Classifications

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  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
  • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
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  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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  • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

• the disclosure is directed towards the field of medicine and, more specifically, the use of a combination of compounds to treat disease and regulate cholesterol levels.
• compositions and methods of the disclosure reduce autoimmune and
• a fatty acid e.g. a statin
• a cholesterol lowering compound e.g. a statin
• the disclosure provides a pharmaceutical composition for the treatment of a disease or disorder comprising i) at least one fatty acid, and ii) at least one cholesterol lowering compound.
• the disclosure provides a pharmaceutical composition for reducing total cholesterol and maintaining total cholesterol homeostasis comprising i) at least one fatty acid, and ii) at least one cholesterol lowering compound.
• maintaining total cholesterol homeostasis comprises maintaining a total cholesterol percent relative range of about 15%, of about 10%, or of about 5% between a maximum total cholesterol level and a minimum total cholesterol level.
• maintaining total cholesterol homeostasis comprises maintaining a total cholesterol range of about 5 mg/dL to about 25 mg/dL or of about 10 mg/dL to about 15 mg/dL between a maximum total cholesterol level and a minimum total cholesterol level.
• a maximum total cholesterol level and a minimum total cholesterol level are maintained below 200 mg/dL, below 175 mg/dL, or below 150 mg/dL. In certain embodiments, total cholesterol is reduced at least 5%, at least 10%, at least 15%, at least 20% or at least 40%.
• compositions of the disclosure comprise at least one fatty acid.
• Exemplary fatty acids include, but are not limited to, a fatty oil, a fatty acid ethyl ester, a fatty acid triglyceride, a saturated acid, an oil, an ester or a triglyceride, or a combination thereof.
• Exemplary fatty acids may further include, but are not limited to, an Omega-3 fatty acid, an Omega-6 fatty acid, an Omega-9 fatty acid, or a derivative thereof.
• compositions of the disclosure comprise at least one cholesterol lowering compound.
• exemplary cholesterol lowering compounds include, but are not limited to, an HMG-CoA reductase inhibitor or statin, Ezetimibe, a fibrate, a carboxylic acid, Benezafibrate, Ciprofibrate, Gemfbroizil, Fenofibrate, Clinofibrate, niacin, bile acid sequestrants, Colestipol, Cholestyramine, Endur-Acin, Colesevelam, a PCSK9 enzyme inhibitor, or any combination thereof.
• the at least one HMG-CoA reductase inhibitor or statin may be Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin, Simvastatin, or any combination thereof.
• compositions of the disclosure may comprise at least one vitamin or hormone.
• exemplary vitamins include, but are not limited to, vitamin B, vitamin C or vitamin D, or a combination thereof.
• the at least one vitamin D may be vitamin D 2 or vitamin D 3 .
• the at least one vitamin C may be ascorbate or ascorbic acid.
• compositions of the disclosure may comprise at least one organic compound, herb or derivative thereof.
• organic compounds, herbs or derivatives thereof include, but are not limited to, bacopa, vinpocetine, an alkaloid, reserpine, reserpinine, akuammicine, majdine, vinerine, ervine,ieridine, tombozine, vincananine, vincanidine, vincamore, apovincamine, vincamore, apovincamine, or vincaminol.
• compositions of the disclosure may be used in the treatment of a disease or disorder including, but not limited to, an autoimmune disease, an inflammatory disorder, a neurodegenerative disorder, a bacterial infection or a viral infection.
• the disease or disorder may be psoriasis, keratosis, spongy gum and bleeding gum disease, atherosclerosis, heart disease, myopathy, neuropathy, common cold, myositis, arthritis, dementia, Parkinson's disease, Alzheimer's disease.
• the keratosis may be actinic, pilaris or seborrheic.
• the pharmaceutical composition may be used in the treatment of the common cold.
• the "common cold" comprises a viral infection of a portion of the upper respiratory tract.
• the disclosure provides a pharmaceutical composition
• a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA) and at least 10 mg of a cholesterol lowering composition.
• the composition may be formulated for daily oral administration for use in the treatment of psoriasis.
• the disclosure provides a pharmaceutical composition
• a pharmaceutical composition comprising at least 1000 mg of a fish oil, at least 667 mg of a EPA, at least 333 mg of a DHA and at least 10 mg of a cholesterol lowering composition.
• the composition may be formulated for daily oral administration for use in the treatment of keratosis, atherosclerosis, heart disease, or any combination thereof.
• the disclosure provides a pharmaceutical composition
• a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition and at least 1000 mg of vitamin C.
• the composition may be formulated for daily oral administration for use in the treatment of spongy gum and bleeding gum disease.
• the disclosure provides a pharmaceutical composition
• a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition and at least 3000 mg of vitamin C.
• the composition may be formulated for daily oral administration for use in the treatment of a bacterial infection, viral infection or the common cold.
• the disclosure provides a pharmaceutical composition
• a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition and at least 2000 IU of vitamin D.
• the composition may be formulated for daily oral administration for use in the treatment of myopathy or neuropathy.
• the disclosure provides a pharmaceutical composition
• a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition, and at least 250 mg of bacopa.
• the composition may further comprise at least 10 mg of vinpocetine.
• the composition may be formulated for daily oral administration for use in the treatment of dementia, Parkinson's disease or Alzheimer's disease.
• the disclosure provides a method for the treatment of a disease or disorder in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising i) at least one fatty acid, and ii) at least one cholesterol lowering compound, such that said disease or disorder is treated.
• the disclosure provides a method for reducing total cholesterol and maintaining total cholesterol homeostasis in a subject in need thereof comprising administering a
• maintaining total cholesterol homeostasis comprises maintaining a total cholesterol percent relative range of about 15%, of about 10%, or of about 5% between a maximum total cholesterol level and a minimum total cholesterol level while the pharmaceutical composition is administered.
• maintaining total cholesterol homeostasis comprises maintaining a total cholesterol range of about 5 mg/dL to about 25 mg/dL or of about 10 mg/dL to about 15 mg/dL between a maximum total cholesterol level and a minimum total cholesterol level while the pharmaceutical composition is administered.
• a maximum total cholesterol level and a minimum total cholesterol level are maintained below 200 mg/dL, below 175 mg/dL, or below 150 mg/dL while the pharmaceutical composition is administered.
• total cholesterol is reduced at least 5%, at least 10%, at least 15%, at least 20% or at least 40%.
• reducing total cholesterol levels comprises reducing triglyceride levels.
• the pharmaceutical composition may comprise at least one fatty acid.
• Exemplary fatty acids include, but are not limited to, a fatty oil, a fatty acid ethyl ester, a fatty acid triglyceride, a saturated acid, an oil, an ester or a triglyceride, or a combination thereof.
