DISSOLVED C60 AND METHOD OF PRODUCING DISSOLVED C60

A method of administering C60 to a user includes combining C60 molecules with a limonene composition to form a C60 mixture, heating the C60 mixture to a predetermined temperature for a predetermined time period to dissolve the C60 molecules into the limonene composition to form a dissolved C60 mixture, and administering the dissolved C60 mixture to a nasal cavity of the user via nasal administration.

FIELD

This disclosure relates to the field of nanomaterials and, in particular, to dissolving nanomaterials in a liquid medium suitable for therapeutic, nutritional, and medicinal applications.

BACKGROUND

Nanomaterials are materials of which a single unit is sized, in at least one dimension, from approximately one nanometer (1 nm) to approximately one thousand nanometers (1,000 nm) and often from approximately one nanometer (1 nm) to approximately one hundred nanometers (100 nm). One type of nanomaterial or sub-nanomaterial is the C60 molecule, which is also referred to as C.60, C-60, C60, Buckminsterfullerene, fullerene, and buckyballs. The C60 molecule is an allotrope of carbon and consists of carbon atoms connected by single and double bonds so as to form a closed mesh. Each C60 molecule includes sixty atoms of carbon arranged in a soccer ball-like shape that includes twenty hexagons and twelve pentagons with a carbon atom at each vertex of each hexagon and pentagon. The C60 molecules have a diameter of approximately 0.72 nm; thus, C60 is typically referred to as either a nanomaterial or a sub-nanomaterial.

C60 is typically formed through a combustion process that isolates C60 molecules from soot. To prepare C60 for therapeutic or nutritional usage, the C60 is mixed with an edible oil, such as olive oil, for example. Known processes for mixing C60 in olive oil are extremely time consuming and expensive because C60 dissolves only to a trivial extent in olive oil. Specifically, the solubility of C60 in olive oil is no more than approximately 0.9 mg/ml. Moreover, when C60 is mixed with olive oil, the C60 tends to agglomerate and to resist dissolution. To overcome this issue, researchers sonicate and stir the C60 and olive oil mixture for five to ten days to attempt to break up clumps of the C60. Even after this extremely lengthy process, however, only a trivial amount of the C60 becomes dissolved in the olive oil with the remainder of the C60 molecules packed together in microscopic clumps. As such, only a trivial amount of the C60 in the olive oil mixture is bioactive and most of the C60 is unavailable for therapeutic, nutritional, and medicinal benefits. Moreover, the mixture of olive oil and C60 is subject to settling and reagglomeration (i.e. the olive oil and C60 mixture is unstable), thereby further reducing therapeutic and nutritional benefits of the C60.

Based on the above, further developments in the area of preparing C60 for therapeutic, nutritional, and medical applications are desired.

SUMMARY

According to an exemplary embodiment of the disclosure, a method of administering C60 to a user includes combining C60 molecules with a limonene composition to form a C60 mixture, heating the C60 mixture to a predetermined temperature for a predetermined time period to dissolve the C60 molecules into the limonene composition to form a dissolved C60 mixture, and administering the dissolved C60 mixture to a nasal cavity of the user via nasal administration.

According to another exemplary embodiment of the disclosure, a nasal spray system includes a reservoir, an applicator, and a nasal mixture. The applicator has a nozzle configured to generate a spray. The applicator is operably connected to the reservoir. The nasal mixture includes a dissolved C60 mixture. The nasal mixture is contained in the reservoir. The nasal mixture is configured to be sprayed by the nozzle. The dissolved C60 mixture includes C60 molecules dissolved in a limonene composition. The nasal mixture is configured for administration to a nasal cavity of a user via nasal administration.

According to a further exemplary embodiment of the disclosure, a method of administering C60 to a user includes combining C60 molecules with a limonene composition to form a C60 mixture, and heating the C60 mixture to a predetermined temperature for a predetermined time period to dissolve the C60 molecules into the limonene composition to form a dissolved C60 mixture. The method further includes mixing the dissolved C60 mixture with a phospholipid to form a plurality of liposomes, combining the plurality of liposomes with a nasal solution to form a nasal mixture, and administering the nasal mixture to a nasal cavity of the user via nasal administration.

In the dissolved state, C60 molecules have many potential therapeutic, nutritional, and medicinal applications. Progress in applying C60 molecules, however, has thus far been hampered by the fact that C60 molecules are insoluble in aqueous media. To date, only inedible and toxic solvents have shown any significant ability to solubilize and/or dissolve C60 molecules without chemical modification or derivatization, which changes the nature and action of the C60 molecule.

The disclosure describes a breakthrough in preparing solubilized C60 for therapeutic, nutritional, and medicinal applications. Specifically, it was discovered that C60 is highly soluble/dissolvable in limonene and d-limonene, which are referred to herein as a limonene composition. The limonene composition is an edible and non-toxic liquid in which C60 molecules readily dissolve when the mixture is heated. The resultant dissolved C60 mixture is produced in a matter of minutes (about thirty minutes, in one embodiment) and, therefore, is many times faster and easier to produce than the mixture of C60 and olive oil. Additionally, the dissolved C60 mixture disclosed herein is stable and includes C60 molecules homogeneously dispersed throughout the mixture. Thus, the dissolved C60 mixture is a huge advancement over the C60 and olive oil mixture, which is unstable (i.e. subject to settling and reagglomeration) and includes C60 molecules in a clumped, non-uniform, and nonhomogeneous mixture. The dissolved C60 mixture disclosed herein is particularly useful in applications in which a specific quantity of C60 molecules are dosed, such as for therapeutic, nutritional, and medical applications.

The dissolved C60 mixture is a safe and edible mixture including C60 molecules at a sufficient concentration and stability to be practical in preparing test applications. The method disclosed herein does not change the nature, action, and structure of the C60 molecule. Additionally, using the dissolved C60 mixture to prepare a liposomal dispersion creates a convenient, stable, and safe aqueous solution of C60 molecules. The method disclosed herein produces a water soluble C60 mixture in a convenient, safe, stable, and inexpensive way. The method is a dramatic improvement over previous attempts to improve the solubility of C60, such as by derivatizing C60 with hydroxyl groups to create a Fullerol.

DETAILED DESCRIPTION

Aspects of the disclosure are disclosed in the accompanying description. Alternate embodiments of the disclosure and their equivalents may be devised without parting from the spirit or scope of the disclosure. It should be noted that any discussion herein regarding “one embodiment,” “an embodiment,” “an exemplary embodiment,” and the like indicate that the embodiment described may include a particular feature, structure, or characteristic, and that such particular feature, structure, or characteristic may not necessarily be included in every embodiment. In addition, references to the foregoing do not necessarily comprise a reference to the same embodiment. Finally, irrespective of whether it is explicitly described, one of ordinary skill in the art would readily appreciate that each of the particular features, structures, or characteristics of the given embodiments may be utilized in connection or combination with those of any other embodiment discussed herein.

The terms “comprising,” “including,” “having,” and the like, as used with respect to embodiments of the disclosure, are synonymous.

As used herein, the term “approximately” means within plus or minus 5% of the stated value.

As shown inFIG. 1, a C60 molecule100includes sixty atoms of carbon104arranged in a soccer ball-like shape. As used herein, the term “C60” refers to a plurality of the C60 molecules100. C60 is available as a powder that is formed by pulverizing masses or crystals of C60. When ingested, C60 is a powerful antioxidant and free radical scavenger. C60 also provides numerous other health and nutritional benefits to humans and animals, such as reducing inflammation, increasing energy, reducing symptoms of arthritis, increasing longevity, and protecting against excessive and uncontrolled free radical exposure as occurs in many disease states. Additional health benefits of C60 are described herein.

