WO2015000064A1 - Composition pour le traitement de la douleur et/ou de l'inflammation comportant de l'eugénol et du béta-caryophyllène - Google Patents

Composition pour le traitement de la douleur et/ou de l'inflammation comportant de l'eugénol et du béta-caryophyllène Download PDF

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WO2015000064A1
WO2015000064A1 PCT/CA2014/000545 CA2014000545W WO2015000064A1 WO 2015000064 A1 WO2015000064 A1 WO 2015000064A1 CA 2014000545 W CA2014000545 W CA 2014000545W WO 2015000064 A1 WO2015000064 A1 WO 2015000064A1
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composition
caryophyllene
eugenol
beta
pain
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PCT/CA2014/000545
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English (en)
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Donna EVANS
Sean Evans
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Evans Donna
Sean Evans
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    • 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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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)
    • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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

Definitions

  • the present invention generally relates to pain and/or inflammation relief, and in particular, relates to a composition useful to treat pain and/or inflammation.
  • Multicomponent therapeutics in which two or more agents interact simultaneously with multiple targets is a rational and efficient form of therapy designed to control complex diseases.
  • One of the advantages of multicomponent therapeutics is the potential synergistic effect of the combination, e.g. an effect which is greater than the sum of the expected individual effects.
  • a multimodal therapeutic approach is best suited to target the complex mechanisms leading to the transition from acute to chronic pain.
  • Multi-target drugs may overcome system robustness and result in reduced side-effects and reduced toxicity that may be associated with high doses of single drugs.
  • composition comprising beta-caryophyllene or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof, and eugenol or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof.
  • a method of treating pain and/or inflammation in a mammal comprising administering to the mammal a composition comprising beta-caryophyllene or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof, and eugenol or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof.
  • an article of manufacture comprising packaging and a composition, wherein the composition comprises beta-caryophyllene or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof, and eugenol or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof, and the packaging indicates that the composition is useful to treat pain and/or inflammation.
  • a composition for use in treating pain and/or inflammation comprising beta-caryophyllene or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof, and eugenol or a functionally equivalent derivative, analogue or pharmaceutically acceptable salt thereof.
  • beta-caryophyllene is used herein to encompass the secondary metabolite, bicyclic sesquiterpene,-4, 1 1,11 -trimethyl-8-methylene-bicyclo[7.2.0]undec-4-ene, which is present in, for example, plant-derived oleoresins, essential oils, solutes, distillates, extracts, fermentations, infusions and leaching, from plants including, but not limited to, Cannabis spp.
  • Cannabis sativa, Cannabis indica and Cannabis ruderalis including Cannabis sativa, Cannabis indica and Cannabis ruderalis, Humulus lupulus, Carum nigrum, Eugenia caryophyllata, Ocimum micranthum, Origanum vulgare, Piper guineense, Cinnamomum zeylanicum, Carthamus tinctorius, Helichrysum italicum, Copaifera spp.
  • Copaiba officinalis including Copaiba officinalis, Copaibaguianensis, Copaiba martii hayne, Copaiba Duckei, Copaiba reticulata, Copaiba multijuga, Copaiba confertiflora, Copaiba langsdorffii, Copaiba coriacea, Copaiba trapezifolia, Copaiba lucens, Copaiba paupera and Copaiba cearensis, Syzygium aromaticum (clove), piper nigrum (black pepper), Zingiber nimmoni, Zingiber officinale, Ocimum canum, Ocimum selloi, Piper cubeba, Aframomum melegueta, Panax ginseng, Zanthoxylum piperitum, Zanthoxylum simulans, Zanthoxylum bungeanum, Zanthoxylum rhesta, Zanthoxylum acanthopodium, Zanthoxylum piperitum, Syzgium aromaticum, Mentha longi
  • canescens Artemisia salsoloides, Thymus zygis subsp. Sylvestris, Teucrium chamaedrys, Origanum minutiflorum, Ocimum basilicum, Thymus x citriodorus, Micromeria Juliana, Origanum onites, Origanum vulgare subsp.
