[go: up one dir, main page]

WO2001054636A1 - Procedes et dispositifs pour prevenir la transmission de maladies sexuellement transmissibles - Google Patents

Procedes et dispositifs pour prevenir la transmission de maladies sexuellement transmissibles Download PDF

Info

Publication number
WO2001054636A1
WO2001054636A1 PCT/US2001/003043 US0103043W WO0154636A1 WO 2001054636 A1 WO2001054636 A1 WO 2001054636A1 US 0103043 W US0103043 W US 0103043W WO 0154636 A1 WO0154636 A1 WO 0154636A1
Authority
WO
WIPO (PCT)
Prior art keywords
agents
hiv
composition
group
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2001/003043
Other languages
English (en)
Other versions
WO2001054636A9 (fr
Inventor
Samuel Baron
Joyce Poast
Derrick Nguyen
Miles W. Cloyd
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
University of Texas at Austin
Original Assignee
University of Texas System
University of Texas at Austin
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Texas System, University of Texas at Austin filed Critical University of Texas System
Priority to AU34665/01A priority Critical patent/AU783242B2/en
Priority to EP01906798A priority patent/EP1253894A4/fr
Priority to CA002398399A priority patent/CA2398399A1/fr
Publication of WO2001054636A1 publication Critical patent/WO2001054636A1/fr
Anticipated expiration legal-status Critical
Publication of WO2001054636A9 publication Critical patent/WO2001054636A9/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • This invention relates generally to methods for prophylaxis against diseases transmittable by sexual contact and more particularly to methods for prophylaxis of HIV transmission.
  • the invention also relates to combinations of compositions and devices used with such methods.
  • condylomata acuminata (veneral warts), gonorrhea, syphilis, herpes simplex, granuloma cenereum, chancroid, granuloma inguinale. non-gonococcal urethritis. acute pelvic inflammatory disease, vaginitis and anorectal disease.
  • Nonoxynol-9® and other spermicidal and bacteriocidal agents in vaginally inserted suppositories, creams, foams or the like are discouraged because of the risk of causing mucosal inflammation.
  • these agents tend to destroy the healthy bacterial flora of the vagina and often lead to yeast infections.
  • the use of Nonoxynol-9® has been reported to result in an increased risk of HIV infection among prostitutes.
  • Kreiss et al., JAMA 268(4):477-482 (1992) which is incorporated by reference herein.
  • Other methods to destroy HIV in seminal fluid involve the use of antiseptics containing iodine, for example. (United States Patent No.
  • the present invention provides a method for preventing the transmission of HIV vaginally or rectally or orally by contacting a bodily fluid suspected of containing HIV with a composition having at least one of polyquaternium, glycerin, and a preservative system.
  • An embodiment of the preservative system in this method and those enumerated below comprises methylparaben and proplyparaben.
  • the invention also provides a method for prophylaxis of HIV transmission vaginally or rectally or orally by contacting a bodily fluid suspected of containing HIV with a composition having at least one of polyquaternium, glycerin, and a preservative system.
  • the invention also provides a method for reducing the risk of transmission of HIV vaginally or rectally or orally by contacting a bodily fluid suspected of containing HIV with a composition having at least one of polyquaternium, glycerin, and a preservative system.
  • the invention also provides a method for inhibiting the transmission of a sexually transmitted disease caused by an agent that is present in a bodily fluid by placing a composition having at least one of polyquaternium, glycerin, and a preservative system in a vagina, rectum, oral cavity, condom or on some other barrier device that can be inserted into a vagina or rectum prior to deposition of the bodily fluid into the vagina or rectum.
  • Yet another aspect of the provides a method for inhibiting the transmission of a sexually transmitted disease caused by an agent that is present in a bodily fluid by placing a composition having at least component selected from the group consisting of surfactants, microbicides, anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions.
  • the composition is placed into the oral cavity prior to deposition of the bodily fluid into the oral cavity.
  • the composition can be combined with a condom or other barrier device that is inserted into the vagina prior to deposition of the bodily fluid into the respective cavities.
  • Yet another aspect of the invention is a method for preventing the transmission of
  • the needle and syringe comprise viable donor cell-free HIV and/or donor HIV infected cells as a result of contamination from one or more of the people using the syringe and needle.
  • the method involves the step of contacting, prior to use of the syringe and needle, the donor cell free HIV and donor HIV infected cells with a composition that inhibits production of HIV by the donor cells, or inhibits the viability or infectivity of cell free HIV.
  • the composition comprises at least one component selected from the group consisting of surfactants, microbicides, anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions.
  • Figure 1 is a graphical representation of the effectiveness of over the counter vaginal preparations at inhibiting VSV multiplication in CEM lymphocytes in seminal fluid.
  • Figure 2 represents the effectiveness of over the counter vaginal preparations at inhibiting HIV multiplication in human CEM lymphocytes in seminal fluid.
  • Figure 3 shows the time required for over the counter vaginal preparations to inhibit production of HIV by infected human CEM lymphocytes.
  • Figure 4 shows the effectiveness of over the counter vaginal preparations at inhibiting the multiplication of cell-free HIV.
  • Figure 5 shows the effectiveness of over the counter vaginal preparations at inhibiting the multiplication of cell-free HIV in seminal fluid.
  • Figure 6 shows the toxicity and inhibitory titers of components of over the counter vaginal preparations. Toxicity and inhibitory activities of the components were absent in concentrations below 8% glycerol, 0.2% polyquaternium 32. 0.2% methylparaben, and 0.004% propylparaben.
  • Figure 7 shows interruption of VSV multiplication in L-cells by surfactants, bile salts, and components of douches.
  • Figure 8 shows interruption of VSV multiplication in L-cells by surfactants, vinegar and vaginal jellies.
  • Figure 9 shows inactivation by detergents of VSV infected CEM lymphocytes suspended in seminal fluid and placed on rectal tissue.
  • FIG 10 shows interruption by detergents of virus (VSV) multiplication in CEM lymphocytes in seminal fluid.
  • Figure 1 1 shows decontamination of syringes containing VSV infected CEM lymphocytes.
  • Figure 12 shows inactivation by detergents of VSV infected CEM lymphocytes suspended in seminal fluid and placed on rectal tissue.
  • Figure 13 shows interruption of virus (VSV) multiplication in L-cells by detergents.
  • FIG 14 shows interruption of virus (VSV) multiplication in L-cells by saliva and surfactants.
  • FIG 15 shows interruption of virus (VSV) multiplication in L-cells by detergents.
  • Figure 16 shows interruption of virus (VSV) multiplication in L-cells by enemas and mouthwashes.
  • FIG 17 shows interruption of virus (VSV) multiplication in L-cells by detergents.
