Liquids rich in noble gas and methods of their preparation and use

Abstract

Provided herein is a novel composition for oral administration and delivery of Noble gas, such as xenon or argon. Methods of treating and preventing neuronal or cardiovascular damage with such compositions are also provided. The present invention relates generally to the fields of molecular biology, medicine and nutraceuticals. More particularly, it concerns methods for oral delivery of inert gas compositions, such as Xenon or Argon, for the treatment and prevention of disease.

What is claimed is: 
     
         1 . A nutraceutical composition comprising:
 (i) a substantially aqueous component comprising a dissolved Noble gas, a portion of the Noble gas being encapsulated with a water-soluble polymer; and/or   (ii) an edible oil component comprising a dissolved Noble gas.   
     
     
         2 . The composition of  claim 1 , wherein the Noble gas is Helium, Neon, Argon, Krypton or Xenon. 
     
     
         3 . The composition of  claim 1 , wherein the Noble gas is Xenon. 
     
     
         4 . The composition of  claim 1 , wherein the composition comprises a mixture of two or more Noble gases. 
     
     
         5 . The composition of  claim 1 , wherein the composition comprises an emulsion. 
     
     
         6 . The composition of  claim 1 , wherein water-soluble polymer is cyclodextrin. 
     
     
         7 . The composition of  claim 6 , wherein the cyclodextrin is gamma- or beta-cyclodextrin. 
     
     
         8 . The composition of  claim 6 , wherein the cyclodextrin is beta-cyclodextrin. 
     
     
         9 . The composition of  claim 6 , wherein the composition comprises about 0.1 to about 1.0 mg/ml of a cyclodextrin molecule. 
     
     
         10 . The composition of  claim 1 , wherein the oil comprises polyunsaturated fatty acids (PUFA). 
     
     
         11 . The composition of  claim 1 , wherein the oil comprises at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% PUFAs. 
     
     
         12 . The composition of  claim 1 , wherein the oil component is saturated with xenon or argon gas. 
     
     
         13 . The composition of  claim 1 , wherein the edible oil component comprises soluble xenon gas. 
     
     
         14 . The composition of  claim 1 , wherein the edible oil is essentially free of oxygen. 
     
     
         15 . The composition of  claim 1 , wherein the oil comprises canola oil, flaxseed oil, rapeseed oil, soybean oil, walnut oil, fish oil, safflower oil, chia seed oil, sunflower seed oil, sesame seed oil, seaweed oil, corn oil, cotton seed oil, peanut oil, palm oil, avocado oil, coconut oil, or olive oil. 
     
     
         16 . The composition of  claim 1 , wherein the oil comprises omega-3 fatty acids. 
     
     
         17 . The composition of  claim 1 , further defined as an emulsion comprising:
 (a) 25% to 50% by volume oil, said oil being saturated with a Noble gas; and   (b) 30% to 75% by volume aqueous solution.   
     
     
         18 . The composition of  claim 1 , further defined as an emulsion comprising:
 (a) 15% to 75% by volume oil, said oil being saturated with a Noble gas; and   (b) 25% to 85% by volume aqueous solution.   
     
     
         19 . The composition of  claim 1 , wherein the aqueous solution comprises water, fruit juice, vegetable juice or an alcohol. 
     
     
         20 . The composition of  claim 1 , further comprising phospholipid, detergent, or protein components. 
     
     
         21 . The composition of  claim 20 , wherein the detergent is a plant surfactant, a synthetic detergent or a bile acid. 
     
     
         22 . The composition of  claim 20 , wherein the detergent is lithocholic acid, deoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, or cholic acid. 
     
     
         23 . The composition of  claim 20 , wherein the phospholipid is egg phosphocholine (egg PC), soybean PC, DPPC or DOPC. 
     
     
         24 . The composition of  claim 20 , wherein the protein is milk protein, whey protein, soy protein isolate, or bovine serum albumin. 
     
     
         25 . The composition of  claim 1 , further comprising between about 1 and 50 g of xenon per ml of oil. 
     
     
         26 . The composition of  claim 1 , comprising:
 (a) 15% to 75% by volume olive oil, said oil being saturated with xenon or argon gas; (b) 25% to 85% by volume aqueous solution; and one or more of a phospholipid, a detergent or a protein.   
     
     
         27 . The composition of  claim 1 , comprising:
 (a) 25% to 50% by volume olive oil, said oil being saturated with xenon or argon gas;   (b) 50% to 75% by volume aqueous solution;   (c) 10-30 mg/ml phosphocholine;   (d) 10-50 mg/ml BSA; and   (e) 1-5 mg/ml lithocholic acid.   
     
