Therapeutically administrable high dose non-aqueous solutions of flavonoids and related molecules

Abstract

The present disclosure provides formulations for biologically active molecules including stilbenes, flavonoids, and flavonoid-related molecules. These formulations comprise liquid formulations containing glycerol to which a salt has been added. The formulations provide for more convenient modes of delivery, such as via orally consumed capsules or by injection. The present disclosure also provides for the use of combinations of biologically active flavonoids and related molecules.

Description

PATENT Attorney Docket No.:115653-1516983-000310WO THERAPEUTICALLY ADMINISTRABLE HIGH DOSE NON-AQUEOUS SOLUTIONS OF FLAVONOIDS AND RELATED MOLECULES CROSS-REFERENCE OF RELATED APPLICATIONS

[0001] This application claims priority to US Provisional Patent Application No.63 / 682,330, filed August 12, 2024, the content of which is hereby incorporated by reference in its entirety for all purposes. FIELD

[0002] This disclosure relates generally to therapeutically administrable high dose non- aqueous solutions of flavonoids and related molecules. BACKGROUND

[0003] A variety of bioactive flavonoids and related molecules are commonly used as therapeutics to address a wide range of health problems. These compounds are often consumed orally, in the diet within foodstuffs, or as nutritional supplements taken in capsule or tablet form. In many cases, it would be desirable to deliver flavonoids or related compounds via injection or within capsules, dissolved in a solvent as a liquid formulation.

[0004] We have previously disclosed liquid formulations for curcuminoids. A well-recognized curcuminoid is curcumin: a bright yellow plant produced compound found in members of the ginger family, Zingiberaceae, including in the rhizomes of the tropical perennial plant turmeric. Chemically, curcumin is a is a diarylheptanoid. As such, curcumin and other curcuminoids are a distinct and different class of chemistry to flavonoids and stilbenes and have different physical and chemical properties to the flavonoids.

[0005] Curcuminoids are insoluble at low pH. These molecules crystallize out of aqueous acidic solutions and rapidly degrade in alkaline aqueous solutions. For example, US20090324703A1 (Frautschy) 31 December 2009 notes that curcumin is unstable in aqueous solutions above pH 7.0 where curcumin hydrolyzes to ferulic acid and vanillin breakdownproducts. Furthermore, according to Physical and Chemical Stability of Curcumin in Aqueous Solutions and Emulsions: Impact of pH, Temperature, and Molecular Environment. Journal of Agricultural and Food Chemistry. Kharat, Mahesh & Du, Zheyuan & Zhang, Guodong & Mcclements, David. (2016) 65. 10.1021 / acs.jafc.6b04815, "Curcumin was highly unstable to chemical degradation in alkaline aqueous solutions (pH > 7.0) and tended to crystallize out of aqueous acidic solutions (pH < 7)".

[0006] As such, administering injections of curcuminoids in water-based solutions is not practical. Furthermore, whereas curcuminoids are soluble in non-aqueous solutions such as dimethyl sulfoxide (DMSO), acetone and ethanol and potentially in other organic solvents, ethanol however is painful and toxic when injected and DMSO is not generally used for injection, has been shown to be a neurotoxin in certain circumstances and causes an unpleasant odor for several hours post-injection.

[0007] We have previously disclosed formulations for curcuminoids which address the above challenges in WO 2020 / 163899.

[0008] Similar to curcuminoids, flavonoids and stilbenes are often rapidly degraded, or rapidly metabolized or excreted from the body. In addition, many flavonoids and stilbenes may be rapidly oxidized by oxygen when in contact with the air or dissolved oxygen. As such, a need therefore exists for a non-aqueous, low pO2, high dose, long shelf life (i.e., greater than 24 hours) solution for flavonoids and stilbenes which can be administered as is without the need of further preparation at the time of application.