• Exemplary fatty acids may further include, but are not limited to, an Omega-3 fatty acid, an Omega-6 fatty acid, an Omega-9 fatty acid, or a derivative thereof.
• the pharmaceutical composition may comprise at least one cholesterol lowering compound.
• cholesterol lowering compounds may include, but are not limited to, an HMG-CoA reductase inhibitor or statin, Ezetimibe, a fibrate, a carboxylic acid, Benezafibrate, Ciprofibrate, Gemfbroizil, Fenofibrate, Clinofibrate, niacin, bile acid sequestrants, Colestipol,
• the at least one HMG-CoA reductase inhibitor or statin may be Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin, Simvastatin, or any combination thereof.
• the pharmaceutical composition may comprise at least one vitamin or hormone.
• the at least one vitamin may include vitamin B, vitamin C, vitamin D or a combination thereof.
• the vitamin D may be vitamin D2 or vitamin D3.
• the vitamin C is ascorbate or ascorbic acid.
• the methods of the disclosure include administering a pharmaceutical composition and at least one organic compound, herb or derivative thereof.
• the at least one organic compound, herb or derivative thereof may include, but is not limited to, bacopa, vinpocetine, an alkaloid, reserpine, reserpinine, akuammicine, majdine, vinerine, ervine,ieridine, tombozine, vincananine, vincanidine, vincamore, apovincamine, vincamore, apovincamine, and vincaminol.
• compositions and methods of the disclosure may be used in the treatment of a disease or disorder, including, but not limited to, an autoimmune disease, an inflammatory disorder, a neurodegenerative disorder, a bacterial infection or a viral infection.
• the disease or disorder may be psoriasis, keratosis, spongy gum and bleeding gum disease, atherosclerosis, heart disease, myopathy, neuropathy, common cold, myositis, arthritis, dementia, Parkinson's disease, Alzheimer's disease.
• the keratosis may be actinic, pilaris or seborrheic.
• the disclosure provides a method for treating psoriasis in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA) and at least 10 mg of a cholesterol lowering composition.
• EPA eicosapentaenoic acid
• DHA docosahexaenoic acid
• compositions may be formulated for oral delivery.
• compositions and methods of the disclosure may be administered daily or weekly.
• the disclosure provides a method for treating keratosis, atherosclerosis, heart disease, or any combination thereof, in a subj ect in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising at least 1000 mg of a fish oil, at least 667 mg of a EPA, at least 333 mg of a DHA and at least 10 mg of a cholesterol lowering composition.
• the pharmaceutical composition may be formulated for oral delivery.
• the pharmaceutical composition may be administered daily or weekly.
• the disclosure provides a method for treating spongy gum and bleeding gum disease in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition and at least 1000 mg of vitamin C.
• the pharmaceutical composition may be formulated for oral delivery.
• the pharmaceutical composition may be administered daily or weekly.
• the disclosure provides a method of treating a bacterial infection, viral infection or the common cold in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition and at least 3000 mg of vitamin C.
• the pharmaceutical composition may be formulated for oral delivery.
• the pharmaceutical composition may be administered daily or weekly.
• the disclosure provides a method of treating myopathy or neuropathy in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition and at least 2000 IU of vitamin D.
• the pharmaceutical composition may be formulated for oral delivery.
• the pharmaceutical composition may be administered daily or weekly.
• the disclosure provides a method of treating dementia, Parkinson's disease or Alzheimer's disease in a subject in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising at least 600 mg of a fish oil concentrate, at least 600 mg of a fish oil, at least 180 mg of an eicosapentaenoic acid (EPA), at least 120 mg of a docosahexaenoic acid (DHA), at least 10 mg of a cholesterol lowering composition, and at least 250 mg of bacopa.
• the pharmaceutical composition may be formulated for oral delivery.
• the pharmaceutical composition may be administered daily or weekly.
• Figure 1 is a graph depicting total cholesterol (mg/dL) as a function of time for Patient A (data points provided in Table 2) over first time period (November 2001 to July 2011).
• Figure 2 is a graph depicting total cholesterol (mg/dL) as a function of time for Patient A (data points provided in Table 2) over second time period (March 2011 to August 2015).
• Figure 3 is a graph depicting total cholesterol (mg/dL) as a function of time for Patient B (data points provided in Table 3) over first time period (November 1998 to May 2013).
• Figure 4 is a graph depicting total cholesterol (mg/dL) as a function of time for Patient B (data points provided in Table 3) over second time period (March 2013 to May 2015).
• Figure 5 is a schematic diagram depicting an exemplary timeline for administration of a composition of the disclosure with exemplary data points following collection of a sample and measurement of total cholesterol from, for example, circulating blood.
• compositions and methods of the disclosure reduce total cholesterol and maintain total cholesterol homeostasis.
• Some cholesterol lowering medicaments may establish a homeostatic cholesterol level.
• TriCor farofibrate
• Vytorin a combination of Zetia and Simvastatin
• both Lipitor and Zetia need an Omega-3 fish oil to establish a homeostatic cholesterol level, as illustrated in Patient A's Experiments 5-15.
• cholesterol lowering agents administered as a monotherapy will not treat autoimmune or inflammatory diseases.
• Cholesterol lowering agents require a coinitiator, including, but not limited to, a fatty acid, a vitamin, a hormone, a flavanoid, a carotenoid, a retinoid, a mineral, or any combination thereof.
• the co-initiator requires a statin, a cholesterol lowering agent, a lipoprotein lowering agent, a triglyceride lowering agent (e.g. statin(s), fibrate(s), PCSK9, monoclonal antibody inhibitors, ApoA-1 milano, succinofuco (AG1-1067), and Apoprotein-B inhibitor Mipomersen) or any combination thereof.
• Omega-3 fatty acids triglyceride or ethyl ester
• vitamin D may serve as a co-initiator with a statin.
• This combination of a fatty acid, a vitamin and a statin may be used to efficaciously treat autoimmune and/or inflammatory diseases, including, but not limited to, myopathy, myositis, psoriasis, keratosis, atherosclerosis, neuropathy and other related diseases such as neurodegenerative diseases.
• compositions and methods of the disclosure may be used to treat a number of conditions having a common underlying feature of increased or unregulated fatty acids and/or cholesterol levels, either as result of the disease or disorder itself, or as a side effect of a treatment for that disease or disorder.
• the compositions and methods of the disclosure establish a homeostatic cholesterol level that is independent from the absolute level (or, magnitude) of the homeostatic cholesterol value.
• the homeostatic cholesterol level is described as a relative level compared to an initial level present either during a disease state or as a consequence of treatment of an underlying disease with another therapy.
