PIVOTING ELECTRODYNAMIC COMPOSITION AND MEDICAMENT
20220362400 · 2022-11-17
Inventors
Cpc classification
A61K47/6949
HUMAN NECESSITIES
C07H1/00
CHEMISTRY; METALLURGY
A61K47/549
HUMAN NECESSITIES
International classification
Abstract
A first derivative of a fullerene is covalently bonded to an adenosine phosphate such as adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, or cyclic adenosine monophosphate. A second fullerene is covalently bonded to a second type of functional group including amines of arginine and lysine. The second fullerene is then van-der-Waals bonded to the first fullerene, to form a biaxially pivoting fullerene molecular composition. This composition can be treated to intercalate and carry a drug or an antibody for later release by directed irradiation. The injected composition with optional drug carrier is electrodynamically activated by irradiation of the injected target organ or tissues by the application of, for example, radio frequency (RF) energy to release the drug and lyse the targeted cells.
Claims
1. A formulation comprising: a first fullerene covalently bonded to an adenosine phosphate.
2. The formulation of claim 1, wherein the first fullerene comprises a C60 fullerene or C70 fullerene.
3. The formulation of claim 1, wherein the adenosine phosphate comprises an adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, or cyclic adenosine monophosphate.
4. The formulation of claim 3 wherein the first fullerene is additionally covalently bonded to a second adenosine phosphate.
5. The formulation of claim 4, further comprising: a second fullerene van-der-Waals bonded to the first fullerene, wherein the second fullerene is also covalently bonded to a first amino acid.
6. The formulation of claim 5, wherein the first amino acid comprises arginine.
7. The formulation of claim 5, wherein the first amino acid comprises lysine.
8. The formulation of claim 7, wherein the second fullerene is also covalently bonded to a second amino acid comprising arginine.
9. A method of preparing an electrodynamic biaxially pivoting fullerene pivot molecules, comprising: adding dry crystalline adenosine triphosphate powder to a dry crystalline fullerene powder in about a molar 1:1 ratio to form a first mixture thereof; reacting the first mixture in a first shear grinding mill at greater than 1000 per second shearing rate at below 55° C. for about 15 minutes to produce fullerene-ATP; dissolving the fullerene-ATP into water including at least 10% glycerol to make a fullerene-ATP dispersion; adding a dry crystalline powder of a first amino acid functional group (R1 ) and a dry crystalline powder of a second amino acid functional group (R2 ) to dry crystalline fullerene powder in a molar ratio of about 1:1:1 to form a second mixture thereof; reacting the second mixture in a second shear grinding mill under shear pressure below 55° C. for about 15 minutes to produce fullerene-R1-R2; dissolving the fullerene-R1-R2 into water including at least 10% glycerol to make a fullerene-R1-R2 dispersion; and combining the fullerene-ATP dispersion with the fullerene-R1-R2 dispersion in a mixer while applying ultrasonic radiation to the combined dispersions to produce an electrodynamic biaxial fullerene pivot.
10. The method of claim 9, wherein R1 comprises a first amine and R2 comprises a second amine.
11. The method of claim 10, wherein R1 comprises L-arginine and R2 comprises L-lysine.
12. The method of claim 9 further comprising combining a therapeutic constituent with the electrodynamic biaxial fullerene pivot.
13. The method of claim 12 wherein the therapeutic constituent comprises a drug, a Ga3+ ion, an antibody, or mRNA.
14. The method of claim 12 wherein combining the therapeutic constituent with the electrodynamic biaxial fullerene pivot includes adding the therapeutic constituent to the combination of the fullerene-ATP dispersion with the fullerene-R1-R2 dispersion in the mixer.
15. The method of claim 12 further comprising adding the electrodynamic biaxial fullerene pivot to a saline solution and adding the saline solution including the electrodynamic biaxial fullerene pivot to blood plasma.
16. A method of treatment, comprising: administering to a patient a formulation of an electrodynamic biaxial fullerene pivot molecule including a retained therapeutic constituent; and stimulating the electrodynamic biaxial fullerene pivot molecule to release the therapeutic constituent molecule to a treatment area of the patient by applying RF electromagnetic radiation with a frequency of between about 5.0 GHz to about 11.5 GHz, or applying an electric current, with a frequency of between about 5.0 GHz to about 11.5 GHz, or applying infra-red electromagnetic radiation with a wavelength of about 800 nm to about 1000 nm.
17. The method of claim 16, wherein the frequency is between about 9.5 GHz to about 11.5 GHz.
18. The method of claim 16, wherein the applied RF radiation or electric current is provided at about 500 watts per liter.
19. The method of claim 16, wherein the formulation comprises blood plasma including the electrodynamic biaxial fullerene pivot retaining the therapeutic constituent.
Description
BRIEF DESCRIPTION OF DRAWINGS
[0025] Preferred embodiments of the invention will now be described, by way of example, with reference to the accompanying drawings, in which:
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[0043] 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.
DETAILED DESCRIPTION
[0044] 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.
[0045] 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.
[0046] 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.
[0047] 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.
[0048] 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 (PO.sub.4). 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.
[0049] 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.
[0050] 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.
[0051] 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.
[0052] 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.
[0053] 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.
[0054] 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.
[0055] 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.
[0056] 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.
[0057] 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.
[0058] 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.
[0059] Referring now to the drawings wherein like elements are represented by like numerals throughout,
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[0063] 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.
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[0068] 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
[0069] 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
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[0071] 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
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[0073] 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.
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[0075] 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.
[0076] 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.
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[0078] 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.
[0079] 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.
[0080] 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.
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[0082] 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.
[0083] 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.
[0084] 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.
[0085] 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.
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[0090] 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.