WO2022091050A1 - Compositions pour le traitement de la cystite interstitielle et d'autres maladies de la vessie - Google Patents

Compositions pour le traitement de la cystite interstitielle et d'autres maladies de la vessie Download PDF

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Publication number
WO2022091050A1
WO2022091050A1 PCT/IB2021/060079 IB2021060079W WO2022091050A1 WO 2022091050 A1 WO2022091050 A1 WO 2022091050A1 IB 2021060079 W IB2021060079 W IB 2021060079W WO 2022091050 A1 WO2022091050 A1 WO 2022091050A1
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bladder
spp
compositions
composition
extracts
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PCT/IB2021/060079
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English (en)
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Stephen Barnhill
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Ai Pharmaceuticals Jamaica Limited
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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L31/00—Edible extracts or preparations of fungi; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • 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
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/066—Clavicipitaceae
    • A61K36/068—Cordyceps
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/074—Ganoderma
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • compositions for the treatment of interstitial cystitis and related urinary tract problems that involve bladder pain syndrome (“BPS”). More particularly this relates to nutraceutical and/or pharmaceutical compositions comprising cannabis extracts and mushroom extracts for the treatment of IC/BPS.
  • Interstitial cystitis is a chronic condition characterized by pressure in the bladder that can lead to a sense of urgency to urinate, or an increase is frequency. It is typically accompanied by pain that can range from mild discomfort to severe pain in the bladder and sometimes, the pelvis. Interstitial cystitis (“IC”) is part of a spectrum of conditions called painful bladder syndrome or bladder pain syndrome (“BPS”), and often, chronic pelvic pain syndrome. There is not a single, universally agreed-upon clinical definition of interstitial cystitis.
  • Oral medications may include NSAIDs such as ibuprofen, or naproxen, drugs to relax the bladder and/or block pain (such as amitriptyline or imipramine), and/or antihistamines to reduce urinary urgency and/or frequency.
  • NSAIDs such as ibuprofen, or naproxen
  • drugs to relax the bladder and/or block pain such as amitriptyline or imipramine
  • antihistamines to reduce urinary urgency and/or frequency.
  • pentosan polysulfate sodium is believed to be involved in protecting or restoring the inner bladder surface or the bladder wall, has been approved by the FDA specifically for interstitial cystitis. While it may work, the course of therapy may be 6 months before any relief is achieved.
  • Surgical intervention options range from relatively minimally invasive procedures such as bladder hydrodistension, and fulguration to remove ulcerated tissue, to bladder resection, catheterization, and bladder augmentation.
  • DMSO dimethyl sulfoxide
  • Instillation can also be performed with other medicaments including sodium bicarbonate, lidocaine, pentosan, and/or heparin. The latter may be alkalinized (buffered) prior to use.
  • Use of sodium hyaluronate or hyaluronic acid as an instillate is used in multiple countries, but not currently approved in the US.
  • compositions generally comprising extracts of cannabis and extracts of mushrooms in various combinations are useful in treating interstitial cystitis.
  • the mushroom or mushroom extract present in the compositions is from any edible or medicinal mushroom species.
  • the edible or medicinal mushroom in various embodiments comprises one or more of Agaricus bisporus, A. blazei, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, A. confluens, Amanita muscaria, Antrodia camphorate, Boletus badius, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Caripia Americansi, Clitocybe maxima, Cordyceps cicadicola, C. gunnii, C.
  • liangshanensis C. militaris, C. pruinose, C. sinensis, Cyathus africanus, C. hookeri, Daldinia childiae, Dictyophora indusiata (synonym: Phallus indusiatus), Elaphomyces granulatus, Flammulina velutipes, Pomes fomentarius, Fomitopsis pinicola, Funalia trogii, Ganoderma lucidum, Geastrum saccatum, Grifola frondosa, Hericium erinaceus, Inocybe umbrinella, Inonotus olbiquus, Lactarius deliciosus, L. flavidulus, L.
  • rufus Lentinula edodes, Lentinus edodes, L. polychrous, Lyophyllum decastes, Phellinus linteus, Pholiota nameko, Pleurotus ostreatus, P. pulmonarius, Poria cocos, Schizophyllum commune, Suillus placidus, Trametes versicolor, or Termitomyces albuminosus.
  • the cannabis extracts present in the compositions can be derived from any Cannabis spp. and may include any cannabinoids.
  • the cannabis extracts may further comprise any number of useful terpenes and/or flavonoids.
  • compositions optionally include other nutraceutical or botanical compounds to provide additional functionality or support for the bladder or urinary tract.
  • nutraceutical or botanical compounds examples include compound such as herbal extracts from one or more of Rehmanniae spp., Achyranthis spp., Corni spp., Moutan spp., Alismatis spp., Dioscorea spp., Plantaginis spp., Hoelen spp., Aconiti spp., Cinnamomi spp., Barosma betulina, Galium aparine, corn silk from Zea mays, horsetail (Equisetum spp.), resiniferatoxin (or extract from Euphorbia resinifera), capsaicin, saw palmetto, bearberry, cranberry, St.
  • Additional compounds contemplated for use herein comprise S- adenosylmethionine, methylfolate, polyphenols, D-mannose, antioxidants, omega-3 fatty acids, or a B vitamin, vitamin A, vitamin C, vitamin D, vitamin E, or a compound providing a biologically available form thereof, or combinations thereof.
  • the combination compositions further optionally comprise one or more solvents, including but not limited to dimethyl sulfoxide or related amphipathic solvents, or other solvent capable of dissolving poorly soluble polar and nonpolar molecules and which are relatively nontoxic in mammals and specifically humans.
  • solvents including but not limited to dimethyl sulfoxide or related amphipathic solvents, or other solvent capable of dissolving poorly soluble polar and nonpolar molecules and which are relatively nontoxic in mammals and specifically humans.
