WO2020046294A1 - Biochemical scaffolds for modulating cell function - Google Patents
Biochemical scaffolds for modulating cell function Download PDFInfo
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- WO2020046294A1 WO2020046294A1 PCT/US2018/048589 US2018048589W WO2020046294A1 WO 2020046294 A1 WO2020046294 A1 WO 2020046294A1 US 2018048589 W US2018048589 W US 2018048589W WO 2020046294 A1 WO2020046294 A1 WO 2020046294A1
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
Definitions
- the present invention relates to compositions and methods for inducing cell activity. More particularly, the present invention relates to biochemical scaffolds and associated methods for inducing, supporting and/or enhancing cell activity and, thereby, function.
- Reduction of cellular energy can also result in dysfunction of various organs, e.g., heart and/or liver failure.
- cellular energy approaches zero, cell death, i.e. apoptosis, is often encountered.
- cellular energy is directly dependent on various biochemical processes; particularly, cell respiration, i.e. metabolic reactions and processes that take place in the cells to convert biochemical energy from nutrients into adenosine triphosphate (ATP).
- cell respiration i.e. metabolic reactions and processes that take place in the cells to convert biochemical energy from nutrients into adenosine triphosphate (ATP).
- ATP adenosine triphosphate
- the metabolic reactions and processes which are often referred to as a metabolic pathway, are typically embodied in the Krebs cycle.
- Fig. 1 there is shown a schematic illustration of a Krebs cycle.
- a two carbon organic product i.e. acetate in the form of acetyl-CoA
- H 2 0 Acetyl-CoA and two equivalents of water (H 2 0) are consumed during the citric acid cycle, producing two equivalents of carbon dioxide (C0 2 ) and one equivalent of HS-CoA.
- one complete evolution of the Kreb cycle converts three equivalents of nicotinamide adenine dinucleotide (NAD + ) into three equivalents of reduced NAD + (NADH), one equivalent of ubiquinone (Q) into one equivalent of reduced ubiquinone (QH?), and one equivalent each of guanosine diphosphate (GDP) and inorganic phosphate (Pi) into one equivalent of guanosine triphosphate (GTP).
- the NADH and QH? generated during the Kreb cycle are in turn used by the oxidative phosphorylation pathway to generate energy-rich adenosine triphosphate (ATP).
- a primary source of acetyl-CoA is carbohydrates, which are broken down by glycolysis to produce pyruvate. Pyruvate, in turn, is decarboxylated by the enzyme pyruvate dehydrogenase. The decarboxylated pyruvate generates acetyl-CoA, according to the following equation:
- Various elements and compositions have thus been employed to modulate one or more Krebs cycle processes to enhance cell activity and, thereby, generation of ATP.
- calcium has been successfully employed to regulate the Krebs cycle.
- Calcium activates pyruvate dehydrogenase phosphatase, which, in turn, activates the pyruvate dehydrogenase complex.
- Calcium also activates isocitrate dehydrogenase and a-ketoglutarate dehydrogenase. This increases the reaction rate of many of the sequences in the cycle, and therefore increases flux throughout the pathway.
- Citrate has also been employed as a feedback inhibitor. Citrate inhibits phosphofructokinase, i.e. an enzyme involved in glycolysis that catalyses formation of fructose 1 ,6-bisphosphate, which is a precursor of pyruvate. This inhibits the formation of a high rate of flux when there is an accumulation of citrate.
- phosphofructokinase i.e. an enzyme involved in glycolysis that catalyses formation of fructose 1 ,6-bisphosphate, which is a precursor of pyruvate. This inhibits the formation of a high rate of flux when there is an accumulation of citrate.
- HIF hypoxia-inducible factors
- HIF is synthesized consititutively. Hydroxylation of at least one of two critical proline residues also mediates their interaction with the von Hippel Lindau E3 ubiquitin ligase complex, which targets them for rapid degradation. This reaction is catalyzed by prolyl 4- hydroxylases.
- biochemical scaffolds that enhance cell activity and function and, thereby, physical and mental function, by inducing the generation and proliferation of selective cells and associated elements.
- biochemical scaffolds that enhance cell activity and function and, thereby, physical and mental function, by modulating at least one Krebs cycle metabolic reaction, process and/or pathway.
- the present invention is directed to biochemical scaffolds and associated methods that induce and/or modulate at least one, more preferably, a plurality of molecular activities, including, without limitation, inducing (i) at least one Krebs cycle metabolic reaction, process and/or pathway, (ii) generation or proliferation of glutathione and/or a member of the glutathione family, (ii) generation or proliferation of at least one n euro transmitter, and/or modulating the transmission thereof by and between neurons, (iv) inducing and/or supporting mitochondrial DNA activity and (v) cell receptor activity.
- biochemical scaffolds of the invention By virtue of the noted modulated molecular activities that are induced by the biochemical scaffolds of the invention, cellular function and, thereby, physical and mental function, is significantly enhanced. It has also been found that administration of the biochemical scaffolds of the invention to a subject can, and in many instances will ameliorate various physical disorders, including neuropathic pain, inflammation and core temperature spikes, and mental disorders, such as post-traumatic stress disorder (PTSD), depression and anxiety.
- PTSD post-traumatic stress disorder
- the biochemical scaffolds of the invention can also be employed to abate drug dependence;
- the biochemical scaffolds comprise two platforms: a vibrational energy platform and a bioenergetic platform.
