AP327A - Method for inactivating enveloped viruses and sperm. - Google Patents
Method for inactivating enveloped viruses and sperm. Download PDFInfo
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- AP327A AP327A APAP/P/1992/000370A AP9200370A AP327A AP 327 A AP327 A AP 327A AP 9200370 A AP9200370 A AP 9200370A AP 327 A AP327 A AP 327A
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- betaine
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/16—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds containing nitrogen-to-oxygen bonds
- A01N33/24—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds containing nitrogen-to-oxygen bonds only one oxygen atom attached to the nitrogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/25—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids with polyoxyalkylated alcohols, e.g. esters of polyethylene glycol
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
- A01N37/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
- A01N37/46—N-acyl derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
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- 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
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
- A61L2/0088—Liquid substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/208—Quaternary ammonium compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/408—Virucides, spermicides
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/452—Lubricants
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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Abstract
There is provided methods for inhibiting the activity of enveloped viruses, treatment of viral infections and method inactivating sperm. There is provided articles for use in these methods.
Description
1· Field of the Invention
The present invention relates to a novel method and novel articles for inhibiting the activity of enveloped viruses. The invention also relates to treatment of viral infections. More particularly, the invention relates to a method for inhibiting the development of diseases and infections caused by enveloped viruses. In one aspect the invention particularly relates to a method of inhibiting the activity of viruses whose major mode of transmission is sexual. In other aspects the invention also relates to methods of inhibiting the activity of enveloped viruses whose mode of transmission is nonsexual. The compositions of use in the invention are also effective in the inhibition of bacteria and fungi which coexist with viruses or viral infections. Additionally, the invention relates to a treatment for virus related diseases, particularly sexually transmitted diseases related to AIDS, and to diseases related to this and other opportunistic infections of the immune-compromised host.
The method of the invention relates to using mixtures of betaines and amine oxides in the inhibition of viruses and treatment of viral infections. The betaine is selected from the group consisting of (a) an alkyl-N-betaine, an alkyl-N-sulfobetaine, an acyl-Nbetaine, an alkyl N-substituted aminopropionic acid and an alkylimidazolinium betaine and the amine oxide is
BAD ORIGINAL selected from the group consisting of (b) an alkyl-N, Ndimethylamine oxide, an alkyl-N, N-dihydroxyethylamine oxide and an acylamide t-amide oxide. The term betaine when used herein means an N-dimethyl glycine and their lower alkyl homologs. The term includes Ndinethyl amino propionic acids and sulfo betaines which are the sulfonic acid analogs of such compounds. Unless otherwise specified a N-dimethyl compound is intended. More particularly, the invention relates to a method for employing mixtures of alkyl N-di(lower alkyl) betaines and alkyl N-di(lower alkyl) amine oxides in the inhibition of enveloped viruses and use of these mixtures in the treatment of infections caused by these viruses. The mixtures may also be used as spermicides, either alone or in combination vith conventional spermicides. These mixtures may be used in combination with contraceptive devices or may be incorporated into the contraceptive device.
2. Description of the Prior Art
It is knovn that certain mixtures of amines are effective antimicrobial agents against gram negative and gram positive bacteria. For instance, it is knovn that certain mixtures of a) alkyl-N-betaine, alkyl-Nsulfobetaine, acyl-N-betaine, alkyl N-substituted aminopropionic acid or an alkylimidazolinium betaine and (b) alkyl-N,N-dimethylamine oxide, alkyl-N, Ndihydroxyethylamine oxide or acylamide t-amide oxide can be used for skin degerming, cleansing and deodorizing (see for example U.S. Patent 4,183,952, issued to E.B. Michaels; U.S. Patent No. 4,075,350 issued to E.B. Michaels, and U.S. Patent No. 4,107,328; issued to E.B. Michaels). These compositions are also useful for long term inhibition of body odor. Mixtures of the same active ingredients are also knovn to enhance oral hygiene by reducing oral microflora and inhibiting formation of dental plaque. (U.S. Patent 4,839,158 issued to E.B. Michaels). Compositions of this type are
AP 0 0 0 3 2 7
- 3 also known to be effective fungicides. Corner, A.M., et a 1. Antimicrobial Agents and Chemotherapy, 3 2 (3): 350 353 (March 1988) ; Corner, A.M. The Journal cf Clinical Dentistry, Vol. 2(2):34 - 38. (1990)). (See also U.S.
Patents 4,075,350, 4,107,328, 4,183,952 and 4,839,158 issued to E.B. Michaels.)
It is also known that nonionic surface-active agents possessing ether or amide linkages betveen the hydrophilic and hydrophobic portions of the molecule rapidly inactivate the infectivity of herpes simplex virus I and II. (Asculai, S.S., et al. Antimicrobial Agents Chemotherapy, Vol. 13:686 - 690 (1978)).
Asculai et al. also states that cytocidal activity has been used as an index of antiviral activity. The compositions utilized in this invention have an advantage over the compositions described in Asculai et al. in that these compositions inactivate viruses and bacteria while exhibiting low cytocidal activity.
The spermicide Nonoxynol-9 (N-9), has been found to have bactericidal and viricidal effects. For example, N-9 has been found to inactivate viruses related to AIDS (e.g. HIV, human immunodeficiency virus) and herpes simplex viruses (HSV I and II). In vitro, N9 has been shown to be effective against the organisms that cause gonorrhea, chlamydia, syphilis, trichomoniasis, and other sexually transmitted diseases. (U.S. Pharmacopeial Convention USPDI Update 1990 pps.
755 - 756).
SUMMARY OF THE INVENTION
It has now unexpectedly been found that certain hereinbelov defined mixtures of betaines such as (a) alkyl-N-betaines, alkyl-N-sulfobetaines, acyl-Nbetaines, alkyl-N-substituted aminopropionic acids and alkylimidazolinium betaines, and amine oxides such as (b) alkyl-N, N-dimethylamine oxides, alkyl-N, Ndihydroxyethylamine oxides or acylamide t-amide oxides in acceptable diluents, carriers and excipients are
BAD ORIGINAL 0 t
effective in inhibiting the activity of enveloped viruses. The invention provides a method of inhibiting the activity of enveloped viruses for vhich a major mode of transmission is sexual. The invention relates to a method for treating diseases and infections caused by enveloped viruses. These compositions are also effective in the inhibition of bacteria and fungi that co-exist vith viruses or viral infections and for treatment of bacterial and fungal infections which coexist vith viruses or viral infections. The invention also provides a method for disinfecting air and surfaces contaminated with enveloped viruses.
