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 modified-release formulation comprising a bovine intestinal alkaline phosphatase (bIAP), and being in the form of a tablet, comprising:
1-10% by weight bovine intestinal alkaline phosphatase (bIAP),
80-95% by weight polymer, wherein the polymer is hypromellose acetate succinate (HPMCAS),
1-10% by weight buffer,
0.01-0.1% by weight zinc,
0.1-1% by weight magnesium stearate,
1-10% by weight protein stabilizer,
and wherein the formulation is compressible releases the bIAP in the intestines, and is coated with a poly(methacrylic acid, methylmethacrylate polymer.
2. The modified-release formulation of claim 1 , wherein the bovine intestinal alkaline phosphatase (bIAP) is released in the small intestine.
3. The modified-release formulation of claim 1 , wherein the bovine intestinal alkaline phosphatase (bIAP) is released in the large intestine.
4. The modified-release formulation of claim 1 , wherein the tablet transforms into a gel in the presence of stomach acid.
5. The modified-release formulation of claim 1 , wherein the tablet comprises:
5% by weight bovine intestinal alkaline phosphatase (bIAP),
87% by weight polymer, wherein the polymer is hypromellose acetate succinate (HPMCAS),
2% by weight buffer;
0.06% by weight zinc;
0.5% by weight magnesium stearate; and
5% by weight protein stabilizer.
6. The modified-release formulation of claim 1 , wherein the tablet comprises:
5% by weight bovine intestinal alkaline phosphatase (bIAP),
87.45% by weight polymer, wherein the polymer is hypromellose acetate succinate (HPMCAS),
2% by weight buffer;
0.06% by weight zinc;
0.49% by weight magnesium stearate; and
5% by weight protein stabilizer.