  • solvents including but not limited to dimethyl sulfoxide or related amphipathic solvents, or other solvent capable of dissolving poorly soluble polar and nonpolar molecules and which are relatively nontoxic in mammals and specifically humans.
  • solvents including but not limited to dimethyl sulfoxide or related amphipathic solvents, or other solvent capable of dissolving poorly soluble polar and nonpolar molecules and which are relatively nontoxic in mammals and specifically humans.
  • CYRENE dihydrolevoglucosenone cyrene
  • compositions may include one or more serotonergic psychedelics as defined herein below.
  • Serotonergic psychedelics useful herein include both tryptamine derivative and analogues and phenylethylamine derivatives and analogues, with affinity or avidity for any of the 5-HT receptors.
  • Such compounds may be useful in a single or periodic treatment to resolve chronic pain in patients, particularly where the underlying cause of the pain has been treated or ameliorated.
  • compositions comprising an extract from one or more edible or medicinal mushrooms and a cannabis extract, in combination, has many benefits for treatment of interstitial cystitis.
  • the compositions provide certain useful properties, such as effectiveness (including over a long period of time), low toxicity, no serious side effects, and good tolerance on the part of a wide range of subjects.
  • methods are provided for optimizing a composition for use in treatment of a subject suffering from a disease comprising interstitial cystitis, BPS, an inflammatory process of the bladder, or bladder cancer.
  • the methods generally employ the use of artificial intelligence algorithms, such as classification algorithms, regression algorithms, clustering algorithms, or a combination thereof.
  • the methods generally comprise:
  • the disease generally comprises a bladder condition or process for which other treatment options are limited or nonexistent.
  • the data for use in the artificial intelligence algorithm can be obtained from original experiments or literature review.
  • this disclosure provides methods for treating a disease process in a patient in need thereof.
  • the methods generally comprise the step of administering a composition comprising at least one edible or medicinal mushroom or extract thereof, and at least one cannabis extract or cannabinoid, in combination, to the patient.
  • Additional compounds such as terpenes, flavonoids, or other compounds derived from cannabis may be included, as may other herbal or nutraceutical compounds or compositions useful in supporting healthy bladder or urinary tract functions, or in treating bladder or urinary tract conditions.
  • the combinations may be administered directly, by any route.
  • Preferred routes, particularly for treatment of interstitial cystitis, or where a solvent such as DMSO is included are administration through instillation, particularly in connection with hydrodistension of the bladder.
  • the at least one Cannabis extract or cannabinoid can be conveniently administered separately from, sequentially to, or simultaneously with the edible or medicinal mushroom or mushroom extract.
  • the at least one edible or medicinal mushroom or extract thereof is also administered separately from, sequentially to, or simultaneously with the cannabis cannabinoid.
  • compositions and methods for treating interstitial cystitis or other bladder disease processes are applicable to acute or chronic conditions in a subject.
  • the compositions allow a modern practitioner to combine the benefits of certain compounds found in edible and medicinal mushrooms (such as used for centuries in Chinese and other traditional medicine practices, and by e.g. herbalists throughout the world), with the positive benefits of another natural substance, cannabis, also used for centuries.
  • the compositions further include certain beneficial compounds derived from Cannabis and other natural or synthetic sources, and other nutraceutical or pharmaceutical compounds, particularly nutraceutical compounds known to be supportive of bladder and urinary tract functions. Used properly, these compositions have little risk, few side effects, and are effective for producing measurable and lasting results in patients suffering from interstitial cystitis or related chronic bladder inflammation or other bladder disease.
  • interstitial cystitis means any disease that is on the spectrum of bladder pain syndrome.
  • bladedder disease includes both acute and chronic conditions including interstitial cystitis, bladder pain syndrome ("BPS"), an inflammatory process of the bladder or urinary tract, prolonged or repeated bladder or urinary tract infections (“UTIs”), inflammation of the epithelial tissues of the bladder or urinary tract, or bladder cancer.
  • BPS bladder pain syndrome
  • UTIs bladder or urinary tract infections
  • Serotonergic psychedelics as used herein mean any of the family of compounds that interact with serotonin pathways in the nervous system, particularly with the class of 5-HT receptors that recognize serotonin compounds, and which produce hallucinogenic effects in a subject. Serotonergic psychedelics can be naturally occurring or synthetically produced.
  • the term "edible” does not mean merely capable of being eaten. In that overly broad sense, even poisonous or toxic mushrooms are 'edible' however lethal or sickening or the like. In contrast “edible mushrooms” is used herein in the sense of mushrooms that are used traditionally or in modern times as sources of food, nutrients, nutraceuticals, flavors, and the like. Edible mushrooms are neither toxic nor poisonous as consumed.
  • "Medicinal mushrooms” as used herein means any mushroom species that has been used traditionally or in modern times as a source of medicinal or therapeutic benefits, healing properties, and / or healthful compounds. It should be noted that the medicinal mushrooms may not be edible in all embodiments herein, and may in fact be poisonous if eaten, however, one or more extracts therefrom or components extracted or isolated therefrom may be perfectly useful herein.
  • mushrooms that are edible or medicinal may be grouped together, as there may be many crossovers and it may be difficult to clearly distinguish between the two groups.
  • Examples of edible and / or medicinal mushrooms useful herein include mushrooms of the genera Agaricus, Agrocybe, Albatrellus, Amanita, Antrodia, Auricularia, Boletus, Calvatia, Cantharellus, Caripia, Clitocybe, Cordyceps, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Pomes, Fomitopsis, Funalia, Ganoderma, Geastrum, Grifola, Hericium, Inocybe, Inonotus, Lactarius, Lentinus, Lentinula, Leucop axillus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, Russula, Sarcodona, Schizo
  • Species of particular interest include Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia widelyi, Cyathus africanus, C.