  • thymoides Hyptis suaveolens, Plectranthus coleoides, Vitex agnus-castus, Calamintha nepeta, Micromeria myrtifolia, Mentha aquatic, Salvia dorisiana, Ocimum suave, Sideritis scardica, Plectranthus incanus, Mentha x piperita, Hyssopus officinalis subsp. aristatus, Rosmarinus x mendizabalii, Satureja subspicata subsp.
  • piperascens Mentha pulegium, Mentha rotundifolia, Mentha spicata, Montanoa tomentosa, Murraya koenigii, Myrciaria dubia, Myristica fragrans, Myrrhis odorata, Nepeta cataria, Ocimum gratissimum, Panax ginseng, Pelargonium citrosum, Perilla frutescens, Petroselinum crispum, Pimenta dioica, Pimenta racemosa, Pimpinella anisum, Pinus strobus, Piper nigrum, Pistacia lentiscus, Populus tacamahacca, Psidium guajava, Ptychopetalum olacoides, Ravensara aromatic, Sambucus nigra, Vaccinium myrtillus, Sassafras albidum, Satureja hortensis, Stevia rebaudiana, Illicium verum,
  • Functionally equivalent derivatives, analogues or salts of beta-caryophyllene which are pharmaceutically acceptable, may replace beta-caryophyllene in the present composition.
  • functionally equivalent refers to compounds which possess the activity or function of beta-caryophyllene, at least in part, to treat pain and/or inflammation.
  • pharmaceutically acceptable refers to derivatives, analogues and salts which are
  • mammals includes human and non-human mammals, including domestic animals, e.g. cats, dogs, rodents, cattle, horses and the like, as well as non- domesticated animals.
  • Functionally equivalent derivatives or analogues, including structural and functional analogues, of beta-caryophyllene include compounds derived from beta-caryophyllene or a precursor thereof, including isomers thereof.
  • Examples of functionally equivalent derivatives or analogues include, but are not limited to, alpha-humulene, 9-epi-(E)- Caryophyllene, [-] -Caryophyllene oxide or (-)-Epoxycaryophyllene, (li?,4i?,6 ?,10S)-9- Methylene-4,12,12-trimethyl-5-oxatricyclo[8.2.0.0 ] Caryophyllene, 9-epi-Caryophyllene or (E)- Caryophyllene, epi-, cis-Caryophyllene, (+)(E)-Caryophyllene or 2-epi-(E)- ⁇ -Caryophyllene, and Isoc
  • salts which are pharmaceutically acceptable salts of beta- caryophyllene are also encompassed herein for use to treat pain and/or inflammation.
  • salts refers to salts or esters of beta-caryophyllene that retain the desired biological activity of the parent compound to treat pain and/or inflammation, at least in part. Examples of such salts include acid addition salts and base addition salts.
  • Acid addition salts include those derived from nontoxic inorganic acids, such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, phosphorous and the like, as well as from nontoxic organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, aromatic acids, aliphatic and aromatic sulfonic acids and the like.
  • nontoxic inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, phosphorous and the like
  • nontoxic organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, aromatic acids, aliphatic and aromatic sulfonic acids and the like.
  • Base addition salts include those derived from alkaline earth metals, such as sodium, potassium, magnesium, calcium and the like, as well as from nontoxic organic amines, such as ⁇ , ⁇ '-dibenzylethylenediamine, N- methylglucamine, chloroprocaine, choline, diethanolamine, ethylenediamine, procaine and the like.
  • beta-caryophyllene for use in the present composition may also be synthetically derived.
  • the term "eugenol” is used herein to encompass the secondary metabolite, phenylpropene, 4-allyl-2-methoxyphenol, which is present in plant-derived oleoresins, essential oils, solutes, distillates, extracts, fermentations, infusions and leaching, from, for example, plants including, but not limited to, Eugenia caryophyllus, Syzygium aromaticum, Cinnamomum tamala, Ocimum spp.
