Alkaline phosphatase formulations
The present invention provides, in part, formulations comprising an alkaline phosphatase (AP)-based agent. Particularly, modified-release powder formulations comprising an AP-based agent are provided which release a substantial amount of the AP-based agent in the intestines. Therapeutic uses of the formulations are also provided.
1 . A method of treating or preventing a microbiome-related disorder in a subject in need thereof comprising, administering to the subject a formulation comprising an alkaline phosphatase (AP)-based agent, and being in the form of a tablet, comprising:
about 1-10% by weight AP-based agent,
about 80-95% by weight polymer,
about 1-10% by weight buffer,
about 0.01-0.1% by weight zinc,
about 0.1-1% by weight magnesium stearate,
about 1-10% by weight protein stabilizer,
and optionally having the capacity to transition into a gel in a pH-dependent manner,
wherein the formulation is suitable for compressing and releases a substantial amount of the AP-based agent in the intestines.
2 . The method of claim 1 , wherein the AP-based agent is mammalian alkaline phosphatase.
3 . The method of claim 1 , wherein the AP-based agent is bovine or human alkaline phosphatase.
4 . The method of claim 1 , wherein the AP-based agent is intestinal alkaline phosphatase.
5 . The method of claim 1 , wherein the polymer is hypromellose acetate succinate (HPMCAS).
6 . The method of claim 1 , wherein the AP-based agent comprises an amino acid sequence having at least 95% sequence identity with any one of SEQ ID NOs: 1-17.
7 . The method of claim 1 , wherein the AP-based agent comprises an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 2.
8 . The method of claim 1 , wherein the AP-based agent is released in the small intestine.
9 . The method of claim 1 , wherein the AP-based agent is released in the large intestine.
10 . The method of claim 1 , wherein the tablet further comprises an enteric agent.
11 . The method of claim 1 , wherein the tablet comprises:
about 5% by weight AP-based agent,
about 87% by weight polymer,
about 2% by weight buffer;
about 0.06% by weight zinc;
about 0.5% by weight magnesium stearate; and
about 5% by weight protein stabilizer.
12 . The method of claim 1 , wherein the tablet comprises:
about 5% by weight AP-based agent,
about 87.45% by weight polymer,
about 2% by weight buffer;
about 0.06% by weight zinc;
about 0.49% by weight magnesium stearate; and
about 5% by weight protein stabilizer.
13 . The method of claim 1 , wherein the polymer is hypromellose acetate succinate (HPMCAS).
14 . The method of claim 1 , wherein the microbiome-related disorder is selected from antibiotic-associated diarrhea (AAD), Clostridium difficile -associated disease (CDAD), an inflammatory disorder, acquired immunodeficiency syndrome (AIDS), HIV-mediated gut dysbiosis, gastrointestinal (GI) barrier dysfunction, hypothyroidism, and obesity.