The invention also provides a method for preventing the transmission of enveloped viruses.
The compositions used in the method of the present invention can also be used as spermicides.
These compositions can be used alone, vith other knovn spermicides and vith or incorporated into contraceptive devices such as condoms, sponges, vaginal inserts, contraceptive films, diaphragms, suppositories, contraceptive patches or sustained release devices.
These compositions can also be incorporated into douches. The compositions can be incorporated into wipes. For use as viricides, these compositions can be applied alone; with other spermicides; and vith or incorporated into the contraceptive devices described above. The compositions can also be applied in the form of a foam, gel, cream, salve, jelly or lotion. The compositions can also be applied in the form of a liquid, aerosol, mist or spray.
DESCRIPTION OF THE DRAWINGS
Figure 1: is a graph showing the effect of C31G (a composition according to the present invention) and the effect of Nonoxynol-9 (N-9) on sperm motility.
Figure 2: is a graph showing the effect of C31G and the effect of Nonoxoynol-9 (N-9) on total sperm count.
AP 0 0 0 3 2 7
- 5 Figure 3: is a graph shoving the effect of C31G and the effect of Nonoxoynol(N-9) on the mean progressive velocity of sperm.
Figure 4: is a graph shoving in vitro toxicity of C31G vs. N-9 on sup-TI cells.
Figure 5: is a graph shoving a five day toxicity study of C31G vs. N-9 on OEM cells.
Figure 6: is a graph shoving comparing the effects on C31G vs. N-9 on HSV.
Figure 7: is a graph shoving the effect of C31G on HIV.
Figure 8: is a graph comparing inactivation of HIV by C31G and N-9.
Figure 9: is a chart comparing inactivation of HIV by C31G and N-9.
DETAILED DESCRIPTION OF THE INVENTION
The method of the invention relates to using mixtures of betaines and amine oxides in the inhibition of enveloped viruses and treatment of viral infections caused by enveloped viruses. The method of the invention also relates to using mixtures of betaines and amine oxides in the inactivation of enveloped viruses. The betaines that can be used in this invention are alkyl-N-betaines, alkyl-N-sulfobetaines, acyl-Nbetaines, alkyl N-substituted aminopropionic acids or alkylimidazolinium betaines or mixtures thereof. The amine oxides that can be used in this invention are alkyl-N, N-dimethylamir.e oxides# alkyl-N, Ndihydroxyethylamine oxides or acylamide t-amide oxides or mixtures thereof. These compositions are also effective for the treatment of viral, fungal, and microbial infections and contaminations. These compositions are effective in inhibiting enveloped viruses that are transmitted sexually or nonsexually. These compositions are also effective in the inhibition of bacteria and fungi which coexist with viruses or viral infections. These compositions can also be used
BAD ORIGINAL ft topically.
Typically, these compositions are applied to areas where viruses are or can be transmitted. This includes application in the vagina, to mucous membranes, and to the skin.
These compositions can also be used as spermicides, either alone or in combination with other spermicides. These compositions can also be used with or incorporated into contraceptive devices such as, for example, condoms, diaphragms, sponges, contraceptive films, suppositories, sustained release devices, and contraceptive patches. For example, the composition may be incorporated into a lubricant applied to a condom or as part of a reservoir at the tip of a condom, or incorporated into a contraceptive sponge, contraceptive film, suppository, sustained release device or contraceptive patch. A contraceptive film can comprise the composition described above, together with, Type A gelatin, cellulose gum and a polyhydric alcohol. The compositions can also be used in contraceptive foams, gels, jellys, creams. The compositions can also be used in douches or use in preventing the transmission of viruses, these compositions can be used alone, with other spermicides and with or incorporated into a contraceptive device as described above. This invention also comprises a method for inhibiting the transmission of viruses that cause sexually transmitted diseases which comprises applying the compositions to those parts of the anatomy that are exposed to body fluids emanating from another during sexual activity.
These compositions have also unexpectedly been found to be less toxic to mammalian cells than
Nonoxoynol-9 (N-9) (See Figures 4 and 5) . Table 1 shows that these compositions have equivalent spermicidal activity to N-9, which is one of the few surfactants approved by the FDA for use as a spermicide.
For use in topical applications, the
BADOW®'*^
AP 0 0 0 3 2 7 coapositions can also be incorporated into liquids, creams, salves, lotions, foams and gels.
The invention also provides a method for disinfecting air and inanimate surfaces, for example, in an operating room or laboratory. More particularly, this invention provides a method for disinfecting areas which are contaminated with enveloped viruses. These compositions can also be incorporated into sprays, mists, wipes, aerosols or devices which produce sprays, mists or aerosols. These compositions can also be applied as liquids.
According to the method of this invention, these compositions may be used as viricides, fungicides and bactericides.
The compositions employed in the method of the irvention comprise an admixture of betaines and amine oxides. The betaines used in this invention are selected from the group consisting of (a) alkyl-Nbetaines, alkyl-N-sulfobetaines, acyl-N-betaines, alkyl N-substituted aminopropionic acid, alkylimidazolinium betaines and mixtures of two or more thereof. Typically the betaines have two lower alkyl groups bonded to the nitrogen atom. Most effectively they have two methyl substituents on the nitrogen atom. The amine oxides used in this invention are selected from the group consisting of b) a an alkyl-N,N-dinethylamine oxides, alkyl-N,N-dihydroxyethylamine oxide or acylamide t-amine oxides and mixtures of tvo or more thereof. Typically, the betaine and amine oxide components are present in a molar ratio of from 1:5 to 5:1, preferably in a molar ratio of 1:1. The alkyl-N-betaine, the alkyl-Nsulfobetaine, the acyl-N-betaine, the alkyl Nsubstituted 2-aminopropionic acid and alkylimidazolinium betaine (also referred to as cocoamphoacetates) employed as the components (a) of the composition of the invention have structures, respectively, as follows:
BAD ORIGINAL <fH3 •N't-CH2C00'
I i ch3
CH3 itΪη•ch2so3'
Ο
II •C
CHCH3
1+ Ii I.
N* CH2COO or RC—*NH(CH2)3-N+έκ3 itt3
RNHCH2CH2COOH or RN(CH2CH2COOH)2 ch2ch2oh :h2coo f?
