Drug – bio-affecting and body treating compositions – Topical body preparation containing solid synthetic organic... – Anti-infective
Reexamination Certificate
2001-05-14
2002-10-01
Dees, Jose′ G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Topical body preparation containing solid synthetic organic...
Anti-infective
C424S422000, C424S430000, C128S837000, C128S844000, C128S918000, C514S934000
Reexamination Certificate
active
06458346
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the prevention of pregnancy and the prevention and control of sexually transmitted and other diseases with the use of compositions having broad spectrum microbicidal and spermicidal activity, including the ability to inactivate particularly resistive pathogens such as human papillomaviruses and other non-enveloped viruses.
BACKGROUND OF THE INVENTION
Sexually transmitted diseases (STDs) are among the most prevalent and communicable diseases and continue to be a significant public health problem. It is e stimated that more than 250 million people worldwide, and close to 3 million people in the United States, are infected annually by gonorrhea. Annual worldwide incidence of syphilis is estimated at 50 million people, with 400,000 in the United States annually needing treatment. More recently, the human immunodeficiency virus (HIV), resulting in fatal acquired immunodeficiency syndrome (AIDS), has spread rapidly in both homosexual and heterosexual groups. The World Health Organization (WHO) and the National Institute for Health (NIH) recommend that mothers who are HIV positive not nurse their babies because of a high risk of transmitting HIV in breast milk. However, failure to nurse often results in infant malnutrition, diarrhea, dysentery, and other infectious diseases, because areas with high endogenous HIV often also have low food stores and poor hygienic quality of food and water.
Strong associations have now also been discovered between cervical cancer and papillomaviruses (PVs). It has been estimated that about 25% of women worldwide have human papillomavirus (HPV) genital infection. The human papillomaviruses (HPVs), of which there are now more than 90 known types, cause papillomas (warts) in a variety of human epithelial targets including common warts of the hands (
verruca vulgaris
) and feet (plantar warts), as well as genital warts in vulvar, vaginal, cervical and penile epithelium. Genital warts represent a ubiquitous STD. Women with genital lesions containing certain HPV types, including types 16, 18, 31, 33 and 35, are at increased risk for progression to cervical cancer. In the United States, 15,000 women per year are diagnosed with cervical cancer, and there are about 5000 deaths per year. In developing countries, cervical cancer is the leading cause of cancer related deaths among women.
PVs present a unique challenge for investigators attempting to identify virucidal agents. PVs are inherently extremely resistive to attack by antimicrobial agents. In addition, PVs do not exist free in nature in the same manner that many non-enveloped viruses exist. Rather, PVs exist encased in the squames of differentiated epithelial cells. Thus, the PVs are not only protected by their own very difficult to penetrate capsids, but also by the surrounding, heavily keratinized and cross-linked squames of epithelial cells.
One approach to the general control of STDs is the use of topically applied, female controlled microbicides that inactivate the relevant pathogens. Most frequently, these microbicides are spermicidal preparations containing NONOXYL-9 (N-9) detergent that inactivates enveloped viruses, such as HSV-2 and HIV-1. To date, these preparations have not been effective, however, against non-enveloped viruses such as the HPVs.
Inability to inactivate HPVs makes N-9 an inadequate virucide against this STD. In addition, chronic use of N-9 was recently associated with increased seroconversion for positivity to HIV-1 antibodies in a group of prostitutes, raising the possibility that N-9 may erode vaginal epithelium. Frequent use of N-9 is also positively correlated with bacterial vaginosis, genital ulcers and vulvitis, vaginal candidiasis, toxic shock syndrome, and epithelial disruption of the cervix and the vagina. The detergent, however, is spermicidal and has been shown to inactivate enveloped viruses. It is present in a large number of condoms and other spermicidal agents.
Other microbicides, such as octoxynol-9 (O-9), benzalkonium chloride (BZK) and chlorhexidine, are also surfactants that can disrupt the envelopes of HSV-2 and HIV-1 via surfactant/detergent properties. Like N-9, however, these microbicides also do not inactivate the non-enveloped PVs. Topical microbicides for inactivation of the PVs and prevention of animal or human transmission are currently not available, but would be highly desirable given the ubiquous nature of HPV infections.
U.S. Pat. No. 5,004,757 is directed to a method of deactivating viruses on surfaces by applying a three-part composition containing gluteraldehyde. The composition also contains hydrogen-bonded glycol molecules to eliminate aldehyde odor, and an anionic surfactant such as sodium dodecyl sulfate (SDS) as a potentiator of the virucidal activity of the gluteraldehyde component. The patent indicates that SDS has limited virucidal activity on its own, but has a synergistic effect when combined with gluteraldehyde. Due to the presence of gluteraldehyde, a well-known mu tagen, the formulation is not useful against STDs or other diseases because it cannot be applied to human epithelium.
What is needed are safe and effective microbicides against STDs which extend microbicidal activity to non-enveloped viruses and, in particular, to papillomaviruses.
SUMMARY OF THE INVENTION
The present invention provides pharmaceutical compositions, articles and methods for preventing pregnancy and transmission of STDs, including safe and effective vaginal compositions for controlling and preventing STDs. The microbicidal compositions of the invention contain an alkyl sulfate, such as SDS, lithium dodecyl sulfate, lauric acids or salts thereof, as an active ingredient capable of inactivating sperm and a broad spectrum of pathogenic microbes, including HPVs and other non-enveloped viruses.
Additionally, the present invention provides articles and methods for inactivating infectious agents such as free HIV and cell-associated HIV as well as non-enveloped viruses, such as HPVs, human papoviruses, human picornavirus (hepatitis A virus), and human parvovirus, B-19, in biological fluids, including, for example, human and animal breast milk, serum and plasma. These articles and methods are provided by attaching SDS or an SDS derivative to a surface or gel matrix in contact with the fluid to be treated or by rapid surfactant removal of the SDS or SDS derivative from the fluid after treatment with the surfactant. In a particularly preferred embodiment, the surface having the surfactant attached thereto is positioned within a baby nursing bottle.
The invention also provides alkyl sulfate topical pharmaceutical compositions and methods for prophylactic avoidance and treatment of various medical conditions which involve bacterial or viral infection of the mucous membranes or skin.
The present invention also provides disinfectant compositions for destroying pathogenic microbes on medical instruments, shower stalls, bathroom fixtures, exercise equipment and other inanimate surfaces, as well as spermicidal barriers coated or impregnated with an alkyl sulfate compound for combined spermicidal and microbicidal effects.
It is interesting and surprising to note that, although SDS has been known for several years to have limited activity against enveloped viruses, and has been used as a surfactant for soaps, cosmetics and various other topical applications, such as shampoos and toothpastes, there have been no reports of its use, or the use of other topical antimicrobics, to control PVs. If indeed any such use occurred, it was unintended and unappreciated; it was an unrecognized accident. None of the reported studies or uses of SDS were conducted with the intent of controlling papillomavirus infections. Their purpose was merely as a surfactant/detergent, or at best as a facilitator of the antimicrobial activity of gluteraldehyde. There is, in fact, no known prior use of SDS for topical application which can be considered to have consistently achieved virucidal activity, as described hereinbelow.
REFERENCES:
patent: 50
Howett Mary K.
Krieder John W.
Dees Jose′ G.
Haghighatian M.
The Pennsylvania State University
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