WO2011043735A1 - A composition for modulating immune responses - Google Patents
A composition for modulating immune responses Download PDFInfo
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- WO2011043735A1 WO2011043735A1 PCT/SG2009/000368 SG2009000368W WO2011043735A1 WO 2011043735 A1 WO2011043735 A1 WO 2011043735A1 SG 2009000368 W SG2009000368 W SG 2009000368W WO 2011043735 A1 WO2011043735 A1 WO 2011043735A1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
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- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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Definitions
- cytokines it is important that the amount or quantity of cytokines within the body is well regulated to maintain bodily homeostatic balance. This is because an imbalance in the production of cytokines, for example an excessive production of cytokines (e.g., a cytokine storm), within the body can cause significant damage to body tissues and organs.
- an imbalance in the production of cytokines for example an excessive production of cytokines (e.g., a cytokine storm) within the body can cause significant damage to body tissues and organs.
- compositions e.g., phytochemical compositions and nutraceutical compositions
- compositions that include at least an extract from Garcinia Mangostana L. (hereinafter referred to as mangosteen) and an extract from Centella Asiatica L. (hereinafter referred to as Gotu Kola) to facilitate or provide an immunomodulating, immune balancing, an anti-viral, anti-cytokine storm, and/or an anti-inflammatory effect within the living organism's body.
- the composition facilitates or effectuates a decrease or reduction in quantity of pro-inflammatory mediators or pro-inflammatory cytokines, and/or an increase in quantity of antiinflammatory cytokines, within living organisms that are infected with viruses.
- compositions including at least a combination of the extract from mangosteen and the extract from Gotu Kola exhibit or provide unexpected effectiveness in the prevention, control, management, and/or treatment of an autoimmune disorder (e.g., SLE or lupus, rheumatoid arthritis, and psoriasis).
- an autoimmune disorder e.g., SLE or lupus, rheumatoid arthritis, and psoriasis.
- Compositions in accordance with the present disclosure can additionally therapeutically affect the progression of diseases known to be exacerbated by the overproduction or dysregulation of particular cytokines.
- a composition in accordance with the present disclosure can include approximately 1 % - 100% (e.g., approximately 5% - 95%, or approximately 10% - 90%, or approximately 20% - 80%, or approximately 25% - 75%, or approximately 35% - 65%, or approximately 50%) by mass, weight, or volume of a combination of the extract from mangosteen and the extract from Gotu Kola (where in some embodiments an uncertainty or error range can be defined as less than approximately 2.5%, or less than approximately 1 %).
- the concentration or quantity (e.g., quantity by weight) of each of the extract from mangosteen and the extract from Gotu Kola, and possibly the concentration or quantity of one or more of the extract from sesame, the extract from soybean, and the extract from guava is selected or varied for enhancing or optimizing a decrease or reduction in a quantity of one or more pro-inflammatory cytokines within the living organism and/or an increase in a quantity of one or more anti- inflammatory cytokines within the living organism.
- approximately 60% of the composition i.e., approximately 333.5 mg out of the composition weight of approximately 416.55 mg
- the remaining weight of such a 500 mg capsule i.e., approximately 83.45 mg in this representative example
- the combination of the extract from mangosteen and the extract from Gotu Kola in the composition provides a synergistic effect, for example, a synergistic anti-inflammatory, anti-cytokine storm, anti-viral (e.g., anti-influenza), immunomodulatory, and/or immune system or cytokine balancing effect, when the composition is consumed by the living organism.
- a synergistic anti-inflammatory, anti-cytokine storm, anti-viral (e.g., anti-influenza), immunomodulatory, and/or immune system or cytokine balancing effect when the composition is consumed by the living organism.
- unexpectedly strong anti-inflammatory, anti-cytokine storm, anti-viral (e.g., anti- influenza), immunomodulatory, and/or immune system or cytokine balancing effects are physically observed and/or recorded in living organisms consuming the composition.
- Extracts of mangosteen generally include xanthones, which are biologically active natural phenols that are found in some plant species.
- a xanthone has a molecular formula Ci 3 H 8 0 2 .
- the general structure of a xanthone is:
- sesame seeds are good sources of iron, magnesium, manganese, copper, calcium, and vitamins such as vitamin Bl and vitamin E.
- sesame seeds include lignans and sesamin. Sesamin are phytoestrogens that have associated anti-oxidant and anti-cancer properties.
- sesame seeds also contain phytosterols, which have been suggested to be capable of reducing blood cholesterol.
- guava Many species of guava are grown commercially. One of the most common species of guava, particularly in tropical regions around the world, is known as the Apple guava or Psidium Guajava L. The nutritional value of the guava fruit is dependant on the species of guava. However, all guava fruits are generally good sources of vitamins A and C, potassium, magnesium, and dietary fiber. In addition, all guava fruits contain both carotenoids and polyphenols, which are major classes of antioxidant pigments. Accordingly, the guava fruit is generally considered to be a particularly good source of antioxidants.
- IL-2 is generally produced by activated T helper cells (also known as effector T cells) during an immune response.
- Pathogens also known as antigens
- IL-2 mediates its effects by binding to IL-2 receptor molecules, which are expressed by lymphocytes.
- the binding of IL-2 to its receptor molecule triggers a signaling cascade, for example Ras/MAPK, JAK/Stat, and PI 3 -kinase/ Akt signaling modules.
- IL-2 has numerous functions including facilitating production of immunoglobulins by B cells.
- a composition carried by a capsule is provided in accordance with the present disclosure.
- the composition includes approximately 8.32% by weight of an extract from mangosteen, approximately 25% by weight of an extract from Gotu Kola, and approximately 16.67% by weight of each of an extract from sesame, an extract from soybean, and an extract from guava.
- the capsule carries a total substance mass of approximately 500mg.
- the capsule includes approximately 41.5mg of the extract from mangosteen, approximately 125mg of the extract from Gotu Kola, and approximately 83.35 mg of each of the extract from sesame, the extract from soybean, and the extract from guava.
- the capsule further carries one or more additional ingredients, such as a known chemical or natural compound (e.g., an additive, stabilizer, or preservative) having a mass of approximately 83.45 mg to yield the total capsule ingredient mass of 500 mg.
- a known chemical or natural compound e.g., an additive, stabilizer, or preservative
- Control culture 1 Includes a predetermined volume of a sample of isolated egg cells that has been diluted in a ratio of 1 :50;
- each of cultures 1 to 6 was made up to a final volume of approximately 200 ⁇ 1 in a well of a standard 96 well plate. It will be understood by a person of ordinary skill in the art that an alternative final volume (e.g., ⁇ ) may also be used.
- the number or concentration of isolated egg cells used for each culture was approximately equal. For instance, in the experiments of example four, the number of isolated egg cells used for each culture was approximately 2 x 10 5 (i.e., 200,000). It will be understood by a person of ordinary skill in the art that the number or concentration of isolated egg cells used for each of cultures 1 to 6 can be adjusted as required by varying the degree of dilution of the cultures (e.g., by increasing total volume of the culture by adding medium).
- the standard 96 well plate can be substituted with alternative tissue culture containers, for example 48 well plates or petri dishes).
- Each of cultures 1 to 6 was incubated at the same physical conditions for an equal length of time. More specifically, each of cultures 1 to 6 was incubated at a temperature of 37°C with 5% of carbon dioxide for 24 hours.
- Figure 3 Effect of concentrations of approximately l .Oug/ml and approximately 5.0ug/ml of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava on the concentration (pg/ml) of IL-1 (i.e., amount of IL-1 released) by isolated egg cells.
- PBMCs were used for the experiments described in this example, the PBMCs may be substituted for other types of immune cells found within the body.
- the PBMCs were isolated and prepared using isolation techniques or methods known to a person of ordinary skill in the art.
- An exemplary method or technique is the differential density gradient centrifugation technique, the steps or process steps of which are known to a person of ordinary skill in the art.
- PBMCs used for each culture were approximately equal.
- the number of PBMCs used for each culture was approximately 1 x 10 5 (i.e., 100,000).
- the number or concentration of PBMCs used for each of cultures of differing days of blood collection can be adjusted as required by varying the degree of dilution of the cultures (e.g., by increasing total volume of the culture by adding medium). The cultures were incubated at the same physical conditions for an equal length of time.
Abstract
A composition includes an extract from mangosteen and an extract from Gotu Kola, and optionally includes at least one of an extract from sesame, an extract from soybean, and an extract from guava for therapeutically affecting a pro-inflammatory cytokine condition (e.g., by decreasing a pro-inflammatory cytokine level) and/or an anti-inflammatory cytokine condition (e.g., by increasing an anti-inflammatory cytokine level) within a body of a living organism. In several embodiments, the composition includes at least 20 % - 80 % by weight of a combination of the extract from mangosteen and the extract from Gotu Kola. Compositions in accordance with the present disclosure can be used to therapeutically treat or alleviate physiologic conditions or symptoms associated with one or more of cytokine storm, viral infections, inflammation, immune system or cytokine imbalance or dysregulation, autoimmune disorders, and neurodegenerative disorders.
Description
A COMPOSITION FOR MODULATING IMMUNE RESPONSES Technical Field
The present disclosure relates generally to compositions for modulating an immune response within a living organism. More specifically, various aspects of the present disclosure relate to compositions that facilitate or provide an anti-cytokine storm, an immune balancing, and/or an anti-inflammatory effect within the living organism.
Background
The immune system of a living organism is essential for fighting pathogens, for example bacteria, viruses, and other foreign matter, that invade, or are introduced into, the body of the living organism. Recognition of pathogens within the body typically triggers an immune response. Generally, the immune response involves increased production of cytokines, more specifically pro-inflammatory cytokines and pro-inflammatory mediators, within the body.
Cytokine storms (also known as hypercytokinemia) can occur in response to recognition of pathogens within the body. During a cytokine storm, there is an increased release of pro-inflammatory mediators, for example pro-inflammatory cytokines such as Interleukin- 1 (IL1), Interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-alpha), oxygen free radicals, and coagulation factors within the body. Cytokine storms can cause significant damage to body tissues and organs, particularly when left uncontrolled. For instance, the occurrence of cytokine storms in the lungs can cause an accumulation of fluids and immune cells (e.g., macrophages) in the lungs, and eventually block off the body's airways, thereby resulting in respiratory distress and even death.
The cause of cytokine storms within living organisms is a subject of ongoing research. A possible cause of cytokine storms within living organisms is an encounter, by the immune system, of a new and highly pathogenic pathogen. In addition, cytokine storms have also been associated with a number of infectious and non-infectious diseases, including influenza (e.g., influenza A), and systemic inflammatory response syndrome (SIRS). For
instance, studies have suggested that the influenza A (H1N1) virus causes cytokine storms within living organisms.
Influenza, which is commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (i.e., influenza viruses). The influenza viruses are airborne viruses that can be transmitted via coughs and sneezes, which create aerosols containing the influenza viruses. The influenza viruses can also be transmitted through contact with contaminated body fluids, such as saliva, nasal secretions, and blood. Common symptoms of influenza include chills, fever, sore throat, coughs, headache, and general discomfort.
It is important that the amount or quantity of cytokines within the body is well regulated to maintain bodily homeostatic balance. This is because an imbalance in the production of cytokines, for example an excessive production of cytokines (e.g., a cytokine storm), within the body can cause significant damage to body tissues and organs.
Accordingly, it is important to be capable of preventing, controlling, or mitigating cytokine storms within living organisms. There are several conventional techniques and compositions associated with preventing, controlling, or cytokine storms (and inflammation in general) within living organisms. For example, research has suggested that angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs), may have clinical utility for modulating immune responses, for example down-regulating cytokine storms and/or inflammation, within living organisms. In addition, corticosteriods and non-steroidal anti-inflammatory drugs (NSAIDS) have also been employed in an attempt to down-regulate cytokine storms and/or inflammation within living organisms.
However, the effectiveness and safety of many conventional techniques and compositions associated with the prevention, control, or mitigation of cytokine storms within living organisms have not been comprehensively or adequately verified. Multiple conventional anti-viral drugs or compositions (e.g., anti-influenza drugs or compositions) have
associated undesirable side effects when administered to patients. Examples of such undesirable side effects include nausea, vomiting, and toxicity. Furthermore, there is a problem of pathogen resistance or adaptation to an increasing number of conventional anti-viral drugs (e.g., anti-influenza drugs).
Novel and enhanced techniques and compositions, methods capable of preventing, controlling, or mitigating cytokine storms within living organisms will be useful for improving public health. Additionally, novel and enhanced techniques and compositions capable of providing anti-viral, for example anti-influenza, functions or effects can be useful for improving public health.
