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US-12622885-B2 - Short chain fatty acid compounds and uses thereof

US12622885B2US 12622885 B2US12622885 B2US 12622885B2US-12622885-B2

Abstract

The present disclosure describes compositions comprising at least one short chain fatty acid (SCFA). The present disclosure describes compositions comprising at least one SCFA wherein one or more hydrogen atoms in the SCFA or the pharmaceutically-acceptable salt thereof is isotopically enhanced in deuterium. The disclosed methods can be used to treat a skin disorder or an autoimmune disorder.

Inventors

  • Christian Schafmeister
  • Alla Arzumanyan
  • Ira C. Spector

Assignees

  • TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

Dates

Publication Date
20260512
Application Date
20250514

Claims (20)

  1. 1 . A pharmaceutical composition comprising: a) an amount of at least 1 mg of: (C(H a1 )(H b1 )(H c1 ))—(C(H d1 )(H e1 ))—(C(H f1 )(H g1 ))—COOH or a pharmaceutically-acceptable salt thereof, wherein: H a1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; H b1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; H c1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; H d1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; H e1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; H f1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; and H g1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium, wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 1% deuterium; and b) a solid pharmaceutically-acceptable excipient.
  2. 2 . The pharmaceutical composition of claim 1 , wherein the amount of butyric acid or the pharmaceutically-acceptable salt thereof is at least 10 mg.
  3. 3 . The pharmaceutical composition of claim 1 , wherein the amount of butyric acid or the pharmaceutically-acceptable salt thereof is at least 100 mg.
  4. 4 . The pharmaceutical composition of claim 1 , wherein the amount of butyric acid or the pharmaceutically-acceptable salt thereof is at least 800 mg.
  5. 5 . The pharmaceutical composition of claim 1 , the pharmaceutical composition comprising the pharmaceutically-acceptable salt of butyric acid, wherein the pharmaceutically-acceptable salt is sodium butyrate.
  6. 6 . The pharmaceutical composition of claim 1 , wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 5% deuterium.
  7. 7 . The pharmaceutical composition of claim 1 , wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 10% deuterium.
  8. 8 . The pharmaceutical composition of claim 1 , wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 25% deuterium.
  9. 9 . The pharmaceutical composition of claim 1 , wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 50% deuterium.
  10. 10 . The pharmaceutical composition of claim 1 , wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 75% deuterium.
  11. 11 . The pharmaceutical composition of claim 1 , wherein at least one of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is a population of isotopes of hydrogen that is at least 80% deuterium, at least 85% deuterium, at least 90% deuterium, at least 95% deuterium, at least 99% deuterium.
  12. 12 . The pharmaceutical composition of claim 1 , wherein at least five of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 are each independently a population of isotopes of hydrogen that is at least 1% deuterium, at least 5% deuterium, at least 50% deuterium, or at least 95% deuterium.
  13. 13 . The pharmaceutical composition of claim 1 , wherein each of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 is independently a population of isotopes of hydrogen that is at least 1% deuterium, at least 5% deuterium, at least 50% deuterium, or at least 95% deuterium.
  14. 14 . The pharmaceutical composition of claim 1 , wherein at least three of H a1 , H b1 , H c1 , H d1 , H e1 , H f1 , and H g1 are each independently a population of isotopes of hydrogen that is at least 1% deuterium, at least 5% deuterium, at least 50% deuterium, or at least 95% deuterium.
  15. 15 . The pharmaceutical composition of claim 1 , wherein the solid pharmaceutically-acceptable excipient is a tablet filler.
  16. 16 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is an oral form.
  17. 17 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a tablet.
  18. 18 . The pharmaceutical composition of claim 1 , further comprising a source of magnesium.
  19. 19 . The pharmaceutical composition of claim 1 , further comprising magnesium chloride.
  20. 20 . The pharmaceutical composition of claim 1 , further comprising vitamin D.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a Continuation of International Patent Application No. PCT/US2024/061643, filed on Dec. 23, 2024, which claims priority to and the benefit of U.S. Provisional Application No. 63/614,077, filed on Dec. 22, 2023, each of which are incorporated herein by reference in their entirety. BACKGROUND Short chain fatty acids (SCFAs) are saturated aliphatic acids consisting of one polar carboxylic acid moiety and hydrophobic hydrocarbon chain. Among these, acetate (C2), propionate (C3) and butyrate (C4) are the most common and well-studied molecules. INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. SUMMARY OF THE DISCLOSURE Disclosed herein is a pharmaceutical composition comprising: (a) an amount of at least 1 mg of butyric acid or a pharmaceutically-acceptable salt thereof, wherein at least 1% of hydrogen atoms in the butyric acid or the pharmaceutically-acceptable salt thereof are deuterium; and (b) a solid pharmaceutically-acceptable excipient. Disclosed herein is a pharmaceutical composition comprising: (a) an amount of at least 1 mg of butyric acid or a pharmaceutically-acceptable salt of butyrate ion, wherein the butyric acid has an average molecular mass of 93 D to 97 D as determined by time-of-flight mass spectrometry, and the butyrate ion has an average molecular mass of 92 D to 96 D as determined by time-of-flight mass spectrometry; and (b) a solid pharmaceutically-acceptable excipient. Disclosed herein is a pharmaceutical composition comprising: (a) an amount of at least 1 mg of: (C(Ha1)(Hb1)(Hc1))—(C(Hd1)(He1))—(C(Hf1)(Hg1))—COOH or a pharmaceutically-acceptable salt thereof, wherein: Ha1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; Hb1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; Hc1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; Hd1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; He1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; Hf1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium; and Hg1 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 1% deuterium, wherein at least one of Ha1, Hb1, Hc1, Hd1, He1, Hf1, and Hg1 is a population of isotopes of hydrogen that is at least 1% deuterium; and (b) a solid pharmaceutically-acceptable excipient. Disclosed herein is a pharmaceutical composition comprising: (a) an amount of at least 1 mg of propionic acid or a pharmaceutically-acceptable salt thereof, wherein at least 1% of hydrogen atoms in the propionic acid or the pharmaceutically-acceptable salt thereof are deuterium; and (b) a solid pharmaceutically-acceptable excipient. Disclosed herein is a pharmaceutical composition comprising: (a) an amount of at least 1 mg of propionic acid or a pharmaceutically-acceptable salt of propionate ion, wherein the propionic acid has an average molecular mass of 77 D to 81 D as determined by time-of-flight mass spectrometry, and the propionate ion has an average molecular mass of 76 D to 80 D as determined by time-of-flight mass spectrometry; and (b) a solid pharmaceutically-acceptable excipient. Disclosed herein is a pharmaceutical composition comprising: (a) an amount of at least 1 mg of: (C(Ha2)(Hb2)(Hc2))—(C(Hd2)(He2))—COOH or a pharmaceutically-acceptable salt thereof, wherein: Ha2 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 5% deuterium; Hb2 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 5% deuterium; He2 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at least 5% deuterium; Hd2 is a population of isotopes of hydrogen that is about a natural abundance of isotopes of hydrogen or a population of isotopes of hydrogen that is at le