A microneedle for exosome injection

Abstract

The present invention relates to a microneedle for exosome injection, which relates to the field of medical instruments. The microneedle comprises a syringe, a pressure rod and a needle body. The syringe is filled with exosomes secreted from neural stem cells, one end of the pressure rod is slidably connected in the syringe, and the other end of the pressure rod extends out of the syringe; the needle body is connected to the syringe, the sharp part of the needle body pierces the acupuncture point, and the pressure rod moves toward the needle body to inject the exosomes into the acupuncture point from inside or outside the needle body. The present invention has the advantages of combining acupuncture and exosome injection, and can play an analgesic role, promote tissue regeneration and repair, regulate immune function and improve the coordination and synergy of nerve function.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a microneedle for exosome injection. Background Art

[0002] Acupuncture, as one of the traditional Chinese medicine therapies, can regulate the balance of qi and blood, yin and yang by stimulating specific acupuncture points on the body, thereby achieving the purpose of treating and preventing diseases. Acupuncture therapy has demonstrated a wide range of therapeutic effects at the intersection of traditional medicine and modern medicine, and continues to be supported by clinical research. Most obviously, acupuncture therapy performs well in relieving various pain symptoms, including chronic pain, neuropathic pain, muscle pain, etc. It can reduce pain through neuromodulation and the release of endogenous analgesics. Under the guidance of a suitable Chinese medicine practitioner or acupuncturist, acupuncture therapy is generally considered safe and does not cause serious side effects. Compared with drug treatment, acupuncture treatment does not involve oral administration of drugs, thus avoiding drug side effects and burden on organs. At the same time, compared with surgical treatment, the cost of acupuncture treatment is relatively low, and it may be more economical for the long-term treatment of some chronic diseases.

[0003] Exosome therapy is an emerging treatment strategy that mainly uses the biological effects of cellular exosomes to regulate disease states. Exosomes are small vesicles secreted by cells that contain a variety of bioactive substances, such as proteins, nucleic acids, hormones, etc. Exosomes have the function of transmitting information between cells and can regulate the physiological processes of cells. Exosomes contain various growth factors, cytokines and other bioactive substances that can promote tissue regeneration and repair. Exosomes have the ability to regulate immune responses, inhibit inflammatory responses, regulate immune cells, etc. Exosomes contain some neurotrophic factors and neuroprotective factors that can promote the growth, differentiation and regeneration of nerve cells. Some components in exosomes may have analgesic and anti-inflammatory effects. Therefore, using exosomes as a treatment method can regulate biological activity at the cellular level and produce repair and regulatory effects on inflammation, injury, disease, etc.

[0004] However, there is currently no means to combine acupuncture and exosomes. Therefore, in order to address the above shortcomings, it is necessary to provide a microneedle for exosome injection. Summary of the invention

[0005] 1. Technical issues to be resolved

[0006] The technical problem to be solved by the present invention is that there is currently no device that combines acupuncture and exosome injection therapy.

[0007] (II) Technical solution

[0008] In order to solve the above technical problems, the present invention provides a microneedle for exosome injection, including a syringe, a pressure rod and a needle body, the syringe is filled with exosomes secreted from neural stem cells, one end of the pressure rod is slidably connected in the syringe, and the other end of the pressure rod extends out of the syringe; the needle body is connected to the syringe, the sharp part of the needle body pierces the acupuncture point, and the pressure rod moves toward the needle body to inject the exosomes into the acupuncture point from inside or outside the needle body.

[0009] As a further illustration of the present invention, preferably, the needle body is a hollow needle, the needle body length is greater than 40 mm, and the outer diameter of the needle body is between 0.30 and 0.45 mm; the space inside the needle body is connected to the inner cavity of the injection barrel, and the pressure rod moves toward the needle body to inject the exosomes from the needle body into the acupuncture point.

[0010] As a further illustration of the present invention, preferably, the needle body is threadedly connected to the injection barrel, and multiple layers of wire are wound around the needle body.

[0011] As a further illustration of the present invention, preferably, the needle body is a solid needle, the length of the needle body is less than or equal to 40 mm, and the outer diameter of the needle body is less than 0.3 mm; a suction cylinder is fixedly connected to the bottom of the injection barrel, the outer diameter of the suction cylinder is smaller than the inner diameter of the injection barrel, the needle body is threadedly connected to the suction cylinder, and the pressure rod moves toward the needle body to make the exosomes flow out from the space between the injection barrel and the suction cylinder, and flow to the acupuncture point along the outer wall surface of the suction cylinder and the needle body.

