WO2022051419A1 - Compositions and methods for treating metabolic disruption - Google Patents

Abstract

Compositions with Aloe vera, including Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate, are disclosed herein. Also disclosed are methods of using said compositions for improving metabolic disruption, or diseases or disorders associated thereto, including the healing, treatment, amelioration, or prevention of metabolic disruption, or diseases or disorders associated thereto.

Description

COMPOSITIONS AND METHODS FOR TREATING METABOLIC DISRUPTION

FIELD

[0001] The present disclosure relates generally to the field of metabolic disruption, including methods and compositions for treating metabolic disruption. In particular, the disclosure relates to compositions having Aloe vera or components thereof for treating metabolic disruption.

BACKGROUND

[0002] The worldwide prevalence of diseases associated with metabolic disruption has reached pandemic proportions, bringing with it a host of associated diseases, such as obesity, type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH), and cancer. Despite extensive efforts to address the issue of metabolic disruption, there remains a need in the art for treatments that can address this need in the art.

[0003] The genus Aloe ( Liliaceae ) is a shrubby tropical/subtropical plant, which has succulent and elongated leaves. Of the more than 360 known Aloe species, Aloe barbadensis Miller (Aloe veraLinne ) is the most widely used, both commercially and for its therapeutic properties. Aloe vera plants contain two major juice materials: 1) a yellow exudate containing a high concentration of anthraquinone compounds; and 2) a clear mucilaginous gel.

[0004] Aloe vera has been used as a traditional remedy in various preparations that have been administered orally and topically, among other administrative routes. These preparations have been used in many ways, such as to heal wounds, support digestive health, and for cosmetic purposes.

SUMMARY

[0005] The present disclosure is directed to compositions including Aloe vera for use in treating metabolic disruption and diseases or disorders associated thereto. Also provided herein are methods of making and using the compositions. [0006] Accordingly, some embodiments provided herein relate to compositions for treatment of a subject suffering from metabolic disruption, or a disease or disorder associated thereto or a symptom thereof. In some embodiments, the compositions include Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate. In some embodiments, the compositions include one or more excipients or pharmaceutically acceptable carriers. In some embodiments, the Aloe vera concentrate is pure Aloe vera juice, Aloe vera juice 2X concentrate, Aloe vera juice 25X concentrate, Aloe vera juice 50X concentrate, Aloe vera juice 75X concentrate, Aloe vera juice 100X concentrate, Aloe vera juice 125X concentrate, Aloe vera juice 150X concentrate, Aloe vera juice 175X concentrate, or Aloe vera juice 200X concentrate. In some embodiments, the one or more excipient is a preservative or a flavorant. In some embodiments, the preservative is one or more of sorbic acid, sorbic acid salt, benzoic acid, benzoic acid salt, lactic acid, lactic acid salt, citric acid, citric acid salt, malic acid, malic acid salt, acetic acid, acetic acid salt, tartaric acid, tartaric acid salt, rosemaiy extract, lovage extract, chitosan, sage essential oil, thymol oil nisin, e- polylysine, grape seed extract, goji berry extract or a combination thereof. In some embodiments, the flavorant is one or more of sugar, honey, fructose, dextrose, maltodextrin, gums, natural or artificial flavors, or a combination thereof. In some embodiments, the one or more excipient is cellulose powder, modified starch, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellose, calcium carbonate, dicalcium phosphate, or silicon dioxide. In some embodiments, the Aloe vera juice is liquid juice, juice concentrate, or dry juice concentrate. In some embodiments, the Aloe vera juice comprises not more than about 10 ppm aloin. In some embodiments, the aloe vera juice comprises at least about 5% acetylated acemannan. In some embodiments, the disease or disorder associated with metabolic disruption is acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia- telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund- Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water-electrolyte imbalance. In some embodiments, the composition is formulated as an oral, topical, or injectable formulation. In some embodiments, the composition is formulated as a pharmaceutical composition.

[0007] Some embodiments provided herein relate to methods for relieving, improving, or ameliorating metabolic disruption, or a disease or disorder associated thereto or a symptom thereof, in a subject in need thereof. In some embodiments, the methods include selecting a subject in need thereof and administering a therapeutically effective amount of any of the compositions described herein. In some embodiments, the compositions include Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate. In some embodiments, the composition inhibits pancreatic lipase activity. In some embodiments, the subject suffers from acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia- telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund- Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water-electrolyte imbalance. In some embodiments, the symptom of a metabolic disruption is lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, or abnormal odor of urine, breath, sweat, or saliva.

[0008] In some embodiments, the Aloe vera concentrate is pure Aloe vera juice, Aloe vera juice 2X concentrate, Aloe vera juice 25X concentrate, Aloe vera juice 50X concentrate, Aloe vera juice 75X concentrate, Aloe vera juice 100X concentrate, Aloe vera juice 125X concentrate, Aloe vera juice 150X concentrate, Aloe vera juice 175X concentrate, or Aloe vera juice 200X concentrate. In some embodiments, the composition includes one or more excipient. In some embodiments, the one or more excipient is a preservative or a flavorant. In some embodiments, the preservative is one or more of sorbic acid, sorbic acid salt, benzoic acid, benzoic acid salt, lactic acid, lactic acid salt, citric acid, citric acid salt, malic acid, malic acid salt, acetic acid, acetic acid salt, tartaric acid, tartaric acid salt, rosemary extract, lovage extract, chitosan, sage essential oil, thymol oil nisin, e-polylysine, grape seed extract, goji berry extract or a combination thereof. In some embodiments, the flavorant is one or more of sugar, honey, fructose, dextrose, maltodextrin, gums, natural or artificial flavors, or a combination thereof. In some embodiments, the one or more excipient is cellulose powder, modified starch, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellose, calcium carbonate, dicalcium phosphate, or silicon dioxide. In some embodiments, the Aloe vera juice is liquid juice, juice concentrate, or dry juice concentrate. In some embodiments, the Aloe vera juice comprises not more than about 10 ppm aloin. In some embodiments, the aloe vera juice comprises at least about 5% acetylated acemannan. In some embodiments, the composition is formulated as an oral, topical, or injectable formulation.