RCNH οι
N
N
-CH-.COO’ ch2
-ch2ch2or ch2ch2oh
I
N-CH2COO' where R is a higher alkyl group having from 10 to 18 carbon atoms, preferably from 12 - 16 carbon atoms.
When used herein the term lower alkyl means an alkyl group of from 1 to 3 carbon atoms.
Illustrative of these aforementioned substances are: (1) coco-N-betaine, cetyl-N-betaine, stearyl-N-betaine, isostearyl-N-betaine, oleyl-N25 betaine; (2) coco-N-sulphobetaine, cetyl-Nsulphobetaine, stearyl-N-sulfobetaine, isostearyl-Nsulfobetaine, oleyl-N-sulfobetaine; (3) cocoamido-Nbetaine, cetylamido-N-betaine, stearylamido-N-betaine, isostearylamido-N-betaine, oleyl-awino-N-betaine; (4) N30 coco-2 aminopropionic acid, N-cetyl-2-aminopropionic acid, N-stearyl-2-aminopropionic acid, N-isostearyl-2aminopropionic acid, N-oleyl-2-aminopropionic acid,
N-stearyl-bis (2-aminopropionic acid), N-oleyl-bis (2-aminopropionic acid), N-coco-bis (2-aminopropionic acid), N-cetyl-bis(2-aminopropionic acic),
Λ
AP 0 0 0 3 2 7 (5) N-lauryl-bis (2-aminopropionic acid) 1-hydroxyethyl1-carboxymethyl-2-decylimidazolium betaine;
1- hydroxyethyl-1-carboxymethy1-2-dodecylimidazolium betaine; 1 -hydr oxy ethyl -1-carboxyme thy 1-2cocoimidazolium betaine; 1-hydroxyethyl-l-carboxymethy12- stearylimidazolium betaine; 1-hydroxyethyl-lcarboxymethyl-2-oleylimidazolium betaine; or mixtures of the same.
When used here the term coca is that used in the CTFA (designations of Cosmetic and Toiletry and Fragrance Association, Wash., D.C.) and is used to indicate alkyl groups present in coconut oil, i.e. a mixture of alkyl groups of from 10 to 18 carbon atoms. The designations of the compounds listed herein are those of the CTFA.
The (1) alkyl-N,N-diethylamine oxide, (2) alkyl-N, N-dihydroxylethylamine oxide, or (3) acylamide t-amine oxide employed as component (b) of the aforementioned mixture, respectively, have the structure:
O
R-i!-NH
CH-»
ch3 where R is a higher alkyl group of from 10 to 18 carbon atoms, for instance, radicals such as decyl, undecyl, lauryl, tridecyl, myristyl, cetyl, stearyl, isostearyl or oleyl. Exemplary of the amine oxides are: decylΝ,Ν-dimethylamine oxide, lauryl-N,N-dimethylamine oxide, stearyl-N-N-dimethylamine oxide, oleyl-N,N-dimethylamine oxide, coco-Ν,Ν dihydroxyethylamine oxide, cetyl-N,NBAD OR1G
dihydroxyethylamine oxide, oleyl-N,N-dihydrcxyethylamine oxide, Ν,Ν-dihydroxyethylamine oxide, oleyl-N,-Ndihydroxyethyl-amine oxide and mixtures of the same.
The components (a) and (b) are usually admixed and acid is then added in an amount necessary to adjust the pH of a 0.5% solution to betveen 4-8, preferably to pH 4.5 - 5.5. The pH of an aqueous solution comprising the above enumerated components of the invention is determined by employing an aqueous solution of 0.5%, by weight, total of active components.typically at a glass electrode, to precisely define the acidity of the composition.
In general, the acid used to adjust the overall composition to the required pH is any organic or inorganic acid that is compatible with the intended use of the composition, for example, hydrochloric acid, phosphoric acid, sulfuric acid, citric acid, acetic acid or nicotinic acid. The balance of the composition, after allowing for the acid is usually an acceptable solvent, such as water or a lower (¢^-04) monohydric aliphatic alcohol, for a total of 100 parts or more. Where vater is employed, small amounts of a lower alkyl alcohol, such as ethanol or propanol, may also be added to provide ease in formulation. Acceptable diluents, carriers and excipients are, for example, ethyl or isopropyl alcohols, polyethylene glycol, povidone, polyhydric alcohols, glycerine, cellulose gums, gelatin, colorants and fragrances. If necessary, the pH of the total composition is then adjusted to the requisite pH by adding a suitable inorganic or organic acid thereto.
The result is a substantially uniform, homogeneous, relatively nontoxic composition having enhanced activity against enveloped viruses, bacteria and fungi.
It has been unexpectedly found that these compositions exhibit (1) low mammalian cell toxicity, a property which is known to correlate with low irritation
AP 0 0 0 3 2 7
- η and low toxicity when used in contact with mucous membranes (Journal Clinical Dentistry 2(2):34 - 38, (1990)), and (2) highly efficacious inactivation of enveloped viruses although cytocidal activity is low.
In the past, research has used cytocidal activity as an index of activity. (Asculai, S.S., Antimicrb. Agents Chemother. 13:678 - 690 (1978)).
In practice, the total amount of the components (a) and (b) of the overall composition can range from .01% - 40%, preferably from .03% - 30% depending on the intended means of use. For example, concentrations used are, approximately 20% - 30% in contraceptive films and 0.2% to 2% in gels.
Compositions for use in this invention comprise alkyl N-di(lover alkyl) glycines and alkyl Ndi (lower alkyl) a-aine oxides, wherein the lower alkyl is cl“3· One class betaines I have found to be partically useful in this invention are the alkyl Ndimethyl betaines, such as cocobetaines and lauryl betaines. Particularly useful amine oxides for use in this invention are the an alkyl N-dimethyl amine oxides, such as cocodimethyl amine oxides and lauryl dimethyl amine oxides.
One particular composition that can be used in this invention comprises cocobetaine, cocamine oxide and citric acid monohydrate.
Another composition that can be used in this invention comprises lauryl betaine, lauramine oxide and citric acid monohydrate.
In such compositions, the molar ratio of betaines to amine oxides is normally from 5:1 to 1:5, preferably in a molar ratio of 2:1 to 1:2, more preferably about 1:1.
Other compositions that can be used in this invention comprise mixtures of betaines, amine oxides, gelatin having a Bloom strength of 100 - 300 and a molecular weight from about 75,000 to about 300,000,
BAD ORIGINAL polyhydric alcohols and cellulose guns. Such compositions are described in a copending U.S.
application being filed simultaneously with the present application and having U.S. application Serial No. 07/673,631.
