Low-intensity pulse ultrasonic instrument for relieving ulcerative colitis inflammation and application thereof

Abstract

The invention relates to the technical field of medical instruments, in particular to a low-intensity pulsed ultrasound instrument for relieving ulcerative colitis inflammation and application of the low-intensity pulsed ultrasound instrument for relieving ulcerative colitis inflammation, low-intensity pulsed ultrasound can effectively reduce inflammatory response of the whole body in intervention treatment and relieving of ulcerative colitis, the conditions of weight loss, loose and loose excrement and stool bleeding are improved, and the treatment effect of ulcerative colitis is improved. The traditional Chinese medicine composition can be used for treating ulcerative colitis, improving the disease activity index (DAI) and improving the life quality of a patient in the acute attack period, has the advantages of no trauma, few side effects, high penetration depth and easiness in home operation of the patient, and provides brand-new effective treatment equipment for ulcerative colitis.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis and application thereof. Background Art

[0002] Inflammation is triggered by harmful stimuli and conditions (such as infection and tissue damage). It is an adaptive response and the basis of many physiological and pathological processes. The site of inflammation drives the aggregation and infiltration of inflammatory cells such as neutrophils, monocytes and macrophages. After activation, they can release inflammatory mediators such as IL-1β, IL-6, TNF-α, IFN-γ, histamine, proteases and reactive oxygen species, which mediate the killing of harmful stimuli. Persistent pathogen stimulation and autoimmune reactions (due to the continued presence of self-antigens) or non-degradable foreign bodies can lead to chronic inflammation. At present, humans know very little about the mechanism of systemic and chronic inflammatory states, and not all types of inflammation conform to the classic pattern from acute inflammation to chronic inflammation. Long-term infection leads to changes in the immune system, laying the foundation for the development of chronic inflammation. After the infection is eliminated, an "immune scar" will be formed, which destroys the complex balance between the immune system and the gastrointestinal microbiome, creating an environment for harmless microorganisms to become pathogens of chronic inflammation, which is also an important reason for the occurrence and development of inflammatory bowel disease.

[0003] At present, the treatment strategy for chronic inflammation is mainly to relieve attacks and symptomatic treatment. Ulcerative colitis, as the main type of inflammatory bowel disease, is mainly treated with drugs, including aminosalicylic acid drugs, glucocorticoids, immunosuppressants and monoclonal antibody biological preparations, etc., and there are certain drug contraindications and adverse reactions. Recently, scientists have tried to treat inflammation by utilizing the physical effects of medical devices, such as ultrasound, electrical stimulation, etc. For example, Chinese patent application CN113873983A discloses a system and method for combined ultrasonic stimulation and electrical stimulation for treating inflammation, autoimmune diseases, rheumatoid arthritis, etc. Non-invasive ultrasonic stimulation can be applied to the spleen, joints, limbs, or areas with local pain and swelling, and electrical stimulation can be applied to the face, neck, or other body areas in an appropriately timed pattern to enter peripheral nerves, vagus nerves, trigeminal nerves, or other nerves to drive therapeutic effects.

[0004] However, the schemes reported in the above literature require the simultaneous use of ultrasound stimulation and electrical stimulation, and do not specifically report on their therapeutic effects on specific diseases, which limits their application. Summary of the invention

[0005] 1. Technical issues

[0006] The present invention aims to at least solve the problem in the prior art that the treatment of ulcerative colitis inflammation mainly relies on drug therapy.

[0007] (II) Technical content

[0008] This protocol provides a low-intensity pulsed ultrasound device for reducing inflammation of ulcerative colitis. Its application in the intervention treatment and relief of ulcerative colitis and related symptoms can effectively reduce systemic inflammatory response, improve weight loss, loose stools and bloody stools, improve the disease activity index (DAI), and improve the quality of life of patients during acute attacks. Its advantages are non-traumatic, few side effects, high penetration depth, and easy operation for patients at home.

