Compositions of small molecule therapeutics
a technology of compositions and therapeutics, applied in the direction of drug compositions, dispersed delivery, capsule delivery, etc., can solve the problems that small molecule drug treatments often enjoy cost benefits, and achieve the effects of reducing the risk of side effects, and increasing the peak plasma level
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example i
[0032]Using Sprague Dawley rats as an animal model, the body weights of the animals were measured prior to dosing to determine the appropriate amount of test article to deliver. Animals were dosed (5 mg / kg) by oral gavage (PO) or subcutaneously (SC) with the test composition in the different formulations as a single bolus. Then blood samples were taken via the lateral tail vein at 0.5, 1, 2, 4, 8 and 24 hours following the dose.
[0033]Blood samples were collected into blood collection tubes containing Na2EDTA, placed on ice and within 30 minutes of sampling the blood samples were centrifuged to obtain plasma. The plasma was separated from the cellular component and placed in microcentrifuge tubes and frozen, then stored at −80° C. until processed for analysis by LC-MS / MS (liquid chromatography-mass spectrometry with peptide mass fingerprinting). Standard samples were created by adding known amounts of paclitaxel to blank rat plasma. Standard curves were created by analyzing the stand...
example ii
[0042]Two small molecule therapeutic compounds were selected from each of BCS Class 2, BCS Class 3, and BCS Class 4 for oral delivery (PO) to jugular vein cannulated (JVC) male Sprague Dawley rats (200-250 gram weight). The BCS Class 2 compounds were haloperidol and sulfasalazine. Haloperidol is an antipsychotic butyrophenone sold under the brand name Haldol® and sufasalazine is an anti-inflammatory sulfa drug derivative of mesalazine sold under the brand name Azulfidine®. The BCS Class 3 compounds were atenolol, and glucosamine (in the salt form glucosamine sulfate). Atenolol is in the class of beta blocker drugs and is sold under the brand names Senormin® and Tenomin. The BCS Class 4 compounds were furosemide (Lasix®) and chlorothiazide (Diuril®), both of which are diuretics.
[0043]The compounds from BCS Class 2, 3 and 4 were each formulated at 5 mg / ml in a liquid carrier of either an aqueous solution of polyethylene glycol 400 (20% PEG 400), or an aqueous solution of DDAIP-HCL (20...
example iii
[0046]Male CD1 mice were used (Harlan, USA) in this study and weighed 20-24 grams at the time of use. A 1.5% aqueous methylcellulose solution was made overnight with continuous heating and stirring. To this, 50 mg Phenol Red was added to 100 ml of 1.5% aqueous methylcellulose. Mice were pre-treated with saline or 20% DDAIP free base (5 ml / kg) with and without lansoprazole (10 mg / kg) 15 minutes before challenge with Phenol Red at T0 (150 μl / mouse) Ten and thirty minutes after Phenol Red challenge, mice were euthanized with isoflurane and the stomachs rapidly excised (clamping the pyloric and cardiac sphincters to avoid loss of contents). Stomachs were then cut into several pieces and placed in 15 ml tubes containing 2 ml water prior to processing for A558 nm measurements. Several mice were sacrificed immediately after gavage with dye to act as an indicator of maximum dye retrieval (75 μg dye was dosed to each mouse).
[0047]Data (n=3) for stomach emptying (i.e., the amount of dye remai...
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