• compositions of the disclosure may comprise one or more of a fatty acid, a fat (unsaturated or saturated fat), a vitamin, a flavanoid, a carotenoid, a retinoid, or a hormone in combination with a statin.
• Compositions of the disclosure may be used to treat any autoimmune or inflammatory disease.
• autoimmune diseases are MHC-Class 1 mediated diseases.
• Statins repress T- lymphocyte activation, however, statins are specific for MHC-Class II and do not involve MHC-Class 1 expression.
• Cholesterol lowering medicaments have little or no direct association with autoimmune diseases or other diseases. Thus, treatment with a statin alone would not be efficacious to treat an autoimmune or inflammatory disease.
• compositions and methods provide a combination of a cholesterol-lowering medicament (e.g. a statin) with a fatty acid to treat disease with unexpectedly superior efficacy, to reduce cholesterol levels and to establish a healthy homeostatic cholesterol level.
• a cholesterol-lowering medicament e.g. a statin
• a fatty acid e.g. a statin
• the compositions and methods of the disclosure are efficacious for treating autoimmune and inflammatory disorders.
• compositions and methods of the disclosure may include any statin, and, therefore, are not reliant on the use of any one particular statin.
• Psoriasis is a common autoimmune disease of the skin characterized by scaly patches, papules and plaques. There are 5 prevalent forms of psoriasis: plaque, pustular, guttate, erythrodermic and invesse. Psoriasis may occur over small areas of the body or over the entire body. Areas of the more common plaque Psoriases are small (e.g. 0.5 in. in diameter) or large (e.g. 1.5-2.0 in. in diameter) patches of skin characterized by a silvery-white epidermal cell morphology.
• psoriasis In a subject suffering from psoriasis, the subject's immune system attacks skin cells because the epidermal cells of the skin cells are recognized, improperly, as a rapidly growing pathogen (similar to the way the immune system would recognize cancer). Consequently, psoriasis may be considered an autoimmune disease.
• a subject having psoriasis may also have one or more mutations in the PSOR1 gene.
• This PSOR1 gene is located on chromosome 6 in the major histocompatibility complex (MHC).
• MHC major histocompatibility complex
• the MHC is a complex responsible in part for distinguishing self-antigens from non-self-antigens and preventing the development of autoimmune conditions.
• Psoriasis vulgaris may be associated with additional mutations in human leukocyte antigen (HLA)-C variant, including HLA-CW6.
• Psoriasis may be associated with an increased abundance of CD8+T cells, HLA-CW6, IL-12b, IL-23b, TNF alpha and NF-KB.
• Keratosis often presents as an excessive accumulation of keratin on the epidermis or mucous membranes.
• Some of the more common types of keratosis include actinic, pilaris and seborrheic keratosis.
• Actinic keratosis is a precancerous skin condition. Actinic keratosis is characterized by usually thick, scaly and rough patches of skin. If untreated, actinic keratosis cells may transform into squamous-cell carcinoma. Keratosis pilaris is
• Seborrheic keratosis is a non-cancerous growth of discolored skin that usually appears brown, black or light.
• Spongy gum and bleeding gum disease are associated with gingivitis and subsequent periodontal disease. Both diseases are associated with bacterial gum infections. Without treatment, the bacterial gum infections may destroy gum tissue and auxiliary bone.
• Gingivitis is a minor bacterial gum inflammation that causes the gums to be soft and bleed. As gingivitis progresses it advances to periodontitis, a severe inflammation around the tooth. Over time the gums pull away from the teeth and form pockets that become infected. If the subject's immune system cannot eliminate the bacterial infection, the gum tissue and bone surrounding the tooth or teeth may be damaged or destroyed.
• the compositions and methods of the disclosure may be used to treat the severe spongy gum and bleeding gum disease that results from taking both blood thinning and high blood pressure medications.
• Myopathy is term used to describe a wide variety of muscular conditions. Myopathies may be inherited or acquired. Inherited myopathies include dystrophies, myotonic, congenital myopathies, mitochondrial myopathy, familial periodic paralysis, and
• Acquired myopathies include substance induced myopathy, glucocorticoid myopathy, dermatomyositis, inclusion body myositis,
• Statin induced myopathy i.e. an acquired myopathy
• Myalgia or muscle pain
• Myositis or muscle inflammation
• Rhabdomyolysis is condition in which damaged muscle (skeletal striated muscle) breaks down. Subjects having rhabdomyolysis often have muscle protein in their bloodstream that may cause severe kidney damage and eventual death.
• the pain associated with myositis (myopathy) and neuropathy may be treated with a composition of the disclosure comprising fish oil, Vitamin D 3 (a hormone) and a statin.
• Vitamin D when administered with fish oil, Vitamin D, in part, also controls the amount of cholesterol manufactured in the liver without negatively influencing the concentration of active statins.
• Cardiovascular disease is the number one cause of death worldwide.
• Atherosclerosis i.e., a hardening of the arteries that happens within blood vessels
• Unsaturated fats cannot pass through the endothelial cell lining of the arterial and venial cell walls; however, oxidized fats can transport themselves across the endothelial cell membrane.
• the transport of oxidized fats across the walls of the blood vessels triggers an autoimmune reaction in which the subject's immune system recognizes the oxidized fat as a pathogen and attacks it.
• Non-oxidized fats and non-oxidized cholesterols do not cause heart disease.
• Oxidative stress damages any and all components of a cell, including, but not limited to, proteins, lipids and DNA.
• Atherosclerosis is characterized by the build-up of stable and unstable plaque.
• a hard fibrous sheath may encase the plaque formed by the autoimmune reaction.
• the plaque formed is called stable plaque.
• the body fails to encapsulate the autoimmune reaction i.e. the formation of an unstable plaque
• the unstable plaque may break loose. Consequently, the inflammatory cells from the reaction spread within the blood causing the blood to coagulate.
• the coagulation is called a blood clot. Blood clots that block the flow of blood through a blood vessel may cause a heart attack.
• Omega-3 oils fatty acids
• statin(s) stabilize the cholesterol in lipoproteins (fat deposits).
• Omega-3 oils and the associated high concentration of EPA, DHA and DPA are responsible for the vasodilatory effects found in blood vessels. As a result the blood vessels widen; thereby, relaxing the smooth muscles and lowering the blood pressure.
• compositions and methods of the disclosure lower the risk of
• Neuropathy is a term describing damage or disease of the nerves. Neuropathy is used more often to describe damage or disease of the peripheral nervous system (PNS) as opposed to the central nervous system (CNS). Neuropathy may be caused by systemic disease, medicaments, injury, inflammation, autoimmune diseases, bacterial infection and/or viral infection. [064] Neuropathy and myopathy share a common feature in that damage to the nerves and muscles, respectively, leads to an inflammatory response. In certain circumstances, damage to the nerves and muscles, respectively, may be caused by an autoimmune reaction to a self- antigen. Compositions and methods of the disclosure may be used to treat neuropathy, at least in part, because the compositions and methods of the disclosure reduce autoimmune and inflammatory responses.
