Compositions and methods for treating or preventing diseases of body passageways
a technology of body passageways and compositions, applied in the direction of drug compositions, cardiovascular disorders, aerosol delivery, etc., can solve the problems of thrombosis, changes in laminar flow patterns, etc., and achieve the effect of avoiding systemic and unwanted side effects, avoiding urethra instrumentation, and potentially reducing total dosages
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example 1
Manufacture of “Pastes”
[0181] As noted above, the present invention provides a variety of polymeric-containing drug compositions that may be utilized within a variety of clinical situations. For example, compositions may be produced: (1) as a “thermopaste” that is applied to a desired site as a fluid, and hardens to a solid of the desired shape at a specified temperature (e.g., body temperature); (2) as a spray (i.e., “nanospray”) which may delivered to a desired site either directly or through a specialized apparatus (e.g., endoscopy), and which subsequently hardens to a solid which adheres to the tissue to which it is applied; (3) as an adherent, pliable, resilient, drug-loaded-polymer film applied to a desired site either directly or through a specialized apparatus, and which preferably adheres to the site to which it is applied; and (4) as a fluid composed of a suspension of microspheres in an appropriate carrier medium, which is applied to a desired site either directly or via ...
example 2
Manufacture of Microspheres
[0214] Equipment which is preferred for the manufacture of microspheres described below include: 200 ml water jacketed beaker (Kimax or Pyrex), Haake circulating water bath, overhead stirrer and controller with 2 inch diameter (4 blade, propeller type stainless steel stirrer—Fisher brand), 500 ml glass beaker, hot plate / stirrer (Corning brand); 4×50 ml polypropylene centrifuge tubes (Nalgene), glass scintillation vials with plastic insert caps, table top centrifuge (GPR Beckman), high speed centrifuge-floor model (JS 21 Beckman), Mettler analytical balance (AJ 100, 0.1 mg), Mettler digital top loading balance (AE 163, 0.01 mg), automatic pipetter (Gilson). Reagents include Polycaprolactone (“PCL”—mol wt 10,000 to 20,000; Polysciences, Warrington Pa., USA), “washed” (see later method of “washing”) Ethylene Vinyl Acetate (“EVA”), Poly(DL)lactic acid (“PLA”—mol wt 15,000 to 25,000; Polysciences), Polyvinyl Alcohol (“PVA”—mol wt. 124,000 to 186,000; 99% hydro...
example 3
Surfactant Coated Microspheres
A. Materials and Methods
[0223] Microspheres were manufactured from Poly (DL) lactic acid (PLA), poly methylmethacrylate (PMMA), polycaprolactone (PCL) and 50:50 Ethylene vinyl acetate (EVA):PLA essentially as described in Example 2. Size ranged from 10 to 100 um with a mean diameter 45 um.
[0224] Human blood was obtained from healthy volunteers. Neutrophils (white blood cells) were separated from the blood using dextran sedimentation and Ficoll Hypaque centrifugation techniques. Neutrophils were suspended at 5 million cells per ml in Hanks Buffered Salt Solution (“HBSS”).
[0225] Neutrophil activation levels were determined by the generation of reactive oxygen species as determined by chemiluminescence. In particular, chemiluminescence was determined by using an LKB luminometer with 1 uM luminol enhancer. Plasma precoating (or opsonization) of microspheres was performed by suspending 10 mg of microspheres in 0.5 ml of plasma and tumbling at 37° C. for...
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Abstract
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