Compositions used in this invention can inhibit the activity of viruses that are related to AIDS. It is also expected that these compositions can inhibit the activity of HSV-1 and HSV-2. It is also expected that the compositions used in this invention can inhibit Hepatitis A, B and C. It is expected that the compositions can be used to inhibit viruses, bacteria and fungi which are associated with sexually transmitted diseases (STD's).
The compositions of this invention may be useful in relation to the following:
1) Transmission of HIV is often associated with the co-transmission of other viral and/or microbial pathogens. Indeed, some investigators have suggested that HIV may not be the sole agent responsible for AIDS (see Duesberg, P.H. (1991) Proc, Natl, Acad, Sci,
88:1575 - 1579; Lemaitre, M., Guetard, D., Henin, Y., Montagnier, L. and Zerial, A. (1990). Res, Virol, 141:5 - 16). For this reason, antimicrobial agents, such as those described in this application, with a broad spectrum of activities against viruses, bacteria, and yeasts such as Candida may be of particular value in the prevention and treatment of Acquired Immune Deficiency Syndrome (AIDS).
2) It is thought that certain bacteria known to cause STD's may aid in HIV transmission. In persons who have been exposed to HIV, certain bacteria which cause STD's often fail to respond to therapies that are otherwise highly effective. HIV infection may help the spread of a bacterial STD that in turn helps to spread HIV. STD's such as chlamydia, chancroid, syphilis, genital herpes and gonorrhea which cause ulcerations of
AP 0 0 0 3 2 7 the genital skin seem to increase the risk of acquiring or transmitting HIV infection sexually. Aral, S.O., et al. Scientific Arcricaru- 264 (2):62 - 69 (February 1991).
The compositions described above may also be of use to inactivate other enveloped viruses, including vaccinia, varicella, herpes zoster, cytomegalovirus, Epstein Barr virus, influenza, mumps, measles, rhinovirus, rabies and rubella. In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purposes of illustrating more specific details thereof. The invention is not to be deemed as limited thereby except as defined in the claims.
Example. 1
The composition described below is a concentrate of C31G, an equimolar preparation of cocobetaine and cocodimethylamine oxides (designations of CTFA Cosmetic and Toiletry and Fragrance Association, Wash., D.c.) [CFTA] which can be used in a number of different configurations.
Cocobetaine; 31.5% active ingredient (Al); 183.9 kg (405.5 lb),
Cocamine oxide, 31.5% (Al): 147.4 kg (325 lb), citric acid monohydrate, USP; 11.8 kg (26 lb), Purified water, USP: 11.8 kg (26 lb),
To make about 354.9 kg (782.5 lb) C31G at
29.6% Al, at a dilution 1% Al; pH « 4.9.
Example 2
The spermicidal activity of C31G of example 1 was compared to the spermicidal activity of nonoxynol-9 (N-9).
The studies were conducted using the HamiltonThorn Sperm Motility Analyzer. Samples of pooled washed semen were incubated with dilutions of the two compounds for fifteen seconds and were analyzed (in triplicate) for determination of the minimum concentration for inactivation by the following criteria;
BAD ORIGINAL
1. Inhibition of sperm motility (Figure 1)
2. Decrease in total sperm count (Figure 2)
3. Inhibition of the mean progressive sperm velocity: (Figure 3)
As shown in Table 1, C31G and N-9 gave identical results:
Table 1
Minimum Concentration fcr Spermicidal Activity
C31G N-9
10 Total Inhibition of Motility | 150 | ppm | 150 | ppm |
90% Decrease in Sperm Count | 150 | ppm | 150 | ppm |
50% Decrease in Progressive | ||||
Velocity | 125 | ppm | 125 | ppm |
£xarple_2
The cytotoxic effects of C31G and N-9 on mammalian cells were determined in several types of assays. Cell toxicity is an indication of the relative safety and comfort in use of surfactants in contraceptives or prophylactics.
As shown in Figure 4, a two week study monitoring drug effects on SUP-TI cells, (a human lymphocytic cell line), C31G demonstrated minimal toxicity at 0.001% [10 ppm] while N-9 at the same concentration was extremely toxic.
Example, 4
Figure 5 shows MMT reduction in CEM cells after five days of continuous exposure. Under these conditions C31G showed no toxicity to mammalian cells at 3 ppm [.0003%] while N-9 showing toxicity, reducing mammalian cell viability by 50% at the same concentration. It is unexpected that a compound having the same spermicidal activity as N-9 would be less toxic to mammalian cells than N-9.
Example 5
Antiviral activity of C31G was tested using HSV-1 and HIV-1.
To test the effect of C31G and N-9 on herpes
AP 0 0 0 3 2 7
- 15 simplex virus type-1 (KOS strain), the virus stock was prepared in Vero (African green monkey kidney) cells.
The virus was released from the cells by one freeze-thaw cycle followed by sonication. The virus titer was 4.5 X 10® plaque forming units (PFU)/ml, as determined on Vero cells. The drug formulations used were identical to the drugs in the spermicidal study.
The stock concentration of each drug was 51. Two-fold serial dilutions were made, down to 0.04$, in
PBS pH 7.4 at | room temperature. | 24 ul of each dilution |
was added to | 220 ul of virus (10 | 8 PFU), giving final |
concentrations of 0.5 - 0.004%. | These samples vere | |
incubated at | room temperature for 10 min, and then lOOul | |
of each was immediately diluted | to 1 ml with ice-cold | |
DMEM/5% FBS. | 10-fold serial dilutions were then made, | |
down to 10-7 | for titration of rerlining infectious virus | |
on Vero cells | in 24-well plates. | Plaques were counted |
36 hours post | -infection. | |
Table 2 | ||
Concentration | ill Residual virus fPFU/ml) | |
C31S | ||
0.004 | 3.5 X 10® | 3.5 X 10® |
0.008 | 2.7 X 10® | 3.3 x 10® |
0.015 | 1.1 X 10® | 2.5 X 105 |
0.03 | 3200 | <167 |
0.06 | <167 | <167 |
0.13 | <167 | <167 |
0.25 | <167 | <167 |
0.5 | <167 | <167 |
Note that these are titers (ie. | PFU/ml) , rather than |
absolute numbers of PFU. The titer determined for untreated virus was 4.7 x 10® PFU/ml in the experiment using N-9 and 4.5 x 10® PFU/ml in the experiment using C31G.
