996-10-24 1997-10-23 Composition et procede de traitement topique des infections a herpesvirus actives Ceased WO1998017264A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU49159/97A AU4915997A (en) 1996-10-24 1997-10-23 Composition and method for topical treatment of active herpesviral infecti ons

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US73652296A 1996-10-24 1996-10-24
US08/736,522 1996-10-24

Publications (1)

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WO1998017264A1 true WO1998017264A1 (fr) 1998-04-30

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PCT/US1997/019186 Ceased WO1998017264A1 (fr) 1996-10-24 1997-10-23 Composition et procede de traitement topique des infections a herpesvirus actives

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WO (1) WO1998017264A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2925856A1 (fr) * 2007-12-28 2009-07-03 Patrick Mamou Mode operatoire specifique pour energiser l'association de differents ingredients naturels et optimiser leurs proprietes afin de leur conferer une plus grande efficacite contre des poussees d'herpes
US8236768B2 (en) 2008-10-03 2012-08-07 3B Pharmaceuticals, Inc. Topical antiviral formulations
WO2013077881A1 (fr) 2011-11-23 2013-05-30 3B Pharmaceuticals, Inc. Préparations antivirales
WO2017029298A1 (fr) * 2015-08-17 2017-02-23 Sanovel Ilac Sanayi Ve Ticaret A.S. Composition antivirale topique

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 120, Abstract 208578y, issued 25 April 1994, UEDA et al., "Volatile Inactivators for Envelope-Containing Virus"; & JP,A,05 306 217, 19 November 1993. *
CHEMICAL ABSTRACTS, Vol. 76, Abstract 103775e, BARANGER PIERRE, "Antineoplastic and Antiviral Terpene and Alicyclic Alcohols for Veterinary Administration"; & FR,A,2 062 871, 06 August 1971. *
WINDHOLZ et al., "The Merck Index", MERCK AND CO., RAHWAY, N.J., Tenth Edition, 1984, Abstract 242, page 138. *
WINDHOLZ et al., Ed., "The Merck Index", MERCK & CO., RAHWAY, N.J., Tenth Edition, 1984, Abstract 140, page 243. *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2925856A1 (fr) * 2007-12-28 2009-07-03 Patrick Mamou Mode operatoire specifique pour energiser l'association de differents ingredients naturels et optimiser leurs proprietes afin de leur conferer une plus grande efficacite contre des poussees d'herpes
US8236768B2 (en) 2008-10-03 2012-08-07 3B Pharmaceuticals, Inc. Topical antiviral formulations
US9144576B2 (en) 2008-10-03 2015-09-29 3B Pharmaceuticals, Inc. Topical antiviral formulations
WO2013077881A1 (fr) 2011-11-23 2013-05-30 3B Pharmaceuticals, Inc. Préparations antivirales
WO2017029298A1 (fr) * 2015-08-17 2017-02-23 Sanovel Ilac Sanayi Ve Ticaret A.S. Composition antivirale topique

Also Published As

Publication number Publication date
AU4915997A (en) 1998-05-15

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