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CN-122028924-A - Porous carbon particles for therapy

CN122028924ACN 122028924 ACN122028924 ACN 122028924ACN-122028924-A

Abstract

The present invention relates to the treatment or prevention of diseases by modulating the microbiome of the intestinal tract with porous carbon particles comprising micropores of diameter 2nm or less and mesopores/macropores of diameter 30nm to 500nm, but substantially no mesopores of diameter greater than 2nm and less than 30nm and substantially no macropores of diameter greater than 500 nm.

Inventors

  • Rajiv Garland

Assignees

  • UCL商业有限公司

Dates

Publication Date
20260512
Application Date
20240620
Priority Date
20230620

Claims (20)

  1. 1. A porous carbon particle for use in a method of preventing or treating a disease, wherein: The porous carbon particles comprise micropores having a diameter of 2nm or less and mesopores/macropores having a diameter of 30nm to 500nm, but substantially no mesopores having a diameter of more than 2nm and less than 30nm and substantially no macropores having a diameter of more than 500nm, and The method comprises administering the porous carbon particles to a subject in need thereof, thereby modulating the microbiome of the gut and preventing or treating the disease.
  2. 2. The porous carbon particle for use according to claim 1, wherein mesopores having a diameter of more than 2nm and less than 30nm and macropores having a diameter of more than 500nm together account for 10% or less of the total pore volume of the porous carbon particle.
  3. 3. The porous carbon particle for use according to claim 1 or 2, wherein 5 to 30% of the total pore volume of the porous carbon particle consists of pores having an average diameter of 0.6nm to 2 nm.
  4. 4. A porous carbon particle for use according to any one of claims 1 to 3, wherein 85% or more of the pore volume of the porous carbon particle consisting of pores having an average diameter of more than 2nm consists of pores having an average diameter of 30nm to 500nm, preferably wherein 90% or more of the pore volume of the porous carbon particle consisting of pores having an average diameter of more than 2nm consists of pores having an average diameter of 30nm to 500nm, preferably 50nm to 300nm, preferably 50nm to 200 nm.
  5. 5. The porous carbon particle for use according to any one of claims 1 to 4, wherein the total pore volume is from 0.5cm 3 g -1 to 2.5cm 3 g -1 .
  6. 6. The porous carbon particle for use according to any one of claims 1 to 5, wherein the total pore volume is from 1.0cm 3 g -1 to 2.0cm 3 g -1 .
  7. 7. The porous carbon particle for use according to any one of claims 1 to 6, wherein the porous carbon particle has a bulk density of 0.10gcm -3 to 0.30gcm -3 .
  8. 8. The porous carbon particle for use according to any one of claims 1 to 7, wherein the porous carbon particle has a bulk density of 0.15gcm -3 to 0.25gcm -3 .
  9. 9. The porous carbon particle for use according to any one of claims 1 to 8, wherein the specific surface area is 700m 2 /g to 2000m 2 /g.
  10. 10. The porous carbon particle for use according to any one of claims 1 to 9, wherein the specific surface area is 900m 2 /g to 1400m 2 /g.
  11. 11. The porous carbon particle for use according to any one of claims 1 to 10, wherein the porous carbon particle has a pore volume of 0.1cm 3 g -1 to 1.1cm 3 g -1 with an average diameter of 0.5nm to 2nm and a pore volume of 0.8cm 3 g -1 to 2.5cm 3 g -1 with an average diameter of 30nm to 500 nm.
  12. 12. Porous carbon particle for use according to any one of claims 1 to 11, wherein the particle is administered orally or rectally, preferably wherein the particle is administered orally in free-flowing form or in tablet form.
  13. 13. The porous carbon particle for use according to any one of claims 1 to 12, wherein the porous carbon particle is coated to control its release and adsorption properties, preferably wherein the porous carbon particle is coated with a membrane that will allow for a major release into the large intestine.
  14. 14. The porous carbon particle for use according to any one of claims 1 to 13, wherein the disease is an inflammatory disease or disorder.
  15. 15. The porous carbon particle for use according to claim 14, wherein modulation of the microbiome of the gut causes a reduction in systemic inflammation, thereby treating or preventing the disease.
  16. 16. Porous carbon particles for use according to claim 14 or 15, wherein the inflammatory disease or condition is selected from coronary heart disease, obesity, alzheimer's disease, dementia, ankylosing spondylitis, osteoarthritis, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary airway disease, encephalitis, allograft rejection, graves' disease, hashimoto's thyroiditis, autoimmune uveoretinitis, giant cell arteritis, asthma, atherosclerosis, regional enteritis, granulomatous enteritis, terminal ileitis, regional ileitis, terminal ileitis, dermatitis, insulin dependent diabetes, non-insulin dependent diabetes mellitus, diverticulitis, fibromyalgia, multiple sclerosis, pernicious anemia, sarcoidosis, scleroderma, systemic lupus erythematosus, nephritis, cholestasis-related diseases and parkinson's disease.
  17. 17. The porous carbon particle for use according to any one of claims 1 to 15, wherein administration of the porous carbon particle protects organs remote from the gut or liver from inflammatory effects.
  18. 18. The porous carbon particle for use according to any one of claims 1 to 13, wherein the porous carbon particle is for use in preventing radiation-induced organ damage.
  19. 19. The porous carbon particle for use according to claim 18, wherein the radiation is nuclear radiation.
  20. 20. The porous carbon particle for use according to claim 18, wherein the subject is exposed to the radiation by radiotherapy.