- the vibrational energy platforms comprise at least one laser activated biologically targeted energy blank or signature.
- the bioenergetic platforms comprise a specially formulated complex proprietary liquid herbal blend, i.e. a tincture, of oxygen enriched glycerin infused water molecules, and a specific assortment of complex-B vitamins.
- the bioenergetic platforms comprise at least one Krebs cycle modulator, glutathione modulator, neurotransmitter modulator, DNA modulator or endocannabinoid modulator.
- the bioenergetic platforms comprise a mixture comprising two or more of the noted modulators.
- the bioenergetic platforms comprise at least one Krebs cycle modulator, neurotransmitter modulator, and endocannabinoid modulator.
- the Kreb cycle modulators induce and/or modulate at least one Krebs cycle metabolic reaction, process and/or pathway, including, without limitation, Krebs cycle product inhibition and/or substrate availability.
- the Kreb cycle modulators also induce the production of C0 2 , acetyl-CoA, FAD FI? and/or adenosine triphosphate (ATP).
- the Krebs cycle modulators comprise, without limitation, ashwaganda, eleuthero root (or extract), maca, an amino acid, e.g., L- arginine and L-citrulline, and vitamins B 2 , Bi, B 3 , B 5 and B 9.
- the glutathione modulators induce the generation or proliferation of glutathione and/or a member of the glutathione family, including, without limitation, glutathione peroxidase, and/or catalase synthesis.
- the glutathione modulators comprise, without limitation, schisandra chinensis berry, damiana and epimedium, maca, nettle leaf, Fe and Cu, and B-vitamins selected from the group comprising B 2 , B 5 , B 6 and B 7 .
- the neurotransmitter modulators comprise, without limitation, nettle leaf, maca, eleuthero root, Yohimbe, cannabidiol (CBD), epimedium, and vitamins Bi and B 6 .
- the DNA modulators support and/or enhance mitochondrial DNA activity.
- the DNA modulators support and/or enhance mitochondrial DNA activity by protecting and/or facilitating the repair of mitochondrial DNA.
- the DNA modulators comprise, without limitation, vitamin Bi?.
- the endocannabinoid system modulators induce cell receptor activity.
- the endocannabinoid system modulators induce cannabinoid receptor activity.
- the endocannabinoid system modulators comprise cannabidiol (CBD).
- the bioenergetic platform includes a cofactor, including, without limitation, organic cofactors, such as flavin and heme, and inorganic cofactor, such as metal ions of magnesium (Mg 2+ ), copper (Cu + ), manganese (Mn 2+ ), and iron-sulfur clusters.
- organic cofactors such as flavin and heme
- inorganic cofactor such as metal ions of magnesium (Mg 2+ ), copper (Cu + ), manganese (Mn 2+ ), and iron-sulfur clusters.
- the vibrational energy platform comprises energy signature components (or extracts) derived from selective herbs and biological agents, including, without limitation, schisandra chinensis, damiana leaf, eleuthero root, stinging nettle leaf, maca root, yohimbe root, epimedium, L-arginine, and L-citrulline.
- the biochemical platforms further comprise a
- pharmacological agent or composition that induces or modulates a physiological or biological process, or cellular activity, e.g., induces proliferation, and/or growth and/or regeneration of cells.
- the biochemical platforms can be delivered to host tissue by various conventional means, including, without limitation, oral, sublingual, nasal, direct injection, topical application, etc.
- FIGURE 1 is a schematic illustration of a Krebs cycle
- FIGURE 2 is a schematic illustration of creatine phosphate - ATP interaction
- FIGURE 3 is a schematic illustration of electrochemical signal transmission
- FIGURES 4 A and 4B are tables of biochemical scaffolds, according to the invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
- vibrational energy platform means and includes biologically targeted complex, stable, and efficient energetic blanks and glycerol water- soluble molecules, which, when programmed with a laser charged imprint of herbs, minerals, vitamins, amino acids, or pharmaceutical properties (creating energy-signature templates), help stimulate/enable/enhance vital cellular biochemical processes necessary to maintain homeostasis.
- Krebs cycle modulator means and includes an element, agent, drug, compound, composition of matter or mixture thereof, including its formulation, which induces and/or modulates a Krebs cycle metabolic reaction, process and/or pathway, including, without limitation, Krebs cycle product inhibition and/or substrate availability.
- suitable Krebs cycle modulators comprise, without limitation, eleuthero root (or extract), maca, an amino acid, e.g., L-arginine and L-citrulline, and vitamins B 2 , B ] , B 3 , B 5 and B 9 vitamins B2, Bl, B3, B5 and B9.
- neurotransmitter modulator means and includes an element, agent, drug, compound, composition of matter or mixture thereof, including its formulation, which induces the generation or proliferation of at least one neurotransmitter and/or modulates the transmission thereof by and between neurons and, hence, cells.
- suitable neurotransmitter modulators comprise, without limitation, nettle leaf, maca, eleuthero root, Yohimbe, and vitamins Bi and B 6 .
- glutathione modulator means and includes an element, agent, drug, compound, composition of matter or mixture thereof, including its formulation, which induces the generation or proliferation of glutathione and/or the glutathione family, including, without limitation, glutathione peroxidase.
- glycosylcholine modulator also means and includes an element, agent, drug, compound, composition of matter or mixture thereof, including its formulation, which induces catalase synthesis.
