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CN-120189496-B - Oral polypeptide composition

CN120189496BCN 120189496 BCN120189496 BCN 120189496BCN-120189496-B

Abstract

The invention belongs to the field of biological medicine, in particular to an oral polypeptide composition for improving gastrointestinal tract absorption of a polypeptide drug, and particularly discloses an oral polypeptide composition which comprises polypeptide molecules, medium-chain fatty acid and salts thereof, amino acid and N- (8- (2-hydroxybenzoyl) amino) caprylic acid (NAC) and salts thereof. The oral polypeptide preparation can effectively improve the blood concentration of the polypeptide and improve the bioavailability of the oral polypeptide.

Inventors

  • Yuan Banghao
  • SUI YUSHENG
  • DOU LIU

Assignees

  • 深圳奥礼生物科技有限公司

Dates

Publication Date
20260512
Application Date
20250324
Priority Date
20240603

Claims (15)

  1. 1. An oral polypeptide composition, wherein the polypeptide composition is formulated as follows: 0.5-10.0% w/w semaglutin; 5-15% w/w arginine; 25-35% w/w SNAC; 25-35% w/w sodium caprate, and An excipient; Wherein the total content of arginine, SNAC and sodium caprate in the polypeptide composition is 70-80% w/w.
  2. 2. The oral polypeptide composition of claim 1, wherein the ratio of SNAC to sodium decanoate in the oral polypeptide composition is 1:1 by mass.
  3. 3. The oral polypeptide composition of claim 1, wherein the mass percent ratio of arginine to SNAC in the oral polypeptide composition is 1:3.
  4. 4. The oral polypeptide composition of claim 1, wherein the mass percentage ratio of arginine, SNAC, sodium decanoate in the oral polypeptide composition is 1:3:3.
  5. 5. The oral polypeptide composition of claim 1, wherein the oral polypeptide composition comprises: 1-32 parts by weight of semaglutin; 50-70 parts of arginine; 120-180 parts by weight of sodium caprate; 120-180 parts by weight of SNAC; 70-140 parts of excipient.
  6. 6. The oral polypeptide composition of claim 1, wherein the oral polypeptide composition comprises 4.0mg of semaglutin, 50.0mg of arginine, 150.0mg of SNAC, 150.0mg of sodium decanoate, and 123.0mg of excipient.
  7. 7. The oral polypeptide composition of claim 1, wherein the oral polypeptide composition comprises 8.0mg of semaglutin, 50.0mg of arginine, 150.0mg of SNAC, 150.0mg of sodium decanoate, and 120.0mg of excipient.
  8. 8. The oral polypeptide composition of claim 1, wherein the oral polypeptide composition comprises 16.0mg of semaglutin, 50.0mg of arginine, 150.0mg of SNAC, 150.0mg of sodium decanoate, and 110.0mg of excipient.
  9. 9. The oral polypeptide composition of any one of claims 6-8, wherein the excipient comprises microcrystalline cellulose, sodium lauryl sulfate, sodium carboxymethyl starch, and povidone.
  10. 10. The oral polypeptide composition of any one of claims 1-8, wherein the oral polypeptide composition is a solid formulation.
  11. 11. The oral polypeptide composition of claim 9, wherein the oral polypeptide composition is a solid formulation.
  12. 12. The oral polypeptide composition of claim 10, wherein the oral polypeptide composition is a tablet.
  13. 13. The oral polypeptide composition of claim 11, wherein the oral polypeptide composition is a tablet.
  14. 14. The oral polypeptide composition of claim 12 or 13, wherein the tablet is 1-50mg in size.
  15. 15. Use of an oral polypeptide composition according to any one of claims 1-14 for the manufacture of a medicament for the treatment of a disease selected from at least one of type 2 diabetes, obesity and non-alcoholic fatty liver disease.

Description

Oral polypeptide composition Priority statement The present disclosure claims priority to chinese patent application publication number 202410710353.4 entitled "an oral polypeptide composition" filed on date 2024/06/03. The present disclosure refers to the entirety of the above-mentioned chinese patent application. The present disclosure claims priority to chinese patent application publication number 202411335782.4 entitled "an oral polypeptide composition" filed on publication date 2024/09/24. The present disclosure refers to the entirety of the above-mentioned chinese patent application. Technical Field The present disclosure relates to the field of biological medicine, and in particular to an oral polypeptide composition. Background Polypeptide drugs are a class of biological macromolecules formed by short chain amino acids linked by peptide bonds, usually consisting of 10 to 50 amino acids, and are an important branch in the current field of drug development. Polypeptide drugs are capable of specifically binding to a target, such as a receptor or enzyme, which binding typically has a high affinity. This allows the accurate modulation of specific biological processes compared to small molecule drugs without affecting other physiological functions. Polypeptides are generally less immunogenic than many macromolecular biopharmaceuticals because their smaller molecular structure and nature closer to natural peptides make them less likely to elicit a strong immune response. The synthesis of polypeptide drugs is simpler and more controllable than complex biopharmaceuticals, which makes the production process more efficient and cost-effective. And the natural polypeptide can be modified by various means, so that the drug effect is enhanced, the pharmacokinetic property is improved or the side effect is reduced. At this stage, the main mode of administration of polypeptide drugs is by injection. Injection is an invasive administration regimen that requires transdermal delivery, which can cause pain and discomfort to the patient. Furthermore, injections often require the operation of a medical professional or the patient himself, which adds to the complexity and inconvenience of administration. Injection may also cause complications such as infection at the injection site, local tissue injury, etc., particularly when the same site is improperly handled or repeatedly injected, the patient may be reluctant to receive injections periodically according to the order due to pain and inconvenience caused by injection, affecting the therapeutic effect. Therefore, development of an oral dosage form of a polypeptide drug is very necessary. Although oral administration of polypeptide drugs has significant advantages in convenience and acceptance, technological problems encountered during their development remain quite serious. These challenges are mainly manifested in the general low bioavailability of polypeptide drugs, mainly due to stability and malabsorption. Under the action of gastric acid and intestinal enzymes, polypeptides are easily decomposed, which greatly reduces their bioavailability by the oral route. In order to achieve an effective therapeutic effect, it is necessary to ensure that a sufficient amount of the drug is able to pass stably through the digestive system and into the blood circulation. Furthermore, due to the large volume and polar nature of polypeptide drug molecules, they are difficult to penetrate the intestinal mucosa and the absorption efficiency may still be low even if the polypeptide remains stable in the intestinal tract. (Oral semaglutin) is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist obtained, which marks a major breakthrough in the field of polypeptide therapy.The success of the polypeptide not only opens up a new way for the self application of the drug of the semaglutin, but also opens up a way for the development and commercialization of other potential oral polypeptide drugs. It demonstrates that by appropriate formulation and techniques, some biologically active molecules that have traditionally been administered only by injection can be converted to oral form. Using a solution developed by EMISPHERE TECHNOLOGIESTechnology, which achieves its effect by using specialized chemical carriers, these carriers are known as "Eligen carriers".Sodium N- (8- (2-hydroxybenzoyl) amino) caprylate (SNAC) in Eligen carrier is used to increase stability and absorption rate of semaglutinin in stomach by regulating pH in stomach and affecting permeability of gastric mucosa. However, clinical data showsThe bioavailability of (2) is only about 0.8%. Bioavailability refers to the proportion of a drug that enters the systemic circulatory system from the site of administration. For drugs, low bioavailability means that only a small fraction of the administered dose eventually reaches the blood circulation and acts. To overcome the low blood concentration problem associated with low b