• the common cold comprises a viral infectious disease of the upper respiratory tract which affects a subject's nose, sinus and throat.
• Infants and preschool children are susceptible to colds because they have not developed an immune system to many viruses. Older children and adults develop immunity to many of the viruses that cause the common cold.
• compositions of the disclosure may be used to treat the common cold.
• those compositions of the disclosure comprising a statin, an Omega-3 fatty acids or polyunsaturated oils and vitamin C may be used to treat the common cold.
• Patient A contracted the common cold.
• the cold was gone within 3 days of initiating treatment with a composition of the disclosure. As the cold may otherwise have lasted several weeks, treatment according to the compositions and methods of the disclosure demonstrate a significant improvement over conventional therapies.
• Dementia also known as senility
• MCI mild cognitive impairment
• a chromic decline in memory with at least one additional cognitive function signals the onset of dementia.
• cognitive functions including, but not limited to, aphasia (communication), apartia (motor execution), agnosiax (recognition) and executive function (synthesis) may be affected.
• Dementia may be classified as vascular dementia, Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia and Lewy body dementia. Compositions and methods of the disclosure preserve a subject's cognitive functions and prevent further deterioration of memory.
• Vinpocetine is an extract of the periwinkle plant that is an effective vasodilator and a nootropic for improving memory and cerebral metabolism.
• compositions of the disclosure and, in particular, those comprising vinpocetine also significantly improved memory retention and muscular coordination in Patient A.
• compositions and methods of the disclosure may be used to treat any one or more of the following diseases and conditions.
• Amyotrophic lateral sclerosis (Also Lou Gehrig's disease; Motor Neuron Disease)
• Fibrosing alveolitis or Idiopathic pulmonary fibrosis
• GFS Guillain-Barre syndrome
• LAD Linear IgA disease
• Mucha-Habermann disease aka Pityriasis lichenoides et varioliformis acuta
• PANDAS pediatric autoimmune neuropsychiatric disorders associated with streptococcus
• IBP Ulcerative colitis
• Omega fatty acids and Omega oils include natural,
• the fatty acid, fatty acid esters or fatty acid oils or ethyl-fatty acids or fatty acid alcohols or fatty acid glycols or fatty acid triglycerides that include, but are not limited to: Omega-3 polyunsaturated short-chain fatty acids with an aliphatic tail less than 6 carbon atoms; polyunsaturated medium-chain fatty acids with an aliphatic tail of 6-12 carbon atoms; polyunsaturated long-chain fatty acids with an aliphatic tail of 13-21 carbon atoms and very-long chain fatty acids with an aliphatic tail greater than 22 carbon atoms.
• the short chain and very-long chain fatty acids or esters include:
• saturated fatty acids include: caprylic, capric, lauric, myristic, palmitic, stearic, arachidic, lignoceric and cerotic acid.
• the Omega-3 fatty acids with a statin(s) have a profound effect on the autoimmune diseases.
• Omega-6 fatty acids and Omega-9 fatty acids with a statin(s) have a similar effect on autoimmune diseases as well as the Omega-3 fatty acids.
• the Omega-6 fatty acids include arachidonic acid and alpha-linoleic acid.
• the Omega-9 fatty acids include oleic, erucic, elaidic, mead and nervonic acid.
• Omega-3, Omega-6 and Omega-9 are effective in treating autoimmune diseases when administered with a statin.
• the ratio of different fatty acids is usually at a minimum of 1 : 1. That is the ratio of EPA to DHA is preferably 1 : 1; however, the ratio could be equally a 1 :0 or 0: 1 or 2: 1. Most over the counter Omega-3 fatty acids are 2: 1 ; however, other Omega-3 fatty acids are 1 :2, EPA to DHA.
• psoriasis required in Patient A an EPA of 180 mg and a DHA of 120 mg with a fish oil concentration of 600 mg and a statin(s).
• Patient A needed 1000 mg of Omega-3 fatty acids that included 667 mg of EPA and 333 mg of DHA. That was the minimum for Patient A.
• Increasing the concentration of fatty acids or fatty oils or fatty esters or fatty triglycerides or fatty acid alcohols did not relieve the symptoms of the disease, because the disease was treated at the lower concentration. The higher concentration just lowered the total cholesterol.
• the total cholesterol's homeostasis was established when an Omega-3 or Omega-6, or Omega-9 was combined with a statin(s).
• the omega fatty acids alone did not effectively treat the diseases rather it was the combination of omega fatty acids or mega oils and statin(s) that effectively treated the diseases.
• Statins are also called HMG-CoA reductase inhibitors. They are drugs used to lower cholesterol levels by inhibiting the enzyme HMG- CoA reductase that is responsible for the preparation of cholesterol in the liver.
• the statins used herein as well as others include Atorvastatin (Lipitor or Torvast), Fluvastatin (Lescol), Lovastatin (Mevacor, Altocor, or Altoprev), Pitavastatin (Livalo or Pitava), Pravastatin (Provachol, Selektine, or Lipostat), Rosuvastatin (Crestor) and Simvastatin (Zocor or Lipex).
• statins there are several combinations of statins that are extremely effective, one such combination includes Ezetimibe/Simvastatin (Vytorin) or combinations of statins and vitamins such as Lovastin/Niacin (Advicor), Simvastatin/Niacin (Simcor) or combinations of 2 different functional drugs such a Atorvastatin/ Amlodipine hesylate (Caduet).
• Ezetimibe Zetia or Ezetrol
• Any drug that lowers cholesterol is a prime candidate for treating diseases with another medicament.
• the cholesterol lowering drug(s) or medicament(s) cannot effectively treat diseases as a monotherapy; they need another medicament to aid in treating the disease.
• cholesterol lowering medicaments include fibrates, amphipathic carboxylic acids, such as Bezafibrate (Bezalip), Ciprofibrate (Modalim), Gemfbroizil (Lopid),
• niacin and bile acid sequestrants such as Colestipol (Colestid), Cholestyramine (Questran), Endur-Acin and Colesevelam (Welchol).
• PCSK9 low density lipoprotein
• the new drugs are Alirocumab and Evolocumab. Any cholesterol lowering medicament in combination with a fatty acid(s), fatty acid ester(s), fatty acid triglycerides(s) or the like will treat diseases. It is proven herein that the concentration of cholesterol lowering
• medicament(s) or fatty acid(s) is not significant and a minimum amount is only needed. Also the type of cholesterol lowering medicament or fatty acid is not significant because the level of total cholesterol homeostasis will be at that level necessary to treat the disease.
