Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-12-18
1998-11-03
Houtteman, Scott W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530331, A61K 4742
Patent
active
058308652
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a new improved storage stable intravenous formulation for infusion of thrombin inhibitors, especially of the peptidic thrombin inhibitors HOOC-CH2-(R)Cha-Pic-Nag and HOOC-CH2-(R)Cgl-Aze-Pab, respectively, to a process for the preparation of said formulation and to a method for treatment by administration of said formulations.
BACKGROUND OF THE INVENTION
Thrombin inhibitors are expected to be effective drugs in a number of diseases characterised by hypercoagulation. Their therapeutic use will be facilitated if stable formulations are available, i.e. formulations having a long shelf-life when stored at room-temperature.
In WO 93/11152, Example P1, a water solution for parenteral administration is disclosed, said formulation is an acetate buffer-solution of HOOC-CH.sub.2 -(R)Cha-Pic-Nag .times.2HBr for parenteral use of pH 3-7, which is within the physiologically acceptable pH range suitable for injections directly into the human body. This solution also includes additives such as sodium chloride to get an isotonic solution.
The active compound HOOC-CH.sub.2 -(R)-Cgl-Aze-Pab is disclosed in PCT/SE94/00535, filed 2 Jun. 1994 now WO 94/29336, published Dec. 22, 1994. Example P2 in this document describes a solution for parenteral administration, namely a water solution of an active compound and sodium chloride, which is adjusted with NaOH to pH 3-9, preferably 5-7.
The stability of peptides is generally a problem in the pharmaceutical industry. Pharmaceutical formulations, especially with a low concentration of peptides, often loose activity during storage.
Each peptide is different with regard to pharmacological properties. When preparing a pharmaceutical formulation of a specific peptide, consideration can not only be taken to the pharmacological properties of the peptide but also other aspects must be considered such as the industrial manufacture, easy and convenient storage and handling for the hospital staff and safety for the patient. The results of these aspects are not predictable when testing different formulations and each peptide often has a unique solution regarding stability.
It is well known that peptides generally are more susceptible to degradation in an acidic or basic environment than in a neutral solution. However, unexpectedly it has been found that for the peptidic thrombin inhibitors HOOC-CH.sub.2 -(R)-Cha-Pic-Nag and HOOC-CH2-(R)Cgl-Aze-Pab their storage stability is improved in acidic aqueous solutions.
DISCLOSURE OF THE INVENTION
The scope of the present invention is a storage stable concentrated, water solution for intraveneous infusion of an active thrombin inhibitor the formula range from 1.0 to 2.5, which solution does not require special storage conditions but can be stored at room temperature, i.e. between 15.degree.-30.degree. C., preferably between 18.degree.-28.degree. C., tentatively 25.degree. C.
Thus, the stable water solution of the present invention which is a concentrated water solution of a thrombin inhibitor, is adjusted with a physiologically acceptable organic or inorganic acid, preferably an inorganic mineral acid such as hydrochloric acid, hydrobromic acid etc., for obtaining the desired pH. The hydrochloric acid is most particularly preferred. The formulation is a straight forward one without any stabilising additives.
In an acidic solution the solubility of the two different drugs, respectively, increases and a more concentrated solution can be produced, which means that small containers which are easy to handle can be used.
It is of importance that the pharmaceutical formulation is easy to handle and to dose. Therefore said formulation suitably should be provided in containers intended for parenteral use, such as plastic or glass containers, e.g. vials, ampoules or prefilled syringes, and be added to infusion bags or bottles i.e. the storage stable concentrated water solution must be diluted before the administration to the patients.
An additional improvement is that the solutions do not require addit
REFERENCES:
patent: 5466131 (1995-11-01), Maraganore
WO 94/29336; Antonsson et al., Abstract, in WPI database, entry No. 95-036397/05, Dec. 1994.
Stjernfelt Ulla
Sundgren Mats
Astra Aktiebolag
Houtteman Scott W.
LandOfFree
Storage stable water solution for infusion containing a thrombin does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Storage stable water solution for infusion containing a thrombin, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Storage stable water solution for infusion containing a thrombin will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-689174