[0009] Flavonoids and stilbenes, both a different class of chemistry to the curcuminoids, present similar formulation challenges to the curcuminoids. The present disclosure provides methods and formulations for delivery of liquid formulations of flavonoids and offers other advantages as well. EMBODIMENTS

[0010] We have now demonstrated that a selection of flavonoids, which are typically insoluble in water, can be dissolved in glycerol in the presence of sodium carbonate to produce injectable liquid formulations. Example compounds tested in this manner include: Apigenin (flavonoid),Quercetin (flavonoid) Luteolin (flavonoid) and Resveratrol (a chemical that falls into the related molecule class comprising the stilbenes, “also known as (aka) stilbenoids”).

[0011] The present disclosure provides a method which comprises preparing a nonaqueous administrable flavonoid solution, and more specifically, comprises dissolving a flavonoid or flavonoid related molecule in glycerol. Glycerol is a non-aqueous solvent suitable for human consumption or injection. However, many flavonoids are barely soluble in glycerol.

[0012] The methods herein may be generally applied to flavonoids and flavonoid related molecules including stilbenoids such as resveratrol.

[0013] Here we disclose that many flavonoids and stilbenes unexpectedly become more readily soluble in glycerol with the addition of an alkali salt for reasons hitherto not yet fully understood, but which may relate to the fact that flavonoids are often weakly acidic as a result of the presence of one or more phenolic hydroxyl groups.

[0014] In the method disclosed herein, an alkali salt is added to glycerol so that the flavonoid dissolves to a concentration greater than what is achievable using glycerol alone. A preferred alkali salt is sodium carbonate although other alkali salts may be used including calcium hydroxide, calcium carbonate or mixtures thereof. Importantly, the presently disclosed method provides for an injectable formulation wherein the flavonoid or stilbene is truly dissolved, as opposed to being present as an emulsion.

[0015] For example, adding 0.l mg to 20 mg sodium carbonate per mL of glycerol may achieve concentrations of 0-300 mg of a flavonoid or stilbene per mL of glycerol.

[0016] As such, the present administrable solution allows for a dose of greater than 0.1 mg of flavonoid or stilbene per mL of glycerol or more than 20 mg of flavonoid or stilbene per mL of glycerol (typically a preferred dose will be 20 - 250 mg of flavonoid or stilbene per mL of glycerol) which, for example, allows for a high dose intramuscular deposition of solution which slowly disperses in interstitial fluid and into the blood stream over the course of days / weeks, avoiding daily injections / clinic visits.

[0017] The present formulations are not aqueous, thereby avoiding problems of flavonoid and stilbene precipitation and degradation. Therefore, the present administrable solutions can bestored for greater than 24 hours without precipitation or chemical degradation and need not be used within 24 hours.

[0018] Furthermore, the present administrable solution can be applied directly, as is, without need for the prior addition of an aqueous emulsion, liposomes, micelles, or carriers.

[0019] The disclosure provides making a nonaqueous administrable solution of a flavonoid and glycerol, wherein an alkali salt is added to the glycerol to increase the solubility of the flavonoid or stilbene in the glycerol to more 0.1 mg, or more than 1 mg, or more than 10 mg, or more than 20 mg of flavonoid or stilbene per mL of glycerol.

[0020] According to one aspect, there is provided a method comprising dissolving a flavonoid in glycerol to make an administrable solution, wherein an alkali salt is added to the glycerol to increase the solubility of the flavonoid in the glycerol to more than 0.1 mg, or more than 1 mg, or more than 10 mg, or more than 20 mg of flavonoid or stilbene per mL of glycerol, and therapeutic administration of the administrable solution.

[0021] An alkali salt may be added to the glycerol to increase the solubility of the flavonoid in the glycerol to more than 0.1 mg, or more than 1 mg, or more than 10 mg, or more than 20 mg of flavonoid per mL of glycerol, and therapeutic administration of the administrable solution.

[0022] In certain instances, more than 1 mg of alkali salt may be added to the glycerol.

