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Methods and compositions for improving pial collateral circulation and treating blood clotting disorders

A technology of collateral circulation and composition, applied in the fields of application, pharmaceutical formulation, food science, etc., can solve problems such as failure to meet expectations

Inactive Publication Date: 2015-04-08
THE OHIO STATES UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Recently, interest in the biological properties of tocotrienols has grown dramatically, as this form of natural vitamin E has unique biological functions not shared by the more well-known tocopherols, which are found in Failure to meet expectations in clinical trials

Method used

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  • Methods and compositions for improving pial collateral circulation and treating blood clotting disorders
  • Methods and compositions for improving pial collateral circulation and treating blood clotting disorders
  • Methods and compositions for improving pial collateral circulation and treating blood clotting disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0063] Example 1. A randomized, blinded, placebo-controlled supplementary program.

[0064] All experimental procedures have been approved by the Ohio State University (The Ohio State University) Research Institution Animal Care and Use Committee. Before being selected for the study, twenty mongrel dogs (2.4 ± 0.9 years, 26.6 ± 2.6 kg) were subjected to a general examination by the Ohio State University's College of Veterinary Medicine, heartworm, complete blood count, and blood chemistry tests. Veterinarians did not observe significant differences in general examination abnormalities, heartworm canine or complete blood counts or blood chemistry. After the baseline physical examination, the dogs were randomized into two treatment groups-one group received TE (n = 11, 200 mg mixed tocotrienol, Carotech Inc, Malaysia), and the other group received vitamin E deficiency Corn oil (n=9, carrier placebo, PBO). For the duration of supplementation, dogs are maintained as standard feed (...

example 2

[0065] Example 2. C-arm fluoroscopy guided preclinical model of acute ischemic stroke.

[0066] Perform a minimally invasive intravascular approach to achieve middle cerebral artery occlusion in dogs. In short, 5 French sheaths (ArrowGE Healthsystems) are used to make anesthetized dogs (1.5%-2.0% isoflurane) enter both femoral arteries and use 4- Fr and 5-Fr guiding catheters (Boston Scientific) were used to provide access to the basilar artery (BA) system and used for conventional contrast media (Onipex) visualization of the MCA area. Microcatheter technology was used to enter and occlude the MCA from BA. One embolization coil (3mm x 20cm Ultrasoft Matrix2Platinum Coil, Boston Scientific) was delivered into the M1 section of any MCA from the microcatheter (SL-10, Boston Scientific) and passed through The 1h occlusion time was recorded every 15 minutes using digital subtraction angiography (DSA) of the internal carotid artery and vertebrobasilar circulation. After 1h of MCAO, ...

example 3

[0067] Example 3. Magnetic resonance imaging (MRI)

[0068] In a 3T MRI (Achieva, Philips Healthcare) MRI imaging system, an 8-channel sensitivity (SENSE) knee joint coil was used to evaluate the infarct volume. Images were obtained 1h and 24h after reperfusion. The sequence includes: diffusion tensor imaging (DTI) [field of view (FOV) = 140x 140mm, matrix = 128x 128, number of stimuli (NEX) = 1, repetition time (TR) / repetition time (TE) 192-2131 / 71, Slice thickness=3mm, b value=1000, total scanning time is close to 4 minutes] and T2 liquid attenuation inversion recovery (FLAIR) [FOV=160mm, matrix=512x512, NEX=1, TR / TE / inversion time (TI )=11000 / 125 / 2800, slice thickness=3mm, total scan time is close to 8 minutes] and 3D time-of-flight magnetic resonance angiography (MRA) (FOV=150mm, matrix=512x 512, TR / TE=8.6 / 3.45, flip Angle=20, slice thickness=1mm, total scanning time is close to 6 minutes). The DTI data was transferred to a workstation, where a mean diffusivity (MD) map wa...

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Abstract

The present invention provides methods of promoting arteriogenesis in a subject. Embodiments include methods comprising: administering an effective dose of tocotrienol to the subject; causing an increase in Tissue Inhibitor of Metalloproteinase Metallopeptidase Inhibitor 1 (TIMP1) in vessels of cerebrovascular collateral circulation in the subject; attenuating the activity of Matrix Metalloproteinase-2 (MMP2); thereby promoting arteriogenesis.

Description

[0001] Inventors: Chandan K. Sen (Kay Dan K Sen), Cameron L. Rink (Cameron L Link), Sashwati Roy (Saschwart Roy), Greg Christoforidis (Greg Christoforidis) [0002] Cross references to related applications [0003] This application claims the benefit of U.S. Provisional Patent Application No. 61 / 657,433 filed on June 8, 2012, the entire disclosure of which is expressly incorporated herein by reference for all purposes. [0004] Statement on research funded by the federal government [0005] The present invention was completed with the support of the US government under the authorization of UL1RR025755 and NIH authorization of NS42617. The government has certain rights in this invention. [0006] Reference to sequence listing [0007] This application is submitted electronically via the USPTO EFS-WEB server, as approved and described in MPEP§1730II.B.2(a)(A), and this electronic archive includes a sequence submitted electronically (SEQ ID) table. The entire content of this sequence list...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/355A23L33/00A23L33/15
CPCA23V2002/00A61K31/727A61K31/355A23L1/302A61K31/353A61K31/4709A23L1/296A61K45/06A61K31/522A23V2200/326A23V2250/712A23L33/15A23L33/40A61K2300/00
Inventor C·森C·瑞克S·罗伊G·克里斯托佛里迪斯
Owner THE OHIO STATES UNIV
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