Sleep products

Abstract

A sleep supplement composition comprising valerian extract, lemon balm extract, and L-theanine. In certain embodiments, the composition also comprises melatonin.

Description

[Technical field]

[0001] A dietary supplement is a product intended to supplement the diet. Dietary supplements may contain one or more nutritional ingredients, including vitamins, minerals, herbs, amino acids, and other substances. Dietary supplements may be taken by mouth as pills, capsules, tablets, or liquids, and may usually be labeled as such on the front panel. Summary of the Invention

[0002] One embodiment disclosed herein is a sleep supplement composition comprising 50 mg to 275 mg of valerian extract, 20 mg to 140 mg of lemon balm extract, and 1.0 mg to 13.0 mg of L-theanine.

[0003] Also disclosed is a dosage unit containing 50 mg to 275 mg of valerian extract, 20 mg to 140 mg of lemon balm extract, and 1.0 mg to 13.0 mg of L-theanine, in the form of a softgel capsule for promoting sleep.

[0004] Further disclosed are methods for promoting sleep in an individual in need thereof by orally administering to the individual a sleep supplement composition or dosage unit described herein.

[0005] [Detailed Description of the Invention] <Terminology> The following explanations of terms and methods are provided to better describe the present compounds, compositions and methods, and to guide those of ordinary skill in the art in the practice of the present disclosure. It should also be understood that the terms used in this disclosure are for the purpose of describing specific embodiments and examples only, and are not intended to be limiting. "Administration" as used herein includes administration to a subject by another person or self-administration by the subject. "Effective amount" refers to an amount of a particular drug sufficient to achieve a desired effect in an individual.

[0006] <Composition> Disclosed herein is a composition in the form of a dietary supplement, which is particularly useful for inducing and maintaining sleep, promoting natural sleep, improving sleep quality, shortening the time it takes to fall asleep, and / or assisting individuals to achieve deep, restful sleep.The composition comprises valerian extract, lemon balm extract, and L-theanine.In certain embodiments, the composition also comprises melatonin.In certain embodiments, melatonin, valerian extract, lemon balm extract, and L-theanine are the only sleep-inducing active ingredients in the composition.

[0007] In certain embodiments, melatonin may be present in an amount of at least 0.5, 1.0, 1.5, 2.0, 2.5, or 3 mg. In certain embodiments, melatonin may be present in an amount of up to 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, or 5.5 mg. In certain embodiments, melatonin is present in an amount of 0.5-5.5 mg, more particularly, 1.0-4.0 mg.

[0008] In certain embodiments, the valerian extract may be present in an amount of at least 50, 75, 100, 125, 150, 175, 200, or 225 mg. In certain embodiments, the valerian extract may be present in an amount of up to 75, 100, 125, 150, 175, 200, 225, 250, or 275 mg. In certain embodiments, the valerian extract is present in an amount of 50-275 mg, more particularly, 100-200 mg.

[0009] In certain embodiments, the lemon balm extract may be present in an amount of at least 20, 30, 40, 50, 60, 70, 80, 90, or 100 mg. In certain embodiments, the lemon balm extract may be present in an amount of up to 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or 140 mg. In certain embodiments, the lemon balm extract is present in an amount of 20-140 mg, more particularly, 50-120 mg.

[0010] In certain embodiments, L-theanine may be present in an amount of at least 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, or 8.0 mg. In certain embodiments, L-theanine may be present in an amount of up to 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, or 13.0 mg. In certain embodiments, L-theanine is present in an amount of 1.0 to 13.0 mg, more particularly, 6.0 mg to 11.0 mg.

[0011] In certain embodiments, the total amount of valerian extract, lemon balm extract, and L-theanine is between 100 mg and 400 mg, more particularly between 150 mg and 300 mg.

[0012] In certain embodiments, the valerian extract is derived from the root of Valeriana officinalis.

[0013] In certain embodiments, the lemon balm extract is derived from the leaves of Melissa officinalis.

