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    • 专利摘要:
    COMPOSITION PRODUCTION METHOD FOR INDUCING TISSUE REGENERATION THROUGH PLATELET-RICH PLASMA ACTIVATION (PRP) This invention is a composition to induce tissue regeneration through activation of platelet-rich plasma (PRP) with a solution of calcium chloride and type I collagen, and the method of production thereof. The revealed method includes the steps of: separating the PRP from the whole blood; mixing the PRP with a calcium chloride solution; and mix the PRP mixture and the calcium chloride solution with type I collagen. The disclosed composition may have a gel-like formation containing PRP, and can be transplanted into any lesion that requires tissue regeneration in cases such as treatment of bone defects and healing of wounds and, correspondingly, PRP can be activated to induce a growth factor that is useful for the regeneration of tissues from the PRP gel, to obtain rapid and effective tissue regeneration. Consequently, the method is very useful to significantly increase the credibility of the application of PRP in injuries and to present a good (...).
    公开号:BR112012009560B1
    申请号:R112012009560-9
    申请日:2009-11-17
    公开日:2021-03-09
    发明作者:Park Hyun-Shin；Yu Ji-Chul；Park Ju-Hee；Kim Jang-Hoon；Kim Hun；Lee Sae-Bom；Jang Jae-Deog；Jang Cheong-Ho
    申请人:Sewon Cellontech Co., Ltd；
    IPC主号:
    专利说明:

    Technical Field
    [001] The present invention relates to a composition to induce tissue regeneration through the activation of platelet-rich plasma (PRP) with a solution of calcium chloride and type I collagen, and the method of production thereof. More specifically, in the present invention, the composition can have a gel-like formation containing PRP, and can be transplanted into any lesion that requires tissue regeneration in cases such as treatment of bone defects and wound healing and, consequently, PRP can be activated to induce a growth factor that is useful for tissue regeneration from the PRP gel to achieve rapid and effective tissue regeneration. Consequently, the method is very useful to significantly increase the credibility of applying PRP to injuries and to present a good image to consumers. Fundamentals of the Invention
    [002] As is common knowledge, platelet-rich plasma (PRP) is an autologous material separated from whole blood through density gradient centrifugation, and consists of an inactive substance that includes a large amount of platelets concentrated in relation to a small amount of plasma, and contains leukocytes in high concentration.
    [003] Platelets inactivated within a blood vessel maintain a round shape while circulating within the blood vessel. It is known that platelets have an approximate life of 10 days, and are present in an amount of approximately 2 ~ 4x108 in relation to 1 mL of blood.
    [004] Platelets within the PRP are activated through substances included within a blood vessel, and then release growth factors and various active substances. Activating substances include collagen, thrombin, adenosine diphosphate (ADP) and epinephrine. Specifically, collagen and thrombin are known to be strong agonists. Collagen is known to induce platelet activation by adhering its specific sequences to platelets as shown in Figure 1.
    [005] When activation factors activate platelets, platelets release growth factors due to the degranulation of their alpha granules. The factors play an important role in the initial healing of injuries. Here, the growth factors released include platelet-derived growth factor (PDGF-AB), transforming growth factor-b1 (TGF-b1), vascular endothelial growth factor (VEGF), epidermal growth factor ( EGF), insulin-like growth factor (IGF) and the like. PRP also releases cytokines, etc., under in vitro conditions, thereby synthesizing the fibroblast DNA. This increases the production of collagen, and consequently allows a structure of collagen to be organized.
    [006] However, when applying PRP in a liquid state, it is difficult to inject PRP into a wound, and there is a loss of surrounding tissue. Consequently, it is necessary to develop a coagulant gelling accompanied by specific physical properties. For gelation, research on the use of thrombin has recently been conducted. However, there is a report that informs that with the use of thrombin (derived mainly from cattle), which is an animal protein, an immune reaction such as lupus has been observed. In other words, thrombin is known to be a factor having clinical problems related to an antibody. Thrombin is the most potent component as a platelet activator. However, when thrombin is used, antibodies to thrombin, prothrombin, factor V and cardiolipin are needed. Also, through research on animals, it has been discovered that clinical problems such as postoperative bleeding and an autoimmune syndrome occur. Although these problems rarely occur, they cannot be overlooked in development. The use of thrombin can cause a damaged wound to spread, abnormal gel resistance, or similar symptoms.
