COMPOSITION FOR NAP PROMOTION

Abstract

The present invention relates to an oral formulation for promoting napping in a subject. The formulation may comprise an outer layer comprising a sedative and/or relaxant, and an inner layer comprising a stimulant.

Claims

1. A nap improving composition comprising a pill with a stimulant and a separate pill with a relaxant or sedative.

2. A nap improving oral formulation comprising an outer layer comprising a sedative and optionally a relaxant, and an inner layer comprising a stimulant.

3. The formulation of claim 2, wherein the inner layer comprises a capsule and the outer layer comprises a coating.

4. A method of promoting napping in a subject, comprising administering the oral formulation of claim 1 to a subject in need thereof.

Description

DETAILED DESCRIPTION

[0015] The inventors have discovered that oral formulations comprising multiple pills or a single controlled release pill with an outer portion comprising a sedative and/or relaxant, and an inner portion comprising a stimulant, are surprisingly effective in promoting napping in a subject for about 10-45 minutes, with no nap hangover or grogginess. In a preferred embodiment, this time period is about 30 minutes. When the formulations are swallowed by the subject, the first pill of an outer portion of a single pill may dissolve in the mouth or stomach, where a released sedative and/or relaxant may aid in relaxation and restful sleep. About 20 to 30 minutes after the formulation has been swallowed, the inner portion may dissolve, releasing the stimulant into the stomach. The stimulant may be absorbed from the stomach and have a pharmacological effect within about 30-60 minutes after the formulation is consumed. The formulation may enhance the nap experience of the subject by improving the quality of sleep, while delivering an energy boost as the subject awakens.

[0016] One pill may help the subject relax to begin their nap and to help improve the quality of their nap; another pill then releases a time-delayed kick of a natural stimulant to help clear the mind 30-45 minutes later when the subject is awakened. The subject then awakes refreshed and not groggy while still enjoying the proven benefits of a short nap. Nap30 and Nap10 are non-addicting and designed for improving short-duration naps that are more restful for the brain than purely consuming caffeine, while avoiding the 3-8 hours of grogginess that can ensue from traditional sleep aids. In some embodiments the components can be put into a single pill with timed release of the relaxant and stimulant or with the coating of the pill forming the initial drug release profile and the inner portion of the pill forming the latter drug release profile.

1. Definitions

[0017] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise.

[0018] For recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the numbers 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated.

2. Nap-Promoting Formulation

[0019] Provided here is a formulation for promoting napping in a subject in need of rest or mental clarity. The napping may not induce grogginess. The formulation may be an oral formulation, and may comprise multiple pills or a single pill with an inner portion and an outer portion. The one pill or the inner portion of some embodiments may comprise a stimulant and the outer portion of a pill of some embodiments may comprise a sedative and/or a relaxant. The first pill or outer portion of a pill may begin dissolving in the subject's mouth and release the sedative and/or relaxant, thereby assisting the subject in achieving restful sleep within about 10 to 15 minutes of consuming the formulation. The second pill or inner portion may dissolve in the subject's stomach within about 20 to 30 minutes, which may release the stimulant. The stimulant may have a pharmacological effect within 10 minutes of being absorbed in the subject's stomach, thereby causing the subject to feel energized. The formulation may thus promote a nap of about 10-45 minutes in the subject.

[0020] a. Stimulant

[0021] The stimulant may comprise caffeine, which may comprise a caffeine from a natural source. The source of the caffeine may be a green tea extract, guarana extract, coffee extract, or yerba mate extract, or a combination thereof. While the stimulant may comprise caffeine in particular, the stimulant may also comprise, or comprise an extract of, Acetyl-L-Carnitine/L-Carnitine, Arginine, Biotin, Betel nut, B-vitamins, Cacao, Cayenne, Chia seeds, Chlorella, Chlorophyll, Chromium picolinate, Coconut oil, Coenzyme Q-10, Cordyceps, Damiana, Dehydroepiandrosterone (DHEA), Eluthero, Ephedra, Fo-Ti, Free form amino acids, Ginkgo, Ginseng, which may be Asian or Red, Gotu kola/kula, Grape seed, Green coffee, Guayusa, Holy basil extract, Hoodia, Indian ginseng, Iodine, L-Theanine, L-Tyrosine, Maca, Mucuna pruriens, Niacin, Rhodiola rosea, Sage, Selenium, St. John's Wort, Taurine, Tea (Cammillia sinensis), Theobroma cacao, Tobacco, Xanthine, or Yohimbe.

