The invention is related to electrodynamic fullerene compositions and pivoting biaxial electrodynamic fullerene compositions (EPF).
Human cells interact quite differently with commensal microbes according to their interdependent and sometimes pathogenic properties as these microbes compete, while surviving inside the human body. The effects of surface charges in contact with water, proteins, and lipid membranes become differently engaged in these interactions.
The study of fungi is generally termed mycology. Fungi are classified to be in a different kingdom from plants, bacteria, or animals. Like animals, fungi secrete enzymes to break down biopolymers into simple sugars and are well known to decompose both living and dead organisms to obtain energy and grow. Fungi are distinguished by the presence of chitin, a complex sugar biopolymer that is present in their cell walls. When a virus colonizes a fungus as a host, this is known as a mycovirus or mycophage. It is commonly understood that virus particles usually colonize bacteria which are present as hosts; in these cases, the invading virus is termed a bacteriophage. The simultaneous predation on both fungi and bacteria hosting of one type of phage (virus) characterizes these virus particles as a mycobacteriophage.
Virus particles are by far the largest mass of evolving carbon-based constructs on planet Earth, wherein most of those viruses colonize or live within bacteria. About 99.99% of viruses are benign, live in balance with their hosts, and do not cause immediate damage to the cells of animals or human beings. The healthy human being is a hierarchy of commensal organisms, where most of the living tissues of a person are microbial, and about 10% of the total genetic mass belongs to cells we recognize to be human; this collection of creatures we call ourselves is therefore better holistically described as a holobiont. Indeed, the loss of some of our symbionts can cause some types of disease. Therefore, any composition that attempts to correct for a disease, had better not create a dysbiosis, or disruption of beneficial microbial relationships that humans rely on to live and help digest food in the process of extracting nutrients.
The highest specialization of animals is neural tissue, where neurons have the greatest need for energy, and therefore also obtain the highest concentration of energy harvesting mitochondria in their structures. In all life, polyphenols have evolved as internal cellular control molecules to regulate the cellular biology of bacteria, plants and animals. Plants have evolved the use of polyphenols as a primary defense against fungal and bacterial invasion. The human consumption of plant derived flavonoids, phytoestrogens, and non-flavonoid polyphenols confer a wide range of long-term nutritional and health benefits. Polyphenols modulate cellular signaling pathways by interacting with molecular receptors to control tissue dilation, inflammation, and to affect the proper function of neurons. Polyphenols interact with neurotransmitters to have a direct effect on cognitive and cerebrovascular, or brain blood flow functions. Mitochondria function as energy harvesting organelles, or sites inside cells where glucose can be used to build proteins and peptides used to build the cellular structure. At least one mitochondrion is present at every branch point of every dendrite in a neuron, and one mitochondrion is always at the growth tip of each dendrite, called the filopodia.
A delicate chemical balance of reduction and oxidation (REDOX) operates mitochondria and drives cellular function, especially neural function, which is the most energy intensive and therefore the most reliant on mitochondria for energy. Nowhere is microbial infection more damaging than in neural tissues, and especially so in the brain. Neural mitochondria can become compromised when virus particles attempt to parasitize the nuclear and mitochondrial genetic processes. The brains of higher organisms have therefore evolved significant redundancy to address viral infection, by becoming larger and more complex. Therefore, it is generally accepted that viruses having host-microbe interactions within animal tissues are responsible for all large brain structure expansion, expressed evolutionarily within all animal life on earth. Because virus particles sometimes recombine and alter their genetic structures to change over time, it is quite likely that the human brain has evolved sporadically to address and adapt to recurrent neural viral infections, by building increased redundancy.
Even as internal isolation barriers, such as the blood brain barrier, aim to prevent most microbial infections from destroying the brain and neural tissues, dietary polyphenols as cell signal molecules are often ineffective in either their recruitment capacity or their antimicrobial capacity to address the viral load in cholesterol or lipid rich regions of cells, being that they prefer to solvate in water rich regions and tend to avoid lipid or cholesterol phase cell membranes. The most sensitive region of the cell where a virus may hide, is therefore in the cholesterol containing membrane that encapsulates the mitochondria, called the endoplasmic reticulum. This is the membrane through which glucose must pass, to change adenosine mono phosphate (AMP), or adenosine diphosphate (ADP) to adenosine triphosphate (ATP), by redox chemistry with active oxygen species, necessary to generate chemical energy and build proteins for use in cellular biomolecules. Animal cells have therefore used the REDOX chemistry within mitochondria to deliberately generate reactive oxygen species (ROS) both to detoxify invasive proteins, and to defend the cell against invasive virus particles having a protein coating around each virus particle, called viral capsids. Of particular interest are the membrane budding viruses, such as the various types of influenza, and herpes simplex virus (HSV), Ebola virus, and also another virus type that has proven to be quite good at hiding from the immune system within phospholipid cell membranes, the human immune deficiency virus (HIV). These viral types are intimately involved with or are greatly amplified in virulence by the acquisition of Adenosine Triphosphate (ATP) and the presence of glucose sugars in the electron charge transfer cycle of cellular respiration.