  • More generally edible and/or medicinal mushrooms can be useful in connection with the current disclosure for treating inflammation, directly or indirectly.
  • the therapeutic uses may include: preventing and/or treating bladder diseases, helping recover from treatments or surgical interventions with respect to such diseases, particularly those with significant toxicity or side effects, stimulating and / or supporting the immune system, reducing or mitigating chronic pain associated with such bladder diseases; or reducing or mitigating the psychological affects (e.g. depression, sexual problems, quality of life perceptions, or the like) of a chronic and painful disease, generally promoting of health, providing antioxidant functionality, stimulating or promoting immune system health, or the like.
  • the psychological affects e.g. depression, sexual problems, quality of life perceptions, or the like
  • Reishi mushrooms have been reported to calm the central nervous system and/or have neuroprotective effect, stimulate the immune system, and act as a prebiotic to support gut health.
  • Reishi has been reported to have a beneficial effect on the adrenals, and to be anxiolytic; reducing anxiety and promoting sleep.
  • Reishi has also been associated with improved memory, and sharpened concentration and focus.
  • Lion's Mane reportedly calms mental activity and modulates certain neurotransmitters.
  • Cordyceps has been reported to have adaptagenic properties and stimulate the adrenals glands and modulates the nervous system. For purposes herein, the publication by Elsayed, Elsayed A et al.
  • “Cannabis” or “Cannabis spp.” as used herein refers to any plant of the genus Cannabis, including plants that may be classified as Cannabis sativa, Cannabis indica, or Cannabis ruderalis. It is well known that despite the foregoing list, some experts believe that there are only 2 species, and still others consider that there is only a single species (generally, C. sativa'). Whatever nomenclature is used, for purposes of this disclosure, “Cannabis” includes all possible members of the genus, without regard to the species to which they are assigned.
  • 'cannabinoids means any of a class of compounds that generally can interact with one or more cannabinoid receptors, including the receptors of the endocannabinoid system, in particular, CB1 and CB2.
  • Cannabinoids include e.g., phytocannabinoids and synthetic cannabinoids.
  • Phytocannabinoids are found in several plant species, especially Cannabis spp. Among the most prevalent and most studied cannabinoids are tetrahydrocannabinol (THC), and cannabidiol (CBD).
  • cannabinoids that have been identified in Cannabis within certain classes including the tetrahydrocannabinols, cannabidiols (including e.g. cannabidiol (CBD) and cannabidivarin (CBDV)), cannabigerols, cannabinols, cannabichromenes, and cannabinodiol.
  • CBD cannabidiol
  • CBDV cannabidivarin
  • cannabigerols cannabinols
  • cannabichromenes cannabinodiol
  • Other cannabinoids, such as cannabicyclol, cannabieslsoin, and cannabitriol are currently classed as 'miscellaneous' by some researchers.
  • THC is not only a major cannabinoid in Cannabis spp., it is generally the compound responsible for the psychoactive effects of consuming Cannabis.
  • cannabinoids such as cannabinol may also be at least mildly psychoactive.
  • Certain other cannabinoids such as CBD may help regulate or attenuate the psychoactive effects of other cannabinoids.
  • compositions may be created with various ratios of cannabinoids, such as the ratio of CBD to THC or other ratios depending the specific person or the specific condition being treated. Synthetic cannabinoids may also be useful herein.
  • cannabinoids are presently FDA-approved, such as MARINOL, SYNDROS, and CESAMET and can be readily incorporated into the compositions and emulsions.
  • FDA- approved cannabinoid compounds such as EPIDIOLEX, a purified, plant- derived (i.e. non-synthetic) cannabidiol may also be useful herein.
  • Herbal extracts as used herein comprise extracts from one or more of Rehmanniae spp., Achyranthis spp., Corni spp., Moutan spp., Alismatis spp., Dioscorea spp., Plantaginis spp., Hoelen spp., Aconiti spp., Cinnamomi spp., Barosma betulina, Galium aparine, corn silk from Zea mays, horsetail (Equisetum spp.), resiniferatoxin (or extract from Euphorbia resinifera), capsaicin, saw palmetto, bearberry, cranberry, St. John's Wort, stinging nettle, and/or combinations thereof. Such herbal extracts may support or improve bladder and urinary tract function.
  • Additional nutraceutical compounds that may support or improve normal bladder and urinary tract functions include but are not limited S- adenosylmethionine, methylfolate, polyphenols, D-mannose, antioxidants, omega-3 fatty acids, or a B vitamin, vitamin A, vitamin C, vitamin D, vitamin E, or a compound providing a biologically available form thereof, or combinations thereof.
  • curcuminoids means any of the compounds associated with turmeric or curcumin, as derived rhizome of the plant Curcuma longa, or synthetic versions or derivative thereof.
  • Curcuminoids include but are not limited to curcumin (aka diferuloylmethane), analogs of curcumin such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, and turmeric oil. Also include are metabolites of curcumin such as tetrahydrocurcumin (THCU), hexahydrocurcumin, and octahydrocurcumin.
  • curcumin aka diferuloylmethane
  • analogs of curcumin such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), turmerones, and turmeric oil.
  • BDMC demethoxycurcumin
  • BDMC bisdemethoxycurcumin
  • turmerones turmerones
  • turmeric oil also include are metabolites of curcumin such as tetrahydrocurcumin (THCU), hexahydrocurcumin, and octahydro
  • Conjugates such as curcumin glucuronide and curcumin sulfate, are also included herein. Conjugation may also provide opportunities for improved delivery of curcumins herein, for example, conjugation to peptide carriers, or polylactic-co-gly colic acid [PLGA]; as well as complexation with essential oils; coadministration with piperine; and encapsulation into nanoparticles, liposomes, phytosomes, polymeric micelles, and cyclodextrins may also be useful herein.
