Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
1993-01-07
2001-05-15
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
active
06232349
ABSTRACT:
Research worldwide is currently underway to develop treatments and cures for Herpes Simplex Virus (HSV) Types 1 and 2. Both HSV Types 1 and 2 show a predilection for infection of the ectodermal tissues wherein such infections by the virus cause lesions in the skin, oral cavity, vagina, conjunctiva, and the nervous system. Generally, infection by HSV Type 1 (HSV1) is associated with oral, facial and ocular lesions. Infection by HSV Type 2 (HSV2) generally results in genital and anal lesions. HSV infections left untreated often lead to blindness, neonatal deaths, and encephalitis. HSV Type 2 infections are at an epidemic portion in the U.S. from venereal transmission. Greater than some twenty million persons are presently afflicted with the disease in this country with new cases and recurrences exceeding half a million annually. The annual cost of HSV infections results in a substantial economic loss to diagnose and treat. Epidemiological control of HSV is poor because the majority of the population, up to 90%, has been exposed to the virus.
Man serves as the natural host for HSV Types 1 and 2 infections whereby the virus is transmitted during close personal contact. Initial or primary infections by HSV Types 1 and 2 are contracted through breaks in the mucus membrane. In the healthy carrier the virus can be isolated in the tears, saliva, vaginal and other secretions, even during the absence of overt disease. From the mucus membrane they are able to replicate and spread to the regional lymph nodes. Occasionally these viruses can infect cells of the haemopoietic system and cause viremia.
Part of the difficulty in treating HSV infections results from the ability of these viruses to persist in a latent, or quiescent form. When the primary infection subsides or recedes, the virus generally resides in a latent form in the sensory nerve ganglia which innervate the site of primary infection. In ocular or oral infections with HSV Type 1, the virus generally resides in the trigeminal ganglia. In HSV Type 2 the virus generally resides in the sacral ganglia serving the genitalia and lower abdoman. The determinative period of latency of the HSV virus is unknown, other than this period can be upset by heat, cold, sunlight, hormonal and emotional disturbances, or by immunosuppressive agents, resulting generally in a recurrent infection.
Treatment of HSV infections have largely been ineffective. A number of strategies to stop the virus have been developed. These agents generally inhibit any one of a number of specific viral functions such as (1) adsorption, (2) uncoating, (3) transcription, (4) protein synthesis, (5) nucleic acid replication, (6) maturation, and (7) release.
Most of the antiviral agents thus far used to treat HSV infections have been compounds that interfere with viral DNA. These compounds include Idoxuridine, Cytosine Arabinoside, Adenine Arabinoside, and Trifluorothymidine. Such agents also interfere with similar host functions which results in general problems with cell toxicity and systemic use in humans. Presently, acyclovir is the preferred medication to treat infections with HSV1 and HSV2 due to its potent antiviral effect and negligable toxicity. Poor solubility at high dosage and the emergence of drug-resistant viruses, however, limit the use of this drug.
A number of RNA and DNA containing viruses have envelopes into which virus-coded glycopeptides are incorporated. HSV and cytomegalovirus (CMV) are two such enveloped viruses. Infection of a host cell by enveloped viruses initially relies on the interaction of various receptors on the host cell surface with the envelope glycoproteins of the viral membrane. Subsequently the virus and cell membranes fuse and the virion contents are released into the host cell cytoplasm. The glycoprotein containing envelope of the virus plays an important role in both the initial interaction of the virion and the host cell and in the later fusion of the viral and host cell membranes. The viral envelope seems to be derived from the cellular membrane, but the specificity is due to the viral encoded glycopeptides. Therefore, an inhibitor capable of interfering with the formation of the virus-specific membranes may prevent formation of infectious progeny virus.