[0014] The compositions can be formulated in a pharma- ceutically acceptable carrier to produce, for example, dietary supplements in the form of dietary supplement dosage forms (such as tablets or capsules), liquids (such as beverages or gels), and consumables (such as foods or powders to be mixed with liquids).

[0015] The composition may include at least one excipient. In certain embodiments, an excipient is an inert substance used as a carrier for the active ingredient of the composition. Excipients may include substances used to bulk up formulations with highly potent active ingredients, allow convenient and accurate administration, stabilize the active ingredients, and make the delivery system optically and / or organically acceptable. Examples of pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerin monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol, etc.

[0016] Remington's Pharmaceutical Sciences, by EW Martin, Mack Publishing Co., Easton, PA, 19th Edition (1995) describes compositions and formulations suitable for pharmaceutical delivery of one or more compositions. The use of pharmaceutically acceptable excipients does not mean that the product so manufactured is useful only for pharmaceutical purposes. Rather, it means that the product is suitable for administration to or ingestion by a subject, for example, as a medicine or dietary supplement suitable for oral ingestion by a subject.

[0017] Generally, the nature of the excipient will depend on the particular mode of administration employed. For example, parenteral formulations usually consist of injectable fluids that contain pharma- ceutically and physiologically acceptable fluids, such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol, and the like, as a vehicle. For solid compositions (e.g., powders, tablets, or capsules), conventional non-toxic solid vehicles include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral vehicles, the compositions to be administered may contain small amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, for example, sodium acetate or sorbitan monolaurate, preservatives, pH buffering agents, and the like.

[0018] The disclosed compositions can be packaged in a multi-dose or single-dose container.The compositions can also be provided in a kit, for example, with components that can be assembled for use.For example, one or more of the disclosed components can be provided in lyophilized form, and suitable diluents can be provided as separate components for combination before use.The container is preferably adapted to the desired mode of administration, including, but not limited to, tablets, gel capsules, sustained release capsules, etc. for oral administration.

[0019] The active ingredient is contained in a pharma- ceutically acceptable carrier in an amount sufficient to exert a therapeutically useful effect without undesirable side effects on the subject of treatment. Therapeutically effective concentrations can be empirically determined by testing the compound in known in vitro and in vivo model systems. In some instances, a therapeutically effective amount of an ingredient is an amount that alleviates or improves at least one condition to which the composition is administered. Generally, the composition is formulated for single administration. The concentration of the active ingredient in the composition depends on the absorption, inactivation, and excretion rates of the active ingredient, the dosing schedule, and the amount administered, as well as other factors known to those skilled in the art.

[0020] In some examples, the active ingredient is combined with at least one physiologically acceptable carrier and / or excipient to form a dosage unit. The amount of active substance in these compositions or preparations is such that a suitable dosage (medication) amount within the indicated range is obtained. The term "dosage unit" refers to a physically discrete unit suitable as a unitary dosage for human subjects and other mammals, each unit containing a predetermined amount of active substance calculated to produce a desired therapeutic effect in association with a suitable pharmaceutical excipient.

[0021] The disclosed compositions can be administered as a single dose or divided into multiple smaller doses administered at intervals of time. The compositions can be administered as a single dose delivery, continuously delivered over an extended period of time, or by a repeated administration protocol (e.g., multiple day, daily, weekly, or monthly repeated administration protocol).

[0022] When administered orally as a suspension, these compositions can be prepared according to techniques well known in the art of pharmaceutical formulations and contain microcrystalline cellulose to provide bulk, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer, and sweeteners / flavorings. As immediate release tablets, these compositions can contain microcrystalline cellulose, dibasic calcium phosphate, starch, magnesium stearate, and lactose and / or other excipients, binders, expanders, disintegrants, diluents, and lubricants. When oral administration is desired, the composition is typically provided in a composition that protects against the acidic environment of the stomach. For example, the composition can be formulated in an enteric coating that maintains its integrity in the stomach and releases the active compound in the intestine. The composition can also be formulated in combination with an antacid or other such ingredient.