  • FIG 18 shows interruption of virus (VSV) multiplication in L-cells by douches.
  • FIG 19 shows interruption of virus (VSV) multiplication in L-cells by detergents and mouthwashes.
  • Figure 20 shows detergents and over the counter vaginal or oral preparations inhibit cell-free HIV.
  • Figure 21 shows inactivation by bile salts and saliva of HIV infected CEM lymphocytes.
  • Figure 22 shows decontamination of syringes containing cell-free HIV in blood using l% ursodeoxycholate.
  • Figure 23 shows inactivation of cell-free HIV by ursodeoxycholate but not by saliva.
  • Figure 25 shows inactivation by bile acids and saliva of cell-free HIV.
  • Figure 26 shows inactivation by bile acids of cell-free HIV.
  • the present invention relates to methods for preventing the transmission of HIV.
  • methods for prophylaxis of HIV transmission methods for reducing the risk of transmission of HIV vaginally or rectally and to methods for inhibiting the transmission of sexually transmitted diseases in general.
  • the methods involve the use of compositions that have at least one of the following components in an aqueous solution: polyquaternium, glycerin, and a preservative system.
  • the compositions for use in the methods of the invention comprise at least one component selected from the group consisting of surfactants, microbicides, anticellular agents, acid agents, alkaline agents, oxidizing agents. inhibitors, organic solvents, and hypotonic solutions.
  • compositions of the invention are relatively inexpensive to produce.
  • the term "barrier device” refers to a device that serves to physically keep one individual's bodily fluid from coming into contact with another individual.
  • examples of such devices include, condoms, female condoms, and can also include cervical caps and sponges, as well as intrauterine devices, and vaginal diaphragms.
  • bodily fluid refers to a fluid or exudate of an individual that emanates, is expelled or released from the body. Examples of such bodily fluids include, blood, saliva, tears, semen, vaginal discharge, pus. mucous, urine and feces. Such bodily fluids can come into contact with a different individual thereby transmitting sexually transmitted diseases.
  • a bodily fluid may contain HIV in free form or HIV-infected cells.
  • Infected mononuclear leukocytes are the major infectious component of a donor- carrier's seminal fluid. In addition, they routinely survive in the isotonic seminal fluid in the recipients vagina. The infected mononuclear leukocytes then penetrate the vaginal epithelium and transmit infection to subepithelial leukocytes or attach to and infect CD4- negative epithelial cells. (Milman et al., AIDS Res. Hum. Retrov. 10: 1305-1312 (1994). which is. as are the other references and patents cited herein, incorporated herein by reference).
  • compositions of the present invention ideally should be placed in contact with the donor bodily fluid preferably within a half hour but in any case within this one hour time period. Most preferably, the compositions will be placed in the vagina or rectum or oral cavity, or even on the penis, before the commencement of sexual contact.
  • sexual contact refers to the deposition of a donor individual's bodily fluid onto or into a recipient individual's mucosal surface or surfaces, that is to say. from a donor to a recipient.
  • compositions of the methods of the invention include at least two commercially available vaginal lubricant products: AstroGlide® (BioFilm, Vista, California) and Vagisil® (Combe Inc., White Plains, NY).
  • AstroGlide® BioFilm, Vista, California
  • Vagisil® Combe Inc., White Plains, NY
  • the AstroGlide® composition is also sold under the brands Silken Secret®, ViAmor®, and Target®.
  • the AstroGlide® product includes water, glycerin, polyquaternium #33, propylene glycol, methylparaben and propylparaben.
  • Vagisil® comprises polyquaternium #32.
  • other polyquaternium-containing vaginal lubricants included in the compositions of the method, are Just Between Us® Personal Lubricant (Key West Aloe Co.),CVS® Personal Lubricant (Sun Mar Laboratories), and Ultra Lube® (Super Brands), all of which contain polyquaternium #5.
  • Enhance® Personal Lubricant (The Xandria Collection) contains polyquaternium #7.
  • non-polyquaternium containing personal lubricants included in the composition of the methods disclosed herein include Replens® Vaginal Moisturizer, K-Y Liquid®, K-Y® Long Lasting Vaginal Moisturizer, K-Y Silk-E® Vaginal Moisturizer, K-Y® Jelly Personal Lubricant. Summer's Eve® Vaginal Moisturizer, Aqua Lube®, and Wet, Light®Personal Lubricant Gel.
  • compositions herein also prevent or reduce the risk of HIV transmission as well as the transmission of other sexually transmitted diseases.
  • the compositions of the present invention may be used to prevent or reduce the likelihood of transmission of the herpes simplex virus, for example, since its morphology and chemistry are similar to that of HIV.
  • viral agents morphologically or chemically similar to HIV are subject to prophylaxis or the transmission-preventative methods of the present invention.
  • selection of morphologically and chemically similar agents are routine to those skilled in the art (Baron et al., Medical Microbiology. 4th ed., Galveston TX, The University of Texas Medical Branch at Galveston,(1996)).
  • inventive methods may be effective with sexually transmitted diseases involving bacterial agents.
  • agents refers to a viral, bacterial or other factor that is the pathogen responsible for the transmission of sexually transmitted disease from one individual to the next.
  • HIV an agent in AIDS
  • HSV an agent in genital herpes
  • the term "effective amount” refers to an amount or concentration of the composition of the present invention which is used in the methods to produce the intended result.
  • effective amounts are generally anti-HIV effective amounts, which may include amounts of the composition which prevent, reduce or are prophylactic for the sexually transmitted spread of HIV, for example.
  • effective amounts can refer to anti-HSV or anti-microbe amounts.
  • anti-HIV effective amounts or concentrations are amounts or concentrations of the compositions herein which inhibit the replication, growth and elaboration of HIV.
  • an effective amount of an anti-HIV composition is approximately 0.5 ml or more.
  • a preferable effective amount is 1 ml, however the user would likely use much more than that.
  • an effective amount can be in the range of 0.5 ml to greater than 10 ml.
  • Concentration ranges of polyquaternium useful in the present invention are from 0.1% to 10%o by weight.
  • any polyquaternium can be used at any concentration that is non-irritating to the mucosal epithelium. It is contemplated that the polyquaternium used herein is cationic in nature, although polyquatemiums which are anionic or non-ionic also find use n the compositions of the method.
  • Wash. D.C. discloses, without limitation, polyquatemiums (and their commercial sources) that are useful in the compositions of the methods of the invention.
  • Concentration ranges of glycerol useful in the present invention are from about 5% to about 60%o by weight.
  • An example of a concentration range of a preservative system useful in the invention involves methylparaben at 0.03% to 0.3% by weight and propylbaraben at 0.015% to 0.15% by weight.