• Vitamins are essential organic compounds that an organism requires for survival, but cannot manufacture the organic compound in sufficient quantities; as is the case of vitamin D that requires sun exposure. There are 13 vitamins that are classified by their biological and chemical activity. Vitamins have many diverse biochemical functions. As shown herein the functions of the vitamins are not well understood.
• vitamin D may be classified as a hormone and functions as a regulator of mineral metabolism, treats rickets in children and osteoporosis in the elderly; but, herein, it has been shown to treat myopathy and neuropathic pain. With the new combination of fatty acid(s), cholesterol lowering medicament(s) and vitamin D the range of disease(s) treated is extended to additional and various inflammatory diseases.
• Vitamin D is a secosteroid comprising vitamin D 3 (Cholecalciferol) and vitamin D 2 (Ergocalciferol). Either forms of vitamin D are beneficial in treating myopathy, myositis and neuropathy.
• the vitamin D used herein was vitamin D 3 and the minimum concentration was 2000 IU that resulted in a blood plasma vitamin D 3 25-OH level greater than 30 ng/ml.
• Vitamin C like vitamin D is an essential in human vertebrates. There are 2 forms found in nature for vitamin C, ascorbate as L-ascorbate and ascorbic acid as L-ascorbic acid. Both are present in human vertebrates and are conformational isomers. Herein, vitamin C was used in the form of L-ascorbic acid. By itself vitamin C has a fluctuating effect in biological reactions. Treating a particular disease requires a certain concentration while treating another disease requires a different concentration and, likewise, treating a viral infection, the common cold, requires a very different concentration.
• Controlling the total cholesterol is a cause and effect result of combining a fatty acid and a cholesterol lowering medicament.
• Adding vitamin C to the matrix adds to the enhanced treating of autoimmune diseases and viral infections.
• the spongy gum disease requires at least 1000 mg/day of vitamin C; whereas, the common cold, a viral disease, requires 8000 mg/day.
• Bacopa is an aquatic plant that belongs to the family
• Plantaginaceae It is an herb used in Indian culture as an ayurvedic medicine to treat anxiety and memory disorders. Bacopa monnieri was used exclusively herein; however, any kingdom of Plantal is contemplated. The minimum is 250 mg/day; however, for a stronger cognitive awakening, 500 mg/day is preferred.
• Vinpocetine has been reported to have vasodilation and nootropic improvement in cognitive functions and cerebral metabolism. Also it has been reported as a dominant antiinflammatory agent in the treatment of Parkinson's disease and Alzheimer's disease.
• a semi synthetic derivative alkaloid of vincamine or any other alkaloid derivative including, but is not limited to, reserpine, reserpinine, akuammicine, majdine, vinerine, ervine,ieridine, tombozine, vincananine, vincanidine, vincamone, apovincamine, vincaminol and perivincine are examples of cognitive enhancing
• Excipients are substances used along with the active ingredient of a medication. Their purposes are many from such important enhancements as absorption and solubility of the active ingredient to viscosity reduction, to shelf life of the overall medication and to enhancement of manufacturing processes.
• the types of excipients include, but are not limited to: anti-adherents, binders, coatings, color, disintegrants, encapsulants, flavors, glidants, lubricants, preservatives, sorbents and sweeteners.
• Compositions and methods of the disclosure may be administered as a solid tablet or gel capsule or injection or vaporizer.
• total cholesterol percent relative range is meant to describe:
• total cholesterol relative range is meant to describe:
• At least two data points are collected to determine a total cholesterol value.
• a first data point may be collected prior to administration of a composition of the disclosure and a second data point may be collected after administration of the composition of the disclosure.
• a third or subsequent data point may be collected following a treatment change in the components of the composition, one or more dosages/dosing schedules of the components of the composition or a change of formulation of one or more components of the composition.
• the first or earlier data point may represent the maximum total cholesterol and the second, third, subsequent or latest data point may represent the minimum total cholesterol.
• the first or earlier data point may represent the minimum total cholesterol and the second, third, subsequent or latest data point may represent the maximum total cholesterol.
• a first data point may be collected after daily administration of a composition of the disclosure for at least three months and additional (second, third, and subsequent) data points may be collected thereafter weekly or monthly for a period of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months.
• Figure 5 provides an exemplary timeline illustrating these embodiments. From collected and analyzed samples, a maximum total cholesterol (or highest cholesterol measurement) is determined and from the same sample, a minimum total cholesterol value (or lowest cholesterol measurement) is determined.
• the at least two data points should be measured/collected monthly for a period of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months. In certain embodiments, the at least two data points should be measured/collected two months apart. In certain embodiments, the last of the at least two data points should be measured/collected after all changes to the medication have been made during, for example, a treatment schedule or clinical trial. In the context of a clinical trial, individual subject data may be kept separate or may be pooled prior to data analysis.
• the term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean within 1 or more standard deviations. Alternatively, “about” can mean a range of up to 20%, or up to 10%, or up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, preferably within 5-fold, and more preferably within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term "about” meaning within an acceptable error range for the particular value should be assumed.
• compositions and methods include the recited elements, but do not exclude others.
• Consisting essentially of when used to define compositions and methods shall mean excluding other elements of any essential significance to the combination when used for the intended purpose. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants or inert carriers.
• Consisting of shall mean excluding more than trace elements of other ingredients and substantial method steps. Embodiments defined by each of these transition terms are within the scope of this invention.
• expression refers to the process by which polynucleotides are transcribed into mRNA and/or the process by which the transcribed mRNA is subsequently being translated into peptides, polypeptides, or proteins. If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell. [099] "Gene expression” refers to the conversion of the information, contained in a gene, into a gene product.
• a gene product can be the direct transcriptional product of a gene (e.g., mRNA, tRNA, rRNA, antisense RNA, ribozyme, shRNA, micro RNA, structural RNA or any other type of RNA) or a protein produced by translation of an mRNA.
• Gene products also include RNAs which are modified, by processes such as capping, polyadenylation, methylation, and editing, and proteins modified by, for example, methylation, acetylation, phosphorylation, ubiquitination, ADP-ribosylation, myristilation, and glycosylation.
• Modulation or “regulation” of gene expression refers to a change in the activity of a gene. Modulation of expression can include, but is not limited to, gene activation and gene repression.
• treating and “treatment” as used herein refer to reduction in severity and/or frequency of symptoms, elimination of symptoms and/or underlying cause, and improvement or remediation of damage.