     
         28 . The composition of  claim 1 , comprising:
 (a) 15% to 75% by volume olive oil, said oil being saturated with xenon or argon gas;   (b) 25% to 85% by volume aqueous solution;   (c) 10-30 mg/ml phosphocholine;   (d) 10-50 mg/ml BSA; and   (e) 1-5 mg/ml lithocholic acid.   
     
     
         29 . The composition of  claim 1 , further defined as a herbal, vitamin or energy-providing nutraceutical beverage. 
     
     
         30 . The composition of  claim 1 , further comprising a preservative, flavoring agent, dye, vitamin, anti-oxidant, or plant extract. 
     
     
         31 . The composition of any one of  claims 1 - 30 , said composition comprised in a gas impermeable container. 
     
     
         32 . The composition of  claim 31 , wherein the container comprises about 1 ml to 2 liters of the composition. 
     
     
         33 . The composition of  claim 32 , wherein the container comprises about 1 mg to 20 g, 1 mg to 10 g, 1 mg to 1 g, 1 to 100 mg, 1 to 50 mg, 1 to 25 mg or 1 to 10 mg of Xe. 
     
     
         34 . The composition of  claim 31 , wherein the container comprises a one-way value to release the composition for oral consumption without exposing the entire content to the atmosphere. 
     
     
         35 . The composition of  claim 32 , wherein the container is pressurized. 
     
     
         36 . The composition of  claim 35 , wherein the container is pressurized with a Noble gas. 
     
     
         37 . The composition of  claim 35 , further comprising CO 2 . 
     
     
         38 . A single serving nutraceutical comprising a composition of any one of  claims 1 - 30 , in a gas impermeable container. 
     
     
         39 . The single serving beverage of  claim 38 , wherein the container is a bottle. 
     
     
         40 . The single serving beverage of  claim 39 , wherein the container has 1 ml to 1.0 1 ml of the composition. 
     
     
         41 . The single serving beverage of  claim 38 , wherein the Noble gas comprises Xe. 
     
     
         42 . The single serving beverage of  claim 41 , having about 1 mg to 20 g, 1 mg to 10 g, 1 mg to 1 g, 1 to 100 mg, 1 to 50 mg, 1 to 25 mg or 1 to 10 mg of Xe. 
     
     
         43 . A single serving nutraceutical composition comprising about 25 to 500 ml of a substantially aqueous component and about 0.1 mg to 20 g of dissolved Noble gas, wherein a portion of the Noble gas in encapsulated to enhance aqueous solubility. 
     
     
         44 . A method of improving the health or well-being of a subject comprising providing a liquid or semi-liquid composition formulated for oral consumption, comprising a dissolved Noble gas. 
     
     
         45 . The method of  claim 44 , wherein the liquid composition is saturated or supersaturated with a Noble gas. 
     
     
         46 . The method of  claim 45 , wherein the Noble gas comprises Xe. 
     
     
         47 . The method of  claim 44 , wherein the liquid composition is a composition in accordance with any one of  claims 1 - 42 . 
     
     
         48 . A method of providing neurological or cardiovascular protection is a subject comprising orally administering an effective amount of a composition comprising dissolved Noble gas. 
     
     
         49 . The method of  claim 48 , wherein the subject has or is risk for atherosclerosis, Alzheimer's disease, thrombotic stroke, hemorrhage stroke, heart failure or cardiac hypertrophy. 
     
     
         50 . The method of  claim 48 , wherein the subject is a human. 
     
     
         51 . The method of  claim 50 , wherein the Noble gas comprises Xe. 
     
     
         52 . The method of  claim 51 , comprising administering about 0.1 mg to 20 g/day of Xe to the subject. 
     
     
         53 . The method of  claim 52 , comprising administering about 500 mg to 10 g, 500 mg to 5 g, 500 mg to 2 g, 1 to 100 mg, 1 to 50 mg, 1 to 25 mg or 1 to 10 mg per day of Xe to the subject. 
     
     
         54 . The method of  claim 48 , wherein the composition is administered weekly, daily, twice a day, three times a day, every six hours, every three hours or hourly. 
     
     
         55 . The method of  claim 54 , wherein the composition is administered over the period of a week, two weeks, a month or a year. 
     
     
         56 . The method of  claim 48 , further defined as a method for treating or preventing a neurological disease or neurological injury. 
     
     
         57 . The method  claim 56 , wherein the neurological disease is Alzheimer's disease. 
     
     
         58 . The method of  claim 57 , further defined as a method reducing beta-amyloid levels in the subject. 
     
     
         59 . The method of  claim 57 , further defined as a method for treating or preventing the progression of Alzheimer's disease is a subject. 
     
     
         60 . The method of  claim 57 , wherein the subject is at risk for developing Alzheimer's disease. 
     
     
         61 . The method of  claim 57 , wherein the subject has or is diagnosed with a genetic predisposition for Alzheimer's disease. 
     