  • Ocimum basilicum such as Ocimum basilicum, Ocimum kilimandscharicum, Ocimum suave, Ocimum selloi., Ocimum gratissimum, Foeniculum vulgare, Sassafras albidum, Cinnamomum loureiroi, Cinnamomum burmannii, Eugenia polyantha, Zanthoxylum piperitum, Zanthoxylum simulans, Zanthoxylum bungeanum, Zanthoxylum rhesta, Zanthoxylum acanthopodium, Zanthoxylum piperitum, Ocimum tenuiflorum, Ocimum sanctum, Ocimum campechianum, Ocimum basiliddler.
  • Ocimum basilicum var. grand vert Ocimum basilicum var. minimum, Euphorbia spp., Aspalathus linearis, Humulus lupus, Lavendula officinalis, Lavendula angustifolia, Panax ginseng, Vaccinium macrocarpon, Vaccinium myrtillus Ocimum gratissimum var. thymoliferum and Ocimum santum ct.
  • Cymbopogon winterianus Pycnanthemum setosum, Origanum minutiflorum, Micromeria fruticosa subsp. barbata, Thymus capitatus, Jasminum officinale, Lavandula latifolia, Micromeria congesta, Calamintha nepeta subsp.
  • Malaleuca bracteata Malaleuca leucadendron, Michelia alba, Myrtus communis, Ocotea pretiosa, Pelargonium graveolens, Pelargonium odoratissum, Peumus boldus,, Pimpinella anisum, Piper cubeba, Ravensara aromatic, Rosa centifolia, Rosa spp.
  • Satureia hortensis Rosa rugosa, Satureia montana, Tagetes minuta, Trachyspermum ammi and all Plantae taxa thereof including life, domain, kingdom, phylum, class, order, family, genus, species, super- species, sub-species, varieties, hybrids and chemotypes, phenotypes and genotypes, whether naturally occuring or genetically modified.
  • Functionally equivalent derivatives, analogues or salts of eugenol which are pharmaceutically acceptable and which possess the activity of eugenol, at least in part, to treat pain and/or inflammation, may replace eugenol in the present composition.
  • Functionally equivalent derivatives or analogues, including structural and functional analogues, of eugenol include compounds derived from eugenol or a precursor thereof, including isomers thereof.
  • Examples of functionally equivalent derivatives or analogues of eugenol or 4-allyl-2-methoxy- phenol; eugenic acid; Caryophyllic acid; allylguaiacol; 2-methoxy-4-allylphenol; 2-methoxy-4- (2-propen-l-yl)-phenol; 4-allylcatechol-2 -methyl ether; 2-methoxy-4-(2-propenyl)-phenol;
  • 2-metoksy-4-allilofenol include, but are not limited to, 2-methoxyphenol; methyl eugenol; and isoeugenol.
  • Pharmaceutically acceptable salts include acid and base addition salts of eugenol.
  • the present composition comprises a mixture of eugenol and beta-caryophyllene.
  • the amount of eugenol in the composition ranges from about 0.001 mg/ml to about 4 mg/ml, and the amount of beta-caryophyllene in the composition ranges about 0.01 mg/ml to about 1.5 mg/ml.
  • the amount of eugenol in the composition ranges from about 0.005 mg/ml to about 1 mg/ml, and the amount of beta-caryophyllene in the composition ranges from about 0.01 mg/ml to about 1 mg/ml. More preferably, the amount of eugenol in the composition ranges from about 0.01 mg/ml to about 0.5 mg/ml, e.g.
  • the beta-caryophyllene and eugenol content of the composition may be from a single source or from a combination of different sources.
  • the beta-caryophyllene content in the composition may be achieved by the inclusion of essential oil from Cannabis spp. alone, or alternatively, may be achieved by a combination of two or more essential oils, for example, from Syzygium aromaticum (clove). Cannabis sativa, piper nigrum (black pepper) and/or, copaiba spp.
  • the eugenol content may be achieved by inclusion of essential oil from Syzygium aromaticum alone, or from a combination of sources of eugenol.