    [007] In addition, due to the high contraction of the thrombin activation gel, there is a surgical difficulty in filling a wound space. Consequently, the importance of a substitute material for thrombin has been recognized.
    [008] Collagen consists of a fibrous protein, and is the main protein component of a connecting mammalian tissue. It makes up 30% or more of the total protein. Collagen provides shape, strength and flexibility to the tissue, and has several functions such as tissue structuring, cell adhesion, cell migration, blood vessel production, tissue morphogenesis, tissue repair and the like. Collagen, as a strong platelet agonist, activates platelets and causes platelet aggregation. Fibrillar collagen more strongly induces platelet aggregation and supports greater platelet adhesion than soluble collagen. Although the reason for this difference has not yet been clearly proven, it is assumed that there is a possibility that fibrillar collagen binds to a molecule by increasing the action of activated platelets.
    [009] Type I collagen consists of most connecting mammalian tissues. Also, as a natural builder, it is more actively researched in the fields of regenerative medicine and tissue engineering. Due to these advantages of type I collagen, type I collagen plays a role in activating platelets with the replacement of thrombin, maintaining the shape.
    [010] However, there is no composition to induce tissue regeneration with the activation of PRP with a solution of calcium chloride and type I collagen. In other words, there is no product that replaces thrombin. Consequently, only thrombin (derived mainly from cattle), that is, a protein derived from animals, was used despite the various problems it presents. Revelation Technical problem
    [011] For this reason, the present invention was developed in view of the aforementioned problems, and provides a composition to induce tissue regeneration through activation of platelet-rich plasma (PRP), and a method of manufacturing it. The present invention achieves the following objectives. First, for the purpose of improving the immune reaction and avoiding clinical problems, type I collagen is used, with the immune reaction and clinical problems being caused when platelet-rich plasma (PRP) is used in conjunction with a protein derived from animals, that is, thrombin (derived mainly from cattle). Second, for treating bone defects or healing wounds, a small amount of whole blood is collected, and the PRP is separated from whole blood and injected in a mixture with type I collagen. In other words, rich plasma in platelets (PRP) consisting of an autologous material and the atelocollage that causes few immune reactions are used to eliminate clinical rejections. Third, the PRP is conveniently and quickly separated at the site of the surgical procedure, and is injected in a mixture with a solution of calcium chloride and type I collagen, in such a way that effective tissue regeneration can be achieved for patients with serious injuries or patients undergoing repetitive surgery. Fourth, when the PRP collected in accordance with the present invention is applied in a region requiring tissue regeneration, mixed with a solution of calcium chloride and type I collagen, type I collagen activates PRP, inducing factors growth agents useful for tissue regeneration from the PRP gel. This method is effective and causes tissue regeneration conveniently and quickly. Specifically, fifthly, clotting type I collagen, as a PRP agonist, can release a similar or greater amount of growth agents according to the types of growth factors, than clotting thrombin as an agonist with PRP. This leads to more effective tissue regeneration. In addition, sixthly, the PRP collected according to the present invention is injected in mixture with a solution of calcium chloride and type I collagen in all regions requiring treatment of bone defects or healing of wounds, thereby obtaining a effective tissue regeneration. Finally, seventhly, as a result, the invention significantly increases the credibility of applying PRP to injuries and presents a good image to consumers. Technical Solution
    [012] In accordance with an aspect of the present invention, a method of manufacturing a composition for inducing tissue regeneration through activation of platelet-rich plasma (PRP) is disclosed, the method including the steps of: separating the PRP from the whole blood; mixing the PRP with a calcium chloride solution; and mix the PRP mixture and the calcium chloride solution with type I collagen.
    [013] In accordance with another aspect of the present invention, a composition is disclosed to induce tissue regeneration through activation of PRP, which is produced by the mentioned method. Advantageous Effects
    [014] As described in detail above, in the present invention, for the purpose of improving the immune reaction and avoiding clinical problems, type I collagen is used, the immune reaction and clinical problems being caused when the plasma rich in Platelets (PRP) are used in conjunction with an animal-derived protein, that is, thrombin (derived mainly from cattle).
