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US-12622938-B2 - Compositions and methods for modulating inflammatory response

US12622938B2US 12622938 B2US12622938 B2US 12622938B2US-12622938-B2

Abstract

Described herein are mushroom compositions and methods for treating, prophylaxis of, or ameliorating symptoms of one or more adverse reactions triggered by an infectious disease or condition that increases an anti-inflammatory response in a subject with such compositions. In one aspect the composition comprises an aqueous or solid fraction of a mycelium, a fermented substrate thereof, or a combination thereof optionally combined with one or more buffering agents, ethanol, and water.

Inventors

  • Paul E. STAMETS

Assignees

  • TURTLE BEAR HOLDINGS, LLC

Dates

Publication Date
20260512
Application Date
20230531

Claims (19)

  1. 1 . A method for treating, prophylaxis of, or ameliorating symptoms of an infectious disease in a subject in need thereof comprising: administering to the subject a therapeutically effective amount of a composition comprising: 580-1,750 mg of an aqueous or solid fraction of Fomitopsis officinalis mycelium, a fermented substrate thereof, or a combination thereof; and 580-1,750 mg of an aqueous or solid fraction of Trametes versicolor mycelium, a fermented substrate thereof, or a combination thereof.
  2. 2 . The method of claim 1 , wherein the aqueous or solid fraction comprises beta-glucans.
  3. 3 . The method of claim 1 , wherein a dose of the composition is administered to the subject 3 times per day.
  4. 4 . The method of claim 1 , wherein the composition is in the form of a capsule.
  5. 5 . The method of claim 3 , wherein the dose comprises at least 4 capsules.
  6. 6 . The method of claim 1 , wherein the composition is administered to the subject for about 10 to 30 consecutive days.
  7. 7 . The method of claim 1 , wherein the composition is administered to the subject for about 14 days.
  8. 8 . The method of claim 1 , wherein the subject has COPD, Cardiovascular disease, diabetes mellitus, hypertension, or a combination thereof.
  9. 9 . The method of claim 1 , wherein the subject is at least 60 years old.
  10. 10 . The method of claim 1 , wherein the composition is administered orally.
  11. 11 . The method of claim 1 , wherein the composition further comprises one or more preservatives, flavorings, colorings, stabilizers, emulsifiers, or other pharmaceutically acceptable excipients.
  12. 12 . The method of claim 1 , wherein the infectious disease comprises one or more symptoms comprising shortness of breath, wheezing, coughing, yellow mucus, green mucus, blood-tinged mucus, chest pain, breathlessness, rapid breathing, hypoxia, inflammation of the lung tissue, rapid heart rate, or increased blood pressure, or decreased blood pressure.
  13. 13 . The method of claim 1 , wherein the infectious disease comprises a bacterial infection.
  14. 14 . The method of claim 13 , wherein the bacterial infection comprises one or more of Streptococcus pneumoniae, Mycobacterium tuberculosis, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Stenotrophomonas maltophila, Staphylococcus aureus, Streptococcus pyogenes, Neisseria meningitidis, Klebsiella pneumoniae , or Non-tuberculosis Mycobacterium.
  15. 15 . The method of claim 1 , wherein the infectious disease comprises a viral infection.
  16. 16 . The method of claim 15 , wherein the viral infection comprises one or more of Paramyxoviridae (respiratory syncytial virus (RSV), parainfluenza virus (PIV), metapneumovirus (MPV), enteroviruses), Picornaviridae (Rhinovirus, RV), Coronaviridae (CoV), Adenoviridae (Adenovirus), Parvoviridae (HBoV), Orthomyxoviridae (influenza A, B, C, D, Isavirus, Thogotovirus, Quaranjavirus), or Herpesviridae (human herpes viruses, Varicella zoster virus, Epstein-Barr virus, cytomegalovirus).
  17. 17 . The method of claim 16 , wherein the CoV comprises one or more of Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV), COVID-19 (2019-nCoV, SARS-CoV-2), 229E, NL63, 0043, or HKU1.
  18. 18 . The method of claim 1 , wherein the symptoms of an infectious disease comprises an inflammatory response associated with a bacterial or viral infection.