[0022] b. Relaxant

[0023] The relaxant may comprise a natural relaxant, which may comprise a chamomile extract, lavender extract, lemon balm extract, or passion flower extract, or a combination thereof. While the relaxant may comprise a chamomile extract in particular, the relaxant may also comprise, or comprise an extract of, Ashwagandha root, Benzoin Resin, Bergamot Oil, Boswellia (Frankincense), Calamus root, Calcium, California poppy, Camphor, Catnip, Cedarwood, Celandine, Chaste tree/vitex/chasteberry, Cherries/cherry juice, Clary Sage, Coriander, Cornflowers, Corydalis, DHEA, Diphenhydramine, Dong quai, Fumitory, Geranium, Hemp Oil, Hyssop, Inositol, Jamaican Dogwood, Jasmine Flower Oil, Juniper Berries, Linden, Lotus, Magnesium, Marjoram, Melatonin, Milk peptides, Motherwort, Myrrh, Nard Oil, Niacinamide, Orange, Patchouli, Periwinkle, Potassium, Red clover, Rose, Sandalwood, Schisandra, Skullcap, Stevia herb, Sweet Woodruff, Tryptophan, Wild Cherry Bark, Wild lettuce, Wintergreen, or Ylang-Ylang.

[0024] c. Sedative

[0025] The sedative may comprise melatonin, which may comprise a melatonin from a natural source. The sedative may also be a valerian root extract, a hops extract, or a kava extract, or a combination thereof.

[0026] d. Nootropic

[0027] The nootropic may comprise a natural or synthetic nootropic, which may comprise niacinamise, pyridoxal 5 phosphate, methyltetrahydrofolate, methylcobalmin, calcium d-pantothenate, alpha-lipoic acid, L-tyrosine, L-glutamine, white willow bark powder, DMAE bitartrate, acetyl L-carnitine, or ginkgo leaves powder, or a combination thereof.

[0028] e. Pill Formation

[0029] The inner portion may comprise a capsule, and the outer portion may comprise a capsule coating. The capsule may be a softgel or a hard-shell capsule. The capsule may comprise a liquid fill, a powder fill, or a semi-solid fill; and a shell.

[0030] 1. Liquid Fill

[0031] The liquid fill may comprise the stimulant, a liquid vehicle, a plasticizer, a surfactant, water, a solubilizing agent, and a suspending agent.

[0032] a. Liquid Vehicle

[0033] The liquid vehicle may comprise a lipophilic liquid or a semi-solid. The lipophilic liquid may comprise a vegetable oil and/or polyether. The semi-solid may comprise a hydrogenated oil, such as castor oil, and/or a wax such as bees wax.

[0034] b. Plasticizer

[0035] The plasticizer may comprise glycerol, glycerin, sorbitol, or propylene glycol, or a combination thereof.

[0036] c. Surfactant

[0037] The surfactant may comprise a lecithin, sorbitol, polysorbate, or sorbitan, or a combination thereof.

[0038] d. Solubilizing Agent

[0039] The solubilizing agent may comprise a beeswax or a mono-, di-, or triglyceride, or a combination thereof.

[0040] e. Suspending Agent

[0041] The suspending agent may comprise maltodextrin, sodium alginate, or xanthan gum, or a combination thereof.

[0042] 2. Powder Fill

[0043] The powder fill may comprise the stimulant, a diluent, an anti-caking agent, and a lubricant.

