Platelet Exosome Concentration Tube

Abstract

Provided is a platelet exosome concentrating tube. 【Solution means】The platelet exosome concentrating tube includes a tube body having a closed end, an open end and an accommodation space, a lid body detachably covered on the open end of the tube body, and a plurality of ground glass beads provided in the accommodation space and having uneven shapes with uniform distribution on each surface. By using the physical principle to destroy the cell membrane of platelets, exosomes of the other three isomers in the cytoplasm of platelets are activated and released, and a platelet exosome concentrate containing multiple types of anti-inflammatory factors and growth factors is obtained.

Description

Technical Field

[0001] This Proposal relates to a blood sampling device, particularly a platelet exosome concentration tube.

Background Art

[0002] Human blood mainly contains two parts: plasma and blood cells. The main components of blood cells are red blood cells, white blood cells and platelets. Whole blood can be prepared into various components and stored under ideal conditions, and can be effectively used for various treatments. Platelets have been found to have the effect of quickly activating blood coagulation and endogenous growth factors in vitro in clinical treatment, and have a good effect of promoting cell growth and repair on the human body.

[0003] With the development of modern medicine, a small amount of blood components such as platelet-rich plasma (PRP) are widely used in clinical surgery and cosmetic medicine. Blood is drawn from the subject itself, platelet-rich plasma is collected, and immediately injected onto the skin or tissue surface of the patient through medical means to achieve the medical effect of treating and recovering the patient's own body. The rejection reaction caused by exogenous blood products can be avoided.

[0004] PRP uses the growth factors and anti-inflammatory factors secreted by exosomes on the platelet surface to treat physical discomfort, and is mainly used for osteoarthritis, muscle ligament injury, anti-inflammation and tissue repair. In addition, PRP can also be applied in cosmetic medicine and dentistry. For example, its application in cosmetic medicine can reduce wrinkles, and its application in dentistry can fill the dental pulp, promote the adhesion between the implant metal and the dental pulp cavity to increase growth, and further improve the success rate of the implant.

[0005] However, platelets can secrete growth factors and anti-inflammatory factors from the exosomes on their surface, and the cytoplasm of platelets further contains exosomes of three isoforms. Well-known PRP only activates the exosomes on the platelet surface, so only the growth factors on the platelet surface are activated and released, and the other three isoforms of exosomes inside the platelet cell membrane are not utilized. Therefore, it is important to develop a clinical medical device that can disrupt the platelet cell membrane and further activate the growth factors and anti-inflammatory factors released by utilizing the three isoforms of exosomes inside the platelet cell membrane to enhance the therapeutic effect and scope of clinical application.

Summary of the Invention

Problems to be Solved by the Invention

[0006] The Proposal objective is to provide a platelet exosome concentrate tube that can disrupt the platelet cell membrane by utilizing physical principles, so that the other three isoforms of exosomes in the cytoplasm of platelets can also be activated and released, and further obtain a platelet exosome concentrate containing multiple types of anti-inflammatory factors and growth factors.

Means for Solving the Problems

[0007] The Proposal embodiment provides a platelet exosome concentrate tube, comprising a tube body having a closed end, an open end opposite to the closed end, and a receiving space formed by the closed end communicating with the open end, a lid detachably covering the open end of the tube body for opening and closing the receiving space, and a plurality of ground glass beads provided in the receiving space and having uneven shapes with their respective surfaces uniformly distributed.

[0008] According to the platelet exosome concentrate tube of the above embodiment, the closed end of the tube body may be arc-shaped.

[0009] According to the platelet exosome concentrate tube of the above embodiment, the tube body may further include a stand portion connected to the closed end and having a flat bottom at the end farther from the closed end.

[0010] According to the platelet exosome concentration tube of the above embodiment, the material of the tube body may be glass or plastic.

[0011] According to the platelet exosome concentration tube of the above embodiment, the lid may be a spiral tube cap, a plastic cap, a safety cap or a rubber cap.

[0012] According to the platelet exosome concentration tube of the above embodiment, a male thread is provided at the open end of the tube body, and a female thread is provided on the inner ring of the lid, and the tube body and the lid are tightly coupled by the male thread and the female thread.