[0009] Some embodiments provided herein relate to any of the compositions described herein for use in relieving, improving, or ameliorating a metabolic disruption, or a disease or disorder associated thereto, or a symptom thereof In some embodiments, the disease or disorder associated with metabolic disruption is acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair- deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thom son syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water- electrolyte imbalance. In some embodiments, the the symptom of a metabolic disruption is lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, or abnormal odor of urine, breath, sweat, or saliva.

[0010] Some embodiments provided herein relate to any of the compositions described herein for use as a medicament.

[0011] These features, together with other features herein further explained, will become obvious through a reading of the following description of the drawings and detailed description.

DETAILED DESCRIPTION

[0012] It is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0013] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.

[0014] Metabolic disruption is one of the major health problems around the world. It is well recognized that unbalanced diets are strongly associated with overweight and metabolic disruption development. Various strategies have been employed to reduce diseases or disorders associated with metabolic disruption with varying degrees of success. Such strategies may include, for example, the consumption of food supplements that reduce fat or sugar incorporation in the body. In folk medicine, a variety of herbs have been used for this intent. Traditionally, the ingestion of Aloe vera whole juice including the latex is used as a laxative and to relieve diabetic symptom and lowering cholesterol levels. In the market, Aloe vera juice is purified of latex constituents such as anthroquinones via a charcoal filtration, process known as decolonization. Limited information is available regarding Aloe vera effects after the decolonization process.

Compositions

[0015] Some embodiments provided herein relate to compositions of Aloe vera for treating metabolic disruption, including diseases or disorders associated thereto, or symptoms thereof. In some embodiments, the compositions include whole leaf (WL) Aloe vera, inner leaf (InL) Aloe vera, or combinations thereof. In some embodiments, the compositions having Aloe vera are obtained after a decolonization process. In some embodiments, the Aloe vera component of the composition is an isolated Aloe vera. In some embodiments, the compositions provided herein inhibit pancreatic lipase (PL). In some embodiments, the compositions provided herein inhibit alphaglucosidase (AG).

[0016] As used herein, the term “composition” or “formulation” has its ordinary meaning in light of the specification, and refers to a combination of elements, components, or compositions presented together for a given purpose.

[0017] As used herein, the term “medicament” has its ordinary meaning as understood in light of the specification, and refers to a substance or composition used in a therapy, for example in the treatment of a disease or disorder.

[0018] The term “isolated” is meant material that is substantially or essentially free from components that normally accompany it in its native state. For example, an “isolated Aloe vera,” as used herein, includes Aloe vera that has been purified from its naturally-occurring state, e.g., Aloe vera that has been removed from the plant material in which it naturally resides.

[0019] The compositions provided herein may further included suitable pharmaceutically acceptable carriers, stabilizers, diluents, buffers, or components for application, storage, bioavailability, solubility, or other component parts that improve the efficacy, aesthetics, or other properties of the compositions.

[0020] “Pharmaceutically acceptable” carriers are ones which are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. “Pharmaceutically acceptable” carriers can be, but not limited to, organic or inorganic, solid or liquid excipients which is suitable for the selected mode of application such as topical, oral, or intravenous application, and administered in the form of a conventional pharmaceutical preparation, such as solid such as tablets, granules, powders, capsules, caplets, and liquid such as solution, spray, emulsion, foam, suspension, cream, lotion, ointment, salve, gel, and the like. Often the physiologically acceptable carrier is an aqueous pH buffered solution such as phosphate buffer or citrate buffer. The physiologically acceptable carrier may also include, for example, one or more of the following: antioxidants including ascorbic acid, low molecular weight (less than about 10 residues) polypeptides, proteins, such as serum albumin, gelatin, immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone, amino acids, carbohydrates including glucose, mannose, or dextrine, chelating agents such as EDTA, sugar alcohols such as mannitol or sorbitol, salt-forming counter ions such as sodium, and nonionic surfactants such as Tween™, polyethylene glycol (PEG), and Pluronics™. Auxiliary, stabilizer, emulsifier, lubricant, binder, pH adjustor controller, isotonic agent, and other conventional additives may also be added to the carriers.

[0021] The pharmaceutically acceptable or appropriate carrier may include other compounds known to be beneficial to a metabolic disruption, or a disease or disorder associated thereto (e.g., antioxidants, such as Vitamin C, Vitamin E, Selenium or Zinc), or a food composition. The food composition can be, but is not limited to, milk, yogurt, curd, cheese, fermented milks, milk based fermented products, ice-creams, fermented cereal based products, milk based powders, infant formulae, tablets, liquid bacterial suspensions, dried oral supplement, or wet oral supplement.

[0022] As described herein, the composition including Aloe vera can be a topical formulation. The topical formulation can further include, for example, a pharmaceutical vehicle that does not interfere with the function and viability of the Aloe vera. The “pharmaceutical vehicle” as described herein refers to an inert substance with which a medication is mixed to facilitate measurement and administration of the topical formulation.