[0012] As a further illustration of the present invention, preferably, the end where the suction tube connects to the needle body extends out of the injection barrel, and the suction tube is not connected to the needle body to suck the exosomes into the injection barrel.

[0013] As a further illustration of the present invention, preferably, the outer wall surface of one end of the suction cylinder extending into the injection cylinder is fixedly connected with a plurality of connection blocks at intervals, and the connection blocks are fixedly connected to the inner wall surface of the injection cylinder.

[0014] As a further illustration of the present invention, preferably, when the suction tube is not connected to the needle body, a sealing cap is inserted into the space between the suction tube and the injection tube, and the sealing cap is an annular structure to seal the space between the suction tube and the injection tube.

[0015] As a further illustration of the present invention, preferably, a handle is fixedly connected to one end of the sealing cap, and one end of the strip-shaped handle extends out of the sealing cap.

[0016] As a further illustration of the present invention, preferably, the exosomes are obtained by centrifugation using cell supernatant free of cells and debris, and the exosomes are collected using PBS buffer.

[0017] As a further illustration of the present invention, preferably, after the exosomes are collected, a Zetaview instrument is used to detect the concentration and particle size of the exosomes.

[0018] (III) Beneficial effects

[0019] The above technical solution of the present invention has the following advantages:

[0020] The present invention transforms acupuncture needles into structures capable of injecting exosomes, and utilizes the stimulation of acupuncture combined with the membrane permeability of exosomes to promote tissue regeneration and repair, regulate immune function, and improve the synergistic effect of nerve function. It can also play an analgesic role and enhance the effect of acupuncture. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is a diagram showing the improved effect of the long acupuncture needle of the present invention;

[0022] Figure 2 is a cross-sectional view of the injection barrel of the long acupuncture needle of the present invention;

[0023] Figure 3 It is a diagram showing the improved effect of the short acupuncture needle of the present invention;

[0024] Figure 4 It is a structural diagram of the cap of the short acupuncture needle of the present invention;

[0025] Figure 5 is a partial cross-sectional view of the short acupuncture needle of the present invention;

[0026] Figure 6 It is a cross-sectional view of the injection barrel of the short acupuncture needle of the present invention.

[0027] In the figure: 1. syringe barrel; 2. pressure rod; 21. inclined cap; 3. needle body; 31. winding wire; 4. suction tube; 41. connecting block; 5. sealing cap; 51. handle. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution 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 part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] A microneedle for exosome injection, divided into two types: long acupuncture needle and short acupuncture needle, combined with Figure 1 , Figure 2The microneedle type of the long acupuncture needle includes a syringe 1, a pressure rod 2 and a needle body 3. The syringe 1 contains exosomes secreted from neural stem cells. One end of the pressure rod 2 is slidably connected to the syringe 1, and the other end of the pressure rod 2 extends out of the syringe 1. The needle body 3 is threadedly connected to the syringe 1. The needle body 3 is a hollow needle. The length of the needle body 3 is greater than 40mm, that is, 40mm (one and a half inches), 50mm (two inches), 60mm (two and a half inches) and 75mm (three inches) can be selected. The outer diameter of the needle body 3 is between 0.30 and 0.45mm, that is, 0.3mm (No. 31), 0.32mm (No. 30), 0.34mm (No. 29), 0.38mm (No. 28), 0.42mm (No. 27) and 0.45mm (No. 26) can be selected. The space inside the needle body 3 is connected to the inner cavity of the syringe 1, and the needle body 3 is wrapped with multiple layers of wire 31 to facilitate needle movement and twisting. The sharp portion of the needle body 3 pierces the acupuncture point, and the pressing rod 2 moves toward the needle body 3 to inject the exosomes from the needle body 3 into the acupuncture point.

[0030] Combination Figure 1 , Figure 2 When a Chinese medicine practitioner or acupuncturist needs to perform acupuncture on a patient, first insert the hollow needle body 3 into the acupuncture point, then screw the syringe 1 containing exosomes into the thread of the needle body 3, then clamp the needle body 3 with the thumb and ring finger, hold the syringe 1 with the middle finger, and push the pressure rod 2 with the index finger to push the exosomes in the syringe 1 into the acupuncture point through the needle body 3. After the exosomes are pushed in, unscrew the syringe 1 and keep the needle body 3 at the acupuncture point until the treatment time is over.