SUMMARY OF THE INVENTION
The sulfated oligomers of this invention are represented by any one of the following formulae:
A) a polyurea of the formula:
wherein:
R represents a hydrogen atom, a C
1
-C
4
alkyl group, a phenyl group, or a phenyl group substituted with from 1 to 2 R
1
moieties and up to 3 substituents independently selected from a chloro or bromo atom or C
1
-C
4
alkyl group;
R
1
represents —SO
3
R
2
, —CO
2
R
2
, —PO
3
(R
2
)
2
, or —OPO
3
R
2
;
R
2
represents represents a hydrogen atom or a pharmaceutically-acceptable cation;
m is an integer 0 or 1, with the proviso that when m is 0, R is a hydrogen atom;
X represents
Y represents —CO
2
—, —C≡C—, —N═N,
n is an integer from 3 to 50; and
R
3
represents —R or —X—NH
2
, where R and X are defined as before;
B) a polycarbonate of the formula:
wherein
X and n are defined as in Formula I above;
X
1
represents a HO—X— group, where X is defined as for Formula I above, or a C
1
-C
4
alkyl group, a phenyl group, or a phenyl group substituted with from 1 to 2 R
1
moieties and up to 3 substituents independently selected from a chloro or bromo atom or C
1
-C
4
alkyl group; and
X
2
represents a hydrogen atom, or —CO
2
X
1
, where X
1
is defined as above;
C) a polyester of the formula
wherein
X and n are defined as in Formula I above;
R
4
represents —R
2
, as defined in Formula I, or —X
2
, as defined in Formula II above;
R
5
represents
where R
4
is defined as in Formula III above, or —R
2
, where R
2
is defined as in Formula I above;
X
3
represents
wherein R
1
and Y are defined as in Formula I above; or
D) a polyamide of the formula:
wherein
X and n are defied as in Formula I above;
X
3
is defined as in Formula III above;
R
6
represents H
2
N—X—NH—, R
2
O—, RNH— or R—C(O)—NH—X—NH—, where R, R
2
and X are defined as in Formula I;
R
7
represents a hydrogen atom,
where R and R
2
are defined as in Formula I above; and
X
3
is defined as in Formula III above.
DETAILED DESCRIPTION OF THE INVENTION
The oligomers of the present invention are illustrated by polyureas, polycarbonates, polyesters or polyamides having a number average molecular weight Mn of <10,000 comprising recurring units coupled by carbonyl linking moieties, said oligomer having anionic groups and predominantly linear geometry such that regular spacing between anionic groups exists in an aqueous medium. The oligomers are preferably linear in their backbone and also may be in their salt form. Particularly preferred salts are those that are pharmaceutically acceptable.
The term “pharmaceutically acceptable cation” means a cation acceptable for pharmaceutical use. Those cations that are not substantially toxic at the dosage administered to achieve the desired effect and do not independently possess significant pharmacological activity are included within the term “pharmaceutically acceptable cation”. Illustratively, these salts include those of alkali metals, such as sodium and potassium; alkaline earth metals, such as calcium and magnesium; ammonium; light metals of Group IIIA including aluminum; and organic primary, secondary and tertiary amines, such as trialkylamines, including triethylamine, procaine, dibenzylaine, N,N′-dibenzylethylenediamine, dihydroabietylamine, N-(C
1
-C
4
)alkylpiperidine, and any other suitable amine. Sodium and potassium salts are preferred. The term “pharmaceutically acceptable” means suitable for administration to warm blooded animals, especially human beings, and includes being nontoxic, e.g., suitable for pharmacetucial use and is not poisonous to the warm blooded animal. The pharmaceutically acceptable cations of the oligomers of the present invention are prepared by conventional ion exchange processes or by treating the R
1
acid with an appropriate base.
The oligomers of the present invention
Cardin Alan D.
Jackson Richard L.
Mullins Michael J.
Gupta Balaram
Jones Dwayne C.
Merrell Pharamaceuticals Inc
LandOfFree
Anti-herpes virus and cytomegalovirus polyurea oligomers does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Anti-herpes virus and cytomegalovirus polyurea oligomers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anti-herpes virus and cytomegalovirus polyurea oligomers will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2572151