Summary
Various aspects of the disclosure provide a composition that includes an extract from Garcinia mangostana and an extract from Centella asiatica. Compositions in accordance with the present disclosure can be used for treating a physiologic symptom associated with at least one of a cytokine storm, a viral infection, an inflammation condition, an autoimmune disorder, and a neurodegenerative disorder within a living organism (e.g., when the living organism consumes the composition). Compositions in accordance with the present disclosure can be used to alleviate or treat physiologic symptoms associated with a cytokine storm or a viral infection. The cytokine storm or viral infection can correspond to or arise in association with, for instance, an influenza virus (e.g., existing as or derived from one of influenza A (H1N1), influenza A (H2N1), influenza A (H2N2), influenza A (H3N2), and an influenza A (H5N1) virus), a Rhinovirus, an enterovirus, a coronavirus, or other pathogen.
Additionally, compositions in accordance with the present disclosure can be used to alleviate or treat physiologic symptoms associated with an autoimmune disorder such as Systemic lupus erythematosus (SLE), rheumatoid arthritis, allergic symptoms, psoriasis, diabetes, chronic fatigue syndrome (CFS), fibromyalgia, Crohn's disease, or Inflammatory Bowel Disease (IBD). Furthermore, compositions in accordance with the
present disclosure can be used to alleviate or treat physiologic symptoms associated with a neurodegenerative disorder such as Parkinson's Disease, Alzheimer's disease, and Multiple Sclerosis. In general, the composition provides at least approximately 10 ug of each of the extract from Garcinia mangostana and the extract from Centella asiatica. In some embodiments, the composition provides at least approximately 1 mg or at least approximately 10 mg of each of these extracts, and in other embodiments at least 25 mg or at least 50 mg of a combination of these extracts.
In one aspect, at least approximately 25% by weight (e.g., approximately 50% by weight) of a composition in accordance with the present disclosure is made up of a combination of the extract from Garcinia mangostana and the extract from Centella Asiatica. In an embodiment, a composition according to the present disclosure provides the extract of Garcinia mangostana and the extract from Centella Asiatica in a ratio of approximately 25% Garcinia mangostana : approximately 75% Centella Asiatica, while in another embodiment, the composition provides the extract of Garcinia mangostana and the extract from Centella Asiatica in a ratio of approximately 50% Garcinia mangostana : approximately 50% Centella Asiatica.
In various aspects, compositions in accordance with the present disclosure further include at least one of an extract from sesame, an extract from soybean, and an extract from guava. Particular compositions according to the present disclosure can include each of an extract from sesame, an extract from soybean, and an extract from guava. Compositions that include one or more of an extract from sesame, an extract from soybean, and an extract from guava can provide at least approximately 20% by weight (e.g., approximately 50% by weight) of a combination of the extract of Garcinia mangostana and the extract from Centella Asiatica. Depending upon embodiment details, compositions in accordance with the present disclosure can be carried by one from the group of a food product, a beverage product, a
capsule, a pill, a tablet, a powder, a suspension, an emulsion, or other substance that can be ingested by a living organism. In several aspects, compositions provided by the present disclosure can be combined with or include an anti-inflammatory substance (e.g., ibuprofen, diclofenac, aspirin, or naproxen) or an anti-viral drug (e.g., oseltamivir or zanamivir).
Compositions according to the present disclosure can facilitate or effectuate a decrease in a quantity of a pro-inflammatory cytokine (e.g., one or more of interleukin-1 , interleukin- 6, interleukin-8, and tumor necrosis factor-alpha) within a living organism. Such a decrease in a quantity of a pro-inflammatory cytokine can be substantially between approximately 25% to approximately 85% (e.g., approximately 50% to approximately75%). Additionally or alternatively, compositions according to the present disclosure can at least one of facilitate and effectuate an increase in a quantity of an antiinflammatory cytokine (e.g., interleukin-2) within a living organism. Moreover, compositions according to the present disclosure can alleviate or treat an immune system or cytokine imbalance condition within a living organism, for instance, a dysregulation between cross-regulating cytokines (e.g., between interleukin-1 and interleukin-2).
In various aspects, a process for manufacturing a composition for treating a physiologic symptom associated with at least one of a cytokine storm, a viral infection, an inflammation condition, an autoimmune disorder, and a neurodegenerative disorder within a living organism when consumed thereby includes obtaining or providing an extract from Garcinia mangostana; obtaining or providing an extract from Centella asiatica; and combining the extract from Garcinia mangostana and the extract from Centella asiatica such that the composition comprises at least approximately 10 ug (e.g., at least approximately 1.0 mg or approximately 10.0 mg) of each of the extract from Garcinia mangostana and the extract from Centella asiatica. In multiple embodiments, the composition includes at least approximately 25 mg (e.g., approximately 50 mg) of a combination of the extract from Garcinia mangostana and the extract from Centella asiatica.
In accordance with particular aspects of the disclosure, a process for manufacturing the aforementioned composition can further include providing the composition with predetermined concentrations of at least one of an extract from sesame, an extract from guava, and an extract from soybean. In some embodiments, at least approximately 25% by weight of the composition is made up of a combination of the extract from Garcinia mangostana and the extract from Centella Asiatica, while in other embodiments, approximately 50% by weight of the composition is made up of a combination of the extract from Garcinia mangostana and the extract from Centella Asiatica. In several embodiments, the remaining weight percentage of the composition is at least partially made up of one or more of the extract from sesame, the extract from guava, and the extract from soybean (e.g., in an embodiment, the remaining composition weight percentage is made up of each of the extract from sesame, the extract from guava, and the extract from soybean). In certain embodiments, a manufacturing process in accordance with the present disclosure can yield a composition that provides the extract of Garcinia mangostana and the extract from Centella Asiatica in a ratio of approximately 25% Garcinia mangostana : 75% Centella Asiatica. Alternatively, a manufacturing process in accordance with the present disclosure can yield a composition that provides the extract of Garcinia mangostana and the extract from Centella Asiatica in a ratio of approximately 50% Garcinia mangostana : 50% Centella Asiatica.
A manufacturing process according to the present disclosure can further include incorporating at least a portion of composition into one of a food product, a beverage product, a capsule, a pill, a tablet, a powder, a suspension, and an emulsion. For instance, in an embodiment, a manufacturing process can include adding the extract of Garcinia mangostana and the extract of Centella Asiatica to an anti-inflammatory substance (e.g., ibuprofen, diclofenac, aspirin) or an anti-viral drug (e.g., oseltamivir and zanamivir).
Detailed Description
A variety of detrimental health conditions are associated with irregularities in or dysregulation of particular cytokine levels within the body of a living organism. For example, an elevated level of a pro-inflammatory cytokine (e.g., considered by itself with respect to a level expected to correspond to a healthy patient state, or considered in association with a level of an anti-inflammatory cytokine) can lead to or exacerbate an auto-immune condition such as Rheumatoid arthritis, or another condition such as Parkinson's Disease (PD). As another example, a cytokine storm (also known as hypercytokinema) is a potentially fatal immune response that is typically associated with a number of infectious and non-infectious diseases, for instance influenza (e.g., influenza A), arthritis, and systemic inflammatory response syndrome (SIRS). Cytokine storms can occur in response to viral infections in living organisms, for instance, influenza viral infections, and more specifically influenza A (H1N1) or similar types of viral infections. During a cytokine storm, an increased amount of pro-inflammatory mediators or proinflammatory cytokines are released into the body of the living organism. Cytokine storms have the potential to cause significant damage to body tissues and organs, especially when uncontrolled. The effectiveness and safety of many conventional compositions, methods, processes, and/or techniques for preventing, controlling, down- regulating, and/or stopping cytokine storms (and inflammation) have not been comprehensively or adequately verified. In addition, many conventional compositions, methods, processes, and/or techniques for preventing, controlling, down-regulating, and/or stopping cytokine storms (and inflammation) have associated undesirable side effects, for example nausea, vomiting, and toxicity. There is also a problem of development of pathogen resistance or adaptation to an increasing number of conventional drugs, such as anti-viral (e.g., anti-influenza) drugs.
Accordingly, there is a need for new and/or enhanced compositions, methods, and processes for modulating immune responses, for example, by providing immune balancing effects (e.g., by way of normalizing levels of particular cross-regulating cytokines) and/or preventing, controlling, down-regulating, and/or terminating cytokine
storms within living organisms. More specifically, there is a need new and/or enhanced compositions, methods, and processes for providing immune balancing, anti-viral (e.g., anti-influenza), and/or anti-inflammatory effects or functions. Various embodiments of the disclosure are directed to compositions that include at least two of an extract from mangosteen, an extract from Gotu Kola, an extract from soybean, and extract from sesame, and an extract from guava to treat physiologic symptoms corresponding to or arising in association with a cytokine storm, a viral infection, an inflammation condition, an autoimmune disorder, and a neurodegenerative disorder within a living organism. In multiple embodiments, compositions in accordance with the present disclosure facilitate or provide an immunomodulating, immune balancing, an anti-viral, an anti-cytokine storm, and/or an anti-inflammatory effect within the body of a living organism. More particularly, many embodiments of the present disclosure are directed to compositions (e.g., phytochemical compositions and nutraceutical compositions) that include at least an extract from Garcinia Mangostana L. (hereinafter referred to as mangosteen) and an extract from Centella Asiatica L. (hereinafter referred to as Gotu Kola) to facilitate or provide an immunomodulating, immune balancing, an anti-viral, anti-cytokine storm, and/or an anti-inflammatory effect within the living organism's body. Depending upon embodiment details, such embodiments can additionally include one or more of an extract from soybean (also known as Soya bean or Glycine Max), an extract from Sesamum indicum L.(hereinafter referred to as sesame), and an extract from Psidium Guajava L. (hereinafter referred to as guava) to further promote or provide a therapeutic effect. In the context of the present disclosure, the term living organism refers to human beings and animals (i.e., organisms belonging to the kingdom Animalia).
Particular embodiments of the present disclosure also relate to methods and processes for manufacturing the aforementioned compositions. In addition, some embodiments of the disclosure relate to uses of the extract from mangosteen and the extract from Gotu Kola, including in certain embodiments one or more of the extract from soybean, the extract from sesame, and the extract from guava for manufacturing said compositions.
In the context of the present disclosure, the term phytochemical shall refer to any compound or chemical that occurs naturally in plants (i.e. living organisms belonging to the kingdom Plantae), or to any artificial or synthetic compound, substance, or chemical having an identical, almost identical, or significantly similar chemical, physical, and/or structural properties to that which occurs naturally in plants, and the term phytochemical composition shall refer to a composition including at least one phytochemical. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by a person of ordinary skill in the relevant art of the present disclosure.
Each of the extract from mangosteen, the extract from Gotu Kola, the extract from soybean, the extract from sesame, and the extract from guava can be considered to be a phytochemical. The compositions (e.g., phytochemical compositions) provided by embodiments of the present disclosure facilitate a decreased likelihood for adverse side effects, for example nausea, vomiting, and toxicity, when consumed by living organisms. In addition, the use of phytochemicals for the manufacture of particular compositions of the present disclosure facilitates an enhanced health safety profile of said compositions.
Multiple embodiments of the present disclosure are directed to compositions that include predetermined concentrations or predetermined quantities (e.g., predetermined percentages by mass or weight of the compositions) of an extract from mangosteen and an extract from Gotu Kola for therapeutically affecting or modulating a pro-inflammatory condition or a cytokine level, state, or relationship within the body of a living organism. Multiple embodiments can additionally include a predetermined concentration of at least one, and in certain embodiments each, of an extract from soybean, an extract from sesame, and an extract from guava to further facilitate or provide such effects. Embodiments of the present disclosure can affect a pro-inflammatory cytokine condition, for instance, by facilitating or effectuating a decrease or reduction in a quantity of proinflammatory mediators or pro-inflammatory cytokines within biological tissue (e.g., the body of the living organism when consumed thereby).
Examples of pro-inflammatory mediators or pro-inflammatory cytokines include interleukin- 1 alpha (IL-la) and interleukin-lbeta (IL-Ιβ) (hereinafter collectively referred to as interleukin- 1 or IL-1), interleukin-6 (IL-6), interluekin-8 (IL-8), interleukin- 1 1 (IL- 1 1), interleukin- 12 (IL-12), interleukin- 17 (IL-17), interleukin- 18 (IL-18), tumor necrosis factor-alpha (TNF-a), interferon-gamma (IFN-γ), granulocyte-macrophage colony stimulating factor (GM-CSF), and transforming growth factor-beta (TGF-β). It will be understood by a person having ordinary skill in the art that references to proinflammatory mediators or pro-inflammatory cytokines in most embodiments of the present disclosure can refer any one or more of pro-inflammatory mediators or pro- inflammatory cytokines that are known in the art, including the above-listed examples.
In some embodiments, the composition therapeutically affects or modulates an antiinflammatory condition or cytokine level, state, or relationship, for instance, by facilitating or effectuating an increase in a quantity of anti-inflammatory mediators or anti-inflammatory cytokines within biological tissue (e.g., the body of the living organism when consumed thereby). Examples of anti-inflammatory cytokines include interluekin-2 (IL-2), interleukin-4 (IL-4), and interleukin- 10 (IL-10). It will be understood by a person having ordinary skill in the art that references to antiinflammatory cytokines in most embodiments of the present disclosure can refer any one or more of anti-inflammatory cytokines that are known in the art, including the above- listed examples.
