HOMEOPATHIC COMPOSITION COMPRISING HYPERICUM PERFORATUM EXTRACT AND ESSENTIAL OILS FOR THE TREATMENT OF NEUROPATHIC PAIN

Abstract

The present invention provides a method of treating neuropathic pain by administering a topical homeopathic composition to a mammalian subject. The homeopathic formulation contains homeopathic active ingredients comprising Hypericum perforatum in a base of essential oils which facilitate delivery of the homeopathic ingredient through the skin.

Claims

1. A composition comprising two or more homeopathic active ingredients selected from the group consisting of Hypericum perforatum, Aconitum napellus and Secale cornutum combined with a base comprising geranium oil, wherein each of the two or more homeopathic active ingredients has a potency ranging from about 3X to about 30C.

2. The composition of claim 1, wherein the composition comprises a combination of Hypericum perforatum, Aconitum napellus, and Secale cornutum.

3. The composition of claim 1, wherein the base further comprises one or more plant essential oils selected from the group consisting of melaleuca, bergamot, eucalyptus, lavender and combinations thereof.

4. The composition of claim 1, wherein the homeopathic active ingredients are added to the base in an amount equal to approximately 0.1 to 50% by volume.

5. The composition of claim 1, wherein the base is a gel base manufactured with a suitable gelling agent.

6. The composition of claim 1, which is a spray, an ointment, or a roll-on or is formulated for administration via a skin patch.

7. The composition of claim 1, wherein each homeopathic active ingredient has a potency of about 12C.

8. The composition of claim 1 wherein the homeopathic active ingredients are Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, and Phosphorus, and wherein the base comprises the plant essential oils geranium, melaleuca, bergamot, eucalyptus, and lavender.

9. The composition of claim 8 wherein the homeopathic ingredients are all at 12C potency.

10. A method for the treatment of neuropathic pain comprising topical administration of a composition comprising one or more homeopathic active ingredients combined with a base of one or more physiologically acceptable plant essential oils.

11. The method of claim 10, wherein one of the one or more homeopathic active ingredients is Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, or Phosphorus.

12. The method of claim 10, wherein each homeopathic active ingredient has a potency ranging from tincture to about 1M, or from about 3X to about 30C, or about 12C.

13. The method of claim 10, wherein the composition comprises a combination of Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, or Phosphorus.

14. The method of claim 10, wherein the plant essential oils are selected from the group consisting of pelargonium, melaleuca, bergamot, eucalyptus, lavender and combinations thereof.

15. The method of claim 10, wherein the homeopathic active ingredients are added to the base in an amount equal to approximately 0.1 to 50% by volume.

16. The method of claim 10, wherein the neuropathic pain is caused by a disorder selected from the group consisting of diabetic peripheral neuropathy, herpes zoster, post herpetic neuralgia, trigeminal neuralgia, complex regional pain syndrome, reflex sympathetic dystrophy, phantom limb syndrome, neuropathic pain due to chronic disease, neuropathic pain due to trauma, neuropathic pain due to impingement, neuropathic pain due to drug exposure or toxic chemical exposure, neuropathic pain due to infection or post infection, neuropathic pain due to impaired organ function, neuropathic pain due to vascular disease, neuropathic pain due to metabolic disease, neuropathic pain due to cancer or cancer treatment, neuropathic pain due to autoimmune disease, neuropathic pain due to fibromylagia, and neuropathic pain with no known cause, or any pain is that is characterized by burning sensations, shooting pain, numbness, tingling, allodynia or a combination thereof.

17. The method of claim 10, wherein the base is a gel base manufactured with a suitable gelling agent.

18. The method of claim 10, wherein the delivery method is via a spray, ointment, device that adheres to the skin, or roll-on.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0034] FIG. 1 graphically depicts the effect of the topical application on pain reduction following the procedure of Example 1.

[0035] FIG. 2 graphically depicts the effect of a composition according to one embodiment of the invention (A) in comparison to a placebo (B).

DETAILED DESCRIPTION OF THE INVENTION

[0036] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0037] Unless the context clearly indicates otherwise, as used herein plural forms of the terms herein are to be construed as including the singular form and vice versa.

