Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Patent
1994-07-12
1997-10-21
Tsang, Cecilia J.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
530345, 514 6, 514 21, 514832, 4241931, 4241941, 42419511, A61K 3514, A61K 39385
Patent
active
056797770
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
Hoffman and Nagai, U.S. Ser. No. 07/194,338, filed May 10, 1988, now U.S. Pat. No. 5,028,588, presently owned by Somatogen, Inc. relates to the use of low oxygen affinity mutant hemoglobins as blood substitutes, and to the expression of alpha and beta globin in nonerythroid cells. Hoffman and Nagai, U.S. Ser. No. 07/443,950, filed Dec. 1, 1989, discloses certain additional dicysteine hemoglobin mutants; it is a continuation-in-part of 07/194,338. Hoffman, et al., Ser. No. 07/671,707, filed Apr. 1, 1991, which is the national stage of PCT/US0/02654, filed May 10, 1990, discusses expression of hemoglobins in yeast, polycistronic coexpression of alpha-and beta-globins and in vivo assembly of biologically active, tetrameric hemoglobin, and the production of di-alpha and di-beta globin pseudodimers and their use in the assembly of pseudotetrameric hemoglobins with increased intravascular retention. Hoffman, et al., Atty. Docket No. HOFFMAN5B-USA, filed Nov. 8, 1991, entitled PRODUCTION AND USE OF HEMOGLOBINS AND ANALOGUES THEREOF, Ser. No. 07/789,179 now U.S. Pat. No. 5,545,727, is a continuation-in-part of Ser. No. 07/671,707, and discloses monocysteine mutants of hemoglobins and the production and use of octomeric and other multimeric hemoglobins built by use, e.g., of pseudodimers. The foregoing related applications are hereby incorporated by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to the controlled release of drugs in the blood.
2. Description of the Background Art
Many pharmaceuticals have a relatively short half-life in the bloodstream due to renal clearance or rapid metabolism. This is particularly true for polypeptide pharmaceuticals which are smaller than the renal filtration limit of about 50,000 to 70,000 daltons. In recent years, many pharmaceutical companies and other institutions have devoted considerable time and resources into extending the duration of a drug in the human body. The advantages of having a patient take a drug less often are numerous; such as, better compliance, more predictable concentrations in the body, and fewer side effects from the sudden rush of medication shortly after it is administered. All medications, especially those given prophylactically or for a long period of time, are more readily accepted by the patient if they need to be taken less often.
For medications which are given parenterally, every injection carries with it a chance for infection and imparts a certain amount of pain. Many patients are hospitalized simply because they need continuous or frequent injections of various pharmaceuticals. If the drug could be administered less often, some hospitalization costs may be avoided.
To overcome the problem of rapid removal of a drug from the body, one may give the patient very large doses so that the body receives an effective dosage for a longer period of time. However, the higher doses may result in more pronounced adverse effects.
Alternatively, one may include incorporation of the drug in a slowly dissolving or decomposing agent. The use of low-dose penicillins in ammonium sterate for the treatment of syphilis and streptococcal infections, and for prophylaxis against rheumatic fever is one example; the use of Freund's adjuvant for increasing the potency of vaccines is another. Polymers such as N-(2-hydroxypropyl)methacrylamide copolymers have also been proposed (Seymour et al, British Journal of Cancer, 63(6): 859-66 (1991)). Loose ion-ion bonding between drug and carrier has also been used for slow release of a pharmaceutical as described in U.S. Pat. No. 4,374,932. Some medications, such as contraceptives, are bound tightly to a carrier for very slow release over a period of months or years. The advantages in patient compliance over taking a pill everyday for the same period of time are readily appreciated. Another slow-release means is an insulin pump.
Clinicians have gone so far to ensure adequate long term dosage that they have even co-administered a different medicati
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Anderson David C.
Mathews Antony James
Cooper Iver P.
Mohamed Abdel A.
Somatogen, Inc.
Tsang Cecilia J.
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