• administering to a subject refers to the process of introducing a composition or dosage form of the invention into the subject (e.g., a human or other mammalian subject) via an art-recognized means of introduction.
• an agent e.g., a human subject or patient.
• a subject or patient e.g., a human subject or patient.
• compositions of the disclosure comprising at least one fatty acid and at least one cholesterol lowering compound may be provided in any formulation or any route of administration.
• compositions of the disclosure are formulated for oral administration as, for example, a liquid, a tablet, a capsule, a caplet, or a particulate (either in a liquid suspension, a solid dosage form, or an encapsulated form).
• Tablets may be manufactured using standard tablet processing procedures and equipment. Direct compression and granulation techniques are preferred. In addition to the active agent, tablets will generally contain inactive, pharmaceutically acceptable carrier materials such as binders, lubricants, disintegrants, fillers, stabilizers, surfactants, coloring agents, and the like.
• Capsules are also preferred oral dosage forms, in which case the active agent- containing composition may be encapsulated in the form of a liquid or solid (including particulates such as granules, beads, powders or pellets). Suitable capsules may be either hard or soft, and are generally made of gelatin, starch, or a cellulosic material, with gelatin capsules preferred. Two-piece hard gelatin capsules are preferably sealed, such as with gelatin bands or the like. See, for example, Remington: The Science and Practice of
• Oral dosage forms can, if desired, be formulated so as to provide for controlled release and/or sustained release, i.e., gradual, release of a composition of the disclosure, from the dosage form to the patient's body over an extended time period, typically providing for a substantially constant blood level of the at least one fatty acid or the at least one cholesterol lowering compound over a specific time period (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 16, 24, 36, or 72 hours or any time period in between). Release of the composition may also be delayed; that is, there is a time lag between administration and the start of release of the composition.
• sustained release dosage forms can be formulated by dispersing the active agent within a matrix of a gradually hydrolyzable material such as a hydrophilic polymer, or by coating a solid, drug-containing dosage form with such a material.
• Hydrophilic polymers useful for providing a sustained release coating or matrix include, by way of example: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, and carboxymethylcellulose sodium; acrylic acid polymers and copolymers, preferably formed from acrylic acid, methacrylic acid, acrylic acid alkyl esters, methacrylic acid alky] esters, and the like, e.g.
• polyvinyl pyrrolidone e.g., Povidone K30, polyvinyl acetate, and ethylene-vinyl acetate copolymer.
• Preferred sustained release polymers herein include those available as "Methocel" polymers from Dow Chemical, particularly the methylcellulose ether polymers in the MethocelTM A group, having a viscosity grade of about 4,000 cps and a methoxyl content of about 27.5% to 31.5%, e.g., MethocelTM A 15LV, MethocelTM A15C, and MethocelTM A4M.
• tablets, granules, powder, capsules, and the like can be produced according to a conventional method after adding excipient, and as necessary, binder, disintegrating agent, lubricant, coloring agent, taste-modifying agent, flavoring agent, and the like.
• additives may be ones generally used in the field, and for example, lactose, sodium chloride, glucose, starch, microcrystalline cellulose, and silicic acid as the excipient, water, ethanol, propanol, simple syrup, gelatin solution, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, shellac, calcium phosphate, and
• polyvinylpyrrolidone as the binder
• agar powder sodium hydrogen carbonate, sodium lauryl sulfate, and stearic acid monoglyceride as the disintegrating agent
• purified talc, stearic acid salt, borax, and polyethylene glycol as the lubricant
• ⁇ -carotene, yellow iron sesquioxide, and caramel as the coloring agent
• saccharose and orange peel as the taste-modifying agent
• microcrystalline cellulose is preferred fillers herein, e.g., Avicel® PHIOI, Avicel® PH 102, and Avicel® PH200 (FMC), with particle sizes of about 50 microns, 100 microns, and 190 microns, respectively.
• Microcrystalline cellulose having a particle size in the range of about 50 microns to 200 microns is preferred herein.
• the dosage forms may also be provided with a delayed release coating, e.g., composed of an acrylate and/or methacrylate copolymers.
• a delayed release coating e.g., composed of an acrylate and/or methacrylate copolymers.
• examples of such polymers are those available under the trade name "Eudragit” from Rohm Pharma (Germany).
• the Eudragit series E, L, S, RL, RS, and NE copolymers are available as solubilized in organic solvent, in an aqueous dispersion, or as a dry powder.
• Preferred acrylate polymers are copolymers of methacrylic acid and methyl methacrylate, such as the Eudragit L and Eudragit S series polymers.
• Other preferred Eudragit polymers are cationic, such as the Eudragit E, RS, and RL series polymers.
• Eudragit EIOO and E PO are cationic copolymers of dimethylaminoethyl methacrylate and neutral methacrylates (e.g., methyl methacrylate), while Eudragit RS and Eudragit RL polymers are analogous polymers, composed of neutral methacrylic acid esters and a small proportion of trimethylammonioethyl methacrylate.
• Preparations according to this invention for parenteral administration include sterile aqueous and nonaqueous solutions, suspensions, and emulsions.
• Injectable aqueous solutions contain the active agent in water-soluble form.
• nonaqueous solvents or vehicles include fatty oils, such as olive oil and corn oil, synthetic fatty acid esters, such as ethyl oleate or triglycerides, low molecular weight alcohols such as propylene glycol, synthetic hydrophilic polymers such as polyethylene glycol, liposomes, and the like.
• Parenteral formulations may also contain adjuvants such as solubilizers, preservatives, wetting agents, emulsifiers, dispersants, and stabilizers, and aqueous suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, and dextran.
• Injectable formulations are rendered sterile by incorporation of a sterilizing agent, filtration through a bacteria-retaining filter, irradiation, or heat. They can also be manufactured using a sterile injectable medium.
• the active agent may also be in dried, e.g., lyophilized, form that may be rehydrated with a suitable vehicle immediately prior to administration via injection.
• compositions of the disclosure may also be administered through the skin using conventional transdermal drug delivery systems, wherein the active agent is contained within a laminated structure that serves as a drug delivery device to be affixed to the skin.
• the drug composition is contained in a layer, or "reservoir,” underlying an upper backing layer.
• the laminated structure may contain a single reservoir, or it may contain multiple reservoirs.
• the reservoir comprises a polymeric matrix of a pharmaceutically acceptable contact adhesive material that serves to affix the system to the skin during drug delivery.
• the drug- containing reservoir and skin contact adhesive are present as separate and distinct layers, with the adhesive underlying the reservoir which, in this case, may be either a polymeric matrix as described above, or it may be a liquid or hydrogel reservoir, or may take some other form.
• Transdermal drug delivery systems may in addition contain a skin permeation enhancer.
