Drug – bio-affecting and body treating compositions – Solid synthetic organic polymer as designated organic active... – Aftertreated polymer
Reexamination Certificate
2001-05-01
2004-05-04
Page, Thurman K. (Department: 1616)
Drug, bio-affecting and body treating compositions
Solid synthetic organic polymer as designated organic active...
Aftertreated polymer
C424S078080, C424S078170, C424S078270
Reexamination Certificate
active
06730295
ABSTRACT:
BACKGROUND OF THE INVENTION
The development of antimicrobial chemotherapeutic agents has significantly reduced the morbidity and mortality associated with bacterial infections over the last century, particularly in developed countries. However, the emergence of drug-resistant bacterial strains threatens the resurgence of diseases long thought to have been conquered. For example, a growing number of cases of drug-resistant tuberculosis have been reported since the mid-1980s, and a recent increase in multiple drug resistant
Staphylococcus aureus
infections has been observed. As the prevalence of drug-resistant bacteria increases, there is a growing need for new antibacterial agents which are suitable for use against a variety of bacterial targets.
SUMMARY OF THE INVENTION
The present invention relates to the discovery that certain anionic polymers have useful antibacterial activity.
In one embodiment, the invention provides a method of treating a bacterial infection in a patient. The method comprises the step of administering to the patient a therapeutically effective amount of a polymer selected from the group consisting of poly(undecenesulfate), poly(undecenephosphate), poly(undecenesulfonate), poly(styrenesulfonate), poly(undecenoic acid-co-undecenesulfate) and poly(monoalkylmaleic acid).
The invention further relates to pharmaceutical compositions comprising one or more polymers comprising pendant anionic groups in a therapeutically effective amount.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a method of treating a bacterial infection in a patient, for example, a mammal, such as a human, by administering to the patient a therapeutically effective amount of a polymer selected from poly(undecenesulfate), poly(undecenephosphate), poly(undecenesulfonate), poly(styrenesulfonate), poly(undecenoic acid-co-undecenesulfate) and poly(monoalkylmaleic acid), copolymers or pharmaceutically acceptable salts thereof.
The polymer can be administered in the acid form, in which 0-100% of the acidic groups are protonated, or in the conjugate base form, wherein 0-100% the acidic functional groups are deprotonated and carry a negative charge. In the conjugate base form, the negative charge of the polymer is balanced by a suitable number of counter cations, such as alkali metal ions, for example, sodium, potassium or cesium ions; alkaline earth metal ions, such as magnesium ions or calcium ions; transition metal ions; or substituted or unsubstituted ammonium, (tetraalkylammonium ions, for example). In one embodiment, the cation is a polyvalent metal ion, such as Ca
2+
, Mg
2+
, Zn
2+
, A1
3+
, Bi
3+
, Fe
2+
or Fe
3+
.
As used herein, a “therapeutically effective amount” is an amount sufficient to inhibit or prevent, partially or totally, a bacteral infection or to reverse the development of a bacterial infection or prevent or reduce its further progression.
The polymer to be administered will, preferably, be of a molecular weight which is suitable for the intended mode of administration and allows the polymer to reach and remain (to the extent and duration necessary) within the targeted region of the body. For example, a method for treating an intestinal infection can utilize a polymer of sufficiently high molecular weight to resist absorption, partially or completely, from the gastrointestinal tract into other parts of the body. The polymers can have molecular weights ranging from about 1 to about 1 million Daltons or more, such as about 500 or about 2,000 Daltons to about 500,000 Daltons, about 5,000 Daltons to about 150,000 Daltons or about 25,000 Daltons to about 1 million Daltons.
In a preferred embodiment, the polymer to be administered is selected from the group consisting of poly(undecenesulfate), poly(undecenephosphate), poly(undecene-sulfonate), poly(styrenesulfonate), poly(undecenoic acid-co-undecenesulfate) and poly(monoalkylmaleic acid), where the alkyl group is a linear or branched C
2
-C
12
-alkyl group. The polymers can include copolymers, such as polymers manufactured by copolymerizing an alkyl-substituted vinyl (e.g., a C
2
-C
12
alkyl, such as styrene.
The bacterial infection is, preferably, an infection by a bacterial species selected from the group consisting of Neisseria species, such as
Neisseria meningitidis
and Branhamella species, such as
Branhamella catarrhalis.
The infection can be a systemic infection or a localized infection. Preferably, the infection is localized to one or more of the oral cavity, the eye, the gastrointestinal tract, including the throat and colon, the skin and the ear, such as the ear canal or the middle ear.
In one embodiment, the bacterial infection is an infection by
Streptococcus sanguis
and the polymer which is administered is poly(styrene sulfonate), poly(undecenesulfate) or poly(undecenesulfonate). The poly(styrene sulfonate) is preferably administered in the anionic form in combination with a suitable cation, as described above. For example, the polymer which is administered can be poly(styrene sulfonate, Na
+
).
In yet another embodiment, the bacterial infection is an infection by
Neisseria meningitidis
and the polymer to be administered is poly(styrene sulfonic acid); poly(styrene sulfonate), poly(undecenesulfonate), poly(undecenesulfate), poly(undecenoic acid-co-undecenesulfate) or poly(monoalkylmaleic acid), where the alkyl group is a linear or branched C
2
-C
12
-alkyl group, preferably a decyl group.
In a further embodiment, the infection is an infection by
Branhamella catarhallis
(formerly,
Moraxella catarhallis
), and the polymer which is administered is poly(styrenesulfonate), poly(styrenesulfonic acid), poly(undecenoic acid), poly(undecenesulfate) and poly(undecenoic acid-co-undecenesulfate).
The quantity of a given polymer to be administered will be determined on an individual basis and will be determined, at least in part, by consideration of the individual's size, the severity of symptoms to be treated and the result sought. The polymer can be administered alone or in a pharmaceutical composition comprising the polymer, one or more acceptable carriers or diluents and, optionally, one or more additional drugs, such as antibiotics, antiinflanmuatory agents or analgesia.
The polymer can be administered systemically or non-systemically, for example, by subcutaneous or other injection, intravenously, topically, orally, parenterally, transdermally, or rectally. The route of administration selected will generally depend upon whether the infection is systemic or localized. The form in which the polymer will be administered, for example, powder, tablet, capsule, solution, or emulsion, will depend on the route by which it is administered. The therapeutically effective amount can be administered in a single dose or a series of doses separated by appropriate time intervals, such as hours. Preferably, the polymer is administered non-systemically, for example, orally or topically, for example, by application to the skin, the eye, oral tissue, such as the oral mucosa, or gastrointestinal mucosa.
The polymers of this invention can be administered to the patient by themselves or in pharmaceutical compositions in which they are mixed with one or more suitable carriers and/or excipients at doses to sufficient to treat the microbial infection. Mixtures of these compounds can also be administered to the patient as a simple mixture or in suitable formulated pharmaceutical compositions. Techniques for formulation and administration of the compounds of the instant application are known in the art and can be found, for example, in “Remington: the Science and Practice of Pharmacy,” 19
th
edition, Mack Publishing Co., Easton, Pa. (1995).
The polymers of use in the present method are preferably substantially non-biodegradable and non-absorbable. That is, the polymers do not substantially break down under physiological conditions into fragments which are absorbable by body tissues. The polymers preferably have a non-hydrolyzable backbone, which is substantially inert un
Barker, Jr. Robert H.
Fitzpatrick Richard J.
Genzyme Corporation
George Konata M.
Hamilton Brook Smith & Reynolds P.C.
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