    [015] In the technical configuration of the present invention described above, for the treatment of bone defects or wound healing, a small amount of whole blood is collected, and the platelet-rich plasma (PRP) is separated from whole blood and injected in mixture with type I collagen. In other words, PRP as an autologous material and atelocollage cause few immune reactions and are used to eliminate clinical rejections.
    [016] Also, in the present invention, the PRP is conveniently and quickly separated at the site of the surgical procedure, and is injected in mixture with a solution of calcium chloride and type I collagen, in such a way that an effective regeneration of tissues can be obtained for patients with severe injuries or patients undergoing repetitive surgery.
    [017] Also, when the PRP collected in accordance with the present invention is applied in a region requiring tissue regeneration, mixed with a solution of calcium chloride and type I collagen, type I collagen activates PRP inducing factors growth agents useful for tissue regeneration from the PRP gel. This method is effective and causes tissue regeneration conveniently and quickly.
    [018] Specifically, in the present invention, coagulation of type I collagen as a PRP agonist can release a similar or greater amount of growth agents according to the types of growth factors, than coagulation of thrombin as a agonist with PRP. This leads to more effective tissue regeneration.
    [019] In addition, the PRP collected according to the present invention is injected in mixture with a solution of calcium chloride and type I collagen in all regions requiring treatment of bone defects or healing of wounds, thereby obtaining an effective tissue regeneration.
    [020] Finally, as a result, the invention significantly increases the credibility of applying PRP to injuries and presents Brief Description of Drawings
    [021] The previous objectives and others, features and advantages of the present invention will become more evident from the detailed description below, when observed in conjunction with the attached drawings in which: - Figure 1 shows a view illustrating a model in which absorption and activation occur sequentially and aggregation occurs through an interaction between platelets and subendothelial proteins; - Figure 2 shows photographs of 1 mL of platelet-rich plasma (PRP) separated from whole blood mixed with a solution of calcium chloride and type I collagen, whereas in Figure 2 (a) the solution of calcium chloride is included in an amount of 0.25 mg / mL, in Figure 2 (b) the calcium chloride solution is included in an amount of 0.3 mg / mL, and in Figure 2 (c) the chloride solution calcium is included in an amount of 0.5 mg / mL; and - Figure 3 shows photographs of a culture of a conventional mixture of thrombin (A) and the type I collagen mixture (B) of the invention. Detailed Description of the Invention
    [022] Here and hereinafter, a preferred embodiment according to the present invention, for the display of these effects, will be described in detail with reference to the accompanying drawings.
    [023] According to the present invention, a composition to induce tissue regeneration with the activation of platelet-rich plasma (PRP), and a method of manufacturing it are configured as illustrated in Figures 2 and 3.
    [024] In the following descriptions of the present invention, a detailed description of the known functions and configurations incorporated herein will be omitted when it is determined that the detailed description of the known functions and configurations may unnecessarily obscure the main subject of the present invention.
    [025] Also, the terms described below are defined in consideration of their functions in the invention, which can be varied according to the manufacturer's purpose or its conventional use. Consequently, its definitions can be based on the description of this specification.
    [026] First, in the present invention, a composition to induce tissue regeneration through activation of platelet-rich plasma (PRP) is manufactured in the following steps: separating the PRP from whole blood; mixing the PRP with a calcium chloride solution; and mix the mixture of the PRP and the calcium chloride solution with type I collagen.
    [027] Meanwhile, in the present invention, the composition can be applied in several ways, and can be produced in several ways.
    [028] It should also be understood that the present invention is not limited to the preferred embodiments mentioned in the detailed description, and includes modifications, equivalences and alternatives situated in the spirit and scope of the appended claims of the present invention.
    [029] Here and below, the operational effects of the inventive method of manufacturing the composition to induce tissue regeneration through PRP activation, as configured above, will be described.
    [030] First, the inventive method includes the step of separating the PRP from whole blood. Here, the step of separating the PRP from whole blood includes the step of collecting 10 mL of whole blood from an animal or a patient in a vacuum test tube containing 3.2% sodium citrate, and first centrifuging the whole blood (1,750 ~ 1,900 g) for 3 to 5 minutes.
    [031] Then, through the configuration, a supernatant liquid (plasma layer) including a leukocyte layer is collected.