[0013] According to the platelet exosome concentration tube of the above embodiment, the lid may include an injection port for injecting and / or extracting a blood sample in cooperation with a blood collection needle.

[0014] According to the platelet exosome concentration tube of the above embodiment, the lid may further include a connection portion protruding from the upper surface of the lid for connection to a negative pressure aspirator.

[0015] According to the platelet exosome concentration tube of the above embodiment, in order to seal the accommodation space, it may further include a rubber stopper provided between the tube body and the lid.

[0016] According to the platelet exosome concentration tube of the above embodiment, the surface roughness (RMS) of the surface of each ground glass bead may be 0.01 μm to 0.5 μm.

[0017] According to the platelet exosome concentration tube of the above embodiment, the average particle diameter of each ground glass bead may be 2 mm to 10 mm.

Brief Description of the Drawings

[0018] This Proposal In order to make the above and other objects, features, advantages and embodiments of this more clearly understood and easier to understand, the description of the drawings is as follows.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Mode for Carrying Out the Invention

[0019] Hereinafter, examples of the present Proposal will be described with reference to the drawings. For the sake of clear explanation, many implementation details will be described in conjunction with the following description. However, it should be understood that these implementation details are not intended to limit the present Proposal . That is, in some embodiments of the present Proposal , these implementation details are not necessary. Furthermore, in order to simplify the drawings, some well-known conventional structures and components are simply schematically shown in the drawings, and overlapping components may be denoted by the same reference numerals.

[0020] Please refer to FIG. 1. FIG. 1 is an exploded view of a platelet exosome concentration tube 100 according to one embodiment of the present Proposal , and the platelet exosome concentration tube 100 includes a tube body 110, a lid body 120, and a plurality of ground glass beads 130.

[0021] The tube body 110 has a closed end 112, an open end 111 opposite to the closed end 112, and an accommodation space 113 formed by the closed end 112 communicating with the open end 111. The closed end 112 of the tube body 110 may be arc-shaped so that the platelet exosome concentration tube 100 can concentrate the blood sample at the bottom of the tube in the use state. The material of the tube body 110 may be glass or plastic, preferably transparent or translucent plastic or glass so that the blood layer separation can be clearly seen when the platelet exosome concentration tube 100 is used. In addition, the outer wall surface of the tube body 110 may have a plurality of scale marks so that the internal volume can be directly recognized in the use state. More preferably, the inner tube diameter of the tube body 110 may be 10 mm to 20 mm, the length of the tube body 110 may be 100 mm to 150 mm, and it can accommodate a blood sample of 10 mL to 15 mL, but is not limited thereto.

[0022] The lid 120 is detachably placed on the open end 111 of the tube body 110 to open and close the accommodation space 113. The lid 120 may be a spiral tube cap, a plastic cap, a safety cap or a rubber cap. When the lid 120 is made of a non-elastic material such as a spiral tube cap, a plastic cap or a safety cap, a male thread is provided at the open end 111 of the tube body 110, and a female thread is provided on the inner ring of the lid 120, whereby the tube body 110 and the lid 120 are tightly coupled by the male thread and the female thread. When the lid 120 is made of an elastic material such as a rubber cap, the lid 120 may be directly covered on the open end 111 of the tube body 110. The lid 120 may include an injection port 121 for injecting and / or extracting a blood sample in cooperation with a blood collection needle, and the blood collection needle may be of a hard connection type or a soft connection type.

[0023] The abrasive glass beads 130 are provided in the accommodation space 113, and the surface 131 of each abrasive glass bead 130 has an uneven shape that is uniformly distributed. The uneven shape that is uniformly distributed on the surface 131 can be formed by a chemical treatment method or a physical treatment method. The chemical treatment method, such as the abrasive glassification treatment method, can obtain the abrasive glass beads 130 by immersing the glass beads in a mixed solution of hydrogen fluoride and ammonium fluoride and chemically treating the immersion surface. The physical treatment method includes performing a blasting treatment of spraying crystalline silica powder, silicon carbide powder, etc. onto the surface of the glass beads using pressurized air to obtain the abrasive glass beads 130, or polishing the glass beads with a brush impregnated with water and adhering crystalline silica powder, silicon carbide powder, etc. to obtain the abrasive glass beads 130. The surface roughness (RMS) of the surface of each abrasive glass bead 130 may be 0.01 μm to 0.5 μm, and the average particle diameter of each abrasive glass bead 130 may be 2 mm to 10 mm. More preferably, 20 to 50 abrasive glass beads 130 can be provided in the accommodation space 113 of the tubular body 110, but it is not limited thereto. Referring to Tables 1 to 3 below, Table 1 shows the properties related to the size of the abrasive glass beads 130, Table 2 shows the chemical properties of the abrasive glass beads 130, and Table 3 shows the physical properties of the abrasive glass beads 130.