  • the present composition may include one or more additional active ingredients that are suitable for topical, sublingual, transdermal, rectal, oral, nasal or inhalation applications.
  • additional active ingredients include anti-inflammatory, analgesic, rubefacient, antiseptic, anti-rheumatic, bruise-, swollen vein- and oedema- reducing, antineuralgic, antiphlogistic, antioxidant, immunomodulatory, cicatrisation (scab forming) and regenerative compounds.
  • any additional active ingredient is also a plant-derived essential oil.
  • essential oil of ginger ⁇ Zingiber officinalis is incorporated in the present composition, preferably in an amount ranging from about 2 to about 22 % by wt, preferably from about 2.7% to about 20.36% by wt of the formulation.
  • the present composition may also be combined with one or more pharmaceutically acceptable adjuvants.
  • pharmaceutically acceptable means physiologically acceptable for use in the pharmaceutical and veterinary arts, i.e. not being unacceptably toxic or otherwise unsuitable.
  • pharmaceutically acceptable adjuvants for inclusion in the present composition include those that are suitable for combination with the essential oil active ingredients. Reference may be made to "Remington's: The Science and Practice of Pharmacy", 21st Ed., Lippincott Williams & Wilkins, 2005, for guidance on drug formulations generally. The selection of adjuvant depends on the intended mode of administration of the composition.
  • the active ingredients are formulated for oral administration via tablet, capsule, lozenge or suspension.
  • Suitable adjuvants include sugars, such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and derivatives thereof, including sodium carboxymethylcellulose, ethylcellulose and cellulose acetates; powdered tragancanth; malt; gelatin; talc; stearic acids; magnesium stearate; calcium sulfate; vegetable oils, such as peanut oils, cotton seed oil, sesame oil, olive oil, and corn oil; polyols such as propylene glycol, glycerine, sorbital, mannitol and polyethylene glycol; agar; alginic acids; water; isotonic saline and phosphate buffer solutions.
  • sugars such as lactose, glucose and sucrose
  • starches such as corn starch and potato starch
  • powdered tragancanth malt
  • Aduvants for a topical, sublingual, transdermal, rectal, oral, nasal or inhalant composition include compounds that may facilitate delivery of plant-derived essential oils, oleoresins, solutes, distillates, extracts, fermentations, infusions and leaching such as meadowfoam seed oil (Limnanthes alba), sweet almond (Amygdalus communis var.
  • riparia grapeseed oil (Vitis vinifera), hemp (Cannabis sativa), jojoba (Simmondsia sinensis), macadamia (Macadamia tetraphylla), St. John's wort (Hypericum perforatum), apricot (Prunus armeniaca ), hazel (Corylus avellana), olive (Olea europea), rosehip (Rosa spp.), sunflower (Helianthus annuus), sesame (Sesamum indicum), Carthamus tinctorius and wheatgerm (Triticum vulgare, Triticum durum, Triticum aestivum) and all Plantae taxa thereof including life, domain, kingdom, phylum, class, order, family, genus, species, genetically modified super-species, subspecies, varieties, hybrids and chemotypes, phenotypes and genotypes thereof.
  • Other exemplary adjuvants include
  • the present composition comprises, as a source of beta- caryophyllene, the essential oils of Clove (Eugenia caryophyllata) ("clove”); Balsam Copaiba; and Black Pepper (Piper nigrum) ("pepper”).
  • Clove bud oil is also the source of eugenol.
  • the amounts of each may be within the following ranges in the composition: clove about 0.194% to 14%, copaiba about 0.005%) to 36%) and pepper about 0.003%> to 25%.
  • These active ingredients may optionally be combined with ginger essential oil in an amount ranging from about 2.7% to 20% and with a non-active ingredient carrier, e.g. Meadowfoam oil, in an amount ranging from about 5% to about 97.098%.
  • a method of treating pain and/or inflammation in a mammal comprises administering a composition comprising a therapeutically effective amount of beta-caryophyllene and eugenol.