The immune response of higher animals has evolved epigenetic marks such as DNA methylation, histone modification, and changes in populations of microRNA that are involved in the transfer of immunity and nutritional history to impact heritable immune responses and metabolic modifications so that real experiences in the environment transfer to the phenotype of expressed traits transcending multiple generations. However, the confluence of the immune system training with mitochondrial ROS has drawbacks. Over time, the individual immune response becomes less able to address environmental assaults, so that the production of defensive ROS must become greater in the ageing organism. This means greater ROS to deflect invasive virus particles and other microbes, also results in increased cellular genetic damage by self-oxidation. Overproduction of ROS then leads to cell senescence and cellular self-termination at the end of a certain number of cell divisions. The observation of an upper average limit on cell division was first discovered and reported by Hayflick in 1969 and is generally known today as the Hayflick limit. The Hayflick limit is now known to be controlled by mitochondria in each species, where the lifespan of that organism is at least partly determined by the amount of ROS generated by the mitochondria in that species. The release of ROS by mitochondria is characterized by hydrogen peroxide (H2O2), and a wide variety of biological molecules involved with REDOX control, including Thioredoxin Interacting Protein or TXNIP, and telomerase, which is involved with control of mitochondrial defects resulting from extensive ROS damage. The shortening of telomeres arising from excessive ROS generation eventually exposes DNA to oxidative damage and increases the rate of cell senescence. The presence of long-term latent virus particles, such as herpes simplex and cytomegalovirus hiding in cell membranes, are a chronic cause of ROS generation and telomere shortening, and the confluence of these are implicated in all long-term neural dysfunction and human mental illness.
The herpes viruses, called herpetic virus, of the Herpesviridae family, infects most people worldwide in both developing and developed countries. Cytomegalovirus (CMV) is the herpes virus, of which herpes simplex 1 is associated with the common cold sore. Because about 90% of the world population is infected with herpetic virus, it is likely that everyone is eventually exposed at least once and probably many times during their lifetimes. Following initial infection, CMV establishes a lifelong latent infection, with likely reactivation and reinfection at later dates. In particular, most investigations have shown an association of herpes simplex virus type 1 (HSV-1) with Alzheimer's disease (dementia), but it was not until recently that that a complex chain of events relating to the role of ROS in the etiology of this disease could be clarified. Many reports now suggest that the long-term effects of what apparently begins as a mild short-term viral infection such as influenza or cold sores, could continue to impair the cognitive functions of infected subjects long after the original symptoms abate. Latent phase infection effects may contribute to a wide range of mental illness, impairments, and accumulated cognitive decline, especially cardiovascular disease, and bipolar disorder. It is of special and major concern, however, that the total impact of hepatic viruses and CMV on mental health and human intelligence, may be quite high.
It has been determined that the Herpes Simplex Virus (HSV) and influenza virus require the use of mitochondrial energy compound adenosine triphosphate (ATP) to replicate, and that inhibition or depletion of cellular ATP blocks the maturation of the viral sheath proteins, especially the viral protein 26 or VP26 that is used to form the reproduced HSV virus. While this is interesting, it is also notable that depletion of ATP inevitably leads to cell death from lack of energy to perform respiration and build essential cellular proteins. Mitochondria exhibit a condensed structure of the cristae, indicating the characteristic state of active respiration. More subtle analysis has led researchers to conclude that the VP26 of HSV-1 requires ATP to form the correct angles of the capsid plates to sheath the virus in its protein case during this process. Unfortunately, aside from vaccines that target antibodies to the outside protein coating or capsid of virus particles, no more generally effective strategy has yet been invented or formulated to take medical advantage of well understood ATP recruitment by budding viruses.
