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CN-122028907-A - Capsule for delivering a carrier system containing a topically acting payload to the intestinal tract of a mammal

CN122028907ACN 122028907 ACN122028907 ACN 122028907ACN-122028907-A

Abstract

The present invention relates to a capsule comprising effervescent pairs for targeted delivery of an active agent to the gastrointestinal tract.

Inventors

  • J. OLSEN

Assignees

  • 恩特罗泰格特有限公司

Dates

Publication Date
20260512
Application Date
20241011
Priority Date
20231013

Claims (20)

  1. 1. A composition for oral administration of an active agent, the composition comprising A. microparticles having a size of 100 μm to 2000 μm, the microparticles comprising a polymer and an active agent, B. The effervescent agent is used for preparing the medicine, Wherein the w/w ratio of microparticles to effervescent agent is between 7:1 and 1.5:1, and wherein the composition is encapsulated.
  2. 2. The composition of claim 1, wherein the composition is a modified release composition.
  3. 3. The composition according to claim 2, wherein the composition releases the active agent at least 1 hour after administration, such as at least 2 hours after administration, such as at least 3 hours after administration, such as at least 4 hours after administration, such as 6 to 8 hours after administration, such as 10 to 20 hours after administration.
  4. 4. The composition according to any of the preceding claims, wherein the microparticles have a size of 150 to 2000 μιη, such as 150 to 1500 μιη, such as 150 to 1000 μιη, such as 150 to 800 μιη, such as 150 to 700 μιη, such as 150 to 600 μιη, such as 200 to 600 μιη.
  5. 5. The composition of any of the preceding claims, wherein the microparticles have a size of 100 μιη to 2000 μιη, such as 150 μιη to 2000 μιη, such as 200 μιη to 2000 μιη, such as 250 μιη to 2000 μιη, such as 300 μιη to 2000 μιη, such as 350 μιη to 2000 μιη, such as 400 μιη to 2000 μιη, such as 245 μιη to 2000 μιη, such as 500 μιη to 2000 μιη,550 μιη to 2000 μιη, such as 600 μιη to 2000 μιη, such as 650 μιη to 2000 μιη, such as 700 μιη to 1100 μιη, such as 800 μιη to 2000 μιη, such as 900 μιη to 2000 μιη, such as 1000 μιη to 2000 μιη, such as 1200 μιη to 2000 μιη, such as 2000 μιη to 2000 μιη, such as 1500 μιη to 2000 μιη.
  6. 6. The composition of any of the preceding claims, wherein the microparticles have a size of 250 μιη to 1000 μιη.
  7. 7. The composition of any one of the preceding claims, wherein the effervescent agent is an effervescent couple comprising or consisting of: a. A base, for example a base selected from sodium bicarbonate, potassium bicarbonate and sodium carbonate, B. Acids, for example acids selected from citric acid, maleic acid and tartaric acid.
  8. 8. The composition of any of the preceding claims, wherein the effervescent agent comprises or consists of citric acid and bicarbonate in a molar ratio of 1 mole citric acid to 3 moles sodium bicarbonate.
  9. 9. A composition according to any preceding claim, wherein the ratio of microparticles to effervescent agent is between 7:1 and 1.5:1, such as between 6:1 and 4:1, such as 1.6:1, such as 2.5:1, such as 3:1, such as 5:1.
  10. 10. A composition according to any preceding claim, wherein the ratio of microparticles to effervescent agent is between 7:1 and 3:1.
  11. 11. A composition according to any preceding claim, wherein the ratio of microparticles to effervescent agent is between 6:1 and 4:1, for example about 3:1.
  12. 12. The composition of any of the preceding claims, wherein the microparticles are from 710 μιη to 1000 μιη in size, wherein the effervescent agent is citric acid and sodium bicarbonate, and wherein the ratio of microparticles to effervescent agent is 5:1.
  13. 13. The composition of any of the preceding claims, wherein the polymer is selected from microcrystalline cellulose, acrylic polymers such as Eudragit RL and Eudragit RS, polyethylene oxide, starches such as amylose, amylopectin and maltodextrin, starch derivatives such as dextrin, acid treated starch, alkali treated starch, starch acetate, bleached starch, alginates, pullulan, scleroglucan, povidone derivatives such as crospovidone (PVPP) and copovidone, natural gums, gelatin, chitosan, polyvinyl alcohol and combinations thereof.
  14. 14. A composition according to any preceding claim, wherein the concentration of polymer in the microparticles is 94% to 98.9% (w/w), such as 97% to 98% (w/w).
  15. 15. A composition according to any of the preceding claims, wherein the microparticles comprise a diluent, for example a diluent selected from lactose, dicalcium phosphate, starches and sugar alcohols such as mannitol, xylitol and sorbitol and combinations thereof.
  16. 16. The composition according to any of the preceding claims, wherein the microparticles comprise microcrystalline cellulose and mannitol in a ratio of 2:1 (w/w) to 6:1 (w/w), for example in a ratio of 5:1 (w/w).
  17. 17. A composition according to any preceding claim wherein the microparticles comprise microcrystalline cellulose and Eudragit RL in a ratio of 4:1.
  18. 18. The composition of any of the preceding claims, wherein the microparticles comprise one or more additives.
  19. 19. A composition according to any preceding claim, wherein the concentration of additive in the microparticles is from 0.1% to 2% (w/w), such as about 1% (w/w).
  20. 20. A composition according to any preceding claim, wherein the microparticles comprise a lubricant, such as a lubricant selected from magnesium stearate, stearic acid and talc, and combinations thereof.