- suitable glutathione modulators comprise, without limitation, schisandra chinensis berry, damiana and epimedium, maca, nettles leaves, iron (Fe) and copper (Cu), and B-vitamins selected from the group comprising B 2 , B 5 , B 6 and B 7 .
- the tenn“DNA modulator,” as used herein, means and includes an element, agent, drug, compound, composition of matter or mixture thereof, including its formulation, that induces and/or modulates mitochondrial DNA, including protecting and/or facilitating the repair of mitochondrial DNA.
- a suitable DNA modulator comprises, without limitation, vitamin Bn.
- endocannabinoid system modulator means and includes an element, agent, drug, compound, composition of matter or mixture thereof, including its formulation, which induces and/or modulates cell receptor activity; particularly, a cannabinoid receptor, i.e. CB1 or CB2.
- a suitable cannabinoid receptor i.e. CB1 or CB2.
- endocannabinoid system modulator comprises, without limitation, cannabidiol (CBD).
- CBD cannabidiol
- the terms“cellular dysfunction” and“cell dysfunction” are used interchangeably herein and mean and include a reduction or impairment in physical structure or function of a cell.
- the term“organ dysfunction”, as used herein, means and includes a reduction or impairment in physical structure or function of a mammalian organ, including, without limitation, the cardiovascular vascular system (heart and lungs), digestive system (salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines, colon, rectum and anus), endocrine system (hypothalamus, pituitary gland, pineal body, thyroid, parathyroids and adrenals), excretory system (kidneys, ureters, bladder and urethra), immune system
- lymphatic system tonsils, adenoids, thymus and spleen
- integumentary system skin, hair and nails
- muscular system nervous system (brain and spinal cord)
- reproductive system ovaries, fallopian tubes, uterus, vagina, mammary glands, prostate and penis
- respiratory system pharynx, larynx, trachea, bronchi and diaphragm
- skeletal system bones, cartilage, ligaments and tendons
- prevent and “preventing” are used interchangeably herein, and mean and include reducing the frequency or severity of a disease, condition, dysfunction or disorder.
- the term does not require an absolute preclusion of the disease, condition, dysfunction or disorder. Rather, this term includes decreasing the chance for disease occurrence.
- “treat” and “treatment” are used interchangeably herein, and mean and include medical management of a patient with the intent to cure, ameliorate, stabilize, or prevent a disease, pathological condition, dysfunction or disorder.
- the terms include“active treatment”, i.e. treatment directed specifically toward the improvement of a disease, pathological condition, dysfunction or disorder, and“causal treatment”, i.e. treatment directed toward removal of the cause of the associated disease, pathological condition, dysfunction or disorder.
- treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, dysfunction or disorder “preventative treatment”, i.e. treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, dysfunction or disorder, and“supportive treatment”, i.e. treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, dysfunction or disorder.
- pharmaceutical agent “active agent” and “drug” are used interchangeably herein, and mean and include an agent, drug, compound, composition of matter or mixture thereof, including its formulation, which provides some therapeutic, often beneficial, effect.
- the terms“pharmacological agent,”“active agent” and “drug” thus mean and include, without limitation, antibiotics, anti-viral agents, analgesics, steroidal anti inflammatories, non-steroidal anti-inflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, enzymes and enzyme inhibitors, anticoagulants and/or antithrombotic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, and vasodilating agents.
- terapéuticaally effective means that the amount of a Krebs cycle modulator, glutathione modulator, neurotransmitter modulator or DNA modulator and/or biochemical scaffold formed therefrom or pharmacological or bioactive agent administered to a subject is of sufficient quantity to ameliorate one or more causes, symptoms, or sequelae of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination, of the cause, symptom, or sequelae of a disease or disorder.
- delivery and“administration” are used interchangeably herein, and mean and include providing a Krebs cycle modulator, glutathione modulator,
- patient and“subject” are used interchangeably herein, and mean and include warm blooded mammals, humans and primates; avians; domestic household or farm animals, such as cats, dogs, sheep, goats, cattle, horses and pigs; laboratory animals, such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like.
- the present invention is directed to biochemical scaffolds and associated methods that induce and/or modulate at least one, more preferably, a plurality of molecular activities, including, without limitation, inducing (i) at least one Krebs cycle metabolic reaction, process and/or pathway, (ii) generation or proliferation of glutathione and/or a member of the glutathione family, (iii) generation or proliferation of at least one neurotransmitter, and/or modulating the transmission thereof by and between neurons, (iv) inducing and/or supporting mitochondrial DNA activity and (v) cell receptor activity.
- biochemical scaffolds of the invention As also indicated above, by virtue of the noted modulated molecular activities that are induced by the biochemical scaffolds of the invention, cellular activity and function and, thereby, physical and mental function, is significantly enhanced. It has also been found that administration of the biochemical scaffolds of the invention to a subject can, and in many instances will ameliorate various physical disorders, including neuropathic pain, inflammation and core temperature spikes, and mental disorders, such as post-traumatic stress disorder (PTSD), depression and anxiety.
- the biochemical scaffolds of the invention can also be employed to abate drag dependence; particularly, opioid and heroin dependence.
- the biochemical scaffolds comprise two platforms (and components associated therewith): a vibrational energy platform and a bioenergetic platform.