In many embodiments, the decrease in quantity of pro-inflammatory cytokines and/or an increase in quantity of anti-inflammatory cytokines provided by compositions in accordance with the present disclosure helps prevent, control, mitigate, down-regulate, and/or stop the occurrence of cytokine storms or inflammation within the living organism. This is to say, in some embodiments, the composition facilitates, provides, or effectuates an anti-cytokine storm and/or an anti-inflammatory effect or function when consumed by the living organism.
In multiple embodiments, compositions provided by the present disclosure facilitate the prevention, control, mitigation, down-regulation, and/or termination of cytokine dysregulation, cytokine storms, or inflammation that is triggered or caused by a viral infection of the living organism. For instance, in many embodiments, the composition facilitates or effectuates a decrease or reduction in quantity of pro-inflammatory mediators or pro-inflammatory cytokines, and/or an increase in quantity of antiinflammatory cytokines, within living organisms that are infected with viruses. As representative examples, compositions in accordance with the present disclosure can be used to treat cytokine dysregulation or cytokine storm conditions triggered by viral infections corresponding to, associated with, or derived from one or more subtypes of an influenza virus (e.g., an influenza A virus such as the H1N1 virus or the H5N1 virus; an influenza B virus; or an influenza C virus), an enterovirus or rhinovirus, or a coronavirus such as the Severe Acute Respiratory Syndrome (SARS) coronavirus), or other viruses. In several embodiments, the composition facilitates the prevention, control, down- regulation, and/or termination of cytokine storms or inflammation triggered or caused by an airborne viral infection of the living organism. For instance, in several embodiments, the composition facilitates or effectuates a decrease or reduction in quantity of proinflammatory mediators or pro-inflammatory cytokines, and/or an increase in quantity of anti-inflammatory cytokines, within living organisms that are infected with airborne viruses.
Viruses and airborne viruses referred to in the present disclosure include any one or more of influenza A (H1N1), influenza A (H2N2), influenza A (H1N2), influenza A (H2N3), and influenza A (H5N1) viruses. However, it will be understood by a person skilled in the art that viruses and airborne viruses referred to in the present disclosure may also be or include other viruses known to trigger, cause, or contribute to, the occurrence of cytokine dysregulation, cytokine storms, inflammation, or increased production of proinflammatory cytokines within living organisms.
In various embodiments, compositions provided by the present disclosure facilitate the homeostatic balance of the living organism's immune system, for instance, by way of normalizing certain cytokine cross-regulation processes. In some embodiments, the composition helps to improve or enhance a condition of the immune system of the living organism. In several embodiments of the present disclosure, the composition facilitates or effectuates a shift from an unbalanced condition of the immune system toward or to a normal or a balanced condition of the immune system. Such a shift can occur by way of an alleviation or elimination of a cytokine imbalance. For example, particular compositions of the present disclosure facilitate or effectuate the regulation or balancing of relative quantities of pro-inflammatory cytokines, for example IL-1 , and antiinflammatory cytokines, for example 11-2, within the body of the living organism.
In numerous embodiments, the composition facilitates or effectuates the prevention, control, management, and/or treatment of an autoimmune disorder (e.g., an immuno- imbalance disease). In specific embodiments, the composition facilitates or effectuates prevention, control, management and/or treatment of at least one of Systemic lupus erythematosus (SLE) or lupus, rheumatoid arthritis, allergic symptoms, psoriasis, diabetes, chronic fatigue syndrome (CFS), fibromyalgia, Crohn's disease, Inflammatory Bowel Disease (IBD), and other autoimmune or autoimmune-related disorders. In certain embodiments, compositions including at least a combination of the extract from mangosteen and the extract from Gotu Kola exhibit or provide unexpected effectiveness in the prevention, control, management, and/or treatment of an autoimmune disorder (e.g., SLE or lupus, rheumatoid arthritis, and psoriasis). Compositions in accordance with the present disclosure can additionally therapeutically affect the progression of diseases known to be exacerbated by the overproduction or dysregulation of particular cytokines. For instance, compositions including an extract from mangosteen and an extract from Gotu Kola in accordance with embodiments described herein can be used alone or in an adjunctive capacity with one or more drugs to treat the symptoms or slow the progression of certain neurodegenerative disorders such as Parkinson's Disease, which is known to be exacerbated by the overproduction of IL-Ιβ.
Such compositions can be used by or administered to individuals that have a family or genetic history of a neurodegenerative condition associated with cytokine overproduction, underproduction, dysregulation, or imbalance (e.g., Parkinson's Disease, Alzheimer's disease, or Multiple Sclerosis) in order to prevent or delay the onset of disease symptoms or the disease itself, or as a part of a therapeutic early intervention treatment regimen following disease diagnosis, or as part of a therapeutic symptom alleviation regimen following disease symptom manifestation.
In various embodiments, a minimum therapeutic daily dose (e.g., for an average size human being) of a composition in accordance with the present disclosure provides at least approximately 10 ug of an extract of mangosteen and at least approximately 10 ug of an extract of Gotu Kola. Depending upon embodiment details, a therapeutic daily dose of a composition formulated in accordance with the present disclosure provides at least approximately 0.1 - 1 mg of each of an extract of mangosteen and an extract of Gotu Kola; or at least approximately 5 - 1000 mg (e.g., about 25 - 750 mg, or about 50 - 500 mg, or about 100 - 300 mg) of a combination of an extract of mangosteen and an extract of Gotu Kola. A given therapeutic daily dose can be divided into sub-doses, for instance, for administration based upon time of day, meal consumption, or a health condition under consideration.
A predetermined concentration or a predetermined quantity (e.g., a predetermined percentage by weight of the composition) of the extract from mangosteen and the extract from Gotu Kola can vary depending upon embodiment details, as can a predetermined concentration or quantity of the extract from soybean, the extract from sesame, and/or the extract from guava (e.g., based upon the predetermined concentration or quantity of the extract from mangosteen and/or the extract from Gotu Kola). In various embodiments, the composition includes between approximately 1% and 99% (for example, approximately 5% - 95%, or approximately 10% - 90%) by mass, weight, or volume of a combination of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava.
In multiple embodiments, a composition in accordance with the present disclosure can include approximately 1 % - 100% (e.g., approximately 5% - 95%, or approximately 10% - 90%, or approximately 20% - 80%, or approximately 25% - 75%, or approximately 35% - 65%, or approximately 50%) by mass, weight, or volume of a combination of the extract from mangosteen and the extract from Gotu Kola (where in some embodiments an uncertainty or error range can be defined as less than approximately 2.5%, or less than approximately 1 %). Any corresponding portion of the composition relative to 100% (e.g., the total composition amount, mass, weight, or volume) can include one or more of the extract from sesame, the extract from soybean, the extract from guava, and another substance (e.g., another phytochemical, or a solid or liquid carrier material or filler).
More particularly, in several embodiments of the present disclosure, a composition having a mass or volume defined as a 100% reference mass or volume includes a) approximately 10% - 90% by mass or volume of a primary composition that includes the extract from mangosteen and the extract from Gotu Kola; and b) a secondary composition in a percentage defined by the 100% reference mass or volume minus the percentage mass or volume of the primary composition, where the secondary composition includes the extract from sesame, the extract from soybean, the extract from guava, and/or another extract or substance. In a representative example, approximately 40% of the composition can be made up of the primary composition, and approximately 60% of the composition can be made up of the secondary composition. In another representative example, approximately 50% of the composition can be formed from the primary composition, and approximately 50% of the composition can be formed from the secondary composition. Depending upon embodiment details, the primary composition itself can include between approximately 5% and 95% (e.g., about 10% - 90%, or about 15% - 85%, or about 20% - 80%, or about 25% - 75%, about 30% - 70%, about 35% - 65%, or about 50%) of one of the extract from mangosteen and the extract from Gotu Kola, with the remaining percentage of the primary composition (i.e., to yield 100% of the primary composition) made up of the other of the extract from mangosteen and the extract from Gotu Kola. As a representative example, approximately 25% of the primary composition can be formed
from the extract from mangosteen, and approximately 75% of the primary composition can be formed from the extract from Gotu Kola. As another representative example, approximately 50% of the primary composition can be made up of the extract of mangosteen, and approximately 50% of the primary composition can be made up of the extract of Gotu Kola. As a further representative example, approximately 75% of the primary composition can be formed from the extract from mangosteen, and approximately 25% of the primary composition can be formed from the extract from Gotu Kola. In multiple embodiments of the present disclosure, the composition includes at least approximately 20% - 25% by mass or weight of a combination of an extract from mangosteen and an extract from Gotu Kola. In several embodiments, the composition includes at least approximately 35% (e.g., approximately 40% - 60%) by mass or weight of a combination of the extract from mangosteen and the extract from Gotu Kola. For instance, a composition according to the present disclosure can include approximately 40%) by mass or weight of a combination of an extract from mangosteen and an extract from Gotu Kola, plus approximately 60%) by mass or weight of one or more of an extract from sesame, an extract from soybean, and an extract from guava. In particular embodiments, the composition includes approximately 50%) by mass or weight of the combination of an extract from mangosteen and an extract from Gotu Kola, plus approximately 50% by mass or weight of one or more of an extract from sesame, an extract from soybean, and an extract from guava. In certain embodiments, the composition includes approximately 25% by mass or weight of an extract from mangosteen, approximately 25% by mass or weight of an extract from Gotu Kola, and approximately 16.67% by mass or weight of each of the extract from sesame, the extract from soybean, and the extract from guava.
It will, however, be understood by a person of ordinary skill in the art that the concentration or quantity (e.g., quantity by weight) of each of the extract from mangosteen and the extract from Gotu Kola, as well as that of the extract from sesame,
the extract from soybean, and/or the extract from guava, can be varied depending upon embodiment details.
In multiple embodiments of the present disclosure, the concentration or quantity (e.g., quantity by weight) of each of the extract from mangosteen and the extract from Gotu Kola is selected or varied for therapeutically affecting a pro-inflammatory cytokine level and/or an anti-inflammatory cytokine level, for instance by facilitating or effectuating a decrease or reduction in a quantity of one or more pro-inflammatory cytokines, within the living organism. In several embodiments, the concentration or quantity (e.g., quantity by weight) of each of the extract from mangosteen and the extract from Gotu Kola, and possibly the concentration or quantity of one or more of the extract from sesame, the extract from soybean, and the extract from guava is selected or varied for enhancing or optimizing a decrease or reduction in a quantity of one or more pro-inflammatory cytokines within the living organism and/or an increase in a quantity of one or more anti- inflammatory cytokines within the living organism.
In accordance with the present disclosure, the composition is, forms a portion of, or is carried by a substance suitable for oral administration to or consumption by a human or animal body. For instance, in many embodiments the composition is, forms a portion of, or is carried by a food product, a beverage product, or a health supplement, drug or pharmaceutical product. In other embodiments, the composition is a supplement, additive, or ingredient for one of a food product, a beverage product, and/or a health supplement, drug, pharmaceutical, or other consumable (e.g., ingestible) product. It will be understood by a person having ordinary skill in the art that the composition can exist in or be incorporated into various forms or formulations, for example, a powder, a paste, a capsule, a pill, an emulsion, a suspension, or a gel or matrix. In certain embodiments, the composition can be delivered by way of controlled or delayed release formulations.
When particular compositions of the present disclosure form portions of food, beverage, and drug or pharmaceutical products, the concentration or the quantity (e.g., by weight) of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract
from sesame, the extract from soybean, and the extract from guava can be varied as required. For instance, the concentration or the quantity (e.g. by weight) of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava can be varied depending on a desired final concentration or quantity (e.g., by weight) of two or more of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava in the final manufactured food or beverage product.
In some embodiments, the composition is carried by a capsule or a pill, where the capsule or pill exhibits a total capsule or pill ingredient capacity of a predetermined size, mass, weight, or volume. Depending upon embodiment details, a fraction, the entirety, or substantially the entirety of the mass, weight, or volume of the capsule or pill can be made up of a composition in accordance with the present disclosure. In several embodiments, a capsule or pill can carry an amount of a composition according to the present disclosure in a manner that provides or corresponds to a predetermined or desired composition dose relative to a given time period for a living organism. For instance, an individual capsule can provide approximately 500 mg of a composition of a type described herein, and a number of capsules or pills (e.g., 1, 2, 3, or more) can be orally administered or consumed to provide a target daily composition dose for a given therapeutic purpose such as the modulation of a cytokine imbalance, the alleviation of a cytokine storm, or the treatment of an auto-immune disorder or a type of neurologic dysfunction or neurodegenerative condition.