[0024]

Table 1

[0025]

Table 2

[0026]

Table 3

[0027] The platelet exosome concentration tube 100 contains, on its surface 131 abrasive glass beads having an uneven shape that is uniformly distributed 130By using the physical principle to disrupt the cell membrane of platelets when manufacturing platelet exosome concentrate, the exosomes of the other three isomers in the cytoplasm of platelets can also be activated and released, and a platelet exosome concentrate containing multiple types of anti-inflammatory factors and growth factors can be obtained. The concentration of various growth factors in the obtained platelet exosome concentrate is several times higher than that of well-known platelet-rich plasma, and the subsequent clinical treatment effect is better.

[0028] Please refer to FIG. 2. FIG. 2 is a Proposal exploded view of a platelet exosome concentrate tube 200 according to another embodiment of the present invention. The platelet exosome concentrate tube 200 includes a tube body 210, a lid body 220, a plurality of ground glass beads 230, and a rubber stopper 240.

[0029] The tube body 210 has a closed end 212, an open end 211 opposite to the closed end 212, and an accommodation space 213 formed by the communication of the closed end 212 with the open end 211. Since other technical details of the tube body 210 are the same as those of the tube body 110, they will not be described further here.

[0030] The lid body 220 is detachably covered on the open end 211 of the tube body 210 to open and close the accommodation space 213. The lid body 220 may include an injection port 221 for injecting and / or extracting a blood sample in cooperation with a blood collection needle. Since other technical details of the lid body 220 are the same as those of the lid body 120, they will not be described further here.

[0031] The ground glass beads 230 are provided in the accommodation space 213, and the surface (not shown) of each ground glass bead 230 has an uneven shape uniformly distributed. Since other technical details of the ground glass beads 230 are the same as those of the ground glass beads 130, they will not be described further here.

[0032] The platelet exosome concentrate tube 200 has an accommodation space 213To seal it, it further includes a rubber stopper 240 provided between the tube body 210 and the lid body 220. The outer diameter of the rubber stopper 240 may be the same as the outer diameter of the tube body 210. In addition, a convex portion 241 with an outer diameter the same as the inner diameter of the tube body 210 may be provided at the end of the rubber stopper 240 closer to the tube body 210. The rubber stopper 240 can be inserted into the open end 211 of the tube body 210 by the convex portion 241. Thus, the rubber stopper 240 is attached to the open end 211 of the tube body 210, and the lid body 220 covers the outside of the rubber stopper 240. The material of the rubber stopper 240 may be butyl rubber, and the cooperating blood collection needle can pierce the rubber stopper 240 from the injection port 221 of the lid body 220 and enter the accommodation space 213 of the tube body 210.

[0033] Please refer to FIGS. 3 and 4. FIG. 3 is a perspective view of another embodiment of the platelet exosome concentrating tube 300 of the present Proposal FIG. 4 is a combined cross-sectional view of the platelet exosome concentrating tube 300 in FIG. 3. The platelet exosome concentrating tube 300 includes a tube body 310, a lid body 320, a plurality of ground glass beads 330, and a rubber stopper 340.

[0034] The tube body 310 has a closed end 312, an open end 311 opposite to the closed end 312, an accommodation space 313 formed by the closed end 312 communicating with the open end 311, and a stand portion 314. The closed end 312 of the tube body 310 may be arc-shaped so that the platelet exosome concentrating tube 300 can concentrate the blood sample at the bottom of the tube in the use state. The tube body 310 of the platelet exosome concentrating tube 300 further includes a stand portion 314 connected to the closed end 312 and having a flat bottom at the end farther from the closed end 312. As shown in FIG. 4, since one end of the stand portion 314 is a flat bottom, the platelet exosome concentrating tube 300 can be made to stand upright on the tabletop where it is used, eliminating the need to arrange or store the platelet exosome concentrating tube 300 using a test tube rack, and improving the convenience of use. Since other technical details of the tube body 310 are the same as the technical details of the tube body 110, no further description will be given here.