     
         62 . The method of  claim 56 , wherein the neurological injury is thrombotic or ischemic stroke. 
     
     
         63 . A method for reducing a marker of inflammation in a subject comprising orally administering an effective amount of a composition dissolved Noble gas. 
     
     
         64 . The method of any one of  claims 48 - 63 , wherein the composition comprises Noble gas that has been encapsulated to enhance aqueous solubility. 
     
     
         65 . The method of any one of  claims 48 - 63 , wherein the composition comprises:
 (i) a substantially aqueous component comprising a dissolved Noble gas, a portion of the Noble gas being encapsulated with a water-soluble polymer; and/or   (ii) an oil component comprising a dissolved Noble gas.   
     
     
         66 . The method of  claim 65 , wherein the Noble gas is Helium, Neon, Argon, Krypton or Xenon. 
     
     
         67 . The method of  claim 65 , wherein the Noble gas is Xenon. 
     
     
         68 . The method of  claim 65 , wherein the composition comprises a mixture of two or more Noble gases. 
     
     
         69 . The method of  claim 65 , wherein the composition comprises an emulsion. 
     
     
         70 . The method of  claim 65 , wherein water-soluble polymer is cyclodextrin. 
     
     
         71 . The method of  claim 70 , wherein the cyclodextrin is gamma- or beta-cyclodextrin. 
     
     
         72 . The method of  claim 70 , wherein the cyclodextrin is beta-cyclodextrin. 
     
     
         73 . The method of  claim 70 , wherein the composition comprises about 0.1 to about 1.0 mg/ml of a cyclodextrin. 
     
     
         74 . The method of  claim 65 , wherein the oil comprises polyunsaturated fatty acids (PUFA). 
     
     
         75 . The method of  claim 65 , wherein the oil comprises at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% PUFAs. 
     
     
         76 . The method of  claim 65 , wherein the oil component is saturated with xenon or argon gas. 
     
     
         77 . The method of  claim 65 , wherein the edible oil component comprises soluble xenon gas. 
     
     
         78 . The method of  claim 65 , wherein the edible oil is essentially free of oxygen. 
     
     
         79 . The method of  claim 65 , wherein the oil comprises canola oil, flaxseed oil, rapeseed oil, soybean oil, walnut oil, fish oil, safflower oil, chia seed oil, sunflower seed oil, sesame seed oil, seaweed oil, corn oil, cotton seed oil, peanut oil, palm oil, avocado oil, coconut oil, or olive oil. 
     
     
         80 . The method of  claim 65 , wherein the oil comprises omega-3 fatty acids, omega-6 fatty acids or omega-9 fatty acids. 
     
     
         81 . The method of  claim 65 , further defined as an emulsion comprising:
 (a) 25% to 50% by volume oil, said oil being saturated with a Noble gas; and   (b) 30% to 75% by volume aqueous solution.   
     
     
         82 . The method of  claim 65 , further defined as an emulsion comprising:
 (a) 15% to 75% by volume oil, said oil being saturated with a Noble gas; and   (b) 25% to 85% by volume aqueous solution.   
     
     
         83 . The method of  claim 65 , wherein the aqueous solution comprises spring water, fruit juice or vegetable juice. 
     
     
         84 . The method of  claim 65 , further comprising phospholipid, detergent, or protein components. 
     
     
         85 . The method of  claim 84 , wherein the detergent is a plant surfactant, a synthetic detergent or a bile acid. 
     
     
         86 . The method of  claim 84 , wherein the detergent is lithocholic acid, deoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, or cholic acid. 
     
     
         87 . The method of  claim 84 , wherein the phospholipid is egg phosphocholine (egg PC), soybean PC, DPPC or DOPC. 
     
     
         88 . The method of  claim 84 , wherein the protein is milk protein, whey protein, soy protein isolate, or bovine serum albumin. 
     
     
         89 . The method of  claim 65 , further comprising between about 1 and 50 mg of xenon per ml of oil. 
     
     
         90 . The method of  claim 65 , wherein the composition comprises:
 (a) 15% to 75% by volume olive oil, said oil being saturated with xenon or argon gas; (b) 25% to 85% by volume aqueous solution; and one or more of a phospholipid, a detergent or a protein.   
     
     
         91 . The method of  claim 65 , wherein the composition comprises:
 (a) 25% to 50% by volume olive oil, said oil being saturated with xenon or argon gas;   (b) 50% to 75% by volume aqueous solution;   (c) 10-30 mg/ml phosphocholine;   (d) 10-50 mg/ml BSA; and   (e) 1-5 mg/ml lithocholic acid.   
     
