Search

EP-4736844-A1 - PHARMACEUTICAL COMPOSITION COMPRISING A GLP-1 ANALOG AND AN INORGANIC MESOPOROUS MATERIAL

EP4736844A1EP 4736844 A1EP4736844 A1EP 4736844A1EP-4736844-A1

Abstract

The present invention relates to pharmaceutical compositions comprising a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa dispersed in an inorganic mesoporous material, said inorganic mesoporous material being in particular mesoporous silica.

Inventors

  • The designation of the inventor has not yet been filed

Assignees

  • Merck Patent GmbH

Dates

Publication Date
20260506
Application Date
20241105

Claims (15)

  1. A pharmaceutical composition comprising a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa, dispersed in an inorganic, mesoporous material.
  2. The pharmaceutical composition according to claim 1, wherein the inorganic mesoporous material is mesoporous silica.
  3. The pharmaceutical composition according to claim 2, wherein the mesoporous silica is non-ordered and/or has a particle size distribution D 50 of about 17 to 25 µm and/or average pore size of about 6 nm and/or a specific surface of more than 400 m 2 /g, in particular of about 500 m 2 /g, and/or a total pore volume of about 75 cm 3 /g, in particular of about 0.75 cm 3 /g.
  4. The pharmaceutical composition according to any one of the preceding claims, wherein the therapeutic peptide is a GLP-1 analog, preferably selected from the group consisting in Exenatide, Liraglutide, Dulaglutide, Semaglutide, Albiglutide, Tirzepatide and Efpeglenatide
  5. The pharmaceutical composition according to any one of the preceding claims, wherein the GLP-1 analog is Semaglutide.
  6. The pharmaceutical composition according to any of the preceding claims, wherein the ratio of the therapeutic peptide having a molecular weight between 1 kDa and 100 kDa to the inorganic mesoporous material is between 1:30 and 1:1, preferably between 1:30 and 1:10, more preferably between 1:20 and 1:10, in particular of about 1:20 or 1:10.
  7. The pharmaceutical composition according to any one of the preceding claims, wherein the pharmaceutical composition further comprises one or more excipients selected from the group consisting in colorants, flavorants, antioxidants, preservatives, surfactants or intestinal permeation enhancers, preferably an intestinal permeation enhancer that is salcaprozate sodium (SNAC).
  8. A pharmaceutical composition according to any of the preceding claims, for use as a drug, in particular in the treatment of a condition selected from the group consisting in type 2 diabetes and obesity.
  9. The pharmaceutical composition for use according to the immediately preceding claim, wherein the pharmaceutical composition is administered orally.
  10. Use of an inorganic mesoporous material for one or more of the following: • improving the bioavailability of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa, • preventing the degradation of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa in gastric fluid, • preventing the release of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa in gastric fluid, • the targeted delivery of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa in the intestine, wherein the therapeutic peptide having a molecular weight between 1 kDa and 100 kDa is dispersed in said inorganic mesoporous material.
  11. The use according to claim 10, wherein the inorganic mesoporous material is mesoporous silica.
  12. The use according to claim 11, wherein the mesoporous silica is non-ordered and/or has a particle size distribution D 50 of about 17 to 25 µm and/or average pore size of about 6 nm and/or a specific surface of more than 400 m 2 /g, in particular of about 500 m 2 /g, and/or a total pore volume of about 75 cm 3 /g, in particular of about 0.75 cm 3 /g.
  13. The use according to any one of claims 10 to 12, wherein the therapeutic peptide is a GLP-1 analog, preferably selected from the group consisting in Exenatide, Liraglutide, Dulaglutide, Semaglutide, Albiglutide, Tirzepatide and Efpeglenatide, preferably semaglutide.
  14. The pharmaceutical composition according to any of the preceding claims, wherein the ratio of the therapeutic peptide having a molecular weight between 1 kDa and 100 kDa to the inorganic mesoporous material is between 1:30 and 1:1, preferably between 1:30 and 1:10, more preferably between 1:20 and 1:10, in particular of about 1:20 or 1:10.
  15. A process for preparing a pharmaceutical composition according to any one of claims 1 to 7, comprising a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa dispersed in an inorganic mesoporous material, comprising the steps of: a. contacting an inorganic mesoporous material with a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa in a liquid medium, to obtain a suspension, b. drying the suspension to obtain the pharmaceutical composition comprising the therapeutic peptide having a molecular weight between 1 kDa and 100 kDa dispersed in an inorganic mesoporous material.

