Intestinal alkaline phosphatase formulations
The present invention provides for a formulation comprising an active alkaline phosphatase (AP)-based agent and an enteric agent, wherein the formulation is suitable for releasing a substantial amount of the active AP-based agent in the intestines.
1. A formulation in the form of a tablet comprising:
42-48% by an intestinal weight alkaline phosphatase (AP)-based agent, wherein the AP-based agent comprises an amino acid sequence of at least 95% sequence identity with the amino acid sequence set forth in SEQ ID NOs: 2, 3, 5, 6 or 7 and wherein activity of the intestinal alkaline phosphatase is maintained at least at 60% until 36 weeks of storage;
42-48% by weight sugar;
7-13% by weight buffer salts; and
0.5-1.5% by weight magnesium stearate.
2. The formulation of claim 1 , further comprising an enteric coating.
3. The formulation of claim 2 , wherein the enteric coating comprises Eudragit L 30 D 55 (poly(methacrylic acid-ethyl acrylate copolymer) 1:1).
4. The formulation of claim 1 , further comprising two coatings.
5. The formulation of claim 4 , wherein the first coating comprises a hydroxypropyl cellulose (HPC) subcoat and the second coating comprises an enteric coating.
6. The formulation of claim 5 , wherein the enteric coating comprises Eudragit L 30 D 55 (poly(methacrylic acid-ethyl acrylate copolymer) 1:1).
7. The formulation of claim 1 comprising:
45% by weight AP-based agent;
45% by weight sugar;
10% by weight buffer salts; and
1% by weight magnesium stearate.
8. The formulation of claim 7 , further comprising an enteric coating.
9. The formulation of claim 8 , wherein the enteric coating comprises Eudragit L 30 D 55 (poly(methacrylic acid-ethyl acrylate copolymer) 1:1).
10. The formulation of claim 7 , further comprising two coatings.
11. The formulation of claim 10 , wherein the first coating comprises a HPC subcoat and the second coating comprises an enteric coating.
12. The formulation of claim 11 , wherein the enteric coating comprises Eudragit L 30 D 55 (poly(methacrylic acid-ethyl acrylate copolymer) 1:1).
13. The formulation of claim 1 , wherein the AP-based agent comprises an amino acid sequence having at least 95% sequence identity with the amino acid sequence set forth in SEQ ID NO: 2.
14. The formulation of claim 1 , wherein at least 75% of the AP-based agent is released within 15 minutes in pH of 4-5.
15. The formulation of claim 1 , wherein the sugar is lactose.
16. The formulation of claim 1 , wherein the buffer salts are selected from Tris, MgCl, and ZnSO 4 .