[0023] In some embodiments, the active ingredients and mixtures of active ingredients can be used, for example, in topical formulations including a pharmaceutically acceptable carrier prepared for storage and subsequent administration. As used herein, “topical” refers to the administration or application of a formulation to the skin or various body orifices. Some embodiments include use of compositions described herein in combination with a pharmaceutically acceptable carrier or diluent. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington’s Pharmaceutical Sciences, 18th Ed., Mack Publishing Co., Easton, Pa. (1990), which is incorporated herein by reference in its entirety. Preservatives and stabilizers can be provided in the topical formulation. Preservatives can be used to keep the nutrients for the skin cells from breaking down. As used herein, the terms “carrier or diluent” may be a solid carrier or diluent for solid formulations, a liquid carrier or diluent for liquid formulations, or mixtures thereof. Solid carriers/diluents include, but are not limited to, a gum, a starch (e.g., cornstarch, pregeletanized starch), a sugar (e.g., lactose, mannitol, sucrose, dextrose), a cellulosic material (e.g., microcrystalline cellulose), an acrylate (e.g., polymethylacrylate), calcium carbonate, magnesium oxide, talc, or mixtures thereof. For liquid formulations, such as for topical or parenteral formulations, pharmaceutically acceptable carriers may be aqueous or non-aqueous solutions, suspensions, emulsions or oils. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Examples of oils are those of petroleum, animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, mineral oil, olive oil, sunflower oil, and fish-liver oil.

[0024] Parenteral vehicles (for subcutaneous, intravenous, intraarterial, or intramuscular injection) include sodium chloride solution, Ringer’s dextrose, dextrose and sodium chloride, lactated Ringer’s and fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishes such as those based on Ringer’s dextrose, and the like. Examples are sterile liquids such as water and oils, with or without the addition of a surfactant and other pharmaceutically acceptable adjuvants. In general, water, saline, aqueous dextrose and related sugar solutions, and glycols such as propylene glycols or polyethylene glycol are preferred liquid carriers, particularly for injectable solutions. Examples of oils are those of petroleum, animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, mineral oil, olive oil, sunflower oil, and fish-liver oil.

[0025] In addition, the compositions may further comprise binders (e.g. acacia, cornstarch, gelatin, carbomer, ethyl cellulose, guar gum, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone), disintegrating agents (e.g. cornstarch, potato starch, alginic acid, silicon dioxide, croscarmelose sodium, crospovidone, guar gum, sodium starch glycolate), buffers (e.g., Tris-HCI, acetate, phosphate) of various pH and ionic strength, additives such as albumin or gelatin to prevent absorption to surfaces, detergents (e.g., Tween 20, Tween 80, Pluronic F68, bile acid salts), protease inhibitors, surfactants (e.g. sodium lauryl sulfate), permeation enhancers, solubilizing agents (e.g., glycerol, polyethylene glycerol), anti-oxidants (e.g., ascorbic acid, sodium metabisulfite, butylated hydroxyanisole), stabilizers (e.g. hydroxypropyl cellulose, hyroxypropylmethyl cellulose), viscosity increasing agents (e.g. carbomer, colloidal silicon dioxide, ethyl cellulose, guar gum), sweeteners (e.g. aspartame, citric acid), preservatives (e.g., Thimerosal, benzyl alcohol, parabens), lubricants (e.g. stearic acid, magnesium stearate, polyethylene glycol, sodium lauryl sulfate), flow-aids (e.g. colloidal silicon dioxide), plasticizers (e.g. diethyl phthalate, triethyl citrate), emulsifiers (e.g. carbomer, hydroxypropyl cellulose, sodium lauryl sulfate), polymer coatings (e.g., poloxamers or poloxamines), coating and film forming agents (e.g. ethyl cellulose, acrylates, polymethacrylates) and/or adjuvants.

[0026] Topical formulations including Aloe vera can be formulated and used as a solution, spray, emulsion, foam, suspension, cream, lotion, ointment, salve, or gel for topical application. Suitable ingredients in the topical formulation can include a for example, water, saline, dextrose, mannitol, lactose, lecithin, albumin, or sodium glutamate, and the like. If desired, absorption enhancing preparations (for example, liposomes), can be utilized.

[0027] As used herein, the term “injectable composition” refers to a formulation that is prepared for administration by injection. These injections may be administered by such routes as intravenous, subcutaneous, intradermal, intramuscular, intraarticular, or intrathecal.

[0028] In some embodiments, the pharmaceutical vehicle is soybean, grapefruit or almond oils, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes.

[0029] Coconut oil, olive oil, sesame oil, peanut oil, and soya can be used as suspension agents or lubricants in the topical formulation.

[0030] The topical formulation including Aloe vera can further include, for example, one or more solvents, at least one botanical, and/or at least one emollient.

Methods of Treating Metabolic Disruption

[0031] Embodiments provided herein relate to methods of administering the compositions provided herein for treating metabolic disruption. In some embodiments, the methods include administering a composition including Aloe vera to a subject in need thereof. In some embodiments, the methods include identifying a subject in need. Identifying a subject in need includes identifying a subject having metabolic disruption, or a disease or disorder associated thereto.

[0032] Metabolism is a process that the body uses to obtain or make energy from the food or nutrients that are ingested by a subject. The proteins, carbohydrates, and fats from foods break down in the digestive system into sugars and acids to generate fuel for the body. A disruption of this process is referred to herein as “metabolic disruption.” Metabolic disruption results in excessive or insufficient food parts that are needed to maintain healthy levels. Metabolic disruption can result from various sources, including for example, from genetic propensity, from organ malfunction, including liver or pancreas malfunction as a result of disease state.

