| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | December 3, 1991 |
| PATENT TITLE |
Systemic antiviral treatment |
| PATENT ABSTRACT | Systemic antiviral treatment using a narrow class of aliphatic straight-chain saturated monohydric alcohols which have from 27 to 32 carbons in the chain in physiologically compatible compositions for injection or trans-mucus membrance introduction into humans and other mammals is disclosed |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | November 2, 1989 |
| PATENT REFERENCES CITED | Borg et al., "Neurotrophic Effect of Naturally Occuring Long-Chain Fatty Alcohols on Cultured CNS Neurons" FEBS Letters, vol. 213, No. 2, 406-410, Mar. 1987. |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
Claims -------------------------------------------------------------------------------- What is claimed is: 1. A method of treating humans or other mammals for viral infections, comprising intravenous introduction into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 2. A method of treating humans or other mammals for viral infections, comprising intramuscular introduction into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 3. A method of treating humans or other mammals for viral infections, comprising trans-mucus membranal introduction into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 4. A method of treating humans or other mammals for viral infections, comprising transdermal penetration into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 5. A method of preventing or inhibiting the infection of humans or other mammals for viral infections, comprising intravenous introduction into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 6. A method of preventing or inhibiting the infection of humans or other mammals for viral infections, comprising intramuscular introduction into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 7. A method of preventing or inhibiting the infection of humans or other mammals, comprising trans-mucus membranal introduction into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 8. A method of preventing or inhibiting the infection of humans or other mammals, comprising transdermal penetration into the human or other mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible carrier. 9. A physiologically compatible solution which can be injected into humans or other mammals for viral infections intravenously or intramuscularly consisting essentially of a composition consisting of one or more C-27 to C-32 aliphatic alcohols in a physiologically compatible, intravenously or intramuscularly injectable carrier. 10. A physiologically compatible transdermal medication for introduction through the mucous membranes into humans or other mammals for viral infections consisting essentially of a composition consisting of one or more C-27 to C-32 aliphatic alcohols and a penetration-enhancing compound. 11. A method of preventing conception and reducing the risk of viral infection comprising introducing a composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in a suitable carrier into the vagina substantially contemporaneously with or before intercourse. 12. An anti-viral suppository for trans-membranal introduction into the vagina or anus of a human or other mammal of a composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in a physiologically acceptable carrier which is a solid at ambient room temperature and which melts at approximately 37.degree. C. 13. A method of treating humans and mammals for viral infections comprising introducing a composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons through a membrane into the circulatory system of a human or mammal suspected of having a viral infection with an effective amount of from about 0.1 mg to about 2 gm per 50 kg of body weight comprising inserting such alcohol composition in a physiologically acceptable liquid, cream, gel or suppository carrier into the anus or vagina of the human or mammal to be treated. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
Description -------------------------------------------------------------------------------- BRIEF DESCRIPTION OF THE DRAWING FIG. 1 depicts data showing the inhibition of Friend virus-induced erythroleukemia. DESCRIPTION OF THE PREFERRED EMBODIMENTS The method may be carried out using compositions in which the sole physiologically active agent(s) is the C-27 to C-32 aliphatic alcohol, or comparable compositions which may also include other physiologically active constituents which do not interfere with the efficacy of the C-27 to C-32 alcohols. Corresponding low-molecular-weight ethers of these alcohols, e.g. methyl-, ethyl-, propyl-, etc., ether derivatives of these alcohols, and corresponding low molecular weight ester derivatives, e.g. formyl-, acetyl-, propyl-, etc., ether derivatives of these alcohols are regarded as less preferred possible equivalents of the alcohols of this invention. The composition of the carrier is not critical so long as the carrier is physiologically compatible with the blood and tissues of the human or other mammal to be treated and is substantially free