Search

KR-20260066102-A - Pharmaceutical composition

KR20260066102AKR 20260066102 AKR20260066102 AKR 20260066102AKR-20260066102-A

Abstract

The present invention provides a pharmaceutical composition comprising tranexamic acid (TXA) and a pH adjuster, specifically, the concentration of TXA in the composition is approximately 2.9 M within the range of about 5%, or about 2.54 M to about 3.18 M, and the pH of the composition is about 4. Such a composition is for intramuscular injection and is used for the treatment of bleeding. Additionally, the invention provides a method for preparing a pharmaceutical composition, a container containing one or more doses of the pharmaceutical composition, and a single-use or multi-use injection device comprising an injection needle and said container.

Inventors

  • 맥키, 파트리시아
  • 레이버리 브라이언
  • 커밍즈 폴

Assignees

  • 갈렌 리미티드

Dates

Publication Date
20260512
Application Date
20240909
Priority Date
20230908

Claims (20)

  1. An aqueous pharmaceutical composition comprising tranexamic acid (TXA) or a pharmaceutically acceptable salt thereof and a pH adjuster, wherein the concentration of TXA or the pharmaceutically acceptable salt thereof in the composition is approximately 2.9 M or from approximately 2.54 M to approximately 3.18 M within the range of approximately 5%, and the pH of the composition is approximately 4.
  2. In claim 1, A composition in which the concentration of TXA or a pharmaceutically acceptable salt thereof in the above composition is approximately 2.9 M.
  3. In any one of claims 1 to 2, The above pH adjuster is an acid, composition.
  4. In any one of claims 1 to 3, A composition in which the above composition substantially does not contain any other pharmaceutical excipients.
  5. In any one of claims 1 to 4, A composition for parenteral administration, preferably intramuscular administration.
  6. In any one of claims 1 to 5, A composition used for the treatment or prevention of a disease or disorder in a subject.
  7. In any one of claims 1 to 5, A composition used for the treatment or prevention of bleeding in a subject.
  8. In claim 6 or claim 7, A composition wherein the above composition is administered parenterally to the subject or optionally or intramuscularly.
  9. In any one of claims 6 to 8, A composition in which the amount of TXA or a pharmaceutically acceptable salt thereof administered to the subject is approximately 6.36 mmol within the range of about 10%.
  10. In any one of claims 6 to 9, A composition comprising TXA, wherein the amount of TXA administered to the subject is approximately 1g within the range of about 10%.
  11. In any one of claims 6 to 10, A composition administered to the subject in a single dose.
  12. In any one of claims 6 to 11, A composition in which the volume of the composition administered to the subject is a total of about 1.5 mL to about 2.5 mL, a total of about 2 mL to about 2.5 mL, preferably a total of about 2.2 mL.
  13. In any one of claims 6 to 12, A composition in which the subject has not been administered TXA or a pharmaceutically acceptable salt thereof within the past 24 hours, 12 hours, 6 hours, 3 hours, 1.5 hours, 1 hour, or 0.5 hours.
  14. A container containing a single dose or multiple doses of the composition of any one of claims 1 to 9 or the composition for use of any one of claims 6 to 13.
  15. In claim 14, A container in which the amount of TXA or its pharmaceutically acceptable salt in the above single dose is approximately 6.36 mmol within the range of about 10%.
  16. In claim 14, A container in which the above composition contains TXA, and the amount of TXA in a single dose is approximately 1g within the range of about 10%.
  17. An injection device for single or multiple use, wherein the injection device comprises an injection needle and a container according to any one of claims 14 to 16.
  18. In claim 17, An injection device for parenteral administration, preferably intramuscular administration, of the above pharmaceutical composition.
  19. A method for preparing a composition according to any one of claims 1 to 5, wherein the method (a) a step of providing an aqueous acid solution; and (b) a step of adding TXA or a pharmaceutically acceptable salt thereof to the aqueous acid solution, and Optionally, the method further comprises the step of adding a concentrated acid, an additional aqueous acid solution, a base, and/or water until the pH of the solution reaches about 4.
  20. In the composition of claim 3 or the method of claim 19, A composition or method in which the above acid is an inorganic acid or an organic acid, preferably an inorganic acid such as hydrochloric acid.

