WO2023096509A1 - A system containing an activator that increases the level of an endogenous inhibitor of the wnt pathway - Google Patents
A system containing an activator that increases the level of an endogenous inhibitor of the wnt pathway Download PDFInfo
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- WO2023096509A1 WO2023096509A1 PCT/PL2022/000065 PL2022000065W WO2023096509A1 WO 2023096509 A1 WO2023096509 A1 WO 2023096509A1 PL 2022000065 W PL2022000065 W PL 2022000065W WO 2023096509 A1 WO2023096509 A1 WO 2023096509A1
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- Prior art keywords
- activator
- inhibitor
- wnt pathway
- tube
- level
- Prior art date
Links
- 239000012190 activator Substances 0.000 title claims abstract description 30
- 102000013814 Wnt Human genes 0.000 title claims abstract description 10
- 108050003627 Wnt Proteins 0.000 title claims abstract description 10
- 239000003112 inhibitor Substances 0.000 title claims abstract description 9
- 230000037361 pathway Effects 0.000 title claims abstract description 8
- 229920000515 polycarbonate Polymers 0.000 claims abstract description 4
- 239000004417 polycarbonate Substances 0.000 claims abstract description 4
- 238000000926 separation method Methods 0.000 claims description 10
- 239000012530 fluid Substances 0.000 claims description 9
- 238000002955 isolation Methods 0.000 claims description 7
- 239000011521 glass Substances 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 5
- 229940121396 wnt pathway inhibitor Drugs 0.000 claims description 5
- 239000003146 anticoagulant agent Substances 0.000 claims description 3
- 229940127219 anticoagulant drug Drugs 0.000 claims description 3
- 239000002801 charged material Substances 0.000 claims description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 102100030074 Dickkopf-related protein 1 Human genes 0.000 abstract description 7
- 101710099518 Dickkopf-related protein 1 Proteins 0.000 abstract description 7
- 239000003102 growth factor Substances 0.000 abstract description 6
- 230000004913 activation Effects 0.000 abstract description 4
- 102000004169 proteins and genes Human genes 0.000 abstract description 3
- 108090000623 proteins and genes Proteins 0.000 abstract description 3
- 230000003068 static effect Effects 0.000 abstract 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 102000004375 Insulin-like growth factor-binding protein 1 Human genes 0.000 description 2
- 108090000957 Insulin-like growth factor-binding protein 1 Proteins 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
- 101150061927 BMP2 gene Proteins 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229940097000 DKK-1 inhibitor Drugs 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- QHLITPHIARVDJI-UHFFFAOYSA-N [1-[4-(2-naphthalenyl)-2-pyrimidinyl]-4-piperidinyl]methanamine Chemical compound C1CC(CN)CCN1C1=NC=CC(C=2C=C3C=CC=CC3=CC=2)=N1 QHLITPHIARVDJI-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 1
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/491—Blood by separating the blood components
Definitions
- the subject of the invention is a single-chamber system comprising an activator that increases the level of an endogenous Wnt pathway inhibitor.
- the solution presented in the present invention application assumes the use of a singlechamber system for the isolation and separation of fractions of autologous fluids of a patient (including but not limited to platelet-rich plasma from peripheral blood) containing an activator.
- the isolated fractions contain additionally a concentrated amount of growth factors and proteins (e.g. BMP2, VEGF, IGFBP-1) characteristic for the activation of morphotic elements and DKK- 1 protein, which is an inhibitor of the Wnt pathway, while, in the isolated fraction, no increase in the amount of pro -inflammatory factors, including cytokines, is observed.
- the process of selective activation and isolation of the desired fraction is performed in a single-chamber system with the addition of an activator. This shortens the time and simplifies the procedure compared to available set-ups, which in turn offers the possibility of intraoperative preparation of autologous fluid fractions with active components which decides about its therapeutic properties. This is important because modulation of Wnt signaling by DKK-1 protein is a promising strategy for prevention and inhibition of disease progression.
- the purpose of the present invention is to provide a single chamber system with an activator to be able to obtain an isolated autologous fluid fraction.
- the present invention provides a system for the isolation and separation of patient autologous fluid fractions, which is a cylindrical Tube made of polycarbonate that contains an activator that increases the level of an endogenous Wnt pathway inhibitor.
- the system wherein the activator is an element made of an electrostatically charged material, preferably glass.
- the system wherein the glass is borosilicate.
- the activator is in the form of spheres or particles having a spherical or oval shape.
- the system wherein the beads or particles have diameters ranging from 0.1 to 10 mm.
- the system wherein the activator comprises from 1 to 10 % of the contents of the Tube.
- the system where it's a sterile system.
- Wnt pathway - a signaling pathway formed from cellular proteins that play a role in embryogenesis and carcinogenesis in normal cells of adult organisms.
- Tube - single-chamber system for the isolation and separation of patient autologous fluid fractions.
- the single-chamber system allows the quick and safe acquisition of high quality blood products.
- Fig. 1 - shows an outline of a system comprising a chamber (Al), an activator (A2) positioned inside said chamber, a cone with stabilizing rings on the outside of the chamber, and a screw cap location followed by a controller screw for moving fluid out of the chamber.
- Fig. 1 also shows the stopper in side view (Bl) and top view (B2), the base of the stopper in side view (B3) and top view (B4), the cap of the tube in side view (B5) and top view (B6) and the stopper of the tube in top view (B7), both sides (B8-9) and bottom view (BIO) allowing processing in a closed system ensuring sterility of the procedure.
