Drug – bio-affecting and body treating compositions – Dentifrices
Reexamination Certificate
1999-07-01
2002-12-03
Gitomer, Ralph (Department: 1623)
Drug, bio-affecting and body treating compositions
Dentifrices
C424S050000
Reexamination Certificate
active
06488912
ABSTRACT:
The present invention is concerned with the combatting tooth and gum infections, in particular severe dental infections which are located within the alveolar region of the jaw.
Oral infections remain a relatively common cause of pain and discomfort to many patients and combatting such infections thus continues to be of clinical importance.
It was originally believed that the primary cause of dentoalveolar infection was a simple combination of Gram positive and Gram negative aerobic bacteria. Improvements in microbiological techniques have however now led to the realisation that such conditions are in fact usually caused by a mixed aerobic/anaerobic bacterial population, with Gram negative anaerobes playing an important part in the polymicrobial process.
The complex aetiology of oral infections results in the observation of widely variable resistance patterns following administration of conventional oral antibacterial preparations. Such preparations may also not be sufficiently active against some of the pathogenic organisms present. There is thus a need for a wide-spectrum agent to treat such mixed infections. Administration of an agent which is ineffective against some of the bacteria present will result in proliferation of the resistant bacterial species and complete elimination of the infection may not be achieved. Typically, the types of bacteria present in dentoalveolar infections include aerobes such as
Streptococcus viridans
qr., Streptococcus gr C., Corynebacterium spy., Neisseria spp and
Haemophilus influenzae.
Anaerobes which are also commonly present include Peptococcus spp:, Bacteroides spp. and Furobacterium spp.
Conventional treatments include bactericidal agents such as chlorophenol-camphor-menthol, chlorhexidine and antibiotics such as chlorteracyclin and tetracinolon. However such agents are not without unpleasant side-effects including allergic reactions, toxic tissue reactions causing inflammation and necrosis, tooth or filling discoloration and affecting the senses of taste and smell. Moreover, conventional agents require a relatively prolonged period of treatment to be completely effective.
The use of Chlortetracycline and Democlocycline is considered inadvisable because of their instability and increased toxicity. It has been shown in this connection, that formation of the highly nephro-toxic anhydro-4-epitetracyclin-hydrochloride occurs in older Tetracycline preparations.
The aminoglycoside antibiotic Neomycin may only be applied locally because of its extreme nephrotoxic, ototoxic and muscle relaxant properties. In this context, it is to be noted that resorption can occur when the ectoderm is damaged (i.e. marginal and apical parodontitis, mucous-membrane ulceration) and repeated usage can lead to analogous side-effects. Because of multiple resistant germ strains and an allergy rate of 15-30%, the withdrawal of this preparation was suggested in 1975. The quinoline derivative Aminoquinuride (Surfen), which increases the spectrum of Neomycin, has not been investigated sufficiently and its effectivity is controversial.
Synthetic corticosteroid derivatives like Prednisolone and Triamcinolone are intended to supercede the role of an analgesic in combination preparations. Although their strong anti-inflammatory and anti-allergic properties make for a quick reduction of pain this would always be accompanied by an immune separation which arises out of a comprehensive inhibition mesenchymal reaction. As well as an inhibition of the lympho-reticular system, damage also arises to the DNA-repair and mitosis capability which can lead to tissue atrophy. The fibrinogen concentration in the plasma is reduced by simultaneously strengthened fibrinolysis. It has been shown that the slow release of the working substance due to the insolubility of glucocortoid, conceals the danger that it will exhaust the efficacy of antibiotic too soon and thereby the infection could either spread unrestrained, or develop into a chronic condition. The unpleasant taste of prednisolone has also proved a deterrant against its use.
Although Chlorophenol-Camphor and Chlorophenol-Camphor-Menthol solutions are often recommended for root canal instillation and no significantly higher or stronger pain sensation following instillation in the pulpen cavity has been reported as against comparative clinical experiments, the high toxic potential is undisputed. In animal experiments strong tissue toxic reactions have been observed in the form of inflammation and necrosis formation.
Chlorhexidine, which has proved itself in extensive experimental and clinical studies as a broad spectrum anti-microbial, is also cell damaging. In tests carried out on human desmodontal fibroblasts, accelerated ageing and a cytopathological effect were demonstrated. The release of p-chloroaniline as a possible by-product of chlorohexidine, which is suspected of causing mutation and of being carcinogenic, is often denied.
It has now been found that taurolidine is effective against oral infections, especially those that are located within the infrastructure of the jaw, but exhibits a much reduced level of side-effects and provides effective relief in a shorter period.
Additionally, administration of suitable taurolidine containing compositions will neutralise bacterially originating endo- and exo-toxins as well as attacking the bacteria themselves.
Taurolidine is a synthetic derivative of the naturally occurring 2-aminoethane sulphonic acid, taurine. The use of taurolidine as a potential anti-microbial substance, acting by a methylol transfer mechanism, has been disclosed in GB 1,124,285. It is sold by Ed. Geistlich Sohne AG. under the registered Trade Mark ‘Taurolin’. The antibacterial substance taurultam is closely related to taurolidine and, indeed, is formed during the methylol transfer reaction between taurolidine and target substances. It is also produced by Ed. Geistlich Sohne AG. Taurultam is slightly more water soluble than taurolidine but possesses fewer methylol transfer groupings.
Taurolidine and taurultam containing toothpastes, toothgels and mouthwashes have also been disclosed in GB 1557163 and it was suggested that such formulations could be used generally in dental care, but were particularly useful in the treatment of parodontosis (a degenerative, non-inflammatory condition of the gums (periodontium) surrounding the teeth which can, result in the destruction of the tissues). The treatment of alveolitis (an infection located within a tooth socket) using a taurolidine gel fine granulate has also been proposed (see Nentwig et al., “Erste klinische Erfahrung mit Taurolin-Feingranulat in der zahnärztlichen Chirugie” in Taurolin-Ein neues Konzept zur antimikrobiellen Chemotherapie chirurgischer Infektion ed. Brückner, 1985, pages 287-289).
However, it was not previously appreciated that taurolidine compositions would be useful in combatting other, more severe dental infections such as gangrene, parodontitis and abscesses. Neither was it known that administration of a taurolidine composition was so much more effective as regards reducing the length of time and the dosage required-for treatment.
Thus, the present invention provides the use of taurolidine and/or taurultam in the preparation of an orally acceptable medicament for combatting severe dental infections or dental infection following dental surgery.
The term “combatting” as used herein includes both therapeutic and prophylactic treatment. The term “severe dental infections” is used herein to refer to those infections which have become established in the interior of the jaw infrastructure, eg. dentoalveolar infections, such as gangrene, parodontitis or dental abscesses.
The condition parodontitis (or periodontitis) is an inflammatory reaction of the tissues surrounding a tooth and can be characterised by formation of periodontal pockets, pus formation, bone resorption, destruction of the periodontal ligament and tooth loss. Parodontitis is a different condition from parodontosis.
One advantage of this aspect of the invention is that the long term pain (to
Geistlich Peter
Pfirrmann Rolf Wilhelm
Ed. Geistlich Soehne AG fuer Chemische Industrie
Gitomer Ralph
Rothwell Figg Ernst & Manbeck
LandOfFree
Treatment of dentoalveolar infections with taurolidine... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treatment of dentoalveolar infections with taurolidine..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treatment of dentoalveolar infections with taurolidine... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2985379