It is noted that complete inhibition of plague formation by C31G occurs at more than one dilution below that of N-9. See Figure 6.
θΑΟ ORIGINAL
ΊΛ
Example 6
The inactivation of HIV-l (AIDS) virus vas studied in two experiments. The first study compared the effects of C31G of HIV-l at two different exposure times, 2 minutes and 45 minutes. The next study compared the relative activity of C31G and N-9 on HIV using the same virus strain and measuring antiviral activity by reduction of virus titer as determined by reduction of P-24 HIV antigen.
The protocol and results of the first study follow: EFFECTS OF C31G ON HUMAN IMMUNODEFICIENCY VIRUS
Materials:
Virus: HIV-l strain 3B (5xl05 ID50 units/ml)
Cells: SUP-ΤΙ cell line (CD4+ lymphoid cells which produce characteristic cell fusion with giant cells and syncytia when infected with HIV)
Protocol:
1. Serial fourfold dilutions of C31G in PBS (4.0% 0.004% and PBS alone as control) were prepared. pH was adjusted to 5.5.
2. Pooled aliquots of viral stock were prepared and C31G vas added at each concentration, at 1:9 detergent:virus ratio (1:10 detergent dilution). These vere incubated for either 2 or 45 minutes.
3. Serial fourfold dilutions of each virus/detergent mixture down to 1:4096 vere prepared.
4. 16.6 ul of each virus/detergent dilution from each series vere added to four replicate wells of sup-Tl cells (104 cells in 150 ul volume; 1:10 detergent dilution followed by further fourfold dilutions).
5. The wells vere examined twice weekly for two weeks and each well was scored positive or negative for the presence of characteristic viral syncytia or non-syncytial ghost formation due to detergent lysis.
Note:
Virus vas exposed to C31G at a 1:10 dilution of
AP 0 0 0 3 2 7
- 17 initial concentration for either 2 or 45 minutes, followed by another 1:10 dilution and then serial four-fold dilutions for the entire period.
Cells were exposed to C31G at a 1:100 and then serial fourfold dilutions of initial concentration for entire period.
See Figure 7.
Swaplft-Z
The protocol and results of the second study follows:
Materials!
Cells: CEM cell line ATCC <119 T cell
Virus: HIVmb
Test compounds: Compounds C31G and N-9, supplied as 5% solutions, were filtered through a low binding 0.22 filter prior to diluting.
Protocol:
1. Serial 2 fold dilutions of compounds N-9 and C31G in PBS adjusted to pH 5.5 were prepared. The highest concentration vas 4% and the lowest was 0.03%. The initial concentrations were 4, 2, 1, 0.5, 0.25, 0.125, 0.06, and 0.03%, as well as a control without drug. The control titration vas done twice.
2. 14 12 x 75mm sterile plastic tubes vith 0.9 ml each of concentrated virus (at least 1 x 106 TCID50/ml) were set-up. 0.1 ml of each compound dilution vere transferred to a tube (dilution of 1:10 of the initial drug concentrations).
3. Incubation was for 10 minutes at room temperature, and was terminated (or slowed) by diluting 1:10 in complete growth medium (on ice).
4. Additional serial 5 fold dilutions (7 dilutions, with the final dilution equal to 1:781250) in complete medium on ice were prepared.
5. 50 ul of the virus dilutions were added to quadruplicate wells of 96 well trays (U bottom) containing 3 X 104 CEM cells in 50 ul.
BAD ORIGINAL
6. 60 minutes vere allowed for virus absorption. The cells vere washed twice by centrifuging the plates at 1500 rpm for 5 minutes and aspirating the supernatents. The final cell pellets were resuspended in 100 ul of medium and transferred to flat bottom 96 well trays. The results are shown in Figures 8 and 9.
Example 8
Formulations for Contraceptive/Antilnfective Preparations
Concentrate (CCon) comprises:
Lauryl Betaine (30% ai) 1000 pts
Lauramine Oxide (30% ai) 870 pts
Citric Acid monohydrate 69 pts
The above are stirred to a uniform solution. At a dilution of one part to 30, the composition should have a pH of 4.85 at the glass electrode. Putative concentration equal to 28.5% active ingredients (ai).
Example 9
Suppositories (inserts) for use with or without Condoms CCon (of Example 8) . 526 pts
PEG-32 4000 pts
PEG-20 1000 pts
Povidone 74 pts
The above are stirred to solution at 45*C. and injected into molds, cooled and ejected for packaging.
Example 10
Contraceptive Sponge
CCon (of Example 8) 3.5 gms
Added to each mold for curing urethane. Charge in mold provided vith polyester loop for post coital removal of the sponge.
Example_lA
Spermicidal Gels, Creams or Jellies for use with Cervical Caps Condoms, Diaphragms or alone prior to coitus.
Gel-1 CCon (of Example 8) 7.0 pts
Gelatin A200 1.5 pts
7.0 pts 1.5 pts
AP 0 0 0 3 2 7
- 19 Glycerine 10.0 pts
Hydroxyethyl Cellulose (high viscosity Grade) 0.4 pts
Water 81.1 pts
Gel-2 As above with the substitution of
1.0 pt of Nonoxynol-9 for 3.5 pts of CCon (of Example 8).
Procedure - The gelating and cellulose cum are triturated in the glycerine and added to the water at 45*C. and stirred to solution. The surfactants are added to the vessel and the warm solution removed for packaging. A uniform fluid high viscosity gel forms on cooling.
Jelly 1 and 2
Clear fluid contraceptive jellies are prepared by substitution of 1.5 pts of high viscosity grade hydroxypropyl or hydroxypropylmethyl cellulose for the gelatin and hydroxyethyl cellulose of the above examples.
Creme 1 and 2
The Gel formulations above are converted to Cream formulations by incorporation of 0.5 pts of cetyl alcohol in Gel 1 or 2 formulations by dissolving the alcohol in the glycerine at 49’C. before trituration of the gelating and cellulose gums.
Example 12
Contraceptive Film
6.2 lbs of gelatin Type A100 is triturated with 0.5 lbs of hydroxyethylcelluose. 31 lbs of glycerine are added. Solution is mixed thoroughly to form a slurry. Add 33 lbs of CCon of Example 8 and 15 lbs of water. Warm to 40*C. Mix until gums and gelatin are completely hydrated. Solution is poured on polyethylene sheet to cast a film of about 3 mm thick to be cut for films to be used as contraceptive films after cooling.