[0038] The term comprising as used herein will be understood to mean that the list following is non-exhaustive and may or may not include any other additional suitable items, for example one or more further feature(s), component(s) and/or ingredients(s) as appropriate.

[0039] The present invention provides a solution to a number of unique and previously unsolved problems. Primarily, as mentioned in the background information, it is generally recognized that there is a limited ability to manage the symptoms of neuropathic pain. Current pharmaceutical treatments are often ineffective or result in unacceptable side effects at the doses necessary for symptom relief. The only approved over-the-counter drug, capsaicin, results in increased pain and burning at the site of application and is therefore not widely tolerated.

[0040] The traditional form of medicine known as homeopathic medicine utilizes a unique materia medica based on compounds found in the natural world. Homeopathic medications are prepared, by one skilled in the art, using the traditional techniques of dilution and succession, to various potencies. Although traditional textbooks of homeopathic medicine make no mention ofneuropathic pain per se, homeopathic remedies can be chosen based on the unique symptoms of the neuropathic pain condition.

[0041] Traditional homeopathic remedies are prepared in an alcohol and water base and administered orally. The current invention is unique in that, for the purpose of relieving neuropathic pain, the formula which is the subject of the invention is applied topically to the area of pain and contains skin permeation enhancers.

[0042] The current invention utilizes traditionally prepared homeopathic medicines, but in a hydrophobic base comprising essential oils as skin permeation enhancers. To facilitate the solubility of the homeopathic active ingredients in a hydrophobic environment, the final dilution of the homeopathic medicines takes place in an alcohol environment (80-100% alcohol by volume). The exclusion of water enables the resultant homeopathic formulation to be soluble in an essential oil mixture or any individual essential oil compounds. This type of formulation is unique since those skilled in the art of homeopathy consider essential oils to be contraindicated for use combined with, or even concurrently with, homeopathics. For the treatment of neuropathic pain, however, it is desirable and efficacious to ensure the delivery of the homeopathics to the site of the aberrant nerve signal. This is accomplished with the addition of the essential oil components to the homeopathic(s), which facilitates transdermal delivery.

[0043] The term essential oil, as used herein, refers to a concentrated, hydrophobic liquid containing volatile aroma plant compounds isolated from a plant or derived synthetically. The essential oil comprises a variety of hydrophobic constituents (e.g., various terpenes, alcohol esters, aldehydes, ketones, phenols etc., typically soluble in water less than 10 wt %).

[0044] In most cases, essential oils are prepared by steam distillation, maceration, expression, and/or solvent extraction of plant materials, for example leaves and/or petals. Synthetic oil blends can also be utilized. Individual synthetic compounds, or natural compounds purified to homogeneity (e.g., synthetic or isolated terpenes, terpenoids, alcohol esters, ketones, phenols etc.) may also be utilized in the composition of the present invention. Similarly, one or more essential oils may be supplemented with one or more of the volatile compounds commonly found in plants or prepared synthetically.

[0045] In accordance with a specific embodiment of the present invention, the essential oil is from pelargonium, melaleuca (tea tree), bergamot, eucalyptus, lavender or a combination thereof.

[0046] All known essential oils are contemplated suitable for use herein. Suitable essential oils are prepared from plant material of one or more plant species using isolation methods well know to those skilled in the art, or prepared synthetically by one skilled in the art.

[0047] Essential oils are highly complex mixtures of often hundreds of individual compounds. A typical plant essential oil chromatogram may contain in the order of 200 or more distinct peaks. Plant essential oils are a complex mixture of terpenes, sesquiterpenes, esters, alcohols, phenols, aldehydes, ketones, organic acids, and various miscellaneous molecular structures. Furthermore, each class of compound above contains many subclasses. For example, the terpene classification includes hemiterpenes, monoterpenes, diterpenes, sesquiterpenes, triterpenes, tetraterpenes, and associated terpenoids formed by the modification or oxidation of the carbon skeleton. Essential oils often have an odour and are therefore used in food flavouring and perfumery. Essential oils are typically distinguished as a group by their minimal solubility in water, and this criteria makes them suitable for use in this invention.

