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Method for regulating barrier permeability by using ultrasound

A permeability and barrier technology, applied in the field of control, can solve problems such as difficult to overcome the effective treatment concentration of the eye barrier, unclear change law of sclera permeability, and can not be directly applied to humans, so as to achieve a wide range of ultrasound applications and safe effects , the effect of convenient operation

Pending Publication Date: 2022-02-25
EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the existence of various barriers in the eye, including static, dynamic and metabolic barriers, the entry of these drugs into the posterior segment of the eye is limited, such as topical eye drops, only less than 1 / 10 8 Drugs can reach the back of the eye, and systemic medication (oral, intravenous, etc.) is also difficult to overcome the eye barrier to reach an effective therapeutic concentration in the back of the eye
However, as far as the current research results are concerned, the change rule of sclera permeability under the action of ultrasound is not clear, and the results obtained from experimental animals cannot be directly applied to humans, especially the thickness of sclera is an important factor affecting the delivery of drugs through the sclera, while rabbits and pigs The average thickness of the sclera is 1 / 10 and 1 / 2 of the human sclera
There are no studies on the effect of ultrasound on conjunctival permeability

Method used

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  • Method for regulating barrier permeability by using ultrasound
  • Method for regulating barrier permeability by using ultrasound
  • Method for regulating barrier permeability by using ultrasound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Ultrasonic regulation of the permeability of a small molecule tracer (sodium fluorescein, molecular weight 376 Da) through isolated human sclera

[0047] 1) Divide the isolated human sclera into an experimental group and a control group, 15 cases in each group.

[0048] The administration pool 3 of the experimental group was filled with 1 ml of 0.03 mg / ml sodium fluorescein solution, and the ultrasonic probe 1 was kept at 15 mm vertically above the orbital surface of the eye barrier 2 (sclera) using a therapeutic-grade ultrasonic instrument, that is, the administration pool 3, the ultrasonic probe 1 is fully in contact with the sodium fluorescein solution in the drug pool 3, and the ultrasonic frequency is adjusted to 1MHz, and the sound intensity is 1.2W / cm 2 1. The duty cycle is 50%, the ultrasonic irradiation is turned on, and the irradiation time is 5 minutes. The contact time of the sclera of the control group with the same concentration and volume of sodium fluor...

Embodiment 2

[0056] Ultrasonic regulation of the permeability of a macromolecular tracer compound (FITC-dextran 40, molecular weight 40kDa) through isolated human sclera

[0057] 1) The experimental grouping was roughly the same as step 1 in Example 1, and the solution in the dosing chamber was replaced with 0.1% FITC-dextran 40 solution. 15 cases in each group,

[0058] 2) The evaluation index of the permeability change of the isolated human sclera is the same as step 2 in Example 1,

[0059] 3) The results showed that immediately after stopping the ultrasonic irradiation, the penetrating sclera distance of the FITC-dextran 40 solution in the experimental group was 1.36 times that of the control group (such as Figure 8 , 9 shown), the average fluorescence intensity was 1.79 times that of the control group (as Figure 10 shown). When 0.25h, 0.5h, 0.75h and 1h, the FITC-dextran 40 unit area accumulative permeation amount of experimental group is respectively 14.38, 6.29, 2.97 and 1.61 ...

Embodiment 3

[0061] Comparison of the permeability of a macromolecular tracer compound (FITC-dextran 40, molecular weight 40kDa) modulated by medium-frequency pulsed ultrasound and low-frequency continuous ultrasound through isolated human sclera

[0062] 1) The experimental grouping is roughly the same as step 1 in Example 1, the solution in the dosing chamber is replaced with 0.1% FITC-dextran 40 solution, the frequency of use is 82kHz, and the sound intensity is 0.12W / cm 2 Continuous wave ultrasound, ultrasonic irradiation time is 5 minutes, a total of 15 cases.

[0063] 2) The evaluation index of the permeability change of the isolated human sclera is the same as step 2 in the embodiment one, and the result is the same as that in the embodiment two (the frequency is 1MHz, the sound intensity is 1.2W / cm 2 , pulsed ultrasound with a duty cycle of 50%) for comparison of results,

[0064] 3) The results showed that immediately after stopping the ultrasound irradiation, the penetration dis...

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Abstract

The invention belongs to the technical field of control, and relates to a method for regulating barrier permeability by using ultrasound, in particular to a method for increasing barrier permeability by using medium-frequency low-intensity pulse ultrasound. According to the invention, an ultrasonic instrument is adopted, an ultrasonic parameter mode is adjusted and optimized, and the permeability of a related barrier is regulated and controlled; and the method further comprises the step of adopting an improved Franz diffusion cell and a drug diffusion tester. According to the invention, the permeability of the related barrier is effectively increased by utilizing the biological effect of ultrasound so as to improve drug delivery, the permeability of the related barrier gradually returns to normal after ultrasonic irradiation is stopped, and damage to the tissue structure of the related barrier does not occur.

Description

technical field [0001] The invention belongs to the technical field of control, and relates to a method for regulating barrier permeability by using ultrasound, in particular to a method for increasing the permeability of an isolated eye barrier by medium-frequency low-intensity pulsed ultrasound. Background technique [0002] According to research reports, age-related macular degeneration, endophthalmitis, uveitis and other diseases of the posterior segment of the eye involving the retina, optic nerve, vitreous body or choroid are important causes of blindness. In clinical practice, antibiotics, hormones, anti-vascular endothelial Drugs such as growth factors are delivered to the posterior segment of the eye for treatment. However, due to the existence of various barriers in the eye, including static, dynamic and metabolic barriers, the entry of these drugs into the posterior segment of the eye is limited, such as topical eye drops, only less than 1 / 10 8 The drug can reach...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/079C12N13/00C12M1/42C12M1/38C12M1/34C12M1/02C12M1/00G01N21/64
CPCC12N5/0621C12N13/00C12M35/04C12M27/02C12M41/22G01N21/6428
Inventor 游舒棋莫晓芬吴甦潜陈向武夏卿熊佳伟姚旺
Owner EYE & ENT HOSPITAL SHANGHAI MEDICAL SCHOOL FUDAN UNIV
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