An obstacle to administering C60 is that the C60 molecules100tend to clump together in masses, especially when prepared according to known processes including edible oil mixtures, such as olive oil mixtures. As such, it is difficult to administer or to dose a predetermined amount of C60, because of the heterogeneous, non-homogenous, and/or non-uniform distribution of the C60 molecules100in the oil. Moreover, known solvents in which C60 is readily dissolvable are not food-grade, are inedible, are toxic, and/or are not safe for human consumption. For example, C60 dissolves in solvents such as carbon disulfide, 1-chloronapthalene, toluene, and p-xylene (xylene), all of which are toxic and inedible. Table 1, included herein, identifies the solubility of C60 in various solvents. C60 dissolves only to a trivial extent in olive oil (0.9 mg/ml), and the process of breaking up clumps of the C60 molecules100in the olive oil is laborious, inconsistent, and largely ineffective.

In an unexpected breakthrough, C60 is dissolved in a limonene composition to form a mixture including dissolved C60 that is homogenous and stable. As used herein, the limonene composition includes limonene and/or d-limonene. The limonene composition may include 100% limonene, 100% d-limonene, and mixtures of limonene and d-limonene.

Limonene and d-limonene are excellent liquid media for dissolving C60 molecules100. Limonene is a colorless and transparent liquid aliphatic hydrocarbon classified as a cyclic terpene, and is a major component in the oil of citrus fruit peels. Limonene is a chiral molecule. Limonene has a very low toxicity, and humans are rarely allergic to limonene. Limonene assists in the absorption of other terpenoids and chemicals through the skin, mucous membranes, and digestive tract. Limonene is also used as a botanical insecticide.

D-limonene is the d-isomer of limonene and has a strong smell of oranges and a bitter taste. D-limonene is used as a fragrance ingredient in cosmetic products and also as a flavoring agent in food manufacturing. D-limonene and limonene are food-grade, edible, non-toxic, and safe for human and animal consumption and ingestion. D-limonene, which is a monoterpene, is obtained commercially from citrus fruits through centrifugal separation or steam distillation, for example. D-limonene is a colorless and transparent liquid. D-limonene is plentiful and inexpensive.

As shown in the flowchart ofFIG. 2and with additional reference toFIG. 3, a method200for dissolving C60304in a liquid medium that is non-toxic and safe for human consumption includes combining C60304with a limonene composition308to form a C60 mixture312. (Block204). The limonene composition308is discussed in connection with the method200, but the limonene composition308may be substituted with orange terpenes or other edible and non-toxic terpenes (or terpene containing liquids). The limonene composition308is used over orange terpenes, because the limonene composition308has a more pleasant and less bitter taste. In one embodiment, the limonene composition308is at least 95% d-limonene by volume, with the remaining 5% including any other liquid, such as limonene, flavoring, fragrances, and the like. In another embodiment, the limonene composition308is at least 75% d-limonene with the remaining 25% including any other liquid, such as limonene, flavoring, fragrances, and the like.

At block204of the method200, the C60304is pulverized into a powdered form and combined with the liquid limonene composition308in a glass vessel (not shown) or any other heat-safe and non-reactive container. Additionally or alternatively, the C60304is not pulverized and is added to the limonene composition308in granular, chunky, or crystalline state.

InFIG. 3, the C60 mixture312, which includes the C60304and the limonene composition308, is illustrated at room temperature of about 70° F. (21° C.). Specifically,FIG. 3is a 1000× magnification view of one gram (1 g) of pulverized C60304mixed with sixty milliliters (60 ml) of the limonene composition308. The molecules of the C60304have formed small clumps316and have not immediately dissolved into the limonene composition308. Moreover, when viewed in color, the limonene composition308is colorless and transparent, and the C60304has a mostly black color. Any apparent color of the limonene composition308inFIG. 3is the result of an incandescent light source giving the limonene composition308a yellowish hue in certain photographic representations.

Next, at blocks208and212of the method200, the C60 mixture312is stirred and heated for a predetermined time period. An exemplary predetermined time period is from twenty to forty minutes. In one embodiment, the predetermined time period is thirty minutes or approximately thirty minutes.

The C60 mixture312is stirred with a magnetic stirring system (not shown) that uses a rotating magnetic field to cause a stir bar immersed in the C60 mixture312to move. In other embodiments, any other stirring system may be utilized to stir the C60 mixture312including hand stirring with a suitable tool, such a glass stirrer shaft (not shown). Moreover, in other embodiments, no stirring of the C60 mixture312is performed and only the heating process is used to dissolve the C60304into the limonene composition308.

The C60 mixture312is heated during the predetermined time period to a predetermined temperature by a hot plate or any other electric heating element system. An exemplary predetermined temperature is from approximately 250° F. to approximately 300° F. (121° C. to 149° C.). In one embodiment, the predetermined temperature is 275° F. (135° C.) or approximately 275° F. (135° C.). Additionally, or alternatively, the C60 mixture312is covered during the heating process (block212), such as with a watch glass or any other suitable cover, to facilitate solvent reflux, returning the condensed solvent (i.e. the limonene composition308) to the body of the solution.

The stirring and heating of blocks208and212dissolves the C60304into the limonene composition308.FIGS. 4 and 5illustrate two additional stages of the stirring and heating process. InFIG. 4, the mixture312has been heated for twenty minutes and fewer clumps316of the C60304remain, as compared toFIG. 3, thereby indicating that more molecules of the C60304have dissolved into the limonene composition308. When viewed in color, the C60 mixture312has become orange at the process stage illustrated inFIG. 4.

InFIG. 5, the C60 mixture312has been heated for twenty-five minutes and even fewer of the clumps316of the C60304remain, as compared toFIG. 4. The remaining clumps316of the C60304are very small. When viewed in color, the C60 mixture312has an orange color at the process stage illustrated inFIG. 5.

InFIG. 6, the C60 mixture312has been heated for thirty minutes and no clumps316of the C60304remain, indicating that inFIG. 6, a dissolved C60 mixture324is formed. As used herein, the dissolved C60 mixture324is a homogenous liquid including molecules of the C60304that are fully dissolved into the limonene composition308with no clumps316of the C60304. The dissolved C60 mixture324is a clear solution (i.e. transparent) with a deep magenta color. Any artifacts illustrated inFIG. 6are air bubbles or other features, but are not clumps316of the C60304.

In some embodiments, at blocks208and212of the method200, the C60 mixture312is sonicated to increase further the dissolution of the C60304into the limonene composition308and to assist in breaking up any of the clumps316of the C60304. Sonication is a process of applying sound energy to the C60 mixture312, thereby agitating the clumps316of the C60304and promoting full and timely dissolution of the molecules of the C60304into the limonene composition308. A sonication system (not shown) may be placed near or in the C60 mixture312to perform the sonication.

As used herein, “dissolving” the C60304into the limonene composition308refers to forming a solution including a homogenous mixture of C60 molecules100(FIG. 1) and molecules of the limonene composition308. In such a solution, the C60304is the solute and the limonene composition308is the solvent. In some embodiments, atomic level changes and bonds may occur between the dissolved C60 molecules100and molecules of the limonene composition308; however, the C60 molecules100retain their shape as shown inFIG. 1and also retain their therapeutic, nutritional, medicinal, and health benefits. The dissolved C60 mixture324may also be referred to as a C60 solution324including solubilized C60304in the limonene composition308.

In an exemplary embodiment of the dissolved C60 mixture324made according to the method200ofFIG. 2, the dissolved C60 mixture324includes 16.67 mg of dissolved C60304per one milliliter (1 ml) of the limonene composition308. At the solubility of 16.67 mg/ml, the dissolved C60 mixture324is “stable,” meaning that no settling or precipitating of the C60304occurs in the limonene composition308, even after six weeks of sitting at room temperature. As disclosed herein, a limit of solubility of the C60304in the limonene composition308is from approximately 16.67 mg/ml to approximately 20.0 mg/ml. Accordingly, in other embodiments, the dissolved C60 mixture324includes from 0.50 mg to 20.0 mg of the dissolved C60304per one milliliter (1 ml) of the limonene composition308.