  • preservative system refers to a chemical or group of chemicals that act to prevent the contamination or degradation of other components in the composition.
  • methylparaben and propylparaben are used as preservatives herein.
  • examples of other preservatives useful in the present invention include, but are not limited to, the following FDA approved preservative systems for food, cosmetics, and food preparations:
  • Vitamin C o-phenyl-phenol
  • Vitamin E tocopherol
  • Vitamin E Propyl Paraben
  • the term “prophylaxis” refers to preventing or reducing the risk of acquiring or transmitting sexually transmitted diseases. In addition, the term refers to inhibiting the growth or replication of HIV transmitted by sexual contact, for example.
  • One method of the present invention involves preventing the transmission of HIV vaginally or rectally by contacting a bodily fluid suspected of containing HIV with an aqueous composition having at least one component selected from the group consisting of polyquaternium, glycerin and a preservative system.
  • the bodily fluid is semen, and, in some circumstances may be vaginal fluid.
  • the method can comprise placing an effective amount of the composition on a penis or in a vagina or rectum within one hour of commencement of sexual contact. Ideally, the composition should be placed before the sexual contact has begun. In one embodiment an effective amount of the composition is 1 ml.
  • One convenient feature of the invention is that the composition can be placed with an applicator.
  • the term "applicator” refers to a device such as, but not limited to a douche or syringe with an elongated neck, sufficient to comfortably reach inside the vagina or rectum and deposit an effective amount of the composition.
  • the composition can be first combined with a device such as a suppository, condom, sponge or other barrier device, and then inserted into the vagina or rectum or cover the penis as appropriate.
  • a device such as a suppository, condom, sponge or other barrier device, and then inserted into the vagina or rectum or cover the penis as appropriate.
  • Preferable compositions used in the present methods include AstroGlide®, Vagisil® or ViAmor®.
  • kits for prophylaxis of HIV transmission vaginally or rectally by contacting a bodily fluid suspected of containing HIV with a composition having at least one component selected from the group consisting of polyquaternium, glycerin and a preservative system.
  • the invention provides methods for reducing the risk of transmission of HIV vaginally or rectally by contacting a bodily fluid suspected of containing HIV with a composition having at least one component selected from the group consisting of polyquaternium, glycerin and a preservative system.
  • the invention provides a method for inhibiting the transmission of a sexually transmitted disease caused by an agent present in a bodily fluid, by placing a composition having at least one component selected from the group consisting of polyquaternium, glycerin and a preservative system in a vagina, rectum, condom, sponge or on some other barrier device that can be inserted into a vagina or rectum, prior to the deposition of the bodily fluid into the vagina or rectum.
  • the agent is HIV.
  • the bodily fluid is semen or vaginal fluid
  • the preservative system is methylparaben and propylparaben.
  • another aspect of the invention is directed to a method for preventing transmission of HIV vaginally or rectally in a recipient who receives a donor's bodily fluid as a result of sexual contact.
  • This method involves the step of contacting donor HIV infected cells, leukocytes for example, in a bodily fluid, for example, semen, with an effective amount of a composition that inhibits production of HIV by the donor cells.
  • the donor source of infected cells may be vaginal fluid.
  • the composition comprises at least one component selected from the following: surfactants, microbicides, anticellular agents, acid agents. alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions.
  • Preferred formulations of the composition are sufficiently viscous for retention in the vagina or rectum and are miscible with seminal fluid.
  • Non-limiting examples of such formulations are lubricants, gels, creams, pessaries, tampons, pastes, foams or spray formulation, and, in particular, vaginal or rectal lubricants, gels or creams.
  • a method of placing the composition in the vagina, rectum, or mouth comprises topical application of the composition.
  • Methods of formulating the compositions into sufficiently viscous compositions are well known in the art. It is a matter of ordinary skill for those in the art of formulation to combine the composition of the method into a lubricant, gel.
  • a component of the composition may be categorized in one or more of the group consisting of surfactants, microbicides. anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions.
  • surfactants microbicides. anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions.
  • anticancer anticellular agents
  • Antibiotic agents may be classified as microbicides. anticellular agents, or as inhibitors.
  • one skilled in the an can select components for formulating a composition for use in the method by using the assay methods disclosed herein to distinguish without undue experimentation components and compositions thereof which kill or inactivate the donor cells from those components and compositions which do not.
  • the assay methods herein one can easily determine or measure a dose required in tissue-culture killing or inactivating of HIV infected donor cells. Cell death or inactivation are clear end points. A dead or inactivated donor cell, for example, cannot produce virus. Therefore any components or composition thereof found effective in the assays would prevent virus multiplication in the donor cells.
  • the surfactant for use in the composition of the method of the invention is selected from one or more of the group consisting of detergents, wetting agents, and emulsifiers. It is understood that surfactants (surface-active agents) involve any compounds that reduces surface tension when dissolved in water or water solutions, or that reduces interfacial tension between two liquids, or between a liquid and a solid. Guides to the properties and uses of surfactants in medicine, biology, and biochemistry are available to those of skill in the art (e.g. A Guide to the Properties and Uses of Detergents in Biology and Biochemistry, Calbiochem Biochemicals, San Diego, CA).
  • Microbicides which include spermatocides are understood to mean natural or synthetic compounds that otherwise kill or inactivate cells (procaryotic or eukaryotic)and/or viruses.
  • Microbicides which are useful in the methods of the invention are those which kill or inactivate donor cells in or from semen, thereby inhibiting production of HIV by the donor cell.
  • One or ordinary skill in the art using the assay methods disclosed herein can distinguish without undue experimentation microbicides which kill or inactivate the donor cells from those which do not.
  • Microbicides for use in the invention can be selected from one or more of the following: antifungal agents, anti- infective agents, AIDS chemotherapeutic agents, amebicide agents, antihelmintic agents, antibiotics, antimalarial agents, anti-protozoan agents, antituberculosis agents, antiviral agents, leprostatic agents, quinolones. sulfonamides, and antineoplastic (anticancer) agents (see Physicians ' Desk Reference. 53 rd ed. (1999), Medical Economics Company)). Microbicides further comprise commercially available disinfectants and components thereof.