[0033] Disorders or diseases associated with metabolic disruption include, for example, acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water-electrolyte imbalance. In some embodiments, a subject is selected having any one or more of the exemplary diseases or disorders associated with metabolic disruption.

[0034] In some embodiments, administering the compositions to a subject treats metabolic disruption, or a disease or disorder associated with metabolic disruption. In some embodiments, administering the compositions to the subject prevents development or start of a metabolic disruption. In some embodiments, administering the compositions provided herein inhibits pancreatic lipase (PL). In some embodiments, administering the compositions provided herein inhibits alphaglucosidase (AG).

[0035] Pancreatic lipase (PL) refers to an enzyme secreted from the pancreas that hydrolyzes dietary fat molecules in the human digestive system, converting triglyceride substrates to monoglycerides and free fatty acids. In some embodiments, inhibition of PL using the compositions provided herein reduces, prevents, alleviates, treats, or otherwise is useful in the maintenance of metabolic disruption, or diseases or disorders associated thereto. Alphaglucosidase (AG) refers to an enzyme that breaks down starch and disaccharides to glucose. In some embodiments, inhibition of AG using the compositions provided herein reduces, prevents, alleviates, treats, or otherwise is useful in the maintenance of metabolic disruption, or diseases or disorders associated thereto.

[0036] As used herein, the term “treatment” refers to an intervention made in response to a disease, disorder, or physiological condition manifested by a subject, particularly a subject suffering from metabolic disruption. The aim of treatment may include, but is not limited to, one or more of the alleviation or prevention of symptoms, slowing or stopping the metabolic disruption, or disease or disorder associated thereto, or the remission of the metabolic disruption, or disease or disorder associated thereto. In some embodiments, “treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already affected by a disease or disorder or undesired physiological condition as well as those in which the disease or disorder or undesired physiological condition is to be prevented. For example, in some embodiments, treatments reduce, alleviate, or eradicate the symptom(s) of the disease(s).

[0037] As used herein, the term “prevention” refers to any activity that reduces the burden of the individual later expressing disease symptoms. This can take place at primary, secondary, and/or tertiary prevention levels, wherein: a) primary prevention avoids the development of symptoms/disorder/condition; b) secondary prevention activities are aimed at early stages of the condition/disorder/symptom treatment, thereby increasing opportunities for interventions to prevent progression of the condition/disorder/symptom and emergence of symptoms; and c) tertiary prevention reduces the negative impact of an already established condition/disorder/symptom by, for example, restoring function and/or reducing any condition/disorder/symptom or related complications. [0038] Symptoms of metabolic disease, disorder, or disruption may include, for example, lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, and/or abnormal odor of urine, breath, sweat, saliva, or other bodily fluid or excretion.

[0039] The term “modulating” includes “increasing” or “stimulating,” as well as “decreasing” or “reducing,” typically in a statistically significant or a physiologically significant amount as compared to a control. An “increased” or “enhanced” amount is typically a “statistically significant” amount, and may include an increase that is 1.1, 1.2, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, or more times (e.g., 500, 1000 times) (including all integers and decimal points in between and above 1, e.g., 1.5, 1.6, 1.7, 1.8, etc.) the amount produced by no composition (the absence of an agent or compound) or a control composition. A “decreased” or reduced amount is typically a “statistically significant” amount, and may include a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18% , 19%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% decrease in the amount produced by no composition (the absence of an agent or compound) or a control composition, including all integers in between. As one non-limiting example, a control in comparing canonical and non-canonical activities could include the activity (e.g., antagonist activity) or of a formulation composition, such as, for example, Aloe vera, towards metabolic disruption relative to no treatment, a placebo treatment, or a control treatment. Other examples of “statistically significant” amounts are described herein.

[0040] A “subject,” as used herein, includes any animal that exhibits a symptom, or is at risk for exhibiting a symptom, of one or more metabolic disruption, or disease or disorder associated thereto. Suitable subjects (patients) include laboratory animals (such as mouse, rat, rabbit, or guinea pig), farm animals, and domestic animals or pets (such as a cat or dog). Non-human primates and, preferably, human patients, are included.

[0041] As used herein, the term “therapeutically effective amount” means on amount of a composition comprising Aloe vera which is capable of alleviating, relieving, preventing, ameliorating, or eliminating metabolic disruption, or disease or disorder associated thereto for which administration of the composition is indicated. In some embodiments, a therapeutically effective amount includes administration of an amount of Aloe vera ranging from about 0.01 mg/kg to about 200 mg/ kg, such as 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 10, 20, 30, 40, 5060, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 mg/kg or an amount within a range defined by any two of the aforementioned amounts. In some embodiments, the composition is formulated having an amount of Aloe vera ranging from about 0.001 to about 50 μg/mL, such as 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 pg/mL, or an amount within a range defined by any two of the aforementioned values.

[0042] In some embodiments, the treatment alleviates or relieves metabolic disruption, or disease or disorder associated thereto, or a symptom thereof. As described herein, the term “alleviate” or “relieve” refers to an improvement in the metabolic disruption, or disease or disorder associated thereto. In some embodiments, an improvement includes an enhancement of the visual and/or sensory aspects of the metabolic disruption, or disease or disorder associated thereto, improved well-being, improved physical state, or improved physiological state.