Description

Capsule for delivering a carrier system containing a topically acting payload to the intestinal tract of a mammal Technical Field The present invention relates to a capsule comprising an effervescent couple for targeted delivery of a carrier system transporting a payload (cargo) to the small and/or large intestine of a mammal. Background In many cases, it is desirable to administer the active agent topically to the small and/or large intestine. Inflammatory Bowel Disease (IBD), such as crohn's disease and ulcerative colitis, is one such condition. Even for healthy subjects who are not diagnosed with any gastrointestinal disorder, it may be desirable to inoculate the whole inner surface of the large intestine with bacteria (probiotics) or to spray nutritional supplements for intestinal microecology (gut microbiota). In such cases, the motivation may be to achieve healthier intestinal microecology, provide energy substrates for the intestinal cells, and/or protect the intestinal cells from oxidative stress. Some oral formulations for delivering active agents consist of capsules with an enteric coating that ensures that the capsule remains intact until it reaches the desired site in the gastrointestinal tract. For agents intended to exert systemic effects, the actual absorption of the drug is likely to occur in a small surface area around the dissolution site of the capsule. However, for agents intended to exert a local effect, it is important to expand the exposed area of the active agent as much as possible. Furthermore, depending on the particular situation, it may also be desirable to keep the release kinetics of the capsule independent of the carrier system used for the active agent. Disclosure of Invention The present disclosure relates to a capsule for delivering a carrier system containing a topically acting payload to the intestinal tract of a mammal. The present disclosure relates to the discovery that carrier systems comprising microparticles (pellets) and effervescent agents in appropriate proportions can achieve a reproducible delayed release of topically acting active ingredients for topical treatment over an extended surface area. A first aspect of the present disclosure relates to a composition for oral administration of an active agent, the composition comprising: a. microparticles having a size of 100 μm to 2000 μm, the microparticles comprising a polymer and an active agent, B. The effervescent agent is used for preparing the medicine, Wherein the w/w ratio of microparticles to effervescent agent is between 7:1 and 1.5:1, and wherein the composition is encapsulated. A second aspect of the present disclosure relates to an orally administered composition of an active agent for use as a medicament, the composition comprising: a. microparticles having a size of 100 μm to 2000 μm, the microparticles comprising a polymer and an active agent, B. The effervescent agent is used for preparing the medicine, Wherein the w/w ratio of microparticles to effervescent agent is between 7:1 and 1.5:1, and wherein the composition is encapsulated. A third aspect of the present disclosure relates to a composition for use in the treatment of inflammatory bowel disease and/or inflammation-induced colorectal neoplasms and/or cancer, wherein the active agent comprises or consists of insulin or an analogue thereof. A fourth aspect of the present disclosure relates to a method of preparing the composition, the method comprising: a. mixing the polymer with an active agent, and optionally with a lubricant; b. extruding microparticles comprising at least one polymer and having a size of 100 to 2000 μm and optionally spheronizing them; c. Mixing the microparticles with an active agent and an effervescent agent, thereby obtaining a mixture; d. the mixture is subjected to encapsulation to obtain a mixture, Thereby obtaining a composition according to the present disclosure. A fifth aspect of the present disclosure relates to a method of making a composition, the method comprising: a. Suspending a polymer, an active agent, and optionally a lubricant in a solvent; b. stirring until the solvent evaporates, collecting and washing particles comprising at least one polymer and having a size of 100 to 2000 μm; c. Mixing the microparticles with an active agent and an effervescent agent, thereby obtaining a mixture; d. the mixture is subjected to encapsulation to obtain a mixture, Thereby obtaining a composition according to the present disclosure. Drawings Fig. 1. Excipients are applied in capsules to promote disintegration (gelatin capsules). i microparticles, ii microparticles+citric acid+bicarbonate, iii microparticles+mgcl 2.A. t=0. B. t=rest for 3min. C. t=rest for an additional 6min, followed by 4min orbital shaking. D. t=0. i is microparticles, ii is microparticles+citric acid+bicarbonate, iii is microparticles+MgCl 2.E. orbitally shaken for 1.5min. F. An additional 4min orbital shaking was performed. Fig. 2. Excipients are