[0044] a. Diluent

[0045] The diluent may comprise dicalcium phosphate, lactose, maltodextrin, microcrystalline cellulose, or a starch, or a combination thereof.

[0046] b. Anti-Caking Agent

[0047] The anti-caking agent may comprise magnesium silicate, silica gel, or talc, or a combination thereof.

[0048] c. Lubricant

[0049] The lubricant may comprise hydrogenated vegetable oil, magnesium stearate, mineral oil, or stearic acid, or a combination thereof.

[0050] 3. Semi-Solid Fill

[0051] The semi-solid fill may comprise the stimulant, a semi-solid vehicle, a surfactant, and an emulsifying agent.

[0052] a. Semi-Solid Vehicle

[0053] The semi-solid vehicle may comprise hydrogenated palm oil, hydrogenated castor oil, cetyl alcohol, cetosteryl alcohol, a stearoyl polyoxylglyceride, a laurolyl polyoxyglyceride, or a combination thereof.

[0054] b. Surfactant

[0055] The surfactant may be a lecithin, sorbitol, polysorbate, or sorbitan, or a combination thereof.

[0056] c. Emulsifying Agent

[0057] The emulsifying agent may be polyethylene glycol, or poloxamer, or a combination thereof.

[0058] 4. Shell

[0059] The shell may comprise a gelling agent, the plasticizer, an opacifier, a colorant, and water.

[0060] a. Gelling Agent

[0061] The gelling agent may comprise gelatin, a plant polysaccharide, a carrageenan, a modified starch, a cellulose or derivative thereof, or a combination of the foregoing. The modified starch may comprise starch hydrolysate. The cellulose derivative may comprise hypromellose or methylcellulose, or a combination thereof.

[0062] b. Opacifier

[0063] The opacifier may comprise titanium dioxide.

[0064] c. Plasticizer

[0065] The plasticizer may comprise glycerol, glycerin, sorbitol, or propylene glycol, or a combination thereof.

[0066] d. Outer Portion or Second Pill

[0067] The first pill or outer portion of a pill may comprise a coating, which may comprise the sedative and/or relaxant.

[0068] (1) Coating

[0069] The coating may comprise the sedative and/or the relaxant, a cellulose or derivative thereof, a polyether, a mineral oil, water, a plant resin or protein, and a surfactant. The polyether may comprise a polyethylene glycol, which may comprise a low molecular weight polyethylene glycol such as a PEG 300-600 or PEG 400, or a high molecular weight polyethylene glycol such as a PEG 4000-10,000, or a combination thereof.

[0070] e. Doses

[0071] The formulation may comprise 50-1000 mg of the stimulant, and more specifically may comprise 200-800, 300-600, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 mg of the stimulant. The formulation may also comprise 0.1-10 mg of the sedative, and more specifically may comprise 0.5-1.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0 mg of the sedative. The formulation may also comprise 0.1-10 mg of the relaxant, and more specifically may comprise 0.5-1.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0 mg of the relaxant.

[0072] If the formulation is a capsule, the capsule may comprise the ingredients listed in Tables 1 and

TABLE-US-00001 EXEMPLARY TABLE 1 Ingredient Amount (mg) Green tea extract 100-1000 Vegetable oil 100-1000 Gelling agent  10-1000 Plasticizer  1-500 Opacifier 0.1-50   Water 0.1-50   Colorant 0-50

TABLE-US-00002 EXEMPLARY TABLE 2 (Table: ‘Redbud Delayed Energy Bulk Capsule’) Ingredients Label Claim NIACINAMIDE (98%), FREE FLOWING 10.00 mg PYRIDOXAL 5 PHOSPHATE 12.50 mg METHYLTETRAHYDROFOLATE 200.00 μg METHYLCOBALAMIN 1% FOOD GRADE 500.00 μg CALCIUM D-PANTOTHENATE (92%) 20.00 mg ALPHA-LIPOIC ACID 15.00 mg CAFFEINE ANHYDROUS (USP) 120.00 mg PROPRIETARY BLEND 500.00 mg GUARANA SEED 22% (CAFFEINE) 170.00 mg L-GLUTAMINE FINE PWD 125.00 mg L-TYROSINE 75.00 mg WHITE WILLOW BARK PWD 55.00 mg DMAE BITARTRATE NAT GRADE 50.00 mg GINKGO LEAVES PWD 25.00 mg EXCIPIENTS QS LONG GRAIN RICE FLOUR MAGNESIUM STEARATE VEG NF SIPERNAT 50S Net Weight: Artificial RED color VCAPS PLUS SIZE 0 30 min DELAYED RELEASE