[0043] In some embodiments, the topical formulation can include at least one thickener, at least one humectant, and/or at least one preservative. Thickeners can include, for example, triglycerides, palmitates, myristates, stearates, polyethylene glycol, vegetable- based fatty alcohols, copolymers, cellulose gum, or xanthan gum. Humectants can be used for their moisturizing capabilities. Without being limiting, humectants can include but are not limited to sodium PCA, nanolipid gels, glycerin, alpha-hydroxy acid, butylene glycol, propylene glycol, hexylene glycol, sorbitol, hyaluronic acid, urea, glyceiyl triacetate, neoagarobiose, glycerol, xylitol, maltitol, polymeric polyols, polydextrose, quillaia, MP diol, seaweed and algae extracts, and lactic acid.

[0044] In some embodiments, the topical formulation further includes at least one preservative. Without being limiting, preservatives can include benzoin resin, jojoba, vitamin E, alcohol, phenoxytthanol, methylparaben, propylparaben, diazolidinyl urea, sorbic acid, and triclosan. In some embodiments, the at least one preservative is benzoin resin, jojoba, vitamin E, alcohol, phenoxy ethanol, methylparaben, propylparaben, diazolidinyl urea, sorbic acid, and/or triclosan.

[0045] A patient suffering from metabolic disruption, or disease or disorder associated thereto, or a symptom thereof, can be treated with the compositions described herein having Aloe vera, alone or in combination with other therapies known to treat metabolic disruption, or disease or disorder associated thereto. As used herein, “therapy” includes but is not limited to a known drug or treatment. In addition, the compositions described herein can be combined with a drug associated with an undesirable side effect.

[0046] In some embodiments are provided methods of treating a patient diagnosed with metabolic disruption, or disease or disorder associated thereto or presenting with metabolic disruption, or disease or disorder associated thereto, or having a symptom thereof, with a therapeutically effective amount of a composition comprising Aloe vera, including administering said composition to said patient such that the metabolic disruption, or disease or disorder associated thereto is ameliorated or reduced. Embodiments include methods of treating a patient diagnosed with metabolic disruption, or disease or disorder associated thereto or presenting with metabolic disruption, or disease or disorder associated thereto with a therapeutically effective amount of the composition, including administering said composition to said patient such that the symptoms of the metabolic disruption, or disease or disorder associated thereto are reduced or inhibited. In one embodiment, the composition functions by accelerating healing functions, including inhibiting PL and/or AG.

[0047] In some embodiments is provided methods of treating metabolic disruption, or disease or disorder associated thereto, or a symptom thereof with a composition comprising Aloe vera as described herein, alone, in combination with metabolic disruption treatments or therapies known in the art.

Pharmaceutical Formulations

[0048] The pharmaceutical compositions of the present disclosure may include an effective amount of Aloe vera in combination with a pharmaceutically acceptable carrier. The compositions may further include other known drugs suitable for the treatment of metabolic disruption, or disease or disorder associated thereto. An effective amount of Aloe vera of the present disclosure is an amount that ameliorates the disorder, or which causes the acceleration of the healing process, compared to that which would occur in the absence of the composition comprising Aloe vera. The effective amount (and the manner of administration) will be determined on an individual basis and will be based on a consideration of the subject (size, age, general health), the severity of the condition being treated, the severity of the symptoms to be treated, the result sought, the specific carrier or pharmaceutical formulation being used, the route of administration, and other factors as would be apparent to those skilled in the art. The effective amount can be determined by one of ordinary skill in the art using techniques as are known in the art. Therapeutically effective amounts of the compounds described herein can be determined using in vitro tests, animal models, or other dose-response studies, as are known in the art. The composition comprising Aloe vera of the present disclosure can be used alone or in conjunction with other therapies. The therapeutically effective amount may be reduced when the composition is used in conjunction with another therapy.

[0049] The pharmaceutical compositions of the disclosure may be prepared, packaged, or sold in formulations suitable for intradermal, intravenous, subcutaneous, oral, rectal, vaginal, parenteral, intraperitoneal, topical, pulmonary, intranasal, buccal, ophthalmic, intrathecal, epidural, or another route of administration. The compounds may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal, and intestinal mucosa, etc.), and may be administered together with other biologically active agents. Administration can be systemic or local. For example, the pharmaceutical compositions of the disclosure can be administered locally to a tumor via microinfusion. Further, administration may be by a single dose or a series of doses.

[0050] The present disclosure thus also provides pharmaceutical compositions suitable for administration to a subject. The carrier can be a liquid, so that the composition is adapted for parenteral administration, or can be solid, i.e., a tablet or pill formulated for oral administration. Further, the carrier can be in the form of a nebulizable liquid or solid so that the composition is adapted for inhalation. When administered parenterally, the composition should be pyrogen free and in an acceptable parenteral carrier. Active compounds can alternatively be formulated or encapsulated in liposomes, using known methods. Other contemplated formulations include projected nanoparticles and immunologically based formulations.

[0051] Liposomes are completely closed lipid bilayer membranes that contain entrapped aqueous volume. Liposomes are vesicles that may be unilamellar (single membrane) or multilamellar (onion-like structures characterized by multiple membrane bilayers, each separated from the next by an aqueous layer). The bilayer is composed of two lipid monolayers having a hydrophobic “tail” region and a hydrophilic “head” region. In the membrane bilayer, the hydrophobic (nonpolar) “tails” of the lipid monolayers orient toward the center of the bilayer, whereas the hydrophilic (polar) “heads” orient toward the aqueous phase.

[0052] Some embodiments are exemplified in the following enumerated alternatives:

[0053] 1. A composition for treatment of a subject suffering from metabolic disruption, or a disease or disorder associated thereto or a symptom thereof, comprising Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate and one or more excipients.