Specific embodiments of the disclosure are embodied within a capsule or pill having a predetermined total mass, weight, or volume, and which carries a predetermined total composition mass, weight, or volume. For instance, the total mass or weight of ingredients carried by a capsule or pill can equal approximately 500mg, and the entirety or a portion of the ingredients carried by the capsule or pill can be made up of a composition in accordance with the present disclosure. In certain embodiments, a capsule or the proportion of the capsule that includes the composition has at least approximately 25% by weight (e.g., approximately 125mg for a 500mg capsule) of the combination of
the extract from mangosteen and the extract from Gotu Kola. In particular embodiments, the capsule includes at least approximately 35% - 65% by weight (e.g., approximately 175mg - 320mg for the 500 mg capsule), or about 50% by weight (e.g., approximately 250 mg for the 500 mg capsule), of the combination of the extract from mangosteen and the extract from Gotu Kola.
In particular embodiments, a capsule includes approximately 50% by weight (e.g., approximately 250mg for a 500 mg capsule) of the combination of the extract from mangosteen and the extract from Gotu Kola, and approximately 50% by weight (e.g., approximately 250mg for the 500 mg capsule) of a combination of the extract from sesame, the extract from soybean, and the extract from guava. In a number of embodiments, a capsule includes approximately 25% by weight (e.g., approximately 125mg for the 500 mg capsule) of each of the extract from mangosteen and the extract from Gotu Kola, and approximately 16.67% by weight (e.g., 83.5mg for the 500 mg capsule) of each of the extract from sesame, the extract from soybean, and the extract from guava.
In specific embodiments, a capsule includes approximately 8.3% by weight (e.g., approximately 41.5mg for a 500 mg capsule) of the extract from mangosteen, approximately 25% by weight (e.g., approximately 125mg for the 500 mg capsule) of the extract from Gotu Kola, and approximately 16.67% by weight (e.g., approximately 83.35mg for the 500 mg capsule) of each of the extract from sesame, the extract from soybean, and the extract from guava, with any additional capsule weight percentage relative to the 100% total capsule weight made from at least one of an extract in accordance with the present disclosure and/or an additional substance such as another phytochemical or a filler or carrier material.
As a representative example, approximately 83.33% of a 500 mg capsule can carry approximately 416.55 mg of a composition formulated in accordance with the present disclosure, in which approximately 40% of the composition (i.e., approximately 166.5 mg out of the composition weight of approximately 416.55 mg in this representative
example) is made up of a combination of the extract from mangosteen and the extract from Gotu Kola (e.g., approximately 25% of which can be the extract from mangosteen, and approximately 75% of which can be the extract from Gotu Kola; or approximately 50% of which can be the extract from mangosteen, and approximately 50% of which can be the extract from Gotu Kola). Additionally, approximately 60% of the composition (i.e., approximately 333.5 mg out of the composition weight of approximately 416.55 mg) is made up a combination of the extract from sesame, the extract from soybean, and the extract from guava, thereby establishing an approximate 40% : 60% relationship between a first set and a second set of composition constituents. The remaining weight of such a 500 mg capsule (i.e., approximately 83.45 mg in this representative example) can be made up of another phytochemical and/or a filler material.
As another representative example, the aforementioned approximate 40% : 60% relationship between composition constituents could instead be, for instance, an approximate 20% : 80%, 25% : 75%, 35% : 65%, 50% : 50%, 65% : 35%, 75% : 25%, or 80% : 20% relationship. In this representative example, a first percentage corresponds to a first set of composition constituents defined as the combination of an extract from mangosteen and an extract from Goto Kola; and a second percentage corresponds to a second set of composition constituents defined as a combination of an extract from sesame, an extract from soybean, and an extract from guava. In various embodiments, the first percentage corresponding to the first set of composition constituents is at least approximately 20% (e.g., about 25%, or about 50%) of the composition.
Analogous or similar considerations to those described above apply to capsules, pills, or tablets having other total capsule, pill, or tablet masses, weights, or volumes (e.g., a 100 mg, 250 mg, or 1000 mg capsule). A given capsule, pill, or tablet can be configured or manufactured to carry a predetermined mass, weight, or volume of composition formulated in accordance with the present disclosure, such that a) intra-composition constituents exhibit predetermined mass, weight, or volume percentages with respect to each other; and b) the mass, weight, or volume of the composition exhibits a predetermined relationship to the mass, weight, or volume of the capsule, pill, or tablet.
In some embodiments, a capsule, pill, or tablet includes between approximately 10% and 89% by weight of a combination of the extract from mangosteen and the extract from Gotu Kola, and the remaining capsule, pill, or tablet contents relative to 100% total capsule, pill, or tablet weight includes at least one of the extract from sesame, the extract from soybean, the extract from guava, and another substance. In particular embodiments, the capsule, pill, or tablet can include a primary composition that includes between approximately 10% and 89% of one of the extract from mangosteen and the extract of Gotu Kola, with the remaining percentage of the primary composition (i.e., to yield 100% of the primary composition) made up of the other of the extract from mangosteen and the extract from Gotu Kola. The capsule, pill, or tablet can correspondingly include a secondary composition that includes one or more of the extract from sesame, the extract from soybean, and the extract from guava to provide 100% of the capsule, pill, or tablet composition with respect to a predetermined or target capsule, pill, or tablet mass, weight, or volume.
In some embodiments of the present disclosure, the composition is in the form of an aqueous or liquid product. In several embodiments, the composition includes a concentration of at least approximately O. lmg/ml of a combination of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava. In several embodiments, the composition includes a concentration at least approximately l .Oug/ml of a combination of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava. In some embodiments, the composition includes a concentration of at least approximately 5.0ug/ml of a combination of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava.
In several embodiments, the composition includes a concentration of at least approximately 0.05ug/ml of the combination of the extract from mangosteen and the extract from Gotu Kola. In some embodiments, the composition includes a concentration of at least approximately 0.5ug/ml of the combination of the extract from mangosteen and
the extract from Gotu Kola. In specific embodiments, the composition includes a concentration of at least approximately 2.5ug/ml of the combination of the extract from mangosteen and the extract from Gotu Kola. It will be understood by a person of ordinary skill in the art that the concentration of each of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava, of the composition in the aqueous or liquid form can be varied as required. In some embodiments of the present disclosure, particular compositions as disclosed above can be combined, mixed, synthesized, or manufactured with other drugs, pharmaceutical compositions, phytochemical compositions, and/or nutraceutical compositions. In several embodiments, the compositions as disclosed above can be combined, mixed, synthesized, or manufactured with anti-viral (e.g., anti-influenza) and/or anti-inflammatory substances, drugs, pharmaceutical compositions, phytochemical compositions, and/or nutraceutical compositions. For instance, particular compositions provided by the present disclosure can be combined, mixed, synthesized or manufactured with anti-viral drugs such as oseltamivir (Tamiflu) and zanamivir (Relenza). In addition, particular compositions provided by the present disclosure can be combined, mixed, synthesized, or manufactured with anti-inflammatory drugs such as ibuprofen, diclofenac, aspirin, or naproxen. Additionally or alternatively, the compositions according to some embodiments of the present disclosure can include, or can be combined, mixed, synthesized, or manufactured with another substance or composition associated with connective tissue, cartilage, or bone maintenance, support, or regeneration, such as one or more of a glucosamine compound (e.g., glucosamine sulfate or glucosamine hydrochloride), a chondroitin compound (e.g., chondroitin sulfate), methylsulfonylmethane (MSM), or an omega-3 fatty acid.
In some embodiments, a combination or mix of a particular composition provided by the present disclosure with a particular drug, pharmaceutical composition, phytochemical composition, and/or nutraceutical composition increases the effectiveness, action, and/or
safety of the drug, pharmaceutical composition, phytochemical composition, and/or nutraceutical composition, for instance, by way of a synergistic effect. In several embodiments, a combination of a particular composition provided by the present disclosure with a particular drug, pharmaceutical composition, phytochemical composition, and/or nutraceutical composition that is associated with anti-viral, antiinflammatory, and/or connective tissue, cartilage, or bone maintenance, support, or regeneration properties increases, enhances, or further facilitates the anti-viral, antiinflammatory, and/or connective tissue, cartilage, or bone maintenance, support, or regeneration effects or actions of said drug, pharmaceutical compositions, phytochemical composition, and/or nutraceutical composition.
In various embodiments of the present disclosure, the combination of the extract from mangosteen and the extract from Gotu Kola in the composition provides a synergistic effect, for example, a synergistic anti-inflammatory, anti-cytokine storm, anti-viral (e.g., anti-influenza), immunomodulatory, and/or immune system or cytokine balancing effect, when the composition is consumed by the living organism. In multiple embodiments, unexpectedly strong anti-inflammatory, anti-cytokine storm, anti-viral (e.g., anti- influenza), immunomodulatory, and/or immune system or cytokine balancing effects are physically observed and/or recorded in living organisms consuming the composition.
In general, the extract of Gotu Kola includes saponins or amphipathic glycosides. The amphipathic glycosides are soluble in water and polar solvents. In view of the synergistic effect provided by the combination of the extract of Gotu Kola and the extract of mangosteen, the amphipathic glycosides that are present in the extract of Gotu Kola appear to facilitate or enhance the absorption or uptake of compounds or active ingredients present in the extract of mangosteen into cells of the living organism. Accordingly, in several embodiments, the combination of the extracts from mangosteen and Gotu Kola provides an unexpectedly strong, synergistic anti-inflammatory, anti- cytokine storm, anti-viral (e.g., anti-influenza), immunomodulatory, and/or or immune system or cytokine balancing effect.
As above-disclosed, several embodiments of the present disclosure relate to uses of at least two of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava, for the manufacture of particular compositions of the present disclosure. In addition, several embodiments of the present disclosure relate to methods, processes, and/or techniques for the manufacture of particular compositions provided by the present disclosure.
In multiple embodiments, a process for the manufacture of particular compositions includes process portions, sequences, or operations directed to extracting or obtaining the extract from mangosteen and the extract from Gotu Kola. In particular embodiments, the process includes process portions, sequences, or operations directed to obtaining the extract from sesame, the extract from soybean, and/or the extract from guava. In many embodiments, aqueous alcoholic or other organic solvents are used for extracting or obtaining the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and/or the extract from guava. In some embodiments, physical or mechanical blending of the mangosteen, Gotu Kola, sesame, soybean, and/or guava is performed to obtain the extract of the mangosteen, Gotu Kola, sesame, soybean, and/or guava. Procedures or techniques used for the extracting of each of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava can be standard industry or laboratory procedures or techniques that are known to a person of ordinary skill in the art. In several embodiments, no sterilization or autoclaving procedures or techniques are required in the manufacture of particular compositions according to the present disclosure. In addition, in many embodiments, the process for the manufacture of particular compositions according to the present disclosure is at least one of simple, fast, and cost-effective.
For increased clarity and understanding, representative examples of compositions of the present disclosure are described. In addition, representative examples of effects, functions, and/or properties of particular compositions of the present disclosure, are included in the following description. In addition, a representative example of a method
or process for manufacturing particular compositions provided by the present disclosure is also included in the following description.
In addition, for the convenience of the reader, general discussions of Garcinia Mangostana L. (mangosteen), Centella Asiatica L. (Gotu Kola), Sesamum Indicum L. (sesame), soybean {Glycine Max), Psidium Guajava L. (guava), pro-inflammatory cytokines, and influenza A (H IN 1) are also provided in the following disclosure prior to the description of the representative examples. It will be understood by a person of ordinary skill in the art that the details presented in the specific examples of the present disclosure are primarily for clarity of illustration and increased understanding, and do not limit the scope of the present disclosure.
General Discussion of Garcinia Mangostana. L (Mangosteen)
Garcinia mangostana L. is commonly known as mangosteen. The mangosteen tree is a tropical evergreen tree from the family of plants known as Guttiferae. The mangosteen tree typically starts bearing fruit when between 6 and 20 years old, and can continue yielding fruit for up to 100 years. The mangosteen fruit is round with a diameter of approximately three to eight centimeters, and typically has a dark-purple to red-purple color when ripe. The mangosteen fruit includes an outer rind or pericarp and an inner edible pulp or aril.
The mangosteen fruit has several conventional uses and functions. For example, the pericarp of the mangosteen fruit, which comprises pectins, tannins, resins and a yellow latex, has been conventionally used in tanning and dyeing industries. The mangosteen rind, leaves, and bark have also been traditionally used in folk medicine, particularly in areas where the mangosteen tree grows indigenously. In addition, the pericarp of the mangosteen fruit can be used as an astringent or in various decoctions for treating catarrh, cystitis, diarrhea, intestinal and skin ailments. The aril of the mangosteen fruit is widely considered to be a delicious food source and can be processed to extract or obtain extracts or juice from mangosteen (or Garcinia mangostana L.).