    [032] The supernatant liquid (plasma layer) including the leukocyte layer is transferred to a new vacuum test tube with the aid of a blunt needle, and is centrifuged a second time (4,500 ~ 5,000 g) for 4 to 6 minutes. .
    [033] Then, the PRP concentrated in a bottom layer (from the bottom to an approximate height of 1 mL of the test tube) is collected with a blunt needle.
    [034] The inventive method also includes the step of mixing the PRP with a calcium chloride solution.
    [035] Here, in the step of mixing the PRP with the calcium chloride solution, approximately 1 mL of the PRP collected in the step of separating the PRP from whole blood is mixed once with a calcium chloride solution with a concentration of 0 , 30 ~ 0.55 mg / mL through a three-way connector.
    [036] The inventive method also includes the step of mixing the PRP and the calcium chloride solution with type I collagen, for the production of the composition to induce tissue regeneration with the activation of the PRP.
    [037] Here, the step of mixing the PRP mixture and the calcium chloride solution with type I collagen includes the step of keeping type I collagen at room temperature.
    [038] Next, the mixture of PRP and the mixture of type I collagen, loaded in a syringe, is injected in all regions that need tissue regeneration, in cases of treatment of bone defects and healing of wounds.
    [039] Type I collagen preferably has a concentration of 20 ~ 50 mg / mL.
    [040] In addition, type I collagen is preferably kept at room temperature for 15 to 30 minutes.
    [041] Here and below, Examples of the present invention will be described. Example 1
    [042] First, a kit for the separation of the PRP is prepared as described below. i. A vacuum test tube containing 3.2% sodium citrate ii. A support for the vacuum test tube iii. A needle for the vacuum test tube iv. A vacuum test tube (of the smooth type) v. A blind needle
    [043] From the components mentioned above, a method of separating PRP can be performed. First, i. From a patient, 10 mL of whole blood is collected in a vacuum test tube containing 3.2% sodium citrate. ii. The whole blood loaded in the vacuum test tube is centrifuged (1,750 ~ 1,900 g) for 3 to 5 minutes. In this step, the acceleration and operating time of the centrifugal separator are set at levels optimized for the separation of whole blood into hemocytes, the leukocyte layer and the plasma. iii. After the test tube cap is opened, a supernatant liquid (plasma layer) including the leukocyte cap is collected and transferred to a new test tube (of the smooth type) using a syringe equipped with a blunt needle. iv. The plasma, including the leukocyte layer, transferred to the new test tube, is centrifuged (4,500 ~ 5,000 g) for 4 to 6 minutes. In this step, the acceleration of gravity and the operating time of the centrifugal separator are adjusted to optimized levels to carry out the concentration of PRP in the plasma. v. After the lid of the test tube is opened, the PRP concentrated in the bottom layer of the test tube (from the bottom to an approximate height of 1 mL of the test tube) is collected using a syringe equipped with a needle blind. saw. For the purpose of determining the separation efficiency of 1 ml of platelets separated from 10 ml of whole blood, a specific platelet surface marker, ie, CD41, and a specific leukocyte surface marker, ie, CD45, are led to react. Then, a flow cytometry is performed to measure the number of expressive cells. As a result, the number of platelets in the separated PRP is 5.8 to 7.6 times higher than at baseline. In the recommended clinical needs, the number needs to be 4.0 to 6.0 times (approximately 1,000,000 platelets / mL) higher than a baseline per unit volume of 6 mL of whole blood. Therefore, the PRP separation method meets the recommendations. In addition, the number of leukocytes is 2.8 to 4.2 times greater than a baseline. Consequently, in the application of PRP, it is expected to achieve an antiviral effect.
    [044] Also, as can be seen in the Table below, whole blood is centrifuged twice (1 ° to 1,750 ~ 1,900 g for 3 to 5 minutes, and 2 ° to 4,500 ~ 5,000 g for 4 to 6 minutes), in order to separate 1 ml of PRP. Then, a specific platelet surface marker, i.e., CD41, and a specific leukocyte surface marker, i.e., CD45, are brought to react. Then a flow cytometry is performed to measure the number of expressive cells. As a result, the number of platelets in the separate PRP is 5.8 ~ 7.6 times greater than a baseline, and the number of leukocytes is 2.8 ~ 4.2 times greater than a baseline. . Table 1
    Example 2
    [045] A kit for transplanting a mixture of PRP with a solution of calcium chloride and a type I collagen is prepared as described below. i. 1 mL and 3 mL syringes ii. Three-way connector iii. A solution of calcium chloride iv. 20 ~ 50 mL of type I collagen
    [046] From the components mentioned above, a method of transplanting the mixture of PRP with calcium chloride solution and type I collagen can be performed. First, I) A syringe loaded with 1 mL of PRP is connected to a syringe loaded with a sodium chloride solution with a concentration of 0.30 ~ 0.55 mg / mL through the three-way connector, and the materials are mixed once.