[0023] Oral compositions generally contain an inert diluent or edible carrier, and can be compressed into tablets or enclosed in gelatin capsules. For the purpose of oral therapeutic administration, the active ingredient can be combined with an excipient and used in the form of tablets, capsules, or lozenges. Pharmaceutically compatible binders and adjuvant materials can be included as part of the composition. Tablets, pills, capsules, lozenges, etc. can contain any of the following ingredients or compounds of similar nature, including, but not limited to: binders such as gum tragacanth, acacia, corn starch, gelatin; excipients such as microcrystalline cellulose, starch, lactose; disintegrants such as alginic acid, corn starch, but not limited to; lubricants such as magnesium stearate, but not limited to; glidants such as colloidal silicon dioxide, but not limited to; sweeteners such as sucrose, saccharin; flavorings such as peppermint, methyl salicylate, fruit flavors, etc.

[0024] When the dosage form is a capsule, it can contain, in addition to materials of the above type, a liquid carrier such as fatty oil. Furthermore, dosage unit forms can contain other various materials that modify the physical form of the dosage unit, for example, coatings of sugar and other enteric agents.

[0025] When administered orally, the composition can be administered in a dosage form for oral administration.These dosage forms include the usual solid unit dosage forms of tablets and capsules, and liquid dosage forms such as solutions, suspensions, and elixirs.When using solid dosage forms, they are preferably of sustained release type, so that the compound only needs to be administered once or twice a day.In some examples, oral dosage forms are administered once, twice, three times, four times, or more times a day.

[0026] For solid compositions such as powders, tablets, pills, or capsules, conventional non-toxic solid carriers can include, for example, pharmaceutical grade mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, the pharmaceutical compositions to be administered can optionally contain minor amounts of non-toxic auxiliary substances or excipients, such as wetting agents, emulsifying agents, preservatives, pH buffering agents, etc.; for example, sodium acetate or sorbitan monolaurate. Other non-limiting excipients include non-ionic solubilizers such as Cremophor, or proteins such as human serum albumin.

[0027] In certain embodiments, a capsule is provided that includes a fill composition and a shell surrounding the fill. The fill composition may be any of the sleep compositions described herein. The fill composition may also include a liquid medium component, as described in more detail below. Optionally, a coating may be provided around the shell.

[0028] The capsules prevent deterioration of the fill composition and can be stored at room temperature for several months. The capsules are adapted for self-administration by an individual. The capsule shell dissolves or disintegrates in the digestive tract after the capsule is ingested, thereby releasing the therapeutic composition for absorption into the body of the individual ingesting the capsule.

[0029] The capsule shell is usually made of animal- or plant-derived ingredients that dissolve or disintegrate easily after ingestion. Animal-derived ingredients can include gelatin, which is made from collagen in the skin and / or bones of animals. In certain embodiments, the capsule is made of gelatin. Other suitable matrix materials, such as fully synthetic polymeric chemicals with gelatin-like properties, may be used in the manufacture of the capsule. Plant-derived ingredients can include vegetable starch, cellulose, hypromellose (a polymer formulated from cellulose) or pullulan (a polysaccharide polymer produced from tapioca starch). In some embodiments, plant-derived ingredients can include carrageenan, potato starch, cassava starch, corn starch, arrowroot, or combinations thereof. The composition, manufacture and use of capsule shells are well known in the art.

[0030] In certain embodiments, the capsule is a softgel capsule, also referred to herein. Softgel capsules are particularly suitable for containing liquid-based components, such as therapeutic components dissolved, dispersed, and / or suspended in a liquid medium. Softgel capsules are also particularly advantageous for materials that require complete protection from air and light. For example, softgel capsules can block a significant amount (e.g., at least 90%, at least 99%, or up to 100%) of ultraviolet light from penetrating the softgel capsule.