[0048] Some examples of essential oils that would be suitable for use in this invention are; Agar (Aquilaria malaccensis), Ajwain (Carum copticum), Angelica root oil (Angelica archangelica), Anise (Pimpinella anisum), Asafoetida, Balsam (Myroxylon pereirae), Basil Bergamot, Black Pepper (Piper nigrum), Buchu, Cannabis, Caraway, Cardamom, Carrot seed, Cedarwood, Chamomile, Calamus, Cinnamon, Cistus species, Citronella, Clary Sage, Coffee, Coriander, Costmary, Costus, Cranberry, Cubeb, Cumin, Cypress, Cypriol, Curry Leaf, (Artemisia pallens), Dill, Elecampane, Eucalyptus, Fennell, Fenugreek, Fir, Frankincense, Galbanum, Geranium (and/or Pelargonium), Ginger, Goldenrod, Grapefruit, Henna, Helichrysum, Hyssop, Idaho Tansy, Jasmine, Juniper, Lavender, Laurus nobilis, Ledum, Lemongrass, Litsea cubeba, Marjoram, Melaleuca (Tea tree), Melissa (Lemon balm), Mentha arvensis (Mint), Mountain Savory, Mugwort, Mustard, Myrrh, Myrtle, Neroli, Nutmeg, Orange, Lemon, Oregano, Orris, Palo Santo, Parsley, Patchouli, Perilla, Petitgrain, Ravensara, Red Cedar, Roman Chamomile, Rose, Rosehip, Rosemary, Rosewood, Sage, Star anise, Sandalwood, Sassafras, Savory, Schisandra, Spearmint, Spikenard, Spruce, Tangerine, Tarragon, Tea tree oil, Thyme, Tsuga, Turmeric, Valerian, Vetiver (khus oil), Wintergreen, Ylang-ylang, and Zedoary.

[0049] In one embodiment of the invention, the essential oils include pelargonium oil, bergamot oil, eucalyptus oil, lavender oil, and/or melaleuca oil.

[0050] Homeopathics are prepared in the manner practiced by one skilled in the art according to the Homeopathic Pharmacopoeia of the United States (HPUS), Good Manufacturing Practice (GMP), and applicable Over the Counter (OTC) regulations. Homeopathics chosen can be any of those based on traditional rubrics (symptom lists) from traditional textbooks of homeopathic medicine by one skilled in the art.

[0051] Examples of homeopathics traditionally used to treat the symptoms of neuropathic pain include Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, Phosphorus, Sulphur, Pulsatilla, Arsenicum, Nux vomica, Thuja occidentalis, Causticum, Kali carbonicum, Sepia, Silica, Conium maculatum, Apis Mellifica, Belladonna, Agaricus, Platina, Calcarea Phosphorica, Chininum, Coccus cacti, Rhododendron chrysanthum OR Rhodium metallicum, Graphites, Colocynthis, Mercurius, Stannum metallicum, Phosphoricum acidum, Lachesis, Capsicum, Staphylococcinum, Natrum mur, Colchicinum, Bryonia, Ferrumphos, Allium cepa, Agrentum metallicum, Baryta-carb, Zincum, Chamomilla, Mezereum. Ranunculus bulbases, Ammonium muriaticum, Euphrasia, Sabadilla officinalis, Asafoetida, Secale comutum, Carbo-veg, Plumbum metallicum, Nit-ac, Spigelia, Carbo animalis, Cina, Kali nitricum, Chelidonium, Dulcamara, Aurum metallicum, Ledum, Sabina officinalis, Ignatia amara, Digitalis, Carbon sulphuratum, Hepar sulph, Kali-bich, Amonium carb, Cuprum metallicum, Magnesia phosphoric, Iodine, Veratinum, Guai, Calcphos, Mercurius corrosivus OR Mercurius cyanatus, Spongia tosta, Nux Moschata, Cantharis, Kreosotum, Taraxacum officinale, Anacardium orientale, Camphor, Oleander, Berberis, Manganum, Muriaticum acidum, Naturm Carb, Valeriana officinalis, Kali-sulph, Laurocerasus officinalis, Ambra Grisea, Asarum, Sulphuricum acidum, Ant crud, Cicuta, Mag-mur, Kali-phos, Clemetiserecta, and Kali arsenicum.

[0052] Six examples of such remedies are hypericum perforatum, phosphorus, rhus toxicodendron, secale cornutum, lycopodium and aconitum napellus.