[0073] And the second pill or, in a single pill formulation the coating, may comprise the ingredients listed in Tables 3 and 4.

TABLE-US-00003 EXEMPLARY TABLE 3 Ingredient Amount (mg) Cellulose derivative 10-200 Polyethylene glycol  1-100 Mineral oil 0.1-10   Sedative 0.1-50   Relaxant 0.1-50  

TABLE-US-00004 EXEMPLARY TABLE 4 (Table: ‘Redbud Sleep Chewable Bulk Tablet’) Ingredients Label Claim Proprietary Blend 200.0 mg GAMMA AMINOBUTYRIC ACID (GABA) 100.0 mg MCT 40% PWD ON ACACIA HIGH FLOW 50% 84.0 mg LEMON BALM LEAVES PWD 10.0 mg LAVENDER FLOWER PWD 1.0 mg VALERIAN ROOT EXT 4:1 1.0 mg L-TRYPTOPHAN GRAN 1.0 mg HOPS FLOWER PWD 1.0 mg PASSION FLOWER PWD 1.0 mg CHAMOMILE FLOWER PE 4:1 1.0 mg Vitamins/Minerals MAGNESIUM CITRATE 30% (MGCI304001) 25.000 mg Other Ingredients SORBITOL GRAN 18-75 MESH PEPPERMINT FLAVOR NAT PWD #2005403 LUO HAN GUO EXTRACT 50% MOGROSIDE V STEARIC ACID NF PWD (TRISTAR NF) MAGNESIUM STEARATE VEG NF Ultramarine Blue E-5100 SIPERNAT 50S

[0074] 5. Method of Nap Promotion

[0075] Provided herein is a method of promoting a nap in a subject. The nap may not induce grogginess. The method may comprise administering a formulation described herein to a subject in need thereof either as one pill or multiple pills

[0076] The present invention has multiple aspects, illustrated by the following non-limiting examples.

Example 1

Oral Capsule for Promoting Naps

[0077] This example describes a formulation of a single pill of Tables 5 and 6 or a coated capsule for promoting naps. The capsule contains the ingredients listed in Table 5 and 6.

TABLE-US-00005 EXEMPLARY TABLE 5 Ingredient Amount (mg) Green tea extract 500 Vegetable oil 300 Gelatin 265 Glycerol 50 Titanium dioxide 10 Purified water 6 Coloring 1

TABLE-US-00006 EXEMPLARY TABLE 6 (Table: ‘Redbud 90 Napjitsu Tincture Pineapple Peach Mango’) Label Claim Ingredients (per serving) PROPRIETARY OIL BLEND 1831 FRACTIONATED COCONUT OIL (MCT OIL) 1801.08 mg Grapefruit Pink 50-6140-02 13.00 mg ORANGE SWEET OIL 50-6200-01 12.00 mg Valerian 50-4739-01 oil 1.00 mg Rosemary Tunisian 50-6230-02 1.00 mg LAV Bulgarian 50-6155-04 Lavender Bulgarian oil 1.00 mg Chamomile Roman 50-6077-04 1.00 mg Lemon Argentina 50-6160-15 1.00 mg Copaiba 50-4237-01 0.01 mg PROPRIETARY BLEND 20.00 GAMMA AMINOBUTYRIC ACID (GABA) 7.00 mg L-THEANINE 7.00 mg L-TYROSINE 3.00 mg ACETYL L-CARNITINE HCL 3.00 mg Other Ingredients LUO HAN GUO EXTRACT 50% MOGROSIDE V ORANGE PINEAPPLE NAT WONF FLAVOR 5418 PDR ALL NAT PEACH TYPE FL #28722 JE45 ALL NAT MANGO TYPE FL #28724 SZ76

[0078] The second pill contains the material of Table 7 or a coating for the pill of Tables 5 or 6, said pill or coating contains the ingredients listed in Table 7.