[0035] The lid 320 is detachably placed over the open end 311 of the tube body 310 to open and close the accommodation space 313. The lid 320 may include an injection port 321 for injecting and / or extracting a blood sample in cooperation with a blood collection needle. Since other technical details of the lid 320 are the same as those of the lid 120, they will not be described further here.

[0036] The ground glass beads 330 are provided in the accommodation space 313, and the surface (not shown) of each ground glass bead 330 has an uneven shape that is uniformly distributed. Since other technical details of the ground glass beads 330 are the same as those of the ground glass beads 130, they will not be described further here.

[0037] The rubber stopper 340 is provided between the tube body 310 and the lid 320 to seal the accommodation space 313 Since other technical details of the rubber stopper 340 are the same as those of the rubber stopper 240, they will not be described further here.

[0038] Please refer to FIGS. 5 and 6. FIG. 5 is a perspective view of a platelet exosome concentration tube 400 according to another embodiment of the present invention, and FIG. 6 is a combined cross-sectional view of the platelet exosome concentration tube 400 in FIG. 5. The platelet exosome concentration tube 400 includes a tube body 410, a lid 420, and a plurality of ground glass beads 430. Proposal

[0039] The tube body 410 has a closed end 412, an open end 411 facing the closed end 412, an accommodation space 413 formed by the closed end 412 communicating with the open end 411, and a stand portion 414. The stand portion 414 is connected to the closed end 412, and the end of the stand portion 414 farther from the closed end 412 is a flat bottom so that the platelet exosome concentration tube 400 can be erected on the tabletop where it is used. Since other technical details of the tube body 410 are the same as those of the tube body 110, they will not be described further here.

[0040] ​The lid 420 is detachably placed on the open end 411 of the tube body 410 to open and close the accommodation space 413. The lid 420 may include an injection port 421 for injecting and / or extracting a blood sample in cooperation with a blood collection needle. The lid 420 of the platelet exosome concentration tube 400 further includes a connection part 422 protruding from the upper surface of the lid 420 for connection to a negative pressure aspirator, thereby expanding the applicable range of the platelet exosome concentration tube 400. Since other technical details of the lid 420 are the same as those of the lid 120, they will not be described further here.

[0041] The ground glass beads 430 are provided in the accommodation space 413, and the surface (not shown) of each ground glass bead 430 has an uneven shape that is uniformly distributed. Since other technical details of the ground glass beads 430 are the same as those of the ground glass beads 130, they will not be described further here.

[0042] Test Example Platelets can secrete multiple types of growth factors and anti-inflammatory factors with functions such as promoting cell movement, differentiation, division, matrix proliferation, angiogenesis, and balance. These include important growth factors, such as Platelet-derived growth factor (PDGF), Transforming growth factor α (TGFα), Transforming growth factor β (TGFβ), Insulin-like growth factor 1 (IGF-1), Vascular endothelial growth factor (VEGF), and Interleukin 1 receptor antagonist (IL1-Ra). PDGF has functions such as attracting stem cells, promoting stem cell division and extracellular matrix secretion, and stimulating bone formation. TGFα can promote extracellular matrix secretion and the maturation of progenitor cells. TGFβ can help improve allergic constitution and regulate the normal development of the immune system, and the TGFβ superfamily includes TGFβ1, TGFβ2, and TGFβ3. IGF-1 can promote the healing of fractures and the growth of skin, muscle, blood vessels, tendons, and ligaments. VEGF can promote angiogenesis and inhibit osteoclasts. IL1-Ra can inhibit the inflammatory factor - interleukin 1 and is an important anti-inflammatory factor.