When the dissolved C60 mixture324is made according to the method200ofFIG. 2with more than 16.67 mg of C60304per milliliter of the limonene composition308, some settling of the C60304occurs when the dissolved C60 mixture324is cooled from the predetermined temperature to room temperature. The settled C60304, however, can be easily “redissolved” by gently shaking and/or agitating the dissolved C60 mixture324at room temperature (i.e. without reheating). Whereas, when the dissolved C60 mixture324is made according to the method200ofFIG. 2with 16.67 mg or less of the C60304per milliliter of the limonene composition308, no settling of the C60304occurs when the dissolved C60 mixture324is cooled from the predetermined temperature to room temperature, and the dissolved C60 mixture324is stable. For a point of reference, the limit of solubility of the C60304in toluene is 2.8 mg/ml and the limit of solubility of the C60304in olive oil is 0.9 mg/ml. Thus, the method200produces an edible solution with a high quantity of dissolved C60 molecules100per milliliter of solvent.

The method200ofFIG. 2works to dissolve all of the commercially available forms of C60304including those types of C60304having a snowflake appearance under magnification and those types of C60304having a crystalline (i.e. cubic or hexagonal) appearance under magnification.

As noted above, the stirring process of block208is optional, but the heating process of block212is typically performed. As disclosed herein, the C60304typically does not dissolve to any significant extent into the limonene composition308when the C60 mixture312is at room temperature 70° F. (21° C.). According to the unexpected breakthrough discovered herein, however, when the limonene composition308and the C60 mixture312is heated dissolution of the C60304occurs. As such, the method200is different than the process of mixing C60304in olive oil, which occurs at room temperature 70° F. (21° C.) over the course of many days without heating. In such a process, heating the olive oil does not produce any significant increase of solubility of C60304, and does not produce any significant decrease in the mixing time. Moreover, heating the olive oil in an attempt to increase solubility of C60304fouls the olive oil, making the olive oil have an undesirable burnt taste and appearance. As such, the known olive oil process of mixing the C60304cannot be made more efficient by heating the olive oil. The known properties of C60304when mixed with olive oil make the high solubility of C60304in the heated limonene composition308even more of a surprise and a breakthrough.

The method200is orders of magnitude faster than the process of mixing C60304in olive oil. Mixing C60304in olive oil takes approximately seven days in order to break up the clumps of C60304, and over the course of the seven days, only a trivial amount of the C60304is actually dissolved in the olive oil with the rest of the C60304being unevenly dispersed through the olive oil in small (e.g. microscopic) clumps. The method200, as disclosed herein, dissolves the C60304in only thirty minutes, thereby offering huge time savings in preparing an edible, non-toxic, liquid-based dissolved C60 mixture324.

The dissolved C60 mixture324of the present disclosure provides a convenient means of dosing a predetermined amount of the C60304by easily measuring a liquid quantity of the dissolved C60 mixture324. That is, a known amount of the C60304can be dosed when the amount of the C60304and the amount of the limonene composition308used to form the dissolved C60 mixture324are known. For example, in an embodiment having one gram (1 gm) of the C60304and sixty milliliters (60 ml) of the limonene composition308, each milliliter of the dissolved C60 mixture324contains 16.67 mg of the C60304, since very little of the limonene composition308evaporates during the method200.

The dissolved C60 mixture324is edible, safe, and non-toxic and is suitable for therapeutic and nutritional dosing of the C60304and the corresponding C60 molecules100. Additionally, the dissolved C60 mixture324has a pleasant citrus taste and aroma. The dissolved C60 mixture324can be administered orally and swallowed, or administered orally and retained in the mouth for sublingual or buccal administration. The dissolved C60 mixture324can also be included in a topical cream for application to the skin and for transdermal administration of the C60 molecules100. The dissolved C60 mixture324can be included in a liposomal dispersion for convenient oral administration.

The dissolved C60 mixture324is also highly bioactive. As used herein, “bioactive” means functional as an antioxidant. Clumped or undissolved C60, as is found in known olive oil mixtures, has little to no bioactivity and does not effectively migrate through cell walls and mitochondrial walls. Moreover, clumped or undissolved C60 is filtered out of the blood by the liver or the intestinal wall, thereby further preventing and/or limiting the bioactivity of the C60 molecules100. The dissolved C60 mixture324is about 18.5× (i.e. (16.67 mg/ml)/(0.9 mg/ml)) more bioactive than olive oil mixtures including C60 (by volume), because the dissolved C60 mixture324includes orders of magnitude more dissolved C60 molecules100than is possible with any C60 and olive oil mixture.

The bioactive effect of the dissolved C60 mixture324, in one embodiment, occurs when the C60 molecules100, which are highly hydrophobic, migrate through cell walls and mitochondrial walls and come into contact with free radicals. Specifically, the C60 molecules100pass through cell walls and the blood/brain barrier to enter mitochondria, where most of the short-lived, highly reactive and, therefore, dangerous free radicals are produced. Consider in an example, the very damaging hydroxyl free radical, which exists on average for less than one ten billionth of a second, but during this time can negatively react with organic material inside a cell mitochondria. The highly-bioactive dissolved C60 mixture324enables the C60 molecules100to migrate into the mitochondria where the hydroxyl free radical and other free radicals are produced. The C60 molecules100neutralize the hydroxyl free radical and other free radicals by absorbing and/or sequestering free electrons from the free radicals. The free electrons are held inside of the carbon “cage structure” (seeFIG. 1) of the C60 molecule100, and cannot escape. Specifically, since the C60 molecule100is a hollow cage of inter-bonded carbon atoms, the free electrons are sequestered inside of the cage, stabilized by the thirty double bonds in the molecule100. The excess electrons go inside the cage and do not come out. Other antioxidants absorb and/or sequester one free electron by holding the free electron on the surface of the antioxidant where the free electron can react and create additional free radicals. Whereas, C60 molecules100of the dissolved C60 mixture324absorb and/or sequester up to thirty-four electrons each and remain stable. The C60 molecule100, unlike most other antioxidant molecules, does not become a prooxidant, releasing the captured electron(s) to create another free radical molecule. The C60 molecules100of the dissolved C60 mixture324diffuse throughout the entire body and then diffuse out of the body with a residence time of about five days, taking with them the sequestered and stabilized free electrons.

As shown inFIG. 7, a system400is configured to prepare an orally dissolving edible thin film404including the C60 molecules100. The thin film404including the C60 molecules100is also referred to herein as a therapeutic dosage form. A dosage form is a structure such as a pill, a capsule, a tablet, and in this example, a thin film. The dosage form delivers a particular dose of a substance, which in this disclosure is a particular dose of the C60 molecules100.

The system400includes a container408fluidically connected to a thin film forming unit412. The container408contains a combination of the dissolved C60 mixture324(made according to the method200) and a thin film liquid to form a thin film mixture416. The thin film forming unit412sprays or deposits the thin film mixture416onto a base420or a polished steel belt to form the thin film404. The thickness of the thin film404is about 0.1 mm. The thin film404is then cut into pieces424(i.e. the therapeutic dosage form) having a predetermined area based on a desired dosage of the C60 molecules100, for example. An exemplary predetermined area is approximately six square centimeters (6 cm2).

Since the C60 molecules100are evenly and fully dissolved in the dissolved C60 mixture324only a brief (a few seconds to one minute) mixing time is required to evenly and fully distribute the C60 molecules100of the dissolved C60 mixture324throughout the thin film liquid when forming the thin film mixture416. Moreover, due to the full dissolution of the C60 molecules100in the dissolved C60 mixture324, the orally dissolvable thin film404has a predetermined amount of bioactive C60 molecules100per unit of area of the thin film404. For example, in one embodiment, the thin film404includes twenty micrograms (20 μg) of the C60 molecules100per square centimeter of the thin film404. The C60 molecules100are homogeneously dispersed throughout the thin film404.

