5-CNAC as oral delivery agent for parathyroid hormone fragments

a parathyroid hormone and oral delivery technology, applied in the field of oral delivery of parathyroid hormone, can solve the problem that the oral delivery of pth in mammals is difficul

Inactive Publication Date: 2006-09-28
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008] Specifically, the instant invention is directed to a pharmaceutical composition for oral delivery comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28) to PTH (1-41). Preferably, the PTH is human parathyroid hormone, hPTH.
[0009] In another embodiment, the invention is directed to a method for orally administering an effective dose of PTH comprising orally administering to a patient in need of PTH a pharmaceutical composition comprising a therapeutically effective amount of a PTH fragment and 5-CNAC, said PTH fragment selected from PTH (1-28) to PTH (1-41).
[0010] The invention is

Problems solved by technology

However, the oral delivery of PTH in mammals has proven difficult due, at least in part, to the insufficient stability of PTH in the

Method used

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  • 5-CNAC as oral delivery agent for parathyroid hormone fragments

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0040] The following capsules are prepared as follows:

Capsules prepared from 800 μg hPTH* (Capsule 1A)

Capsules prepared from 400 mg 5-CNAC** / 800 μg hPTH* (Capsule 1B)

*The PTH fragment is human parathyroid hormone, fragment 1-34 commercially available from Sigma. **The 5-CNAC is the disodium salt of N-(5-chlorosalicyloyl)8-aminocaprylic acid.

[0041] The hPTH only capsules are prepared by weighing out 400 μg of the hPTH and placing it directly into each capsule. The hPTH / 5-CNAC capsules are prepared as dry blends by weighing out the individual components blending them together to make a homogeneous mix and then hand filling 400 mg of the mix into each capsule.

example 2

Primate Administration

[0042] The capsules prepared in Example 1 are administered to Rhesus monkeys as follows: four monkeys in a group are each dosed with one capsule prepared as in Example 1 as follows:

[0043] The Rhesus monkeys fast overnight prior to dosing and are restrained in chairs fully conscious, for the duration of the study period. The capsules are orally administered via a gavage tube followed by 10 mL of water.

[0044] Blood samples are collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, and 6 hours after administration. Plasma hPTH levels are determined by radioimmunoassay. The primate plasma PTH results from each group of monkeys are averaged and the maximum mean plasma calculated. The results for the PTH only group are reported in Table 1 and the results for the hPTH / 5-CNAC group are reported in Table 2.

TABLE 1hPTH ONLYhPTH PLASMA CONCENTRATIONS (pg / mL) AFTERORAL ADMINISTRATION TO THE RHESUS MONKEYDose: 1 Capsule 1DAnimalTime [hours]no.00.250.500.7511.523456R92700...

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PUM

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Abstract

Pharmaceutical compositions for the effective oral delivery of a parathyroid hormone, PTH, as well as methods for administration of the compositions are provided. Additionally, methods for stimulating new bone formation and treating and/or preventing osteoporosis are also provided.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The present invention relates to the oral delivery of parathyroid hormone (PTH). The mammalian parathyroid hormones, e.g. human (hPTH), bovine (bPTH) and porcine (pPTH), are single polypeptide chains of 84 amino acid residues having molecular weights of approximately 9500. Specifically, the present invention relates to PTH fragments incorporating at least the first 28 N-terminal amino acid residues (PTH (1-28)) up to and including the first 41 N-terminal amino acid residues (PTH (1-41)). More particularly, the invention is directed to pharmaceutical compositions for the oral delivery of PTH, said compositions comprising PTH (1-28) to (1-41) and N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC). [0003] 2. Description of the Related Art [0004] PTH studies done in animals and humans with PTH, PTH-related peptides, and PTH analogues have demonstrated its usefulness in increasing bone formation and bone resorption and...

Claims

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Application Information

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IPC IPC(8): A61K38/29A61K31/60A61K9/48A61K31/198A61K38/22A61K47/18A61P5/18A61P19/08A61P19/10
CPCA61K9/4858A61K31/198A61K38/29A61K47/183A61K2300/00A61P19/00A61P19/08A61P19/10A61P5/18A61K47/18
Inventor AZRIA, MOISEBATEMAN, SIMON DAVID
Owner NOVARTIS AG
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