One method to improve the human physical condition and cognitive well-being to combat viruses budding from lipid membranes can be achieved by a careful design consideration of cholesteric affinity to enable a synergy with the evolutionary defense at cellular membranes. Such molecules should also operate to confer protective functions to the normal operation of mitochondria, especially those mitochondria in human neural cells and brain tissue. Zanamivir® and Oseltamivir® are antiviral drug examples of molecules having both a lipophilic end to interface with hydrophobic cellular membranes, and ionic portions, usually containing an amine group that allow these ends to interface will with the cellular cytosol. Yet these tools are limited in their ability to help control influenza pandemics or confer immunity to chronic viral infections. These industrial examples are only one part of a complex biological solution, genetic factors, environmental immunity reinforcement, and physical training play interactive roles in the extension of healthy cellular homeostasis.
There is considerable basic science and epidemiological evidence that infectious agents may be contributing to the neuropathology and clinical manifestations of Alzheimer's disease and other neuropathology, and that the herpes simplex virus particle types are present and implicated in these diseases. This viral hypothesis has been in the literature for many decades, and evidence to support this hypothesis has been widely supported. HSV and other viruses are usually also infectious to bacteria, which provide an interesting way to hide from the human immune system to induce recurrent infection via the many microbes that are commensal to the gut and beneficial or used for the survival of humans. Existing treatments for chronic viral initiated diseases have failed, and the need for extended care incurs severe economic costs as well as impairment of the quality of human life in aged individuals. The failure of treatments tested in clinical trials in patients with Alzheimer's Disease during the last decades, together with demographic increases in the age of our populations, underlies the urgency for new sorts of thinking to address these matters.
What is therefore needed is a multiplexed solution for effectively extinguishing influenza, as well as eradicating other budding or latent virus particles such as CMV. Desirably, a general treatment for budding viruses should include a prophylactic prevention of genetic or proteomic damage to human cells, especially neural cells, in response to infection.
These and other advantages of the present invention will be further understood and appreciated by those skilled in the art by reference to the following written specifications, claims and appended drawings.
The present invention provides a composition having a fullerene covalently bonded to a phosphate of adenosine where the phosphorus is in a +5 oxidation state. The fullerene is one of C60 fullerene or C70 fullerene, for example. Where “fullerene” is mentioned, it is to be understood to refer to any fullerene, including C60 fullerene and C70 fullerene. In a first fullerene, the fullerene is covalently bonded to one functional group of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), or cyclic adenosine monophosphate (cAMP). The fullerene derivative is additionally covalently bonded to a second functional group of ATP, ADP, AMP, or cAMP. A second fullerene is van-der-Waals bonded to the first fullerene, where the second fullerene is covalently bonded to at least one preselected amino acid and where the composition includes an electrodynamic biaxially pivoting fullerene pivot molecules. The second fullerene is covalently bonded to a first amino acid that includes arginine. Additionally, the second fullerene is covalently bonded to a first amino acid that includes lysine. Further, the second fullerene is covalently bonded to two amino acids that include arginine and lysine.
The invention also includes a method of exciting fullerene pivot molecules dispersed in an organ or region of treatment, where the treatment may be applied to a cancer, an organ, a portion of a limb, or the entire body of a person.
In one aspect, the method of excitation of fullerene molecular pivots is by the directed application of electromagnetic waves capable of penetrating tissues such as radio waves of greater than 7 GHz, or in some embodiments, electromagnetic infrared light waves being of greater than 800 nanometers.
In another aspect, the method of excitation of fullerene molecular pivots is by the directed application of electric energy pulses, where in some embodiments, the electric waves are sinusoidal or alternating current, and in other embodiments, the electric waves are square waves or can have triangular wave forms.
The invention also includes a method of preparing the foregoing composition, including adding an excess of dry crystalline powder of adenosine triphosphate (ATP) to solvent-free and dry crystalline powder of fullerene in a first predetermined ratio; combining a mixture of the dry crystalline powders in a shear grinding mill under shear pressure below 55° C. for about 15 minutes to produce fullerene-ATP; dissolving fullerene ATP into water and at least 10% glycerol solvent to make a dispersion, wherein the solvents are selected to expedite the delivery of medicament in the finished product mixture and wherein a fullerene-ATP dispersion is produced; adding an excess of dry crystalline powder of at least a first amino acid functional group (R1 ) and a second amino acid functional group (R2) to solvent-free and dry crystalline fullerene in a second predetermined ratio; combining a mixture of the dry crystalline (fullerene and R1 and R2 ) powders in a shear grinding mill under shear pressure below 55° C. for about 15 minutes to produce fullerene-R1-R2; dissolving fullerene-R1-R2 into water and at least 10% glycerol solvent to make a dispersion, wherein the solvents are selected to expedite the delivery of medicament in the finished product mixture and wherein a fullerene-R1-R2 dispersion is produced; combining the fullerene -ATP dispersion with the fullerene-R1-R2 dispersion in a mixer equipped with ultrasonic irradiation to produce an electrodynamic biaxial fullerene pivot; and actuating the electrodynamic biaxial fullerene pivot by irradiating it with ultrasound at about 200 watts and about 40 kilohertz for about 20 min. In one embodiment, R1 includes a first amine and R2 includes a second amine. In further embodiments, R1 includes L-Arginine (Arg) and R2 includes L-Lysine (Lys).