In an exemplary embodiment, the thin film liquid of the thin film mixture416is formed from or includes pullulan, which is a polysaccharide polymer that is edible, mostly tasteless, and is easily and quickly dissolvable in the mouth. The thin film liquid may also include gum arabic or any other chemical typically used in the production of orally dissolvable thin films.

The therapeutic dosage form424includes an effective dose of the C60 molecules100. An effective dose is an amount of the C60 molecules100that is sufficient or desirable for providing a therapeutic, nutritional, and/or medicinal effect. An exemplary effective dose is approximately twenty micrograms (20 μg) of the C60 molecules100. Since the thin film404includes a homogenous mixture of the C60 molecules, the effective dose is easily determined based on the area of the therapeutic dosage form424. The therapeutic dosage form424is stable and has a long shelf life, unlike the olive oil and C60 mixture.

In some embodiments, the thin film mixture416is an emulsion that is sprayed or deposited on the base420. In another embodiment, as illustrated inFIG. 8, instead of mixing directly the dissolved C60 mixture324with the thin film liquid, the dissolved C60 mixture324is first mixed with a phospholipid504to form a plurality of liposomes500. Each of the liposomes500includes a shell of the phospholipid504surrounding or encapsulating a quantity of the dissolved C60 mixture324. The liposomes500are mixed with the thin film liquid to form the thin film mixture416that is sprayed or deposited on the base420. The resulting thin film404includes liposomes500uniformly and homogeneously dispersed throughout the orally dissolvable thin film404.

In another embodiment, the dissolved C60 mixture324is combined with a medication that is suitable for topical, intravenous, oral, intra-articular, spray, nebulized mist topical, nasal, pulmonary, or transcutaneous administration methods. For example, in one embodiment, the dissolved C60 mixture324is combined with cortisone and/or dapsone and is administered to a patient according to at least one of the administration methods listed above.

As shown inFIG. 9, an adhesive bandage600(i.e. a Band-Aid® brand bandage) includes the dissolved C60 mixture324. The bandage600includes an adhesive strip604, a pad608mounted on the adhesive strip604, and the dissolved C60 mixture324applied to the pad608. The adhesive strip604is configured to adhere to the skin of a user with the pad608placed over a wound and/or in contact with the wound. When the bandage600is adhered to a user, the dissolved C60 mixture324is topically applied to the wound from the pad608. The terms “user” and “patient” are used synonymously herein. The dissolved C60 mixture324aids in healing of the wound by at least reducing inflammation at the wound site and reducing free radicals at the wound site that prevent healing. For example, the dissolved C60 mixture324can be sprayed on burns covering a large surface area to promote faster healing.

The method200of producing the dissolved C60 mixture324is distinguished from a mixture of C60 and olive oil based on the amount of the C60304that is dissolved in the solvent. For example, in the mixture of C60 and olive oil, only a trivial amount of the C60 actually dissolves in the olive oil even after one week of stirring. In the method200, however, up to approximately 16.67 mg of the C60304per one milliliter (1 ml) of the limonene composition308is fully dissolved in the dissolved C60 mixture324. As such, the dissolved C60 mixture324includes more bioactive C60 molecules100by volume than any mixture of C60 and olive oil, and is also easier and faster to produce. The dissolved C60 mixture324and the associated method200is and/or produces a soluble form of C60304using an edible food grade solvent (i.e. the limonene composition308), which enables the human body to benefit from the full therapeutic, medicinal, and health effects of the C60304, as compared to existing C60 mixtures using olive oil and the like.

The C60 mixture324is well-suited for administering to patients (both human and animal) during tests of the therapeutic, medical, and health benefits of C60304unlike mixtures of C60 and olive oil. Tests done to date using C60 and olive oil, are largely invalid because C60 dissolves only to a trivial extent in olive oil and the resultant mixture includes mostly undissolved and non-bioactive clumps of C60. Therefore, doses of the C60 and olive oil mixture have an inaccurate, unknowable, and/or inconsistent amount of C60 included therein. The tests are largely invalid, because the subjects were not given a precise amount of C60 with some subjects likely to have received little to no bioactive C60 in their dosage. The clumped and undissolved C60 in an olive oil mixture is removed by filtering mechanisms in the body, including the intestines, liver, and lungs, by at least the reticuloendothelial system (RES), which involves macrophages that engulf the particulate material through phagocytosis. Discovering a safe and stable way to dissolve the C60304(as is done by the method200) enables accurate dosing, facilitates free movement of the C60 molecules100throughout the body in minutes, and permits the C60 molecules100to pass through cell membranes in order to be located inside cells and inside mitochondria where most free radicals are produced. The result is a reduction in damage to proteins, fats, and DNA caused by highly-reactive, short-lived, free radical molecules produced as a natural byproduct of respiration and oxidative stress produced by intense exercise. For example, cell respiration and energy production by the breakdown of glucose yields three free radicals per glucose molecule of hydrogen peroxide and hydroxyl radicals. C60 molecules100bond to these free radicals and remove them from the body. In addition, the C60 mixture324protects against environmental free radicals from exposure to UVA and UVB from intense sunlight, air pollution, cigarette smoke, and cosmic rays from high altitude airplane travel. Moreover, uncontrolled free radical production by the body is the causative factor of cellular damage and disease symptoms in almost all diseases. These diseases start out with a normal response of the body to foreign material, which is the production of free radicals to destroy the foreign material. For unknown reasons, the control mechanism gets stuck in the “on” position, resulting in the continued production of free radicals. The free radicals cause cellular damage, which then results in inflammation, and further production of free radicals in an increasing and uncontrolled spiral that results in the symptoms of the disease. There is evidence that C60 may be able to stop the overproduction of free radicals, allowing the body to repair, stopping the disease spiral.

With reference again toFIG. 1, the antioxidant properties of the C60 molecules100are based on the thirty-two aromatic rings of alternating conjugated double bonds with lowest unoccupied molecular orbitals (LUMO), which enable the molecule100to easily take up an electron from reactive oxygen species (e.g. free radicals). Free electrons from up to thirty-four methyl radicals have been absorbed onto a single C60 molecule100. The quenching process is catalytic, such that the C60 molecule100can react with many superoxide molecules without being consumed. Due to this feature, C60 molecules100are the most efficient radical scavenger and are described as radical “sponges.” An advantage of using C60 molecules100as an antioxidant is their ability to localize within the cell, such as in mitochondria and other cell compartment sites, where, in healthy and especially in diseased states, the production of destructive free radicals takes place.

Excess free radicals have been implicated in cell damage or death, neurologic damage, diseases such as Alzheimer's, Lou Gehrig's disease (ALS), cardiovascular disease, diabetes, hypertension, irritable bowel syndrome (IBS), autism, atherosclerosis, psychiatric conditions including anxiety, depression, and schizophrenia, and multiple skin conditions including atopic dermatitis, eczema, psoriasis and acne. Additional areas of potential application of the dissolved C60 mixture324include: radioprotective effects, burn dressing, chronic wound healing, osteoporosis, preventing UVA and UVB damage to skin, treating viral infections and psoriasis.

The dissolved C60 mixture324and the method200opens the door to medical applications of C60, including: antiviral, antioxidant, anti-inflammatory, immune system modulation, and enabling photo induced biological activities, as a potential scaffold for photodynamic therapy and diagnostic applications, as a carrier for gene and drug delivery systems, and in serum protein profiling as material-enhanced laser desorption/ionization (MELDI) material for biomarker discovery.

