Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-09-19
1998-07-14
Russel, Jeffrey E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
424452, 424465, 514807, A61K 920, A61K 948, A61K 3811, A61K 4742
Patent
active
057804346
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to pharmaceutical compositions in solid form for oral administration of small and medium size peptides, particularly vasopressin, oxytocin, and their analogues. The present invention also relates to a method of manufacturing a single dose of said composition for oral administration of small and medium-size peptides, particularly vasopressin, oxytocin, and their analogues.
The invention further relates to a method of administering said composition to a patient.
BACKGROUND
A number of medicines for treatment of a variety of diseases contain, as the active ingredient, naturally occurring peptides or their synthetic analogues.
Saffran et al. (can. J. Biochem. 57 (1979) 548-522) described a Sprague Dawley rat model for the study of the oral administration of peptide hormones. Urine retention after gastric administration of an aqueous solution of the vasopressin analog (1-deamino-4-valine)-8-D-arginine-vasopressin was found to be moderately enhanced in the presence of aprotinin.
Similarly, EP-A2 127 535, EP-A2 130 779, EP-A2 507 573, and J. Controlled Release 23 (1993) 56-74 (R. S. Geary and H. W. Schlameus), disclose the use of peptidase inhibitors as ingredients in solid pharmaceutical compositions containing biologically active peptides and their analogues. The aforementioned compositions, EP-A2 127 535, EP-A2 130 779, EP-A2 507 573, J. Controlled Release 23 (1993) 65-74 (R. S. Geary and H. W. Schlameus) have been designed, by providing them with an appropriate enteric coat, for release of their active ingredients in the small intestine, where some peptides, particularly insulin, are known to be better absorbed.
Because of the instability of small and medium size peptides, particularly vasopressin, oxytocin, and their analogues, in the environment of the gastrointestinal tract their uptake, when given as a medicine or for similar reasons, is still very unsatisfactory. Thus, better delivery systems for non-parenteral, particularly oral, administration of peptides and their analogues are desirable, cf. Davies, S.: "Developing delivery systems for peptides and proteins", Scrip Magazine 1992, 34-38.
OBJECTS OF THE INVENTION
It is an object of the present invention to provide a pharmaceutical composition which provides for better absorption of said small or medium-size peptides, particularly vasopressin, oxytocin, and their analogues.
It is another object of the present invention to provide a method of manufacture of a single dose of said pharmaceutical composition for oral administration of small and medium-size peptides, particularly vasopressin, oxytocin, and their analogues.
It is a further object of the invention to provide a method of administration of said composition to a patient.
Additional objects of the present invention will become evident by study of the detailed description of preferred embodiments of the invention.
SUMMARY OF THE INVENTION
The above and other objects of the invention are provided by a pharmaceutical composition of the kind described above, said composition comprising small and/or medium size peptides, particularly vasopressin, oxytocin, or an analog of vasopressin or oxytocin; a protease inhibitor; an enteric coat; and a pharmaceutically acceptable carrier containing a buffering agent buffering at a pH of from 3 to 6, preferably at about pH 5.
It is preferred for the protease inhibitor to be natural or structurally modified aprotinin. Other specific and unspecific protease inhibitors may be used; it is also possible to use mixtures of protease inhibitors. The expert will select the protease inhibitor(s), particularly serine protease inhibitors, suitable for protecting the respective peptide in the particular gastrointestinal environment. Besides native aprotinin isolated from natural sources, such as, for instance, native bovine aprotinin isolated from bovine lungs or pancreas, useful serine proteinase inhibitors comprise aprotinin and aprotinin analogues encoded by synthetic genes expressed in, e.g., yeast (Norris, K. e
REFERENCES:
patent: 4139504 (1979-02-01), Coy et al.
patent: 4849227 (1989-07-01), Cho
patent: 5047398 (1991-09-01), Hagstam et al.
patent: 5120710 (1992-06-01), Liedtke
patent: 5206219 (1993-04-01), Desai
patent: 5534494 (1996-07-01), Bowers et al.
M.E.K. Kraeling et al., "Development of A Colonic Release Capsule Dosage Form and the Absorption of Insulin", Meth Find Exp Clin Pharmacol, vol. 14, No. 3, 1992, pp. 199-209.
M. Saffran et al., "A Model for the Study of the Oral Administration of Peptide Hormones", Canadian Journal of Biochemistry, vol. 57, 1979, pp. 548-553.
R.S. Geary et al., "Vancomycin and Insulin Used as Models for Oral Delivery of Peptides", Journal of Controlled Release, vol. 23, 1993, pp. 65-74.
A.N. Elias et al., "Effective Portal Insulin Delivery With Enzyme-Protected Capsules in Pancreatectomized Pigs", Gen. Pharmac., vol. 23, No. 1, 1992, pp. 55-59.
Ferring B.V.
Russel Jeffrey E.
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