[0023] The administrable solution may comprise a concentration of greater than 100 mg of flavonoid per mL of glycerol.

[0024] In certain instances, more than 6 mg of alkali salt may be added to the glycerol.

[0025] The administrable solution may comprise a concentration of approximately 200 mg flavonoid per mL of glycerol.

[0026] In certain instances, more than 13 mg of alkali salt may be added to the glycerol.

[0027] The administrable solution may comprise a concentration of approximately 250 mg flavonoid per mL of glycerol.

[0028] In certain instances, more than 16 mg of alkali salt may be added to the glycerol.

[0029] Administration may comprise administration of the administrable solution more than 24 hours after dissolving the flavonoid in the glycerol.

[0030] In certain instances, the disclosure provides a dose of about 0.1 mg of flavonoid or stilbene per mL of glycerol to about 250 mg of flavonoid or stilbene per mL of glycerol. For example, the amount can be 0.1 mg, 1 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, or 250 mg and numbers in-between.

[0031] In certain instances, the amount of alkali salt is about 1 mg to 30 mg such as 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, or 30 mg and numbers in-between.

[0030] In certain instances, the weight ratio of stilbene, a flavonoid, or a flavonoid related molecule to alkali salt is about 10:1 to about 25:1 wt / wt and ratios in-between.

[0031] In certain instances, the weight ratio of stilbene, a flavonoid, or a flavonoid related molecule to alkali salt is about 12:1 to about 20:1 wt / wt and ratios in-between.

[0032] In certain instances, the method further comprises therapeutic administration of the administrable solution.

[0033] Administration may comprise administration of the administrable solution as is (e.g., without a carrier).

[0034] Administration may comprise administration of the administrable solution without the addition of water.

[0035] The administrable solution may not comprise propylene glycol or polyethylene glycol.

[0036] The flavonoid may be quercetin.

[0037] The flavonoid may be at least one of a flavonoid selected from the group consisting of quercetin, luteolin, apigenin, kaempferol, or an analog of any of the foregoing.

[0038] The alkali salt may comprise sodium carbonate.

[0039] The alkali salt may comprise at least one of calcium hydroxide and calcium carbonate.

[0040] The method may further comprise filtering the flavonoid or stilbene solution to remove any undissolved alkali salt.

[0041] The method may further comprise allowing the flavonoid solution to cool and filtering the solution to remove any undissolved or precipitated flavonoid or stilbene.

[0042] The method may further comprise antibacterial filtration of the flavonoid solution through a 0.2 - 0.22 micrometer filter.

[0043] Administration may comprise injection.

[0044] Injection may comprise intramuscular injection.

[0045] Injection may comprise at least one of subcutaneous, intradermal, intraperitoneal, and intra-abdominal injection.

[0046] Administration may comprise at least one of intranasal spray delivery, delivery using orally consumed capsules, delivery using enteric coated capsules to bypass stomach acid, rectal or colonic delivery by suppository, and delivery as a topical cream or lotion.

[0047] According to another aspect, there is provided an administrable solution comprising flavonoid or stilbene dissolved in glycerol, wherein an alkali salt is added to the glycerol so that the curcuminoid dissolves to a concentration of greater than 20 mg flavonoid or stilbene per mL of glycerol.

[0048] The administrable solution may comprise a concentration of approximately 200 mg flavonoids per mL of glycerol and more than 13 mg of alkali salt may be added to the glycerol.

[0049] Other aspects of the invention will become more apparent with reference to the following detailed description. Definitions:

[0050] “Cucurminoid” refers to a member of a class of chemistry that comprises a linear diarylheptanoid (i.e. a linear bridge comprising seven carbons, separating ring structures); this is a relatively small and distinct class of plant secondary metabolites that includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin, all of which are isolated from turmeric (Curcuma longa).