  • the terms “treat”, “treating” and “treatment” are used broadly herein to denote methods that moderate, ameliorate, reverse the progression of, reduce the severity of, or prevent pain and/or inflammation. In this regard it is noted that because a wide range of inter-individual variability exists in the perception of pain, the perceived result of the present treatment may vary from mammal to mammal.
  • pain is used broadly herein to refer to any neural or non-neural pain including, for example, cancer pain, multiple sclerosis pain, HIV pain, diabetic pain, chemotherapeutic pain, ischemic pain, arthritic pain and pain from inflammation.
  • Neural or neuropathic pain refers to pain resulting from an injury to or malfunction in the peripheral or central nervous system. Neural pain may be triggered by an injury, but does not necessarily involve actual damage to the nervous system. Neuropathic pain is frequently chronic.
  • neuropathic pain examples include, but are not limited to, lower back pain, repetitive strain injury, migraine and headache, and pain resulting from a disease state such as any type of cancer and/or from other substances to treat said disease state such as chemotherapeutic substances doxorubicin, cisplatin, paclitaxel and any neuroinflammatory pain, disease associated with the immune system, multiple sclerosis, arthritis, trigeminal neuralgia, peripheral neuropathy, complex regional pain syndrome (CRPS), fibromyalgia, TMJ (temporal mandibular joint) pain and inflammatory myopathy.
  • Non-neural or nociceptive pain refers to pain from tissue injury, including for example, sprains, bone breaks or fractures, burns, bumps, bruises, inflammation, obstructions and myofascial pain.
  • inflammation refers to a complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Signs of inflammation include pain, redness, swelling and/or loss of function. Types of inflammation include, but are not limited to, localized inflammation, systemic inflammation, neuroinflammation, appendicitis, bursitis, colitis, cystitis, dermatitis, phlebitis, rhinitis, tendonitis, tonsillitis and vasculitis.
  • the present method includes administration of the composition using any suitable administrable form, formulated accordingly, including one or more appropriate carriers and/or adjuvants.
  • suitable administrable forms include, for example, by oral, subcutaneous, intravenous, intraperitoneal, intranasal, enteral, topical, sublingual, intramuscular, intra-arterial, intramedullary, intrathecal, inhalation, ocular, transdermal, vaginal or rectal forms.
  • the method includes topical application of the composition to a mammal in need of pain and/or inflammation treatment.
  • the composition may be applied to an affected area on the skin of the mammal, or to a site appropriate to target an affected area, e.g. an affected internal area such as the sciatic nerve, joints, muscle, brain (migraine), liver (hepatitis pain), ischemic pain, etc.
  • the composition is preferably rubbed into the skin to promote absorption of the active ingredients.
  • the composition is administered at a dosage suitable to treat pain and/or inflammation.
  • the dosage administered is generally in the range of between about 1 to 2 ml of a composition comprising from about O.OOlmg/ml to about 4mg/ml eugenol, and from about 0.01 mg/ml to about 1.5mg/ml beta-carophyllene.
  • the dosage may be adjusted upwards or downwards to address the severity of the pain and/or inflammation, or the size of an affected area.
  • the composition is generally applied one to two times a day for a period of time sufficient to treat pain and/or inflammation. For more severe cases, however, the composition may be applied more frequently, e.g. three or more times a day for a period of time sufficient to treat the pain and/or inflammation.
  • the activity of the present composition is specific to the cannabinoid-2 receptor (CB2 receptor), and thus, functions as a CB2 agonist, selectively targeting the CB2 receptor, while not interacting with the psychoactive cannabinoid 1 -receptor (CBl receptor).
  • CBD2 receptor cannabinoid-2 receptor
  • This selectivity of the present composition renders it very effective to treat pain and/or inflammation with minimal side effects.
  • the combination of components unexpectedly result in a high degree of pain relief and inflammation reduction, e.g. greater than 80%, for example, greater than 90%, including essentially complete pain relief.
  • the present composition may also provide, or be adapted to provide, one or more of neuroprotective, chemoprotective, DNA protective, hepatoprotective, cardioprotective, blood brain barrier protective, antiproliferative, antimetastatic, glial protective, neurogenerative, nephroprotective, immunomodulatory, anticarcinogenic, anti-ischemic, anti-neuroinflammatory or anti-nociceptive properties.