[0009] A low-intensity pulsed ultrasound apparatus for alleviating inflammation of ulcerative colitis, comprising: a low-intensity pulsed ultrasound device and an ultrasound probe matched with and connected to the low-intensity pulsed ultrasound device;

[0010] The low-intensity pulsed ultrasound device is used to generate a driving signal to drive the ultrasound probe to emit low-intensity pulsed ultrasound;

[0011] The ultrasound probe is placed in the left lower abdomen of the patient (ulcerative colitis often occurs in the rectum and sigmoid colon, which are located in the left lower abdomen), and the patient is treated by outputting low-intensity pulsed ultrasound.

[0012] Preferred technical solution 1: The low-intensity pulsed ultrasound device also includes a signal generating module, a power amplifying module, a power supply module, and is equipped with a touch display screen and a transducer channel;

[0013] The signal generating module is responsible for generating an electrical signal of a specific frequency and waveform;

[0014] The power amplification module is connected to the signal generation module to amplify the weak electrical signal generated by the signal generation module;

[0015] The transducer channel is connected between the power amplifier module and the ultrasonic probe, transmits the electrical signal amplified by the power amplifier module, and realizes the conversion between electrical energy and mechanical energy;

[0016] The touch display screen is used to adjust and display the values ​​of the output low-intensity pulsed ultrasound parameters, and the ultrasound probe connected to the transducer channel outputs the corresponding ultrasound parameters;

[0017] The power supply module provides a stable power supply for the entire low-intensity pulsed ultrasound device, ensuring that each module can work normally.

[0018] Preferred technical solution 2: The low-intensity pulsed ultrasound parameters input into the low-intensity pulsed ultrasound device include pulsed ultrasound frequency, duty cycle, spatial average time average sound intensity and output time.

[0019] Preferred technical solution three: the pulse ultrasonic frequency of the low-intensity pulse ultrasonic device is set to 1 MHz;

[0020] The duty cycle of the low-intensity pulsed ultrasound device is set to 20%;

[0021] The spatial average time average sound intensity of the low intensity pulsed ultrasound device is set to 30 mW / cm2;

[0022] The output time of the low-intensity pulsed ultrasound device was set to 10 min.

[0023] Preferred technical solution 4: The treatment frequency is set to 1 week, 7 days a week.

[0024] Preferred technical solution five: A low-intensity pulsed ultrasound instrument for alleviating inflammation of ulcerative colitis, comprising a low-intensity pulsed ultrasound device and a plurality of independent ultrasound probes connected thereto to meet the needs of batch use.

[0025] Preferred technical solution six: The low-intensity pulsed ultrasound device and the ultrasound probe are connected by a cable

[0026] (III) Technical Effect

[0027] The above structure enables this solution to have the following beneficial effects:

[0028] Low-intensity pulsed ultrasound can effectively reduce systemic inflammatory response, improve weight loss, loose stools and bloody stools, improve disease activity index, and improve the quality of life of patients during acute attacks in the intervention treatment and relief of ulcerative colitis. Its advantages are that it is non-traumatic, has few side effects, has a high penetration depth, and is easy for patients to operate at home. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0030] Figure 1 This is a photo of the left lower abdomen of a mouse with ulcerative colitis irradiated by low-intensity pulsed ultrasound in this protocol;

[0031] Figure 2 This is the change of disease activity index in mice;

[0032] Figure 3 The changes in the contents of inflammatory factors IL-1β, IL-6, TNF-α, and IFN-γ;

[0033] Figure 4Examples of mouse colon length and HE staining histological evaluation results. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0035] A low-intensity pulsed ultrasound apparatus for alleviating inflammation of ulcerative colitis, comprising: a low-intensity pulsed ultrasound device and an ultrasound probe that cooperates with the low-intensity pulsed ultrasound device and is connected to the device via a cable;

[0036] The low-intensity pulsed ultrasound device is used to generate a driving signal to drive the ultrasound probe to emit low-intensity pulsed ultrasound, and adopts existing technology;

[0037] At the same time, the ultrasound probe also adopts the existing technology and is placed in the left lower abdomen of the patient when in use. Because ulcerative colitis is prone to occur in the rectum and sigmoid colon, it is located in the left lower abdomen and treats the patient by outputting low-intensity pulsed ultrasound.