[0051] “Flavonoid” or “Flavanoid” refers to a class of polyphenolic secondary metabolites which possess a characteristic fused ring structure. Chemically, flavonoids have the general structure of a 15-carbon skeleton, have a characteristic defining feature in that they possess two phenyl rings (A and B) and a heterocyclic ring (C, the ring containing the embedded oxygen). This carbon structure can be abbreviated C6-C3-C6. Flavonoid subtypes include Flavanols, Flavan-3-ols, Flavones, Flavanones, Isoflavones, and Anthocyanins. Flavonoids (also sometimes referred to as bioflavonoids) are categorized as part of the broader class of compounds known as “polyphenols”. The name “Flavonoid” comes from the Latin word “flavus”, meaning yellow, a common color of such compounds in nature and the molecules. The compounds luteolin, kaempferol, apigenin, and quercetin are examples of flavanols, however curcumin, although a phenolic compound, is not a flavonoid, as it lacks the requisite defining fused multi-ring structure.

[0052] “Glycerol” which is also known as “Glycerin,” “Glycerine,” “1,2,3- Trihydroxypropane,” means the molecule with the IUPAC name propan-1,2,3-triol.

[0053] “Polyphenols” refers to the large family of naturally occurring phenols that is abundant in plants and structurally diverse. Although the term polyphenol is not well-defined in the art, it is generally agreed that a polyphenol is a natural product that possesses one or more hydroxyl groups on aromatic rings and which include four principal classes: phenolic acids, flavonoids, stilbenes, and lignans.

[0054] “Stilbenes” and their hydroxylated derivatives the “Stilbenoids” are phenylpropanoid molecules that comprise two six membered carbon rings joined by a two-carbon bridge (i.e., aC6-C2-C6 conformation). An example is Resveratrol (3,5,4 -trihydroxy-trans-stilbene) which is astilbenoid, that is produced by various plants in response to injury or when the plant is under attack by pathogens. Sources of resveratrol in foodstuffs include the skin of grapes, blueberries, raspberries, mulberries, and peanuts. Stilbenes and Stilbenoids belong to a different class of chemistry than the Cucurminoids. A further example of a stilbene is (E)-3,5-Dihydroxy-4- isopropyl-trans-stilbene (also known as 3,5-Dihydroxy-4-isopropylstilbene) which has antibiotic properties and which is the active ingredient of “Tapinarof” (also known as “benvitimod” and sold under the brand name “Vtama”), a medication used for the treatment of plaque psoriasis

[0055] Notwithstanding any other forms which may fall within the scope of the present invention, preferred embodiments of the disclosure will now be described by way of example. Examples

[0056] A method for preparation of an administrable quercetin solution in accordance with an embodiment. It should be noted that the method is an exemplary embodiment of the method of preparation and variations may be made thereto within the purposive scope of the present invention.

[0057] Step a is to obtain a volume of glycerol or a solvent with comparable properties to glycerol. Optionally, the method may comprise heating the glycerol or comparable solvent above room temperature to between the melting point and the boiling point (17°C - 290°C) thereof.

[0058] At step b, an alkali salt, such as sodium carbonate is dissolved in the solution of glycerol to raise the amount of flavonoid (e.g. quercetin) or stilbene (e.g. resveratrol) that can be diluted in the glycerol to greater than 0.1 mg, or greater than 1.0 mg, or greater than 10 mg, or greater than 20 mg per mL of glycerol, in step d.

[0059] Step c, optionally, may entail filtering the resultant solution to remove any residue and / or any undissolved salts.

[0060] Step d comprises the addition of a flavonoid (such as quercetin) or stilbene (e.g. resveratrol) to the solution and stirring or otherwise mixing or agitating the solution until the flavonoid is partially or substantially dissolved. In alternative embodiments, the flavonoid may be added prior to the addition of the alkali salt. In alternative embodiments, the flavonoid or stilbene may comprise metabolites of quercetin, luteolin, apigenin, kaempferol, resveratrol, or an analog of any of the foregoing, and mixtures thereof.