Extracts of mangosteen generally include xanthones, which are biologically active natural phenols that are found in some plant species. A xanthone has a molecular formula Ci3H802. The general structure of a xanthone is:
The chemical structure of xanthone forms the central core of xanthones found in natural sources. Xanthones are formed naturally by a condensation reaction of a phenylpropanoid precursor with two malonyl coenzyme A units. Over 200 xanthones have been identified to date. Pharmacological and chemical studies on xanthones suggest that xanthones possess significant pharmacological properties, for example antidepressant, antitubular, antimicrobial and antiallergenic activities and actions.
General Discussion of Centella Asiatica L. (Gotu Kola)
Centella Asiatica L. (also known as Gotu Kola) is a small herbaceous annual plant from the family Mackinlayaceae or the subfamily Mackinlayoideae of the family Apiaceae. The Gotu Kola plant has slender stems and green to reddish green creeping stolons, which interconnect multiple Gotu Kola plants. The Gotu Kola plant also has long-stalked, green, reniform leaves. The rootstock of the Gotu Kola plant includes rhizomes that are creamish in color and covered with root hairs. The Gotu Kola plant typically matures in approximately three months and can be harvested manually.
The Gotu Kola plant has several conventional uses or functions. The Gotu Kola plant is a traditional food source in areas where it is grown natively. The Gotu Kola plant has been said to have, or provide, anti-bacterial, diuretic, and anti-oxidant functions and effects. In addition, several scientific reports have suggested that certain parts of the Gotu Kola plant is useful for aiding wound healing, treating leprosy, increasing attention span and
concentration, and combating aging. However, many purported functions, effects, and properties of the Gotu Kola plant have not been substantively or adequately verified.
General Discussion of Sesamum indicum L. (Sesame)
Sesamum indicum L. (also known as sesame) is an annual flowering plant in the genus Sesamum. Sesame is widely naturalized in tropical regions around the world. Sesame is primarily cultivated for its edible seeds, which grow in pods. The sesame seeds exist in a variety of colors that range from cream-white to charcoal-black. Sesame seeds are commonly used for cooking, and are often added to breads such as bagels and burger buns. Sesame seeds yield sesame oil, which can be used for cooking. Sesame seeds have been associated with several health benefits and properties. For instance, studies have suggested that sesame seeds (and sesame oil) are good sources of iron, magnesium, manganese, copper, calcium, and vitamins such as vitamin Bl and vitamin E. In addition, sesame seeds include lignans and sesamin. Sesamin are phytoestrogens that have associated anti-oxidant and anti-cancer properties. Furthermore, sesame seeds also contain phytosterols, which have been suggested to be capable of reducing blood cholesterol. General Discussion of Soybean (Glycine max)
Soybean or Soya bean (also known as Glycine max) is a species of legume that is native to East Asia. Soybean is an oilseed plant that is widely cultivated in many countries around the world, including the United States, Brazil, Argentina, China, and India. Soybeans occur in various sizes, and have several hull or seed colors, including black, brown, blue, yellow, green and mottled. The hull of the mature bean is hard and wafer resistant, and therefore helps to protect the cotyledon and hypocotyls from damage.
Soybeans are an important global crop for providing oil and protein. Generally, the combined oil and protein content of soybeans is approximately 60% by weight. In addition, soybeans generally include approximately 35% by weight of carbohydrate and approximately 5% by weight of ash. Majority of protein obtained from soybean is
relatively heat stable, enabling food products derived from soybean (e.g., tofu and soy milk) to withstand high cooking temperatures. In addition, soybeans contain significant amounts of phytic acid, alpha-linolenic acid, the isoflavones genistein, and daidzein. Soybeans have been purported to be a source of complete protein (i.e., protein that contains significant amounts of all the essential amino acids that are required by the human body). In addition, soybeans have been associated with several health benefits, for example cholesterol reduction, brain-enhancing, anti-cancer, and anti-oxidant, properties or functions.
General Discussion ofPsidium Guajava L. (Guava)
Psidium Guajava L. (also known as guavas) is a plant from the family Myrtaceae of the genus Psidium. Guavas are generally considered to be native to Mexico, Central America, and northern South America. However, guavas are currently widely cultivated throughout many tropical and subtropical regions of the world for their edible fruit. Guava plants have tough dark leaves that are elliptic to ovate in shape and approximately 5- 15cm in length. The flowers of the guava plant are white, with five petals and numerous stamens. The guava fruits are typically round or oval, and between 4cm and 12cm in length.
Many species of guava are grown commercially. One of the most common species of guava, particularly in tropical regions around the world, is known as the Apple guava or Psidium Guajava L. The nutritional value of the guava fruit is dependant on the species of guava. However, all guava fruits are generally good sources of vitamins A and C, potassium, magnesium, and dietary fiber. In addition, all guava fruits contain both carotenoids and polyphenols, which are major classes of antioxidant pigments. Accordingly, the guava fruit is generally considered to be a particularly good source of antioxidants.
General Discussion of Pro-inflammatory Cytokines
A pro-inflammatory cytokine or a pro-inflammatory mediator is an immuno-regulatory cytokine that favor inflammation. Pro-inflammatory cytokines generally up-regulate or increase the synthesis of secondary pro-inflammatory mediators and other pro- inflammatory cytokines by immune cells. In addition, pro-inflammatory cytokines can stimulate production of acute phase proteins that mediate inflammation and attract inflammatory cells.
Examples of pro-inflammatory cytokines include IL-1, IL-6, IL-8, IL-1 1 , and TNF-a. Other examples of pro-inflammatory mediators include Granulocyte-macrophage colony- stimulating factor (GM-CSF), Interferon gamma (IFN-γ), Tumor growth factor beta (TGF-β), leukemia inhibitory factors (LIF), oncostatin M (OSM), and a variety of chemokines that attract inflammatory cells. IL-1 is an important pro-inflammatory cytokine. IL-1 is a soluble protein having a mass of approximately 17 kilo-Daltons (kD). IL-1 is produced by a variety of cells, for example macrophages, white blood cells, lymphocytes, monocytes, dendritic cells, and accessory cells that are involved in activation of T-lymphocytes and B-lymphocytes. IL-1 is typically released by such cells during an immune response. The cytokines or interleukins of the IL-1 superfamily (e.g. IL-1 a and IL-Ιβ) are generally produced as precursor peptides, which are then processed to become mature proteins (or mature interleukins). For example, each of IL-1 a and IL-1 β is produced as a precursor peptide. The precursor peptide of each of IL-1 a and IL-Ιβ is then processed by specific enzymes to release a smaller active molecule, which is the mature protein.
IL-1 is produced during immune responses. A common function of IL-1 (e.g. IL-1 a and IL-1 P) is an increasing of expression of adhesion factors on endothelial cells to enable transmigration of leukocytes (which are immune cells that fight pathogens) to sites of infection. In addition, IL-1 stimulates the hypothalamus thermoregulatory center to cause an increase in body temperature (i.e. a fever). The increased body temperature helps the body's immune system to fight pathogens or infection within the body. In addition, IL-1
is an important mediator of inflammatory response, and is also involved in a range of cellular activities, for example cell proliferation, cell differentiation, and cell apoptosis.
TNF-a is also an important pro-inflammatory cytokine. TNF-a is involved in systemic inflammation and works in tandem with a variety of other cytokines to stimulate the acute phase immune reaction. TNF-a is capable of inducing apoptotic cell death, induce inflammation, as well as inhibit tumorigenesis and viral replication. TNF-a and IL-1 commonly works simultaneously and synergistically in stimulating and sustaining inflammation within the body.
General Discussion of Ant-inflammatory Cytokines
Anti-inflammatory cytokines and anti-inflammatory mediators refer generally to immuno-regulatory cytokines that inhibit or counteract various aspects of inflammation. In other words, anti-inflammatory cytokines counteracts various biological effects of pro- inflammatory cytokines and pro-inflammatory mediators. Anti-inflammatory cytokines generally facilitate control or mitigation of the magnitude of inflammation in vivo. Functions of anti-inflammatory cytokines include inhibiting production of proinflammatory cytokines and inhibiting cell activation. Examples of anti-inflammatory cytokines include IL-2, IL-4, IL-10, and IL-13. IL-2 is a variably glycosylated single protein molecule having as mass of approximately 15.5kD. IL-2 is generally produced by activated T helper cells (also known as effector T cells) during an immune response. Pathogens (also known as antigens) that invade or are introduced within the body bind to receptors that are found on the surfaces of lymphocytes. Binding of such pathogens or antigens to T cell receptors (TCR) stimulates secretion of IL-2. IL-2 mediates its effects by binding to IL-2 receptor molecules, which are expressed by lymphocytes. The binding of IL-2 to its receptor molecule triggers a signaling cascade, for example Ras/MAPK, JAK/Stat, and PI 3 -kinase/ Akt signaling modules.
IL-2 has numerous functions including facilitating production of immunoglobulins by B cells. In addition, IL-2 induces differentiation and proliferation of natural killer cells. IL- 2 also causes a stimulation of growth, differentiation, and proliferation of antigen- selected cytotoxic T cells via an activation of expression of specific genes. IL-2 is considered to be important for the development of T cell immunologic memory. IL-2 is necessary during T cell development in the thymus for enabling the maturation of regulatory T cells, which are a unique subset of T cells.
General Discussion of Influenza A (H1N1)
Influenza, which is commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (i.e. influenza viruses). Influenza is typically transmitted through the air or contact with infected body fluids. Common symptoms of influenza include chills, fever, sore throat, muscle pains, headaches, coughing, and general discomfort.
Influenza A (H1N1) is a specific type of influenza that is caused by the influenza A (H1N1) virus. The influenza A (H1N1 ) virus is a subtype (i.e. a particular strain) of influenza virus A. Influenza A virus strains are typically categorized according to two proteins that are found on the surface of the influenza A virus, namely hemagglutinin (H) and neuraminidase (N). The structure, and number, of each of the two proteins differ between different influenza A virus strains. This difference is due to rapid genetic mutations of the influenza A viral genome. Each influenza virus A strain is assigned a H number and an N number based on the particular structure, form, or number of the H and N proteins on the surface of the influenza A virus.
The influenza A (H1N1) virus is approximately 80 - 120 nanometers in diameter and is generally spherical in shape. The influenza A (H1N1) virus includes a viral envelope. The viral envelope includes two main types of glycoproteins, which are wrapped about a central core. The central core includes a viral RNA genome and a number of viral proteins that package and protect the viral RNA genome. The viral RNA genome of the
influenza A (HlNl) virus includes seven or eight pieces of segmented negative-sense RNA, wherein each piece of RNA includes either one or two genes.
Symptoms of influenza A (HlNl) are similar to that of a regular human flu, and include chills, fever, sore throat, muscle pains, headaches, coughing, and general discomfort. Influenza A (HlNl) has been classified as a global pandemic by the World Health Organization (WHO). The full extent of severity of Influenza A (HlNl) has not been ascertained. However, Influenza A (HlNl) is generally considered to be a significant threat to public health.
Representative examples of compositions provided by the present disclosure are described in example one, example two, and example three below. It will be understood by a person of ordinary skill in the art that the scope of the present disclosure is not limited to the following compositions.
EXAMPLE ONE
A composition in the form of a capsule is provided in accordance with the present disclosure. The capsule includes approximately at least approximately 25% by weight of an extract from mangosteen and at least approximately 25% by weight of an extract from Gotu Kola.
The capsule carries ingredients having a total mass of approximately 500mg. Accordingly, in some embodiments, the capsule includes at least approximately 125mg of each of the extract from mangosteen and the extract from Gotu Kola. In most embodiments, the remaining capsule mass up to 500mg is made up of at least one of an extract from sesame, an extract from soybean, an extract from guava, a chemical substance (e.g., a synthetic chemical), and a natural compound.
The capsule is formulated or manufactured by standard methods, processes, and/or techniques known to a person of ordinary skill in the art. Chemicals, for example
additives, stabilizers, emulsifiers, and preservatives, or other natural compounds (e.g., phytochemicals) can be added to the capsule as required.
A dosage of 3 capsules per day is recommended for an individual (e.g., a human being). This dosage of 3 capsules per day is suggested to provide optimal health benefits for the individual. It will however be understood by a person of ordinary skill in the art that alternative dosages (e.g., 4, 5, or 6 capsules per day) may be suggested or used. Health benefits include at least one of anti-inflammatory, anti-viral, anti-bacteria, immune system or cytokine balancing, anti-autoimmune disorder or disease, and/or anti-tissue (e.g. anti-cartilage) degradation effects and/or properties. In addition, the composition can facilitate or effectuate enhanced immunity and increased quality of life of the individual.
EXAMPLE TWO
A composition carried by a capsule is provided in accordance with the present disclosure. The composition includes approximately 8.32% by weight of an extract from mangosteen, approximately 25% by weight of an extract from Gotu Kola, and approximately 16.67% by weight of each of an extract from sesame, an extract from soybean, and an extract from guava. The capsule carries a total substance mass of approximately 500mg. The capsule includes approximately 41.5mg of the extract from mangosteen, approximately 125mg of the extract from Gotu Kola, and approximately 83.35 mg of each of the extract from sesame, the extract from soybean, and the extract from guava. The capsule further carries one or more additional ingredients, such as a known chemical or natural compound (e.g., an additive, stabilizer, or preservative) having a mass of approximately 83.45 mg to yield the total capsule ingredient mass of 500 mg.