    [047] In other words, Figure 2 shows photographs of 1 mL of PRP separated from whole blood mixed with a solution of calcium chloride and type I collagen, whereas in Figure 2 (a) the solution of calcium chloride is included in an amount of 0.25 mg / mL, in Figure 2 (b) the calcium chloride solution is included in an amount of 0.3 mg / mL, and in Figure 2 (c) the chloride solution calcium is included in an amount of 0.5 mg / mL. In the present invention, for the aggregation of platelets from the mixture of the calcium chloride solution and type I collagen, the optimized concentration of calcium chloride is preferably in the range of 0.30 to 0.55 mg / mL.
    [048] A calcium ion (Ca2 +) as a component of a calcium chloride solution plays the role of converting solubility into non-solubility in blood clotting. This characteristic of the calcium ion (Ca2 +) induces platelet aggregation from the mixture of 1 mL of the separate PRP and type I collagen. So, if the concentration of the calcium chloride solution for platelet aggregation is 0.25 mg / mL or less, platelet aggregation does not happen. On the other hand, if the concentration is 0.55 mg / mL or greater, cell damage occurs due to osmotic pressure. II) Type I collagen with a concentration of 20 ~ 50 mg / mL is kept at room temperature for 15 to 30 minutes to transform the soluble collagen into fibrillar collagen. The reason why collagen I is kept at room temperature is as follows: first, type I collagen is heated so that type I collagen in a state of soluble collagen can be fibrillar-collagen; second, there is hardly any difference in the amount of growth factors released between the mixture of type I fibrillar-collagen collagen with PRP and the mixture of type I collagen in a state of soluble collagen with PRP; and thirdly, in general, type I fibrillar-collagen collagen can more efficiently induce platelet aggregation and support platelet adhesion than soluble collagen. III) A syringe loaded with 1 ml of PRP with the calcium chloride solution is connected to the same amount of fibrillar collagen type I with a concentration of 20 ~ 50 mg / ml through the three-way connector, and the materials are mixed with each other four times. IV) The mixture of PRP, calcium chloride solution and type I collagen, loaded in a syringe, is injected in all regions that need tissue regeneration in cases such as treating bone defects and healing wounds. Example 3 I) The mixture of PRP, calcium chloride solution and type I collagen, loaded in a syringe, is loaded into a round-bottomed glass tube. II) The mixture is cultured at 37 ° C in an incubator for 15 minutes, and coagulated. In this step, during the culture of the mixture at 37 ° C in an incubator, it is possible to obtain the same condition as the transplanted and coagulated mixture in a tissue region. III) The coagulated mixture is placed in a sterile culture vessel with 24 containers together with 1 ml of DMEM, and placed in culture at 37 ° C in an incubator.
    [049] Using the method described above, 10 mL of whole blood is collected from a patient and subjected to two centrifugation steps to obtain 1 mL of concentrated PRP. PRP is first mixed with a calcium chloride solution and then mixed with type I collagen. Then, the mixture is transplanted to all regions that need tissue regeneration in cases such as treating bone defects and healing wounds. . In this method, there is no clinical rejection. It is also possible to separate the PRP, mix the PRP with type I collagen, and transplant the mixture in a short period of time. Consequently, it is possible to effectively induce rapid tissue regeneration in the treatment of bone defects and wound healing.
    [050] Figure 3 shows, specifically, cultures in which the separate PRP was activated with thrombin and type I collagen, and a culture medium was placed in culture in an incubator at 5% CO2 (37 ° C) . After 15 days, most of the conventional mixture of thrombin (A) was degraded. On the other hand, the inventive mixture of collagen (B) maintained its initial shape with few changes in size during the 15 days.