The present invention also includes a method of stimulating the foregoing composition by activating the composition by one of RF radiation or an applied electric current. The applied electric current can be either an AC current or a pulsed DC current, for example, and either at a frequency between about 5.0 GHz to about 11.5 GHz. The RF radiation can also be applied at a frequency between about 5.0 GHz to about 11.5 GHz. However, an upper limit of 10.6 GHz is recommended to avoid heating water in the affected tissues. In still further embodiments stimulating the composition comprises applying infra-red electromagnetic radiation with a wavelength from 800 nm to 1000 nm where living tissues are translucent.
The present invention includes yet another method of preparing the foregoing composition, including combining a dry crystalline powder of adenosine phosphate with solvent-free fullerene powder to produce a first mixture; shearing the first mixture in a shearing mill while maintaining a temperature below 55° C. to produce a covalently reacted first mixture; combining a dry crystalline amino acid powder with solvent-free fullerene powder to produce a second mixture; shearing the second mixture in a shearing mill while maintaining temperature below 55° C. to produce a covalently reacted second mixture; combining the first mixture with the second mixture to create a heterogeneous combination of each; adding about 20 parts water to one part of the combined mixture; irradiating the aqueous mixture for about 3 minutes with microwave radiation at 500 watts per liter to homogenize unlike fullerene derivatives by inductive van-der-Waals intercalation to produce homogenized ATP-fullerene pivot amino acid-fullerene conjugates; mixing ATP-fullerene pivot amino acid-fullerene into water containing about 10% glycerol to produce an ATP-fullerene pivot amino acid-fullerene conjugate solution; and mixing the ATP-fullerene pivot amino acid-fullerene solution with a predetermined substrate to form an ATP-fullerene pivot amino acid-fullerene formulation.
The present invention provides yet another method of preparing the foregoing composition, including combining a dry crystalline powder of adenosine phosphate with solvent-free fullerene powder to produce a first mixture; shearing the first mixture in a shearing mill while maintaining temperature below 55° C. to produce a covalently reacted first mixture; combining a dry crystalline amino acid powder with solvent-free fullerene powder to produce a second mixture; shearing the second mixture in a shearing mill while maintaining temperature below about 54° C. to produce a covalently reacted second mixture; combining the first mixture with the second mixture to create a heterogeneous combination of each; adding about 20 parts water to one part of the combined mixture; irradiating the aqueous mixture with ultrasound at 200 watts and 40 kilohertz for about 20 minutes to homogenize unlike fullerene derivatives by inductive van-der-Waals intercalation to produce homogenized ATP-fullerene pivot amino acid-fullerene conjugates; mixing ATP-fullerene pivot amino acid-fullerene into water containing about 10% glycerol to produce an ATP-fullerene pivot amino acid-fullerene conjugate solution; and mixing the ATP-fullerene pivot amino acid-fullerene solution with a predetermined substrate to form an ATP-fullerene pivot amino acid-fullerene formulation.
Some embodiments are described in detail with reference to the related drawings. Additional embodiments, features, and/or advantages will become apparent from the ensuing description or may be learned by practicing the invention. In the FIGURES, which are not drawn to scale, like numerals refer to like features throughout the description. The following description is not to be taken in a limiting sense but is made merely for describing the general principles of the invention.
Preferred embodiments of the invention will now be described, by way of example, with reference to the accompanying drawings, in which:
Embodiments are described in detail with reference to the related drawings. Additional embodiments, features, and/or advantages will become apparent from the ensuing description or may be learned by practicing the invention. In the FIGURES, which are not drawn to scale, like numerals refer to like features throughout the description. The following description is not to be taken in a limiting sense but is made merely for describing the general principles of the invention.
The following detailed description, taken in conjunction with the accompanying drawings, is merely exemplary in nature and is not intended to limit the described embodiments or the application and uses of the described embodiments. Any implementation described herein as “exemplary” or “illustrative” is not necessarily to be construed as preferred or advantageous over other implementations.
Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary or the following detailed description. It is also understood that the specific devices, systems, methods, and processes illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the inventive concepts defined in the appended claims that there may be variations to the drawings, steps, methods, or processes, depicted therein without departing from the spirit of the invention. All these variations are within the scope of the present invention. Hence, specific structural and functional details disclosed in relation to the exemplary embodiments described herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the present embodiments in virtually any appropriate form, and it will be apparent to those skilled in the art that the present invention may be practiced without these specific details.