  • curcumins for example, conjugation to peptide carriers, or polylactic-co-gly colic acid [PLGA]; as well as complexation with essential oils; coadministration with piperine; and encapsulation into nanoparticles, liposomes, phytosomes, polymeric micelles, and cyclodextrins may also be useful herein.
  • terpenes means any of the organic compounds commonly known as terpenes or terpenoids. Terpenes are generally aromatic compounds classified as isoprene derivatives. Terpenes suitable for use herein include hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, sesquaterpenes, tetraterpenes, polyterpenes, and norisoprenoids.
  • Exemplary terpenes that are particularly useful herein include alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, and valencene.
  • phytol, limonene, humulene, myrcene, cineol, phellandrene, caryophyllene, terpinolene, linalool, ocimene, pinene, or a combination thereof are presently preferred.
  • flavonoids includes any of the class of polyphenolic molecules containing 15 carbon atoms that are naturally produced in plants and are soluble in water. Also included herein as “flavonoids” are natural or synthetic derivative or analogs thereof that have biological activity. Flavonoids of use herein can generally be divided in to 6 groups of structurally related compounds: chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, and anthocyanins. Also useful are flavanols and catechins, as well as glucosides or other derivatives or analogs of any of the foregoing. The flavonoids are found in most fruits and vegetables, particular colorful ones. They are also prevalent in legumes (including soybeans), grains, green and black teas, as well as red wine.
  • Flavonoids have numerous functions in plants, and act as important cell messengers. Various flavonoids are believed to provide healthful benefits and functions to humans such as anti-cancer, anti-inflammatory, anti-allergic, and antioxidant properties. They may also be cardio-protective, cholesterol-lowering, and anti-atherosclerotic. Natural or synthetic flavonoids from any source may be used herein. Generally natural flavonoids are preferred. Flavonoids isolated from Cannabis, such as cannaflavins A, B, and or C, are of interest in certain applications, as are vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, and luteolin, as well as the catechins found in Cannabis.
  • subject-specific data are data that pertain to a specific subject or patient's health status and/or disease condition.
  • Bioinformatic data as used herein are data pertaining to the genome, transcriptome, proteome, metabolome, or any portion thereof, for a specific subject. In preferred embodiments, subject-specific data can be used to "personalize" a treatment.
  • compositions and “in combination” are used to indicate that a composition may be a single composition comprising all components in a single e.g. container, bottle, package, or portion, or such compositions may comprise different components in separate containers, bottles, packages, or portions.
  • Composition A might include bottle 1, which is administered to a subject.
  • Composition B might include bottle 2 and bottle 4, where bottles A and B have different components within them.
  • Composition B can be administered to a subject by providing both bottle 2 and bottle 3 simultaneously, or providing the bottles sequentially, one after the other.
  • Composition B can be administered by providing bottles 2 and 3 separately, by different route of administration, or by the same route of administration with a given period of time.
  • Composition A might include bottle 1, which is administered to a subject.
  • Composition B might include bottle 2 and bottle 4, where bottles A and B have different components within them.
  • Composition B can be administered to a subject by providing both bottle 2 and bottle 3 simultaneously, or providing the bottles sequentially, one after the other.
  • Composition B can be
  • bottles 2 and 4 must be given within not more than 4 hours, or not more than 2 hours in certain embodiments.
  • the two bottles of Composition B may have to be administered within 1 hour, 30 minutes, or 15 minutes in other embodiments.
  • Bottle 2 may require refrigeration or have a short shelf life, while bottle 3 is shelf stable. Or bottle 3 may precipitate.
  • Bottle 2 may be best instilled and need to be pharmaceutical grade, while bottle 3 may be administered orally and be a nutraceutical or dietary supplement formulation that is food grade.
  • Administering the components together or within a given time frame of each other allows the overall composition to have its affect in the subject without the requirement that the components be combined in a single bottle, package, portion, or the like.
  • ranges are provided in shorthand, so as to avoid having to list and describe each and every value within the range. Any appropriate value within the range can be selected, where appropriate, as the upper value, lower value, or the terminus of the range.
  • APM "Apollon Medical” strain of C. sativa
  • CBD cannabidiol
  • CBG cannabigerol
  • 5-HT 5-hydroxytryptamine
  • KNN K Nearest Neighbor
  • NK natural killer cells
  • NS AID nonsteroidal anti-inflammatory drugs
  • OCD obsessive compulsive disorder
  • SVM Support Vector Machines
  • THC tetrahydrocannabinol
  • compositions generally comprising one or more edible or medicinal mushrooms or extracts, fractions, isolates, or components thereof are provided.
  • the compositions alternatively or further generally comprise one or more cannabis extracts, or purified or partially purified cannabinoids.
  • the edible or medicinal mushroom(s) comprise one or more of the species Agaricus blazei, A. bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps militaris, C. pruinose, Caripia widelyi, Cyathus africanus, C.
  • the mushroom(s) in other embodiments comprise one or more species such as Albatrellus confluens, Antrodia camphorate, Boletus badius, Clitocybe maxima, Cordyceps sinensis, Cordyceps liangshanensis, Cordyceps gunnii, Cordyceps cicadicola, Pomes fomentarius, Funalia trogii, Hericium erinaceus, Inocybe umbrinella, Lactarius flavidulus, Pleurotus ostreatus, Schizophyllum commune, Suillus placidus, or Trametes versicolor, Cordyceps sinensis, C. liangshanensis, C. gunnii, or C. cicadicola.
  • mushrooms are all well-known edible and / or medicinal mushrooms with a long history of use. Without limiting the invention to any particular theory of operation, mushrooms, such as Reishi, shitake, maitake, turkey tail, and many others have a plethora of beneficial and potentially therapeutic compounds present in them.