TABLE-US-00007 TABLE 7 Coating ingredients Ingredient Amount (mg) Hypromellose 52 Polyethylene glycol 400 28 Mineral oil  6 Melatonin  1 Chamomile extract  1

[0079] The formulation is made by mixing green tea extract, vegetable oil, glycerol, and purified water, with heating as necessary, to form a liquid fill solution or uniform suspension. The gelatin is heated to obtain the proper viscosity, and then the titanium oxide and coloring agents are added to form the capsule shell. Additional water is added as needed to obtain the desired viscosity for the shell. The gelatin is then formed into ribbons on encapsulation equipment, and the liquid is encapsulated within the gelatin using Oval No. 12 dies. The resulting softgel capsules are dried at the appropriate temperature and airflow.

[0080] The second pill or coating ingredients from Table 7 are mixed with water and heated as necessary to form a solution. As a coating, the solution is applied to the softgel capsules using a 60″ coating pan operated at the appropriate airflow, input temperature, and exhaust temperature.

Example 2 Core Tablet

[0081] A core tablet comprising guarana extract, lactose, microcrystalline cellulose, sodium starch glycolate, hypromellose, and magnesium stearate, as shown in Table 8, was tested for its caffeine dissolution profile. The results are shown in Table 9.

TABLE-US-00008 TABLE 8 Tablet ingredients Ingredient Amount (mg) Guarana extract 250 Lactose 245 Microcrystalline cellulose 476 Sodium starch glycolate  15 Hypromello se  10 Magnesium stearate   4

TABLE-US-00009 TABLE 9 Tablet dissolution Time (hr) % dissolution 1 34.1 2 50.3 3 67.0

[0082] Because less than 90% of the caffeine was dissolved after 2 hours, this core tablet formulation is not well-suited for use in promoting non-grogginess-inducing naps of short duration.

Example 3 Core Tablet

[0083] A core tablet comprising guarana extract, calcium sulfate, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, polyvinyl pyrrolidone, and sodium starch glycolate, as shown in Table 10, was tested for its caffeine dissolution profile. The results are shown in Table 11.

TABLE-US-00010 TABLE 10 Tablet ingredients Ingredient Amount (mg) Guarana extract 250 Calcium sulfate 200 Croscarmellose sodium  25 Magnesium stearate   1 Microcrystalline cellulose 504 Polyvinyl pyrrolidone  10 Sodium starch glycolate  10

TABLE-US-00011 TABLE 11 Tablet dissolution Time (hr) % dissolution 0.5 31.0 1   57.5 2   87.5

[0084] Because less than 90% of the caffeine was dissolved after 1 hour, the core tablet formulation described is not well-suited in promoting short non-grogginess-inducing naps.

Example 4

[0085] Each participant used a separate relaxing pill. All participants received the relaxing pill and the Nap 30 nootropic pill. Half of all participants were randomly assigned to a comparison group (coffee+placebo pill), while the other half were randomly assigned to a pure placebo group (placebo pill only). The Nap30 relaxant pill contained as described herein. The full study design is shown in the table below.

TABLE-US-00012 Day 1 Day 2 Arm 1 20 Participants Blue pill + Nap 30 pill 10 Placebo pill (Zeebo) + no coffee 10 Placebo + coffee Arm 2 20 Participants 10 Placebo pill (Zeebo) only Blue pill + Nap 30 pill 10 Placebo pill + coffee

[0086] Participants were asked to abstain from coffee for 6 hours prior to the anticipated time of their nap on both study days. Comparison and placebo arms were not instructed to nap on that day.