As set forth above, the concentration of solubilized C60 achieved in the dissolved C60 mixture324and by the method200is much higher than achieved by other edible solvents. This higher concentration enables further innovation in terms of the delivery format of the C60 molecules100. Known edible C60 mixtures are extremely low solubility liquid-based delivery formats, i.e. olive oil. The method200and the dissolved C60 mixture324enables the development of a product in edible strip format due to the higher concentration of soluble C60 molecules100. Moreover, as shown in Table 1, d-limonene is the only known safe and edible solvent that has sufficient solubility to be practical for preparation and use in developing products that deliver non-trivial amounts of solubilized and bioactive C60. In Table 1, “ND” indicates that C60 in insoluble in the identified solvent. The solubility of C60 in d-limonene is included in the chart according to the results achieved by the method200and was not previously known in the art.

In addition to the above-described benefits, the C60 mixture324is a novel treatment for severe lung trauma. Many people suffer from severe respiratory distress syndrome (RDS) caused by inflammation and cytokine storm syndrome and other inflammatory disorders, which may occur as a result of viral infection such as the novel coronavirus (COVID-19), asthma, chronic obstructive pulmonary disease (“COPD”), lung irritation due to air pollution and/or smoking, other inflammatory conditions of the lungs, and other causes. For example, a viral infection or insult to a patent's lung tissue causes some patients to exhibit an over-reaction of the immune system known as hypercytokinemia or colloquially as a “cytokine storm.” Hypercytokinemia is a severe immune reaction in which the body releases too many cytokines. While cytokines are part of a healthy immune response, an abundance of cytokines harms the body and may result in fever, inflammation, fatigue, and nausea among other negative responses. The cytokine storm then builds upon itself in a positive feedback loop, because these negative responses result in the release of additional cytokines, which may cause further severe damage to healthy lung tissue, fluid accumulation in the alveoli, loss of lung function, and in severe cases death. Moreover, these negative responses to the abundance of cytokines also result in the production of many free radical molecules, which of course are also harmful to the patient. Problematically, there are not always adequate treatments available for severe lung trauma and hypercytokinemia. Moreover, at times, the treatment for severe RDS includes supplemental oxygen via mechanical ventilation, which is an undesirable and often fatal option for most patients.

As shown inFIG. 10, a method1000is disclosed herein that delivers C60 molecules100in the form of the dissolved C60 mixture324directly into a patent's lungs to mitigate the patient's negative response(s) to viral infections, lung tissue trauma, and hypercytokinemia by at least reducing inflammation, removing free radicals, down regulating the overactive immune response, and helping restore homeostasis in the patient's airways. As such, the dissolved C60 mixture324reduces, prevents, and/or treats lung damage and other damage as a result of viral infection and/or hypercytokinemia.

At block1004of the method1000, the C60304is combined with the liquid limonene composition308in a glass vessel (not shown) or any other heat-safe and non-reactive container. The C60304is added to the limonene composition308in any desired form including granular, chunky, crystalline, or pulverized.

Next, at blocks1008and1012of the method1000, the C60 mixture312is stirred and heated for a predetermined time period. An exemplary predetermined time period is from twenty to forty minutes. In one embodiment, the predetermined time period is thirty minutes or approximately thirty minutes.

The stirring and heating of blocks1008and1012dissolves the C60304into the limonene composition308, such that no clumps316of the C60304remain, and forms the dissolved C60 mixture324. As noted above, the dissolved C60 mixture324is a homogenous liquid including molecules of the C60304that are fully dissolved into the limonene composition308with no clumps316of the C60304.

The C60 mixture324is then cooled to room temperature. Due to the unique and critical process used to dissolve the C60304, the C60 mixture is stable and no settling or precipitating of the C60304occurs in the limonene composition308, even after six weeks of sitting at room temperature. As disclosed herein, a limit of solubility of the C60304in the limonene composition308is from approximately 16.67 mg/ml to approximately 20.0 mg/ml.

Next, at block1016of the method1000the dissolved C60 mixture324is administered directly to the lungs of a patient or animal via at least one form of inhalation administration or inhalation therapy including nebulization (FIG. 11), vaporization (FIG. 12), and a dry powder inhalation (FIG. 13). As illustrated herein and as described below, inhalation administration enables the dissolved C60 mixture324to pass into a patient's mouth or nose, through the trachea, and directly into the patient's lungs through the left and right bronchus.

From the bronchus, the inhaled dissolved C60 mixture324passes into the bronchioles and makes direct contact with the alveoli. Thus, the inhaled dissolved C60 mixture324contacts the patient's entire airway and is available to contact directly and to treat the entire airway including the trachea, the left and right bronchus, the bronchioles, and the alveoli. The key action site is at the level of the alveoli in injured lung cells and vascular tissues. Stabilization is achieved by preventing further local damage by modulating numerous signaling pathways and inhibiting inflammatory mediators including cytokines and chemokines. Moreover, the inhaled dissolved C60 mixture324passes to the patient's bloodstream due to the direct contact of the dissolved C60 mixture324with the alveoli. As a result, the inhaled dissolved C60 mixture324is also carried throughout the patient's whole body via blood flow. This makes the inhaled dissolved C60 mixture324available to remove free radicals, treat inflammation, and provide numerous other health benefits to substantially all cells in the patient's body. As a powerful antioxidant, the C60 molecules100in this unique form, administered directly to the lung tissue, sufficiently moderates free radical production by the immune system to reduce or eliminate damage to healthy lung tissue, reduce inflammation and accumulation of fluid in the alveoli, maintain effective lung function, allow the damaged tissue to heal, while permitting the immune system to effectively destroy viral pathogens, for example.

With reference toFIG. 11, a nebulizer system1100is shown and nebulization is the form of inhalation administration. The nebulizer system1100includes a nebulizer unit1104operably connected to a reservoir1108. The nebulizer unit1104and the reservoir1108are located within a housing1112. Flexible tubing1116is operably connected to the nebulizer unit1104, the reservoir1108, and/or the housing1112. The tubing1116is terminated in a mouthpiece1120. The nebulizer system1100is shown as a stationary device, but in other embodiments the nebulizer system1100is provided as a handheld system or any other suitable system for nebulization of a liquid. In another embodiment, the mouthpiece1120is provided as a mask (not shown) that is placed over the patient's mouth and nose.

The nebulizer unit1104is configured to nebulize the liquid contents of the reservoir1108in order to form a mist and/or an aerosol1124that travels through the tubing1116to the mouthpiece1120. The nebulizer unit1104is provided as a jet nebulizer unit, an ultrasonic nebulizer unit, and/or a mesh nebulizer unit. The nebulizer unit1104is supplied with electrical energy from a suitable power source such as a wall outlet or a battery (not shown).

The patient places the mouthpiece1120in his mouth and inhales through the mouthpiece1120. When the patient inhales, the aerosol1124is drawn out of the housing1112, through the tubing1116, out of the mouthpiece1120, into the patient's mouth1128, through the patient's trachea1132, and into the patient's lungs1136. The nebulizer unit1104is configured to form a fine aerosol without large droplets, so that the aerosol1124is drawn deep into the lungs1136and in contact with the alveoli1140.

According to block1016of the method1000ofFIG. 10, the dissolved C60 mixture324is added to the reservoir1108and then the nebulizer unit1104is activated. The nebulizer unit1104generates the aerosol1124directly from the dissolved C60 mixture324, such that the dissolved C60 mixture324is inhaled deep into the patient's lungs1136through tubing1116and the mouthpiece1120. In one embodiment, the nebulization unit1104is configured to nebulize the dissolved C60 mixture324into the aerosol1124having liquid particles between 0.1 and 10 μm in diameter that are suitable for breathing and administering the C60 molecules100directly into the lungs1136.

The tubing1116may also be connected to an oxygen mask (not shown), a ventilator tube of a mechanical ventilator (not shown), or an intubation tube (not shown) as an alternative to supplying the aerosol1124to the patient's lungs1136through the mouthpiece1120.