     
         92 . The method of  claim 65 , wherein the composition comprises:
 (a) 15% to 75% by volume olive oil, said oil being saturated with xenon or argon gas;   (b) 25% to 85% by volume aqueous solution;   (c) 10-30 mg/ml phosphocholine;   (d) 10-50 mg/ml BSA; and   (e) 1-5 mg/ml lithocholic acid.   
     
     
         93 . A method of making an aqueous composition comprising a Noble gas comprising:
 (a) incubating a Noble gas with a water soluble encapsulating polymer; and   (b) exposing the encapsulated Noble gas to an aqueous to produce an aqueous composition comprising the Noble gas.   at a pressure of between about 2 atm and 10 atm, at a temperature of between about 4° C. and −180° C. for at least 4 hours to produce an encapsulated Noble gas   solution at a pressure of between about 2 atm and 10 atm, at a temperature of between about 20° C. and 1° C. for at least 4 hours   
     
     
         94 . The method of  claim 93 , wherein the incubating of step (a) is performed at a pressure of between about 2 atm and 8 atm, 2 atm and 5 atm, 2 atm and 4 atm or at a pressure of about 3 atm. 
     
     
         95 . The method of  claim 93 , wherein the incubating of step (a) is performed at a temperature of between about 0° C. and −150° C., −20° C. and −150° C., −20° C. and −100° C., −40° C. and −100° C. or at a temperature of about −80° C. 
     
     
         96 . The method of  claim 93 , wherein the incubating of step (a) is for a period of at least 8 hours, 12 hours, 24 hours, 48 hours or for between 8 hours and three days. 
     
     
         97 . The method of  claim 93 , wherein the exposing of step (b) is performed at a pressure of between about 2 atm and 8 atm, 2 atm and 5 atm, 2 atm and 4 atm or at a pressure of about 3 atm. 
     
     
         98 . The method of  claim 93 , wherein the exposing of step (b) is performed at a temperature of between about 15° C. and 1° C., 10° C. and 1° C., 8° C. and 2° C., 6° C. and 2° C. or at a temperature of about 4° C. 
     
     
         99 . The method of  claim 93 , wherein the exposing of step (b) is for a period of at least 8 hours, 12 hours, 24 hours, 48 hours or for between 8 hours and three days. 
     
     
         100 . The method of  claim 93 , wherein the aqueous solution comprises a dissolved Noble gas. 
     
     
         101 . The method of  claim 99 , wherein the aqueous solution is saturated with a Noble gas. 
     
     
         102 . The method of  claim 100 , wherein the aqueous solution is saturated with a Noble gas by a method comprising:
 (i) obtaining a degassed aqueous solution; and   (ii) exposing the degassed aqueous solution to a Noble gas at a pressure of between about 2 atm and 10 atm, at a temperature of between about 20° C. and 1° C. for at least 4 hours to produce an aqueous solution saturated with the Noble gas.   
     
     
         103 . The method of  claim 93 , wherein the Noble gas is argon or xenon. 
     
     
         104 . The method of  claim 103 , wherein the Noble gas is xenon. 
     
     
         105 . The method of  claim 93 , wherein the Noble gas comprises a mixture of two or more Noble gases. 
     
     
         106 . The method of  claim 93 , wherein water-soluble encapsulating polymer is cyclodextrin. 
     
     
         107 . The method of  claim 106 , wherein the cyclodextrin is gamma- or beta-cyclodextrin. 
     
     
         108 . The method of  claim 106 , wherein the cyclodextrin is beta-cyclodextrin. 
     
     
         109 . The method of  claim 108 , wherein the beta-cyclodextrin is hydroxypropyl-beta-cyclodextrin. 
     
     
         110 . The method of  claim 93 , further defined as a method for making a pharmaceutical or nutraceutical composition. 
     
     
         111 . The method of  claim 93 , wherein the aqueous solution comprises a preservative, flavoring agent, dye, vitamin, anti-oxidant, or plant extract. 
     
     
         112 . The method of  claim 93 , further comprising the step of (c) packaging the aqueous composition comprising the Noble gas in a gas impermeable container. 
     
     
         113 . The method of  claim 112 , wherein the container is pressurized. 
     
     
         114 . The method of  claim 113 , wherein the container is pressurized with a Noble gas. 
     
     
         115 . The method of  claim 112 , wherein the container is a pill, a capsule, a foild or polymer packet or a bottle. 
     
     
         116 . An aqueous composition comprising a Noble gas produced by a method according to any one of  claims 93 - 115 . 
     
     
         117 . A method of making a composition for oral administration of a Noble gas comprising:
 (a) solubilizing a Noble gas in an edible oil by mixing the oil and gas at a pressure of between about 2 atm and 6 atm, at a temperature of between about 0° C. and 25° C. to produce an edible oil comprising soluble Noble gas.