Various terms used in the following detailed description are provided and included for giving a perspective understanding of the function, operation, and use of the present invention, and such terms are not intended to limit the embodiments, scope, claims, or use of the present invention.
A composition of partly exposed hydrophobic fullerene cores can be provided with abutting rotational and pivoting carbon faced surfaces, where these fullerene cores are provided with at least one derivatized adenosine (mono, di, tri) phosphate, and desirably also an equal proportion of derivatized amino acids. Anti-viral methods of treatment incorporating this composition as a medicament are directed at the prevention, treatment, and cure of diseases such as influenza (flu), Alzheimer's Disease, as well as virulent virus infections that may lead to some types of cancer. Both C60 and C70 fullerenes may be used, in various embodiments. Pivoting biaxial electrodynamic fullerene compositions can be used to treat budding virus infections by disrupting the electrostatic replication environment in their buds or pockets within the membranes of infected cells.
One aspect of the composition of the present invention is a phosphate fullerene derivative provided with phosphorus with a +5 oxidation state within a desired multiplicity of pendant functional groups containing phosphate or (PO4). This phosphate component acts to distribute an analog to adenosine triphosphate (ATP) into cells as prophylactic molecules to disrupt the geometric angular assembly of HSV and other budding viral capsids. It is conceived that viral and cancer disease states that rely on the recruitment of cellular ATP can be mitigated by the careful design of this chemical structural geometry, to interrupt and deter electrostatic symmetry or electrostatic self-assembly by means of a dynamic change in the electrostatic environment and cytosol medium in which viral replication takes place.
The provided ATP-fullerenes are analogs of ATP that can contribute to cell homeostasis while conferring distorting electric fields to the stable electric environment needed to replicate nearly any known virus. These dynamic pivoting antiviral molecules are especially targeted to avoid chronic neurological pathologies based on viral recruitment of ATP in Alzheimer's disease, as well as to significantly reduce the pathology of budding virus pandemics. Inhibition of herpes simplex virus HSV-1 by penetration of these phosphate fullerenes into the endoplasmic reticulum of cellular mitochondria will prevent the correct angular fitting of viral proteins to form HSV capsids. The ATP-fullerenes attract viral proteins to create incorrect spacing and geometry of charges in the viral assembly process to form mismatched regions that will no longer align to mate with partner capsid proteins to allow the formation of the mature virus.
In a related aspect, the fullerene phosphates are configured to function in the manner of ATP by the reversible loss of a pendant phosphate group to form fullerene-AMP (adenosine monophosphate) pendant groups, while allowing the cell to survive and operate the typical electron transfer pathways used by native cellular ADP and ATP used to respire and sustain life.
Advantageously, at least some of the poly-phosphorylated fullerene molecules express geometric localization of polyphosphates to one pivot molecules at one face or hemisphere of the substantially spherical carbon molecular cage of the fullerene structure, to enable a hydrophilic face directed at mitigating reactive oxygen species (ROS) at the interface between the endoplasmic reticulum (ER) of the mitochondrial cell membrane and the cytosol or water based fluids abutting the ER, while allowing one region of the fullerene core to attach to a cell lipid membrane or a microtubule used in cellular transport. This may avoid molecular damage of cell structures through oxidative stress that can leave cells susceptible to invasive pathogens.
In an embodiment, the composition of the medicament includes additional fullerene molecules that express pendant amino acids, to enable a hydrophilic face directed at reactive oxygen species (ROS) at the interface between the endoplasmic reticulum (ER) of the mitochondrial cell membrane and the cytosol or water-based fluids abutting the ER. The amino-fullerenes function to deactivate viral capsids by binding with them to provide both an anchor and a more permanent seal to prevent infection by the release of viral contents to the cell and the cell nucleus.
In one aspect, the fullerenes destabilize and destroy mycobacteriophages, and thereby assist commensal fungi or bacterial organisms normally in human tissue from indirectly performing genetic DNA methylation via microbial defense mechanisms that release toxins as part of their normal viral toxification mechanisms when being infected by virus particles. This significantly helps to reduce and avoid the creation of improperly folded proteins such as tau and beta amyloid associated with neurological pathologies found in Alzheimer's disease and may reduce the likelihood of environmentally assisted mutagenicity that may in some cases lead to cancer.