In one embodiment, only the dissolved C60 mixture324is added directly to the reservoir1108with no other liquid inhalation agents. In another embodiment, the dissolved C60 mixture324is combined with a liquid inhalation agent, such as a saline solution or any other suitable liquid for the nebulization process, to form an inhalation mixture. The inhalation mixture is added to the reservoir1108, and the aerosol1124is generated from the inhalation mixture. In each embodiment, the dissolved C60 mixture324provides a convenient means of dosing a predetermined amount of the C60304by easily measuring a liquid quantity of the dissolved C60 mixture324. Accordingly, the dissolved C60 mixture324is easily dosed into a quantity of saline solution or other solution.

In a further embodiment, an aqueous liposomal dispersion including the liposomes500ofFIG. 5and an inhalation agent are added to the reservoir1108of the nebulizer system1100to form an inhalation mixture. Suitable inhalation agents include saline solution and any other suitable liquid. The nebulization unit1104is configured to nebulize the inhalation mixture into the aerosol1124having liquid particles between 0.1 and 10 μm in diameter that are suitable for breathing and delivering the liposomes500directly into the lungs1136. Nebulization in this manner has been shown to be effective in delivering the liposomes500deep into the lungs1136including reaching the alveoli1140. The inhalation mixture does not include any toxic or irritating components that could cause damage to the highly-sensitive lung tissue.

The aqueous, saline liposomal dispersion of C60 (i.e. the inhalation mixture) contains the solubilized C60 molecules100at a concentration of 100 μg per ml. Such a dosage is a safe and sufficient to mitigate excess free radical damage and reduce inflammation, without any negative side effects. C60 molecules100from the liposomes500in the body diffuse within minutes into cells and mitochondria to absorb excess free radical electrons where they are produced. C60 molecules100diffuse readily through cell walls and have been shown to have a residence time of about five days in the body, diffusing into and out of cells, and eventually being removed from the body in urine via a diffusion process.

Using the method200ofFIG. 2to prepare the dissolved C60 mixture324is critical in performing the inhalation administration of the method1000ofFIG. 10. The method200dissolves C60304from a crystalline nanomaterial into a liquid mixture (such as limonene) including fully dissolved, unassociated, and free C60 molecules100. Stated differently, there are no clumps or substantially no clumps of the C60 molecules100in the dissolved C60 mixture324, and the C60 molecules100in the dissolved C60 mixture324are unattached to other molecules. Accordingly, the dissolved C60 mixture324(which may also include an inhalation agent and/or the liposomes500) is easily and effectively formed into an aerosol having very small droplets that are inhalable deep into the patient's lungs1136without precipitating or adhering to the tubing1116or the mouthpiece1120. Moreover, the droplets of the aerosol1124include typically a uniform dosage of the C60 molecules100so that the entire air tract of the patient is coated with C60 molecules100upon inhalation of the aerosol1124.

Other preparations of C60 molecules100that are mixed with oil (such as olive oil) are entirely unsuitable for inhalation administration of C60. Olive oil cannot be nebulized or vaporized into the lungs1136without causing irritation and damage to the patient. Moreover, known non-toxic mixtures of C60304do not have the high concentration and uniform distribution of unassociated, fully-dissolved, and free C60 molecules100that makes the dissolved C60 mixture324particularly suited for accurately dosing C60 molecules100to a patient. Instead, known mixtures of C60304include clumps of C60304that make the mixtures unsuitable for accurate dosing and unsuitable for forming an effective aerosol through the nebulization process. Also, known liquid carriers (such as olive oil) are unsuitable for inhalation administration. The dissolved C60 mixture324and the method1000ofFIG. 10solve all of these problems by using the critical steps of method200to dissolve the C60 material304in an non-toxic liquid that highly solubilizes C60 molecules100.

As shown inFIG. 12, a vaporizing system1200is shown and vaporization or “vaping” is the form of inhalation administration. The vaporizing system1200includes a heating element1204operably connected to a reservoir1208and a power source1210, such as a rechargeable battery. The heating element1204, the reservoir1208, and power source1210are located within a housing1212(not shown to scale). A mouthpiece1220extends from the housing1212. In another embodiment, the mouthpiece1220is provided as a mask (not shown) that is placed over the patient's mouth and nose.

The heating element1204is provided as a resistive heating element, for example, and is configured to vaporize the liquid contents of the reservoir1208in order to generate a vapor1224that is drawn out of the mouthpiece1220by the patient. The heating element1204vaporizes the liquid contents of the reservoir1208without combusting or burning the liquid contents of the reservoir1208. In one embodiment, the patient places the mask over his mouth and nose to deliver the vaporized liquid into the nose, nasopharynx, mouth, and oral pharynx through the patient's trachea1132, and into the patient's lungs1136. The vapor1224includes very small particles that are drawn deep into the lungs1136and in contact with the alveoli1140.

With reference again to block1016of the method1000ofFIG. 10, the dissolved C60 mixture324is added to the reservoir1208and then the heating element1204is activated. The heating element1204vaporizes the dissolved C60 mixture324to form the vapor1224. The vapor1224includes the C60 molecules100.

In one embodiment, only the dissolved C60 mixture324is added directly to the reservoir1208with no other liquid vaporization agents. In another embodiment, the dissolved C60 mixture324is combined with a liquid vaporization agent such as propylene glycol, glycerin, or any other suitable liquid for the vaporization process, to form a vaporization mixture. The vaporization mixture is then added to the reservoir1208. The dissolved C60 mixture324provides a convenient means of dosing a predetermined amount of the C60304by easily measuring a liquid quantity of the dissolved C60 mixture324. Accordingly, the dissolved C60 mixture is easily dosed into a quantity of suitable vaporization agent.

Moreover, the vaporizing system1200is compatible with an aqueous liposomal dispersion including the liposomes500ofFIG. 5and an inhalation agent. Again, suitable inhalation agents include propylene glycol, glycerin, and the like. The heating element1204is configured to vaporize the aqueous liposomal dispersion into the vapor1224that includes the C60 molecules100and the liposomes500. Vaporization in this manner has been shown to be effective in delivering the C60 molecules100and the liposomes500of the vapor1224deep into the lungs1136including reaching the alveoli1140. The aqueous liposomal dispersion does not include any toxic or irritating components that could cause damage to the highly-sensitive lung tissue.

As shown inFIG. 13, an inhaler system1300is shown and dry powder inhalation is the form of inhalation administration. The inhaler system1300is a dry powder inhaler or a metered-dose dry inhaler and includes a dosage chamber1308configured hold a powdered dose of C601316(also referred to herein as a C60 dry powder), a housing1312, and a mouthpiece1320operably connected to the dosage chamber1308and extending from the housing1312(not shown to scale). In another embodiment, the mouthpiece1320is provided as a mask (not shown) that is placed over the patient's mouth and nose.

With reference again to block1016of the method1000ofFIG. 10, the dissolved C60 mixture324formed into the C60 dry powder1316and then is added to the dosage chamber1308. For example, the C60 dry powder1316is formed by mixing the C60 mixture324with a carrier powder, such as corn starch or powdered sucrose. The inhaler system1300administers the C60 dry powder1316directly into the lungs1136. In particular, when the patient inhales, the C60 dry powder1316is drawn out of the dosage chamber1308, into the patient's mouth1128, through the patient's trachea1132, and into the patient's lungs1136. The C60 dry powder1316includes very small particles that are drawn deep into the lungs1136and in contact with the alveoli1140. The inhaler system1300is typically more portable and may be more convenient for the patient than the nebulizer system1100.

In one embodiment, the C60 dry powder1316contains C60 molecules100at a concentration designed to deliver 100 μg per dose. Our experience is that this is a safe and sufficient dose to mitigate excess free radical damage and reduce inflammation, without any negative side effects.