[0038] The existing low-intensity pulsed ultrasound device mainly includes a signal generation module, a power amplification module, a power supply module, and is also equipped with a touch display screen and a transducer channel, wherein:

[0039] The signal generating module is responsible for generating an electrical signal of a specific frequency and waveform;

[0040] The power amplification module is connected to the signal generation module to amplify the weak electrical signal generated by the signal generation module;

[0041] The transducer channel is connected between the power amplifier module and the ultrasonic probe, transmits the electrical signal amplified by the power amplifier module, and realizes the conversion between electrical energy and mechanical energy;

[0042] The touch display screen is used to input and display the values ​​of the output low-intensity pulsed ultrasound parameters (the input low-intensity pulsed ultrasound parameters include pulsed ultrasound frequency, duty cycle, spatial average time average sound intensity and output time), and the ultrasound probe connected to the transducer channel outputs the corresponding ultrasound parameters;

[0043] The power supply module provides a stable power supply for the entire low-intensity pulsed ultrasound device, ensuring that each module can work normally.

[0044] The application process of a low-intensity pulsed ultrasound device for reducing inflammation of ulcerative colitis in the intervention treatment and relief of ulcerative colitis and related symptoms is as follows:

[0045] 1. Construction of mouse ulcerative colitis model:

[0046] Eight-week-old male C57BL / 6 mice were selected and fed with sterile drinking water containing 3% dextran sulfate sodium salt (DSS) every day for 7 days to establish the ulcerative colitis state;

[0047] 2. Animal position preparation:

[0048] After the abdomen was shaved, the mice were anesthetized and placed in a supine or left lateral position to facilitate ultrasound intervention by the ultrasound probe;

[0049] 3. Ultrasound stimulation:

[0050] During the 7-day period of DSS feeding, low-intensity pulsed ultrasound stimulation was given once a day for a total of 7 days in the small animals;

[0051] (1) Stimulation mode: Ultrasound stimulation was performed on the left lower abdomen of the mouse (operation as Figure 1 ), combined with previous studies, according to the characteristics of the ultrasound effect, the following parameters were selected, namely, the pulse ultrasound frequency was 1 MHz, the pulse repetition frequency was 1 kHz, and the duty cycle was 20%; by adjusting the output power, the output pulse ultrasound with a spatial average temporal average intensity (ISATA) of 30 mW / cm2 was output, and the continuous stimulation time was 10 minutes;

[0052] Table 1 Experimental grouping

[0053]

[0054] 4. Fifteen male adult mice were selected and randomly divided into a positive control group (DSS) and an ultrasound treatment group (LIPUS), with 5 mice in each group, see Table 1;

[0055] In order to further verify that this method improves the basic systemic condition after inflammation, the disease activity index scoring standard was used to reflect it; according to the disease activity index scoring standard (Table 2), the weight, stool characteristics and stool bleeding of mice were accurately recorded and scored every day, with each item scored 0-4 points. The total value of these three scores was used as the disease activity index score (DAI), ranging from 0 to 12 points. The changes in the disease activity index of mice are shown in the figure. Figure 2 As shown; stool bleeding can be detected by fecal occult blood test strips;

[0056] Table 2 Disease Activity Index Scoring Criteria

[0057]