  • the polysaccharides, peptides, and/or other small molecules in various mushrooms have been shown to regulate the production of certain molecular mediators of inflammation and functions of immune cells (e.g. B- and/or T-cells) as well as pro-inflammatory lymphocytes, T-helper cells, T- killer cells, and macrophages.
  • immune cells e.g. B- and/or T-cells
  • the beta-1,3 D-glucans from certain mushrooms and other glycans may suppress cytokines such as interleukins tumor necrosis factor (TNF-a), and still other compounds
  • compositions preferably comprise the benefits of such edible or medicinal mushroom(s) as described above.
  • the edible or medicinal mushrooms or extracts can be present as fresh mushrooms, or as a dried mushroom or extract thereof, a lyophilized mushroom preparation, a mushroom powder, or an aqueous or alcohol extract (e.g. an ethanolic or other alcohol extract) of mushroom. Extracts for purposes herein can include hot- or cold-water extracts. Mushroom concentrates, or partially purified or even extensively purified mushroom fractions, or fully purified components or isolates from a mushroom are also useful herein.
  • various extracts, concentrates, or partially purified fractions, or the like are enriched for one or more advantageous mushroom component, or compounds with desirable effects on treatment of inflammation, immune status, or general health.
  • the extract, concentrate, partially purified fraction, or the like are enriched for one or more phenolic acids, flavonoids, triterpenes, carotenoids, stilbenes, sterols, fatty acids, lignans, chitosan, polyphenols, polysaccharides, glycosides, glucans, polysaccharide-protein complexes, glycoproteins, polysaccharopeptide, krestin, tocopherols, peptides, cyclic peptides, or other amino compounds found in the mushroom.
  • compositions in various embodiments therefor also include cannabinoids, comprising one or more of cannabidiol (CBD), cannabidivarin (CBDV), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC).
  • CBD cannabidiol
  • CBDV cannabidivarin
  • CBN cannabinol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • the cannabinoids are derived from hemp, or the THC content is removed from the cannabinoids such that THC is present in the composition at less than about 0.3 percent. In various embodiments, the THC content may be less than 0.2%, or even less than 0.1% of the composition.
  • the ratio of cannabinoids is set in the compositions.
  • the ratio of CBD to THC ranges from about 1:5 to about 30:1 or more. In other embodiments the ratio may range from about 1:2 to about 10:1. In still other embodiments, the ratio of CBD to THC may be about 1:1 to 5:1. In other cases, the ratio of e.g. CBD to CBG or CBN may be set based on any of a variety of factors, including the health status of the subject being treated, the symptoms of the subject, the condition(s) being treated, and or one or more physiological or genetic criteria.
  • the compositions may be provided in completely customized or personalized formulations for each person being treated - i.e. as personalized medicines.
  • the compositions may be adjusted based on initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), the nature of the inflammation, specific markers, antigen, or mediators of the interstitial cystitis or bladder disease process, specific symptomology, or the like.
  • the formulation of the compositions may also be changed based on the results from an initial treatment, subsequent treatment, or based on subsequent tests.
  • the cannabinoids are derived from Cannabis spp. or an extract thereof.
  • Cannabis can generally be concentrated or extracted (e.g. via mechanical or chemical means) to obtain cannabinoids.
  • Extraction via chemical means includes extraction with various volatile solvents that range from hydrocarbon solvents such as butane, hexanes, or propane, to supercritical fluids, alcohol (e.g. isopropanol, butanol, or ethanol), steam, or even water.
  • Two very common methods are extraction with supercritical carbon dioxide, or ethanol, both of which are particularly useful herein. Extracts can be also be distilled e.g. to remove additional compounds of interest, or to concentrate them.
  • Certain components can be removed, e.g. by treatment with steam to strip certain volatiles, which can be captured as an additional component from the Cannabis.
  • cannabinoids present in an ethanolic extract or supercritical CO 2 extract of Cannabis sativa are preferred for use herein.
  • the extract comprises one or more of Ringo's Gift, OG Kush, Strawberry Cough, Orange Cookies, Jack Herer-derived strains (e.g. Black Jack, Super Jack, JI, and XJ13), and the Lemon family of strains of Cannabis sativa.
  • the extracts comprise Ringo's Gift, Harle Tsu, ACDC, Charlotte's Web, The Gift, or Pineberry strains.
  • Proprietary strains commercially available from Apollon Formularies, are also useful herein, including but not limited to "Apollon Medical" ("APM").
  • compositions include terpenes comprising one or more monoterpenes, one or more sesquiterpenes, or a combination thereof.
  • the terpenes generally comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene.
  • the terpenes comprise phytol, limonene, humulene, myrcene, cineol, phellandrene, caryophyllene, terpinolene, linalool, ocimene, pinene, or a combination thereof.
  • the terpenes preferably comprise one or more of limonene, myrcene, beta-caryophyllene, linalool, alpha pinene, or a combination thereof.
  • the terpenes include beta- ocimene, 1,8-cineole, alpha-pinene and / or beta-pinene, linalool, limonene, phytol, humulene, myrcene, phellandrene, caryophyllene, terpinolene, linalool, or other cineols or ocimenes, or any combination thereof, and the strains used to isolate terpenes are high in those terpenes, relative to other strains.
  • the terpenes are derived from Cannabis spp. or an extract thereof.
  • the terpenes can be derived from any source and in certain embodiments, they can be present in steam distillate or an ethanolic extract of Cannabis sativa.
  • compositions in certain embodiments include extracts of Cannabis spp., such as C. sativa, as a source of cannabinoids and/or terpenes.
  • the extract comprises compounds from one or more C. sativa strains, Of current interest are Ringo's Gift, OG Kush, Strawberry Cough, Orange Cookies, Jack Herer-derived strains, Lemon family strains, Harle Tsu, ACDC, Charlotte's Web, The Gift, or Pineberry strains.