Claims (19)
1 - 11 , vherein the betaine and amine cxide composition is incorp-orated into or applied in the fora of a foam, gel, cream, salve, jelly, lotion, liquid, spray, mist, aerosol or wipe.
1 - 9, vherein the alkyl N-di(lover alkyl) betaine is cocctetair.e or lauryl-betaIne, and the alkyl N-di (lover alkyl) amine oxide is coccamine oxide or lauramine oxide.
1 - 8 , vherein the composition comprises:
a) an alkyl dimethyl glycine;
b) an alkyl dimethyl amine oxide and
c) acid in an amount sufficient to adjust the pH cf the composition from 4-8 vhen measured in an aqueous solution of components (a) and (b) in an acceptable carrier.
1-7, vherein the composition comprises alkyl N-di(lover alkyl) betaine, alkyl N-di(lover alkyl) amine oxide and acid in an amount sufficient to adjust the pH of the composition from 4-8 vhen measured in an aqueous solution in an acceptable carrier.
1-6, vherein the alkyl N-di(lover alkyl) betaines and alkyl N-di(lover alkyl) amine cxides are in a molar ratio cf from 1:5 to 5:1.
1-5, vherein the composition comprises an alkyl N-di (lever alkyl) betaine and an alkyl N-di(lover alkyl) oxide vhere the lover alkyl is C^-Cj.
2. A method of inhibiting activity of sperm comprising using as a spermicide a composition comprising a/ /'
SAX* AP Ο Ο Ο 3 2 7 mixture of a betaine and an amine oxide said betaine being selected iron an alkyl-N-betaine, an alkyl-N-sul fobetair.e, an acyl-N-betaine, an alkyl N-substituted aminopropionic acid or an alkyl imidazol inium betaine or a mixture of two or core thereof and said amine oxide being selected from an atkyl-N,N-dimethylamine oxide, an alkyl-N,Ndihydroxyethylamine oxide or an acylamide t-amine oxide or a mixture of two or more thereof, but excluding any medical method of treatment of the human or animal body.
3. A contraceptive device containing a composition comprising a mixture of a betaine and an amine oxide said betaine being selected from an alkyl-N-betaine, an alkyl-Nsulfobetaine, an acyl-N-betaine, an alkyl N-substituted aminopropionic acid or an alkylimidazolinium betaine or a mixture of two or more thereof and said amine oxide being selected from an alkyl-N, N-dimethylamine oxide, an alkyl-N, N-dihydroxycthylamine cxide or an acylaaide t-aaine oxide or a mixture of two or mere thereof.
4 r- 22
4. Use of a composition comprising a mixture of a betaine and an amine cxide; said betaine being selected frcm an alkyl-N-betaine, an alkyl-N-sulfobetaine, an acyl-Nbetaine, an alkyl N-substituted aminopropionic acid or an alkylimidazolinium betaine or a mixture of tvo or more thereof and said amine oxide being selected from an alkyl-N, N-dimethylamine oxide, an alkyl-N,N-dihydroxyethylamine oxide or an acylamide t-aaine oxide or a mixture of tvo or acre thereof for preparing a medicament for use in inhibiting the activity of enveloped viruses or for use as a spermicide.
5. A medicine for treating viral infections comprising a mixture of a betaine an,d an amine oxide; said betaine being selected froa an alkyl-N-betaine, an alkyl-Nsul fobeta ine , an acyl-N-betaine, an alkyl N-substituted aminopropionic acid or an alkylimidazolinium betaine or a mixture of tvo or aore thereof and said aaine oxide being selected froa an alkyl-N,N-dimethylanine oxide, an alkylN,N-dihydroxyethylamine oxide or an acylaaide t-aaine oxide or a mixture of two or more thereof.
BAD ORIGINAL
6. A method or device according to any one of claims
7. A method or device according to any one of claims
8. A method or device according to any one of claims
9. A method or device according to any one of claims
10. A method or device according to any one of claims
11. A method according to any one of claims 1, 2, or 4, vherein the composition is applied to a mucous membrane, to skin, to the vagina, to an inaminate surface or dispersed in air.
12. A method or device according to any one of claims
13. A method according to any one of claims 1, 4, or 5,vherein the virus is HIV, a virus associated vith
AP Ο Ο Ο 3 2 7 aids, HSVI, HSVII, Hepatitis A, Hepatitis B, Hepatitis C, vaccinia, varicella, herpes zester, cytcmega1ovirus, Epstein Barr Virus, Influenza, mumps, measles, rhinovirus, rabies or rubel1 a ,
14.
method according to any one of claims 1, 2, 410, wherein the composition is used vith or incorporated into a contraceptive device.
.
15.
A contraceptive device according to claim 3 wherein the composition is incorporated into a lubricant applied to a condom or the composition is part of a reservoir at the tip of a condom, the composition is incorporated into a contraceptive sponge, contraceptive film, sustained release device, suppository, foam, gel, cream or jelly.
16. A douche comprising a mixture of a betaine and an amine oxide said betaine selected from an alkyl-N-betaine, an alkyl-N-sulfcbetair.e, an acyl-K-beta ir.e, an alkyl Nsubstituted aminopropionic acid or an alkylimidazolinium betaine or a mixture of two or more thereof; and said omir.e oxide selected froa an alkyl-N,N-dieethylamine oxide, an alkyl-N, N-dihydrcxyethylaaine oxide or an acylamide t-amir.e oxide or a mixture of two or more thereof.
17. A wipe comprising a mixture of a betaine and an amine oxide said betaine selected from the an alkyl-Nbetaine, an alkyl-N-sulfobetaine, an acyl-N-betaine, an alkyl N -substituted aminopropionic acid or an a Iky1imidazolinium betaine and a mixture of two or more thereof; and said amine oxide selected from an alkyl-N, Ndimethylamine oxide, an alkyl-N,N-dihydrc xyethy1 amine oxide or an acylamide t-amine oxide cr a mixture of two or more thereof .
BAD OWGINAI
18.
- A cream comprising a mixture of a betaine and an amide oxide said betaine selected from an alkyl-N-betaine, an alkyl-N-sulfobetaine, an acyl-N-betaine, an alkyl N-substituted aminopropionic acid or an alky 1imidazoliniurr. betaine or a mixture of two or more thereof; and said amine oxide selected from an alkyl-N, Ndimethylamine oxide, an alkyl-N,Ν-dihydroxyethylamine oxide or an acylamide t-amine oxide or a mixture of two or more thereof.
