Stabilized teriparatide solutions

a technology of teriparatide and solution, which is applied in the field of teriparatide and pth, can solve the problems that the formulation of parathyroid hormone presents challenges not commonly encountered by the pharmaceutical industry

Inactive Publication Date: 2007-01-25
CHANG CHIN MING +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The solution provides a stable and storage-friendly PTH formulation with extended shelf-life, maintaining bioactivity and ease of preparation, suitable for parenteral administration, and is effective in treating osteoporosis and aiding in medical diagnosis.

Problems solved by technology

Because it is a protein and thus far more labile than the traditionally small molecular weight drugs, however, the formulation of parathyroid hormone presents challenges not commonly encountered by the pharmaceutical industry.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0041] 0.1 mg rhPTH (1-34) (SEQ ID NO: 2), 50 mg mannitol, 2.5 mg m-cresol, 0.52 mg acetic acid and 0.12 mg sodium acetate were mixed into a solution with 1 ml of distilled water.

example 2

[0042]0.25 mg rhPTH (1-34) (SEQ ID NO: 2), 45.4 mg mannitol, 3 mg m-cresol, 0.41 mg acetic acid and 0.1 mg sodium acetate were mixed into a solution with 1 ml of distilled water.

[0043] The formulations of the present invention, Examples 1 and 2 were compared to solutions containing no stabilizer, 0.9% NaCl, 20 mM acetate and 10 mM acetate as primary stabilizer. The stability was measured by determining the amount in % of rhPTH (1-34) (SEQ ID NO: 2) remaining after a certain time. The measurement was made by HPLC. The results are shown in Tables 1 and 2.

TABLE 1Effect of Primary Stabilizer on Chemical Stabilityof rhPTH (1-34) at 50° C.Water0.9% NaCl20 mM acetate10 mM acetateTime, days% RemainingInitial100100100100 7748184801455586771

[0044]

TABLE 2Comparison of Stability of rhPTH (1-34) at 30° C.20 mM acetate10 mM acetateExample 1Example 2Time, days% RemainingInitial100100100100 79694100—1494929610021909397—30—819696

example 3

[0045] The following experiment was carried out to show that lyophilized powder formulations prepared from stabilized solutions of the present invention are more stable than a control which was prepared from PTH(1-34) and mannitol alone.

[0046] A control solution and solutions for samples A through O were prepared as previously described with the ingredients and concentrations shown in Table 3. The solutions were then freeze-dried and the resulting lyophilized powder formulations were stored at 40° C. for a one month period. The amount of PTH(1-34) remaining in each sample was then measured by HPLC. The results are shown in Table 3.

TABLE 3Stability of PTH(1-34) Lyophilized Formulationsat 40° C. for One MonthBulkingBuff-Agenter% PTHPTH(1-34)BulkingConc.Conc.Remain-Samplemg / mLAgentmg / mLBuffermMingControl0.2mannitol40——78A0.5mannitol30acetate590B0.5glycine30acetate598C0.5sucrose30acetate598D0.5trehalose30acetate597E0.5raffinose30acetate599F0.75mannitol30tartrate1595G1.5sucrose &5 / 25t...

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Abstract

A stabilized pharmaceutical composition in the form of a solution for parenteral administration of a parathyroid hormone is described wherein the therapeutically active ingredient is stabilized with a buffer and a polyol. Preferred preparations contain in an aqueous solution human PTH (1-34), mannitol, an acetate or tartrate buffering agent and m-cresol or benzyl alcohol as a preservative.

Description

TECHNICAL FIELD [0001] This invention relates to pharmaceutical compositions containing a parathyroid hormone. More particularly, the invention relates to teriparatide, PTH(I1-34), stabilized solution formulations BACKGROUND OF THE INVENTION [0002] Parathyroid hormone (PTH) is a secreted, 84 amino acid product of the mammalian parathyroid gland that controls serum calcium levels through its action on various tissues, including bone. Studies in humans with certain forms of PTH have demonstrated an anabolic effect on bone, and have prompted significant interest in its use for the treatment of osteoporosis and related bone disorders. [0003] Using the N-terminal 34 amino acids of the bovine and human hormone for example, which by all published accounts are deemed biologically equivalent to the full length hormone, it has been demonstrated in humans that parathyroid hormone enhances bone growth particularly when administered in pulsatile fashion by the subcutaneous route. A slightly diff...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K38/29A61K9/00A61K9/19A61K47/10A61K47/26
CPCA61K9/0019A61K9/19A61K47/26A61K47/10A61K38/29
InventorCHANG, CHIN-MINGHAVEL, HENRY A.
OwnerCHANG CHIN MING