  • the extract comprises compounds from proprietary Apollon Formularies' C. sativa strains, which may be strain dependent and adapted for specific therapeutic purposes.
  • the compositions feature extracted or enriched cannabinoids from Cannabis comprising one or more of cannabidiol (CBD), cannabidivarin (CBDV), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC).
  • CBD cannabidiol
  • CBD cannabidivarin
  • CBN cannabinol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • preferred ratios of various cannabinoids to other cannabinoid present are set forth (see above).
  • there are little to no psychoactive cannabinoids present e.g. THC ⁇ 0.3%).
  • C. sativa plants that are hemp are particularly useful.
  • the compositions may further comprise one or more flavonoids.
  • the flavonoids can comprise chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof, and combinations of any number of the foregoing.
  • flavonoids are included in the compositions are isolated or derived from a plant, mushroom, or other natural source.
  • the composition still further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp. Any of the traditional Jamaican or Carribbean medicinal plants may be useful herein.
  • Jamaican plants useful herein include ackee, aloe vera, avocado, breadflower, ginger, leaf of life, sorrel, soursop, tamarind, and trumpet.
  • the traditional medicinal plants comprise Jamaican sorrel Hibiscus sabdariffa), guinea hen weed (Petiveria alliacea), and/or soursop (Annona murata).
  • the compositions include a whole plant extract, or an extract from any parts or portion thereof including but not limited to leaves (dried, fresh, or extracted), stems, flowers, roots, fruit, seeds, or the like.
  • compositions in certain embodiments may comprise one or more serotonergic psychedelics, for example as part of a mushroom extract or fraction.
  • serotonergic psychedelics for example as part of a mushroom extract or fraction.
  • Such compounds may be particularly useful for disrupting chronic pain in patients suffering therefrom due to chronic interstitial cystitis or bladder pain syndrome.
  • such compositions may help a patient overcome certain psychological ramifications (such as depression or problems with intimacy) resulting from prolonged pain and suffering, chronic pelvic pain, and the like). They may be particular useful where the underlying physical pain has been treated successfully but psychological issues persist.
  • compositions In terms of compounding the compositions, the skilled artisan will appreciate that methods of maximizing the efficacy of the composition such as by enhancing the bioavailability of one or more components, or by providing the components in optimized ratios, for example one component to another with which it interacts, or each component to the others in ratio(s) that optimize the absorption into the gut or bloodstream, or enhance the therapeutic effect of the composition. The skilled artisan will also understand that some information useful in improving the compounding may be obtained empirically.
  • the compositions, or one or more components thereof may be solubilized, micronized, provided as, for example, extracts, powders, lyophilized powders, concentrates, tinctures, essential oils, aqueous or lipid suspensions, emulsions, microemulsions, or nano-emulsions, or in whole or part as liposomal, vesicular, or other delivery systems.
  • the compounding or formulation of any of the compositions provided herein may be optimized for the intended delivery route.
  • compositions may be administered and delivered as pharmaceuticals, however, it is also contemplated that one or more of the compositions may be formulated for administration and delivery by oral routes that include as food and beverages, including solid, semisolid, and liquid foods, such as smoothies, shakes, pudding, broths, teas, and soups.
  • the food and or beverage compositions can also include hot, cold, or even frozen foods (such as frozen desserts).
  • the compositions may also be administered by instillation either via a practitioner, or at home using a urinary catheter kit.
  • kits for treating a subject suffering from a bladder disease comprising administering a therapeutically effective dose of a composition to the subject.
  • the composition typically comprises one or more edible or medicinal mushrooms or an extract, fraction, or isolate thereof, and one or more cannabinoids, in various combinations.
  • the compositions may optionally comprise an amphipathic solvent such as DMSO.
  • preferred routes of administration include direct bladder instillation with a urinary catheter, particularly with bladder hydrodistension.
  • the bladder disease in various embodiments comprises interstitial cystitis or another bladder disease, such as bladder cancer, prolonged or repeated bladder infection(s) or UTIs, or inflammation of the epithelial tissues of the bladder or urinary tract.
  • composition for use in the methods is generally as described above for the first aspect.
  • description of the compositions above is incorporated by reference herein for purposes of the present methods.
  • compositions for use in the methods further comprise one or more optional ingredients comprising e.g. herbal extracts from Rehmanniae spp., Achyranthis spp., Corni spp., Moutan spp., Alismatis spp., Dioscorea spp., Plantaginis spp., Hoelen spp., Aconiti spp., Cinnamomi spp., Barosma betulina, Galium aparine, corn silk from Zea mays, horsetail (Equisetum spp.), resiniferatoxin (or extract from Euphorbia resinifera), capsaicin, saw palmetto, bearberry, cranberry, St.
  • optional ingredients comprising e.g. herbal extracts from Rehmanniae spp., Achyranthis spp., Corni spp., Moutan spp., Alismatis spp., Dioscorea s
  • compositions may further comprise nutraceutical or vitamins or the like such as polyphenols, antioxidants, D-mannose, S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin A, vitamin C, vitamin D, vitamin E, or a compound providing a biologically-available form thereof.
  • nutraceutical or vitamins or the like such as polyphenols, antioxidants, D-mannose, S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin A, vitamin C, vitamin D, vitamin E, or a compound providing a biologically-available form thereof.
  • fish oil primrose oil, or an extract of one or more of black cumin, Echinacea, Astralagus, sorrel, ginger, ginseng, bee propolis, bee pollen, honey, fenugreek, goldenseal, licorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, pomegranate, or date, or any combination thereof, can also be included.
  • Garlic extract alpha lipoic acid (ALA), conjugated linoleic acid (CLA), phytoestrogens, soy isoflavones, selenium, zinc, copper, magnesium, niacin, and/or nicotinamide are also contemplated for use herein.
