Patent Application: US-104501-A

Abstract:
an aqueous douche or enema is disclosed , containing a water - soluble zinc salt at an anti - viral concentration , designed for use shortly before and / or shortly after intercourse . unlike a lubricant for use during intercourse , this type of rinsing liquid will not contain glycerine or similar lubricating components , and will be designed to not leave behind a film - type residue . however , this type of “ pericoital ” rinse will leave behind positively - charged zinc ions . due to electrostatic attraction , these zn ++ ions will cling to negatively - charged canyons and other “ binding sites ” in proteins that are exposed and accessible on the surfaces of cells and virus particles . the binding of zn ++ ions to negatively - charged sites in these surface proteins will alter and disrupt the ability of viruses to bind to and infect human cells . accordingly , this type of rinse can reduce the risk of infection by sexually transmitted viruses , in a person who is not previously infected . in addition , due to the skin - protective properties of zinc , a pericoital rinse containing a water - soluble zinc salt can help accelerate the healing and closure of microabrasions , lesions , and other breaches or deficits in genital skin or mucous membranes , thereby further decreasing the risk of viral infections following intercourse .

Description:
as summarized above , this invention discloses the use of an aqueous liquid which is designed for use as a vaginal or rectal rinse , in a form directly comparable to a douche or enema . this rinse formulation contains a water - soluble zinc salt , which will release zinc ions at an anti - viral concentration . by using this type of rinse as a douche or enema , shortly before and / or shortly after sexual intercourse , the anti - viral zinc ions can reduce the risk of a previously uninfected person becoming infected by sexually transmitted viruses , such as herpes viruses , human immunodeficiency viruses , hepatitis viruses , and papilloma viruses . this type of rinse is also believed to be able to reduce the risk of infection by other types of sexually transmitted diseases as well , including syphilis , gonorrhea , and chlamydia . to provide maximal protection , this type of zinc - containing douche or enema should be used both before and after each act of intercourse in which there is a significant risk of transmission of a sexually transmitted microbe . however , a substantial degree of protection can be provided by a single use , either before or after intercourse . in particular , a recent report ( vernazza 2001 ) has indicated that hiv particles are actively shed into vaginal fluids , even among women who are taking anti - hiv drugs that suppress viral concentrations in the blood to very low or even undetectable levels . this appears to suggest that , if someone has only a limited supply of an anti - viral rinse , use prior to intercourse may be more beneficial than use after intercourse . however , this will need to be confirmed by actual tests , and if only a single rinsing step is planned , it should be done either very soon before or very soon after intercourse . preferably , an anti - viral zinc rinse as disclosed herein should be used in conjunction with a condom , during intercourse in which a significant risk of hiv , herpes , or other viral transmission exists ; however , since that doesn &# 39 ; t always happen , this type of rinse can be used regardless of whether a condom is also used , to provide at least some increased level of protection . a zinc - containing douche or enema as disclosed herein must be suited in all respects for repeated periodic use , such as several times each week , or on a daily basis . as such , it must be free of any compounds that would inflict gradual accumulating damage , or an accumulating risk of carcinogenicity or other toxicity , when used repeatedly , such as before and after each act of intercourse . as used herein , the term “ rinse ” excludes “ genital lubricants ”. as used herein , a “ genital lubricant ” is a friction - reducing formulation that is effective , desirable , and comfortable , when used topically , as a lubricant , during intercourse . as such , a genital lubricant ( as that term is used herein ) must contain at least one agent that is conventionally used as a lubricating agent . glycerin ( also called glycerine , glycerol , 1 , 2 , 3 - propanetriol , and trihydroxypropane ) and certain types of polyethylene glycol ( peg ), such as peg 200 or peg 400 ( the numbers indicate different molecular weight averages ) are widely used as lubricating agents in topical formulations . various other polymers ( such as polypropylene glycol , polyisobutene , and polyoxyethylene ) and behenic acid and behenyl alcohol are also used as lubricants in cosmetics and other formulations that contact the skin . in addition , some sugar - alcohols such as sorbitol , and some silicon compounds such as polydimethyl - siloxane , are also used as skin and / or genital lubricants . when rubbed between two fingers , it quickly becomes clear that any of these agents will impart a “ slippery ” feel to the skin , in a manner which easily surpasses the lubricating traits of water . as part of its ability to impart sustained lubrication and comfort throughout a complete act of intercourse , an effective genital lubricant must have an affinity for skin . this is evidenced by two