Source: http://www.google.com/patents/US6071896?dq=4,923,986
Timestamp: 2016-02-08 02:09:36
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Matched Legal Cases: ['Application No. 3', 'Application No. 3', 'Application No. 1', 'Application No. 1', 'Application No. 1', 'Application No. 1', 'Application No. 61', 'Application No. 61', 'Application No. 2', 'Application No. 2']

Patent US6071896 - Suppression of thromboxane levels by percutaneous administration of aspirin - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsA method is disclosed for inducing thromboxane suppression in a mammalian subject by percutaneously administering a pharmaceutical composition containing aspirin. Articles useful for practicing the therapeutic methods of the invention are also disclosed....http://www.google.com/patents/US6071896?utm_source=gb-gplus-sharePatent US6071896 - Suppression of thromboxane levels by percutaneous administration of aspirinAdvanced Patent SearchPublication numberUS6071896 APublication typeGrantApplication numberUS 09/040,901Publication dateJun 6, 2000Filing dateMar 18, 1998Priority dateJun 16, 1992Fee statusLapsedPublication number040901, 09040901, US 6071896 A, US 6071896A, US-A-6071896, US6071896 A, US6071896AInventorsRudolph M. Keimowitz, Desmond J. FitzgeraldOriginal AssigneeGundersen Clinic, Ltd.Export CitationBiBTeX, EndNote, RefManPatent Citations (28), Non-Patent Citations (33), Classifications (18), Legal Events (7) External Links: USPTO, USPTO Assignment, EspacenetSuppression of thromboxane levels by percutaneous administration of aspirin
US 6071896 AAbstract
The preservation of vascular cyclooxygenase is consistent with the low bioavailability of the dermal aspirin. Plasma aspirin and salicylate were determined using a highly sensitive assay that can measure levels of <0.1 ng/ml. Following oral aspirin 325 mg or 162 mg, peak plasma aspirin levels were 2.0 and 1.3 ug/ml, respectively. In contrast, following dermal aspirin, plasma levels peaked at 237�114 ng/ml and plasma salicylate peaked at 788�114 ng/ml.
0.2 ml of serum or heparinized plasma were used as sample specimens. 0.2 ml of each standard and each sample was pipetted into respectively labeled disposable polystyrene tubes. Into another polystyrene tube, 0.2 ml of deionized water was pipetted to be used as a reagent blank. 1.0 ml of deionized water was added to all tubes. 1.0 ml of Trinder's reagent was then added to all tubes, which were mixed and let stand tubes for 5 minutes. The tubes were then centrifuged for 10 minutes. The clear supernatant (minimum of 1.0 ml) was placed into respectively labeled 10�75 nm cuvettes. Samples were analyzed by reading % T at 540 nm against the reagent blank set at 100% T. Sample values were compared with standard values to determine levels. Results over 75 mg percent were diluted and re-analyzed.
Blood without anticoagulant was obtained for serum TXB2, the stable metabolite of TXA2, prior to and at intervals during and following aspirin administration. The blood was allowed to clot in glass at 37� C. for 60 min and the serum removed and stored at -20� C. until analyzed. Urine was collected over 24 hours at corresponding times for measurement of 2,3-dinor-TXB2 (TX-M) and 2,3-dinor-6-keto-PGF1a (PGI-M), major enzymatic metabolites of TXA2 and PGI2, respectively [Lawson et al., Analyt. Biochem. 150:463 (1985); FitzGerald et al., N. Engl. J. Med. 310: 1065 (1984)]. Excretion of these products is an index of the in vivo formation of their parent compounds [FitzGerald et al., supra; Reilly and Fitzgerald, Blood 69: 180 (1987)]. Serum TXB2 and urinary metabolites were determined by negative ion-chemical ionization, gas chromatography-mass spectrometry (NICI-GCMS) using authentic deuterated standards, as previously described [Braden et al., supra].