[0054] 2. The composition of alternative 1, wherein the Aloe vera concentrate is pure Aloe vera juice, Aloe vera juice 2X concentrate, Aloe vera juice 25 X concentrate, Aloe vera juice 50X concentrate, Aloe vera juice 75X concentrate, Aloe vera juice 100X concentrate, Aloe vera juice 125X concentrate, Aloe vera juice 150X concentrate, Aloe vera juice 175X concentrate, or Aloe vera juice 200X concentrate.

[0055] 3. The composition of any one of alternatives 1-2, wherein the one or more excipient is a preservative or a flavorant.

[0056] 4. The composition of alternative 3, wherein the preservative is one or more of sorbic acid, sorbic acid salt, benzoic acid, benzoic acid salt, lactic acid, lactic acid salt, citric acid, citric acid salt, malic acid, malic acid salt, acetic acid, acetic acid salt, tartaric acid, tartaric acid salt, rosemary extract, lovage extract, chitosan, sage essential oil, thymol oil nisin, e-polylysine, grape seed extract, goji berry extract or a combination thereof.

[0057] 5. The composition any one of alternatives 3-4, wherein the flavorant is one or more of sugar, honey, fructose, dextrose, maltodextrin, gums, natural or artificial flavors, or a combination thereof.

[0058] 6. The composition of any one of alternatives 1-5, wherein the one or more excipient is cellulose powder, modified starch, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellose, calcium carbonate, dicalcium phosphate, or silicon dioxide.

[0059] 7. The composition of any one of alteratives 1-6, wherein the Aloe vera juice is liquid juice, juice concentrate, or dry juice concentrate. [0060] 8. The composition of any one of alternatives 1-7, wherein the Aloe vera juice comprises not more than about 10 ppm aloin.

[0061] 9. The composition of any one of alternatives 1-8, wherein the aloe vera juice comprises at least about 5% acetylated acemannan.

[0062] 10. The composition of any one of alternatives 1-9, wherein the disease or disorder associated with metabolic disruption is acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair- deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water- electrolyte imbalance.

[0063] 11. The composition of any one of alteratives 1-10, wherein the composition is formulated as an oral, topical, or injectable formulation.

[0064] 12. The composition of any one of alteratives 1-11, wherein the composition is formulated as a pharmaceutical composition.

[0065] 13. A method for relieving, improving, or ameliorating metabolic disruption, or a disease or disorder associated thereto or a symptom thereof, in a subject in need thereof, comprising: selecting a subject in need thereof; and administering a therapeutically effective amount of a composition comprising Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate.

[0066] 14. The method of alternative 13, wherein the composition inhibits pancreatic lipase activity.

[0067] 15. The method of any one of alteratives 13-14, wherein the subject suffers from acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water-electrolyte imbalance.

[0068] 16. The method of any one of alternatives 13-15, wherein the symptom of a metabolic disruption is lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, or abnormal odor of urine, breath, sweat, or saliva.

[0069] 17. The method of any one of alternatives 13-16, wherein the Aloe vera concentrate is pure Aloe vera juice, Aloe vera juice 2X concentrate, Aloe vera juice 25X concentrate, Aloe vera juice 5 OX concentrate, Aloe vera juice 75X concentrate, Aloe vera juice 100X concentrate, Aloe vera juice 125X concentrate, Aloe vera juice 150X concentrate, Aloe vera juice 175X concentrate, or Aloe vera juice 200X concentrate.

[0070] 18. The method of any one of alternatives 13-17, wherein the composition comprises one or more excipient.

[0071] 19. The method of alternative 18, wherein the one or more excipient is a preservative or a flavorant.

[0072] 20. The method of alternative 19, wherein the preservative is one or more of sorbic acid, sorbic acid salt, benzoic acid, benzoic acid salt, lactic acid, lactic acid salt, citric acid, citric acid salt, malic acid, malic acid salt, acetic acid, acetic acid salt, tartaric acid, tartaric acid salt, rosemary extract, lovage extract, chitosan, sage essential oil, thymol oil nisin, e-polylysine, grape seed extract, goji berry extract or a combination thereof.

[0073] 21. The method of any one of alternatives 19-20, wherein the flavorant is one or more of sugar, honey, fructose, dextrose, maltodextrin, gums, natural or artificial flavors, or a combination thereof. [0074] 22. The method of any one of alteratives 18-21, wherein the one or more excipient is cellulose powder, modified starch, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellose, calcium carbonate, dicalcium phosphate, or silicon dioxide.

[0075] 23. The method of any one of alternatives 13-22, wherein the Aloe vera juice is liquid juice, juice concentrate, or dry juice concentrate.

[0076] 24. The method of any one of alternatives 13-23, wherein the Aloe vera juice comprises not more than about 10 ppm aloin.

[0077] 25. The method of any one of alternatives 13-24, wherein the aloe vera juice comprises at least about 5% acetylated acemannan.

[0078] 26. The method of any one of alternatives 13-25, wherein the composition is formulated as an oral, topical, or injectable formulation.

[0079] 27. The composition of any one of alternatives 1-12 for use in relieving, improving, or ameliorating a metabolic disruption, or a disease or disorder associated thereto, or a symptom thereof.

[0080] 28. The composition for use of alternative 27, wherein the disease or disorder associated with metabolic disruption is acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair- deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water- electrolyte imbalance.

[0081] 29. The composition for use of any one of alternatives 27-28, wherein the symptom of a metabolic disruption is lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, or abnormal odor of urine, breath, sweat, or saliva.

[0082] 30. The composition of any one of alternatives 1-12 for use as a medicament.

Examples

[0083] Some aspects of the embodiments discussed above are disclosed in further detail in the following examples, which are not in any way intended to limit the scope of the present disclosure. Those in the art will appreciate that many other embodiments also fall within the scope of the invention, as it is described herein above and in the claims.