  • ALA alpha lipoic acid
  • CLA conjugated linoleic acid
  • phytoestrogens soy isoflavones
  • selenium zinc, copper, magnesium, niacin, and/or nicotinamide
  • the terpenes for use with the compositions can comprise one or more monoterpenes, one or more sesquiterpenes, or a combination thereof.
  • the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene.
  • the terpenes can comprise beta- ocimene, 1,8-cineole, alpha-pinene and / or beta-pinene, linalool, limonene, phytol, humulene, myrcene, phellandrene, caryophyllene, terpinolene, linalool, or other cineols or ocimenes, or any combination thereof,
  • the terpenes are derived from Cannabis spp. or an extract thereof.
  • the terpenes can be present in steam distillate or an ethanolic extract of Cannabis sativa, and can comprise limonene, myrcene, betacaryophyllene, linalool, alpha pinene, or a combination thereof, in some embodiments.
  • the Cannabis sativa in one embodiment includes one or more of Ringo's Gift, OG Kush, Strawberry Cough, Orange Cookies, Jack Herer-derived strains or extract formulations (e.g. Black Jack, Super Jack, JI, and XJ13), and the Lemon family of strains of Cannabis sativa.
  • Ringo's Gift, Harle Tsu, ACDC, Charlotte's Web, The Gift, or Pineberry strains or extract formulations are useful. Proprietary strains or extract formulations commercially available from Apollon Formularies are also useful herein.
  • compositions for use with the methods also may comprise one or more flavonoids that can be chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof, and preferably they are from a plant, mushroom, or other natural source.
  • flavonoids can be chaicones, flavones, isoflavonoids, flavanones, anthoxanthins, anthocyanins, flavonols, or glucosides or other biologically active derivatives or analogs thereof, and preferably they are from a plant, mushroom, or other natural source.
  • presently preferred flavonoids include cannaflavin A, cannaflavin B, or cannaflavin C, vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, luteolin, a catechin found in Cannabis, or a combination of any of the foregoing.
  • the methods further comprise one or more steps of administering an additional therapeutically effective dose of the composition.
  • the additional administering steps are performed on a periodic basis of any frequency or schedule.
  • the administration or dosing can conveniently be on e.g. a daily, thrice weekly, twice weekly, weekly, biweekly, monthly, bimonthly, quarterly, semi-annual, or annual basis.
  • the administration need not be the same over every period of time.
  • administration could be daily for a week, then weekly for a month.
  • the administration could be every 4 months for a year, then every 6 months thereafter.
  • the actual amount of the composition or dosage administration can vary.
  • a monthly dosage schedule could feature a dose of x for the first dosage each quarter, and a dose of O.lx for the remaining months in each quarter.
  • the methods further comprise the step of periodically assessing one or more of the subject's medication levels, enzyme levels, or other indicators of physiological health or status, genetic markers or metabolic markers or mediator presence, or the like, in order to determine the periodic basis for administration.
  • compositions via any useful route, including parenteral (intravenous, intra-arterial, intramuscular, intraperitoneal, or subcutaneous), oral, nasal, ocular, transmucosal (buccal, vaginal, or rectal), transdermal, or via inhalation.
  • parenteral intravenous, intra-arterial, intramuscular, intraperitoneal, or subcutaneous
  • oral nasal, ocular, transmucosal (buccal, vaginal, or rectal), transdermal, or via inhalation.
  • transmucosal e.g. via a urinary catheter.
  • compositions are relatively safe enough that they can be adapted for home use by the patient, who is also directed to administer the compositions and then to retain the mixture in the bladder for at least 30 minutes if possible (so as to maximize exposure to bladder tissues, allow for transport to the bladder wall, and to mitigate or alleviate the inflammation of the bladder epithelial cells.
  • the composition may be administered by multiple routes of administration in the same patient e.g., one aspect of the compositions might be given by direct bladder instillation via urinary catheter while another aspect of the compositions might be administered orally or sublingually.
  • kits can be provided for home administration.
  • the kits can include one or more catheters and any connections useful therefore, as well as detailed instructions for the instillation process and / or hydrodistension of the bladder in a home setting.
  • the route of dosing or administration of compositions can vary over the course of treating a subject or patient with multiple steps of treatment, as well as from subject to subject, or with different types of bladder disease.
  • administration via one route may be useful when administering a larger dose and a different route may be useful for smaller doses.
  • administration via a particular route may be appropriate initially, with subsequent doses conveniently administered through another route.
  • the method further comprises a step of providing to the subject additional treatment of the interstitial cystitis or other bladder disease comprising: i) one or more doses of a pharmacological agent to reduce pain; ii) one or more doses of an antibiotic; iii) one or more treatments to expand the bladder mechanically; iv) one or more other treatments specifically provided to support the subject during recovery from the interstitial cystitis or other bladder disease process; or any combination of any of the foregoing.
  • compositions further optionally comprise any combination of one or more of polyphenols, antioxidants, D-mannose, S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin, vitamin A, vitamin C, vitamin D, vitamin E, or a compound providing a biologically available form thereof.
  • the one or more edible or medical mushrooms comprise Agaricus, Agrocybe, Albatrellus, Amanita, Antrodia, Auricularia, Boletus, Calvatia, Cantharellus, Caripia, Clitocybe, Cordyceps, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Pomes, Fomitopsis, Funalia, Ganoderma, Geastrum, Grifola, Hericium, Inocybe, Inonotus, Lactarius, Lentinus, Lentinula, Leucop axillus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, Russula, Sarcodona, Schizophyllum, Suillus, Termitomyces, Trametes, or Xerocomus;
  • the cannabinoids comprise one or more of cannabidiol (CBD), cannabidivarin (CBDV), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC).