Using the method200ofFIG. 2to prepare the dissolved C60 mixture324is critical in preparing the C60 dry powder1316. The method200dissolves C60304from a crystalline nanomaterial into a liquid (such as limonene) including fully dissolved, unassociated free C60 molecules100. Stated differently, there are no clumps or substantially no clumps of the C60 molecules100in the dissolved C60 mixture324, and the C60 molecules100in the dissolved C60 mixture324are unattached to other molecules. Accordingly, the dissolved C60 mixture324is easily and effectively mixed with the carrier powder without excess clumping.

With reference toFIG. 14, a nasal spray device1400is shown positioned for nasal administration of the dissolved C60 mixture324, which is included in a nasal mixture1404. The nasal spray device1400includes a reservoir1408, a pump1412, and an applicator1416having a nozzle1420. The reservoir1408is configured to contain the nasal mixture1404. In one embodiment, the nasal spray device1400is multi-dose device and the reservoir1408is configured to contain approximately sixteen milliliters (16 ml) of the nasal mixture1404which, as described herein, is sufficient for providing approximately one hundred twenty sprays1424of the nasal mixture1404. In another embodiment, the reservoir1408is sized from five milliliters (5 ml) to one hundred milliliters (100 ml). In one embodiment, each spray1424is approximately 0.13 milliliters of the nasal mixture1404and includes approximately 2.17 mg of the C60 molecules100.

The pump1412is operably connected to the reservoir1408and includes a pickup tube1428that extends into the reservoir1408. The pickup tube1428is also referred to herein as a siphon tube. In one embodiment, the pump1412is a positive displacement pump that is powered by the user. Specifically, the user presses on a portion of pump1412that moves relative to the reservoir1408to activate the pump1412and to pump a predetermined amount of the nasal mixture1404toward the applicator1416and through the nozzle1420. The pump1412is configured to pump the predetermined amount once per activation of the pump1412. In one embodiment, the predetermined amount of the nasal mixture1404that is pumped by an activation of the pump1412is from 0.05 milliliters (0.05 ml) to 0.30 milliliters (0.30 ml). Accordingly, the spray1424includes from 0.05 milliliters (0.05 ml) to 0.30 milliliters (0.30 ml) of the nasal mixture1404, and the spray1424includes from 0.83 mg to 5.0 mg of the C60 molecules100when the nasal mixture1404is only the dissolved C60 mixture324.

The applicator1416and the nozzle1420are operably connected to the pump1412and the reservoir1408. As shown inFIG. 14, the applicator1416is sized to fit within a nostril1432of the user. Accordingly, the applicator1416is approximately five to seven millimeters (5 mm to 7 mm) across and is approximately thirty millimeters (30 mm) long. In one embodiment, the applicator1416has a frustoconical configuration. The applicator1416, in other embodiments, has any other size and shape suitable for placement in the nostril1432of the user.

The nozzle1420is mounted at an end of the applicator1416. The nozzle1420is configured to convert the predetermined amount of the nasal mixture1404, as pumped by the pump1412, into the spray1424. The spray1424may be configured as a coarse spray, a medium spray, a fine spray, a mist, a fog, and an aerosol depending on the configuration of the nozzle1420. The spray pattern of the spray1424generated by the nozzle1420, in one embodiment, is a full cone spray and is configured to contact as much of a nasal cavity1436of the user as is accessible through the nostril1432(as may be assisted by the inhalation of the spray1424by the user). In another embodiment, the shape of the spray1424is a fan or a hollow cone as may be appropriate for the anatomy of a particular user. The nozzle1420is configured to emit and/or to generate the spray1424.

In another embodiment of the nasal spray device1400, the pump1412is not included, and the reservoir1408is configured to be squeezed by the user to generate the spray1424through the nozzle1420. In such an embodiment, the reservoir1408is formed from a resilient material, such as plastic. Squeezing the reservoir1408forces the nasal mixture1404through the nozzle1420to generate the spray1424.

The nasal mixture1404is contained in the reservoir1408and includes the dissolved C60 mixture324. The nasal mixture1404is pumped by the pump1412through the applicator1416and the nozzle1420to form the spray1424. The spray1424is formed from the nasal mixture1404. Accordingly, the nasal mixture1404includes the C60 molecules100dissolved in the limonene composition308. The nasal mixture1404is configured for nasal administration directly to the nasal cavity1436of the user. Nasal administration includes intranasal delivery and intranasal administration. Nasal administration causes the nasal mixture1404to be applied directly to the surfaces, features, and elements of the user's nasal cavity1436.

In one embodiment, the nasal mixture1404includes only the dissolved C60 mixture324. In another embodiment, the nasal mixture1404includes a nasal solution mixed with the dissolved C60 mixture324. For example, the nasal mixture1404may be approximately 75% of the dissolved C60 mixture324and 25% of the nasal solution. The amount of the nasal solution mixed with the dissolved C60 mixture324may range from 5% to 90%. Exemplary nasal solutions include water and saline.

In another embodiment, the nasal mixture1404includes the liposomes500ofFIG. 8. Specifically, the nasal mixture1404includes the liposomes500mixed with the nasal solution, such as water and/or saline. In such an embodiment, the spray1424of the nasal mixture1404is configured to spray the liposomes500directly into the nasal cavity1436of the user. The shell504of the liposomes500is configured to dissolve in response to being in contact with the surfaces, the features, and the elements of the nasal cavity1436. When the liposomes500dissolve and/or break, the dissolved C60 mixture324escapes from the liposomes500and contacts directly the surfaces, the features, and the elements of the nasal cavity1436, thereby providing therapeutic benefits. The nasal solution is selected so as not to dissolve the shell504of the liposomes500. That is, the liposomes500remain intact and homogenously distributed through the nasal solution when included in the nasal mixture1404. The liposomes500are stable and do not breakdown in the nasal mixture1404.

As shown inFIG. 15, a method1500delivers the C60 molecules100to the user's nasal cavity1436to mitigate the user's negative response(s) to allergens, viral infections, and/or pathogens by reducing inflammation, removing free radicals, helping the injured cells to heal and return the surrounding environment to homeostasis.

At block1504of the method1500, the C60304(i.e., the C60 molecules100) is combined with the liquid limonene composition308in a glass vessel (not shown) or any other heat-safe and non-reactive container. The C60304is added to the limonene composition308in any desired form including granular, chunky, crystalline, or pulverized.

Next, at blocks1508and1512of the method1500, the C60 mixture312is stirred and heated for a predetermined time period. An exemplary predetermined time period is from twenty to forty minutes. In one embodiment, the predetermined time period is thirty minutes or approximately thirty minutes.

The stirring and heating of blocks1508and1512dissolves the C60304into the limonene composition308, such that no clumps316of the C60304remain, and forms the dissolved C60 mixture324. As noted above, the dissolved C60 mixture324is a homogenous liquid including the molecules of the C60304that are fully dissolved into the limonene composition308with no clumps316of the C60304.

The C60 mixture324is then cooled to room temperature. Due to the unique and critical process used to dissolve the C60304, the C60 mixture324is stable and no settling or precipitating of the C60304occurs in the limonene composition308, even after six weeks of sitting at room temperature. As disclosed herein, a limit of solubility of the C60304in the limonene composition308is from approximately 16.67 mg/ml to approximately 20.0 mg/ml.

Next, the dissolved C60 mixture324is added to the reservoir1408of the nasal spray device1400. In particular, the dissolved C60 mixture324is add directly without being mixed with the nasal solution. Alternatively, the dissolved C60 mixture324is mixed with the nasal solution to form the nasal mixture1404, and the nasal mixture1404is added to the reservoir1408.

Optionally, at block1516a plurality of liposomes500are formed from the C60 mixture324. The liposomes500are formed by mixing the dissolved C60 mixture324with the phospholipid504and/or another suitable lipid. Each of the liposomes500includes the shell504of the phospholipid504surrounding or encapsulating a quantity of the dissolved C60 mixture324. The liposomes500are then mixed with the nasal solution to form the nasal mixture1404. The nasal mixture1404including the liposomes500is added to the reservoir1408.

