US-20260124193-A1 - PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF RADIATION INDUCED TOXICITY

Abstract

The present invention relates to parenteral pharmaceutical compositions of suitable Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, particularly to Desidustat or suitable pharmaceutically acceptable salts thereof. The invention also relates to processes for preparing such compositions. The present invention also relates to the development of therapeutic compound for the treatment of radiation induced toxicity. Specifically, present invention relates to use of Desidustat or its pharmaceutically acceptable salt or oral and parenteral pharmaceutical composition thereof for the treatment of radiation induced toxicity.

Inventors

• Mukul Jain
• Amit JOHARAPURKAR
• Vishal Patel
• Jay Kothari
• Muthaiyyan Essakimuthu KANNAN
• Ritu LADDHA
• Mukesh UKAWALA
• Sunil Sahu

Assignees

• ZYDUS LIFESCIENCES LIMITED

Dates

Publication Date

20260507

Application Date

20251229

Priority Date

20240913

Claims (20)

1. 1 . A parenteral pharmaceutical composition comprising desidustat: or a pharmaceutically acceptable salt thereof.
2. 2 . The composition of claim 1 , wherein the desidustat is present at a concentration of 1 mg/mL to 125 mg/mL.
3. 3 . The composition of claim 2 , wherein the concentration of the desidustat is 15 mg/mL to 35 mg/mL.
4. 4 . The composition of claim 2 , wherein the concentration of the desidustat is 30 mg/mL to 50 mg/mL.
5. 5 . The composition of claim 2 , wherein the concentration of the desidustat is 40 mg/mL to 60 mg/mL.
6. 6 . The composition of claim 2 , wherein the concentration of the desidustat is 90 mg/mL to 110 mg/mL.
7. 7 . The composition of claim 2 , wherein the concentration of the desidustat is 25 mg/mL.
8. 8 . The composition of claim 2 , wherein the concentration of the desidustat is 40 mg/mL.
9. 9 . The composition of claim 2 , wherein the concentration of the desidustat is 50 mg/mL.
10. 10 . The composition of claim 2 , wherein the concentration of the desidustat is 90 mg/mL.
11. 11 . The composition of claim 2 , further comprising an isotonic agent/cosolvent.
12. 12 . The composition of claim 11 , wherein the isotonic agent/cosolvent is selected from glycerine, sodium chloride, and a mixture thereof.
13. 13 . The composition of claim 12 , wherein the isotonic agent/cosolvent is glycerine.
14. 14 . The composition of claim 13 , wherein the isotonic agent/cosolvent is present at a concentration of 1% to 1.5% (w/v).
15. 15 . The composition of claim 14 , wherein the concentration of the isotonic agent/cosolvent is 1.25% (w/v).
16. 16 . The composition of claim 2 , further comprising an alkalizing agent.
17. 17 . The composition of claim 16 , wherein the alkalizing agent is selected from sodium hydroxide, meglumine, tromethamine, and a mixture thereof.
18. 18 . The composition of claim 16 , wherein the alkalizing agent is sodium hydroxide.
19. 19 . The composition of claim 18 , wherein isotonic alkalizing agent is present at a concentration of 0.5% to 1% (w/v).
20. 20 . The composition of claim 19 , wherein the concentration of the isotonic alkalizing agent is 0.65% (w/v).

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No. PCT/IN2025/051488, filed on Sep. 12, 2025, which application claims the benefit of, and priority to, IN Application No. 202421069288, filed Sep. 13, 2024 and IN Application No. 202421073122, filed Sep. 27, 2024, the contents of which are hereby incorporated by reference herein in their entirety. FIELD OF THE INVENTION The present invention relates to parenteral pharmaceutical compositions of suitable Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, particularly to Desidustat or a pharmaceutically acceptable salt thereof. The invention also relates to processes for preparing such compositions. The present invention also relates to the development of therapeutic compound for the treatment of radiation induced toxicity. Specifically, present invention relates to use of Desidustat or its pharmaceutically acceptable salt or oral and parenteral pharmaceutical composition thereof for the treatment of radiation induced toxicity. BACKGROUND OF THE INVENTION Desidustat is a novel small-molecule drug for the treatment of anemia associated with chronic kidney disease (CKD). It functions as a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, which stabilizes HIF-α and stimulates endogenous erythropoietin production, thereby promoting red blood cell formation and improving iron metabolism. Structurally, Desidustat is a quinolinone derivative with the chemical formula C16Hi6N2O6. Desidustat was first approved in India in 2022 and has undergone extensive clinical evaluation, including comparative studies with erythropoietin analogs. Desidustat was disclosed in WO2014102818. WO2021186356 focuses on optimized pharmaceutical compositions, particularly oral formulation. There is no parenteral composition available for Desidustat. Despite the advances that have been made to date, there is still an ongoing need for different dosage forms of Desidustat that can be used for treating various medical disorders. SUMMARY OF THE INVENTION The present invention relates to parenteral pharmaceutical compositions of suitable the prolyl hydroxylase inhibitors, particularly to Desidustat or suitable pharmaceutically acceptable salts thereof. The invention also relates to processes for preparing such compositions. The present invention also relates to the development of therapeutic compound for the treatment of radiation induced toxicity. Specifically, present invention relates to use of Desidustat or its pharmaceutically acceptable salt or oral and parenteral pharmaceutical composition thereof for the treatment of radiation induced toxicity. The structure of Desidustat is set forth below: Parenteral drug formulations have become a very important component in the arsenal of available drug delivery options, particularly for drugs having effect on anemia. Parenteral routes of administration, including subcutaneous, intramuscular and intravenous injection, offer numerous benefits over oral delivery in particular situations, for a wide variety of drugs. For example, parenteral administration of a drug typically results in attainment of a therapeutically effective blood serum concentration of the drug in a shorter time than is achievable by oral administration. This is especially true of intravenous injection, whereby the drug is placed directly in the bloodstream. Parenteral administration can also result in more predictable blood serum concentrations of a drug, because losses in the gastrointestinal tract due to metabolism, binding to food and other causes are eliminated. For similar reasons, parenteral administration often permits dose reduction. Parenteral administration is generally the preferred method of drug delivery in emergency situations and is also useful in treating subjects who are uncooperative, unconscious, or otherwise unable or unwilling to accept oral medication. Thus, due to above listed benefits scientists of the present invention have developed parenteral composition of Desidustat. Radiation therapy or acute radiation syndrome or radiation sickness caused by exposure to high amounts of ionizing radiation in a short period of time or prolong exposure. Depending upon the amount and time of exposure the effect of radiation may last for several days to months or years. If exposure is high and for prolong period of time, it may damage specific organ systems and that can lead to death within hours or months [1]. Radiation mainly affects hematopoietic, gastrointestinal, and neurovascular systems. Radiation therapy used in cancer also affects these systems. Radiation mostly affects the rapidly dividing cell and causes irreparable damage to DNA. Chemotherapeutic agents such as cisplatin, melphalan and cyclophosphamide also causes indirect bone marrow cell damage by preventing DNA replication. Current treatment of radiation exposure includes blood transfusions, antibiotics, colony-stimulating factors, or stem