- the bioenergetic platforms comprise a composition comprising oxygen enriched glycerin infused water molecules.
- the bioenergetic platforms comprise an herbal/vitamin composition comprising selective herbs, e.g., eleuthero root and Yohimbe, and B-vitamins.
- the bioenergetic platforms comprise at least one Krebs cycle modulator, glutathione modulator,
- neurotransmitter modulator DNA modulator or endocannabinoid modulator.
- the bioenergetic platforms comprise a Krebs cycle modulator and/or glutathione modulator and/or neurotransmitter modulator and/or DNA modulator and/or endocannabinoid modulator.
- the bioenergetic platforms comprise a plurality of Krebs cycle modulators and/or glutathione modulators and/or neurotransmitter modulators and/or DNA modulators and/or endocannabinoid modulators.
- the Kreb cycle modulators induce and/or modulate a Krebs cycle metabolic reaction, process and/or pathway, including, without limitation, Krebs cycle product inhibition and/or substrate availability.
- the Kreb cycle modulators also induce multiple Krebs cycle reactions and/or pathways, resulting in the production of C0 2 , and/or acetyl-CoA, and/or FADH 2 , and enhanced adenosine-5'- triphosphate (ATP) energy potential.
- ATP adenosine-5'- triphosphate
- ATP is a multifunctional nucleoside triphosphate that is used as a coenzyme in cells. ATP is one of the end products of photophosphorylation and cellular respiration, and is used by structural proteins in many cellular processes, including biosynthetic reactions, motility, and cell division.
- Mammalian mitochondria are organelles that produce more than 90% of cellular ATP. In addition to supplying ATP, i.e. cellular energy, mitochondria are also involved in other cellular mechanisms, including cellular differentiation, apoptosis, as well as cell cycle modulation and cell growth. [00096] Mitochondria provide intracellular ATP via a process called glycolysis, which breaks down monosaccharides into ATP through a series of biochemical processes.
- Mitochondria contain, among other things, the Krebs cycle enzymes that are involved in heme biosynthesis and the electron transport chain, i.e. the Oxidative Phosphorylation pathway (OxPHOS) system. Due to the large flux of redox reactions necessary to maintain oxidative phosphorylation, mitochondria are the primary site of production of reactive oxygen species (ROS).
- ROS reactive oxygen species
- the OxPHOS system is composed of five large multi-protein enzyme complexes, which collectively transform the reducing energy ofNADH and FADFR to ATP.
- NADH ubiquinone oxidoreductase (Complex I) contains 45 different subunits, and succinate ubiquinone reductase (Complex II), ubiquinone-cytochrome c oxidoreductase (Complex III), cytochrome c oxidase (Complex IV) and the ATP synthase (Complex V) have 4, 11, 13 and 16 subunits, respectively.
- Transient ischemia results in the local production of extremely high levels of ROS, which can cause long term damage to mitochondria.
- oxygen is scarce, but tissue demands for ATP remain high, resulting in continued functioning of the OxPhos system except for the terminal reduction of oxygen to water by Complex IV. Therefore, reduced electron acceptors "upstream" of Complex IV accumulate to abnormally high levels.
- the Krebs cycle modulators of the invention preferably comprise, without limitation, ashwaganda, eleuthero root (or extract), maca, an amino acid, e.g., L-arginine and L-citrulline, and vitamins B 2 , Bi, B 3 , B 5 and B9 .
- the glutathione modulators of the invention induce the generation or proliferation of glutathione and/or a member of the glutathione family, including, without limitation, glutathione peroxidase, and/or catalase synthesis.
- the glutathione modulators comprise, without limitation, schisandra chinensis berry, damiana and epimedium, maca, nettle leaf, Fe and Cu, and B- vitamins selected from the group comprising B 2 , B5, B 6 and B 7 .
- the neurotransmitter modulators of the invention induce and/or modulate the generation of neurotransmitters and modulates the transmission thereof by and between neurons and, hence, cells.
- the neurotransmitter modulators comprise, without limitation, nettle leaf, maca, eleuthero root, Yohimbe, cannabidiol (CBD), epimedium, and vitamins Bi and B 6 .
- the DNA modulators of the invention support and/or enhance mitochondrial DNA activity.
- the DNA modulators support and/or enhance mitochondrial DNA activity by protecting and/or facilitating the repair of mitochondrial DNA.
- the DNA modulators comprise, without limitation, vitamin B I 2 .
- the endocannabinoid system modulators induce cell receptor activity.
- the endocannabinoid system modulators induce cannabinoid receptor activity.
- the endocannabinoid system modulators comprise cannabidiol (CBD) or a component thereof.
- CBD cannabidiol
- the vibrational energy platforms of the invention comprise at least one energy signature component comprising or derived from, without limitation, schisandra chinensis, damiana leaf, eleuthero root, stinging nettle leaf, maca root, yohimbe root, epimedium, L-arginine, and L-citrulline.
- the vibrational energy platforms of the invention comprise at least one energy signature component derived from a selective herb, e.g., schisandra chinensis, or biological agent, e.g., L-arginine.
- a selective herb e.g., schisandra chinensis
- biological agent e.g., L-arginine
- the vibrational element can be approximated by the quantum harmonic oscillator, where the vibrational energy Ev is determined as follows:
- vO is the natural frequency of the harmonic oscillator.