[0058] 5. 24 hours after the completion of ultrasound intervention, serum and colon tissues of mice were collected, and the mRNA expression levels of inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in mouse serum were detected by enzyme-linked immunosorbent assay (ELISA). The experimental results are as follows: Figure 3 As shown; and the length of mouse colon tissue was measured and hematoxylin-eosin staining was performed to reflect the histological level. The experimental results are shown in Figure 4 As shown;

[0059] 6. Experimental evaluation of improvement of mice's general condition:

[0060] Figure 2 The experimental results showed that ultrasound intervention can significantly improve the disease activity index of mice. The DAI index of the positive control group (DSS) gradually increased with the increase in the number of days of drinking 3% DSS drinking water, reaching a peak on the 8th day, while the DAI index of the ultrasound treatment group reached its peak on the 6th day and decreased on the 7th day. The body weight recovered, the stool characteristics gradually returned to normal, and there was no bleeding in the stool.

[0061] 7. Experimental evaluation of anti-inflammatory effect:

[0062] Figure 3 The experimental results showed that ultrasound intervention can reduce the levels of inflammatory factors such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mouse serum. As shown in the figure, after administration of DSS, the levels of inflammatory factors such as IL-1β, IL-6, TNF-α and IFN-γ in mouse serum were significantly higher than those in the ultrasound treatment group, and ultrasound intervention was beneficial to reduce the levels of the above inflammatory factors in serum.

[0063] 8. Macroscopic observation of colon tissue and experimental evaluation of histological changes:

[0064] Figure 4The experimental results showed that drinking DSS shortened the colon length, while the colon length was longer after ultrasound intervention. HE staining also showed that the intestinal wall in the DSS group was thickened, the morphology changed, the glands in the intestinal tissue decreased, the inflammatory cell infiltration increased, local adhesions and abnormal intestinal wall protrusions were seen in the intestinal lumen, while the intestinal tissue after ultrasound stimulation had no obvious pathological changes, and the thickness and morphology of the intestinal wall and the distribution of glandular cells in the intestine were normal.

[0065] The undisclosed parts in the present invention are all prior art, and their specific structures and working principles are not described in detail.

[0066] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis, characterized in that: Application in intervention treatment and relief of ulcerative colitis.

2. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to claim 1, characterized in that: Used to provide low-intensity pulsed ultrasound, mainly acting on the rectum and sigmoid colon in the lower left abdomen where ulcerative colitis often occurs.

3. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to claim 2, characterized in that: It includes a low-intensity pulsed ultrasound device and an ultrasound probe that cooperates with and is connected to the low-intensity pulsed ultrasound device; The low-intensity pulsed ultrasound device is used to generate a driving signal to drive the ultrasound probe to emit low-intensity pulsed ultrasound; The ultrasound probe is placed on the left lower abdomen of the patient to output low-intensity pulsed ultrasound.

4. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to claim 3, characterized in that: The low-intensity pulsed ultrasound device is provided with a touch display screen; The touch display screen is used to input and display the output value of the low-intensity pulsed ultrasound parameter, and the ultrasound probe outputs the corresponding low-intensity pulsed ultrasound parameter.

5. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to claim 4, characterized in that: The low-intensity pulsed ultrasound parameters input into the low-intensity pulsed ultrasound device include pulsed ultrasound frequency, duty cycle, spatial average time average sound intensity and output time.

6. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to any one of claims 1 to 5, characterized in that: The pulsed ultrasonic frequency of the low-intensity pulsed ultrasonic device is set to 1 MHz; The duty cycle of the low-intensity pulsed ultrasound device is set to 20%; The spatial average time average sound intensity of the low intensity pulsed ultrasound device is set to 30 mW / cm2; The output time of the low-intensity pulsed ultrasound device was set to 10 min.

7. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to claim 6, characterized in that: The treatment frequency was set to 1 week, 7 days per week.

8. A low-intensity pulsed ultrasound device for alleviating inflammation of ulcerative colitis according to claim 3, characterized in that: The low-intensity pulsed ultrasound device has multiple independent ultrasound probes connected by cables.

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