19. A cream according to claim 20 further comprising gelatin having a Bloom strength of 100 - 300 and a molecular weight of about 75,000 to about 300000, a polyhydric alcohol and cellulose gums.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/673,784 US5314917A (en) | 1991-03-22 | 1991-03-22 | Method for inactivating enveloped viruses and sperm |
PCT/US1991/005060 WO1992016201A1 (en) | 1991-03-22 | 1991-07-17 | Method for inactivating enveloped viruses and sperm |
Publications (2)
Publication Number | Publication Date |
---|---|
AP9200370A0 AP9200370A0 (en) | 1992-04-30 |
AP327A true AP327A (en) | 1994-03-21 |
Family
ID=24704111
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
APAP/P/1992/000370A AP327A (en) | 1991-03-22 | 1992-03-23 | Method for inactivating enveloped viruses and sperm. |
Country Status (12)
Country | Link |
---|---|
US (2) | US5314917A (en) |
EP (2) | EP0733361B1 (en) |
JP (2) | JP3228928B2 (en) |
KR (1) | KR100221486B1 (en) |
AP (1) | AP327A (en) |
AT (2) | ATE201593T1 (en) |
AU (1) | AU661968B2 (en) |
CA (1) | CA2106683C (en) |
DE (2) | DE69130871T2 (en) |
OA (1) | OA09911A (en) |
RU (1) | RU2110256C1 (en) |
WO (1) | WO1992016201A1 (en) |
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Publication number | Priority date | Publication date | Assignee | Title |
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US5389676A (en) * | 1991-03-22 | 1995-02-14 | E. B. Michaels Research Associates, Inc. | Viscous surfactant emulsion compositions |
AU725432B2 (en) * | 1996-04-17 | 2000-10-12 | Centaur Pharmaceuticals, Inc. | Nitrone free radical trap treatment of dementia associated with AIDS virus (HIV-1) infection |
WO1998010744A1 (en) * | 1996-09-12 | 1998-03-19 | Simon Everard Barton | Composition comprising an antiviral or antibacterial agent for preventing transmission of diseases |
IT1305313B1 (en) | 1998-07-17 | 2001-05-04 | Colla Paolo | 3,4 - DIHYDRO- 6- BENZYL-4-OXOPYRIMIDINE REPLACED AND RELATED PROCESS OF PRODUCTION AND USE IN THE THERAPY OF HIV-1 INFECTIONS. |
US6830557B2 (en) * | 2000-02-17 | 2004-12-14 | Leonard Paul | Liquid foaming soap compositions and dispensing system therefor |
WO2002040021A2 (en) * | 2000-11-17 | 2002-05-23 | Idenix (Cayman) Limited | Methods for inhibiting the transmission of hiv using topically applied substituted 6-benzyl-4-oxopyrimidines |
US7086403B2 (en) * | 2000-12-05 | 2006-08-08 | Church & Dwight Co., Inc. | Condom with male genital desensitizer lubricant |
US6616922B2 (en) | 2001-03-27 | 2003-09-09 | The Dial Corporation | Antibacterial compositions |
US6635679B2 (en) * | 2001-05-14 | 2003-10-21 | Akzo Nobel N.V. | Methods and compositions for inactivating viruses |
US6581775B1 (en) * | 2001-08-10 | 2003-06-24 | Garo Hagopian | Method of external genital cleansing and prophylactic kit |
US7544696B2 (en) * | 2003-01-24 | 2009-06-09 | Research Triangle Institute | Spermicidal and/or antifungal composition and methods of using the same |
US20050037508A1 (en) * | 2003-08-12 | 2005-02-17 | Juan Hernandez | Microfluidic titration apparatus |
WO2005019417A2 (en) * | 2003-08-14 | 2005-03-03 | The Bio Balance Corporation | Bacterial strains, compositions including same and probiotic use thereof |
AR057623A1 (en) * | 2005-11-28 | 2007-12-05 | Omega Bio Pharma H K Ltd | MATERIALS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS |
WO2007101238A2 (en) * | 2006-02-28 | 2007-09-07 | Biofilm Innovations Group, Llc | Antimicrobial compositions and method |
US20090118352A1 (en) * | 2007-11-07 | 2009-05-07 | Esawtech, Ltd. | Broad spectrum microbicidal and spermicidal compositions and methods |
US9751834B2 (en) | 2011-05-26 | 2017-09-05 | Gri Bio, Inc. | Oxygenated amino- or ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives and their medical use |
DK2809318T3 (en) | 2011-05-26 | 2019-07-22 | Gri Bio Inc | Ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives and their medical use |
CA2887385C (en) | 2011-05-26 | 2017-01-10 | Glycoregimmune, Inc. Carrying On Business As Gri Bio, Inc. | Hydroxy-substituted amino and ammonium derivatives and their medical use |
DK2879691T3 (en) | 2012-08-06 | 2019-06-11 | Biogen Ma Inc | METHODS AND COMPOSITIONS FOR DISABLING CREATIVE WEAR |
GB201617063D0 (en) * | 2016-10-07 | 2016-11-23 | Cambridge Design Research Llp | Condoms |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4075350A (en) * | 1975-12-18 | 1978-02-21 | Michaels Edwin B | Antimicrobial compositions employing certain betaines and certain amine oxides |
US4839158A (en) * | 1986-02-25 | 1989-06-13 | E. B. Michaels Research Associates Inc. | Process and composition for oral hygiene |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2169976A (en) * | 1934-01-26 | 1939-08-15 | Ig Farbenindustrie Ag | Process of producing assistants in the textile and related industries |
US2888383A (en) | 1956-09-12 | 1959-05-26 | Int Minerals & Chem Corp | Oral prophylactic compositions comprising a betaine derivative |
BE622461A (en) | 1959-04-20 | |||
US3296145A (en) * | 1965-10-21 | 1967-01-03 | Millmaster Onyx Corp | Quaternary ammonium-tertiary amine oxide compositions |
US4215144A (en) | 1972-08-25 | 1980-07-29 | Oxford Hill Ltd. | Method of treating and controlling gingivitis |