In a related aspect, a scissoring action of fullerene pivot molecules containing both positively charged amino fullerenes and negatively charged adenosine phosphate fullerenes act to pierce amyloid plaque salt bridges and to unfold misfolded proteins, thereby allowing these to be more easily disentangled, dispersed, and cleared from the brain extracellular environment as mobile detritus.
Another aspect is the provision of fullerene phosphates and amino fullerenes to cooperatively treat and reduce the spread of budding viruses such as influenza and HSV. One function of the derivatized fullerenes includes the protection of undefended positive ends of dynamic actin filaments used by herpes simplex virus particles (HSV) to invade the cell, and then at a later stage of the viral reproductive cycle, to leave the cell using the negative ends of the microtubule after replication. Fullerene polyphosphates prepared with points of negative charge at their distal spikes are provided to bind to the same positive charged regions of the actin filaments used to transport proteins and glucose into the cell, where the HSV also arrives. If this prevention by displacement fails, then an amino-acid-fullerenes are provided to bind to the same negative charged regions of the actin filaments used to transport proteins and wastes out of the cell.
In another embodiment, pivoting electrodynamic fullerenes diffuse to virus bud cavities, where they then charge-attract and bind with replicating viral components and capsids, especially where the viral proteins have not yet completed the formation of the capsid enclosure, to denature the assembly process, and disrupt the ambient electric fields of electrostatic charge maintenance to allow eviction of the invasive proteins and virus particles by normal diffusion.
In a related aspect, the diffusion eviction process of the electrodynamic fullerene moiety is amplified with the assistance of the application of concentrated radio waves broadcast to the infected person, or an AC electric signal applied to the targeted tissues to treat the targeted organ of infection and inflammation. This action has the effect of magnifying the torsional twist about abutting fullerene centers in any pivot molecules, as well as inducing an out of plane twist motion among or between the oppositely charged ionic functional groups of these fullerene pivot molecules. These dynamic motions are associated with local directional electric field changes in the immediate vicinity of the pivoting derivatized electrodynamic fullerene pivot molecules, thereby destroying those electrostatic field conditions that are necessary to preserve the structural integrity of viral structures and disabling the static conditions needed to promote viral component self-assembly at membrane-based buds providing viral molecular self-assembly platforms. Such energy can be delivered by RF radiation or by electric waves at a frequency of about 8 GHz to about 10.6 GHz.
Recently has it become apparent that these virus-inspired cytoskeleton changes in cells infected with herpes virus, also promote the cell to transform into a cancerous cell. This is because the cells are made to counteract normal growth, after they have been genetically altered to “obey” the virus, thereby causing cancer and the spread of cancer, long after the virus has left. The application of the compositions herein allows the treatment of viral infection to reduce a significant risk of cancer or propagation of cancerous cell growth. Because other neuropathies such as multiple sclerosis (MS) and Alzheimer's disease (AD) also implicate viral infection as a causative agent, the present invention is to be directed at MS, AD, and any other diseases having certain types of virus particles as part of their etiology and disease progression, especially when these virus particles require utilization of cellular ATP, and may be treated by a molecular masquerade of fullerenes that have been decorated or derivatized with ATP.
Referring now to the drawings wherein like elements are represented by like numerals throughout,
However, unlike conventional ATP, the ATP-fullerene nanoparticle creates a geometric size anomaly when it is incorporated into the regular structure of a virus particle, thereby throwing off the angular dependence and symmetry needed to knit together the seams of the abutting viral protein plates using multiple identical ATP molecules as part of the HSV protective covering. This three-dimensional complexity of ATP-fullerene confers artificial innate immunity to cells against virus particles using intelligent three-dimensional geometric design and constitutes a novel and critical new biological defense function for this nanoparticle.
