Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-11-09
2003-04-08
Cook, Rebecca (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06545039
ABSTRACT:
The invention relates to a process for the administration of racemic &agr;-lipoic acid or its enantiomers or pharmaceutically acceptable salts, esters or amides thereof within a certain rate range.
&agr;-Lipoic acid is a naturally occurring antioxidant and a cofactor of the glucose-metabolizing pyruvate dehydrogenase (Packer, L. et al., Free Radicals in Biology & Medicine 19 (2): 227-250; 1995) and is used to a wide extent for the treatment of diabetic polyneuropathy (Ziegler, D. et al., Diabetologia 38: 1425-1433; 1995). Moreover, &agr;-lipoic acid has been used for decades for the treatment of liver disorders (Bode, J. Ch. et al., DMW 112 (9), 349-352; 1987) and fungal intoxications (Brunn, J. et al., Internist. Prax. 19: 475-478, 1979). The molecular mode of action has recently been characterized as that of a diabetes-specific antioxidant (Nagamatsu, M. et al., Diabetes Care 18 (8): 1160-1167; 1995).
Medicaments containing &agr;-lipoic acid are obtainable in the form of tablets for oral assimilation as well as ampoules and ready-to-use infusion devices for infusion or intramuscular injection. According to standard technical information &agr;-lipoic acid injection solution, BfArM 8.3.96, No. Fi44002V.doc, of the Federal Institute for Pharmaceutical Products (BfArM), i.v. injection was previously restricted to low infusion rates and i.m. injection was not recommended. The parenteral products contain water-soluble salts of &agr;-lipoic acid. At present, the trometamine salt, the ethylenediamine salt and the meglumine salt are used. The tolerability is regarded as dose-dependent (Ziegler, et al., loc.cit.). In the above-mentioned information of the BfArM, the physician is explicitly warned against carrying out the administration more rapidly than 50 mg of &agr;-lipoic acid or an equivalent amount of the salt per minute.
Resulting from this, the parenteral administration of &agr;-lipoic acid until now has been dependent on clinical or clinic-like infrastructures in medical practice such as a bed for the infusion and technical assistance during the infusion period. The acceptance of the patient is usually adversely affected by this time-consuming mode of administration. The costs of the administration are increased by the necessity of additional solutions for the dissolution of the active compound or dilution of concentrated solutions. The parenteral administration of the products in general medical practice is nearly impossible under these circumstances and the oral formulations predominate in the case of prescriptions (Rathmann, W. et al., Pharmaepidemiology and Drug Safety 7: 51-57; 1998).
This preference of the oral formulations, however, can only be regarded as suboptimal for the success of treatment in many patients, because the oral formulations have a critical bioavailability with high inter- and intraindividual variations and are associated with additional problems such as the in-vivo interaction with foodstuffs (Gleiter, C. H. et al., Eur. J. Clin. Pharmacol., 50: 513-514, 1996; Hermann, R. et al., Eur. J. Pharm. Sci., 4: 167-174, 1996). Oral formulations are therefore only second choice for reasons of bioavailability.
The aim of the invention is to create a process which is equally easy to carry out in medical practice and is tolerable for the patients and also ensures an optimal bioavailability.
Surprisingly, it has been found that the trometamine salt of racemic &agr;-lipoic acid can be administered at an infusion or injection rate of more than 200 to 1200 mg of active compound, based on &agr;-lipoic acid.
The product can thus be administered in a simple manner as a direct intravenous injection in the course of less than twelve, better still six or three minutes, in fact even within one minute. Clinical or clinic-like infrastructures are no longer necessary. Cost-intensive infusion sets and dilution solutions are likewise unnecessary. Optimal administration of &agr;-lipoic acid with clearly reduced costs is achieved, which can benefit more patients than previously, since the administration can be carried out in any medical practice and the patients agree more willingly.
The process according to the invention can preferably be practised by direct manual i.v. injection but also by rapid infusion using an infusion device or using an automatic infusion pump, e.g a perfusor, which can also be provided with a butterfly needle.
The infusion or injection solution used according to the invention can be withdrawn from ampoules or ready-to-use infusion or injection bottles by syringes, it also being possible to use a butterfly needle for withdrawal from bottles.
The ampoules or bottles have a volume of 4 to 120 ml, preferably 4 to 24 ml, ampoules more likely being in the lower range and bottles in the upper range, and contain 25 to 1200 mg of active compound, preferably 200 to 1200 mg of active compound, based on &agr;-lipoic acid.
The following examples illustrate the invention without restricting it.
REFERENCES:
patent: 4411649 (1983-10-01), Kamen
patent: 5445621 (1995-08-01), Poli et al.
patent: 5948810 (1999-09-01), Wessel et al.
patent: 5990153 (1999-11-01), Wood et al.
patent: WO 99/55331 (1999-11-01), None
Auge Mechthild
Hermann Robert
Wessel Klaus
Wicke Claudia
Cook Rebecca
Hobbs Ann S.
Viatris GmbH & Co. KG
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