[0043] This Proposal To test the platelet exosome concentration tube of this, a platelet exosome concentrate containing multiple types of anti-inflammatory factors and growth factors can be produced. This test example further uses a blood sample collected from a subject for this ProposalInject into the platelet exosome concentration tube with a blood collection needle, leave it in an incubator at 37°C to stabilize the activity of platelets, take it out of the incubator after 1 - 4 hours, place it in the inner sleeve of a flywheel type centrifuge, and centrifuge at 4000 rpm / min for 5 minutes. At this time, the blood sample is separated into a platelet exosome concentrate layer and a blood cell layer. After centrifugation, take out the platelet exosome concentration tube, insert a long needle from the injection port of the lid into the tube body, and extract the upper layer of platelet exosome concentrate to obtain the manufactured platelet exosome concentrate, which can then be injected into the site that needs to be used by the subject. The used platelet exosome concentration tube may be the platelet exosome concentration tube shown in FIG. 1, FIG. 2, FIG. 3 or FIG. 5.

[0044] In the test, this Proposal The concentrations of various growth factors and cytokines in the platelet exosome concentrate (hereinafter abbreviated as "PRPII") produced by the platelet exosome concentration tube were compared with the concentrations of various growth factors and cytokines in the platelet-rich plasma (hereinafter abbreviated as "PRP") produced by a well-known method. Referring to Table 4 and Table 5, Table 4 shows the increased multiples of the concentrations of the growth factors of PRPII required for the clinical application of the repair of various tissues, and the numerical values are based on PRP. Table 5 shows the concentrations of various cytokines of PRPII and PRP. The numbers in parentheses after PRPII indicate the time (hour) left in the incubator, and the concentration units of all various cytokines were all pg / mL.

[0045]

Table 4

[0046]

Table 5

[0047] According to the results of Table 4, this ProposalIt has been shown that the concentration of growth factors necessary for the repair of various tissues contained in PRPII produced in the platelet exosome concentration tube of [[ID=]] is significantly increased compared to well-known PRP. According to the results in Table 5, the growth factor concentration is related to the standing time of the blood sample at 37 °C. To obtain the best results, the optimal standing time is 3 - 4 hours. It has been shown that the concentration of the anti-inflammatory factor IL1-Ra contained in PRPII is 4.15 times that of PRP, and the concentration of the PDGF growth factor contained in PRPII is 5.4 times that of PRP. The concentration of tumor necrosis factor α (TNFα) contained in PRPII is slightly higher than that of PRP, but it does not increase significantly due to the long culture time. This Proposal It has been shown that high-concentration PRPII containing various types of growth factors can actually be prepared using the platelet exosome concentration tube of [[ID=]].

[0048] In the test, this Proposal The effect of PRPII, that is, the pain level decreases after injection into patients with osteoarthritis, was further verified by using PRPII produced in the platelet exosome concentration tube of [[ID=]] in a clinical trial. The subjects of the test were 30 patients in the third stage of osteoarthritis (VAS pain level: 8 - 10). The above subjects received PRPII treatment once every two weeks for a total of 5 treatments. The test included subjects who received PRP treatment as a control, and the policy of PRP treatment was the same as that of PRPII treatment. Referring to Table 6 and Table 7, Table 6 shows the percentage of pain improvement of the subjects, and Table 7 shows the pain level results of the subjects after the end of the course.

[0049]

Table 6

[0050]

Table 7

[0051] The results in Table 6 and Table 7 showed that all the subjects who received PRPII treatment had their pain improved after the cool-down, and furthermore, the pain level of 80% of the subjects decreased from the original 8 - 10 to 2 - 4, indicating that Proposal PRPII produced with the platelet exosome concentration tube of the present invention has been proven to have a significant effect in improving the pain of patients with osteoarthritis.

