Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Conjugate or complex
Patent
1996-09-25
1999-03-09
Smith, Lynette F.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Conjugate or complex
4241841, 4242341, 4242371, 514 1, 514 2, A61K 39385, A61K 3938, A61K 3902, A61K 3909
Patent
active
058796835
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a novel composition with antibacterial activity and its use. In particular, the composition has activity against methicillin-resistant Staphylococcus aureus (MRSA).
Staphylococcus aureus is a gram-positive bacteria which is recognised in the clinical microbiology laboratory by its ability to make coagulase. S. aureus is often carried by humans. Reference may be made to Bergey's manual of Determinative Bacteriology (9th edition, 1993) for details of further classification of S. aureus. S. aureus may acquire resistance to antibiotics. Patients in hospitals can become infected with MRSA which can lead to serious illness or even death. Strains of S. aureus which can be considered resistant to methicillin are those strains in which growth occurs in the presence of 8 .mu.g/ml methicillin (National Committee for Clinical Laboratory Standards, 1990--Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically (second edition). Document M7-A2. NCCLS, Villanova, Pa., U.S.A.).
MRSA are pathogens of major and growing importance. They are set apart from other Staph. aureus by their resistance to all antibiotics of .beta.-lactam group--e.g. penicillins and cephalosporins. These compounds act on sensitive strains by binding to bacterial proteins called "Penicillin Binding Proteins" (PBPs). In MRSA, one particular PBP, namely PBP2', has altered to such an extent that .beta.-lactam antibiotics bind poorly to it. PBP2' is thus the key to resistance in MRSA. In addition, Staph. aureus has the ability to produce the enzyme .beta.-lactamase. This ability is present in both MRSA and non-methicillin-resistant Staph. aureus. This enzyme destroys benzylpenicillin and ampicillin. Other .beta.-lactam antibiotics such as methicillin or cephalothin are resistant to .beta.-lactamase.
Infections with MRSA can be treated with a group of antibiotics called the glycopeptides; these are expensive and potentially toxic. What is most worrying is that this is the only widely available treatment; resistance to the glycopeptides has emerged in closely related bacteria, and could easily emerge too in MRSA.
From a clinical point of view, glycopeptides such as vancomycin have to be used to treat MRSA; however, the more they are used, the more likely is glycopeptide resistance to emerge. This would leave a lack of any reliable treatment for MRSA infections.
Other types of staphylococcus have methicillin-resistant strains, some of which are resistant due to the presence of PBP2'. Examples are Staph. epidermidis and Staph. haemolyticus, both of which are coagulase negative species.
It has been found that an extract of tea has antibacterial properties. For example, EP-A443,090 shows that an extract of tea at a concentration of about 0.2-2.0 g/100 ml is capable of preventing the growth of a number of types of bacteria, including some strains of MRSA.
In this context, tea refers to the dried, processed leaves of the plant Camellia sinensis. This plant is regarded as a single species, although botanical variants occur and two varieties are recognised: assamica, a large-leaved (15-20 cm) plant and sinensis, a smaller-leaved (5-12 cm) variety. The growing point of the plant, consisting of terminal buds and immature leaves (known technically as "flush"), is picked. Green tea (such as "Sencha" tea) is made from flush by heating, macerating and drying in hot air until the moisture content is reduced to 34%. Black tea is made by allowing flush to wither until the moisture content falls to 50-60% after which it is macerated and then "fermented". This occurs by spreading tea thinly and allowing it to stand at room temperature for 1-3 hours. During this time it turns black due to the action of catechol oxidase on the polyphenols. It is then dried in hot air until the moisture content reaches 3%. A further type of tea, oolong tea, is prepared using a partial fermentation. The processing of tea is described in further detail in the Kirk-Othmer Encyclopedia of Chemical Technology (third edition, 1983), pu
REFERENCES:
patent: 5610139 (1997-03-01), Ohta et al.
Robertson, et al.: Production and HPLC analysis of Black tea theaflavins . . . : Phytochemistry: vol. 22, No. 4: pp. 883-887, 1983.
Database WPI, Section Ch, Week 9107 Derwent Publications Ltd., London, GB; Class A96, AN91-047285 & JP-A-02 311 474 (Ito En KK), 27 Dec. 1990.
Database WPI, Section Ch, Week 9008 Derwent Publications Ltd., London, GB; Class B04, AN 90-054131 & JP-A-02 006 499 (Taiyo Kagaku KK), 10 Jan. 1990.
Nelson Brem
Royal Free Hospital School of Medicine
Smith Lynette F.
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