This invention relates to the sampling of blood and body fluids to inactivate or destroy infective viruses.
Those who deal with blood and other invasively obtained body fluid samples risk infection from the samples. Those at risk include the doctor, nurse or clinical technician who takes the sample, the technicians who handle the sample and who use the sample in conducting analyses and tests, those who handle the sampling and testing equipment and apparatus, and the entire chain of individuals who attend to the disposal of sampling apparatus and the like, from the individuals who pick up the used apparatus through those who ultimately dispose of the apparatus, usually in specially designed high-temperature furnaces.
The risk is substantial, as evidenced by the fact that nearly all health care professionals with long experience carry the Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), the latter being probably the most ubiquitous of the pathogenic viruses. Other pathogenic viruses to which health care workers, and those who handle blood and fluid sampling and handling apparatus, are exposed include hepatitis and human immunodeficiency virus (HIV) as well as a large number of less life-threatening viruses.
CMV is frequently associated with Pneumoncystis carinii and may cause or contribute to encephalitis and colitis and may be associated with Kaposi's sarcoma in AIDS patients. CMV carriers frequently exhibit no symptoms of infection; however, the direct and contributory effects of CMV in infectious diseases is so pervasive and subtle that a CMV infection is to be presumed if another causative agent cannot be established.
CMV is a member of the human herpesvirus (HV) group, which are responsible for much of mankind's discomfort and pain. The herpesviruses represent a very large, clearly defined group of viruses which are responsible for, or involved in, cold sores, shingles, a venereal disease, mononucleosis, eye infections, birth defects and probably several cancers. Three subfamilies are of particular importance. The alpha subfamily includes HV-1 (herpes virus simplex 1) which causes cold sores, fever blisters, eye and brain infections, HV-2 (herpes virus simplex 2) which cause genital ulceration, and HV-3 (HV varicella zoster) which causes chicken pox, shingles and brain infections. The beta subfamily includes HV-5, the principal member of which is CMV discussed above. The gamma subfamily includes HV-4 (Epstein-Barr) which causes infectious mononucleosis and is involved in Burkitt's lymphoma and nasopharyngeal carcinoma. Additional possibly pathogenic herpes viruses no doubt exist, one type of which, HV-6, of unknown pathogenicity has been identified. (Niederman, J. C. et al., The Lancet, Oct. 8, 1988, 817.) There is evidence that the methods of this invention are effective in inhibiting the transmission of infections caused by many and perhaps all of the pathogenic herpes viruses.
At least one of the retroviridae is susceptible to the treatment of this invention, according to presently available data. The most notorious of the retroviridae, HIV-1, the only virus thus far identified as inducing AIDS in humans, is inactivated and/or killed using the methods and compositions of this invention. Other retroviridae are considered to be susceptible to the present invention. The enormity of the AIDS threat is so great as virtually to defy analysis. While the fear of HIV-caused AIDS is so pervasive in the United States and the more developed western world as to strike fear into all who are exposed to blood and other body fluids of a large number of individuals, the magnitude of the potential for disaster posed by HIV is, perhaps, better gauged by the fact that in central Africa and other third-world countries AIDS infects up to one-third of the population.
HIV antibody screening of blood and organ donors has become an important but routine step in preventing the infection of the donee patient, (see Wilhelmus, K. R. et al., Ophthalmologica (Switzerland) 1987, 195(2) 57; Mal'khanov, V. B. et al., Vopr Virusol 1987, 32(2) 21; Salisbury, J. D. et al., Ophthalmic Surg 1984, 15(5) 406; Beekhuis, W. H., Doc Ophthalmol 1983, 55(1-2) 31; Collin, H. B., Arch Ophthalmol 1976, 94(10) 1726), but the risk to those who treat a large number of individuals, some of whom are certain to carry HIV, remains a very serious problem indeed.
The addition of detergents to various blood fractions has been described. My European Patent Specification 0 050 061, published Dec. 11, 1985, in which the term "detergent" is equated with the term "amphophil" to encompass cationic, anionic and nonionic detergents, describes the addition of various detergents to plasma protein products and suggests the addition thereof to other blood derivative products to inactivate virus and for other purposes, followed by the removal of the detergent from the product. High concentrations of detergents, from 0.25 to 10%, were required the process described in the European patent specification.
Bosslet and Hilfenhause, European Patent Specification 0 278 487, discloses that high concentrations of selected detergents inactivate certain envelope viruses.
Neurath and Horowitz, e.g. U.S. Pat. Nos. 4,540,573, 4,481,189, and 4,591,505, indicate, however, that detergent alone is not effective as an antiviral agent in blood plasma and related products. In spite of these teachings, however, it seems safe to conclude that at least some classes of detergents in high concentrations in some types of blood derivatives do have some inactivating effect. The extent and efficacy of such procedures seems open to considerable doubt, however.
My copending patent application Ser. No. 07/321,522, filed Mar. 9, 1989, describes and claims a method for inactivating virus in blood samples using glycyrrhizic triterpenoid compounds.
The invention described and claimed herein is an improvement thereof and is based upon the discovery of unique synergistic improvement results when detergent, even trace amounts of detergent, are combined in the blood or blood product sample with glycyrrhizic triterpenoid compounds.
The invention described and claimed herein is an improvement thereof and is further based upon the discovery of unique synergistic improvement results when glycerol, even trace amounts of glycerol, are combined in the blood or blood product sample with glycyrrhizic triterpenoid compounds.
Further, the invention described and claimed herein is an improvement thereof and is further based upon the discovery of unique synergistic improvement results when glycerol, even trace amounts of ethylene diamine tetraacetic acid or salts thereof (EDTA), are combined in the blood or blood product sample with glycyrrhizic triterpenoid compounds.