- a diatomic molecule can be represented by the difference between the energy of the molecule idealized by setting the rotational energy equal to zero, and that of a further idealized molecule which is obtained by gradually stopping the vibration of the nuclei without placing any new constraint on the motions of electrons.
- Another way a diatomic molecule can move is to have each atom oscillate or vibrate along a line (the bond) connecting the two atoms.
- the vibrational energy is approximately that of a quantum harmonic oscillator.
- the energy signature components of the invention are chosen for their synergistic and intrinsic values to be of catalytic benefit in the cellular respiration process to produce adequate oxygen in the cell, thereby being of catalytic benefit in the production of the necessary energy (ATP).
- the energy signature components comprise or are derived from, without limitation, schisandra chinensis, damiana leaf, eleuthero root, stinging nettle leaf, maca root, yohimbe root, epimedium, L- arginine, and L-citrulline.
- a composition comprising at least one of the aforementioned energy signature components and at least one B-vitamin comprising Bi, B?, B 3 , B 5 , B 6 , B 7 , B9 and B l2 is initially prepared.
- the composition is oscillated for 3-48 hours at a frequency in the range of approximately 23 Flz - 1000 GFIz, more preferably 102 GHz - 250 GHz to obtain a positive charge.
- the composition is subjected to further oscillation for approximately 3 hours at a frequency ranging from approximately 23 Flz - 1000 GHz.
- the bioenergetic platforms of the invention comprise at least one Krebs cycle modulator, glutathione modulator, neurotransmitter modulator, DNA modulator or endocannabinoid system modulator.
- the bioenergetic platforms comprise a Krebs cycle modulator and/or glutathione modulator and/or neurotransmitter modulator and/or DNA modulator and/or endocannabinoid system modulator.
- the Kreb cycle modulators of the invention induce and/or modulate at least one Krebs cycle metabolic reaction, process and/or pathway, including, without limitation, Krebs cycle product inhibition and/or substrate availability.
- a seminal process associated with the Krebs cycle is the catabolism of carbohydrates, fats and proteins, which results in the production of a two carbon organic product, i.e. acetate in the form of acetyl-CoA.
- Acetyl- CoA and two equivalents of water (H 2 0) are consumed during the Krebs cycle, producing two equivalents of carbon dioxide (C0 2 ) and one equivalent of EIS-CoA.
- one complete cycle of the Kreb cycle converts three equivalents of nicotinamide adenine dinucleotide (NAD + ) into three equivalents of reduced NAD + (NADH), one equivalent of ubiquinone (Q) into one equivalent of reduced ubiquinone (QH 2 ), and one equivalent each of guano sine diphosphate (GDP) and inorganic phosphate (Pi) into one equivalent of guanosine triphosphate (GTP).
- the NADH and QH 2 generated during the Kreb cycle are in turn used by the oxidative phosphorylation pathway to generate energy-rich adenosine triphosphate (ATP).
- a primary source of acetyl-CoA is carbohydrates, which are broken down by glycolysis to produce pyruvate. Pyruvate is decarboxylated by the enzyme pyruvate dehydrogenase to generate acetyl-CoA.
- the Krebs cycle modulators of the invention are capable of inducing and/or modulating at least one Krebs cycle metabolic reaction, process and/or pathway, including, without limitation, product inhibition and/or substrate availability.
- the Krebs cycle modulators can comprise, without limitation, ashwaganda, eleuthero root, maca, an amino acid, e.g., L-arginine and L-citrulline, and vitamins B 2 , Bi, B 3 , B 5 and Bs > .
- the Krebs cycle modulators of the invention modulate product and/or substrate availability.
- the Krebs cycle modulators comprise eleuthero root, which Applicant has found facilitates the formation of glucose 6 phosphate.
- glucose 6 phosphate eventually converts to pyruvate, which enters into the Krebs cycle as Acetyl-coA.
- the Krebs cycle modulators comprise eleuthero root, which also enhances the activity of succinate dehydrogenase, an enzyme that facilitates the formation of FAD to FADHb. These processes aid in the generation of ATP.
- the Krebs cycle modulators comprise maca.
- maca works synergistically with eleuthero root by inducing co-factor proliferation, which supports activation of the Krebs cycle.
- Maca also facilitates the production of super oxide dismutase, i.e. an important antioxidant.
- Intracellular super oxide dismutase converts a highly undesirable free radical known as superoxide to hydrogen peroxide and oxygen.
- the Krebs cycle modulators comprise ashwaganda, which facilitates the lowering of cortisol and balancing of thyroid hormones. Ashwaganda also reduces the breakdown of ATP.
- the Krebs cycle modulators comprise an amino acid comprising, without limitation, L-arginine and L-citrulline. Applicant has found that L-arginine and L-citrulline facilitate the production of nitrous oxide. Nitrous oxide induces vasodilation and, hence, enhanced blood flow. The enhanced blood flow results in an increase in delivered 0 2 and, thereby, enhanced cellular energy.
- the Krebs cycle modulators comprise a B- vitamin selected from the group comprising, without limitation, Bi, B 2 , B 3 , B 5 and B9.
- Bi i.e. thiamine
- Bi is involved in RNA and DNA production, as well as nerve function.
- Bl s active form is a coenzyme called thiamine pyrophosphate (TPP), which converts pyruvate to acetyl Coenzyme A (Co A).
