Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Patent
1996-03-18
1999-12-21
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
424489, 424470, 424461, 424450, 424 45, A61K 914, A61K 9127
Patent
active
060045744
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to powder formulations containing medically useful polypeptides.
TECHNICAL BACKGROUND
Polypeptide powders containing medically useful polypeptides and pharmaceutically acceptable carriers or diluents may be prepared for administration by inhalation or otherwise. Inhalable polypeptide powder preparations have been described in WO95/00127 and WO95/00128.
Diluents are commonplace in pharmaceutical preparations, especially in formulations for inhalation. They are used to stabilise various drugs during manufacture and storage and to adjust the amount of powder making up unit doses--in general, powder inhalers are capable of delivering a drug substance with good dose accuracy only for certain dose sizes, while different drugs have different potencies and must therefore be delivered in different amounts. As these amounts are often too small for proper dose accuracy to be ensured, diluents are added to give the desired dose size.
Previously, reducing sugars such as lactose and glucose have been used as diluents in polypeptide powder formulations. These however have a tendency to react with polypeptides and are therefore unsatisfactory.
It is suggested in WO95/00127 and WO95/00128, relating to polypeptide powders for inhalation, that non-reducing sugars such as raffinose, melezitose, lactitol, maltitol, trehalose, sucrose, mannitol and starch may be preferred additives for the polypeptide powders.
It has now been found that melezitose is an exceptionally good diluent compared with other possible non-reducing sugar diluents for polypeptide powder formulations, giving an unexpectedly high respirable fraction of powder when inhaled.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a powder formulation for the administration of medically useful polypeptides, comprising a medically useful polypeptide with melezitose as diluent.
Administration is preferably by inhalation.
The melezitose may comprise for example D-melezitose (.alpha.-D-melezitose), 0-.alpha.-D-glucopyranosyl-1,3,-.beta.-D-fructofur anosyl-.beta.-D-glucopyranoside(.beta.-D-melezitose) or isomelezitose. The melezitose may be for example in the form of the monohydrate or dihydrate.
The powder formulation of the present invention has been found to be very effective upon oral inhalation, giving a superior fraction of respirable particles compared with powder formulations with other diluents, as is described herein. As a result, a higher fraction of the inhaled powder will reach the lungs and a higher fraction of the polypeptide is utilised.
The powder formulation of the present invention is also suitable for use in nasal inhalation.
The powder formulation of the present invention is suitable for both systemic and local treatment. When local action is desired in the respiratory tract, no other ingredient is necessary in the powder formulation. When systemic action is required, an enhancer, i.e. a substance which enhances the absorption of the polypeptide in the respiratory tract, should generally be included in the formulation. Such substances are included in WO95/00127 and WO95/00128, incorporated herein by reference. In certain cases, small polypeptides are absorbed in the respiratory tract without the aid of an enhancer. In these cases an enhancer may be excluded from the formulations of melezitose and the medically useful polypeptide. In different embodiments therefore the present invention provides a powder comprising a medically useful polypeptide and melezitose; a powder comprising a medically useful polypeptide and melezitose and specifically including an enhancer; and a powder comprising a medically useful polypeptide and melezitose, specifically excluding an enhancer. The powder according to the present invention excluding an enhancer, is most useful (a) when local action of the polypeptide is desired; or (b) when systemic action of smaller polypeptides which are absorbed in the respiratory tract without the aid of an enhancer is desired. Polypeptides which are absorbed in
REFERENCES:
patent: 3014844 (1961-12-01), Thiel et al.
patent: 3671625 (1972-06-01), Altounyan
patent: 4232002 (1980-11-01), Nogrady
patent: 4462983 (1984-07-01), Azria
patent: 4613500 (1986-09-01), Suzuki et al.
patent: 4690952 (1987-09-01), Kagatani et al.
patent: 4788221 (1988-11-01), Kagatani et al.
patent: 4895719 (1990-01-01), Radhakrishnan et al.
patent: 5011678 (1991-04-01), Wang et al.
patent: 5179079 (1993-01-01), Hansen et al.
patent: 5202129 (1993-04-01), Samejima et al.
patent: 5284656 (1994-02-01), Platz et al.
patent: 5341800 (1994-08-01), Clark et al.
patent: 5354562 (1994-10-01), Platz et al.
patent: 5506203 (1996-04-01), Backstrom et al.
patent: 5518998 (1996-05-01), Backstrom et al.
Bjork, Degradable Startch Microspheres as a Nasal Delivery System for Insulin, ACTA Univ. Appsala, Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 103, 1993.
Bjork, Starch Microspheres as a Nasal Delivery System for Drugs, ACTA Univ. Upsaliensis, Uppsala, Comprehensive Summaries of Uppsala Dissertations from the FAculty of Pharmacy, 103: parts 1-5, 1993.
Komada et al., Intratracheal Delivery of Peptide and Protein Agents: Absorption from Solution and Dry Powder by Rat Lung, J. Pharm. Sci. 83:863-867, 1994.
Lee et al., Internasal Bioavailability of Insulin Powder Formulations: Effect of Permeation Enhancer-to-Protein Ratio, J. Pharm. Sci. 80:725-729, 1991.
Nagai et al., Powder Dosage Form of Insulin for Nasal Administration, J. Controlled Release 1:15-22, 1984.
Schipper et al., Nasal Insulin Delivery with Dimethyl-.beta.-Cyclodextrin as an Absorption Enhancer in Rabbits: Power more Effective than Liquid Formulations, Pharmaceutical Research 10:682-686, 1993.
Trimsina et al., Drug Delivery to the Respiratory Tract Using Dry Powder Inhalers, Int. J. Pharmaceutics 101:1-13, 1994.
Wearley, Recent Progress in Protein and Peptide Delivery by Noninvasive Routes, Critical Reviews in Therapeutic Drug Carrier Systems, 8(4):331-94, 1991.
Backstrom Kjell
Johansson Ann
Linden Helena
Astra Aktiebolag
Benston, Jr. William E.
Page Thurman K.
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