[0031] One advantage of softgel capsules is that the rate and extent of absorption is improved and variability per dose is reduced, especially for water-soluble drugs. Another advantage of softgel capsules is that they are substantially easier to swallow than tablets or hard-shell capsules, for example. Yet another advantage is that they do not have the poor taste, aftertaste, sharp edges, or other sensory issues associated with alternatives such as tablets and hard-shell capsules. Another advantage is improved patient compliance compared to tablets and hard-shell capsules.

[0032] Another advantage is the ease and convenience of oral administration of pharmaceuticals that must be formulated in liquid dosage forms. Yet another advantage is the increased ability to control the exact amount of therapeutic agent in a liquid compared to a solid or powder form. Another advantage is the prevention of tampering and / or alteration of the dosage after formulation and before administration. Yet another advantage is that the active therapeutic agent is sealed.

[0033] Another advantage is improved formulation homogeneity compared to tablets, granules, or powders. Yet another advantage is improved stability of the therapeutic agent in the softgel capsule. Another advantage is easier storage and extended shelf life of the softgel capsule compared to hard shell capsules. Yet another advantage is the rapid disintegration of the softgel capsule upon administration, which increases the rate of absorption of the therapeutic agent, thereby increasing the rate of therapeutic effect, compared to, for example, tablets. Another advantage is a substantial reduction in plasma fluctuation of the therapeutic agent, thereby increasing the level of bioavailability, when administered, compared to tablets or hard shell capsules.

[0034] The shell of a softgel capsule is typically a combination of animal-derived and / or plant-derived ingredients with a plasticizer such as glycerin and a solvent such as water. In some embodiments, plant-derived ingredients such as cellulose, hypromellose, vegetable starch, tapioca starch, carrageenan, potato starch, cassava starch, corn starch, arrowroot, or combinations thereof may be used instead of gelatin to produce vegetarian softgel capsules. Other animal- or plant-derived ingredients with properties similar to gelatin or starch that are suitable for polymerization or activated crosslinking may also be used. The shell of a softgel capsule is typically manufactured and filled with a therapeutic formulation in a continuous process known in the art.

[0035] The term "plasticizer" refers to a substance that is added to gelatin or starch to form a softgel capsule. Plasticizers include glycerin, sorbitol, propylene glycol, other suitable polyols, or combinations thereof. The amount of plasticizer can be adjusted to provide a softgel shell with a desired level of softness and flexibility. Some embodiments may include about 30 to about 50% by weight of plant-derived ingredients; at least 18% by weight, preferably up to about 40% by weight of plasticizer; and about 20 to about 50% by weight of water. These blends are formed into capsules and dried to provide softgel capsules that include about 40 to about 75% by weight of plant-derived ingredients; about 18 to about 40% by weight of plasticizer; and about 5 to about 15% by weight of water. Softgel capsule shells can be prepared by placing appropriate amounts of plant-derived ingredients, water, plasticizer, and any optional ingredients in a suitable container and agitating and / or stirring with heating until a homogenous solution is obtained.

[0036] In some embodiments, the softgel shell comprises a layer or coating. The coating may include a film coating or an enteric coating that allows for controlled, delayed or sustained release of the capsule's contents upon administration.

[0037] The term "preservative" refers to compounds used to prevent the growth of bacteria, fungi, molds, and other microorganisms. They are used for their respective antibacterial (destruction and inhibition of growth of bacteria), antifungal (destruction and inhibition of growth of fungi), antimicrobial, antimycoplasmic, antiviral, and / or antiprion properties. Suitable preservatives may include, but are not limited to, at least one of benzalkonium chloride, benzethonium chloride, chlorhexidine, phenol, m-cresol, benzyl alcohol, alkylparabens (such as methylparaben, ethylparaben, propylparaben, butylparaben, etc.), sodium dehydroacetate, o-cresol, p-cresol, chlorocresol, phenylmerpotassium nitrate, thimerosal, benzoic acid, and any mixture of one or more thereof. See, for example, Wallhauser, K., Develop. Biol. Standard. 24, pp. 9-28 (Basel, S. Krager, 1974). In some embodiments, the soft gelatin shell may contain a preservative to prevent fungal growth. In certain embodiments, the preservative may include parabens such as methylparaben, propylparaben, isopropylparaben, butylparaben, and isobutylparaben, and their salts such as sodium butylparaben, benzoic acid and its salts, and esters, benzyl alcohol, urea derivatives such as diazofidinyl urea, imidazolidinyl urea, and DMDM ​​hydantoin, sorbic acid and its salts, and the like. In various embodiments, the preservative may be absent.