  • anticelluar agent means a broad category of natural or synthetic substances which, for use in the method of the invention, otherwise effectively kill or inactivate cells (procaryotic or eukaryotic)and/or viruses.
  • Anticellular agents which are useful in the methods of the invention are those which kill or inactivate donor cells in or from semen, thereby inhibiting production of HIV by the donor cell.
  • One or ordinary skill in the art using the assay methods disclosed herein can distinguish without undue experimentation anticellular agents which kill or inactivate the donor cells from those which do not.
  • the term “inactivate” means inhibition of HIV production by donor infected cells.
  • Anticellular agents for use in the method of the invention include, without limitation, antineoplastic (anticancer) agents, peptides (non-limiting examples include cytokines, chemokines. defensins. and tumor necrosis factor), apoptotic agents, enzymes (non-limiting examples include Upases, proteases, carbohydrases, DNAse. RNAse), antibodies targeted to donor cells (preferably antibodies and conjugated with a toxic agent), and spermicidal agents. Inhibitors are a diverse group of compounds which otherwise kill or inactivate donor HIV infected cells.
  • Groups of inhibitor compounds from which a composition is selected for use in the method of the invention include DNA synthesis inhibiting agents, RNA synthesis inhibiting agents, protein synthesis inhibiting agents, metabolic inhibitors and metabolic antagonists, which include various inhibitors of mitochondria and various respiratory chain inhibitors, and antibiotics (see Inhibitor Tools in Cell Research, (1969) edited by Th. Bucher and H. Sies. Springer-Verlag. NY)).
  • Acid agents for use in the method of the invention are selected from the group consisting of inorganic acid agents, such as but not restricted to hydrochloric acid, nitric acid, and sulfuric acid; and organic acids, which include but are not restricted to preservative acids (e.g. benzoic acid, citric acid, sorbic acid, and acetic acid (vinegar)and acidic amino acids, which includes glycine. It has been shown (Ongradi, J., et al. AIDS Res. Hum Retroviruses (1990) 6(12): 1433-1436) that virus producing cells lose their ability to infect as the pH decreases.
  • preservative acids e.g. benzoic acid, citric acid, sorbic acid, and acetic acid (vinegar)and acidic amino acids, which includes glycine.
  • Alkaline agents for use in the method of the invention include inorganic alkaline agents, such as but not restricted to sodium hydroxide, potassium hydroxide, and calcium hydroxide; and organic alkaline agents.
  • Oxidation agents for use in the method of the invention include but are not restricted to hydrogen peroxide, salts of periodate, superoxide, nitric oxide, and glutathione disulfide.
  • Organic solvents for use in the method of the invention are selected from the group consisting of alcohols, ethers, esters, fatty acids and derivatives (saturated or unsaturated), diglycerides, triglycerides, lipids including phospholipids, glycolipids, sphingolipids, chromophoric lipids.
  • Examples of organic solvents for use in the compositions of the methods of the invention are available in commercial chemical catalogs, for example, Burdick & Jackson Laboratories, Inc. Small molecule organic solvents include propylene glycol and chloroform.
  • Hypotonic solutions for use in the method of the invention include water or solutions with low solute content, e.g. salts or sugars or any physiologically compatible solute.
  • the composition an effective amount of which is contained in at least a volume of 0.5 ml, is placed in a recipient's vagina or rectum or mouth or on a donor's penis before or after sexual contact has begun, and preferably within one hour of the commencement of sexual contact.
  • An applicator may be used to place the composition in the vagina or rectum or mouth of the recipient.
  • Embodiments of the method involve use of the composition in combination with a device, which could be a suppository, condom, sponge or other barrier device.
  • a device which could be a suppository, condom, sponge or other barrier device.
  • compositions that find use in the method include, without limitation, commercially branded soaps, enemas, mouthwashes, and douches.
  • Nonlimiting examples of these branded products include Jergens® soap and Ivory soap detergent, vaginal jelly by Walgreen® or by KY®, mouthwash by Walgreen® and by Listerine®. douches by Summer's Eve® or Massengil or by Walgreen®.
  • compositions comprising at least one component selected from the group consisting of surfactants, microbicides.
  • anticellular agents acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solution involve both inactivating vims extracellulary and by killing or inactivating donor cells in which the vims resides.
  • Human peripheral blood mononuclear leukocytes PBL or PBML
  • human lymphocyte cell line CEM
  • RPMI 1640 medium containing 10%> fetal bovine semm and antibiotics, as described in Baron et al.. Arch. Intern. Med.. supra.
  • Human peripheral blood macrophages were obtained by Ficoll-
  • Hypaque purification of normal peripheral blood leukocytes To obtain macrophages. the purified PBL were allowed to adhere to a glass surface for three hours at 37 °C. Unattached mononuclear leukocytes were rinsed away with medium and the adherent macrophages used in the experiments involving cell viability in the presence of saliva. Human CEM lymphocytes and THP-1 macrophages were propagated by established procedures, reported in Baron et al.. Arch. Intern. Med.. supra.
  • THP-1 macrophages peripheral blood mononuclear leukocytes, or L929 cells.
  • the multiplication of HIV in PBLs was determined as the yield of infectious HIV from 2x10 6 Ficoll-Hypaque purified normal peripheral blood mononuclear cells that had been cultured with phytopemagglutinin (4 ug/ml) for 2 days before treatment with interleukin 2 (40 units/ml) for an additional 2 days and then infected with 10 5 , 50%) tissue culture infectious doses of HIV, strain 213.
  • the infected cells were then incubated with 20u/ml interleukin 2 for five days, washed four times, and then incubated with or without samples, the various mixtures of samples, or culture medium for 15 or 60 minutes. These leukocytes were subsequently washed and cultured for HIV production in RPMI 1640 tissue culture medium, plus 15% fetal bovine semm and 20 u/ml of interleukin 2 for 24 hours before harvesting the cell-free medium for assay of HIV yield as described according to the assays described in EXAMPLE III. In experiments using the human CEM lymphocyte cell line, described in McKeating et al.. J. Gen. Virol. 80(12):3327-3333 (1989).
  • VSV vesicular stomatitis vims
  • VSV multiplication are measured similarly as the yield of infectious vims in the culture medium from the CEM lymphocytes. THP-1 macrophages, or murine L cells. This is done following infection with 3.000 viral plaque- forming units. Pilot experiments were done initially using VSV-infected human CEM lymphocytes, THP-1 macrophages or murine L cells. Confirmatory experiments were done using HIV-infected CEM lymphocytes and peripheral blood mononuclear leukocytes. All studies were replicated three times.
