Composition for regulating cortisol homeostasis and improving sleep quality, as well as method for using and manufacturing the same.

Abstract

The present invention provides a composition used for regulating host cortisol homeostasis and improving sleep quality. [Solution] A composition is provided comprising an extract, wherein the extract is enriched with one or more phenylpropanoid acids and one or more benzoxazinoids for the purpose of establishing and regulating the homeostasis of the host stress hormone cortisol and improving the quality of sleep.

Claims

1. A composition comprising an extract, wherein the extract is enriched with one or more phenylpropanoid acids and one or more benzoxazinoids for the purpose of establishing and regulating the homeostasis of the host stress hormone cortisol and improving the quality of sleep.

2. The composition according to claim 1, wherein the phenylpropanoid acid and benzoxazinoid in the composition are in the range of 0.05% to 99.95% by weight and 99.95% to 0.05% by weight of each type of compound, and have an optimized weight ratio of 40%:60%.

3. A composition comprising an extract from corn leaves or corn shoots, wherein the extract is enriched with one or more benzoxazinoids, including benzoxazole, benzoxazinoid, benzoxazolinonoid aglycone, or both benzoxazole, benzoxazinoid, and benzoxazolinonoid glycoside.

4. One or more phenylpropanoid acids and benzoxazinoids are found in Zea mays, Oryza species, Oryza sativa, Oryza glaverima, Oryza australiensis, Oryza brachyantha, Secale cereale, Acanthus arboreus; Acanthus ebracteatus, Acanthus illicifolius, and Acanthus mollis. mollis), Avena sativa, Avena abyssinica, Avena byzantine, Avena nuda, Avena strigosa, Hordeum vulgare, Coix lachryma-jobi, Triticum aestivum, Triticum compactum, Triticum sphaerococcum *Sphaerococcum*, *Triticum turanicum*, *Sorghum bicolor*, *Agropyron repens*, *Blepharis edulis*, *Balsamocitrus paniculate*, *Peristrophe roxburghiana*, *Strobilanthes cusia*;The composition according to claim 1, extracted, enriched, and standardized from a plant species selected from the group including Lamium galeobdolon, Lobelia chinensis, Leymus chinensis, Aphelandra sp., Scoparia dulcis, Capparis sikkimensis ssp., or a combination thereof.

5. The composition according to claim 1, wherein one or more phenylpropanoid acids and benzoxazinoids are extracted, enriched and standardized from a plant part selected from the group consisting of shoots, germination from plant seeds, sprouts of germinated grain, immature leaves, mature leaves, whole plants, roots, seeds, flowers, stems, stem bark, root bark, silk, grains, root hairs of germinated grain, stem cells, cell culture tissue, or any combination thereof.

6. The composition according to claim 1, wherein one or more phenylpropanoid acids and benzoxazinoids are extracted, enriched and standardized from Zea mays shoots and immature leaves, Zea mays extract, or a combination thereof.

7. Phenylpropanoid acid is one or more 7-methoxy-2,7-dihydroxy-2h-1,4-benzoxazine-3(4H)-one; (R) isomer 2-O-β-d-glucopyranoside (HMBOA-Glc), 2-hydroxy-2H-1,4-benzoxazine-3(4H)-one; (R) isomer 2,7-dihydroxy-2H-1,4-benzoxazine-3(4H)-one; (R) isomer N-hydroxy-2-hydroxy-2H-1,4-benzoxazine-3(4H)-one; (R The composition according to claim 1, wherein (R) is 7-methoxy-2,7-dihydroxy-2H-1,4-benzoxazine-3(4H)-one; (R) is N-hydroxy-7-methoxy-2,7-dihydroxy-2H-1,4-benzoxazine-3(4H)-one; (R) is capamensine A, N-methoxy-7-methoxy-2,7-dihydroxy-2H-1,4-benzoxazine-3(4H)-one; (R) is monosilinol A, monosilinol B, or any combination thereof.

8. The composition according to claim 1, wherein the benzoxazinoid is one or more aglycones and glycosides of 6-methoxy-2-benzoxazolol (MBOA); 2-benzoxazolol (BOA); 4-methylbenzoxazole; 2,4-dimethylbenzoxazole; 2,6-dimethylbenzoxazole; 2,6-benzoxazolediol; 2,4-benzoxazolediol; 4-acetyl-2(3H)-benzoxazolone; 6-methoxy-N-methyl-2(3H)-benzoxazolone; 3-hydroxy-6-methoxy-2-benzoxazolin-2(3H)-one; 2-hydroxy-6,7-dimethoxybenzoxazole; 5,6-dimethoxy-2-benzoxazolinone; 3,6-dimethoxybenzoxazolin-2(3H)-one; 5-chloro-6-methoxy-2-benzoxazolinone; trehalamine; or any combination thereof.

9. The composition according to claim 1, wherein one or more phenylpropanoid acids and benzoxazinoids in the composition are extracted with any suitable solvent, including supercritical fluid of CO2, water, acidic water, basic water, acetone, methanol, ethanol, propenol, butanol, alcohols mixed with water, mixed organic solvents, or combinations thereof.

10. The composition according to claim 1, wherein one or more phenylpropanoid acids and benzoxazinoids in the composition are synthesized, metabolized, biodegraded, bioconverted, in vivo converted, or biosynthesized from low-carbon units by transgenic microorganisms, P450 enzymes, glycosyltransferases or combinations of enzymes, or by microbacteria.

11. The composition according to claim 1, wherein one or more phenylpropanoid acids and one or more benzoxazinoids in the composition are enriched individually and / or in combination by solvent precipitation, neutralization, solvent partitioning, ultrafiltration, enzymatic digestion, column chromatography using silica gel, XAD, HP20, LH20, C-18, aluminum oxide, polyamide, ion exchange, and CG161 resin.