The capsule is formulated or manufactured by standard methods, processes, and/or techniques known to a person of ordinary skill in the art. Chemicals, for example additives, stabilizers, emulsifiers, and preservatives, or other natural compounds (e.g., phytochemicals) can be added to the capsule as required.
A dosage of 3 capsules per day is recommended for an individual (e.g., a human being). This dosage of 3 capsules per day is suggested to provide optimal health benefits for the individual. It will however be understood by a person of ordinary skill in the art that alternative dosages (e.g., 4, 5, or 6 capsules per day) may alternatively be suggested or used. Health benefits include at least one of anti-inflammatory, anti-viral, anti-bacteria, immune system or cytokine balancing, anti-autoimmune disorder or disease, and/or anti- tissue (e.g. anti-cartilage) degradation effects and/or properties. In addition, the composition can facilitate or effectuate enhanced immunity and increased quality of life of the individual.
EXAMPLE THREE
Another composition in the form of a capsule is provided. The capsule carries a composition formulated in accordance with the present disclosure. The capsule includes between approximately 10% and 89% by weight of the combination of an extract from mangosteen and an extract from Gotu Kola. In addition, the capsule includes at least one of an extract from sesame, an extract from soybean, an extract from guava, and a known chemical (e.g., synthetic) or natural compound to yield a total capsule weight of 100%. The capsule is formulated or manufactured by standard methods, processes, and/or techniques known to a person of ordinary skill in the art. Chemicals, for example additives, stabilizers, emulsifiers, and preservatives, or other natural compounds (e.g., phytochemicals) can be added to the capsule as required. A dosage of 3 capsules per day is recommended for an individual (e.g., a human being). This dosage of 3 capsules per day is suggested to provide optimal health benefits for the individual. It will however be understood by a person of ordinary skill in the art that alternative dosages (e.g., 4, 5, or 6 capsules per day) may alternatively be suggested or used. Health benefits include at least one of anti-inflammatory, anti-viral, anti -bacteria, immune system or cytokine balancing, anti-autoimmune disorder or disease, and/or anti- tissue (e.g. anti-cartilage) degradation effects and/or properties. In addition, the
composition can facilitate or effectuate enhanced immunity and increased quality of life of the individual.
Representative examples four through seven describe experiments showing effects, functions, and/or properties of a composition in accordance with the present disclosure, in which approximately 40% of the composition is made up of a combination of an extract from mangosteen and an extract from Gotu Kola; and approximately 60% of the composition is made up of a combination of each of an extract from sesame, an extract from soybean, and an extract from guava. More particularly, in representative examples four through seven, 40% of the composition corresponds to a primary composition or a first set of composition constituents made up of 25% of the extract of mangosteen and 75% of the extract from Gotu Kola; and 60% of the composition corresponds to a secondary composition or a second set of composition constituents made up of approximately 33.33% of each of the extract of sesame, the extract of soy, and the extract of guava. It will be understood by a person of ordinary skill in the art that the scope of the present disclosure is not limited to the following representative examples.
EXAMPLE FOUR
Experiments were conducted to evaluate the effect of particular compositions provided by the present disclosure on the amount or quantity of tumor necrosis factor-alpha (TNF- a) released by specific virus-infected cells. Virus-infected cells used for the experiments described in example four were influenza A (H1N1) virus-infected cells. More specifically, the virus-infected cells used for the experiments described in this example were influenza A (H1N1) virus-infected egg cells.
Influenza A (H1N1 ) viruses that were used to infect the egg cells were isolated from patients infected with the influenza A (H1N1) using standard techniques known to a person of ordinary skill in the art. In addition, the isolation of the egg cells and the infection of the egg cells are performed using standard techniques or method known to a person of ordinary skill in the art. The egg cells used in the experiments were chicken egg cells. However, it will be understood by a person of ordinary skill in the art that egg cells
from alternative sources (e.g., pigs, primates, or human beings) can be used. It is also understood by a person having ordinary skill in the art that the egg cells used for the experiments of example four may be substituted for other types of tissue cells found within a living organism, for instance, cells that that are involved in inflammatory responses within the organism's body.
Six cultures of cells, i.e., culture 1 to culture 6, were prepared. The contents of each of cultures 1 to culture 6 were as follows:
(i) Culture 1 : Control culture 1. Includes a predetermined volume of a sample of isolated egg cells that has been diluted in a ratio of 1 :50;
(ii) Culture 2: Control culture 2. Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 2 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500;
(iii) Culture 3 : Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 3 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500. Further includes a volume of a composition providing O.lug/rhl of a combination of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava;
(iv) Culture 4: Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 4 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500. Further includes a volume of a composition providing 0.5ug/ml of a combination of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava;
(v) Culture 5: Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 5 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500. Further includes a volume of a composition providing
l .Oug/ml of a combination of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava; and
(vi) Culture 6: Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 6 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500. Further includes a volume of a composition providing 5.0ug/ml of combination of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava.
In the experiments of example four, each of cultures 1 to 6 was made up to a final volume of approximately 200μ1 in a well of a standard 96 well plate. It will be understood by a person of ordinary skill in the art that an alternative final volume (e.g., ΙΟΟμΙ) may also be used. The number or concentration of isolated egg cells used for each culture was approximately equal. For instance, in the experiments of example four, the number of isolated egg cells used for each culture was approximately 2 x 105 (i.e., 200,000). It will be understood by a person of ordinary skill in the art that the number or concentration of isolated egg cells used for each of cultures 1 to 6 can be adjusted as required by varying the degree of dilution of the cultures (e.g., by increasing total volume of the culture by adding medium). In addition, the standard 96 well plate can be substituted with alternative tissue culture containers, for example 48 well plates or petri dishes).
Each of cultures 1 to 6 was incubated at the same physical conditions for an equal length of time. More specifically, each of cultures 1 to 6 was incubated at a temperature of 37°C with 5% of carbon dioxide for 24 hours.
The concentration or quantity of TNF-a in each of cultures 1 to 6 was quantified using the ELISA technique (e.g., Biotrak Easy ELISA Amersham). The concentration or quantity of TNF-a in each of cultures 1 to 6 as determined using the ELISA technique reflects the quantity of TNF-a released by the cells of that culture.
Results
As shown in figure 1, the concentration of TNF-a (pg/ml) increases from approximately 98pg/ml in culture 1 to approximately 170pg/ml in culture 2. This represents an approximately 73% increase in the concentration of TNF-a from culture 1 (where the isolated egg cells were not infected with the influenza A (H1N1) virus) to culture 2 (where the isolated egg cells were infected with the influenza A (H1N1) virus).
In addition, Figure 1 shows that the concentration of TNF-a decreases when the isolated egg cells were incubated with compositions that included at least 0.5ug/ml.of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., culture 4, culture 5, and culture 6) as compared to when the isolated egg cells were not incubated with any amount or concentration of extracts of mangosteen, Gotu Kola, sesame, soybean, and guava. More specifically, Figure 1 shows that the concentration of TNF-a was approximately 127pg/ml when the isolated egg cells were incubated with approximately 0.5ug/ml of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 4), the concentration of TNF-a was approximately 107pg/ml when the isolated egg cells were incubated with approximately l .Oug/ml of extracts of mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 5), and the concentration of TNF-a was approximately 1 1 Opg/ml when the isolated egg cells were incubated with approximately 5.0ug/ml of extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 6). This represents an approximately 25%, 37%, and 35% decrease in the concentration of TNF-a present when the isolated egg cells were incubated with 0.5ug/ml, l .Oug/ml, and 5.0ug/ml respectively of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava. As indicated in Figure 1, compositions in accordance with the present disclosure can provide a surprising or unexpectedly large shift in a TNF-a concentration toward a normal or baseline condition.
Control Control 0.1 0.5 1.0 5.0
1 2
Concentration of
Composition (ug/ml)
Figure 1 : Effect of concentrations of approximately 0. lug/ml, approximately 0.5ug/ml, approximately l .Oug/ml and approximately 5.0ug/ml of extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava on the released concentration of TNF-a (pg/ml).
Figure 2 shows the percentage of quantity of TNF-a released by isolated egg cells (diluted in a ratio of 1 :50) for each of cultures 1 to 6, where the quantity of TNF- a released by control culture 1 is defined as a 100% percentage release. As shown in figure 2, the percentage of quantity of TNF-a relative to the quantity of isolated egg cells (diluted in a ratio of 1 :50) increased when the isolated egg cells were infected with the influenza A (H1N1) virus diluted at a ratio of 1 :7812500. More specifically, the percentage of quantity of TNF-a relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) increased from approximately 100% when the isolated egg cells were not infected with influenza A (H1N1) (i.e., culture 1) to approximately 172% when the isolated egg cells were infected with influenza A (H1N1) (i.e., culture 2).
Figure 2 also shows that the percentage of quantity of TNF-a relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) decreased when the cells that were infected with the influenza A (H1N1) virus diluted at a ratio of 1 :7812500 were incubated with
the compositions that included at least 0.5ug/ml of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava.
More specifically, figure 2 shows that the percentage of quantity of TNF-a relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) was approximately 127% when the isolated egg cells were incubated with approximately 0.5ug/ml of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 4), approximately 107% when the isolated egg cells were incubated with approximately l .Oug/ml of the extracts from each of mangosteen, Gotu Kola, sesame,, soybean, and guava (i.e., in culture 5), and approximately 110% when the isolated egg cells were incubated with approximately 5.0ug/ml of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 6). This represents an approximately 45%, approximately 65%, and approximately 62% decrease in the percentage of quantity of TNF-a relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) when the isolated egg cells were incubated with approximately 0.5ug/ml, approximately l .Oug/ml, and approximately 5.0ug/ml respectively of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava. In a manner analogous to that indicated by Figure 1 , Figure 2 indicates that compositions in accordance with the present disclosure can provide a surprising or unexpectedly large shift in a TNF-a concentration toward a normal or baseline condition.
Composition (ug ml)
Figure 2: Effect of concentrations of approximately O. l g/ml, approximately 0.5ug/ml, approximately l .Oug/ml and approximately 5.0ug/ml of extracts of mangosteen, Gotu Kola, sesame, soybean, and guava on the relative percentage of TNF-a released by H1N1 infected isolated egg cells (diluted in a ratio of 1 :50).
Conclusion
The experiments of example four indicate that compositions that include extracts from mangosteen, Gotu Kola, sesame, soybean, and guava are capable of facilitating or effectuating a decrease in the quantity of TNF-a released from viral infected cells found in the body. More specifically, the experiments of example four suggest that compositions that include at least approximately 0.5ug/ml of extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava are capable of facilitating or effectuating decrease in quantity of TNF-a released from influenza A (H1N1) viral infected isolated egg cells. Although cells used for experiments of example four are isolated egg cells, the effects of the compositions including extracts from mangosteen, Gotu Kola, sesame, soybean, and guava can be replicated or demonstrated with other viral-infected cells found within the body.
EXAMPLE FIVE
Experiments were conducted to evaluate the effect of particular compositions provided by the present disclosure on amount or quantity of interleukin-1 (IL-1) released by specific virus-infected cells. Virus-infected cells used for the experiments described in example five were influenza A (H1N1) virus-infected cells. More specifically, the virus- infected cells used for the experiments described in this example were influenza A (H1N1) virus-infected egg cells.
Influenza A (H1N1) viruses used to infect the egg cells are be isolated from patients or subjects that are infected with the influenza A (H1N1) using standard techniques known to a person of ordinary skill in the art. In addition, the isolation of the egg cells and the infection of the egg cells were performed using standard techniques or method known to a person of ordinary skill in the art. The egg cells used in the experiments were chicken egg cells. However, it will be understood by a person of ordinary skill in the art that egg cells from alternative sources (e.g., pigs, primates, or human beings) can be used. It is also understood by a person having ordinary skill in the art that the egg cells used for experiments of example five may be substituted for other types of tissue cells found within the body, for instance, cells that that are involved in inflammatory responses within the body.
Four cultures of cells, i.e., culture 1 to culture 4, were prepared. The contents of each of cultures 1 to culture 4 were as follows:
Culture 1 : Control culture 1. Includes a predetermined volume of a sample of isolated egg cells that has been diluted in a ratio of 1 :50;
Culture 2: Control culture 2. Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 2 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500;
Culture 3: Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control
culture 3 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500. Further includes a volume of composition providing a concentration of l .Oug/ml of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava; and
Culture 4: Includes a predetermined volume of the sample of isolated egg cells that has been diluted in a ratio of 1 :50. The isolated egg cells of control culture 4 are infected with the influenza A (H1N1) virus that has been diluted at a ratio of 1 :7812500. [[Further includes a volume of composition providing a concentration of 5.0ug/ml of the extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava.