- TPP thiamine pyrophosphate
- B 2 i.e. riboflavin, is involved in energy production for the electron transport chain and catabolism of fatty acids, i.e. beta oxidation.
- B3 i.e. niacin
- NAD nicotinamide adenine dinucleotide
- NADP nicotinamide adenine dinucleotide phosphate
- NAD carries H? and associated electrons during metabolic reactions, including the pathway from the Krebs cycle to the electron transport chain.
- NADP is a key coenzyme in lipid and nucleic acid synthesis.
- Bs i.e. pantothenic acid
- Coenzyme A which can be synthesised from panothenic acid, is involved in the synthesis of amino acids, fatty acids, ketones, cholesterol, phospholipids, steroid hormones, neurotransmitters, such as acetylcholine, and antibodies.
- B9 i.e. folic acid
- THF tetrahydrofolate
- Folate also aids in erythropoiesis, i.e. the production of red blood cells.
- the glutathione modulators of the invention induce (i) the generation or proliferation of glutathione and/or the glutathione family, including, without limitation, glutathione peroxidase, and/or (ii) catalase synthesis.
- glutathione peroxidase is an important intracellular antioxidant that induces conversion of hydrogen peroxide to H 2 0 and O2.
- Glutathione reduces disulfide bonds formed within cytoplasmic proteins to cysteines by serving as an electron donor. In the process, glutathione is converted to its oxidized form glutathione disulfide (GSSG), as known as L-(-)- glutathione.
- GSSG glutathione disulfide
- glutathione is reduced back to glutathione reductase, using NADPH as an electron donor.
- the glutathione modulators of the invention induce the generation or proliferation of glutathione and/or a member of the glutathione family, including, without limitation, glutathione peroxidase.
- the glutathione modulators can comprise, without limitation, schisandra chinensis berry, damiana and epimedium, and vitamin B 2 .
- B 2 i.e. riboflavin, facilitates energy production for the electron transport chain and catabolism of fatty acids, i.e. beta oxidation.
- the glutathione modulator is effective to induce the synthesis of catalase, another key antioxidant.
- the glutathione modulator can comprise, without limitation, maca, nettles leaves, Fe and Cu, and B-vitamins selected from the group comprising B 2 , B 5 , B 6 and B 7 .
- B 6 i.e. pyridoxine
- PBP pyridoxal 5'-phosphate
- Pyridoxine is also involved in the metabolism of amino acids and lipids; in the synthesis of neurotransmitters and hemoglobin, as well as in the production of nicotinic acid (vitamin B 3 ). Pyridoxine also plays an important role in gluconeogenesis.
- B7 i.e. biotin
- B7 also plays a key role in the metabolism of lipids, proteins and carbohydrates. It is a critical co-enzyme of four carboxylases: acetyl CoA carboxylase, which is involved in the synthesis of fatty acids from acetate; propionyl CoA carboxylase, which is involved in gluconeogenesis; b-methylcrotonyl Coa carboxylase, which is involved in the metabolism of leucin; and pyruvate CoA carboxylase, which is involved in the metabolism of energy, amino acids and cholesterol.
- Neurotransmitter Modulators acetyl CoA carboxylase, which is involved in the synthesis of fatty acids from acetate
- propionyl CoA carboxylase which is involved in gluconeogenesis
- b-methylcrotonyl Coa carboxylase which is involved in the metabolism of leucin
- pyruvate CoA carboxylase which is involved in the metabolism of energy, amino acids
- the human brain contains large numbers of highly specialized cells called neurons. As illustrated in Fig. 3, the neurons 10 connect to and
- neurotransmitters 12 i.e. endogenous electrochemical signals
- a sender neuron 10 when a sender neuron 10 generates and transmits neurotransmitters 12, the neurotransmitters 12 activate target receptors 16 on the receiver neuron 10 and, hence, cell.
- the neurotransmitter modulators of the invention induce (and/or modulate) the generation and proliferation of neurotransmitters and modulate the transmission thereof by and between neurons and, hence, cells.
- a key neurotransmitter is acetylcholine (ACh).
- Acetylcholine stimulates the central nervous system to enhance mental acuity, i.e. learning ability, short term memory and mental focus.
- Dopamine functions as an inhibitory and excitatory neurotransmitter. As inhibitory neurotransmitter, it causes balance and general sense of well-being. As excitatory neurotransmitter, it improves cognition, concentration and focus.
- a further key neurotransmitter is norepinephrine, which effects cognition, mood and mental concentration.
- the neurotransmitter modulators of the invention induce the generation or proliferation of at least one neurotransmitter, including ACh, dopamine and norepinephrine, and/or the transmission thereof by and between neurons.
- the neurotransmitter modulators of the invention can comprise, without limitation, nettle leaf, maca, eleuthero root, Yohimbe, epimedium, cannabidiol (CBD), and vitamins Bi and B 6 .
- nettle leaf increases the level of neurotransmitters available to act on the neuron receptors; particularly, dopamine and acetylcholine, thus improving several mental processes, e.g. learning and recollection abilities.
- Maca supports acetyl cholinesterase and, thereby, similarly enhances the proliferation of acetylcholine.
- eleuthero root enhances neuron activities, e.g., short term memory.
- Yohimbe is a pre- and post-synaptic, alpha-2 adrenergic blocker that enhances neurotransmitter release and, thereby, enhanced cognitive functioning.