12. The composition according to claim 1, wherein the composition further comprises a pharmaceutically or nutritionally acceptable active substance, an adjuvant, a carrier, a diluent, or an excipient, and the pharmaceutically or nutritionally acceptable preparation contains about 0.1% by weight (wt%) to about 99.9% by weight of the active compound in the enriched one or more phenylpropanoid acids and one or more benzoxazinoid compositions.

13. The active ingredient, auxiliaries, excipients, or carriers may include: Cannabis sativa oil or CBD / THC, turmeric extract or curcumin, Terminalia extract, aloe vera leaf gel powder, valerian root, Valeriana officinalis, Ginkgo biloba, Kava kava, lavender, passionflower (Passiflora incarnata or maypop), chamomile flower, hops, Humulus lupulus, Hibiscus sabadarifa Sabdariffa, St. John's Worth, Calif Griffonia simplicifolia, fermented milk, fish oil, Rhodiola rosea, lotus seeds, lotus seed germ, Oryza sativa, Zea mays, jujube, Schisandra chinensis, Magnolia officinalis, Astragalus membranaceus, Ganoderma lucidum Lucidum, Echinacea purpurea, Echinacea angustifolia, Poria cocos 'Wolf', Wolfiporia extensa, Withania somnifera, Bupleurum falcatum, Glycyrrhiza sp., Panax quinquefolium, Panax ginseng C. A. Meyer (Panax ginseng C.A. Meyer), Korean red ginseng, Eurycoma longifolia (Malaysian ginseng)(ginseng), Lentinula edodes (shiitake mushroom), Inonotus obliquus (chagama mushroom), melatonin, magnesium, gamma-aminobutyric acid (GABA), vitamins B1, B2, B3, B6, B12, pyridoxine, methylcobalamin, niacinamide, folic acid, ascorbic acid, vitamin C, vitamins D & E, zinc, omega-3 fatty acids, glycine, glutamine, arginine, tryptophan, L-theanine, 5-hydroxytryptophan (%-(5-HTP), SAMe, chlorella, magnolol, honokiol, taurine, boron, branched-chain amino acids (B The composition according to claim 11, which is selected from one or more of the following: CAA, phospholipids, phosphatidylserine, phosphatidic acid, theaflavin, rosmarinic acid, catechin, epicatechin, EGCG, ECG, conjugated catechins such as epigallocatechin, baicalein, baicalin, oroxylin, wagonin, kaempferol, genistein, quercetin, butein, betaine, luteolin, chrysin, apigenin, curcumin, resveratrol, glomeratose A, 6-shogaol, gingerol, berberine, and piperine.

14. The composition according to claim 1, wherein the composition is formulated in the form of tablets, hard capsules, soft gel capsules, powders or granules, compressed tablets, pills, gums, chewing gums, sachets, wafers, bars or liquid forms, tinctures, airborne sprays, semi-solids, semi-liquids, solutions, emulsions, creams, lotions, ointments, gel bases, and the like.

15. The composition according to claim 1, wherein the route of administration is selected from the group consisting of oral, topical, suppository, intravenous, intradermal, intragastric, intramuscular, intraperitoneal, or intravenous.

16. The composition according to claim 1, wherein one or more phenylpropanoid acids and one or more benzoxazinoids in the composition selectively bind to the MT2 receptor rather than the MT1 receptor.

17. The composition according to claim 1, wherein one or more phenylpropanoid acids and one or more benzoxazinoids in the composition improve sleep quality by enhancing the deep sleep stage, increase total sleep time and deep sleep time, improve overall mental health as measured by the Pittsburgh Sleep Quality Index (PSQI) and Mood Profile Scale (POMS), support positive mood, enhance emotional health, and maintain homeostasis of biomarkers—serotonin, melatonin, and GABA—in the formulation in mammals.

18. The composition according to claim 1, wherein one or more phenylpropanoid acids and one or more benzoxazinoids in the composition prevent and treat the most common sleep disorders, including insomnia, hypersomnia, circadian rhythm disorders, shift work sleep disorders, non-24-hour sleep-wake disorders, periodic limb movement disorders, restless legs syndrome (RLS), sleep apnea, narcolepsy, parasomnia, night terrors, sleepwalking, nightmares, sleep-eating disorders, sleep hallucinations, sleep paralysis, sleep talking, and REM sleep behavior disorder.

19. The composition according to claim 1, wherein one or more phenylpropanoid acids and one or more benzoxazinoids in the composition maintain cortisol homeostasis, thereby improving symptoms of chronically high cortisol, including but not limited to anxiety, depression, fatigue, gastrointestinal problems such as constipation, bloating or diarrhea, headaches, heart disease, hypertension, irritability, impaired memory and concentration, decreased libido, erectile dysfunction or reproductive problems such as irregular menstruation and ovulation, difficulty sleeping, slow recovery from exercise, eating disorders and weight gain.

20. The composition according to claim 1, wherein one or more phenylpropanoid acids and one or more benzoxazinoids in the composition are administered to a mammal in an effective amount of 0.01 mg to 1000 mg per kg of body weight.

21. A composition comprising an extract of corn shoots or corn leaves, wherein the extract is enriched with one or more phenylpropanoid acids and one or more benzoxazinoids.

22. The composition according to claim 1, wherein the extract is derived from corn leaves or corn shoots.

23. A composition enriched with one or more phenylpropanoid acids and one or more benzoxazinoids for establishing and regulating the homeostasis of the host stress hormone cortisol, and for improving sleep quality.

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