Additionally, the presence of positive charges on the amine groups of pendant amino acids 850, 860, or like amino acid functional groups as shown in
Moreover, the presence of negative charges on the phosphate groups of pendant adenosine phosphate molecules 850, 860, or like fullerene phosphate functional groups as shown in
Core fullerene 930 obtains a partial negative charge in the region away from the direction of attraction 950 towards core fullerene 940. Simultaneously, the core fullerene 940 obtains a partial positive charge in the region away from the direction of attraction 960 towards core fullerene 930. This process of electrostatic attraction by dispersed partial electronic charges of opposing type is generally known and well described in the scientific literature as the van-der-Waals effect. The pivoting electrodynamic fullerenes relies on van-der-Waals attraction 950, 960 to implement the pivoting function of abutting core fullerenes exemplified by representative core fullerenes 930, 940 in the manner of two abutting ball-bearings that are constructed using nanometer-sized molecules. The van-der-Waals attractive forces 950, 960 serve as self-supporting attractive anchors for the core fullerenes 930, 940 to permit a forceps or pincer type of fulcrum function where the pair of large arrows 970, 980 show the directions used to bring together the molecular armatures provided by the adenosine tri-phosphate derivative 910, and the exemplary arginine amino acid derivative 920 into proximal distance indicated by D1. Under cytosol conditions of physiological pH, adenosine triphosphate group 910 obtains a negative charge at a terminal phosphate group, and arginine amino acid group 920 obtains a positive charge at the amine group, both of which opposing electrostatic charges allow each to become reversibly attracted to each other or to become reversibly attracted to counter-opposing charges in viral proteins or viral nucleic acids. Optionally, the collective structures of the electrodynamic biaxially pivoting fullerene derivatives composition are attracted to and carry a therapeutic molecular drug cargo indicated by the intercalated substance 990, being an antibody, an anti-cancer gallium ion Ga3+, or other therapeutic substance that is to be delivered to an intended organ and cellular site such as a tumor or a cancerous growth that can be associated with pathogenic viral infection as an initiator of the tumor or cancer. Extraction of the delivered therapeutic cargo 990 is provided by the widening of distance D1, such as when the surrounding electronic conditions permit. For example, when the negatively charged phosphate group on pendant phosphate armature derivative 910 becomes attracted to a positive surface charged cell membrane lipid such phosphatidyl serine. As another example, when the positively charged amine group on pendant amino-acid armature 920 becomes attracted to a negative surface charged cell membrane lipid such as phosphatidyl choline. In addition, other factors can influence the electrostatic field near or abutting to electrodynamic biaxially pivoting fullerene pivot molecules 900, such as the provision of electromagnetic irradiation as illustrated in
The electromagnetically actuated electrodynamic biaxially pivoting fullerene molecules 1000 are provided with proximal counter-ionic functional groups 1010, 1020 which bond to and stretch apart the angularized viral proteins and serve to displace and distort nucleic components growing from their protected positions against the inner membrane wall bud of the cell that has been pinched off and overtaken by the micromachinery of replicating virus. The application of a dynamically changing electric environment provides the pivoting antiviral fullerene composition the ability to lyse, scissor, disrupt, and ‘chop’ viral replication platforms and cancers. This serves to disrupt their electrostatic stasis, thereby creating a dynamic viral disassembler. The irradiation amplitude and frequency of the irradiation 1050 actuates the molecular armatures 1010, 1020 to reversibly cycle the stretched distance of the gap D2 between a negative charged phosphate group 1010 and a positive charged amine group 1020. This action also allows the controlled release of the optional drug constituent 1060, and the deactivation of virus or virus components as well as the cell lysing of cancer cells provided by the electromagnetically induced rotation and twist of the pivoting fullerene molecule 1000. The region of the irradiation 1050 defines the treatment area that contains a multiplicity of fullerene molecular pivots 1000. The region of the irradiation 1050 can be targeted to a single tumor, or it can be a larger targeted region such as an organ or portion of a limb, or in some embodiments, such as for example to treat a diffuse cancer such as leukemia, it can be the entire body of a person, in accordance with the intent of the present invention.
The electromagnetic radiation 1110 can also be optionally introduced to the virally infected region or a tumor as an electrical voltage in the form of, without limitation, sinusoidal, square, or sawtooth waves. Electromagnetic radiation 1110 is desirably resonant with the structure of the electrodynamic biaxially pivoting fullerene composition 1140, 1150, thereby enhancing and further energizing the natural biaxial pivoting and changing local electric fields of these molecules. The electromagnetic radiation 1110 provides more energy than that associated with random thermal vibrations, so that the electrostatic environment is disrupted sufficiently to prevent the viral assembly and replication conditions within membrane buds 1120 by removing the state of unchanging electrostatic fields needed to self-assemble virus particle components such as representative viral proteins and nucleotides 1135.
The electromagnetic radiation 1110 can also be light waves between the wavelengths of about 800 nm to about 1000 nm where living tissues are translucent. It is to be understood that any combination of the RF, light, and electrical types of irradiated waves can be applied to the electrodynamic biaxially pivoting fullerene composition 1140, 1150, in any sequence and in any combination whatsoever to help energize the therapeutic treatment using this composition.
In a step S1240, an excess of dry crystalline powder of L-lysine and L-arginine are added to solvent-free and dry crystalline fullerene in a nominal ratio of 1 mole fullerene to 1 mole of lysine and 1 mole of arginine. Any amino-acid capable of providing an amine functional group near or at the terminal end of the amino-acid, can provide the desired positively charged molecular armature. However, the selection of two different types or lengths of amino-acid as pendant fullerene functional groups helps to ensure a complex electrodynamic environment for this ingredient of the composition.