[0053] The potency of the homeopathic ingredients may vary from mother tincture (undiluted) to 1M, however the preferred embodiment recommends a homeopathic OTC potency of 3X to 30C, with 12C ideal. The homeopathic ingredients may be added to the essential oils in an amount varying from 0.1% by volume to 50% by volume, with 1% to 10% by volume preferred.

[0054] The composition described herein can be delivered to the skin overlying the area of aberrant nerve function or neuropathic pain in a number of ways. The composition can be applied topically directly to the area using the finger or other instrument of application. The composition can also be delivered via a container suitable for topical applications to the skin, such as a container with the ability to spray, roll or otherwise apply the composition to the skin. The composition can also be added to a suitable material containing a reservoir and adhesive for application to the skin.

[0055] In accordance with a particular embodiment of the present invention, the composition consists only of an essential oil or mixture of essential oils as a base and one or more homeopathic active agents. Alternatively, the composition additionally comprises a pharmaceutically acceptable diluent or excipient suitable for use in a topical composition. Selection of such additional diluents or excipients is within the abilities of a person of ordinary skill in the field and is made based on the intended use of the product. The additional diluents or excipients do not affect the therapeutic efficacy of the composition.

[0056] In accordance with another embodiment of the invention, the composition is or can be incorporated into a device containing a reservoir for the sustained release of medication to be absorbed topically through the skin. The medication within the reservoir migrates over time from within the reservoir to the site of action. The reservoir is supported by a backing structure and is attached to the skin via a suitable adhesive. Alternatively, the composition and adhesive are comingled in the reservoir. Treatment involves placing the device on the skin for a prescribed duration.

[0057] In accordance with one embodiment of the invention, the composition is prepared using a suitable gelling agent. For example, a combination of bees wax and sorbitan monopalmitate can be used as a gelling agent. Selection of a suitable gelling agent is made to ensure proper consistency and absorption without negatively affecting therapeutic activity or being an irritant.

[0058] The compositions of the present invention are useful in treating neuropathic pain. Neuropathic pain can be caused by a disorder selected from, but not limited to, diabetic peripheral neuropathy, herpes zoster, post herpetic neuralgia, trigeminal neuralgia, complex regional pain syndrome, reflex sympathetic dystrophy, phantom limb syndrome, neuropathic pain due to chronic disease (multiple sclerosis, HIV, etc), neuropathic pain due to trauma (causalgia), neuropathic pain due to impingement (ie. sciatica, carpal tunnel, etc), neuropathic pain due to drug exposure or toxic chemical exposure, neuropathic pain due to infection or post infection, neuropathic pain due to impaired organ function, neuropathic pain due to vascular disease, neuropathic pain due to metabolic disease, neuropathic pain due to cancer or cancer treatment, neuropathic pain due to autoimmune disease, neuropathic pain due to fibromylagia, and neuropathic pain with no known cause (idiopathic), or any pain is that is characterized by burning sensations, shooting pain, numbness, tingling, allodynia or a combination thereof

[0059] To gain a better understanding of the invention described herein, the following examples are set forth. It should be understood that these examples are for illustrative purposes only. Therefore, they should not limit the scope of this invention in any way.

EXAMPLES

Example 1

[0060] Community-dwelling individuals with diagnosed neuropathic pain were recruited from the community. No distinction was made with respect to the underlying cause of the neuropathic pain. Potential participants were excluded from the study if they presented with (1) an inability to walk at least 20 meters independently, (2) a history or evidence of central nervous system dysfunction, (3) musculoskeletal injury and or deformity that may influence gait and posture, (4) a history of vestibular dysfunction, (5) evidence of plantar cutaneous ulcer, and (6) any uncontrolled metabolic, cardiovascular, or respiratory disease. Following explanation of all the details of the study, each participant signed an informed consent. The project was approved by the Institutional Review Board.