  • the production of HIV in the experiments was determined by the standard tissue culture infectious dose 50%) assay using MT-2 human lymphocytes, as described in McKeating et al., supra. Specifically, the culture fluids harvested from the HIV-infected human cells were serially diluted in 0.5 log, 0 increments using RPMI culture medium containing 10%> fetal bovine semm. 50ul of each dilution was added to quadruplicate microtiter wells, each containing 1 10 ul of 2x10 4 MT-2 cells in culture medium. After the serial dilutions, 120 ul of nutrient medium was added to each well.
  • microtiter plates were then incubated at 37 °C for three days in a CO 2 incubator, and then re-fed culture medium containing 10% fetal bovine semm. The wells were read for HIV multinucleated giant cell cytopathic effect on day 5 or 6.
  • the 50%> tissue culture infections dose was determined using the Reed-Muench method, as described in Reed et al., Am. J. Hyg, 27:493-497 (1938), which is incorporated herein by reference.
  • the production of VSV was determined as plaque-forming units in L cells.
  • VSV vesicular stomatitis vims
  • Nonoxynol-9® showed an almost identical degree of inhibition. Only Vagisil® showed a slightly less inhibition when it was mixed with the cells. Although Nonoxynol-9® exhibits strong inhibitory properties, its use in vivo is impractical due to its propensity to cause mucosal inflammation, which may be the cause of its ineffectiveness in human clinical trials.
  • compositions of the methods of the invention including without limitation AstroGlide® and Vagisil®, can penetrate seminal fluid sufficiently to reach cells infected with the virus and can kill those cells preventing multiplication and production of the vims.
  • compositions of the methods of the invention including without limitation AstroGlide® and Vagisil® are extremely effective at inhibiting the multiplication of HIV infected CEM lymphocytes in seminal fluid.
  • This example identifies the time required for the compositions of the methods of the invention, and in particular, vaginal preparations to inhibit production of HIV by infected CEM lymphocytes.
  • the vaginal preparations began to act within 5 minutes and within 20 minutes of incubation they produced a maximal level of inhibition of greater than 100 fold. This level of inhibition remained steady for at least 60 minutes.
  • HIV infected lymphocytes and HIV in cell-free form can remain in seminal fluid inside a vagina or rectum for up to one hour before the virus enters the recipient's epithelial tissue, assuming no trauma to the surrounding epithelial tissue has occurred. Accordingly, these results show that timely placing of the compositions of the invention in the vagina or rectum after sexual contact would destroy HIV before it could be transmitted in this manner.
  • compositions of the methods of the invention to inhibit cell-free HIV. It is generally reported by the scientific literature that in seminal fluid, most HIV is found sequestered in cells, with a ratio of 10 HIV sequestered to 1 free HIV. Accordingly, the ability of the vaginal preparations to inhibit cell-free HIV was studied as well.
  • Vagisil® produced a significant inhibition of cell-free HIV.
  • Vagisil® produced an inhibition of approximately 45 fold
  • ViAmor® produced approximately 15 fold inhibition
  • Astroglide® produced approximately 45 fold inhibition of HIV.
  • compositions of the methods of the invention including without limitation the over the counter vaginal preparations Astroglide® (ViAmor®),and Vagisil® are highly effective at inhibiting cell-free HIV as well.
  • This example was performed to determine whether the compositions of the method of the invention would also inhibit cell-free HIV in seminal fluid.
  • each of the vaginal preparations was effective at inhibiting cell-free HIV in seminal fluid. For example, an inhibition of approximately 6 fold was observed with each of Vagisil® and AstroGlide®. Accordingly, these results demonstrate that the vaginal preparations were able to penetrate the somewhat protective seminal fluid, and strongly inhibited cell-free HIV.
  • AstroGlide® had protective chemical compound(s)independent of hypotonicity. and that it was not the lack of salts but one or more chemical compounds which accounted for the inactivation of HIV by the compositions useful in the methods of the invention. Further studies will be performed using the compositions on HIV-infected leukocytes. In further studies , salts are added to create an isotonic condition to further demonstrate that AstroGlide® and the compositions of the method of the invention retain highly protective properties even when present or dissolved in an isotonic environment.
  • This example demonstrates that compounds of the methods of the invention strongly inhibit multiple strains of HIV.
  • Three additional HIV isolate strains, 213, AC- 1 and 9H are used to infect human CEM lymphocytes suspended in seminal fluid.
  • Stocks of the 213, Ac-1 and 9H strains of HIV are propagated in human H9 lymphocytes using the standard procedure described in Baron et al., Arch. Intern. Med.. supra and Williams et al., Virologv 184(2):723-728 (1991). both of which are incorporated by reference herein.
  • Two groups of infected cells are prepared, and one group is treated with, for example, AstroGlide® and the other is not. It is determined that AstroGlide® strongly inhibits the multiplication of the three HIV strains. Cells that are not treated remain viable. The results confirm the general applicability of the protection AstroGlide® among the compounds of the methods of the invention provides against multiple strains of HIV, which has utility for HIV infection in humans.
  • the following experiment are performed to determine whether the compounds of the methods of the invention, including AstroGlide®, can protect against HIV-infected monocytes as well as lymphocytes.
  • THP-1 monocytes are suspended in seminal fluid. Two groups of cells are prepared. One group is treated with AstroGlide® and the other group is not. The results show that AstroGlide® strongly inhibits HIV-infected monocytes. Therefore, the findings demonstrate that AstroGlide® can protect against all types of HIV-infected leukocytes in seminal fluid.
  • This example is performed to demonstrate whether the compounds of the methods of the invention, including AstroGlide®, could provide protection against HIV-infected primary peripheral blood leukocytes.
  • Human seminal fluid normally contains primary peripheral blood leukocytes rather than the cell lines used in previous studies. Normal human peripheral blood mononuclear leukocytes are purified from human blood, according to established protocols, which are known to those skilled in the art. Next, they are suspended in seminal fluid, infected with HIV and then treated or not with AstroGlide®. The results demonstrate that AstroGlide® is highly effective at inhibiting HIV-infected primary peripheral blood leukocytes. Therefore, these findings are applicable to human therapy.
  • This example is performed using the assay methods disclosed herein to determine whether compounds of the method of the invention, including AstroGlide®. inactivate four strains of cell-free HIV. Four strains of cell-free HIV suspended in seminal fluid are treated or not treated with AstroGlide®. The results demonstrate that AstroGlide® inactivates at a level greater than 90%> all strains of cell-free HIV in the absence of seminal fluid and at an