  • components of the present composition namely essential oils that comprise beta-caryophyllene and eugenol, may exhibit one or more of such properties.
  • Additional components may also be added to the present composition to impart one or more of such properties.
  • EXPIAN A formulation, herein termed "EXPIAN", was prepared including the essential oil of clove (Eugenia caryophyllata or Syzygium aromaticum), balsam copaiba (Copaiba martii haynes), and black pepper (Piper nigrum) in the amounts shown in Table 1. Table 1.
  • the essential oils comprised the following percentages of beta-caryophyllene:
  • EXPIAN was used to treat back pain resulting from scoliosis. EXPIAN was applied in an amount of about l-2ml to the area in need of treatment on the back. Pain reduction was noted within a very short period of time (e.g. within the hour) following application, with complete relief from pain resulting with further application of EXPIAN 1-3 times a day.
  • Example 3 Overnight Back Pain from Mild to Severe
  • EXPIAN was topically applied in an amount of about 1-2 ml to the affected area of the back to treat overnight back pain. Pain relief was noted shortly following the application of EXPIAN, with complete relief from pain resulting with further applications of EXPIAN 1 -3 times a day.
  • EXPIAN was also used to treat sciatica pain. Sciatic pain was treated with a single topical application of EXPIAN (1-2 ml) to the affected area to result in relief of pain, with complete relief from pain with further application of EXPIAN 1-3 times a day. .
  • Knee pain resulting from long-term cartilage damage was treated by topical application of 1 -2 ml of EXPIAN to the affected area of the knee. This treatment resulted in pain relief, with complete relief from pain with further application of EXPIAN 1 -3 times a day.
  • Example 8 Muscular Aches and Strains from Mild to Debilitating
  • EXPIAN was used as described in Example 5 to treat knee pain resulting from strain due to sports. As described, pain relief was achieved following a single application, with complete pain relief resulting following further applications.
  • EXPIAN was used as described in Example 5 to treat chronic knee pain resulting from cartilage damage. Pain relief was achieved within 48 hours, with complete pain relief resulting following further applications.
  • Example l The EXPIAN formulation described in Example l was modifed to exclude ginger, and this formulation was found to be as effective as EXPIAN in the treatment of knee pain.
  • the EXPIAN formulation was also modified to replace the beta-caryophyllene source, the essential oil of Copaiba martii haynes, with a different beta-caryophyllene source, namely, the essential oil of Copaiba officinalis.
  • the modified formulation included an amount of the latter essential oil that was about the same as that of the former in the EXPIAN formulation (as shown in Example 1). This modified formulation was used as described in Example 5 and was found to be similarly effective in achieving pain relief of chronic knee pain.
  • Example 13 Comparison of Formulations
  • EXP IAN formulation comprising beta-caryophyllene in the amount of 0.03 mg/ml, eugenol in the amount of 0.016 mg/ml and ginger in the amount of 0.02 mg/ml in Meadowfoam seed oil, was compared to a similar formulation comprising clove, pepper and ginger oils in Meadowfoam seed oil but lacking copaiba oil.
  • Example 5 Each formulation was used as described in Example 5 to treat knee pain. While the latter composition provided only partial pain relief (approximately 50%) over the treatment period, EXPIAN provided complete relief of pain (100%). The EXPIAN formulation exhibited an unexpectedly greater effect than the comparison formulation in its complete treatment of the pain indicating that the components of the formulation, when combined, exhibited a synergistic effect.

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  • Mycology (AREA)
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Abstract

La présente invention concerne une nouvelle composition pharmaceutique comportant du béta-caryophyllène ou un dérivé fonctionnellement équivalent, un analogue ou un sel pharmaceutiquement acceptable de celui-ci, et de l'eugénol ou un dérivé fonctionnellement équivalent, un analogue ou un sel pharmaceutiquement acceptable de celui-ci. La composition est utile pour le traitement de la douleur et/ou de l'inflammation.