Example 1

Aloe Vera Compositions

[0084] This example demonstrates various Aloe vera compositions and formulations.

[0085] Aloe vera whole leaf juice or Aloe vera diy whole leaf juice powder was manufactured as follows: mature leafs were harvested and transported to a processing plant within 24 hours of harvest. Leaves were washed and sanitized with chlorinated water. The tip and butt of a leaf were mechanically removed. The rest of leaf went through a grinder and then into a processing tank. At ambient temperature to 60°C, 0 to 500 g of enzyme was added into the tank. After removing cellulose material, the temperature of the juice was raised to 95°C. The juice was passed through an activated charcoal column to remove aloin to no more than 0.1 ppm. The juice was further concentrated via vacuum evaporation to aloe vera juice concentrate.

[0086] Several chemical differences were observed between different Aloe vera extract preparations based on either inner leaf (InL) or whole leaf (WL) extracts. Notable differences in major minerals (16.8% InL to 19.3% DL), organic acids (38.1% InL to 52.6% DW) and major oligosaccharides (23.8% InL to 7.3% DL) content was observed.

[0087] Preparations were obtained using either InL or WL extracts, or combinations thereof, with content of Aloe vera in amounts ranging from 0 (control) to 5 mg/mL. Example 2

Enzyme Inhibition using the Aloe Vera Compositions

[0088] This example demonstrates the inhibitory effects of Aloe vera compositions on enzymes associated with metabolic disruption.

[0089] The compositions of Example 1 were used to determine the efficacy in inhibiting enzymatic function of pancreatic lipase (PL) and alphaglucosidase (AG).

[0090] Twenty different preparations of Aloe vera (WL or InL) after the decolorization process were evaluated in terms of: a) chemical composition; b) in vitro inhibition of PL; and c) in vitro inhibition of AG, as shown in Table 1. Several chemical differences were found among the InL and WL preparations, notably in mineral (16.8% InL to 19.3% WL), organic acid (38.1% InL to 52.6% DW) and major oligosaccharide (23.8% InL to 7.3% WL) content. InL were effective as in vitro PL inhibitors, showing an inhibitory rate up to 25%. The does response of the compositions in terms of PL inhibition is shown in Table 2. One type of WL extract shown inhibitory activity. IC50 of the preparations were between 1.9-5.1 mg/mL. None of the samples produced a statistically significant inhibition in AG activity under the experimental conditions used.

[0091] This is the first report that shown that decolorized Aloe vera leaf preparation showed strong inhibitory PL activity, and this could be related to the presence of a unique blend of polysaccharides.

Table 1: Effects of extracts on PL activity at a fixed concentration (2 mg/mL)

Table 2: Effects on PL activity: Dose-response of selected samples

Example 3

Aloe vera Compositions for Treating Metabolic Disruption [0092] This example demonstrates the treatment of metabolic disruption using the compositions provided herein.

[0093] The composition of Example 1 is administered to a subject suffering from a metabolic disruption. Administration of the composition improves the metabolic disruption, or a disease or disorder associated thereto. [0094] In at least some of the previously described embodiments, one or more elements used in an embodiment can interchangeably be used in another embodiment unless such a replacement is not technically feasible. It will be appreciated by those skilled in the art that various other omissions, additions and modifications may be made to the methods and structures described above without departing from the scope of the claimed subject matter. All such modifications and changes are intended to fall within the scope of the subject matter, as defined by the appended claims.

[0095] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. All patents, applications, published applications and other publications referenced herein are expressly incorporated by reference in their entireties unless stated otherwise. For purposes of the present disclosure, the following terms are defined below.

[0096] By “about” is meant a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much as 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.

[0097] Throughout this specification, unless the context requires otherwise, the words “comprise, " " comprises,” and “comprising” will be understood to imply the inclusion of a stated step or element or group of steps or elements but not the exclusion of any other step or element or group of steps or elements.

[0098] By “consisting of’ is meant including, and limited to, whatever follows the phrase “consisting of.” Thus, the phrase “consisting of’ indicates that the listed elements are required or mandatory, and that no other elements may be present. By “consisting essentially of’ is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of’ indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they materially affect the activity or action of the listed elements. [0099] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.

[0100] It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “ a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.)· It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

[0101] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0102] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non- limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into sub-ranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 articles refers to groups having 1, 2, or 3 articles. Similarly, a group having 1-5 articles refers to groups having 1, 2, 3, 4, or 5 articles, and so forth.

[0103] While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims.

Claims

WHAT IS CLAIMED IS:

1. A composition for treatinent of a subject suffering from metabolic disruption, or a disease or disorder associated thereto or a symptom thereof, comprising Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate and one or more excipients.

2. The composition of claim 1, wherein the Aloe vera concentrate is pure Aloe vera juice, Aloe vera juice 2X concentrate, Aloe vera juice 25X concentrate, Aloe vera juice 50X concentrate, Aloe vera juice 75X concentrate, Aloe vera juice 100X concentrate, Aloe vera juice 125X concentrate, Aloe vera juice 150X concentrate, Aloe vera juice 175X concentrate, or Aloe vera juice 200X concentrate.

3. The composition of any one of claims 1-2, wherein the one or more excipient is a preservative or a flavorant.

4. The composition of claim 3, wherein the preservative is one or more of sorbic acid, sorbic acid salt, benzoic acid, benzoic acid salt, lactic acid, lactic acid salt, citric acid, citric acid salt, malic acid, malic acid salt, acetic acid, acetic acid salt, tartaric acid, tartaric acid salt, rosemary extract, lovage extract, chitosan, sage essential oil, thymol oil nisin, e- polylysine, grape seed extract, goji berry extract or a combination thereof.