[0052] The Proposal PRPII produced with the platelet exosome concentration tube of the present invention can be applied not only to the clinical applications such as injection treatment of osteoarthritis and tendon injury, but also to various clinical treatments such as dental implant treatment, medical aesthetic treatment, hair removal treatment, orthopedic treatment, trauma treatment, ophthalmic treatment, and obstetric and gynecological treatment. When used in dental implant treatment, it can be mixed with hyaluronic acid to form a semi-solid filler and filled into the dental implant site, thereby promoting the tight bonding between the dental implant and the bone and increasing the success rate of dental implants. When used in medical aesthetic treatment, it can be injected subcutaneously to promote collagen regeneration and improve the skin, and the effect can also be doubled by using it simultaneously with facial injection of hyaluronic acid. When used in hair removal treatment, it can be injected into the scalp to regenerate hair. When used in orthopedic treatment, it can be directly injected into the fracture defect site after surgery to promote bone healing or injected into bone cavities to promote growth. When used in trauma treatment, it can be combined with artificial skin to cover the feet of diabetic patients and chronic ulcerative wounds that are difficult to heal such as bedsores and burns, and promote healing. When used in ophthalmic treatment, it can be manufactured into eye drops for treating dry eye syndrome, chronic corneal ulcers, or corneal dystrophy. When used in obstetric and gynecological treatment, by injecting PRPII from the cervix into the uterus to thicken the endometrium, infertility caused by insufficient endometrial thickness can be improved and the success rate of pregnancy can be increased.

[0053] As described above, the ProposalThe platelet exosome concentration tube contains ground glass beads with uneven shapes uniformly distributed on the surface. Therefore, when manufacturing the platelet exosome concentrate, by utilizing the physical principle to break the cell membrane of platelets, in addition to the exosomes on the surface of platelets, the exosomes of the other three isomers in the cytoplasm can also be activated and released. Furthermore, a platelet exosome concentrate containing multiple types of anti-inflammatory factors and growth factors can be obtained, and the concentrations of various types of growth factors in the obtained platelet exosome concentrate are several times higher than those in well-known platelet-rich plasma. The subsequent clinical treatment effect is better, and it can be applied to various clinical treatments, with great future potential for clinical application.

[0054] This Proposal has been disclosed in the embodiments as described above. However, the above-described embodiments are not used to limit this Proposal Anyone skilled in the art can make various changes and modifications without departing from the spirit and scope of this Proposal Therefore, the protection scope of this Proposal should be based on what is defined in the appended Utility Model Registration claims.

Description of Reference Numerals

[0055] 100, 200, 300, 400: Platelet exosome concentration tube 110, 210, 310, 410: Tube body 111, 211, 311, 411: Open end 112, 212, 312, 412: Closed end 113, 213, 313, 413: Accommodation space 120, 220, 320, 420: Lid 121, 221, 321, 421: Injection port 130, 230, 330, 430: Ground glass beads 131: Surface 240, 340: Rubber stopper 241: Convex part 314, 414: Stand part 422: Connection part

Claims

1. A platelet exosome concentration tube, comprising: a tube body having a closed end, an open end opposite to the closed end, and a receiving space formed by the closed end communicating with the open end; a lid detachably covering the open end of the tube body for opening and closing the receiving space; a plurality of ground glass beads provided in the receiving space and having uneven shapes with their respective surfaces uniformly distributed.

2. The platelet exosome concentration tube according to claim 1, wherein the closed end of the tube body is arc-shaped.

3. The platelet exosome concentration tube according to claim 2, further comprising a stand portion connected to the closed end of the tube body and having a flat bottom at the end farther from the closed end.

4. The platelet exosome concentration tube according to claim 1, wherein the material of the tube body is glass or plastic.

5. The platelet exosome concentration tube according to claim 1, wherein the lid is a spiral tube cap, a plastic cap, a safety cap or a rubber cap.

6. The platelet exosome concentration tube according to claim 1, wherein a male thread is provided at the open end of the tube body, a female thread is provided on the inner ring of the lid, and the tube body and the lid are tightly coupled by the male thread and the female thread.

7. The platelet exosome concentration tube according to claim 1, wherein the lid includes an injection port for injecting and / or extracting a blood sample in cooperation with a blood collection needle.

8. The platelet exosome concentration tube according to claim 7, further comprising a connection portion protruding from the upper surface of the lid for connection to a negative pressure aspirator.

9. The platelet exosome concentration tube according to claim 1, further comprising a rubber stopper provided between the tube body and the lid for sealing the receiving space.

10. The platelet exosome concentration tube according to claim 1, wherein the surface roughness (RMS) of the surface of each of the ground glass beads is 0.01 μm to 0.5 μm.

11. The platelet exosome concentration tube according to claim 1, wherein the average particle diameter of each of the ground glass beads is 2 mm to 10 mm.

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