  19. 19 . The method of claim 1 , wherein the administration modulates one or more of cytokine storms, neuroinflammation, or blood clotting.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. patent application Ser. No. 17/221,437, filed on Apr. 2, 2021, which claims priority to U.S. Provisional Patent Application No. 63/004,788, filed on Apr. 3, 2020 and U.S. Provisional Patent Application No. 63/029,830, filed on May 26, 2020, the entire contents of each of which are fully incorporated herein by reference. REFERENCE TO SEQUENCE LISTING This application is filed with a Computer Readable Form of a Sequence Listing in accord with 37 C.F.R. § 1.821(c). The text file submitted by EFS, “888690-9006-US06_sequence_listing_30-MAY-2023_5 T25,” was created on May 30, 2023, contains 13, sequences, has a file size of 11.0 Kbytes, and is hereby incorporated by reference in its entirety. TECHNICAL FIELD Described herein are mushroom compositions and methods for treating, prophylaxis of, or ameliorating symptoms of one or more adverse reactions triggered by an infectious disease or condition that increases an anti-inflammatory response in a subject with such compositions. In one aspect the composition comprises an aqueous or solid fraction of a mycelium, a fermented substrate thereof, or a combination thereof optionally combined with one or more buffering agents, ethanol, and water. BACKGROUND Cytokines are a broad group of small proteins involved in immunomodulatory cell signaling, including interleukins, interferons, and growth factors. These peptides are secreted by immune cells and cannot permeate the cell membrane; however, by interacting with their matching receptors on the cell's surface, cytokines trigger intracellular signaling cascades, altering gene expression and inducing an immune response. Several factors can influence a cytokine's effect, including peptide and/or receptor abundance, downstream signaling cascades, expression of genes and transcription factors, feedback loops, and complementary or competing interactions associated with other cytokines. Depending on their activity, cytokines may either be pro-inflammatory or anti-inflammatory, and may be associated with an acute or sustained response. A healthy cellular immune response involves a pro-inflammatory reaction conferring immunological protection, delicately balanced by anti-inflammatory responses that protect host tissues from incurring damage. However, certain pathogens may upset this balance by inducing an overactive host immune response, leading to systemic expression of inflammatory cytokines called hypercytokinemia, or a “cytokine storm.” First applied to SARS-CoV-1, the term “cytokine storm” refers to an overproduction of inflammatory cytokines, resulting in an immune response that damages the body. Although cytokine storms can also be associated with non-infectious diseases, they are archetypically associated with severe lung infections. When a lower respiratory infection causes acute lung injury, local inflammatory cytokines can spread via the circulatory system, resulting in multiple organ failure and symptomatology akin to systemic sepsis syndrome. In the case of COVID-19, the disease caused by SARS-CoV-2, critically ill patients often develop acute respiratory disease syndrome (ARDS) and display hyperinflammation consistent with a cytokine storm. When afflicted by ARDS, patients display elevated levels of proinflammatory cytokines TNF-α and IL-1β in the lungs. Consistent with other hyperinflammatory syndromes, several inflammatory markers are predictive of mortality in COVID-19 patients, including elevated ferritin, IL-2, IL-6, IL-7, and TNF-α. Analyses of patients infected with the related SARS-CoV-1 also found high levels of inflammatory cytokines (IL-1, IL-6, IL-12) and extremely low levels of the anti-inflammatory IL-10. However, studies of SARS-CoV-2 infected patients suggest that IL-10 levels may actually be directly correlated with COVID-19 severity. A retroactive analysis of 113 deceased patients with COVID-19 found elevated levels of IL-2, IL-6, IL-8, TNF-α, and IL-10 compared to those who recovered. Another study found that patients with severe SARS-CoV-2 seem to present with significantly elevated IL-2, IL-6 and IL-10 compared to febrile controls; of these three cytokines, IL-2 and IL-6 appear to be indicators of disease severity. Various methods have been attempted to reduce inflammation in COVID-19 patients, ranging from steroids to acupuncture; however, the medical science community has not reached consensus regarding the impact that various anti-inflammatory agents can have on SARS-CoV-2 viral infection and/or COVID-19 disease development. In the case of SARS-CoV and MERS-CoV, corticosteroid treatment did not prove a beneficial therapy and actually impaired viral clearance, suggesting a need for alternative means of controlling dysregulated inflammation associated with a cytokine storm. Since immune dysregulation and induced cytokine storms are associated with disease severity and mortality, antiviral agents may prove insufficient