[0031] Combination Figure 3 , Figure 5 The microneedle type of the short acupuncture needle includes a syringe 1, a pressure rod 2, a needle body 3, a suction tube 4 and a sealing cap 5. The syringe 1 contains exosomes secreted from neural stem cells. One end of the pressure rod 2 is slidably connected to the syringe 1, and the other end of the pressure rod 2 extends out of the syringe 1. The cylindrical suction tube 4 is fixedly connected to the end of the syringe 1 away from the pressure rod 2. The outer diameter of the suction tube 4 is smaller than the inner diameter of the syringe 1. The needle body 3 is threadedly connected to the suction tube 4, and the end where the suction tube 4 and the needle body 3 are connected extends out of the syringe 1. The needle body 3 is a solid needle, and the length of the needle body 3 is less than or equal to 40mm, that is, 25mm (one inch) and 13mm (half inch) can be selected. The outer diameter of the needle body 3 is less than 0.3mm, that is, 0.28mm (No. 32), 0.26mm (No. 33), 0.24mm (No. 34), and 0.22mm (No. 35) can be selected. The sharp part of the needle body 3 pierces the acupuncture point, and the pressing rod 2 moves toward the needle body 3 to make the exosomes flow out from the space between the injection cylinder 1 and the suction cylinder 4, and flow to the acupuncture point along the outer wall surface of the suction cylinder 4 and the needle body 1. The sealing cap 5 is a flexible annular structure. When the suction cylinder 4 is not connected to the needle body 1, the sealing cap 5 is inserted into the space between the suction cylinder 4 and the injection cylinder 1 to close the space between the suction cylinder 4 and the injection cylinder 1.

[0032] Combination Figure 4, Figure 6 The outer wall surface of the end of the suction tube 4 extending into the injection barrel 1 is fixedly connected with a plurality of connection blocks 41 at intervals, and the connection blocks 41 are fixedly connected to the inner wall surface of the injection barrel 1. The connection blocks 41 are provided to realize that the suction tube 4 is not directly and completely closed with the injection barrel 1. A handle 51 is fixedly connected to one end of the sealing cap 5, and one end of the strip-shaped handle 51 extends out of the sealing cap 5, so that the sealing cap 5 can be torn off the injection barrel 1 during injection. In addition, an inclined cap 21 is fixedly connected to one side of the pressure rod 2, which is used to fit the index finger joint and increase the contact area with the index finger, so that the Chinese medicine practitioner or acupuncturist can better control the injection measurement.

[0033] Combination Figure 4 , Figure 5 When a Chinese medicine practitioner or acupuncturist needs to perform acupuncture on a patient, first insert the solid needle body 3 into the acupuncture point. At this time, the suction tube 4 is not connected to the needle body 3. First, insert the suction tube 4 into the exosome container. Due to the closure of the sealing cap 5, the exosome can be sucked into the syringe 1. Then, the suction tube 4 is threadedly connected to the needle body 3. By holding the needle body 3 with one hand, the sealing cap 5 is torn off with the other hand, and then the thumb and middle finger clamp the syringe 1 and twist the syringe 1. The index finger pushes the pressure rod 2 to make the exosomes in the syringe 1 flow out through the space between the syringe 1 and the suction tube 4, and flow along the outer wall of the suction tube 4 and the needle body 1 to the acupuncture point. During the twisting process, the needle body 3 introduces the exosomes into the acupuncture point. After the exosomes are pushed in, the syringe 1 is unscrewed, and the needle body 3 is retained at the acupuncture point until the treatment time is over.

[0034] Among them, both microneedles use a kind of exosomes, which are cell supernatants without cells and debris. The specific method of obtaining exosomes is as follows:

[0035] Neural stem cells were cultured under culture conditions containing appropriate culture medium and growth factors to produce exosomes. Cell debris was removed by centrifugation to obtain cell culture supernatant. Cell supernatant was first centrifuged at 2000rpm for 10min to remove cells and debris, and then residual debris or impurities were filtered with a 0.22μm filter. Centrifuge at 120000×g (Beckman) at 4℃ for 2h, resuspend and wash with 1mL pre-cooled PBS, centrifuge at 120000×g at 4℃ for 2h, and finally collect exosomes with 100μL PBS. Finally, the Zetaview (ParticleMetrix) instrument was used to detect the concentration and particle size of exosomes using the light scattering detection system and the Brownian motion of nanoparticles.