Description

The oral administration of therapeutic peptides presents significant challenges due to their inherent biochemical properties. Peptides, including glucagon-like peptide-1 (GLP-1) analogs such as Exenatide (Byetta, Bydureon), Liraglutide (Victoza, Saxenda), Dulaglutide (Trulicity), Semaglutide (Ozempic, Rybelsus, Wegovy), Lixisenatide (Adlyxin), Albiglutide (Tanzeum), Tirzepatide and Efpeglenatide, are increasingly used in the treatment of type 2 diabetes and obesity. However, their effectiveness and patient compliance are often hindered by the limitations associated with their oral delivery. One of the primary challenges with the oral administration of peptides is their susceptibility to enzymatic degradation in the gastrointestinal (GI) tract. The GI tract is rich in proteolytic enzymes that rapidly degrade peptides, rendering them inactive before they can exert their therapeutic effects. In addition, the stability of peptides in the acidic environment of the stomach is a critical concern. The acidic pH can lead to the denaturation and degradation of peptide molecules. Formulation strategies, such as enteric coatings and pH-sensitive delivery systems, have been investigated to protect peptides from the harsh gastric environment, but achieving consistent and reliable protection remains a challenge. Another significant issue is indeed the poor absorption of peptides across the intestinal epithelium. Peptides are large, hydrophilic molecules that do not easily cross the lipid-rich cell membranes of the intestinal lining. This results in low bioavailability when peptides are administered orally. Various approaches, such as the use of absorption enhancers, mucoadhesive agents, and nanoparticle carriers, have been explored to improve the intestinal absorption of peptides, but these strategies often come with their own set of challenges and limitations. GLP-1 analogs, in particular, exemplify these challenges. These molecules are used extensively in the management of type 2 diabetes and obesity due to their ability to enhance insulin secretion, inhibit glucagon release, slow gastric emptying, and promote satiety. However, their therapeutic potential is often limited by the need for frequent injections, which can lead to poor patient compliance and reduced quality of life. The development of an effective oral delivery system for GLP-1 analogs would represent a significant advancement in the treatment of these conditions, offering a more convenient and patient-friendly administration route. To date however, only Semaglutide is approved as an oral formulation (Rybelsus®) that is tailored for gastrointestinal absorption to ensure bioavailability. This necessitates the development of strategies to protect peptides from enzymatic degradation while at the same time ensuring their bioavailability. It is an object of the present invention to address these issues by providing a pharmaceutical formulation that protects therapeutic peptides, in particular GLP-1 analogs, and enhances their bioavailability, thereby improving patient compliance and treatment outcomes. The present invention concerns in a first aspect, a pharmaceutical composition comprising a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa dispersed in an inorganic mesoporous material, said inorganic mesoporous material being in particular mesoporous silica. The present invention also concerns in a second aspect, a pharmaceutical composition comprising a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa in particular a GLP-1 analog, dispersed in an inorganic mesoporous material, said inorganic mesoporous material being in particular mesoporous silica, for use as a drug, in particular in the treatment of type 2 diabetes or obesity. It also concerns the use of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa, in particular a GLP-1 analog, dispersed an inorganic mesoporous material, said inorganic mesoporous material being in particular mesoporous silica, for the manufacture of a medicament, said medicament being intended for the treatment of type 2 diabetes or obesity. It further concerns a method for treating a condition, in particular type 2 diabetes or obesity, wherein a pharmaceutical composition comprising a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa, in particular a GLP-1 analog dispersed in an inorganic mesoporous material, said inorganic mesoporous material being in particular mesoporous silica, is administered to a subject in need thereof. The present invention also concerns in a third aspect the use of an inorganic mesoporous material, in particular mesoporous silica, for preventing the degradation of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa, in particular a GLP-1 analog, in gastric fluid and/or for preventing the release of a therapeutic peptide having a molecular weight between 1 kDa and 100 kDa, in particular a GLP-1 anal