TXA2 biosynthesis demonstrated a similar response. Thus, there was a dose dependent reduction in the urinary excretion of TX-M. At 750 mg/day of dermal aspirin. TX-M declined gradually and was 32�7% of baseline by day 10 (n=5; p=0.002) of drug application. By 8 days following drug withdrawal, excretion of the metabolite had recovered to 65�9% of the pretreatment value (FIG. 2). Despite the evidence of marked inhibition of platelet cyclooxygenase, there was only a small fall in PGI2 biosynthesis, based on urinary PGI-M determinations (FIG. 3). Although the changes did not achieve statistical significance (p=0.074 by ANOVA), there was an apparent dose response relationship. Thus, urinary excretion of PGI-M fell to 84�4% and 76�7% of baseline on aspirin 250 mg/day and 750 mg/day, respectively (FIG. 3). The peak decrease in PGI-M excretion occurred by day 4 on both doses, in contrast to TX-M excretion
In 4 subjects (2 male, 2 female) demonstrating a marked (>90%) decrease in serum TXB2, plasma aspirin and salicylate were determined at timed intervals (0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr) following the application of aspirin on days 1 and 14. Aspirin was applied in a dose of 750 mg on one limb over a 15 min interval. Samples were drawn from the opposite arm. Blood was withdrawn into heparin (10 U/ml final concentration) and potassium fluoride (5% final concentration), the latter to prevent ex vivo metabolism of aspirin by plasma esterases. The plasma was separated immediately and stored at -700� C. until analyzed. Aspirin and its metabolite, salicylic acid, were measured by NICI-GCMS using deuterium-labelled analogues as internal standards, as previously described [Clark, supra].
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ASTIERPharmaceutical composition with acetylsalicylic acid in gel formEP0162239A1 *Mar 29, 1985Nov 27, 1985Kao CorporationPercutaneous absorption accelerator and preparation containing sameFR2295753A1 * Title not availableWO1991000096A1 *Jun 23, 1989Jan 10, 1991Moh Samir AmerLow-dosage sublingual aspirinWO1993012799A1 *Dec 16, 1992Jul 8, 1993Lohmann Therapie Syst LtsTransdermally administered system containing acetylsalicylic acid for thrombosis therapy and cancer prophylaxisWO1995008330A1 *Sep 16, 1994Mar 30, 1995Gerd HoffmannTransdermal therapeutic system with acetylsalicylic acid as active substance* Cited by examinerNon-Patent CitationsReference1 *Aspirsol Product Insert Sheet, Terri Pharmaceuticals, Inc., Kingwood, Texas (2 pages, indicates expiration date of Apr. 12, 1991).2 *Chem Abst. 108 (1988) 180111s, Arai.3Chem Abst. 108 (1988)--180111s, Arai.4 *Chem Abst. 110 (1989) 141529f, McKie et al.5Chem Abst. 110 (1989)--141529f, McKie et al.6 *Chem Abst. 111 (1989) 89965Z, Danesh et al.7Chem Abst. 111 (1989)--89965Z, Danesh et al.8 *Chem Abst. 98 (1983) 46600x, Bertele et al.9Chem Abst. 98 (1983)--46600x, Bertele et al.10 *Chest, vol. 95, No. 2, Feb. 1989, J. 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Heggers et al.: Thromboxane inhibitors for the prevention of progressive dermal ischemia due to the thermal injury , pp. 466 468.29The Journal of Burn Care & Rehabilitation, vol. 6, No. 6, Nov./Dec. 1985, J.P. Heggers et al.: Thromboxane inhibitors for the prevention of progressive dermal ischemia due to the thermal injury, pp. 466-468.30 *The Journal of Clinical Investigation, vol. 69, No. 6, Jun. 1982, P. Patrignani et al.: Selective Cumulative Inhibition of Platelet Thromboxane Production by Low dose Aspirin in Healthy Subjects , pp. 1366 1372.31The Journal of Clinical Investigation, vol. 69, No. 6, Jun. 1982, P. Patrignani et al.: Selective Cumulative Inhibition of Platelet Thromboxane Production by Low-dose Aspirin in Healthy Subjects, pp. 1366-1372.32 *Van Moorleghem G L, Derwent WPI, Derwent Publications, Ltd., Week 7647, WPI Acc No: 76 87300X (Abstract of French Patent Application No. 2,297,612, Sep. 17, 1976).33Van Moorleghem G L, Derwent WPI, Derwent Publications, Ltd., Week 7647, WPI Acc No: 76-87300X (Abstract of French Patent Application No. 2,297,612, Sep. 17, 1976).* Cited by examinerClassifications U.S. Classification514/165, 424/449, 514/947International ClassificationA61K47/10, A61K31/60, A61K9/00, A61K45/06Cooperative ClassificationY10S514/947, A61K31/60, A61K9/0014, A61K45/06, A61K31/616, A61K47/10European ClassificationA61K31/60, A61K45/06, A61K47/10, A61K9/00M3, A61K31/616Legal EventsDateCodeEventDescriptionOct 30, 2001ASAssignmentOct 22, 2002CCCertificate of correctionDec 8, 2003FPAYFee paymentYear of fee payment: 4Dec 6, 2007FPAYFee paymentYear of fee payment: 8Jan 16, 2012REMIMaintenance fee reminder mailedJun 6, 2012LAPSLapse for failure to pay maintenance feesJul 24, 2012FPExpired due to failure to pay maintenance feeEffective date: 20120606RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services