At block1520of the method1500, the dissolved C60 mixture324is administered to the nasal cavity1436of a user (human or animal) via the nostril1432through a process of nasal administration. In a first embodiment, the nasal mixture1404includes only the dissolved C60 mixture324, and the nasal mixture1404is administered directly to the nasal cavity1436as the spray1424. In another embodiment, the dissolved C60 mixture324is mixed with the nasal solution to form the nasal mixture1404, and the nasal mixture1404is administered to the nasal cavity1436as the spray1424. In embodiments having the liposomes500, the liposomes500are mixed with the nasal solution to form the nasal mixture1404, and the nasal mixture1404having the liposomes500is administered to the nasal cavity1436as the spray1424.

As shown inFIG. 14, administering the nasal mixture1404includes placing the applicator1416and the nozzle1420within a selected nostril1432of the nose1440of the user. In an example, the applicator1416is placed at least partially into the nostril1432and the nozzle1420is placed fully within the nostril1432in the nasal vestibule1444.

Next, during administration of the nasal mixture1404, the user activates the pump1412in order to generate the spray1424of the nasal mixture1404. The pump1412is activated by squeezing the pump1412. In embodiments of the nasal spray device1400not having the pump1412, the user squeezes the reservoir1408to generate the spray1424.

The spray1424exits the nozzle1420and spreads in the spray pattern. The spray1424is directed into the nasal cavity1436. In some embodiments, the user inhales to draw the spray1424deeper and/or further into the nasal cavity1436. The spray1424directly contacts all the surfaces, the features, and the elements of the nasal cavity1436. As shown inFIG. 14, exemplary surfaces, features, and elements of the nasal cavity1436that are contacted by the spray1424include, but are not limited to, the superior turbinate1448, the middle turbinate1452, the inferior turbinate1456, the nasopharynx1460, the Eustachian tube orifice1464, the fossa of Rosenmüller1468, and the adenoid pad1472.

When the spray1424enters the nasal cavity1436, the C60 molecules100are positioned directly on the surfaces, the features, and the elements of the nasal cavity1436. Moreover, in embodiments having the liposomes500, when the spray1436contacts the surfaces, the features, and the elements of the nasal cavity, the shell504of the liposomes500melt, break, and/or dissolve, and the C60 molecules100escape the liposomes500and contact the surfaces, the features, and the elements of the nasal cavity1436. Accordingly, the dissolved C60 mixture324is administered directly to the nasal cavity1436, and the C60 molecules100are positioned to treat the entire nasal cavity1436. Moreover, at least some of the dissolved C60 mixture324passes to the patient's bloodstream due to the direct contact of the dissolved C60 mixture324with the surfaces, the features, and the elements of the nasal cavity1436. As a result, at least some of the sprayed C60 molecules100are carried throughout the patient's whole body via blood flow and makes the C60 molecules100available to the body.

The sprayed C60 molecules100are available to remove free radicals, reduce inflammation, and provide numerous potential health benefits to substantially all cells in the user's body. For example, the C60 molecules100, when in contact with the surfaces, features, and elements of the nasal cavity1436, reduce signs and symptoms caused by allergic rhinitis. Allergic rhinitis is a chronic upper respiratory disease caused by exposure to allergens that induce immunoglobulin E (IgE) mediated inflammation to the mucus membranes lining the nose and within the nasal cavity1436. It is estimated that 10-40% of the world's population is affected by allergic rhinitis and it is associated with significant medical and economic burden. The C60 molecules100administrated via nasal administration significantly reduce IgE levels, thereby reducing the inflammation and histamine release associated with allergic rhinitis and increasing the comfort of the user. Moreover, in animal models C60 molecules100have demonstrated the ability to reduce IgE significantly when applied topically. Accordingly, topical and/or nasal therapies including the C60 molecules100offer many advantages over oral therapies, such as (i) delivery of the C60 molecules100in greater concentrations to nasal receptor sites at the source of the allergic inflammation, and (ii) a reduction in the risk of systemic side effects. The method1500of administering the C60 molecules100is an adjuvant or treatment of allergic rhinitis.

Moreover, as a powerful antioxidant, the C60 molecules100, administered to the nasal cavity1436according to the method1500, modulate the user's immune system by causing a significant reduction in IgE production caused by chronic airborne environmental allergens. Accordingly, the sprayed C60 molecules100reduce the release of histamines and other cytokines in mast cells, basophils, and eosinophils leading to improvements in the user's allergic response to environmental allergens such as dust mites. The reduction in free radicals caused by the sprayed C60 molecules100also helps healing in the nose including healing of the surfaces, features, and elements of the nasal cavity1436. Accordingly, the nose and nasal administration is an effective delivery system for the C60 molecules100that enables the C60 molecules100to remove excess free radicals, which are part of the pathogenesis of several diseases.

The C60 molecules100nasally administered according to the method1500are useful for additional applications including treating cardiac disease, because the C60 molecules100are delivered to the central nervous system (CNS) through the olfactory and/or trigeminal nerves. As a result, delivery of the C60 molecules100according to the method1500enables treatment for cardiovascular issues, migraine headaches, hypertension, Alzheimer's disease, and multiple sclerosis. Moreover, administration of the C60 molecules100according to the method1500also administers the C60 molecules100for use as a dietary and/or nutritional supplement.

With reference toFIG. 16, a process is described for intranasal treatment for cardiovascular and CNS issues using the C60 molecules100and the method1500. As shown inFIG. 16, the user's nasal cavity1436includes several regions and elements including the olfactory bulb1550, the olfactory epithelium1554, the squamous mucosa1558located at the opening of the nostril1432, and the respiratory epithelium1562including the inferior turbinate1456, the middle turbinate1452, and the superior turbinate1448. The spray1424generated according to the method1500is configured to administer the sprayed C60 molecules100to each of these regions and elements. Specifically, the spray1424including the C60 molecules100contacts directly the olfactory epithelium1554and is absorbed directly into the user's bloodstream. In particular, from the olfactory epithelium1554, the absorbed C60 molecules100travel to the olfactory bulb1550and then directly into the user's brain1566, thereby bypassing the blood-brain barrier. As such, administration of the C60 molecules100according to the method1500delivers a higher dose and a more effective dose of the C60 molecules100directly into the brain1566, as compared to other administration methods of delivering C60.

FIG. 17shows several exemplary pathways for the C60 molecules100through the olfactory epithelium1554. First, the C60 molecules100sprayed according to the method1500bind to a receptor such as an olfactory sensory neuron (OSN)1570and then are internalized by, for example, receptor-mediated endocytosis. According to an intracellular path (left), the internalized C60 molecule100travels through the OSN1570towards the olfactory bulb1550. According to a paracellular path (middle), the internalized C60 molecules100uses leaky passages within the olfactory epithelium1554and travels paracellular into the lamina propria1574. According to a transcellular path (right), the internalized C60 molecule100is transported through the sustentacular cells1578to the lamina propria1574. From there, the internalized C60 molecules100on each path are (i) absorbed by local blood vessels1582reaching blood circulation and/or (ii) absorbed by lymphatic vessels1584and drained into the deep cervical lymph nodes of the neck (not shown). The internalized C60 molecules100may also use perineural spaces between the olfactory ensheathing cells (OECs)1586and olfactory nerve fibroblasts1588to travel to the olfactory bulb1550. According to this approach after passing the cribriform plate1590, the internalized C60 molecules100reach the cerebrospinal fluid1592and distribute through the different regions of the brain1566.

Moreover, depending on the application there may be specific benefits to delivering the C60 molecules100to the user via combinations of nasal administration, oral administration, buccal administration, topical administration, intravenous (IV) administration, and/or inhalation administration including nebulization, vaporization, and dry powder directly to the lungs.