distinct but consistent and overlapping factors . first , a lubricant will remain on the skin , as a fairly consistent and uniform coating , for a substantially longer period of time than water , or a rinsing formulation that does not contain a lubricant . the second factor is this : most types of lubricants , if allowed to dry on the skin without being wiped off , will leave a residue , usually in the form of a film , which often goes through a somewhat adherent “ sticky ” phase , and which may remain sticky until washed off . by contrast , a genital “ rinse ”, when defined in a manner that explicitly excludes lubricating ingredients such as glycerin , polyethylene glycol , etc ., will not create the type of coating layer and / or sticky residue that a lubricant will create . a rinse should , instead , behave in a manner which is closer or even directly comparable to the performance of plain water , or salt water , when used to wash off the skin . in the same way that water can be used to rinse off something , a rinse , as defined herein , can also wash things off , and wash things out , in an effective manner that will not leave a sticky residue or film caused by an ingredient in the rinse . however , this does not imply that a rinse will be able to wash off a pre - existing oily layer . just as plain water , when applied gently to a sensitive area of skin , will not cleanly wash off an oily layer , neither should a rinse . a rinse generally should not act as a “ stripping ” agent , and should not contain substantial quantities of solvents , detergents , or surfactants that are designed to break down oils , lipids , or other hydrophobic compounds that are normally present on skin surfaces . nevertheless , it should be recognized that a rinse can contain a moisturizing ingredient , if desired , to counteract the astringent effects of nearly all zinc salts . moisturizing agents which do not function effectively as lubricants are widely used in , for example , hand and face lotions and cosmetics which are non - oily , and which are designed to generate a clean and non - greasy feeling when used . as just one example , aloe vera gel is widely used as a moisturizing agent , but it would not perform adequately as a lubricating agent , if added to a genital lubricant . various other such moisturizing ingredients are known to those who manufacture lotions and cosmetics , and may be incorporated if desired into a rinse formulation as disclosed herein , at appropriate concentrations ( which in most cases are likely to be in the range of about 0 . 1 to 5 %, by weight ). if desired , a rinse ( as defined herein ) may be labelled or otherwise regarded or presented as a rinse , douche , and / or enema formulation . the terms “ douche ” and “ enema ” are used in laymen &# 39 ; s terms throughout this application ; a “ douche ” as used herein is a liquid which is used to rinse out the vaginal cavity , while an “ enema ” as used herein is a liquid which is used to rinse out the rectal cavity . unless otherwise noted , the term “ rinse ” refers to a liquid which can perform at least one and possibly both functions . because preferred formulations for enemas and douches do not differ greatly , an anti - viral zinc rinse as disclosed herein may be suitable for either cavity , and preferred formulations should indeed be suited for either cavity . it should be noted that the anti - viral zinc rinses disclosed herein are intended for rinsing out the vaginal and / or rectal cavities , and not the mouth . some types of mouthwashes contain small quantities of zinc salts , mainly in the form of zinc chloride . accordingly , although it is highly doubtful that such mouthwashes contain enough zinc to function effectively as an anti - viral agent , nevertheless , any mouthwashes or other formulations designed for oral use are excluded from coverage or consideration herein . this invention relates solely to products that are labelled or otherwise clearly intended to include vaginal and / or rectal use . preferred formulations for a zinc - containing rinse as disclosed herein can be based on formulations already in widespread use for douches and enemas . the compositions for such preparations are well - known to companies that market them , or can be determined through simple chemical analysis . however , if any such composition contains an ingredient that would act as a “ chelating ” agent for zinc ions , the chelating agent should be removed , and replaced if necessary by a similar agent that does not have chelating properties . as is known to chemists , chelating relates to a molecular binding reaction , wherein a chelating molecule binds to a certain atom or molecule with a tightness or avidity that effectively sequesters and inactivates the bound atom or molecule . as just one example , vitamin c ( ascorbic acid ) tends to inactivate zinc ions , by binding to them . accordingly , vitamin c should not be included as an ingredient in an anti - viral zinc rinse as disclosed herein . rinse formulations as disclosed herein can be sold in fully hydrated form , if desired . alternately , to reduce bulk , shipping costs , and the risk of storage and leakage problems , and to increase their shelf life , they can be sold as powders or concentrates , which can be converted into rinse formulas by dissolving them in water . they can be packaged in any desired manner , such as in a disposable squeeze bottle with a nozzle , if desired . to maximize anti - viral efficacy when used before intercourse ( i . e ., precoital or pre - coital ), a zinc - containing rinse preferably should be used a reasonable and relatively short period of time before intercourse commences , such as within an hour or possibly two hours before intercourse begins . in general , it is assumed that a rinsing step , using a zinc - containing douche or enema , is likely to have some significant beneficial effect , if carried out at any time within roughly 12 hours ( and possibly more ) prior to intercourse . however , since any viral load in an infected person will tend to return and build up gradually , over a span that can be measured in hours , and since any protective residual zinc ion concentrations that remain on accessible vaginal or rectal surfaces will gradually be absorbed and dissipated over time , a relatively short delay ( such as only an hour , or less ) before intercourse will provide a better margin of safety and protection than a longer delay ( such as more than two hours ). accordingly , as a compromise which is intended to reasonably define and delimit phrases such as “ before intercourse ” or “ prior to intercourse ” in the claims , use of a rinse as disclosed herein within a period of up to 6 hours , prior to commencing intercourse , is deemed to be use “ prior to intercourse ” as covered by the claims below . since zinc salts tend to have an astringent effect , a precoital rinse can be followed by application of a moisturizing and / or lubricating compound ( various vaginal moisturizers are well - known in the art ). if desired , a moisturizer and / or lubricant containing a water - soluble zinc salt can be used , for greater anti - viral efficacy . to maximize anti - viral efficacy when used after intercourse ( i . e ., postcoital or post - coital ), a zinc - containing rinse preferably should be used within about 10 to 15 minutes after ejaculation . this shorter time limitation is based on data reported in zacharopoulos et al 1992 , phillips & amp ; bourinbaiar 1992 , and pearce - pratt & amp ; phillips 1993 , which indicate that within about 15 minutes , hiv - infected lymphocytes commence a cellular process in which infected cells , rather than free virus particles , begin binding to uninfected epithelial cells , and begin shoving large numbers of hiv particles or genomes at and into the epithelial cells . accordingly , use of a zinc - containing rinse within about 15 minutes or less after ejaculation is preferable , since it can reduce the risk of that type of cell - to - cell infection process . however , since the 15 minute period observed in those tests was based on various parameters and conditions ( including high - titer viral concentrations ) that were designed to facilitate easily observable tests with clear outcomes , it is not believed that a 15 minute delay is a rigid boundary line , beyond which using an anti - viral zinc rinse would be a wasted effort . instead , it is believed and assumed that post - coital use of a rinse at any time up to roughly 12 hours after intercourse may be able to significantly reduce the risk of infection . accordingly , as above , a six - hour period following ejaculation is used as a compromise which is intended to reasonably define and delimit phrases such as “ after intercourse ” or “ following intercourse ” in the claims . use of an anti - viral zinc rinse as disclosed herein within a period of up to 6 hours , after intercourse , is deemed to be use “ after intercourse ” as covered by the claims below . since a single rinse as disclosed herein can be used either pre - coitus or post - coitus , this type of rinse is also referred to herein as a “ peri - coital ” rinse . the prefix “ peri -” ( which appears in words such as perinatal , pericardial , etc .) arises from a greek word which means around , near , adjacent , etc . different formulations and additives may be preferred for pre - coital and post - coital rinses , since they will remain in contact with the genital membranes for different periods of time . as one example , a pre - coital rinse might contain a moisturizer , to counteract the astringent effects of zinc salts , while a post - coital rinse might contain a small concentration of vitamin e , retinol , and / or other agent ( s ) that can promote better long - term benefits if allowed to remain in place for a longer period of time . any zinc salt that has adequate solubility in water can be evaluated for use as disclosed herein . candidate organic salts include zinc acetate , zinc lactate , zinc propionate , zinc butyrate , zinc gluconate , zinc formate , zinc glycerate , and zinc glycolate , which are derived from carboxylic acids having a single carboxylic acid group , as well as dicarboxylic acids , such as zinc maleate and zinc malonate . preferred organic salt candidates include zinc acetate , propionate , and / or lactate ( all of which are readily soluble in water ). zinc gluconate is also a preferred candidate , since it has a decades - long record of safe internal use ; it is less soluble in water , but its solubility can be increased by adding glycine or certain other amino acids to the solution , as described in pct patent application wo 01 / 06985 ( godfrey , 2001 ). solubility and dissociation data on these and various other organic zinc salts is provided in table 1 . this table has also appeared in various us patents issued to kelly , as listed above . additional information on those salts ( and certain other salts , as well ) is provided in those patents . zinc lactate is presumed to be preferred for douche formulations , since there are already large quantities of lactate ions in vaginal fluids , and the vaginal epithelium is well - adapted to handling lactate ions . if desired , a mixture of several different salts can be used , and may provide various advantages ; for example , if a 3 % concentration of zinc salt is provided by incorporating 1 % zinc acetate , 1 % zinc lactate , and 1 % zinc gluconate , a balanced blend of three different anions ( acetate , lactate , and gluconate ions ) is less likely to disrupt various chemical equilibria in the vaginal fluids , if the concentration of each type of ion is reduced by using a blend of all three . furthermore , since the dissociation kinetics of different salts are different , a balanced blend of all three salts is likely to provide a more sustained and long - lasting plateau of high concentrations of zinc ions . as an example , zinc acetate , which has very high dissociation rates , can release a large initial surge of anti - viral zinc ions . due to chemical equilibrium factors , this surge of free zinc ions will tend to suppress the early release of even more zinc ions , by zinc lactate . as the surge of zinc ions from zinc acetate gradually subsides and is absorbed , over a span of hours , zinc lactate will begin releasing more zinc ions ; and , as the zinc lactate is gradually depleted of its ions , the zinc gluconate will gradually release more zinc ions . inorganic salt candidates ( such as zinc chloride or zinc sulfate ) can also be evaluated for use as disclosed herein , if desired . however , it should be recognized that they tend to acidify an aqueous mixture , so they may need to be accompanied by a buffer or alkaline neutralizing agent . inorganic zinc salts as candidate anti - viral additives are discussed in more detail in u . s . pat . no . 5 , 980 , 477 ( kelly , november 1999 ). in general , preferred concentrations of zinc salts in anti - viral rinses as disclosed herein are likely to range from about 0 . 5 to about 5 percent , by weight , depending on which particular salt is used . higher concentrations can also be used , if desired . in one preferred approach which takes varying individual factors ( such as skin sensitivity , perceived degree of risk , etc .) into account , an assortment of different rinses with varying zinc concentrations can be sold , and anyone who wishes to use one will be free to try several different concentrations , and choose one based on their own preferences . this is comparable to sunblocking agents being sold with a range of different “ sun protection factors ”. it should also be noted that zinc salts that release zinc ions at very high concentrations ( such as zinc chloride or sulfate ) generally should be used at lower concentrations , while salts that release ions at lower concentrations ( such as zinc gluconate ) can be used at higher concentrations . in addition , a peri - coital zinc rinse as disclosed herein can also contain one or more other anti - microbial or other medical agents ( such as an anti - fungal agent for preventing or treating vaginal yeast infections ), formulated in a manner and concentration which establishes maximum compatibility , efficacy , and synergistic effects when combined and administered along with zinc ions in a non - viscous formulation . such formulations can be regarded as “ zinc boosted ” formulations , which are designed to be applied topically to one or more genital surfaces or mucus membranes shortly before or after intercourse . in at least some users , peri - coital formulations of this nature can help promote more regular , consistent , and efficacious use of other active pharmaceutical agents . various examples , confirming that water - soluble organic zinc salts did not cause any irritation in human volunteers when added to genital lubricant formulations and used during actual intercourse , are provided in the above - cited us patents issued to kelly . those examples are incorporated herein by reference , to support the assertion that zinc salts , when dissolved in aqueous solutions at appropriate concentrations , do not irritate the highly sensitive genital membranes . thus , there has been shown and described a new and useful means for creating pre - coital and post - coital rinses containing anti - viral water - soluble zinc salts that , when used shortly before or shortly after intercourse , can reduce the risk of infection by sexually transmitted viruses and possibly other microbes as well . although this invention has been exemplified for purposes of illustration and description by reference to certain specific embodiments , it will be apparent to those skilled in the art that various modifications , alterations , and equivalents of the illustrated examples are possible . any such changes which derive directly from the teachings herein , and which do not depart from the spirit and scope of the invention , are deemed to be covered by this invention , and by the claims which follow . agren , m . s ., “ studies on zinc in wound healing ,” acta dermato - venereology , supplement 154 : 1 - 36 ( 1990 ) arens , m . and travis , s ., “ zinc salts inactivate clinical isolates of herpes simplex virus in vitro ,” j . clin . microb . 38 : 1758 - 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