New applications of cytidine diphosphate in treating ischemic diseases

A citicoline, ischemic technology, applied in the new use field of citicoline in the treatment of ischemic diseases, can solve the problem of short time, less research on nerve repair, aggravating cerebral edema and cerebral hemorrhage, etc. question

Inactive Publication Date: 2009-06-03
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the time window of t-PA treatment is short, and there is a risk of aggravating cerebral edema and cerebral hemorrhage, so less than 3% of patients benefit from T-PA thrombolysis (Birmingham K, 2002; Iadecola C, 2004)
A large number of studies have shown that citicoline has a strong neuroprotective effect, but there are relatively few studies on nerve repair after cerebral ischemia, and so far there has been no research on vascular repair and remodeling (M.D.Ginsberg, 2008)

Method used

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  • New applications of cytidine diphosphate in treating ischemic diseases
  • New applications of cytidine diphosphate in treating ischemic diseases
  • New applications of cytidine diphosphate in treating ischemic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: In Vitro Experiment of Citicoline-Induced Axonal Growth of Rat Cerebral Cortical Neurons

[0031] Under aseptic conditions, the cerebral cortex of suckling mice within 24 hours after birth was taken out, the corpus callosum and other white matter were cut off, washed twice with D-Hank solution, digested with 0.2% trypsin solution at 37°C for 5 minutes, and the cell suspension was prepared at 1×10 5 The cell density was seeded in two 96-well plates, 100 μl per well. At 37°C, 5% CO 2 Cultured in an incubator, the medium is DF12, and the serum concentration is 15%. After 24 hours of culture, the whole amount was replaced with Neurobasal A neuron-specific medium (containing 2% B27) to selectively culture neurons, and the medium was changed every 3 days in half. Cortical neurons were identified after the 6th day of culture, and the corresponding drug intervention was started in groups, and index detection was performed after 48 hours of culture. The experiment ...

Embodiment 2

[0038] Example 2: Behavioral Evaluation of Citicoline in Promoting Neurorestoration in Rats with Cerebral Ischemia

[0039] 1. Prepare a model of focal cerebral ischemia, start intraperitoneal injection of different doses of citicoline for intervention 6 hours after modeling, and use neurobehavioral evaluation methods to observe the neurological recovery of rats in each group at different time points after modeling. Preliminary To determine whether citicoline has a positive effect on the recovery of neurological function in rats with cerebral ischemia. At the same time, set up a group of treatment groups given medium dose of citicoline for the first time 24 hours after model establishment, to preliminarily understand whether the delayed administration of citicoline after cerebral ischemia in rats is effective, and to explore the effective administration of citicoline Time Window. The experiment was divided into 7 groups, namely the sham operation group, the model group, the n...

Embodiment 3

[0045] Example 3, Citicoline increases the number of synapses after cerebral ischemia in rats

[0046] 1. Using projection electron microscopy combined with stereology to observe the changes in the number of synapses of neurons in the residual cerebral cortex around the ischemic focus of rats in each experimental group after focal cerebral ischemia, and to understand whether citicoline Can promote effective axonal sprouting after focal cerebral ischemia in rats. The experiment was divided into 5 groups, namely the sham operation group, the model group, the normal saline group, and the middle-dose citicoline treatment group. 3 in each group.

[0047] 2. Immunofluorescence histochemical technique and Western blot analysis were used to detect the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB protein in the residual brain tissue around the ischemic focus of rats in each experimental group after focal cerebral ischemia To explore the possible mechan...

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Abstract

The invention discloses new applications of cytidine diphosphate in promoting vessels and nerves repair. The cytidine diphosphate can promote angiogenesis in cerebral ischemic area, increase the number of neural axons, and accelerate the growth of the neural axons in vitro culture; and the recovery of the nerve function of affected limbs after cerebral ischemia can be promoted prominently. The cytidine diphosphate can be mixed with excipients which are acceptable in pharmacology to prepare various dosage forms, so as to promote endothelial cell proliferation, promote brain angiogensis in the cerebral ischemic area, and help to rebuild circulation in the cerebral ischemic area; the number of neural axons is increased, the growth of the neural axons in vitro culture is promoted, so that recovery of the nerve function of affected limbs after cerebral ischemia is promoted. The cytidine diphosphate can be mixed with other nerve repairing drugs and cerebrovascular plasticity drugs according to various different proportions for preparing a composition with the functions, and various dosage forms which is acceptable in pharmacology is prepared. Meanwhile, the cytidine diphosphate can be applied to other systems for treating ischemic diseases caused by insufficient new blood vessels.

Description

technical field [0001] The present invention relates to the new medical application of citicoline, in particular to the role of citicoline in promoting angiogenesis and neural remodeling in ischemic brain regions, treating ischemic cerebrovascular diseases and various ischemic angiogenesis deficiencies use in diseases. Background technique [0002] Cerebrovascular disease is recognized as one of the three major fatal diseases in the world, with the characteristics of high morbidity, high mortality and high disability rate. The long-term dysfunction of stroke survivors brings a heavy burden to the society, family and patients. If cerebral ischemia can restore blood supply and rebuild blood circulation in time, the ischemic injury can be reversed. The early application of t-PA thrombolysis shows good clinical effect is an obvious example (Birmingham K, 2002). However, the time window of t-PA treatment is short, and there is a risk of aggravating cerebral edema and cerebral h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7068A61P9/10A61P3/10
Inventor 祝慧凤徐晓玉万东
Owner SOUTHWEST UNIV
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