[0061] Participants were randomly assigned into a treatment or no treatment group. The cause of the peripheral neuropathy included diabetes mellitus (n=6) and trauma (n=2), with the remaining cases of indeterminate cause (n=6). The treatment group received external application of a composition containing the homeopathic ingredient hypericum perforatum combined with an essential oil mixture of lavender, pelargonium, bergamot, eucalyptus and tea tree oil. Before each application pain level was monitored on a 0-10 visual scale. 15 subjects were recruited for each group, but only five (1 man, 4 women, age=6617 years, height=1658 cm, body mass=7925 kg) and nine (5 men, 4 women, age=6415 years, height=1771 cm, body mass=10124 kg) completed all the required testing.

[0062] Pain level associated with the feet was self-monitored on a 0-10 scale (10 being most severe) three times every session. Participants recorded their pain level immediately upon arrival (PRE), five minutes following composition application in the treatment group (or five minutes of quiet sitting in no treatment group) (5 MIN), and immediately following one hour of exercise (POST). The pain relieving composition was applied with a spray top applicator for a total of five pumps per foot, with one pump over (1) the dorsal aspect of the toes, (2) the dorsal foot roughly halfway between the toes and the ankle, (3) the inside of the foot midway along the longitudinal arch, (4) the outside of the foot midway between the toes and ankle, and (5) the plantar surface of the foot halfway between the heel and toes. Total volume of composition applied was approximately 0.75 ml to each foot.

[0063] Pre- and post-test comparison within each group were statistically tested with one tailed T-Tests. Longitudinal pain level changes of the two groups were tested using trend analysis. The slopes of the regression lines were compared to a horizontal line for an absolute effect and with each other for group comparison. The relative post- to pro-test changes of each criterion measure were compared between groups with one tailed T-Tests. Significance was set at =0.05.

[0064] The effect of the topical application on pain reduction are presented in FIG. 1, in which pain scales were averaged across the six weeks of the study. Average PRE pain levels were 3.7 and 3.8 for the treatment and no treatment groups, respectively. Application of the topical homeopathic/essential oil composition significantly reduced the 5 MIN (2.2) and POST (1 hr) (1.7) pain levels.

Example 2

[0065] A composition containing the homeopathic ingredient hypericum perforatum combined with an essential oil mixture of lavender, pelargonium, bergamot, eucalyptus and tea tree was tested in a double blind placebo controlled fashion. Sixty subjects with plantar cutaneous (foot sole) pain due to all cause neuropathy were recruited from the community. Each subject was assessed for inclusion/exclusion based on standard criteria for neuropathic pain studies. Subjects found suitable were given the opportunity to participate once they signed a consent form. Each subject was also be provided with an adverse events report form, and instructed in its use.

[0066] Change in average pain levels (10 point numeric scale) at 30 min, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr, 6 hr, 7 hr, and 8 hr after application of the pain relieving homeopathic/essential oil composition was recorded. Change in pain as reported on the McGill Pain Questionnaire (short form) 30 min after application was also measured. Each participant received either the active treatment or mineral oil placebo in random order, based on a balanced latin square design. The identities of the supplied bottled sprays were not known to the investigators or the participants. Each treatment was repeated at least once in each participant to test the reliability of the testing. The 10 point numerical pain scale was programmed in a pocket PC and presented to the participants automatically on the PC's screen accompanied with an audio reminder.

[0067] The pain relieving composition was applied with a spray top applicator for a total of five pumps per foot, with one pump over (1) the dorsal aspect of the toes, (2) the dorsal foot roughly halfway between the toes and the ankle, (3) the inside of the foot midway along the longitudinal arch, (4) the outside of the foot midway between the toes and ankle, and (5) the plantar surface of the foot half way between the heel and toes. Total volume of composition applied was approximately 0.75 ml to each foot.

[0068] Treatment with the homeopathic/essential oil composition resulted in a statistically significant reduction in spontaneous pain (p<0.005) which was in effect within 30 minutes and lasted approximately 8 hrs (FIG. 2).

Example 3

[0069] M.D. a 56 yr old woman with a 34 yr history of DM Type I reported to the clinic. Her complaints included angina, poor vision, swollen feet, chronic pain in feet as well as numbness and burning sensations. Her weight was 249 lb and her height 55.