• the composition may be formulated as a depot preparation for controlled release of the at least one fatty acid or the at least one cholesterol lowering compound, preferably sustained release over an extended time period.
• sustained release dosage forms are generally administered by implantation (e.g., subcutaneously or intramuscularly or by intramuscular injection).
• compositions will generally be administered orally, parenterally, transdermally, or via an implanted depot, other modes of administration are suitable as well.
• administration may be transmucosal, e.g., rectal or vaginal, preferably using a suppository that contains, in addition to the active agent, excipients such as a suppository wax.
• Formulations for nasal or sublingual administration are also prepared with standard excipients well known in the art.
• the pharmaceutical compositions of the invention may also be formulated for inhalation, e.g., as a solution in saline, as a dry powder, or as an aerosol.
• dosage form denotes any form of a pharmaceutical composition that contains an amount of active agent sufficient to achieve a therapeutic effect with a single administration.
• the dosage form is usually at least one such tablet or capsule.
• the frequency of administration that will provide the most effective results in an efficient manner without overdosing will vary with the characteristics of the particular active agent, including both its pharmacological characteristics and its physical characteristics, such as hydrophilicity.
• pharmaceutically acceptable is meant a material that is not biologically or otherwise undesirable, i.e., the material may be incorporated into a pharmaceutical composition administered to a patient without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the composition in which it is contained.
• pharmaceutically acceptable refers to a pharmaceutical carrier or excipient, it is implied that the carrier or excipient has met the required standards of toxicological and manufacturing testing or that it is included on the Inactive Ingredient Guide prepared by the U.S. Food and Drug administration.
• “Pharmacologically active” as in a “pharmacologically active” (or “active”) derivative or analog, refers to a derivative or analog having the same type of pharmacological activity as the parent compound and approximately equivalent in degree.
• subject or “individual” or “patient” refers to any subject for whom or which therapy is desired, and generally refers to the recipient of the therapy to be practiced according to the invention.
• the subject can be any vertebrate, but will typically be a mammal. If a mammal, the subject will in many embodiments be a human, but may also be a domestic livestock, laboratory subject or pet animal.
• EXAMPLE 1 Patient Demographics.
• Patient A had several heart attacks in 1991, 1995 and 2001.
• the heart attack in 1991 resulted in administering a balloon angioplasty.
• the attack in 1995 resulted in the placement of a stent in the coronary artery.
• the heart attack resulted in a quadruple bypass.
• Patient A suffered arterial fibrillation in March 2010.
• Patient A was implanted with a defibrillator in the upper left chest along with cardiac ablation.
• statins prescribed for Patient A beginning in 2001 with Lipitor, Vytorin, Provachol and Zetia.
• Statins were changed continually because the insurance provider no longer listed a particular statin on its formulary.
• the only non-statin was Tricor, a fenofibrate, which reduces cholesterol and triglycerides.
• Patient A After suffering arterial fibrillation, Patient A was prescribed a series of medicaments to control the fibrillation, blood pressure and water retention.
• the prescribed medications included Lisinopril, Digoxin, Warfarin, Metroprolo and Lasix.
• Metoprolol and statin are known to cause psoriasis and other autoimmune diseases.
• MRI Magnetic resonance imaging
• Patient B The reason to include Patient B in this study is because Patient B and Patient A are spouses and work and eat meals together. Whatever Patient A consumes so does Patient B.
• the vitamins, hormones, fatty acids and minerals are taken by both Patients under the same conditions.
• Patient B becomes a baseline (negative control) to measure the effects of vitamins, hormones, fatty acids, organic compounds and minerals taken without statins.
• the effect of taking a fatty acid, hormone, vitamin or organic compound while taking a statin or other cholesterol lowering medicine(s) was measured in Patient A using Patient B as a negative control.
• Both Patients A and B took the same fatty acids, hormones, vitamins, minerals, organic compounds and antioxidants. Also they had the same meals each day, 7 days a week.
• Figure 1 (Patient A) and Figure 3 (Patient B) reveals striking results provided herein.
• the concentration of medicaments will vary depending on numerous factors, such as, for example, the seriousness of the disease; use of other medications; the subjects physiology; other comorbidities; medicament preparation, for example, pill versus gel capsule; medicament administration and the type of disease being treated.
• Table 3 has 2 interesting data points that will be used later in establishing the meaning of vitamin D. Those data points are September, 2010 and June, 2012. The total cholesterol increases and the blood plasma concentration of total vitamin D increases. From 2 data points and the high blood plasma concentration of vitamin D, one can conclude that very high concentrations of vitamin D in blood serum will increase total cholesterol.
• Experiment 4 is a subset of Experiment 3.
• Patient B was given Crestor (20 mg) and her cholesterol level was measured from January, 2015 through April, 2015.
• she experienced auras (preictals), brief moments where she was unable to form a vocal sentence. It is usual that her preictals occur before a grand mal seizure.
• her auras occurred monthly. In April they increased to every other day without a grand mal seizure.
• she discontinued Crestor, but the auras continued with the same frequency. The following month, June, she was given vinpocetine and Coenzyme Q10 (trans-form). The auras discontinued the next day.
• apolipoproteins apolipoproteins, chylomicrons, enzymes, vitamins, hormones, fats, proteins, lipids, glycerol, etc.
• Patient A was prescribed a number of medications in addition to Lipitor and Zetia.
• the additional medications included Lisinopril, Digoxin, Warfarin, Metoprolol and later Lasix.
• Table 4 lists the medication and their concentrations in milligrams per day (mg/day).
• Patient A was prescribed a number of medications. One of which was Metoprolol. As an adverse side effect, Metoprolol is known to cause psoriasis.
• Warfarin taken daily as a blood thinner, caused the psoriasis on the calves to bleed excessively due to the dermal skin layer cracking and separating from the epidermal layer.
• vitamin C was the first medicament to be removed. Taking vitamin C for 2 months was enough to stop the gum bleeding and strengthen the gum tissue. Removal of vitamin C consequently had no effect. Also, there was no effect on the total cholesterol. [0168] The vitamin C was replaced and Omega-3 fish oil removed. Within 2 weeks in August, 2013, psoriasis returned as well as another skin disease known as keratosis, both pilaris and seborrheic. Patient A was given 2000 mg of Omega-3 fish oils as outlined in Table 2 and cross-referenced in Table 4. Within 2 weeks the psoriasis and pilaris keratosis were gone. The seborrheic keratosis took 4-6 months to disappear.
• the dosage of vitamin D3 ranged from 3000 IU to 5000 IU and to 6000 IU with no apparent effect on the total cholesterol level.