Results

[0087] Nap 30 performed well across 7 of 8 metrics with self-reported improvement ranging from a low of 8% for mood to a whopping 56% for overall good feelings—defined as the combination of energy, focus, and sharpness.

IMPROVED . . .

[0088] Overall, feeling good (energy, focus, sharpness) increased by 56% [0089] Energy increased by 27% [0090] Memory increased by 21% [0091] Sharpness increased by 16% [0092] Tiredness was reduced by 13% [0093] Focus increased by 13% and 17% at its peak (3 hours later) [0094] Mood increased by 8%

[0095] Compared with the Comparative arm (coffee+placebo) . . .

Nap 30 arm was superior for all of the metrics except for a tie for Mood at 8%.
Below is a comparison of percent change for Nap 30 and the Coffee Comparison arm from baseline to 5 hour follow-up showing unexpected superiority of the formulation: [0096] Overall good feeling (energy, focus, sharpness): Nap 30 improved 56%|Coffee arm worsened −2% [0097] Energy: Nap 30 improved 27%|Coffee arm improved 13% [0098] Memory: Nap 30 improved 21%|Coffee arm improved 5% [0099] Sharpness: Nap 30 improved 16%|Coffee arm improved 82% [0100] Tiredness: Nap 30 improved 13%|Coffee arm worsened 15% [0101] Focus: Nap 30 improved 13%|Coffee arm worsened 2% [0102] Mood: Nap 30 improved 8%|Coffee arm tied at 8% improved

[0103] In general, Nap 30 respondents were significantly more likely to report a steady increase across seven metrics (mean comparisons), peaking at 5 hours—with far greater consistency than the comparison and the placebo arms. Results underscore the nootropic value of Nap 30. In effect, compared with coffee, Nap 30 gives staying power. Asked how satisfied they were with their experience with Nap 30, 92% reported feeling “satisfied”, while a total of 46% of respondents reported feeling “extremely satisfied”. Likelihood of recommendation reached 85% with 39% “extremely likely” to recommended to friends or family Over 90% (92%) of participants said they were likely to purchase with 24% “extremely likely”>. Asked which of 13 possible reasons participants would use Nap 30, “sleeping poorly” and “feeling tired” were affirmed by a majority (over 50%), with “need energy” being affirmed by 46%.

[0104] Taken only once during the 2-day study period, Nap 30 performed very well with respondents indicating a positive gain across all metrics at one or more time-points.

[0105] Data collected over 4 post-baseline intervals (30 minutes to 5 hours post-pill) found the greatest gains were realized at the 5-hour mark in most cases. By comparison, the coffee arm performed next best, but failed to achieve the long-lasting effects of Nap 30; particularly at the 5-hour mark.

[0106] Asked about their experience with Nap 30, participants reports were most favorable with a majority satisfied, likely to recommend to friends/family, and likely to purchase. While the foregoing disclosure discusses illustrative embodiments, it should be noted that various changes and modifications could be made herein without departing from the scope of the described aspects and/or embodiments as defined by the appended claims. Furthermore, although elements of the described aspects and/or embodiments may be described or claimed in the singular, the plural is contemplated unless limitation to the singular is explicitly stated. Additionally, all or a portion of any embodiment may be utilized with all or a portion of any other embodiment, unless stated otherwise.

[0107] While certain exemplary embodiments have been described and shown in the accompanying specification, it is to be understood that such embodiments are merely illustrative of and not restrictive on the broad invention, and that this invention is not be limited to the specific constructions and arrangements shown and described, since various other changes, combinations, omissions, modifications and substitutions, in addition to those set forth in the above paragraphs, are possible. Those skilled in the art will appreciate that various adaptations and modifications of the just described embodiments can be configured without departing from the scope and spirit of the invention. Therefore, it is to be understood that, within the scope of the appended claims, the invention may be practiced other than as specifically described herein.