Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1995-03-27
1997-10-28
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424464, 424469, 424470, 424490, 424495, 424497, 5147723, A61K 922, A61K 926, A61K 954
Patent
active
056815816
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Field of the invention
This invention is directed to a controlled release pharmaceutical formulations of 3'-azido-3'-deoxythymidine, also known as AZT or zidovudine and methods of use thereof. The controlled release formulations of AZT achieve and maintain a therapeutic level of AZT, while substantially reducing the side affects of AZT caused by its catabolite, 3'-amino-3-deoxythymidine (AMT), by reducing the amount of AMT produced.
Retroviruses, AIDS and AZT
A virus is a biologic particle containing a nucleic acid core of DNA (deoxyribonucleic acid) or RNA (ribonucleic acid). The nucleic acid is surrounded by a protein membrane, the nucleocapsid. In some viruses there is another coat about the nucleocapsid, the envelope. The envelope is composed of vital specific proteins, lipids and carbohydrates. A viral particle is referred to as a virion.
When an infective virion enters the human body it adheres to a specific cell. This adherence is termed adsorption, which leads to a cell-virion attachment. After the virus particle attaches itself to a cell, it is transported into the cell where the envelope and the nucleocapsid are removed (uncoating). At this stage the virus is copied or replicated (replication). Transcription is the synthesis of RNA from DNA. To transcribe the viral nucleic acid into RNA, the enzyme transcriptase is required. In retroviruses, the nucleic acid is RNA. Therefore this process of transcription into DNA from RNA, is called reverse transcription and utilizes a specific enzyme, reverse transcriptase. This reverse enzyme transcription is the distinguishing feature of retroviruses.
Once in the form of DNA, the Genetic code of the virus is incorporated into the host DNA allowing it to take full advantage of the host cell's reproductive capabilities. The viral DNA incorporated into the host is virtually indistinguishable from the host DNA. Because of this, the viral code survives for the life of the cell.
A species of retroviruses was identified in the 1980's associated with the human disease, AIDS (Acquired Immune Deficiency Syndrome). The agent for this disease is called the HIV virus, (Human Immune Deficiency Virus). The HIV virus preferentially infects thymus derived lymphocytes (T4). HIV has a proclivity for these particular cells because they contain a protein coat, CD4, which preferentially binds with the HIV virus. Once infected, the immune cells decrease in number and lose their capability to produce an immune response.
There are a number of clinical manifestations of AIDS. In the initial stages when a person is infected, but does not have symptoms, they are sero-positive, referring to a positive blood test for the AIDS virus. It is in this sero-positive stage when people are carriers, capable of passing on the disease by blood transfusion, sexual intercourse or contaminated syringes. The patient may progress to the second stage, which is a persistent and chronic enlargement of their lymph nodes, or persistent generalized lymphadenopathy (PGL). In a further decline of their immune function, with a decrease in T4 cells, there is s a stage characterized by diarrhea, weight loss, fatigue and skin rashes. This condition is termed ARC (Aids Related Complex). The patient is termed as having Acquired Immune Deficiency Syndrome (AIDS). When the T4 cells fall below <200/ul, the symptoms can include fever persisting for more to than a month, involuntary weight loss of 10 percent of baseline, diarrhea lasting for more than a month or any series of opportunistic infections occur.
AIDS is a progressive, fatal disease. Currently the only Is approved primary treatment for AIDS is AZT (zidovudine). AZT is a synthesized chemical, 3'-azido-3'-deoxythymidine. Zidovudine was first identified in 1964 (J. P. Horowitz et al., J. Org. Chem., 28:2076 (1964)). The compound was later found to have antiviral activity (E. DeClerq et al., Biochem. Pharmacol., 29:1849 (1980). U.S. Pat. Nos. 4,724,232; 4,818,750; 4,828,838; 4,833,130; 4,837,208 and 4,874,609 describe uses, as
REFERENCES:
patent: 4917900 (1990-04-01), Jones et al.
Page Thurman K.
Spear James M.
LandOfFree
Controlled release pharmaceutical formulations of 3'-azido-3'-de does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Controlled release pharmaceutical formulations of 3'-azido-3'-de, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Controlled release pharmaceutical formulations of 3'-azido-3'-de will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1024347