- Yohimbe also induces elevation of norepinephrine from the locus coeruleus, resulting in enhanced memory. It is also been found that Yohimbe can abate one or more symptoms associated with post-traumatic stress disorder (PTSD).
- PTSD post-traumatic stress disorder
- Epimedium which includes the active element icariin, lowers the amyloid precursor protein (APP) level and, hence, reduces amyloid beta peptide (AB).
- APP amyloid precursor protein
- AB amyloid beta peptide
- Tau protein is used in the brain as axonal microtubule stabilizers.
- Icariin abates hyperphosphorylation and, thus, reduces AB.
- Icariin is also an acetylcholinesterase inhibitor. Thus, more acetylcholine is available for memory and cognitive functions.
- CBD cannabidiol
- the DNA modulators of the invention support and/or enhance mitochondrial DNA activity by, among other activities, protecting and/or facilitating the repair of mitochondrial DNA.
- mammalian mitochondria are organelles that produce more than 90% of cellular ATP.
- mitochondria are also involved in other cellular mechanisms, including cellular differentiation, apoptosis, as well as cell cycle modulation and cell growth.
- Go phase When a cell has temporarily or reversibly stopped dividing or regenerating it is often deemed to have entered a quiescent or senescent state referred to as the Go phase.
- Non-proliferative cells generally enter the senescent Go phase or state from the Gi phase and may remain senescent for long periods of time, possibly indefinitely (as is often the case for neurons). This is very common for cells that are fully differentiated.
- telomere shortening i.e. a form of DNA damage or degradation
- telomeres Due to DNA replication mechanisms and oxidative stress, telomeres become progressively shorter with each round of replication. As increasing numbers of cell division occur, the telomeres reach a critically short length, which present as double-stranded DNA breaks, resulting in telomere-initiated senescence.
- the DNA modulators of the invention support mitochondrial DNA by protecting and/or facilitating the repair of mitochondrial DNA.
- the DNA modulators of the invention comprise vitamin B12.
- Bi? supports DNA activity; specifically, synthesis and, in some instances, inhibits megaloblastic anemia.
- Bi2 is also involved in the cellular metabolism of carbohydrates, proteins and lipids. It functions as a co-enzyme in intermediary metabolism for the methionine synthase reaction with methylcobalamin, and the methylmalonyl CoA mutase reaction with
- the endocannabinoid system modulators of the invention induce cell receptor activity; preferably, cannabinoid receptor activity, i.e. receptors CB1 or CB2.
- the endocannabinoid system modulators comprise cannabidiol (CBD).
- CBD is one of many cannabinoid molecules produced by Cannabis, second only to THC in abundance.
- CBD activates the two seminal cannabinoid receptors (CB1 and CB2) and, hence, as discussed below, induces several significant physiological activities.
- One significant physiological activity induced by activating the CB1 and CB2 receptors is modulation of inflammatory activity and diseases associated therewith, e.g. arthritis.
- the inflammation modulation i.e. reduction thereof, is achieved by (among other factors) reducing the neurochemical effects of beta-amyloid proteins and, thereby, reactive oxidative stress and reactive oxygen.
- CBD can, and in many instances will, enhance the levels of naturally-produced endocannabinoids, e.g., anandamide and 2-arachidonoyl glycerol (2-AG), by inhibiting the enzymes that break them down.
- endocannabinoids e.g., anandamide and 2-arachidonoyl glycerol (2-AG)
- CBD also activates multiple serotonin receptors in the brain; particularly, serotonin 1 A receptors. As a result, CBD can ameliorate various disorders, including neuropathic pain and motivational disorders, such as depression and anxiety.
- CBD also modulates opioid receptor activity.
- opioid receptors are the key targets of pharmaceutical pain killers and drugs of abuse, such as morphine, heroin, and fentanyl.
- CBD ' s ability to modulate opioid receptor activity and enhance the activation of serotonin 1 A receptors dampens drug cravings and, hence, can, and in many instances will, abate drug dependence; particularly, opioid and heroin dependence.
- CBD is also an effective neurotransmitter modulator.
- CBD activates the two seminal cannabinoid receptors CB1 and CB2.
- anandamide is increased and the associated elevation of corticosterone (stress hormone) and 2-arachidonoyl glycerol (2-AG) are reduced, which have a direct effect (and in many instances a calming effect) on the amygdala, i.e. emotional center.
- CBD is a cannabinoid
- CBD does not directly interact with and, hence, activate the CB1 and CB2 receptors. Instead, CBD indirectly activates the CB1 and CB2 receptors by modulating signaling through the CB1 and CB2 receptors by inhibiting the enzyme fatty acid amide hydrolase (FAAH).
- FAAH fatty acid amide hydrolase
- FAAH inactivates anandamide and also converts 2-AG to mono acylglycerol. By inhibiting FAAFI more of anandamide and 2-AG available, which further enhances the calming effect on the amygdala.
- the biochemical scaffolds of the invention thus modulate various seminal molecular activities, including inducing (i) at least one Krebs cycle metabolic reaction, process and/or pathway, (ii) generation or proliferation of glutathione and/or a member of the glutathione family, (iii) generation or proliferation of at least one neurotransmitter, and/or modulating the transmission thereof by and between neurons, (iv) inducing and/or supporting mitochondrial DNA activity and (v) cell receptor activity.
