Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2000-11-28
2004-01-13
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S431000, C514S967000, C514S843000, C514S841000
Reexamination Certificate
active
06676957
ABSTRACT:
BACKGROUND
Some microbial products may affect the human host. For example,
Staphylococcus aureus
(
S. aureus
) can produce and excrete into its environment a variety of exoproteins including enterotoxins, Toxic Shock Syndrome Toxin-1 (TSST-1), and enzymes such as proteases and lipase.
S. aureus
is found in the vagina of approximately 16% of healthy women of menstrual age. Approximately 25% of the
S. aureus
isolated from the vagina are capable of producing TSST-1. TSST-1 and some of the staphylococcal enterotoxins have been identified as causing Toxic Shock Syndrome (TSS) in humans.
Menstrually occurring toxic shock syndrome (TSS), a severe and sometimes fatal multi-system disease, is associated with colonization by
Staphylococcus aureus
. This disease has been associated with the use of tampons during menstruation. The disease is caused by toxic shock syndrome toxin-1 (“TSST-1”) and other staphylococcal enterotoxins.
Symptoms of TSS generally include fever, diarrhea, vomiting and a rash followed by a rapid drop in blood pressure. Systemic vital organ failure occurs in approximately 6% of those who contact the disease.
S. aureus
does not initiate TSS as a result of the invasion of the microorganism into the vaginal cavity. Instead as
S. aureus
grows and multiplies, it can produce TSST-1. Only after entering the bloodstream does the TSST-1 toxin act systemically and produce the symptoms attributed to Toxic Shock Syndrome.
There have been numerous attempts to reduce or eliminate pathogenic microorganisms and menstrually occurring TSS by incorporating into a tampon pledget one or more biostatic, biocidal, and/or detoxifying compounds. For example, L-ascorbic acid has been applied to a menstrual tampon to detoxify toxin found in the vagina of the human female during menstruation.
Others have incorporated monoesters and diesters of polyhydric aliphatic alcohols and a fatty acid containing from 8 to 18 carbon atoms. For example, glycerol monolaurate (GML) has been used to retard the production of
S. aureus
enterotoxins and TSST-1. However, as noted above, esterase is abundantly present in the vaginal epithelium and menstrual fluid. This esterase, in combination with esterase and lipase produced by, bacteria can enzymatically degrade the esters into non-effective compounds. Thus, one or more ester compounds may have to be added to the absorbent article, such as a tampon pledget, in sufficiently high concentrations to detrimentally effect the normal flora present in the vaginal area. When the natural condition is altered, overgrowth by pathogen(s) may take place resulting in a condition known as vaginitis. The use of other non-ionic surfactants, such as alkyl ethers, alkyl amine and alkyl amides, has been reported as a means of avoiding the problem of degradation by esterase (see, e.g., U.S. Pat. Nos. 5,685,872; 5,618,554 and 5,612,045).
Accordingly, there continues to exist a need for agents that will effectively inhibit the production of exoproteins, such as TSST-1, from Gram positive bacteria. The material may be coated on a non-absorbent substrate or have the agent incorporated in other forms, e.g., or in the form of an absorbent product or formulated with a pharmaceutically acceptable carrier. Such agents preferably would be substantially unaffected by the enzymes lipase and esterase and, in addition, should not substantially alter the natural flora found in the vaginal area. The selection of active compounds to inhibit the production of exoproteins is not so readily apparent as some surface active compounds, such as block copolymers of propylene oxide and ethylene oxide, can stimulate toxin production by Gram positive bacteria.
SUMMARY
It has been found that alkyl polyglycoside compounds can inhibit the production of exoprotein(s) of Gram positive bacterium. Exposure to effective amounts of the alkyl polyglycoside(s) can inhibit the production of harmful toxins, such as those produced by Staphylococcus and/or Streptococcal species. For example, alkyl polyglycoside(s) can be utilized to inhibit the production of TSST-1, alpha toxin and/or enterotoxins A, B and C from
S. aureus
bacterium. The alkyl polyglycoside typically has an hydrophilic/lipophilic balance (“HLB”) of at least about 10 and/or an average number of carbon atoms in the alkyl chain of about 8 to about 12. The alkyl polyglycoside may be used alone or in combination with one or more other surface active agents, e.g., in combination with compounds such as myreth-3-myristate, glycerol monolaurate and/or laureth-4.
The present invention relates to non-absorbent substrates for use in inhibiting the production of exoproteins from Gram positive bacteria. The substrates are particularly useful for inhibiting the production of TSST-1, alpha-toxin and/or enterotoxins A, B and C from
S. aureus
bacteria. Examples of suitable non-absorbent substrates which have alkyl polyglycoside incorporated in or on at least a portion of the device include non-absorbent incontinence devices, barrier birth control devices and contraceptive sponges. One example of a non-absorbent incontinence device is a female barrier incontinence device, such as an incontinence pledget formed from a resilient material like rubber. Another suitable a non-absorbent substrate is the applicator used with a tampon. For example, the applicator may have alkyl polyglycoside coated on an outer surface, such that when the applicator is used to introduce a tampon into a women's vagina alkyl polyglycoside (e.g., formulated in a cream or wax) is transferred from the applicator onto the wall of the vagina. The non-absorbent substrates typically contain at least about 3 wt. % and, preferably, about 5 to about 10 wt. % alkyl polyglycoside (as add-on wt. %).
The present alkyl polyglycosides are materials which, when exposed to
S. aureus
or other Gram positive bacteria in absorbent products, can reduce the production of exoproteins, such as TSST-1 toxin. It is also believed that the active compounds in the compositions of this invention are effective in combating the production of other types of bacterial toxins, in particular, alpha toxin and Staphylcoccal enterotoxins A, B, and C. The alkyl polyglycosides described herein are also effective at inhibiting the production with respect to these aforementioned exoproteins when the active compound is placed on an absorbent material or caused to come into contact Gram positive bacterium in other forms, e.g., when formulated with a pharmaceutically acceptable carrier or incorporated in or on a non-absorbent substrate.
The present alkyl polyglycosides are particularly useful for inhibiting the production of bacterial exotoxins when incorporated as part of non-absorbent products. For example, the incorporation of alkyl polyglycoside onto an outer surface of a non-absorbent product, such as an incontinence device, can be very effective. The non-absorbent products are exemplified herein in connection with incontinence or contraceptive devices but would be understood by persons skilled in the art to be applicable to other disposable non-absorbent articles where inhibition of exoproteins from Gram positive bacteria would be beneficial.
When employed as part of an incontinence or contraceptive devices or otherwise introduced into a region affecting the vagina, the alkyl polyglycoside preferably is utilized in a manner and amount so as to minimize its effect on the natural vaginal flora. The present alkyl polyglycoside compositions are generally capable of substantially inhibiting the production of exoproteins from Gram positive bacteria, e.g., by reducing the amount of proteins produced by at least about 75% and preferably by at least about 90%.
The alkyl polyglycoside compositions of the present invention may additionally include adjunct components conventionally found in pharmaceutical compositions in their art-established fashion and at their art-established levels. For example, the compositions may contain additional compatible pharmaceutically active materials for combination therapy, such as supplementary antim
Resheski-Wedepohl Kim L.
Syverson Rae Ellen
Bennett Rachel M.
Kimberly--Clark Worldwide, Inc.
Page Thurman K.
Senniger Powers Leavitt & Roedel
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