from any interfering physiological effect. Compositions suitable for intravenous or intramuscular injection into the human or mammal patient consist essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of the alcohol(s) in a suitable carrier. For example, a suspension of from 0.1 mg/ml to 300 mg/ml of the indicated alcohol(s) suspended in a carrier solution of isotonic sodium chloride solution containing a suitable preservative, such as 0.1 to 1.5% benzyl alcohol, stabilizers such as from 0.25 to 1% carboxymethylcellulose sodium and 0.005 to 0.1% polysorbate 80, and sufficient sodium hydroxide or hydrochloric acid to adjust the pH to 5.0 to 7.5, all percentages by weight, may be used for either intravenous or intramuscular injection. Another composition suitable for intravenous or intramuscular injection into the human or mammal patient may consist essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of the alcohol(s) in a suitable carrier in suspension of from 0.1 mg/ml to 300 mg/ml of such alcohol(s) suspended in a carrier solution of alcohol (1-10%), glycerin (10-20%) and water (balance 70-89%), along with suitable preservative. Such compositions may be injected in suitable amounts to provide a dose to the patient of from 0.1 mg/50 kg body weight to 2 gm/50 kg body weight. It is desirable to achieve and maintain a level of the specified alcohol(s) in the body in the range of at least about 0.1 mg/kg of body weight. The alcohol(s) to which this invention is directed may effectively be introduced through the mucus membrane system of the human or mammal patient. Such introduction may be, for example, through the vaginal, anal, or nasal membranes. The above liquid compositions which consist essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) in a suitable liquid carrier may, for example, be used for trans-mucus membranal introduction of such alcohol(s) into the circulatory system of the human or mammal to be treated by, for example, introducing such liquid as an aerosol into the oral or nasal passages or as liquid into the vaginal or anal passages of the body where these compounds inactivate virus locally, inhibit the passage of virus into the membrane, and pass through the membrane into the circulatory system of the patient where the compounds act as inhibitors of viral activity and infectivity and inactivate virus. In the latter applications, however, gels, creams or suppositories are more conveniently used. In one convenient embodiment, the method of the invention comprises a composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) into the vagina, where it will inhibit the activity of the sperm and interfere with fusion of the sperm cell with the female egg cell. The alcohol composition of interest may, of course, be used in connection with a diaphragm or other contraceptive device if desired. As indicated above, the alcohols of interest here will serve as contraceptive compositions. The mode of action has not been fully explored, but it is believed that these alcohols reduce the activity and viability of sperm and inhibit or prevent the sperm from attaching to and penetrating the egg, thus preventing fertilization. Likewise, the alcohol-containing composition may be introduced through the anus where it also inactivates virus, inhibits the passage of virus into the membrane, and passes through the membrane into the circulatory system of the patient where it acts as an inhibitor of viral activity and infectivity and inactivates virus in the circulatory system and cells nourished by the circulatory system. The specified alcohol(s) may be in any physiological acceptable form such as in cream or suppository compositions. An exemplary suppository may consist essentially of a composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) alone or in a concentration of from 0.05 mg alcohol(s)/gm of carrier to 400 (or higher) mg alcohol(s)/gm of carrier. Cocoa butter is a commonly used suppository carrier component, alone or in mixture with, for example, tartaric acid and malic acid. Polyethylene glycols of suitable molecular weight are also suitable suppository carriers. Suppositories may also include a preservative such as methylparaben or benzethonium chloride, and such acid or base components as are desired to adjust the pH to the range of about pH 5 to pH 7.5. Any of the above, or other, suitable suppository carrier compositions may be used with composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) to form a suitable contraceptive and/or anti-viral suppository. The suppository, to be commercially and aesthetically acceptable, must be a solid at ambient room temperature, i.e. generally in the range of about 27.degree. C., and must melt at or slightly below normal body temperature, i.e. in the general range of about 37.degree. C. These temperatures are, of course, only general ranges, and the precise melting point is not critical. Trans-membranal introduction of such alcohol(s) may be accomplished by introducing small amounts of such alcohols neat, but such introduction is difficult to control and not efficient. Cream and gel compositions consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) in concentrations of from about 0.1 mg/ml to 300 mg/ml (or higher) in a suitable cream or gel carrier may also be used effectively. Such a gel may, for example, comprise a suspension agent such as Carbomer.RTM. polyacrylic acid cross-linked with allyl sucrose, polyethylene glycol, water and suitable preservatives. A suitable cream base may, for example, comprise white petrolatum, polyoxyethylene stearate, cetyl alcohol, stearyl alcohol, propylene glycol, isopropyl myristate, sorbitan monooleate and water along with suitable preservatives adjusted to a pH of from pH 5 to pH 7.5. The alcohols of interest here may also be introduced for trans-membranal passage into the human or mammal patient's circulatory system, as well as a prophylaxis against infection from airborne virus, through inhalation of a composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) in a suitable physiologically acceptable carrier. The liquid compositions mentioned before may, for example, be packaged in a nebulizer and introduced through nasal or oral passages in the customary manner. An exemplary composition consisting essentially of one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of such alcohol(s) suspended in aerosol propellant such as trichloromonofluoromethane and/or dichlorodifluoromethane, along with diluents, preservatives, pH adjusting reagents, etc. The exemplary aerosol composition delivers essentially neat alcohol(s) to the mucus membrane. An exemplary ear drop composition delivers essentially neat alcohol(s) to the tympanic membrane. Comparable liquid drops may be applied using appropriate droppers to the eyes, ears and mouth for application to and passage through the membranes in these respective organs. All trans-membranal compositions may, in addition to other ingredients, may also include penetration enhancers. A number of such enhancers are known as penetration enhancers and may be used in the compositions of this invention. One such vehicle is dimethyl sulfoxide, which is described in U.S. Pat. No. 3,551,554. Other such penetration enhancers are disclosed in U.S. Pat. Nos. 3,989,816; 3,991,203; 4,112,170; 4,316,893; 4,415,563; 4,423,040; 4,424,210; 4,444,762, sometimes referred to as Azone.RTM.. The discovery that these alcohols, which are naturally occurring and are essentially non-toxic in concentration ranges of interest have significant anti-viral effect is considered to be of major import inasmuch as the way is open to providing a safe and effective method for the treatment for virus diseases and for preventing or at least significantly reducing the likelihood of virus infection to the human or other mammal patient, without any significant side effects and without the need for as intense monitoring by the treating physician as is required with inherently toxic compounds. As a treatment for acquired immunodeficiency syndrome (AIDS), as a method for prophylatic treatment of persons exposed to AIDS and/or carrying AIDS virus but without demonstrating, AIDS symptoms, and as methods and compositions for preventing or reducing the risk of infection by AIDS and virus-induced diseases, the present invention is regarded as a significant improvement. Another important aspect of the invention is that it may provided a safe and effective mode of treatment of diseases resulting from infection of the patient with such lipid-containing virus as HTLV-1, HSV-1, HSV-2, cytomegalovirus (CMV), Epstein-Bar (EBV), and influenza viruses. The risk of infection by such viruses as HIV, HSV-1, HSV-2, CMV, EBV, influenza viruses and other viruses which are communicated by personal contact, contact with contaminated blood or tissue or laboratory instruments or devices, aerosol transmission, etc., may be substantially reduced by the methods and compositions of the present invention. It is believed that another mode of action of the alcohols of this invention is in the inhibition or prevention of malignant growth and/or metastasis. If, for example, cancer cells cannot metastasize, or the rate of metastasis is reduced, then the spread of cancer may be blocked or reduced. Significant inhibition of cancer cell metastasis coupled with natural or drug-induced death or destruction of existing cancerous cells will lead to partial or total remission of the disease. The same principle applies, of course, to any disease which is propagated by cell metastasis. Accordingly, the present invention is considered useful in the treatment of nonvirus-induced disease and diseases which are not dependent upon viral replication but which are spread by metastasis. It will be readily understood from the foregoing that the essential constituent(s) of the compositions useful in the present method is one or more aliphatic alcohols having from 27 to 32 carbons in the aliphatic chain of the alcohol(s), and that the composition of the carrier is non-critical and subject to great variation. INDUSTRIAL APPLICATION This invention is useful in treating and suppressing virus-induced diseases of humans and other mammals. |
| PATENT PHOTOCOPY | available on request |
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