- biochemical scaffolds of the invention As also indicated above, by virtue of the noted modulated molecular activities that are induced by the biochemical scaffolds of the invention, cellular activity and function and, thereby, physical and mental function, is significantly enhanced. Indeed, it has also been found that administration of the biochemical scaffolds of the invention to a subject can, and in many instances will ameliorate various physical disorders, including neuropathic pain, inflammation and core temperature spikes, and mental disorders, such as post-traumatic stress disorder (PTSD), depression and anxiety.
- the biochemical scaffolds of the invention can also be employed to abate drug dependence; particularly, opioid and heroin dependence.
- the biochemical scaffold is processed as set forth in U.S. App. No. 14/233,392 or described herein, and preferably comprises the following bioenergetic platform, i.e. vitamins and herbs:
- the biochemical scaffold further comprises a cofactor, including, without limitation, organic cofactors, such as flavin and heme, and inorganic cofactor, such as the metal ions Mg 2+ , Cu + , Mn 2+ , and iron-sulfur clusters.
- a cofactor including, without limitation, organic cofactors, such as flavin and heme, and inorganic cofactor, such as the metal ions Mg 2+ , Cu + , Mn 2+ , and iron-sulfur clusters.
- biochemical scaffolds of the invention administered to a subject will enhance cognitive function and/or ameliorate a physical or mental disorder.
- a method of enhancing cognitive function comprising providing a biochemical scaffold of the invention and administering same to a subject.
- a method treating a physical or mental disorder comprising providing a biochemical scaffold of the invention and administering same to a subject.
- the physical disorder can comprise, without limitation, neuropathic pain, inflammation, and core temperature spikes.
- the mental disorder can comprise, without limitation, post-traumatic stress disorder (PTSD), depression and anxiety.
- PTSD post-traumatic stress disorder
- depression depression
- anxiety anxiety
- a method of enhancing cognitive function of a subject comprising (i) providing a biochemical scaffold comprising a bioenergetic platform component and a vibrational energy platform
- the bioenergetic platform component comprising vitamin B ]2 , ashwaganda, yohimbe, epimedium and/or camiabidiol (CBD)
- the vibrational energy platform component comprising an energy signature component comprising schisandra chinensis, damiana leaf, eleuthero root, stinging nettle leaf, maca root, yohimbe, epimedium, L-arginine and/or L- citrullinen
- the vibration energy component being subjected to harmonic oscillation at a frequency in the range of approximately 23 Hz - 1000 GHz for a period of time in the range of approximately 3 - 48 hrs., and (ii) delivering the biochemical scaffold to the subject.
- the vibrational energy platform further comprises an energy signature component comprising Bi, B 2 , B 3 , B 5 , B 6 , B 7 , B 9 or Bn.
- a method of treating PTSD of a subject that similarly comprises (i) providing a biochemical scaffold comprising a bioenergetic platform component and a vibrational energy platform component, the bioenergetic platform component comprising vitamin B 12 , ashwaganda, yohimbe, epimedium and/or cannabidiol (CBD), the vibrational energy platform component comprising an energy signature component comprising schisandra chinensis, damiana leaf, eleuthero root, stinging nettle leaf, maca root, yohimbe, epimedium, L-arginine and/or L- citrullinen, the vibration energy component being subjected to harmonic oscillation at a frequency in the range of approximately 23 Hz - 1000 GHz for a period of time in the range of approximately 3 - 48 hrs., and (ii) delivering the biochemical scaffold to the subject.
- a biochemical scaffold comprising a bioenergetic platform component and a vibrational energy platform component
- the vibrational energy platform similarly further comprises an energy signature component comprising Bi, B 2 , B 3 , B 5 , B 6 , B 7 , B 9 or B l? .
- the biochemical scaffolds of the invention can be delivered to host tissue by various conventional means, including, without limitation, oral, sublingual, nasal, direct injection, topical application, etc.
- the biochemical scaffolds are in liquid form.
- a dose of the liquid form biochemical scaffold comprises in the range of approximately range of 0.006 - 0.070 oz, more preferable, in the range of approximately 0.006 - 0.018 oz.
- the present invention provides numerous advantages compared to prior art formulations and methods for enhancing cell function and, thereby physiological performance. Among the advantages are the following:
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US5405613A (en) * | 1991-12-11 | 1995-04-11 | Creative Nutrition Canada Corp. | Vitamin/mineral composition |
US20040204746A1 (en) * | 1999-08-28 | 2004-10-14 | Ovokaitys Todd F. | Enhanced bioavailability of nutrients, pharmaceutical agents, and other bioactive substances through laser resonant homogenization or modification of molecular shape or crystalline form |
US20150216923A1 (en) * | 2014-02-05 | 2015-08-06 | Ralph L. Peterson | Biochemical Scaffolds for Modulating Cell Function |
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US5405613A (en) * | 1991-12-11 | 1995-04-11 | Creative Nutrition Canada Corp. | Vitamin/mineral composition |
US20040204746A1 (en) * | 1999-08-28 | 2004-10-14 | Ovokaitys Todd F. | Enhanced bioavailability of nutrients, pharmaceutical agents, and other bioactive substances through laser resonant homogenization or modification of molecular shape or crystalline form |
US20150216923A1 (en) * | 2014-02-05 | 2015-08-06 | Ralph L. Peterson | Biochemical Scaffolds for Modulating Cell Function |
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