In the experiments of example five, each of cultures 1 to 4 was made up to a final volume of approximately 200μ1 in a well of a standard 96 well plate. It will be understood by a person of ordinary skill in the art that an alternative final volume (e.g., ΙΟΟμΙ) may also be used. The number or concentration of isolated egg cells used for each culture was approximately equal. For instance, in the experiments of example five, the number of isolated egg cells used for each culture was approximately 2 x 105 (i.e., 200,000). It will be understood by a person of ordinary skill in the art that the number or concentration of isolated egg cells used for each of cultures 1 to 4 can be adjusted as required by varying the degree of dilution of the cultures (e.g., by increasing total volume of the culture by adding medium). In addition, the standard 96 well plate can be substituted with alternative tissue culture containers, for example 48 well plates or petri dishes).
Each of cultures 1 to 4 was incubated at the same physical conditions for an equal length of time. More specifically, each of cultures 1 to 4 was incubated at a temperature of 37°C with 5% of carbon dioxide for 24 hours.
The concentration or quantity of IL-1 in each of cultures 1 to 4 was quantified using the ELISA technique (e.g., Biotrak Easy ELISA Aersham). The concentration or quantity of IL-1 in each of cultures 1 to 6 as determined using the ELISA technique reflects the quantity of IL- 1 released by the cells of that culture.
Results
As shown in figure 3, the concentration of IL-1 increases from approximately 19pg/ml when the isolated egg cells were not infected with the influenza A (H1N1) virus (i.e., in culture 1) to approximately 31pg/ml when the isolated egg cells were infected with the influenza A (H1N1) virus (i.e., in culture 2). This represents an approximately 63% increase in the concentration of IL-1 from culture 1 (where the isolated egg cells were not infected with the influenza A (H1N1) virus) to culture 2 (where the isolated egg cells were infected with the influenza A (H1N1) virus).
In addition, figure 3 shows that the concentration of IL-1 decreases when the isolated egg cells were incubated with compositions that included approximately l .Oug/ml and approximately 5.0ug/ml of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., culture 3 and culture 4) as compared to when the isolated egg cells were not incubated with any amount or concentration of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 2).
More specifically, figure 3 shows that the concentration of IL-1 was approximately 6.5pg/ml when the isolated egg cells were incubated with approximately l.Oug/ml of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 3), and the concentration of IL-1 was approximately 6.0pg/ml when the isolated egg cells were incubated with approximately 5.0ug/ml of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 4). This represents an approximately 79%, and 81% decrease in the concentration of IL- 1 present when the isolated egg cells were incubated with l .Oug/ml, and 5.0ug/ml respectively of the extracts from mangosteen, Gotu Kola, sesame, soybean, and guava.
Composition (ug/ml)
Figure 3: Effect of concentrations of approximately l .Oug/ml and approximately 5.0ug/ml of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava on the concentration (pg/ml) of IL-1 (i.e., amount of IL-1 released) by isolated egg cells.
Figure 4 shows the percentage of quantity of IL-1 relative to the quantity of isolated egg cells (diluted in a ratio of 1 :50) for each of cultures 1 to 4. As shown in figure 4, the percentage of quantity of IL- 1 relative to the quantity of isolated egg cells (diluted in a ratio of 1 :50) increased when the isolated egg cells were infected with the influenza A (HlNl) virus diluted at a ratio of 1 :7812500. More specifically, the percentage of quantity of IL-1 relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) increased from approximately 100% when the isolated egg cells were not infected with influenza A (HlNl) (i.e., culture 1) to approximately 158% when the isolated egg cells were infected with influenza A (HlNl) (i.e., culture 2).
Figure 4 also shows that the percentage of quantity of IL-1 relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) decreased when the cells that were infected with the influenza A (HlNl) virus diluted at a ratio of 1 :7812500 were incubated with the compositions that included approximately l .Oug/ml and approximately 5.0ug/ml of the extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., culture 3 and culture 4).
More specifically, figure 4 shows that the percentage of quantity of IL-1 relative the quantity of isolated egg cells (diluted in a ratio of 1 :50) was approximately 35% when the isolated egg cells were incubated with approximately l .Oug/ml of the extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 3), and approximately 30% when the isolated egg cells were incubated with approximately 5.0ug/ml of the extracts from mangosteen, Gotu Kola, sesame, soybean, and guava (i.e., in culture 4). This represents an approximately 123% and an approximately 128% decrease in the percentage of quantity of IL-1 relative the quantity of isolated egg cells (diluted in a ratio of 1 : 50) when the isolated egg cells were incubated with approximately l .Oug/ml and approximately 5.0ug/ml respectively of the extracts from mangosteen, Gotu Kola, sesame, soybean, and guava.
ompos t on ug m
Figure 4: Effect of concentrations of approximately l .Oug/ml and approximately 5.0ug/ml of extracts from mangosteen, Gotu Kola, sesame, soybean, and guava on the relative percentage of IL-1 released by HlNl infected isolated egg cells (diluted in a ratio of 1 :50).
Conclusion
The experiments of example five suggest that compositions that include extracts from mangosteen, Gotu Kola, sesame, soybean, and guava are capable of facilitating or effectuating decrease in quantity of pro-inflammatory cytokines (e.g. IL-1) released from viral infected cells found in the body. More specifically, the experiments of example five suggest that compositions that include approximately l .Oug/ml and 5.0ug/ml of extracts from each of mangosteen, Gotu Kola, sesame, soybean, and guava are capable of facilitating or effectuating decrease in quantity of IL-1 released from influenza A (H1N1) viral infected isolated egg cells. As indicated by Figures 3 and 4, compositions in accordance with the present disclosure can provide a substantial, surprising, unexpectedly large, or dramatic decrease in an IL-1 concentration. The magnitude of the IL-1 concentration decrease indicates that a combination of an extract of mangosteen and an extract of Gotu Kola function synergistically to enhance beneficial or therapeutic effects. Such synergistic interaction between the extract of mangosteen and the extract of Gotu Kola arises as a result of the saponins or amphipathic glycosides provided by Gotu Kola. The amphipathic glycosides are soluble in both water and polar solvents, and appear to significantly facilitate or enhance the absorption or uptake of compounds or active ingredients (e.g., particular xanthones) present in the extract of mangosteen into cells of the living organism. Although cells used for experiments of example five are isolated egg cells, the effects of the compositions including extracts from mangosteen, Gotu Kola, sesame, soybean, and guava can be replicated or demonstrated with other viral-infected cells found within the body.
EXAMPLE SIX
Experiments were conducted to evaluate the effect of particular compositions provided by the present disclosure on the quantity of IL-1 released by specific cells extracted from living organism (e.g., a human being) over a period of 15 days.
More specifically, experiments were conducted to evaluate the effect of particular compositions provided by the present disclosure on the quantity of IL-1 released by a sample group of seven persons over a 15-day time period, each person having consumed
a daily dosage of 3 capsules over the 15-day time period. Throughout the 15-day time period, each person performs his typical or normal daily routine or activities (e.g., dietary and exercise patterns of each person during the 15 -day time period is similar or identical to that prior to the 15 -day time period).
Cultures of peripheral mononuclear cells (PBMCs) were isolated from blood samples obtained or extract from each person of the sample group at day 3, day 6, day 8, day 10, and day 15. Each culture of PBMCs isolated from blood samples of persons of the sample group was made up to a final volume of approximately ΙΟΟμΙ in wells of a standard 96 well plate.
Although PBMCs were used for the experiments described in this example, the PBMCs may be substituted for other types of immune cells found within the body. The PBMCs were isolated and prepared using isolation techniques or methods known to a person of ordinary skill in the art. An exemplary method or technique is the differential density gradient centrifugation technique, the steps or process steps of which are known to a person of ordinary skill in the art.
It will be understood by a person of ordinary skill in the art that alternative volumes (e.g., 200μ1) may also be used. The number or concentration of PBMCs used for each culture was approximately equal. For instance, the number of PBMCs used for each culture was approximately 1 x 105 (i.e., 100,000). It will be understood by a person of ordinary skill in the art that the number or concentration of PBMCs used for each of cultures of differing days of blood collection can be adjusted as required by varying the degree of dilution of the cultures (e.g., by increasing total volume of the culture by adding medium). The cultures were incubated at the same physical conditions for an equal length of time. More specifically, each of cultures of PBMCs was incubated at a temperature of 37°C with 5% of carbon dioxide for 24 hours. The concentration or quantity of IL-1 in each of the cultures of PBMCs was quantified using the ELISA technique (e.g., Biotrak Easy ELISA Amersham). The concentration or
quantity of IL-1 in each culture of PBMCs as determined using the ELISA technique reflects the quantity of IL-1 released by the PBMCs of that culture.
Results
As shown in figure 5, the level or quantity of IL-1 decreases from day 0 to day 15 as the PBMCs were incubated with compositions including an extract from mangosteen, an extract from Gotu Kola, an extract from sesame, an extract from soybean, and an extract from guava. More specifically, the figure 5 shows an average decrease of IL-1 of approximately 17.5% at day 3, an average decrease of IL-1 of approximately 14% at day 6, an average decrease of IL-1 of approximately 30% at day 8, an average decrease of IL- 1 of approximately 35% at day 10, and an average decrease of IL-1 of approximately 32.5% at day 15.
Ex erimental Day Figure 5: Effect of composition including an extract of mangosteen, an extract of Gotu Kola, an extract of sesame, an extract of soybean, and an extract of guava on quantity of IL-1 released by PBMCs over a 15-day time period
Conclusion
The experiment of example six indicates that compositions including extracts from mangosteen, Gotu Kola, sesame, soybean, and guava are capable of reducing the quantity of IL-1 produced by specific cells found within the body (e.g., PBMCs). The average decrease in IL-1 facilitated or effected by the compositions generally increases over time. As indicated by Figure 5, compositions in accordance with the present disclosure can provide a substantial, surprising, unexpectedly large, or dramatic decrease in an IL-1 level in vivo, further indicating that a combination of an extract of mangosteen and an extract of Gotu Kola function synergistically to provide enhanced therapeutic effects. Although the cells used for the experiments described in example five are PMBCs, the effects of the compositions including extracts from mangosteen, Gotu Kola, sesame, soybean, and guava can be replicated or demonstrated with other immune cells found within the body.
EXAMPLE SEVEN
Experiments were conducted to evaluate the effect of particular compositions provided by the present disclosure on the level or quantity of IL-2 in the serum of living organisms (e.g., a human being) over a period of 15 days.
More specifically, experiments were conducted to evaluate the effect of particular compositions provided by the present disclosure on the level or quantity of IL-2 in the serum of a sample group of seven persons over a 15-day time period, each of the seven persons having consumed a daily dosage of 3 capsules over the 15-day time period. Blood samples were extracted or obtained from each person of the sample group at each of day 0, day 3, day 6, day 8, day 10, and day 15. The quantity of IL-2 present in the serum of the extracted blood samples was determined using the ELISA technique (e.g., Biotrak Easy ELISA Amersham). The ELISA technique (e.g., Biotrak Easy ELISA Amersham) is well known to a person of ordinary skill in the art.
Results
As shown in figure 6, the level or quantity of IL-2 in serum increases from day 0 to day 15 when provided with compositions including an extract from mangosteen, an extract from Gotu Kola, an extract from sesame, an extract from soybean, and an extract from guava.
More specifically, an average percentage increase in IL-2 in serum of approximately 70%, approximately 100%, approximately 120%, approximately 125%, and approximately 140% is observed at day 3, day 6, day 8, day 10, and day 15 respectively when provided with a composition including the extract from mangosteen, an extract of Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava.
Day 0 Day 3 Day 6 D ay 8 Day 10 Day 15
Experimental Day Figure 6: Effect of composition including an extract of mangosteen, an extract of Gotu Kola, an extract of sesame, an extract of soybean, and an extract of guava on quantity or level of IL-2 in serum over a 15 -day time period
Conclusion
Experiments of example eight indicate that compositions including extracts from mangosteen, Gotu Kola, sesame, soybean, and guava are capable increasing IL-2 levels or quantity in serum. Accordingly, the experiments by example eight suggest that particular compositions provided by the present disclosure are capable of increasing IL-2 levels in living organisms when consumed thereby.
As indicated by Figure 6, compositions in accordance with the present disclosure can provide a substantial, surprising, unexpectedly large, or dramatic increase in an IL-2 level in vivo, further indicating that a combination of an extract of mangosteen and an extract of Gotu Kola function synergistically to provide therapeutic effects.
When considered individually as well as in combination, Figure 5 and Figure 6 indicate that compositions in accordance with the present disclosure can provide a surprisingly significant or unexpectedly strong in vivo immunomodulating effect and/or immune system balancing or cytokine regulating effect. Compositions in accordance with the present disclosure can be used to modulate or therapeutically affect particular immune system processes, and can be beneficially administered or consumed to treat physiologic symptoms or conditions associated with one or more of cytokine storm, viral infections, inflammation, immune system or cytokine imbalance or dysregulation, autoimmune disorders, and neurodegenerative disorders.