[0038] The term "opacifier" refers to an agent or mixture of agents that, when added to a formulation, renders the subsequent system opaque. Exemplary opacifiers include, but are not limited to, pharma-ceutically acceptable metal oxides, particularly titanium dioxide. Certain embodiments may include about 0.2% to about 1.2% by weight of an opacifier mixed with the botanical component mass of the softgel. In some embodiments, the opacifier may be absent.

[0039] The term "flavorant" refers to a compound that provides a desired taste and / or odor. Flavorants may be natural or artificial compounds and may, but need not, be oil-soluble. Flavoring agents include isoamyl acetate (or other banana flavoring), benzaldehyde (or other almond flavoring), cinnamaldehyde (or other cinnamon flavoring), ethyl citric acid or propionate (or other fruity flavoring), methyl anthranilate (or other grape flavoring), limonene (or other orange flavoring), ethyl decadienoate (or other pear flavoring), allyl hexanoate (or other pineapple flavoring), ethyl maltol (or other sugar or cotton candy flavoring), ethyl vanillin (or other vanilla flavoring), methyl salicylate (or other wintergreen flavoring), glyceryl monoacetate (E1516 food additive), glyceryl diacetate (E1517 food additive), and combinations thereof. Some embodiments may include about 0.1% to about 2% by weight of flavoring agent. The term "colorant" refers to compositions or compounds such as pigments, dyes, tints, etc. that impart color. Representative colorants include carotenoids (E160, E161, E164), chlorophyllins (E140, E141), anthocyanins (E163), and betanins (E162). Colorants such as annatto (E160b), a red-orange pigment made from achiote seeds, caramel color (E150a-d), carmine (E120), a red pigment derived from the cochineal insect Dactylopius coccus, elderberry juice (E163), lycopene (E160d), paprika (E160c), and turmeric (E100) can also be used.

[0040] The term "excipient" as used herein includes, but is not limited to, the preservatives, plasticizers, opacifiers, colorants and flavoring agents described above, or any combination thereof. The term excipient may also include solvents, binders, surfactants, emulsifiers, wetting agents, suspending agents, or any combination thereof. Suitable excipients or additives that can be used in the formulation of softgel capsules are described, for example, in Lachman, et al., "The Theory and Practice of Industrial Pharmacy," 4th Edition (2013); Rowe et al., "Handbook of Pharmaceutical Excipients," 8th Edition (2017); and Remington, "The Science and Practice of Pharmacy," 22nd Edition (2015). From a regulatory perspective, it is desirable that all excipients and additives used in the formulation of the softgel capsules described herein are approved for use in oral pharmaceutical dosage forms.

[0041] The capsule softgel shell is filled with a sleep composition. The sleep composition can be mixed, dissolved, dispersed, suspended, or emulsified in the liquid medium. The liquid medium can be hydrophilic or lipophilic in character. In certain embodiments, the liquid medium can include a combination of hydrophilic and lipophilic materials. In various embodiments, the hydrophilic material, lipophilic material, or combinations thereof are encapsulated within the softgel shell in the form of a preconcentrate. In some embodiments, the preconcentrate further includes one or more surfactants. In certain embodiments, the components of the liquid medium are present in the form of an emulsion either before, during, or after oral administration of the softgel capsule. In various embodiments, the emulsion includes a microemulsion, a nanoemulsion, and combinations thereof.