US3898186A (en) | 1973-04-09 | 1975-08-05 | Procter & Gamble | Dishwashing compositions containing gel forming gelatin |
US3976765A (en) | 1973-11-01 | 1976-08-24 | Colgate-Palmolive Company | Antibacterial oral preparations |
US4062976A (en) * | 1975-12-18 | 1977-12-13 | Michaels Edwin B | Antimicrobial compositions employing certain substituted alanines and certain t-amine oxides |
US4183952A (en) * | 1975-12-18 | 1980-01-15 | Michaels Edwin B | Antimicrobial compositions |
CH600878A5 (en) | 1975-04-28 | 1978-06-30 | Gaba Ag | |
US4117107A (en) | 1975-10-17 | 1978-09-26 | Noxell Corporation | Method and composition for improving oral hygiene |
CA1052273A (en) * | 1975-12-18 | 1979-04-10 | Edwin B. Michaels | Antimicrobial compositions |
US4093711A (en) | 1976-08-13 | 1978-06-06 | Noxell Corporation | Oral hygiene |
US4439355A (en) | 1976-12-02 | 1984-03-27 | Colgate-Palmolive Company | Elastic detergent product of improved foaming power after use |
US4554097A (en) | 1976-12-02 | 1985-11-19 | Colgate-Palmolive Company | Elastic detergent product containing anionic and amphoteric synthetic organic detergents |
US4207198A (en) | 1976-12-02 | 1980-06-10 | Colgate-Palmolive Company | Elastic detergent cake of improved foaming power after use |
US4130637A (en) | 1977-01-31 | 1978-12-19 | Colgate-Palmolive Company | Anti-plaque agents |
US4145436A (en) * | 1977-11-07 | 1979-03-20 | Michaels Edwin B | Antimicrobial compositions and method for using same |
DE2852124A1 (en) | 1977-12-07 | 1979-06-13 | Unilever Nv | TOOTHPASTE |
US4213961A (en) | 1978-03-23 | 1980-07-22 | Beecham, Inc. | Oral compositions |
US4209533A (en) | 1979-01-25 | 1980-06-24 | University Of Pittsburgh | Antibacterial agent and method |
DE3138770A1 (en) | 1981-09-30 | 1983-04-14 | Hoechst Ag, 6230 Frankfurt | "HAIR AND BODY CLEANING AGENT CONTAINING ALKYLSULFATOBETAINES" |
US4521827A (en) | 1981-10-23 | 1985-06-04 | Thermalloy, Inc. | Heat sink mounting |
US4451385A (en) | 1982-03-15 | 1984-05-29 | Colgate-Palmolive Company | Agent for reducing detergent irritation to skin and eyes |
US4490353A (en) | 1983-07-13 | 1984-12-25 | Colgate-Palmolive Company | Antiplaque dentifrice with improved fluoride stability |
DE3528209C2 (en) * | 1984-08-07 | 1993-10-28 | Fresenius Ag | disinfectant |
DE3613944C1 (en) | 1986-04-24 | 1987-08-13 | Goldschmidt Ag Th | Process for the production of a highly concentrated, flowable and pumpable betaine solution |
DE3706484A1 (en) * | 1987-02-27 | 1988-09-08 | Bernhard Dr Janiak | Virucides and spermicides containing quaternary ammonium salts |
US5244652A (en) | 1991-03-22 | 1993-09-14 | E. B. Michaels Research Associates, Inc. | Viscous surface active composition |
-
1991
- 1991-03-22 US US07/673,784 patent/US5314917A/en not_active Expired - Lifetime
- 1991-07-17 RU RU93056144A patent/RU2110256C1/en not_active IP Right Cessation
- 1991-07-17 AT AT96108577T patent/ATE201593T1/en active
- 1991-07-17 CA CA002106683A patent/CA2106683C/en not_active Expired - Fee Related
- 1991-07-17 WO PCT/US1991/005060 patent/WO1992016201A1/en active IP Right Grant
- 1991-07-17 EP EP96108577A patent/EP0733361B1/en not_active Expired - Lifetime
- 1991-07-17 EP EP91913586A patent/EP0576425B1/en not_active Expired - Lifetime
- 1991-07-17 DE DE69130871T patent/DE69130871T2/en not_active Expired - Fee Related
- 1991-07-17 AU AU82227/91A patent/AU661968B2/en not_active Ceased
- 1991-07-17 AT AT91913586T patent/ATE176399T1/en not_active IP Right Cessation
- 1991-07-17 JP JP51247491A patent/JP3228928B2/en not_active Expired - Fee Related
- 1991-07-17 DE DE69132621T patent/DE69132621T2/en not_active Expired - Fee Related
- 1991-10-22 KR KR1019910018612A patent/KR100221486B1/en not_active IP Right Cessation
-
1992
- 1992-03-23 AP APAP/P/1992/000370A patent/AP327A/en active
-
1993
- 1993-09-16 OA OA60412A patent/OA09911A/en unknown
-
1994
- 1994-04-04 US US08/223,096 patent/US6297278B1/en not_active Expired - Lifetime
-
2001
- 2001-06-05 JP JP2001170022A patent/JP3940568B2/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4075350A (en) * | 1975-12-18 | 1978-02-21 | Michaels Edwin B | Antimicrobial compositions employing certain betaines and certain amine oxides |
US4839158A (en) * | 1986-02-25 | 1989-06-13 | E. B. Michaels Research Associates Inc. | Process and composition for oral hygiene |
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US6297278B1 (en) | 2001-10-02 |
EP0576425A1 (en) | 1994-01-05 |
JP2002037733A (en) | 2002-02-06 |
DE69130871D1 (en) | 1999-03-18 |
WO1992016201A1 (en) | 1992-10-01 |
DE69130871T2 (en) | 1999-09-23 |
JP3940568B2 (en) | 2007-07-04 |
ATE176399T1 (en) | 1999-02-15 |
AP9200370A0 (en) | 1992-04-30 |
AU661968B2 (en) | 1995-08-17 |
EP0733361A2 (en) | 1996-09-25 |
DE69132621T2 (en) | 2002-04-18 |
KR920017649A (en) | 1992-10-21 |
JP3228928B2 (en) | 2001-11-12 |
KR100221486B1 (en) | 1999-09-15 |
CA2106683C (en) | 2002-09-24 |
EP0733361B1 (en) | 2001-05-30 |
US5314917A (en) | 1994-05-24 |
AU8222791A (en) | 1992-10-21 |
EP0733361A3 (en) | 1996-10-23 |
CA2106683A1 (en) | 1992-09-23 |
RU2110256C1 (en) | 1998-05-10 |
OA09911A (en) | 1994-09-15 |
DE69132621D1 (en) | 2001-07-05 |
EP0576425B1 (en) | 1999-02-03 |
JPH06505700A (en) | 1994-06-30 |
ATE201593T1 (en) | 2001-06-15 |
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