In a step S1250, the combined mixture of dry powders is placed into a shear grinding mill and allowed to react at greater than 1000 per second below 55° C. for about 15 minutes. Because this reaction takes place in air, the temperature may not exceed 60° C. or be operated in the grinding process for a longer time, because of thermal degradation and oxidative decomposition of the amine reactants. A desired lower limit of one or two amino acid functional groups, with an upper limit of about 3 to 4 amino acid functional groups can easily be achieved as derivatives to the core fullerene in this process. Some excess amino acid molecules will become entrapped or intercalated between Lysine-Arginine-fullerene molecules, however these do not otherwise reduce the efficacy of the product, providing enough bare carbon fullerene core remains present to enable the pivoting action of the core fullerenes in the final composition. In a step S1260, the reacted products of step S1240 are dissolved into water with about 10% glycerol solvent, where the solvents are selected to expedite the desired delivery of medicament in the finished product mixture.
In a step S1270, the Lysine-Arginine-fullerene solution and the ATP-fullerene solution are combined in a mixer equipped with ultrasonic actuation. The purpose of the ultrasonic irradiation is to allow inter-dispersion of unlike fullerene derivatives to create the desired hybrid fullerene pivot molecules in suspension. At this point, an optional desired medicament may be added into this mixture. This medicament can be driven into and between the unlike derivatized fullerene molecules to confer enhanced transport into cells, using any physical method of delivery. Exemplary medicaments to be incorporated as a payload to the electrodynamic fullerene pivot molecules may include a drug, multiple drugs, nutraceutical, nootropic, senolytic, anti-cancer, other types of derivatized fullerenes, and any combination thereof without limit, when the dosage is used to cure or prevent disease.
In a step S1330, a cellulose dialysis disc having a molecular weight cutoff of 3500 Daltons, for example, is rinsed with distilled water to remove any packaging glycerol. An exemplary 33 mm disc is the Spectra/Por™ RC, manufacturer number 132488, provided by Repligen at 18617 South Broadwick Street, Rancho Dominguez, Calif. 90220, USA.
In a step S1340, the aqueous EPF solution is dialyzed, in a cellulose dialysis bag for example, into blood plasma to obtain the desired concentration of EPF in sterile blood plasma at a physiological pH. By passing through the dialysis filter, potential impurities greater than 3500 Daltons as well as possible dust is removed. This composition is then transferred to a substrate, which can be a predetermined mixture of other antiviral medicaments, amino acid derivatized fullerenes, or optional preselected polyphenols desired to complete the intended formulation or serving. Ideally, these materials are substantially water soluble or water dispersible, and can be driven into the spaces between ATP-fullerene with ATO-LYS-ARG pivot molecules while mechanically stirring and using ultrasound applied to the combined mixture at, for example, about 200 watts and about 40 kilohertz for about 20 minutes.
In a step S1350, the sterile dialyzed blood plasma EPF solution is administered, for example by injection or intravenous (IV) drip to the patient as specified by an attending physician. A drip rate may be adjusted by an infusion pump to vary depending on the prescribed dosage and concentration, which can relate to the body weight of the patient as well as the severity of the microbial load to be addressed, which has been determined in the patient.
In step a S1360, electromagnetic radiation of, for example, 10.6 gigahertz of radio frequency (RF) is applied to the region or tissues that are the target of the drug release therapy or that are the target of localized tumor treatment. The function of cell lysis is provided by the RF energy supplied to the pivoting electrodynamic biaxial fullerenes to enable their scissoring which is used to actuate the EPF fullerene composition for the purpose of substantially destroying the tumor or cancer cells, or for sterilizing the local region of infected tissues.
As variations, combinations and modifications may be made in the construction and methods herein described and illustrated without departing from the scope of the invention, it is intended that all matter contained in the foregoing description or shown in the accompanying drawings shall be interpreted as illustrative rather than limiting. Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments but defined in accordance with the foregoing claims appended hereto and their equivalents.
This application is a Continuation-in-Part of International Application PCT/US20/32976 filed on May 14, 2020 which claims the benefit of U.S. provisional patent application No. 62/977,352 filed on Feb. 16, 2020 both entitled “Pivoting Electrodynamic Composition and Medicament,” and both incorporated herein in their entireties.
| Number | Date | Country | |
|---|---|---|---|
| 62977352 | Feb 2020 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US20/32976 | May 2020 | US |
| Child | 17874669 | US |