[0042] In some embodiments, the liquid medium is selected from the group consisting of silicone oils, vegetable oils, glycerin, hydrogenated vegetable oils, lecithin, beeswax, tocopherol, polyethylene glycol (e.g., PEG 200, 300, 400, or 600), polyoxyethylene-polyoxypropylene copolymers (poloxamers), propylene glycol, triglycerides of medium chain fatty acids, omega oils, soybean oil, canola oil, sunflower oil, macadamia oil, peanut oil, grapeseed oil, pumpkin seed oil, linseed oil, olive oil, corn oil, safflower oil, sesame oil, pine kernel oil, conjugated linoleic acid, almond oil, peach kernel oil, apricot kernel oil, walnut oil, rapeseed oil, raspberry seed oil, oleic acid ... Oils, bilberry seed oil, cranberry seed oil, pomegranate seed oil and other fruit seed oils, sea buckthorn oil, chia oil, perilla oil, diglycerol (DAG) oil, plant-derived omega-3 sources, fermented sources of eicosapentaenoic acid (EPA), fermented sources of docosahexaenoic acid (DHA), fermented sources of EPA, DHA and other omega-3 combinations, including fish oil, leech oil, sources of gamma linolenic acid (GLA) or stearidonic acid (SA), fractionated coconut oil, and combinations thereof. Sources of DHA, EPA and alpha-linoleic acid (ALA) can include, but are not limited to, one or more of the following oils: fish oil, yeast and other microbial or single-cell sources, and vegetable oils (mainly flaxseed, soybean, canola). Sources of GLA include, but are not limited to, evening primrose oil, blackcurrant seed oil, borage oil, echium oil, etc.

[0043] In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are merely preferred examples of the invention and should not be taken as limiting the scope of the invention.

Claims

1. 1. A sleep supplement composition comprising: 1.0 mg to 4.0 mg of melatonin; 100 mg to 200 mg of valerian extract; 50 mg to 120 mg of lemon balm extract; and 6.0 mg to 11.0 mg of L-theanine.

2. 2. The sleep supplement composition of claim 1, wherein the total amount of the valerian extract, lemon balm extract, and L-theanine is 100 mg to 400 mg.

3. 10. The sleep supplement composition of claim 1, wherein the melatonin, valerian extract, lemon balm extract, and L-theanine are the only sleep-inducing active ingredients of the composition.

4. 10. The sleep supplement composition of claim 1, further comprising at least one excipient.

5. 1. A dosage unit comprising 50 mg to 275 mg of valerian extract, 20 mg to 140 mg of lemon balm extract, and 1.0 mg to 13.0 mg of L-theanine, in the form of a softgel capsule for promoting sleep.

6. 6. The dosage unit of claim 5, further comprising melatonin.

7. 7. The dosage unit of claim 6 comprising from 0.5 mg to 5.5 mg of melatonin.

8. 7. The dosage unit of claim 6 comprising 1.0 mg to 4.0 mg of melatonin, 100 mg to 200 mg of valerian extract, 50 mg to 120 mg of lemon balm extract, and 6.0 mg to 11.0 mg of L-theanine.

9. 9. The dosage unit of claim 8, wherein melatonin, valerian extract, lemon balm extract, and L-theanine are the only sleep-inducing active ingredients of the dosage unit.

10. 7. The dosage unit of claim 6, wherein the softgel capsule comprises a shell and a fill composition, the shell being made from at least one botanical ingredient and the fill composition comprising valerian extract, lemon balm extract, L-theanine, and melatonin.

11. 11. The dosage unit of claim 10, wherein the fill composition further comprises a triglyceride of a medium chain fatty acid.

12. 13. Use of the sleep supplement composition of claim 1 in the manufacture of a dietary supplement for promoting sleep in an individual in need of sleep.

13. 10. Use of a dosage unit according to claim 5 in the manufacture of a medicament for promoting sleep in an individual in need of sleep.