In the United States, more than 12 million new cases of sexually transmitted diseases (STDs) occur each year. Of the top 10 reportable diseases in the United States, five are STDs including chlamydia, gonorrhea, syphilis, the Acquired Immune Deficiency Syndrome (AIDS) and hepatitis B virus (HBV) infection of which AIDS and HBV infection have no cures.
In the case of AIDS, the World Health Organization estimates that 40 (between 34 and 46) million people worldwide are living with human immunodeficiency virus (HIV), the virus that causes (AIDS). Among the 40 million, 2.5 (between 2.1 and 2.9) million are children under the age of 15. Globally, an estimated 5 (4.2-5.8) million people were newly infected and 3 (2.5-3.5) million people died of AIDS in 2003. The incidence of HIV and AIDS is on the rise in Asia, and the CIA (Central Intelligence Agency) estimates that India will have the largest population of infected people by 2010 (Weniger B C, Brown T., The march of AIDS through Asia. N Eng J Med 1996; 335: 343-5.). Hepatitis infections affect 5 times more people than HIV. It has been reported by the World Health Organization that 2 billion people alive today are infected with HBV virus, of whom 350 million are chronically infected and therefore at risk of death from liver disease.
Although mortality rates from AIDS are dropping due to new therapies, AIDS remains the second leading cause of death in adults between the ages of 29 and 40. Combination anti-HIV therapy is now the standard of care for people with HIV. There are now 11 anti-HIV drugs available by prescription. These anti-HIV drugs fall into three categories: nucleosides analogs, which include zidovudine, didanosine, zalcitabine, stavudine and lamivudine; protease inhibitors which include indinavir, nelfinavir, saquinavir and ritonavir and non-nucleoside reverse transcriptase inhibitors (NNRTI) which include nevirapine, delavirdine and efavirenz. Compared to HIV, there is presently only two-licensed therapy for chronic hepatitis B virus infection, which are interferon and lamivudine. Other drugs are currently under clinical trials including lamivudine, famciclovir, lobucavir and adefovir. But many studies have shown that most patients relapse after completion of therapy and develop resistance to the drugs.
Development of resistance has recently become a major concern in the treatment of HIV and HBV infections. Resistance usually occurs when the drugs being used are not potent enough to completely stop virus replication. If the virus can reproduce at all in the presence of drugs, it has the opportunity to make changes in its structure, called mutations, until it finds one that allows it to reproduce in spite of the presence of the drugs. Once a mutation occurs, it then grows unchecked and soon is the dominant strain of the virus in the individual. The drug becomes progressively weaker against the new strain. There is also increasing concern about cross-resistance. Cross-resistance occurs when mutations-causing resistance to one drug also cause resistance to another. Several studies have proven that combining two drugs delays the development of resistance to one or both drugs compared to when either drug is used alone. Other studies suggest that three-drug combinations extend this benefit even further. As a result, it is commonly believed that the best way of preventing, or at least delaying resistance is to use multi-drug combination therapies. The risk of drug interactions and toxicity to the patient increases as the number of drugs increases.
The current standard care is a three-drug combination, of two nucleoside analogues and one protease inhibitor. Unfortunately, non-availability, high cost, toxicity concerns and emergence of drug resistance of present anti-viral drugs, pose difficulty in therapeutic management of many patients (K Vermani, S Garg, J Ethnopharmacol, 80 (1): 49-66, 2002; J. A. Wu, A S Attele, L Zhang, C S Yuan, Am J Chin Med, 29 (1): 69-81, 2001).
Plant extracts have also been reported to have anti-viral activity. For example, the plant extract of Buxus sempervirens (code named SPV 30) had shown beneficial effect in asymptomatic HIV patients and was found to delay the progression of HIV disease (Durant J et al., Phytomedicine, 5, 1-10, 1998). However, in this investigation, a very high dose (330 mg×3/day) was given to the HIV patients. A polyherbal formulation consisting of extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia has been reported to protect nonspecific host defence mechanisms (S Chatterjee and S N Das, Ani Sci Life, 16, 200-205, 1997; Ani Sci Life, 15 (4): 250-253, 1996). Chatterjee et al also have shown that in immunodeficient and immunocompromised host, this polyherbal preparation restored and improved the immune status. A polyherbal formulation consisting of 100 mg each of extracts of Tinospora cordifolia, Withania somnifera, Emblica officinalis and Ocimum sanctum has been reported to have a favorable effect in patients with HIV infection by decreasing the mean viral load and increasing the CD4 cell count (P R Usha, Naidu M U R, and Raju Y S N, Evaluation of Antiretroviral Activity of a New Polyherbal Drug “Immu-25” in Patients With HIV Infection, Drugs R&D, 2003, 4(2), 103-109.) U.S. Pat. No. 5,529,778 has described a composition consisting of eight different plant extracts which have beneficial effects against AIDS, flu, tuberculsis, hepatitis, cirrhosis and immunodeficiency conditions. This patent also describes the use of a very high dose (1 g×2/day) to the patients. Plant extracts are not standardized against their bioactive principles. Hence, consistency of results is expected to be compromised and questionable.
It is necessary to approach the treatment of HIV disease from as many directions as possible. Complementary therapies—nutritional intervention in particular because it enhances the immune system and reduces drug side effects—are an important aspect of HIV management. Simply taking a multivitamin, in addition to eating a nutrient-rich diet, may make the difference in an HIV-positive person's life span. For many patients, combining dietary supplements with drug cocktails may be one of the most cost-effective and beneficial therapeutic protocols. In a recent study, Lu et al have concluded that AIDS is a reversible disease and using medicinal herbs to enhance the immune function will facilitate the appearance of seroconversion, which has not been reported before (Lu W B, Wen R X, Guan C F. A report on 8 seronegative converted HIV/AIDS patients with traditional Chinese medicine. Zhongguo Zhong Xi Yi Jie He Za Zhi May 1997;17(5):271-3). Accordingly, the present invention offers one such alternative in the form of a poly-herbal formulation as a stand-alone therapy or as an adjuvant to the drug cocktails.
USPTO Backgrounds
USPTO Backgrounds