[0070] Blood work was as follows: [0071] Fasting Glucose 8.3 (3.6-5.6) [0072] HA1C 9.2% (4.6-6.5) [0073] Creatinine 194 (35-88) [0074] Urea 11.6 (2.9-9.3) [0075] Liver enzymes normal

[0076] Her only medication was insulin for diabetes. She was assessed for pain using a 0-10 digital scale with the yardsticks 0=no pain and 10=worst possible pain. She rated her pain level as 8/10 in both feet. Her left foot was then treated with a thin film of a cream consisting of 1% homeopathic ingredients (equal parts Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, and Phosphorus all at 12C potency) prepared in a non-medicinal cream base consisting of water, glycerin, distearyldimonium chloride, petrolatum, isopropyl palmitate, cetyl alcohol, benzoyl alcohol and sodium chloride). Her right foot was treated with a thin film of the same 1% homeopathic ingredients (Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, and Phosphorus all at 12C potency) prepared in a base consisting of an essential oil mixture of 28.29% v/v lavender. 28.29% v/v pelargonium graveolens. 14.14% v/v citrus bergamia. 14.14% v/v eucalyptus globulus and 14.14% v/v melaleuca alternfolia. After 5 minutes of quiet sitting she reported a pain level of 6/10 in the left foot and 2/10 in the right foot. After one hour she reported that her left foot was still painful and she asked to use the essential oil formula on the left foot. She proceeded to do so and received the same degree of pain relief as experienced in the right foot.

[0077] Table 1 provides a list of the components within the essential oil blend used as the base in this Example.

TABLE-US-00001 TABLE 1 Compound cis-3-hexen-1-ol hexyl butyrate <-thujene nerol <-pinene citronellol camphene neral sabinene cis-iso-geraniol <-pinene geraniol myrcene linalyl acetate <-phellandrene geranial <-terpinene citronellyl formate p-cymene neryl formate limonene lavandulyl acetate 1,8-cineole geranyl formate benzyl alcohol citronellyl acetate cis-<-ocimene neryl acetate trans-<-ocimene <-copaene <-terpinene <-bourbonene trans-linalool oxide (fur.) geranyl acetate terpinolene longifolene cis-linalool oxide (fur.) <-caryophyllene linalool decyl acetate cis-rose oxide trans<bergamotene phenylethyl alcohol <-guaiene trans-rose oxide 6,9-guaiadiene dihydrolinalool muurola-3,5-diene camphor citronellyl propionate menthone <-humulene isoborneol alloaromadendrene isomenthone geranyl propionate borneol lavandulol terpin-1-en-4-ol isomenthol <-terpineol <-terpineol

Example 4

[0078] R.M. a 58 year old male with post shingles pain (post herpetic neuralgia) of the left lateral trunk region of 6 months duration. He reported almost constant pain, with pricking and burning sensations, worse from touch. He was taking 20 mg Lipitor per day for cholesterol management and no other medications. He was treated with a thin film of a cream consisting of 1% homeopathic ingredients (equal parts Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, and Phosphorus all at 12C potency) prepared in a non-medicinal cream base consisting of water, glycerin, distearyldimonium chloride, petrolatum, isopropyl palmitate, cetyl alcohol, benzoyl alcohol and sodium chloride). He reported a reduction in pain from 7/10 pre treatment to 4/10 five minutes post treatment. On a subsequent clinic visit he was treated with a thin film of the same 1% homeopathic ingredients (Hypericum perforatum, Aconitum napellus, Secale cornutum, Rhus toxicodendron, Lycopodium, and Phosphorus all at 12C potency) prepared in a base consisting of a synthetic essential oil blend (Table 2). After 5 minutes of sitting he reported a pain level of 1/10, the most relief he had experienced from any treatment tried since the onset of his pain.

TABLE-US-00002 TABLE 2 cis-hex-3-en-1-ol trans-iso-geraniol linalool neral phenylethyl alcohol cis-iso-geraniol cis rose oxide geraniol trans rose oxide linalyl acetate menthone geranial isoborneol citronellyl formate isomenthone neryl formate borneol geranyl formate P-terpineol furanopelargone A nerol geranyl tiglate citronellol

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[0085] All publications, patents and patent applications mentioned in this Specification are indicative of the level of skill of those skilled in the art to which this invention pertains and are herein incorporated by reference to the same extent as if each individual publication, patent, or patent applications was specifically and individually indicated to be incorporated by reference.

[0086] The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.