  • CBD cannabidiol
  • CBDV cannabidivarin
  • CBN cannabinol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • compositions are specifically for treating interstitial cystitis and the compositions further comprises DMSO, CYRENE, or another amphipathic solvent.
  • compositions further comprise one or more herbal extracts comprising from Rehmanniae spp., Achyranthis spp., Corni spp., Moutan spp., Alismatis spp., Dioscorea spp., Plantaginis spp., Hoelen spp., Aconiti spp., Cinnamomi spp., Barosma betulina, Galium aparine, corn silk from Zea mays, horsetail (Equisetum spp.), resiniferatoxin (or extract from Euphorbia resinifera), capsaicin, saw palmetto, bearberry, cranberry, St. John's Wort, stinging nettle, or any combinations thereof.
  • herbal extracts comprising from Rehmanniae spp., Achyranthis spp., Corni spp., Moutan spp., Alismatis spp., Dioscorea spp.
  • compositions further comprise terpenes comprising one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene; and [111] iv) flavonoids comprising one or more of chai cones, flavones, isoflavonoids, flavanones, antho
  • the terpenes preferably comprise beta-ocimene, 1,8- cineole, alpha-pinene and/or beta-pinene, linalool, limonene, phytol, humulene, myrcene, phellandrene, caryophyllene, terpinolene, linalool, or other cineols or ocimenes, or any combination thereof.
  • the composition further comprises an extract or fraction from one or more traditional Jamaican medicinal plants other than Cannabis spp.
  • the traditional medicinal plants comprise Jamaican sorrel Hibiscus sabdariffa), guinea hen weed (Petiveria alliacea), or soursop (Annona murata) in certain embodiments.
  • methods of optimizing a composition for use in treatment of a subject suffering from interstitial cystitis or a bladder disease process using artificial intelligence are provided herein.
  • the methods generally comprise, for each disease process of interest, or for each subject in need of therapeutic compositions for such disease process:
  • the methods can further comprise the additional steps of: d) providing data on the therapeutic effect on the disease process of any or all of:
  • the artificial intelligence algorithm can comprise any useful software or algorithm approach capable of making the distinctions required.
  • the algorithm comprises a classification algorithm, a regression algorithm, a clustering algorithm, or a combination thereof.
  • the methods comprise a classification algorithm that is a naive Bayes algorithm, decision tree, random forest algorithm, Support Vector Machines, or K Nearest Neighbor algorithm.
  • the methods comprise a regression algorithm that is a liner regression, lasso regression, logistic regression, or multivariate regression.
  • the methods comprise a clustering algorithm that is a K-means clustering, fuzzy C-means algorithm, expectation-maximization algorithm, or hierarchical clustering algorithm.
  • a clustering algorithm that is a K-means clustering, fuzzy C-means algorithm, expectation-maximization algorithm, or hierarchical clustering algorithm.
  • the methods comprising the additional step of providing subject-specific data comprising, e.g. initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), specific symptomology, or the like.
  • subject-specific data comprising, e.g. initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), specific symptomology, or the like.
  • the artificial intelligence algorithm is then used to further optimize the composition based on those data in addition to the disorder-specific data.
  • the optimized formulation of the compositions may also be changed based on data from the results from an initial treatment, subsequent treatment, or based on subsequent tests of the subject.
  • the plurality of edible or medicinal mushrooms, mushroom extracts, or components for which data are analyzed generally comprise one or more of the species Agaricus blazei, Albatrellus confluens, Antrodia camphorate, Boletus badius, Clitocybe maxima, Cordyceps militaris, Flanulina velutipes, Pomes fomentarius, Punalia trogii, Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Inocybe umbrinella, Inonotus olbiquus, Lactarius flavidulus, Lentinula edodes, Phellinus linteus, Pleurotus ostreatus, Schizophyllum commune, Suillus placidus, Trametes versicolor, Cordyceps sinensis, C. liangshanensis, C. gunnii, or C. cicadicola.
  • the mushroom or mushroom extract can comprise Agaricus bisporus, A. subrufescens, Agrocybe aegerita, A. cylindracea, Albatrellus caeruleoporus, Amanita muscaria, Boletus edulis, Cantharellus cibarius, C. tubaeformis, Cordyceps pruinose, Caripia commonlyi, Cyathus africanus, C.
  • the mushroom or mushroom extract can come from any the following species: Agaricus, Agrocybe, Albatrellus, Amanita, Antrodia, Auricularia, Boletus, Calvatia, Cantharellus, Caripia, Clitocybe, Cordyceps, Cyathus, Daldinia, Dictyophora, Elaphomyces, Flammulina, Pomes, Fomitopsis, Funalia, Ganoderma, Geastrum, Grifola, Hericium, Inocybe, Inonotus, Lactarius, Lentinus, Lentinula, Leucop axillus, Lyophyllum, Phellinus, Pholiota, Pleurotus, Poria, Russula, Sarcodona, Schizophyllum, Suillus, Termitomyces, Trametes, or Xerocomus.

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Abstract

L'invention concerne des compositions et des procédés pour le traitement de la cystite interstitielle et d'autres processus de maladie de la vessie. Les compositions comprennent généralement au moins un extrait de champignon comestible ou médicinal de celui-ci, et au moins un extrait de cannabis, en combinaison. Les compositions comprennent facultativement du DMSO ou un solvant amphipathique utile pour dissoudre des molécules polaires et non polaires et peuvent être instillées directement dans une vessie affectée par l'intermédiaire d'un cathéter urinaire. L'invention concerne également des procédés d'optimisation de compositions à l'aide d'algorithmes d'intelligence artificielle.
PCT/IB2021/060079 2020-10-31 2021-11-01 Compositions pour le traitement de la cystite interstitielle et d'autres maladies de la vessie WO2022091050A1 (fr)

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