5. The composition any one of claims 3-4, wherein the flavorant is one or more of sugar, honey, fructose, dextrose, maltodextrin, gums, natural or artificial flavors, or a combination thereof.

6. The composition of any one of claims 1-5, wherein the one or more excipient is cellulose powder, modified starch, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellose, calcium carbonate, dicalcium phosphate, or silicon dioxide.

7. The composition of any one of claims 1-6, wherein the Aloe vera juice is liquid juice, juice concentrate, or dry juice concentrate.

8. The composition of any one of claims 1-7, wherein the Aloe vera juice comprises not more than about 10 ppm aloin.

9. The composition of any one of claims 1-8, wherein the aloe vera juice comprises at least about 5% acetylated acemannan.

10. The composition of any one of claims 1-9, wherein the disease or disorder associated with metabolic disruption is acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water- electrolyte imbalance.

11. The composition of any one of claims 1-10, wherein the composition is formulated as an oral, topical, or injectable formulation.

12. The composition of any one of claims 1-11, wherein the composition is formulated as a pharmaceutical composition.

13. A method for relieving, improving, or ameliorating metabolic disruption, or a disease or disorder associated thereto or a symptom thereof, in a subject in need thereof, comprising: selecting a subject in need thereof; and administering a therapeutically effective amount of a composition comprising Aloe vera extract, decolorized Aloe vera juice, or Aloe vera concentrate.

14. The method of claim 13, wherein the composition inhibits pancreatic lipase activity.

15. The method of any one of claims 13-14, wherein the subject suffers from acid- base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water-electrolyte imbalance.

16. The method of any one of claims 13-15, wherein the symptom of a metabolic disruption is lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, or abnormal odor of urine, breath, sweat, or saliva.

17. The method of any one of claims 13-16, wherein the Aloe vera concentrate is pure Aloe vera juice, Aloe vera juice 2X concentrate, Aloe vera juice 25X concentrate, Aloe vera juice 50X concentrate, Aloe vera juice 75X concentrate, Aloe vera juice 100X concentrate, Aloe vera juice 125X concentrate, Aloe vera juice 150X concentrate, Aloe vera juice 175X concentrate, or Aloe vera juice 200X concentrate.

18. The method of any one of claims 13-17, wherein the composition comprises one or more excipient.

19. The method of claim 18, wherein the one or more excipient is a preservative or a flavorant.

20. The method of claim 19, wherein the preservative is one or more of sorbic acid, sorbic acid salt, benzoic acid, benzoic acid salt, lactic acid, lactic acid salt, citric acid, citric acid salt, malic acid, malic acid salt, acetic acid, acetic acid salt, tartaric acid, tartaric acid salt, rosemary extract, lovage extract, chitosan, sage essential oil, thymol oil nisin, e- polylysine, grape seed extract, goji berry extract or a combination thereof.

21. The method of any one of claims 19-20, wherein the flavorant is one or more of sugar, honey, fructose, dextrose, maltodextrin, gums, natural or artificial flavors, or a combination thereof.

22. The method of any one of claims 18-21, wherein the one or more excipient is cellulose powder, modified starch, microcrystalline cellulose, magnesium stearate, stearic acid, sodium croscarmellose, calcium carbonate, dicalcium phosphate, or silicon dioxide.

23. The method of any one of claims 13-22, wherein the Aloe vera juice is liquid juice, juice concentrate, or dry juice concentrate.

24. The method of any one of claims 13-23, wherein the Aloe vera juice comprises not more than about 10 ppm aloin.

25. The method of any one of claims 13-24, wherein the aloe vera juice comprises at least about 5% acetylated acemannan.

26. The method of any one of claims 13-25, wherein the composition is formulated as an oral, topical, or injectable formulation.

27. The composition of any one of claims 1-12 for use in relieving, improving, or ameliorating a metabolic disruption, or a disease or disorder associated thereto, or a symptom thereof.

28. The composition for use of claim 27, wherein the disease or disorder associated with metabolic disruption is acid-base imbalance, metabolic brain diseases, disorders of calcium metabolism, hypocalcemia, hypercalcemia, DNA repair-deficiency disorders, ataxia-telangiectasia, Bloom syndrome, Cockayne syndrome, Fanconi anemia, Progeria, Rothmund-Thomson syndrome, trichothiodystrophy, Werner syndrome, xeroderma pigmentosum, glucose metabolism disorders, diabetes, lactose intolerance, fructose malabsorption, galactosemia, glycogen storage disease, hyperlactatemia, iron metabolism disorders, lipid metabolism disorders, Gaucher’s disease, Niemann-Pick disease, Tay-Sachs disease, Fabry’s disease, sitosterolemia, Wolman’s disease, Refsum’s disease, cerebrotendinous xanthomatosis, malabsorption syndromes, obesity, metabolic syndrome X, inborn error of metabolism, mitochondrial diseases, phosphorus metabolism disorders, porphyrias, proteostasis deficiencies, metabolic skin diseases, wasting syndrome, or water- electrolyte imbalance.

29. The composition for use of any one of claims 27-28, wherein the symptom of a metabolic disruption is lethargy, poor appetite, abdominal pain, vomiting, weight loss, jaundice, failure to gain weight, failure to grow, developmental delay, seizures, coma, or abnormal odor of urine, breath, sweat, or saliva.

30. The composition of any one of claims 1-12 for use as a medicament.