[0036] In summary, the present invention uses the communication property of exosomes to inject exosomes into acupuncture and moxibustion, and acts as a messenger in the acupuncture intervention process, so that the acupuncture effect is fully adjusted and utilized by the body's homeostasis, and the body's balance is maintained endogenously. And it is possible to use the permeability of exosomes to penetrate the cell membrane, and the surface specific molecules carried by the exosomes themselves bind to the target cells, promote the growth, differentiation and regeneration of nerve cells, and enhance the acupuncture treatment effect. At present, there is acupuncture Zusanli for rats with adjuvant arthritis, and exosomes are injected, and proteomics and metabolomics techniques are used to detect the whole protein components and metabolites contained in the exosomes in the serum of rats after acupuncture, and it is found that some special signal molecules are contained in the exosomes, including calcitonin gene-related peptide (CGRP), norepinephrine (NE), interleukin (IL), tumor necrosis factor (TNF-α) and other chemicals. It is proved that exosomes can cascade amplify acupuncture stimulation signals, activate the body's nerve-endocrine-immune network regulation system, and exert the acupuncture network regulation effect.

[0037] The present invention can design two types of microneedles with injection functions according to different acupuncture positions, wherein the long needle is suitable for areas with rich muscle tissue that require deep puncture, such as the limbs and abdomen, and even the buttocks, and the long needle can be processed into a hollow structure according to standardization, and the manufacturing cost is low. The short needle is suitable for areas with relatively shallow subcutaneous tissue such as the face, and the short needle has a small diameter and is not easy to process into a hollow structure. Therefore, a solid structure is adopted, and the fluid viscosity of the exosomes and the twisting during acupuncture are utilized to enable the exosomes to penetrate into the subcutaneous tissue, avoiding the use of thick hollow needles to stimulate the face too strongly and cause greater pain, thereby reducing the stimulation and damage to the skin in sensitive areas. In addition, the production cost is low, the operation difficulty is also low, and it is easy for novice acupuncturists to get started.

[0038] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A microneedle for exosome injection, characterized in that: The invention comprises an injection barrel (1), a pressure rod (2) and a needle body (3), wherein the injection barrel (1) contains exosomes secreted from neural stem cells, one end of the pressure rod (2) is slidably connected to the injection barrel (1), and the other end of the pressure rod (2) extends out of the injection barrel (1); the needle body (3) is connected to the injection barrel (1), the needle body (3) is a solid needle, the length of the needle body (3) is less than or equal to 40 mm, and the outer diameter of the needle body (3) is less than 0.3 mm; a suction cylinder (4) is fixedly connected to the bottom of the injection barrel (1), the outer diameter of the suction cylinder (4) is less than the inner diameter of the injection barrel (1), the needle body (3) is threadedly connected to the suction cylinder (4), the sharp part of the needle body (3) pierces the acupuncture point, and the pressure rod (2) moves toward the needle body (3) to make the exosomes flow out from the space between the injection barrel (1) and the suction cylinder (4), and flow to the acupuncture point along the outer wall surface of the suction cylinder (4) and the needle body (3).

2. A microneedle for exosome injection according to claim 1, characterized in that: The end of the suction tube (4) connected to the needle body (3) extends out of the injection tube (1), and the suction tube (4) is not connected to the needle body (3) so as to suck the exosomes into the injection tube (1).

3. A microneedle for exosome injection according to claim 2, characterized in that: The outer wall surface of one end of the suction cylinder (4) extending into the injection cylinder (1) is fixedly connected with a plurality of connection blocks (41) at intervals, and the connection blocks (41) are fixedly connected to the inner wall surface of the injection cylinder (1).

4. A microneedle for exosome injection according to claim 3, characterized in that: When the suction tube (4) is not connected to the needle body (3), a sealing cap (5) is inserted into the space between the suction tube (4) and the injection tube (1). The sealing cap (5) is an annular structure so as to seal the space between the suction tube (4) and the injection tube (1).

5. A microneedle for exosome injection according to claim 4, characterized in that: A handle (51) is fixedly connected to one end of the sealing cap (5), and one end of the strip-shaped handle (51) extends out of the sealing cap (5).

6. A microneedle for exosome injection according to claim 5, characterized in that: Exosomes were obtained by centrifugation of cell supernatant free of cells and debris, and exosomes were collected using PBS buffer.

7. A microneedle for exosome injection according to claim 6, characterized in that: After collecting the exosomes, the Zetaview instrument was used to detect the exosome concentration and particle size.

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