• the total vitamin D, 25-OH in the blood serum measured 44.6 ng/mg; however, at a very high concentration of vitamin D 3 , 12,000 IU; total vitamin D, 25- OH measured was 89.3 ng/ml; the total cholesterol level increases, but there was no change in autoimmune disease characteristics or other disease characteristics.
• Vitamin D 3 may lower active statin metabolites. Thus, increasing the vitamin D 3 concentration may lower the efficacy of Atorvastatin.
• Patient A went back to his normal medicament concentrations in October, 2013 and returned to a total cholesterol value of 132 mg/dL.
• Vitamin D 3 was increased to 3000 IU. Again the same statins were administered as before without any myositis (myopathy). For 3 months, Patient A had no psoriasis, no keratosis, no bleeding gums and no myopathy. However, because the statin combination of
• Zetia/Simvastatin is not as efficacious as the statin combination Zetia/Lipitor, the total cholesterol increased, but remained in a narrow range.
• the total cholesterol range was 23 mg/dL and the percent relative range was 13.1% that is higher than the Lipitor/Zetia combination.
• Region 1 begins May, 2013 through October, 2013.
• Region 2 begins January, 2014 through March, 2014.
• Region 1 was influenced by Lipitor/Zetia and Omega-3 fish oil.
• Region 2 was influenced by Simvastatin/Zetia and Omega-3 fish oil.
• Each region had a different total cholesterol range. Lipitor had a lower range than Simvastatin, but Lipitor was at twice the concentration as Simvastatin. At the same concentrations each statin would perform in a similar manner.
• Region 1 had average total cholesterol of 132 mg/dL.
• Region 2's average total cholesterol was 175 mg/dL.
• Patient A had no recurrence of psoriasis, no recurrence of keratosis, no recurrence of bleeding gums, no recurrence of neuropathy and no recurrence of myositis.
• the level of total cholesterol was indifferent to the treating of an autoimmune disease.
• the Omega-3 fatty oils are responsible for the narrow total cholesterol range and responsible along with a statin(s) for treating autoimmune diseases and other diseases.
• Vitamin D 3 was an active ingredient for treating myopathy that required the combination of Omega-3 fish oil(s) and statin(s) to attain a superior efficacy of treatment.
• Patient A was administered Omega-3 fish oil(s) at a concentration of 3000 mg.
• the fish oil(s) EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) were now 3 times what they were in previous months.
• the result was a drastic decrease in total cholesterol.
• the percentage change was -20%; it represented the total cholesterol for April, 2014 of 137 mg/dL to May, 2014 whose total cholesterol was 109 mg/dL. There was no change in the autoimmune diseases.
• Experiment 11 was designed to check the results found in Experiment 10.
• Patient A changed his Crestor (40 mg) to Lipitor (80 mg).
• the total cholesterol increased substantially, because Crestor is a more efficacious inhibitor of the enzyme HMG-CoA reductase.
• the Lipitor/Zetia statins maintained a very tight total cholesterol range from July, 2014 through October, 2014.
• Patient A was administered Crestor (40 mg) as a substitute for Lipitor (80 mg) and administered 3000 mg of Omega-3 fish oil(s).
• the total cholesterol decreased drastically to 103 mg/dL from a previously total cholesterol value of 136 mg/dL, a decrease of approximately 24%.
• the previous medicaments were the same as illustrated in Table 2.
• Patient A experienced a root canal extraction. There was no problem in the repair of the root canal; however, Patient A experienced no pain for months while the roots were decaying, a result of vitamin D therapy.
• Vitamin D 3 was lowered to 1000 IU and Omega-3 fish oil(s) was lowered to 600 mg.
• Vitamin D 3 was increased to 2000 IU per day in February, 2015. The pain associated with myositis soon disappeared; however, due to the low concentration of Omega- 3 (s) a small skin rash or seborrheic keratosis appeared. Early May, 2015 the Omega-3 fish oil(s) was increased to 1600 mg (600+1000 mg) whose EPA concentration was 847 mg and whose DHA concentration was 453 mg. After the medicament Omega-3 oil(s) was administered, the skin condition disappeared.
• Omega-3 oils were broken-down as: EPA-800 mg, DHA-400 mg, Omega 6-276 mg and Omega 9-170 mg.
• seborrheic keratosis returns and is believed due to the Omega 6 oil.
• Vitamin C and vitamin B complex were removed without any adverse effects to the disease patterns.
• the soft gum and bleeding gums were repaired where the gums were hard and no bleeding occurred.
• Vinpocetine at 30 mg was added as a medicament in June, 2015.
• Omega-3 oil(s) were removed as a medicament for Patient A.
• Patient A was covered entirely on the front right chest and on the right upper and lower back with pilaris keratosis.
• the Omega-3 oil(s) were introduced at a concentration of 2100 mg and the pilaris keratosis disappeared within 2 weeks; hence, vinpocetine will not treat the autoimmune disease of keratosis; however, it has a strong effect on controlling the total cholesterol after Omega-3 oil(s) has been administered as well as controlling dementia.
• Table 2 is an accumulation of Patient A's data for total cholesterol illustrated as total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), drug type and their concentrations and the comments associated with the drugs, vitamins, hormones, oils, fish oils, statins, organic compounds, vitamin D, vitamin D3 blood concentration, and adsorption parameters.
• TC total cholesterol
• HDL high density lipoprotein
• LDL low density lipoprotein
• TG triglycerides
• Table 3 is an accumulation of Patient B's data for total cholesterol illustrated as total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), drug type and their concentrations and the comments associated with the drugs, vitamins, hormones, oils, fish oils, statins, organic compounds, vitamin D, vitamin D3 blood concentration, and adsorption parameters.
• TC total cholesterol
• HDL high density lipoprotein
• LDL low density lipoprotein
• TG triglycerides
• Table 4 describes the drugs and organic compounds administered to Patient A as well as the concentrations of each drug and organic compound.
• Table 5 describes the drugs and organic compounds administered to Patient B as well as the concentrations of each drug and organic compound.
• Table 6 describes the Detox Schedule for Patient A (see also Figure 1).
• Table 7 is a list of autoimmune diseases and the cellular and cytokine characteristics/markers that may be used to identify a patient having one or more of these conditions.
• Table 8 illustrates the various fatty acids and their concentrations as fatty acid triglycerides and fatty acid ethyl esters measured from the blood serum of Patient A. Also shown are the concentrations of vitamin D 3 , as cholecalciferol D 3 in its powder and gel forms as well as the total vitamin D and 25-OH.
• Table 9 A copy of the Lipid-modifying Effects 10 mg and 20 mg Crestor (AstraZeneca Pharmaceuticals) in Primary Dysbetalipoproteinemia (Type III hyperlipo)

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