    [051] In the inventive composition for the induction of tissue regeneration with the activation of PRP, and in the method of manufacturing it, the current technical spirit can be obtained repeatedly with the same results. Specifically, the realization of the invention can facilitate technical development and contribute to industrial development. Consequently, the invention has protective merit.
    [052] It should be understood that any specific order or hierarchy of steps in any revealed process consists of an example of a sample approach. Based on design preferences, it should be understood that the specific order or hierarchy of process steps can be rearranged while remaining within the scope of the present disclosure. The attached claims of the method present the elements of the various steps in a sample order, and should not be limited to the specific order or hierarchy of steps presented.
    [053] Although the invention has been described in relation to several aspects, it should be understood that the invention can be subjected to further modifications. This application is intended to cover any variations, uses or adaptations of the invention, generally following the principles of the invention, and considering the variations of the present disclosure as part of the known and usual practice of the art to which the invention belongs.
    权利要求:
    Claims (7)
    [0001]
    1. COMPOSITION PRODUCTION METHOD FOR INDUCING TISSUE REGENERATION THROUGH PLATELET RICH PLASMA ACTIVATION (PRP), the method characterized by the fact that it comprises the steps of: separating PRP from whole blood; mixing the PRP with a calcium chloride solution; and mix the PRP mixture and the calcium chloride solution with type I collagen.
    [0002]
    2. METHOD according to claim 1, characterized by the fact that the step of separating the PRP from whole blood comprises the steps of: collecting 10 mL of whole blood from an animal or a patient in a vacuum test tube containing 3.2% sodium citrate, and to first centrifuge whole blood (1,750 ~ 1,900 g) for 3 to 5 minutes; collect the supernatant liquid (plasma layer) including the leukocyte layer through the aforementioned centrifugation; transfer the supernatant liquid (plasma layer) including the leukocyte layer to a new vacuum test tube with the aid of a blunt needle, and centrifuge it a second time (4,500 ~ 5,000 g) for 4 to 6 minutes; and collect the PRP concentrated in a bottom layer (from the bottom to an approximate height of 1 mL of the test tube) with the aid of a blunt needle.
    [0003]
    3. METHOD according to claim 1, characterized by the fact that in the step of mixing the PRP with the calcium chloride solution, approximately 1 mL of the PRP collected in the step of separating the PRP from whole blood is mixed once with a calcium chloride solution with a concentration of 0.30 ~ 0.55 mg / mL through a three-way connector.
    [0004]
    4. METHOD according to claim 1, characterized by the fact that the step of mixing the PRP and the calcium chloride solution with type I collagen comprises the steps of: maintaining type I collagen at room temperature; mixing the PRP mixture and the calcium chloride solution with type I collagen with a concentration of 20 ~ 50 mg / mL, in an opaque phase, four times through the connection with the three-way connector; and inject the mixture of PRP and type I collagen, loaded in a syringe, in all regions that need tissue regeneration, in cases of treating bone defects and healing wounds.
    [0005]
    5. METHOD according to claim 4, characterized by the fact that type I collagen has a concentration of 20 ~ 50 mg / mL.
    [0006]
    6. METHOD according to claim 4, characterized by the fact that type I collagen is kept at room temperature for 15 to 30 minutes.
    [0007]
    7. COMPOSITION TO INDUCE TISSUE REGENERATION THROUGH PLATELET RICH PLASMA ACTIVATION (PRP) characterized by the fact that it is produced by the method according to claim 1.
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    法律状态:
    2020-11-24| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-12-08| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-02-17| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-03-09| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 10 (DEZ) ANOS CONTADOS A PARTIR DE 09/03/2021, OBSERVADAS AS CONDICOES LEGAIS. |
    2021-06-22| B16C| Correction of notification of the grant|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 17/11/2009, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO |
    优先权:
    申请号 | 申请日 | 专利标题
    KR10-2009-0101387|2009-10-23|
    KR1020090101387A|KR101114712B1|2009-10-23|2009-10-23|A Platelet rich plasma using regeneration constituent manufacturing method thereof|
    PCT/KR2009/006745|WO2011049263A1|2009-10-23|2009-11-17|Composition for inducing tissue regeneration by activating platelet-rich plasma , and method for manufacturing same|
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