The following example describes a representative method or process for manufacturing particular compositions of the present disclosure. It will however be understood by a person of ordinary skill in the art that the changes and alterations may be made to the method or process as described below.
EXAMPLE EIGHT
A process for manufacturing particular compositions of the present disclosure includes a first process step of extracting an extract from mangosteen and an extract from Gotu Kola, plus optionally one or more of an extract from sesame, an extract from soybean, and an extract from guava. The extraction of each of the extract of mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract of guava can be performed using extraction methods, processes, and/or techniques that are known to a person of ordinary skill in the art. For example, blending of the mangosteen, Gotu Kola, sesame, soybean, and/or guava can be carried out for extracting or obtaining the extracts of mangosteen, Gotu Kola, sesame, soybean, and/or guava. In addition, aqueous alcohol or an alternative organic solvent is used in the extraction method, process, or technique. Extraction temperatures can range from approximately room temperature to slightly below the boiling point of a solvent under consideration. A second process step includes mixing or combining a predetermined quantity or volume of each of the extract from mangosteen and the extract from Gotu Kola, plus optionally mixing or combining one or more of the extract from sesame, the extract from soybean, and the extract from guava to obtain a manufactured composition is then performed. The concentration or quantity (e.g., percentage by weight) of each of the extract from mangosteen, the extract from Gotu Kola, the extract from sesame, the extract from soybean, and the extract from guava can be varied as required.
No sterilization or autoclaving procedure or process is required in the manufacturing of the composition (i.e., sterilization and/or autoclaving is optional). A composition manufactured using the method or process described in example eight can exist in the form of or be added to (e.g., by way of an additional process step) a capsule, pill, or tablet. In some embodiments, each capsule, pill, or tablet can have a final weight of approximately 50mg, lOOmg, 250mg, 500mg, or lOOOmg. Formulation of the capsule can be achieved using methods, processes, or techniques that are known to a person of ordinary skill in the art. Alternatively, a composition manufactured in accordance with
the present disclosure can be added to (e.g., by way of an additional process step) a food product, a consumable liquid or beverage product, or another substance.
Embodiments of the present disclosure provide compositions (e.g., phytochemical compositions) that include predetermined concentrations or quantities of an extract from mangosteen and an extract from Gotu Kola. Multiple embodiments additionally provide one or more of an extract from sesame, an extract from soybean, and an extract from guava. In multiple embodiments, the composition includes between approximately 10% and approximately 89% of a combination of an extract of mangosteen and an extract of Gotu Kola, and is made up to 100% by at least one of the extract from sesame, the extract from soybean, and the extract from guava. In several embodiments, the composition includes at least approximately 20% - 80% (e.g, approximately 40% - 60%, or approximately 50%) by weight of the combination of the extract from mangosteen and the extract from Gotu Kola. In some embodiments, the composition includes approximately 50% by weight of the combination of the extract from mangosteen and the extract from Gotu Kola, and approximately 16.67% of each of the extract from sesame, the extract from soybean, and the extract from guava.
Compositions in accordance with the present disclosure can therapeutically affect an inflammatory condition, for instance, by decreasing a quantity of a pro-inflammatory cytokines, within a living organism. Compositions in accordance with the present disclosure can further facilitate and/or effectuate an increase in a quantity of an antiinflammatory cytokine in the living organism when consumed thereby. The reduction in a quantity of the pro-inflammatory cytokine, and/or the increase in a quantity of the anti- inflammatory cytokine within the body of the living organism can facilitate at least one of prevention, control, down-regulation, or termination of cytokine storms or un-regulated inflammation within the body of the living organism. Compositions in accordance with the present disclosure can thus be used to therapeutically treat physiologic conditions or symptoms corresponding to or associated with cytokine storms or inflammation.
In numerous embodiments, compositions provided by the present disclosure facilitate at least one of prevention, control, down-regulation, or termination of cytokine storms or inflammation caused or triggered by viral infections. In several embodiments, compositions according to the present disclosure correspondingly provide an anti- pathogenic (e.g., anti-viral) effect or property, and can be used to therapeutically treat physiologic conditions corresponding to or associated with one or more of an influenza virus (e.g., an influenza A virus such as the HlNl virus or the H5N1 virus; an influenza B virus; or an influenza C virus), an enterovirus or rhinovirus, or a coronavirus such as the Severe Acute Respiratory Syndrome (SARS) coronavirus), or another type of virus.
A reduction in a quantity of a pro-inflammatory cytokine, and/or an increase in a quantity of an anti-inflammatory cytokine provided by compositions in accordance with the present disclosure can additionally or alternatively facilitate the alleviation of an immune system or cytokine imbalance or cytokine dysregulation condition, for instance, by way of simultaneously decreasing the production of a pro-inflammatory cytokine and increasing the production of an anti-inflammatory cytokine, or vice versa, such that cross- regulating pro-inflammatory and anti-inflammatory cytokines are shifted toward homeostatic balance. Compositions in accordance with the present disclosure can thus be used to therapeutically affect auto-immune conditions, for instance, one or more of Systemic lupus erythematosus (SLE) or lupus, rheumatoid arthritis, allergic symptoms, psoriasis, diabetes, chronic fatigue syndrome, fibromyalgia, Crohn's disease, Inflammatory Bowel Disease (IBD), or other autoimmune conditions.
Although embodiments and specific examples and experiments of the present disclosure are described above, the present disclosure is not to be limited to specific details so described. A person having ordinary skill in the art will understand that numerous changes and modifications can be made to the embodiments, examples, and experiments described herein without departing from the scope or spirit of the present disclosure.
Claims
A composition comprising an extract from Garcinia mangostana and an extract from Centella asiatica for treating a physiologic symptom associated with at least one of a cytokine storm, a viral infection, an inflammation condition, an autoimmune disorder, and a neurodegenerative disorder within a living organism.
The composition of claim 1 , wherein the composition comprises at least 10 ug of each of the extract from Garcinia mangostana and the extract from Centella asiatica.
The composition of claim 1, wherein the composition comprises at least 1 mg of each of the extract from Garcinia mangostana and the extract from Centella asiatica.
The composition of claim 1 , wherein the composition comprises at least 25 mg of a combination of the extract from Garcinia mangostana and the extract from Centella asiatica.
The composition of claim 1, wherein the composition comprises at least 50 mg of a combination of the extract from Garcinia mangostana and the extract from Centella asiatica.
The composition of claim 1, wherein at least approximately 25% by weight of the composition is made up of a combination of the extract from Garcinia mangostana and the extract from Centella Asiatica.
The composition of claim 1, wherein approximately 50% by weight of the composition is made up of a combination of the extract from Garcinia mangostana and the extract from Centella Asiatica.
The composition of claim 1, wherein the composition provides the extract of Garcinia mcmgostana and the extract from Centella Asiatica in a ratio of approximately 25% Garcinia mangostana : approximately 75% Centella Asiatica.
The composition of claim 1, wherein the composition provides the extract of Garcinia mangostana and the extract from Centella Asiatica in a ratio of appro imately 50% Garcinia mangostan : approximately 50% Centella Asiatica.
The composition of claim 1, further comprising at least one of an extract from sesame, an extract from soybean, and an extract from guava.
The composition of claim 10, wherein the composition comprises at least approximately 20% by weight of a combination of the extract of Garcinia mangostana and the extract from Centella Asiatica.
The composition of claim 10, wherein the composition comprises approximately 50% by weight of a combination of the extract of Garcinia mangostana and the extract from Centella Asiatica.
The composition of claim 1, further comprising each of an extract from sesame, an extract from soybean, and an extract from guava.
The composition of claim 1, wherein the composition is carried by one from the group of a food product, a beverage product, a capsule, a pill, a tablet, a powder, a suspension, and an emulsion.
The composition of claim 1, wherein one of the cytokine storm and the viral infection corresponds to one of an influenza virus, a Rhmovirus, an enterovirus, and a coronavirus.
The composition of claim 12, wherein the influenza virus corresponds to one of influenza A (H1N1), influenza A (H2N1), influenza A (H2N2), influenza A (H3N2), and influenza A (H5N1).
The composition of claim 1, wherein the autoimmune disorder corresponds to one of Systemic lupus erythematosus (SLE), rheumatoid arthritis, allergic symptoms, psoriasis, diabetes, chronic fatigue syndrome (CFS), fibromyalgia, Crohn's disease, and Inflammatory Bowel Disease (IBD).
The composition of claim 1, wherein the neurodegenerative disorder corresponds to one of Parkinson's Disease, Alzheimer's disease, and Multiple Sclerosis,
Use of the composition as in claim 1 for decreasing a quantity of a proinflammatory cytokine within the living organism by substantially between approximately 25% to approximately 85%.
Use of the composition as in claim 16, wherein the pro-inflammatory cytokine is one of interleukin-1 , interleukin-6, interleukin-8, and tumor necrosis factor-alpha.
Use of the composition of claim 1 for decreasing a quantity of a pro-inflammatory cytokine within the living organism by substantially between approximately 50% to approximately 75%.
Use of composition of claim 1, wherein the composition at least one of facilitates and effectuates an increase in a quantity of an anti -inflammatory cytokine within a living organism when consumed thereby.
Use of the composition of claim 1, wherein the composition alleviates a cytokine imbalance within the living organism when consumed thereby.
24. The composition of claim 1, further comprising at least one of an atiti- ioflammatoiy substance and an anti-viral drug.
25. The composition of claim 21, "wherein the anti-inflammatory substance is selected from one of ibuprofen, diclofenac, aspirin, and naproxen, and the antiviral drug is selected from one of oseltamivir and zanamivjj.
26. A process for manufacturing a composition for treating a physiologic symptom associated with at least one of a cytokine storm, a viral infection, an inflammation condition, an autoimiiraae disorder, and a neurodegenerative disorder within a liidng organism when consumed thereby, the process comprising:
obtaining an extract from Garcmia mangostana;
obtaining an extract from Centella asiatica; and
combining the extract from Garcinia mangostam and the extract from Centella aslatica such that the composition comprises at least approximately 10 tig of each of the extract from Garcinia mangostam and the extract from Centella asiatica.
27. The process as io claim 23, wherein the composition comprises at least approximately 1.0 rug of each of the extract from Garcinia mangostana and the extract from Centella aslatica.
28. The process of claim 23, wherein the composition comprises at least approximately 25.0 mg of each of the extract from Garcinia mangostana and the extract from Centella asiatica.
29. The process of claim 23, wherein the composition comprises at least approximately 50.0 mg of each of the extract from Garcinia mangostana and the extract from Centella asiatica.
30. The process of claim 23, further comprising providing the composition with predetermined concentrations of at least one of an extract from sesame, an extract irora guava, and an extract from soybean.
31. The process of claim 23, wherein at least approximately 25% by weight of the composition is made up of a combination of the extract .from Garcinia mangostana and the extract from Centella Asiatic*.
32. The process of claim 23, wherein approximately 50% by weight of the composition is made up of a combination of the extract from Garcinia mangostana and the extract from Centella Asiatics
33. The process of claim 23, wherein the composition provides the extract of Garcinia mango& ana and the extract from Centella Asiatica in a ratio of approximately 25% Garcinia mangostam : 75% Centella Asiatica.
34. The process of claim 23, wherein the composition provides the extract of Garcinia mangostana and the extract from Centella Asiatica in a ratio of approximately 50% Garcinia mangostana : 50% Centella Asiatica.
35. The process of claim 23, further comprising incorporating the composition into one of a food product, a beverage product, a capsule, a pill, a tablet, a powder, a suspension, and an emulsion.
36. The process of claim 23, further adding the extract of Garcinia mangostana and she extract of Centella Asiatica to one of an anti-Inflammatory substance and an anti-viral drug.
37. The process of claim 33, wherein the anti-inflammatory substance is selected from one of ibuprofen, diclofenac, aspirin, and naproxen and the anti-viral drug is selected from one of oseltamivir and zanamivir.
38. The process of claim 23, wherein one of the cytokine storm and the viral infection corresponds to one of an influenza, virus, a Rhinovirus, an enterovirus, and a coronavirus.
39. The process of claim 35, wherein the influenza virus corresponds to one of influenza A (HIN1), influenza A (H2NI), influenza A (H2N2), influenza A (H3N2), and influenza A (H5N1).
40. The process of claim 23, wherein the autoimmune disorder corresponds to one of Systemic lupus erythematosus (SLE), rheumatoid arthritis, allergic symptoms, psoriasis, diabetes, chronic fatigue syndrome (CFS), fibromyalgia, Crohn's disease, and Inflarnmatory Bowel Disease (JBD).
41. The process of claim 23, wherein the neurodegenerative disorder corresponds to one of Parkinson's Disease, Alzheimer's disease, and Multiple Sclerosis.
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