Description

Porous carbon particles for therapy Technical Field The present invention relates to the treatment or prevention of diseases by modulating the microbiome of the intestinal tract with porous carbon particles comprising micropores of diameter 2nm or less and mesopores/macropores of diameter 30nm to 500nm, but substantially no mesopores of diameter greater than 2nm and less than 30nm and substantially no macropores of diameter greater than 500 nm. The invention also relates to methods of using such porous carbon particles to modulate the microbiome of the gut to treat or prevent disease. Background Recent studies have shown that intestinal microbiomes play a central role in the regulation of inflammation. Intestinal microbiota consists of various microflora that inhabit the intestinal tract. Microorganisms are responsible for performing many functions including metabolizing nutrients, modulating the immune system, and providing natural defenses against infection, all of which in combination affect host health. In the intestinal microbiome, specific microorganisms are associated with markers of inflammation. Various multisystem conditions are associated with inflammation, including atherosclerosis, diabetes, arthritis, and alzheimer's disease. Inflammation may be stimulated by specific bacteria that promote intestinal leakage and allow bacterial components to reach the blood stream, triggering a cascade of interleukins and other cytokine pathways that promote inflammation throughout the body. Multiple organ dysfunction may result when dysbiosis and translocation of bacterial components including Lipopolysaccharide (LPS) stimulate systemic inflammation. For example, enterotoxemia and bacterial translocation have been shown to play a central role in the acceleration of atherosclerosis. However, therapeutic options for these factors are currently limited to the long-term use of antibiotics, and are associated with problems of resistant microbial infection. Absorbent porous carbon particles for oral administration have been used for centuries to treat or prevent various conditions without any major side effects. Activated carbon is widely used for the treatment of poisoning. Microporous carbon AST-120 (commercially available from Kureha corporation, japan under the trade name KREMEZIN) is used to treat patients with renal failure. However, clinical trials evaluating the efficacy of AST-120 in the treatment of hepatic encephalopathy have been shown to be negative. WO 2013/136094 discloses the use of carbon particles with a bimodal pore size distribution in the treatment of liver diseases. Disclosure of Invention The present invention relates to the treatment or prevention of diseases by modulating the microbiome of the gut. Accordingly, the present invention provides porous carbon particles for use in a method of preventing or treating a disease, wherein the porous carbon particles comprise micropores having a diameter of 2nm or less and mesopores/macropores having a diameter of 30nm to 500nm, but substantially no mesopores having a diameter of more than 2nm and less than 30nm, and substantially no macropores having a diameter of more than 500nm, and the method comprises administering the porous carbon particles to a subject in need thereof, thereby modulating the microbiome of the intestinal tract and preventing or treating the disease. The present invention also provides a method of treating or preventing a disease comprising administering to a subject in need thereof an effective amount of such porous carbon particles, thereby modulating the microbiome of the gut and preventing or treating a disease. The invention also provides the use of such porous carbon particles in the manufacture of a medicament for modulating the microbiome of the gut to treat or prevent a disease. Drawings FIG. 1 pore distribution of phenolic resin derived carbon measured by nitrogen adsorption and determined using BJH method for TE9 carbon not activated to activation to 29% and 47% burn-out rate. Activation mainly increases the pores (< 2nm diameter) in the microwells. The small macropores (50 nm to 500 nm) were substantially unchanged and no pores (mesopores) in the range of 2nm to 50nm were introduced. FIG. 2 representative pore size distribution of the porous carbon particles of the present invention (A: TE7 test carbon; B: TE8 test carbon) measured by mercury intrusion. The larger peaks above 30,000 are due to the voids between the carbon particles rather than the porosity. FIG. 3 the macropore volume (50 nm to 500 nm) increases as the porogen concentration increases from TE3 to TE7 for carbon activated to about 50% burn-out rate. No significant introduction of pores in the mesoporous range (2 nm to 50 nm) or no change of pores in the microporous domain. FIG. 4A. Influence of the degree of activation on the pore structure (as measured by mercury intrusion), based on the evolution of the pore volume in cm3/gm and the reduction of the