PCT/CA2014/000545 2013-07-05 2014-07-04 Composition pour le traitement de la douleur et/ou de l'inflammation comportant de l'eugénol et du béta-caryophyllène WO2015000064A1 (fr)

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WO2017145958A1 (fr) * 2016-02-24 2017-08-31 Kao Corporation Agent de blanchiment comprenant du syzygium polyanthum ou un extrait de celui-ci utilisé comme principe actif
US10188599B2 (en) 2016-09-17 2019-01-29 Bordoloi Biotech, Llc Anti-inflammatory activity with synergism of herbal essential oils
US10499584B2 (en) 2016-05-27 2019-12-10 New West Genetics Industrial hemp Cannabis cultivars and seeds with stable cannabinoid profiles
WO2020016210A1 (fr) * 2018-07-17 2020-01-23 Laboratorios Litaphar, S.L. Compositions pour le traitement de la vulvodynie
EP3500235A4 (fr) * 2016-08-16 2020-04-29 Afgin Pharma, Llc Thérapie neuro-affective régionale topique comprenant des caryophyllènes.
WO2021207813A1 (fr) * 2020-04-15 2021-10-21 Beraca Ingredientes Naturais S.A. Composition contenant du terpène et son utilisation cosmétique
US11202765B2 (en) * 2018-07-18 2021-12-21 John Enrique Mata Multifunctional topical cream comprising beta-caryophyllene, essential oils, in a phospholipid and triglyceride base
US11318179B2 (en) * 2017-06-20 2022-05-03 Jessica Kado Topical formulation for binding to dermatological cannabinoid receptors
RU2773173C2 (ru) * 2017-03-20 2022-05-31 Пьер Фабр Медикамент Применение олеорезинов копаиферы при патологиях простаты
WO2024003686A1 (fr) * 2022-06-27 2024-01-04 Prodeco Pharma S.R.L. Nouvelle composition à usage topique pour états douloureux et inflammatoires

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017145958A1 (fr) * 2016-02-24 2017-08-31 Kao Corporation Agent de blanchiment comprenant du syzygium polyanthum ou un extrait de celui-ci utilisé comme principe actif
US11090351B2 (en) 2016-02-24 2021-08-17 Kao Corporation Whitening agent
US10499584B2 (en) 2016-05-27 2019-12-10 New West Genetics Industrial hemp Cannabis cultivars and seeds with stable cannabinoid profiles
US11304393B2 (en) 2016-05-27 2022-04-19 New West Genetics Inc. Industrial hemp cannabis cultivars and seeds with stable cannabinoid profiles
EP3500235A4 (fr) * 2016-08-16 2020-04-29 Afgin Pharma, Llc Thérapie neuro-affective régionale topique comprenant des caryophyllènes.
US10188599B2 (en) 2016-09-17 2019-01-29 Bordoloi Biotech, Llc Anti-inflammatory activity with synergism of herbal essential oils
RU2773173C2 (ru) * 2017-03-20 2022-05-31 Пьер Фабр Медикамент Применение олеорезинов копаиферы при патологиях простаты
US11318179B2 (en) * 2017-06-20 2022-05-03 Jessica Kado Topical formulation for binding to dermatological cannabinoid receptors
WO2020016210A1 (fr) * 2018-07-17 2020-01-23 Laboratorios Litaphar, S.L. Compositions pour le traitement de la vulvodynie
US11202765B2 (en) * 2018-07-18 2021-12-21 John Enrique Mata Multifunctional topical cream comprising beta-caryophyllene, essential oils, in a phospholipid and triglyceride base
WO2021207813A1 (fr) * 2020-04-15 2021-10-21 Beraca Ingredientes Naturais S.A. Composition contenant du terpène et son utilisation cosmétique
WO2024003686A1 (fr) * 2022-06-27 2024-01-04 Prodeco Pharma S.R.L. Nouvelle composition à usage topique pour états douloureux et inflammatoires

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