  • AstroGlide® is protective against cell-free as well as HIV-infected cells.
  • This example is performed to determine whether compounds of the methods of the invention, including AstroGlide®. provide protection against sexually transmitted agents, other than HIV, as well.
  • the agent of herpes is herpes simplex vims (HSV).
  • the compositions of the method of the invention, including AstroGlide ®. are also tested for their ability to inhibit the Papilloma virus through study of its virus family. Papoviruses. Protection against the genital strain of Papovims is studied in infected cells and cell-free vims suspended in seminal fluid. AstroGlide® is added to the culture. The cells are then assayed according to the procedure described previously herein. The results demonstrate that AstroGlide® strongly inhibits the genital strain of papovims. Accordingly, they provide protection against genital wart transmission.
  • AstroGlide® and the other compositions are additionally tested for their ability to inhibit other sexually transmitted microbes, such as gonorrhea, syphilis, chlamydia and mycoses.
  • each organism is cultured in nutrient medium according to procedures that are well known to those skilled in the art.
  • the cultures are either treated or not treated with AstroGlide® at systematically varying concentrations, all of which can be determined by those skilled in the an. and which are further described in Baron et al., Medical Microbiology. 4 th ed., Galveston TX, The University of Texas Medical Branch at Galveston, (1996). which is incorporated herein by reference.
  • the results demonstrate that AstroGlide® is highly effective at destroying these organisms, as indicated by the antimicrobial titer. In addition, they provide protective action.
  • compositions of the method of the invention including AstroGlide®. in the vagina and rectum.
  • AstroGlide® placed in the rectum. Samples are also removed at four hours and tested in a similar fashion. The results demonstrate that AstroGlide® retains high anti-HIV activity after four hours in the body. Accordingly, AstroGlide® is useful for human application.
  • VIRUSES AND CELLS a. Viruses Stocks of the 213 strain of HIV were propagated in human H9 lymphocytes using the standard procedure described in Baron et al., Arch. Intern. Med. 159(3):303-310 (1999) and Williams et al., Virologv 184(2):723-728 (1991), each of which is incorporated herein by reference. Aliquots were stored frozen at -70°C. The Indiana strain of vesicular stomatitis vims (VSV) was propagated in murine L cells using the method in Coppenhaver et al.. New Eng. J. Med. 330d 8.:1314-1315 (1994). which is incorporated herein by reference. VSV stocks were stored frozen at -70°C. b. Cells
  • the human lymphocyte cell line, CEM. were prepared and propagated in RPMI 1640 medium containing 10% fetal bovine semm and antibiotics, as described in Baron et al., Arch. Intern. Med.. supra. Human CEM lymphocytes and THP-1 macrophages were propagated by established procedures, reported in Baron et al., Arch. Intern. Med.. supra and Baron et al, J. Infect. Pis. 181 :498-504 (2000).
  • Multiplication was determined as the yield of infectious VSV from 2x10 5 CEM lymphocytes that were infected with 10 5 , 50%) tissue culture infectious doses of VSV and suspended or not in seminal fluid. The cells were then incubated for 60 minutes and washed four times before 30 to 60 minute treatments with the various preparations. These infected lymphocytes were subsequently washed four times and cultured for 24 hours before harvesting for assay of VSV production as described in EXAMPLE III.
  • the production of HIV in the experiments was determined by the standard TCID 5 ⁇ assay with MT-2 human lymphocytes, described in McKeating et al.. J. Gen. Virol. 70:3327-3333 (1989). Specifically, culture fluids harvested from the HIV-infected human CEM lymphocytes, as described in Baron et al.. Arch. Intern. Med. 159(3):303-310 (1999). were serially diluted in 0.5-log, 0 increments in RPMI culture medium containing 10% fetal bovine semm. Next. 50 ml of each dilution was added to quadmplicate microtiter wells. each containing 1 10 ml of 2 x 10 4 MT-2 cells in culture medium. After the serial dilutions.
  • TCID 50 of HIV was determined by the method of Reed and
  • VSV vesicular stomatitis virus
  • VSV-infected CEM lymphocytes were exposed to the preparations and/or components thereof and the log 10 inhibition of multiplication recorded.
  • VSV was chosen for this experiment since it has similar structural properties to HIV. but is considerably more safe and practical to handle in a laboratory.
  • Syringes of the sizes commonly used for d g injection were contaminated by drawing into the syringe 0.1 of normal blood to which was added either cell-free VSV (10 5 infectious units/0.1 ml), or for comparison, infected CEM cells (10 5 cells/0.1 ml).
  • cell-free VSV 10 5 infectious units/0.1 ml
  • infected CEM cells 10 5 cells/0.1 ml.
  • the syringes were rinsed with a total volume of 3 ml of a solution of the composition. Controls were rinsed with nutrient medium. Then residual vims or cells were collected from the syringes in 1 ml of culture medium, which was assayed for infectious vims as described.
  • Figure 7 shows the interruption of VSV multiplication in L-cells by surfactants (bile salts) and by components of douches.
  • surfactants bile salts
  • benzoic acid 0.8%in dilutions up to three-fold had a 5 log inhibitory titer, and from three-fold to about 15-fold dilutions, showed a 0.5 log inhibitory titer. Beyond fifteen fold dilution, an inhibitory influence on VSV multiplication in L-cells was not demonstrated.
  • Figure 8 shows interruption of VSV multiplication in L-cells by surfactant bile salts. soap solutions, vaginal jellies, an organic solvent, an acid, and the surfactants TritonXlOO combined with tributyl phosphate.
  • Figures 9, 10, 12, 13, 14. 15, and 17 demonstrate inactivation by detergents of VSV infected CEM lymphocytes suspended in seminal fluid by bile salts and Triton xlOO® detergent.
  • Figure 16 shows interruption of VSV multiplication in L-cells by enemas and mouthwashes, and by douches in Figure 11.
  • Figure 19 illustrates that detergents and mouthwashes interrupted VSV multiplication in L-cells.
  • Figure 20 demonstrates that over the counter vaginal preparations (douches) or oral preparations (mouthwashes) inhibited cell-free HIV.
  • Figure 21 shows inactivation by bile salts and saliva of HIV-infected CEM lymphocytes, while Figure 19 shows their inhibitory effects on cell-free HIV.
  • Figure 20 shows inactivation by bile acids of cell free HIV.
  • Figure 23 shows inactivation of cell-free HIV by ursodeoxycholate but not by saliva.
  • Figures 11, 22, and 24 show the decontamination (i.e. either the inhibition of VSV production or the inhibition of cell free HIV) of syringes containing either cell-free HIV or VSV infected cells using ursodeoxycholate, colic acid, deoxycholate, Triton XlOO. tributyl phosphate, combination of Triton XlOO and tributyl phosphate, and tap water.
  • the method of the invention prevents or inhibits HIV transmission from a needle and syringe contaminated with either free HIV or VSV-infected cells, and that the method is effective for disinfecting the needle and syringe between users by using a composition that carries less risk to the user than bleach solutions, which are in common use for disinfecting or decontaminating needles and syringes but which pose a significant health hazard if inadvertently injected into a user.