Description

Pharmaceutical composition A pharmaceutical composition comprising tranexamic acid is provided. This composition is suitable for treating bleeding and can be administered intramuscularly. Tranexamic acid (TXA) is an antifibrinolytic agent that inhibits the breakdown of fibrinoclonal clots by blocking plasminogen and plasmin from binding to fibrin. TXA is a synthetic lysine amino acid derivative that acts to prevent and reduce hemorrhage. TXA is commercially available in tablet form (Cyklokapron 500 mg) and intravenous form (Cyklokapron 100 mg/mL). TXA is used to treat and suppress bleeding and is most effective when administered immediately after injury. Delayed treatment with TXA reduces the life-saving potential. In response to trauma, TXA is generally administered intravenously; however, securing an intravenous line can take time and the drug must be infused slowly. Therefore, there is a need to improve the method of TXA administration. In a pharmacokinetic study, an additional 1g intramuscular dose was administered to trauma patients who received a 1g intravenous dose of TXA at least 90 minutes after the intravenous dose. The intramuscular dose was administered as two 5mL injections (0.5g TXA per injection) into the thigh, gluteal muscle, or deltoid. This study revealed that intramuscular TXA is well tolerated and rapidly absorbed in bleeding trauma patients (Grassin-Delyle et al. Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial. Br J Anaesth. 2021 Jan;126(1):201-209. doi: 10.1016/j.bja.2020.07.058). US 2023/0248643A1 relates to a concentrated injectable tranexamic acid composition and a method of using the same. WO 2024/023813A1 relates to a method for improving the solubility of tranexamic acid, comprising the step of first dissolving tranexamic acid in water. The present invention aims to improve existing technology by providing a stable pharmaceutical composition containing TXA, which can be administered by a single intramuscular injection of a smaller volume, thereby improving the administration of a therapeutically effective dose of TXA for the treatment or prevention of bleeding. The present invention provides an aqueous pharmaceutical composition comprising tranexamic acid (TXA) or a pharmaceutically acceptable salt thereof, wherein the concentration of TXA or the pharmaceutically acceptable salt thereof in the composition exceeds about 0.637 M, and the pH of the composition is about 3 to about 5. The concentration of TXA or its pharmaceutically acceptable salt in the composition may be greater than 1.06 M, at least about 1.27 M, at least about 1.59 M, at least about 1.91 M, at least about 2.23 M, at least about 2.54 M, or at least about 2.86 M. The concentration of TXA or its pharmaceutically acceptable salt in the composition may be about 3.18 M or less, about 3.50 M or less, about 3.68 M or less, or about 3.82 M or less. The concentration of TXA or its pharmaceutically acceptable salt in the composition may be about 2.9 M or about 2.54 M to about 3.18 M within a range of about 25%. The composition may contain TXA at a concentration of about 455 mg/mL within a range of about 25%. The pH of the composition may be about 3.5 to about 4.5 or about 3.75 to about 4.25, preferably about 4. The composition may include a pH modifying agent, optionally the pH modifying agent is an acid. The composition may substantially exclude pharmaceutical excipients, optionally the pharmaceutical excipient is a solubilizing agent. The composition may be for parenteral administration, preferably for intramuscular administration. The composition may be used to treat or prevent disease or disorder in a subject. The composition may be used to treat or prevent bleeding in a subject. The composition may be administered parenterally to a subject and, optionally, may be administered by intramuscular injection to a subject. The amount of TXA or its pharmaceutically acceptable salt administered to a subject may be approximately 6.36 mmol within a range of about 10%. The composition may contain TXA, and the amount of TXA administered to a subject may be approximately 1 g within a range of about 10%. The composition may be administered to a subject as a single dose. The volume of the composition administered to the subject may be about 5 mL or less in total, about 4 mL or less in total, about 3 mL or less in total, about 1.5 mL to about 2.5 mL in total, about 2 mL to about 2.5 mL in total, and preferably about 2.2 mL in total. The subject may not have received TXA or a pharmaceutically acceptable salt thereof within 24 hours, 12 hours, 6 hours, 3 hours, 1.5 hours, 1 hour, or 0.5 hours prior to administration. Preferably, the subject has not received TXA or a pharmaceutically acceptable salt thereof within 24 hours prior to administration. The present invention provides a container containing a single dose or multiple doses of a composition according to the present invention. The am