[0061] Addition of approximately between 0.1 - 20 mg of sodium carbonate or more per mL of glycerol may result in a concentration of approximately 0.001 - 300 mg of quercetin (or other flavonoid or flavonoid like molecule) or more per mL of glycerol. Both sodium carbonate and the flavonoid or flavonoid like molecule can be used at higher concentrations if required.

[0062] Step e may comprise filtering the resultant solution to remove any particulate residue such as undissolved quercetin or undissolved alkali salt, or other potential contaminants.

[0063] Step f may comprise filtering the resultant solution in a sterile system, such as through a 0.02-0.22 micrometer (μm) filter, to remove any contaminants and microbes including spores, or any other suitable method to sterilize the solution including pre-filtration of the glycerol, pre- filtration of the flavonoid while dissolved in ethanol followed by evaporation of the ethanol, heat sterilization of individual or combined ingredients, or ultra-violet sterilization.

[0064] Step g may comprise the therapeutic administration / human application of the prepared solution, such as by way of injection.

[0065] Injection may comprise intramuscular injection, but in embodiments, may also comprise subcutaneous, intradermal, intraperitoneal, and intra-abdominal injection.

[0066] The solution may alternatively be delivered as an intranasal spray, potentially with the addition of thinners to the solution or with the use of an atomizer.

[0067] The solution may also be used to create a nano-suspension suitable for administration via injection by mixing with water or other antisolvent prior to injection which may cause the flavonoid to precipitate out of solution as very fine particles in suspension. The solution may also be used in suppositories or enteric coated capsules for intestinal use, or potentially increased absorption into the liver or bloodstream via absorption in the intestines.

[0068] In accordance with a preferred embodiment, the human administrable flavonoid solution may comprise: 1. Glycerol; 2. An alkali salt or compound that can dissolve in the glycerol and not react excessively with curcumin or the solvent such as sodium carbonate; 3. a flavonoid or flavonoid like molecule, or a stilbene (including quercetin, luteolin, apigenin, kaempferol, or resveratrol, or an analog of any of the foregoing, and mixtures thereof); and 4. optionally, a preservative or preservatives in embodiments (or anti-fungal or anti- bacterial agent such as benzoic acid which is soluble in glycerol.)

[0069] Whereas sodium carbonate may be suitable because of the relatively high solubility thereof in glycerine, sodium carbonate may raise the pH of the surrounding tissue when injected, especially for correspondingly high dose ratio flavonoid solutions. As such, possible suitable alternatives include calcium hydroxide, calcium carbonate or any alkaline compound that is soluble in a suitable non-aqueous solvent.