  • compositions comprising at least at least one component selected from the group consisting of surfactants, microbicides, anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions. Similar to Examples X through XVI above, these studies include Examples XXIII through XXIX, and are focused upon methods of the invention which use compositions or candidate compositions comprising at least one component selected from the group consisting of surfactants, microbicides. anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions:
  • composition comprising at least at least one component selected from the group consisting of surfactants. microbicides, anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors.
  • THP-1 monocytes are suspended in seminal fluid.
  • Two groups of cells are prepared. One group is treated with a candidate composition and the other group is not.
  • the results show that the candidate composition comprising at least one component selected from the group consisting of surfactants, microbicides. anticellular agents, acid agents, alkaline agents, oxidizing agents, inhibitors, organic solvents, and hypotonic solutions strongly inhibits HIV-infected monocytes. Therefore, the findings demonstrate that the candidate composition can protect against all types of HIV-infected leukocytes in seminal fluid.
  • This example is performed to demonstrate whether the compounds of the methods of the invention could provide protection against HIV-infected primary peripheral blood leukocytes.
  • Human seminal fluid normally contains primary peripheral blood leukocytes rather than the cell lines used in previous studies. Normal human peripheral blood mononuclear leukocytes are purified from human blood, according to established protocols. which are known to those skilled in the art. Next, they are suspended in seminal fluid, infected with HIV and then treated or not with a candidate composition used in the method of the invention. The results demonstrate that the candidate composition is highly effective at inhibiting HIV-infected primary peripheral blood leukocytes. Therefore, these findings are applicable to human therapy.
  • This example is performed to determine whether candidate compounds of the method of the invention inactivate four strains of cell-free HIV. Four strains of cell-free HIV are tested.
  • HIV suspended in seminal fluid are treated or not treated with a candidate composition.
  • the results demonstrate that the candidate composition inactivates at a level greater than 90%) all strains of cell-free HIV and at an 80%> level in seminal fluid. Accordingly, the candidate composition is protective against cell-free as well as HIV-infected cells.
  • This example is performed to determine whether candidate compounds of the methods of the invention provide protection against sexually transmitted agents, other than HIV, as well.
  • the agent of herpes is herpes simplex vims (HSV).
  • HSV herpes simplex vims
  • Vero cells are suspended in seminal fluid.
  • a candidate composition is added to the cells.
  • the cells are assayed according to procedures described previously herein.
  • the results demonstrate that the candidate composition strongly inhibits HSV as well. Accordingly, they provide protection against herpes transmission.
  • the candidate compositions of the method of the invention are also tested for their ability to inhibit the Papilloma vims through study of its vims family, Papovimses.
  • Candidate compositions are additionally tested for their ability to inhibit other sexually transmitted microbes, such as gonorrhea, syphilis, chlamydia and mycoses. To determine the protective effect against these microbes, each organism is cultured in nutrient medium according to procedures that are well known to those skilled in the art.
  • the cultures are either treated or not treated with a candidate composition at systematically varying concentrations, all of which can be determined by those skilled in the art, and which are further described in Baron et al., Medical Microbiology. 4 th ed., Galveston TX, The University of Texas Medical Branch at Galveston, (1996), which is incorporated herein by reference.
  • the results demonstrate that a candidate composition is highly effective at destroying these organisms, as indicated by the antimicrobial titer. In addition, they provide protective action.
  • This example demonstrates the duration of anti-HIV activity of the compositions and candidate compositions of the method of the invention in the vagina and rectum.
  • Five rabbit vaginas are treated with a composition and sampled at four hours. Additionally, five rabbit rectums are treated with a composition and sampled at four hours.
  • compositions used in the claimed methods are useful for human application.
  • the compositions used in the method are those which inactivate donor infected cells but which do not cause inflammation of the recipient's mucosa.
  • Components and compositions thereof which are already FDA-approved for safety find use in the methods of the invention.
  • the methods of the invention lend themselves to female- controlled prevention methods, i.e. methods intended primarily, but not exclusively, for vaginal use, and includes compositions which can be used without a partner's knowledge. Further, the methods of the invention are not limited to an exclusive focus on vaginal application. The methods and compositions disclosed herein may be used primarily for vaginal application, however, it should be recognized that they will also be applied to the penis, and used orally and rectally by both heterosexual and homosexual couples.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des méthodes de prévention de la transmission du VIH, des méthodes de prophylaxie de la transmission du VIH et des méthodes visant à réduire le risque de transmission vaginale, rectale, ou orale du VIH à l'aide de compositions contenant au moins un des éléments du groupe constitué par polyquaternium, glycérine, méthylparaben et propylparaben. Dans un autre aspect, la composition renferme au moins un des éléments du groupe comprenant tensioactifs, microbicides, agents anticellulaires, agents acides, agents alcalins, agents oxydants, inhibiteurs, solvants organiques et solutions hypotoniques. L'invention concerne en outre des méthodes visant à inhiber, à l'aide de ces compositions, la transmission d'une maladie sexuellement transmissible. Des méthodes de désinfection d'aiguilles et de seringues sont également décrites. L'invention concerne de plus des combinaisons de compositions et de dispositifs utilisés dans les méthodes mentionnées.
PCT/US2001/003043 2000-01-28 2001-01-29 Procedes et dispositifs pour prevenir la transmission de maladies sexuellement transmissibles Ceased WO2001054636A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU34665/01A AU783242B2 (en) 2000-01-28 2001-01-29 Methods and devices for preventing transmission of sexually transmitted diseases
EP01906798A EP1253894A4 (fr) 2000-01-28 2001-01-29 Procedes et dispositifs pour prevenir la transmission de maladies sexuellement transmissibles
CA002398399A CA2398399A1 (fr) 2000-01-28 2001-01-29 Procedes et dispositifs pour prevenir la transmission de maladies sexuellement transmissibles