[0070] Furthermore, because the prepared solution may be relatively viscous, especially for high dose solutions, the solution may be treated prior injection to reduce the viscosity thereof. Such may include warming the solution prior to injection or addition of a diluent prior to injection or during the manufacturing process. Preferably, the diluent comprises less than 50% volume of the injected solution. EMBODIMENTS Embodiment 1. A method, the method comprising dissolving a stilbene, a flavonoid, or a flavonoid related molecule in glycerol to make an administrable solution, wherein an alkali salt is added to the glycerol to increase the solubility of the flavonoid in the glycerol to more than 0.1, 1.0, 2.0, 5.0, 10.0 or more than 20 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule, and therapeutic administration of the administrable solution. Embodiment 2. The method of embodiment 1, wherein more than 1 mg of alkali salt is added to the glycerol or glycerol related molecule. Embodiment 3. The method of embodiment 1, wherein the administrable solution comprises a concentration of greater than 100 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule. Embodiment 4. The method of embodiment 3, wherein more than 6 mg of alkali salt is added to the glycerol or glycerol related molecule. Embodiment 5. The method of embodiment 1, wherein the administrable solution comprises a concentration of approximately 200 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule.Embodiment 6. The method of embodiment 5, wherein more than 13 mg of alkali salt is added . to the glycerol or glycerol related molecule. Embodiment 7. The method of embodiment 1, wherein the administrable solution comprises a concentration of approximately 250 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule. Embodiment 8. The method of embodiment 7, wherein more than 16 mg of alkali salt is added to the glycerol or glycerol related molecule. Embodiment 9. The method of embodiment 1, wherein administration comprises administration of the administrable solution more than 24 hours after dissolving the stilbene, flavonoid, or flavonoid related molecule in the glycerol or glycerol related molecule. Embodiment 10. The method of embodiment 1, wherein administration comprises administration of the administrable solution as is. Embodiment 11. The method of embodiment 1, wherein administration comprises administration of the administrable solution without the addition of water. Embodiment 12. The method of embodiment 1, wherein the flavonoid is quercetin. Embodiment 13. The method of embodiment 1, wherein the stilbene, flavonoid, or flavonoid related molecule is at least one of a molecule selected from the group consisting of quercetin, luteolin, apigenin, kaempferol, resveratrol, or an analog of any of the foregoing. Embodiment 14. The method of embodiment 1, wherein the alkali salt comprises sodium carbonate. Embodiment 15. The method of embodiment 1, wherein the alkali salt comprises at least one of calcium hydroxide and calcium carbonate. Embodiment 16. The method of embodiment 1, further comprising an optional heating of the glycerol to between the melting and the boiling point of glycerol. Embodiment 17. The method of embodiment 1, further comprising filtering the flavonoid solution to remove any undissolved alkali salt.Embodiment 18. The method of embodiment 17, further comprising allowing the stilbene, flavonoid, or flavonoid related molecule solution to cool and filtering the flavonoid solution to remove any undissolved or precipitated material. Embodiment 19. The method of embodiment 1, further comprising antibacterial filtration of the flavonoid solution through a 0.02 - 0.22 micrometer filter. Embodiment 20. The method of embodiment 1, wherein administration comprises injection. Embodiment 21. The method of embodiment 20, wherein injection comprises intramuscular injection. Embodiment 22. The method of embodiment 20, wherein injection comprises at least one of subcutaneous, intradermal, intraperitoneal, and intra-abdominal injection. Embodiment 23. The method of embodiment 1, wherein administration comprises at least one of intranasal spray delivery, delivery using enteric coated capsules to bypass stomach acid, rectal or colonic delivery by suppository and topical cream or lotion. Embodiment 24. An administrable solution comprising one at least one stilbene, flavonoid, or flavonoid related molecule dissolved in glycerol or a glycerol related molecule, wherein an alkali salt is added to the glycerol or glycerol related molecule so that the stilbene, flavonoid, or flavonoid related molecule dissolves to a concentration of greater than 0.1 mg, or greater than 0.5 mg, or greater than 1 mg, or greater than 2 mg, or greater than 5 mg, or greater than 10 mg, or greater than 20 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule. Embodiment 25. The administrable solution of embodiment 24, wherein the administrable solution comprises a concentration of approximately 200 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule and wherein more than 13 mg of alkali salt is added to the glycerol or glycerol related molecule.

[0071] The foregoing description, for purposes of explanation, used specific nomenclature to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that specific details are not required in order to practice the invention. Thus, the foregoing descriptions of specific embodiments of the invention are presented for purposes of illustrationand description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed; obviously, many modifications and variations are possible in view of the above teachings. The embodiments were chosen and described in order to best explain the principles of the invention and its practical applications, they thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the following claims and their equivalents define the scope of the invention.

[0072] It is to be understood that, if any prior art information is referred to herein, such reference does not constitute an admission that the information forms part of the common general knowledge in the art, in the United States or any other country.

Claims

WHAT IS CLAIMED IS:

1. A method, the method comprising: dissolving a stilbene, a flavonoid, or a flavonoid related molecule in glycerol to make an administrable solution, wherein an alkali salt is added to the glycerol to increase the solubility of the flavonoid in the glycerol to more than 0.1, 1.0, 2.0, 5.0, 10.0 or more than 20 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule.