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US49420100A 2000-01-28 2000-01-28
US09/494,201 2000-01-28
US54838100A 2000-04-15 2000-04-15
US09/548,381 2000-04-15

Publications (2)

Publication Number Publication Date
WO2001054636A1 true WO2001054636A1 (fr) 2001-08-02
WO2001054636A9 WO2001054636A9 (fr) 2002-10-24

Family

ID=27051337

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/003043 Ceased WO2001054636A1 (fr) 2000-01-28 2001-01-29 Procedes et dispositifs pour prevenir la transmission de maladies sexuellement transmissibles

Country Status (5)

Country Link
EP (1) EP1253894A4 (fr)
CN (1) CN1418077A (fr)
AU (1) AU783242B2 (fr)
CA (1) CA2398399A1 (fr)
WO (1) WO2001054636A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114652741A (zh) * 2022-01-19 2022-06-24 昆明野水生物科技有限公司 一种用于抑制hpv的组合物、制剂及其应用

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2010008148A (es) * 2008-01-25 2010-10-20 Chimerix Inc Métodos de tratamiento de infecciones virales.
CA2906642A1 (fr) * 2013-03-15 2014-09-18 Conrad Preparations a faible taux de glycerol destinees au traitement et a la prevention du vih

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5466463A (en) * 1993-12-03 1995-11-14 Lafor Laboratories Limited Viracidal, bactericidal and spermicidal vaginal suppository
US5527534A (en) * 1992-10-21 1996-06-18 Gynetech Laboratories, Ltd. Vaginal sponge delivery system

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2717497B2 (ja) * 1993-12-28 1998-02-18 不二ラテックス株式会社 酸性多糖類被覆コンドーム
US5545401A (en) * 1994-06-02 1996-08-13 Shanbrom; Edward Antiviral, spermicidal vaginal gel and foam containing low molecular weight povidone-iodine
US6581775B1 (en) * 2001-08-10 2003-06-24 Garo Hagopian Method of external genital cleansing and prophylactic kit

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5527534A (en) * 1992-10-21 1996-06-18 Gynetech Laboratories, Ltd. Vaginal sponge delivery system
US5466463A (en) * 1993-12-03 1995-11-14 Lafor Laboratories Limited Viracidal, bactericidal and spermicidal vaginal suppository

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1253894A4 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114652741A (zh) * 2022-01-19 2022-06-24 昆明野水生物科技有限公司 一种用于抑制hpv的组合物、制剂及其应用
CN114652741B (zh) * 2022-01-19 2023-08-25 昆明野水生物科技有限公司 一种用于抑制hpv的组合物、制剂及其应用

Also Published As

Publication number Publication date
WO2001054636A9 (fr) 2002-10-24
CN1418077A (zh) 2003-05-14
CA2398399A1 (fr) 2001-08-02
AU3466501A (en) 2001-08-07
EP1253894A1 (fr) 2002-11-06
AU783242B2 (en) 2005-10-06
EP1253894A4 (fr) 2005-01-26

Similar Documents

Publication Publication Date Title
RU2274442C2 (ru) Композиции и способы улавливания и инактивации патогенных микроорганизмов и сперматозоидов
US8853272B2 (en) Method for treating an inflammation or lesion caused by a virus
SK153398A3 (en) Antimicrobial composition and its use for the preparation of product for treatment of diseases induced by herpex simplex virus and other infectious diseases
US6635242B2 (en) Broad spectrum microbicidal and spermicidal compositions, devices, and methods
US20120046556A1 (en) Methods and Kits for Preventing the Spread of Sexually Transmitted Microorganisms
EP1372389B1 (fr) Compositions virucides
US6949255B2 (en) Inhibitory chemical formulation with preservative system
AU2002251933A1 (en) Virucidal compositions
AU783242B2 (en) Methods and devices for preventing transmission of sexually transmitted diseases
US8518434B2 (en) Antiseptic spermicidal composition and means for its application
WO2000072839A1 (fr) Composition spermicide antiseptique et son instrument d'application
US20050241645A1 (en) Composition for preventing the transmission of human immunodeficiency syndrome virus
HK1054859A (en) Methods and devices for preventing transmission of sexually transmitted diseases

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2398399

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 34665/01

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2001906798

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 01806843X

Country of ref document: CN

AK Designated states

Kind code of ref document: C2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: C2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

COP Corrected version of pamphlet

Free format text: PAGES 1/26-26/26, DRAWINGS, REPLACED BY NEW PAGES 1/16-16/16; DUE TO LATE TRANSMITTAL BY THE RECEIVING OFFICE

WWP Wipo information: published in national office

Ref document number: 2001906798

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: JP

WWG Wipo information: grant in national office

Ref document number: 34665/01

Country of ref document: AU

WWW Wipo information: withdrawn in national office

Ref document number: 2001906798

Country of ref document: EP