2. The method of claim 1, wherein more than 1 mg of alkali salt is added to the glycerol or glycerol related molecule.

3. The method of claim 1, wherein the administrable solution comprises a concentration of greater than 100 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule.

4. The method of claim 3, wherein more than 6 mg of alkali salt is added to the glycerol or glycerol related molecule.

5. The method of claim 1, wherein the administrable solution comprises a concentration of approximately 200 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule.

6. The method of claim 5, wherein more than 13 mg of alkali salt is added to the glycerol or glycerol related molecule.

7. The method of claim 1, wherein the administrable solution comprises a concentration of approximately 250 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule.

8. The method of claim 7, wherein more than 16 mg of alkali salt is added to the glycerol or glycerol related molecule.

9. The method of claim 1, wherein the weight ratio of stilbene, a flavonoid, or a flavonoid related molecule to alkali salt is about 10:1 to about 25:1 wt / wt.

10. The method of claim 1, wherein the weight ratio of stilbene, a flavonoid, or a flavonoid related molecule to alkali salt is about 12:1 to about 20:1 wt / wt.

11. The method of claim 1, further comprising therapeutic administration of the administrable solution.

12. The method of claim 1, wherein administration comprises administration of the administrable solution more than 24 hours after dissolving the stilbene, flavonoid, or flavonoid related molecule in the glycerol or glycerol related molecule.

13. The method of claim 1, wherein administration comprises administration of the administrable solution as is.

14. The method of claim 1, wherein administration comprises administration of the administrable solution without the addition of water.

15. The method of claim 1, wherein the flavonoid is quercetin.

16. The method of claim 1, wherein the stilbene, flavonoid, or flavonoid related molecule is at least one of a molecule selected from the group consisting of quercetin, luteolin, apigenin, kaempferol, resveratrol, or an analog of any of the foregoing.

17. The method of claim 1, wherein the alkali salt comprises sodium carbonate.

18. The method of claim 1, wherein the alkali salt comprises at least one of calcium hydroxide and calcium carbonate.

19. The method of claim 1, further comprising an optional heating of the glycerol to between the melting and the boiling point of glycerol.

20. The method of claim 1, further comprising filtering the flavonoid solution to remove any undissolved alkali salt.

21. The method of claim 20, further comprising allowing the stilbene, flavonoid, or flavonoid related molecule solution to cool and filtering the flavonoid solution to remove any undissolved or precipitated material.

22. The method of claim 1, further comprising antibacterial filtration of the flavonoid solution through a 0.02 - 0.22 micrometer filter.

23. The method of claim 1, wherein administration comprises injection.

24. The method of claim 23, wherein injection comprises intramuscular injection.

25. The method of claim 23, wherein injection comprises at least one of subcutaneous, intradermal, intraperitoneal, and intra-abdominal injection.

26. The method of claim 1, wherein administration comprises at least one of intranasal spray delivery, delivery using enteric coated capsules to bypass stomach acid, rectal or colonic delivery by suppository and topical cream or lotion.

27. An administrable solution comprising one at least one stilbene, flavonoid, or flavonoid related molecule dissolved in glycerol or a glycerol related molecule, wherein an alkali salt is added to the glycerol or glycerol related molecule so that the stilbene, flavonoid, or flavonoid related molecule dissolves to a concentration of greater than 0.1 mg, or greater than 0.5 mg, or greater than 1 mg, or greater than 2 mg, or greater than 5 mg, or greater than 10 mg, or greater than 20 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule.

28. The administrable solution of claim 27, wherein the administrable solution comprises a concentration of approximately 200 mg stilbene, flavonoid, or flavonoid related molecule per mL of glycerol or glycerol related molecule and wherein more than 13 mg of alkali salt is added to the glycerol or glycerol related molecule.