- Fig. 2 - shows the average concentration of DKK-1 in platelet-rich plasma prepared according to the standard procedure used for this purpose in the Xerthra device and the preparation procedure of the patent claim, averaged over no less than 8 patients (SEM error bars, t-student test, p* ⁇ 0.05).
- the invention is illustrated by the following example of implementation, which is not a limitation thereof.
- Peripheral blood of the patients was collected into the syringe with anticoagulant (sodium citrate in the amount of 10% of the volume of the target suspension). From the syringe the blood was transferred to the tube with activator, where it was mixed with the activator. After 10 minutes of incubation during which the blood was stirred for 1 minute at room temperature, the blood in the Activator tube was separated by 5 minutes centrifugation at an acceleration of 1200 G into a red blood cell fraction, an enriched platelet-rich plasma fraction, and a platelet-poor plasma fraction. The different fractions were then transferred into syringes.
- anticoagulant sodium citrate in the amount of 10% of the volume of the target suspension
- the concentration of DKK-1 inhibitor in platelet-rich plasma was determined with an ELISA kit that allows the determination of DKK-1 protein in plasma, and the levels of selected cytokines and growth factors were determined using a multiplex panel for the assessment of growth factors, cytokines, and chemokines during a single analysis.
- the platelet-rich preparation obtained in the Activator tube is safe in a manner analogous to plasma obtained in many other products, however it is enriched with DKK - 1, an inhibitor of the Wnt pathway.
- Electrostatically charged material preferably glass
- the polycarbonate tube is cylindrical in shape (round body), tapering upwards to form a neck, around the circumference of which it has four stabilisers in the form of rings; at the lower end, the body of the tube has a thread into which a round stopper is inserted.
- the elements of the tube are the tube stopper, the base of the tube stopper and the tube cap.
- the stopper of the tube is pressed from the bottom into the centre of the tube.
- the base of the tube stopper is then placed in the middle of the stopper by pressing it in.
- the round cap is then screwed onto the thread, thereby closing the tube from below.
- At the end of the neck there is a stopper with a closure.
- the entire single-chamber system for isolation and separation of patient autologous fluid fractions with activator (Activator tube) is a sterile system.
- Sterilization is by radiation (e-beam or gamma).
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Ecology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- External Artificial Organs (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The subject of the invention is a single-chamber system made of polycarbonate, containing in its interior an activator endowed with a surface static charge. This system allows selective activation of a fraction of the plasma so that it is enriched with growth factors and proteins including DKK-1 protein, which is an inhibitor of the Wnt pathway.
Description
A system containing an activator that increases the level of an endogenous inhibitor of the Wnt pathway
The subject of the invention is a single-chamber system comprising an activator that increases the level of an endogenous Wnt pathway inhibitor.
Currently, there is a growing interest in the use of autologous therapies in medicine. This has led to the need to develop an autologous device aimed at activating platelet-rich plasma resulting in the release of increased amounts of growth factors, which is often also accompanied by an increase in proinflammatory cytokines resulting from full activation of the coagulation cascade.
The solution presented in the present invention application assumes the use of a singlechamber system for the isolation and separation of fractions of autologous fluids of a patient (including but not limited to platelet-rich plasma from peripheral blood) containing an activator. The isolated fractions contain additionally a concentrated amount of growth factors and proteins (e.g. BMP2, VEGF, IGFBP-1) characteristic for the activation of morphotic elements and DKK- 1 protein, which is an inhibitor of the Wnt pathway, while, in the isolated fraction, no increase in the amount of pro -inflammatory factors, including cytokines, is observed.
The process of selective activation and isolation of the desired fraction is performed in a single-chamber system with the addition of an activator. This shortens the time and simplifies the procedure compared to available set-ups, which in turn offers the possibility of intraoperative preparation of autologous fluid fractions with active components which decides about its therapeutic properties. This is important because modulation of Wnt signaling by DKK-1 protein is a promising strategy for prevention and inhibition of disease progression.
The purpose of the present invention is to provide a single chamber system with an activator to be able to obtain an isolated autologous fluid fraction.
The present invention provides a system for the isolation and separation of patient autologous fluid fractions, which is a cylindrical Tube made of polycarbonate that contains an activator that increases the level of an endogenous Wnt pathway inhibitor.
The system wherein the separation of a fraction containing increased levels of a Wnt pathway inhibitor is possible despite the use of an anticoagulant.
The system wherein the separation of a fraction containing increased levels of a Wnt pathway inhibitor is produced by centrifugal force.
The system, wherein the increase in Wnt glass inhibitor content is achieved by contacting the activator for 1 to 15 minutes.
The system wherein the activator is an element made of an electrostatically charged material, preferably glass.
The system wherein the glass is borosilicate.
The system, wherein the activator is in the form of spheres or particles having a spherical or oval shape.
The system, wherein the beads or particles have diameters ranging from 0.1 to 10 mm.
The system, wherein the activator comprises from 1 to 10 % of the contents of the Tube. The system where it's a sterile system.
The terms used above and in the patent description and claims, have the following meanings:
Wnt pathway - a signaling pathway formed from cellular proteins that play a role in embryogenesis and carcinogenesis in normal cells of adult organisms.
Tube - single-chamber system for the isolation and separation of patient autologous fluid fractions. The single-chamber system allows the quick and safe acquisition of high quality blood products.
Activator tube - single chamber system for isolation and separation of patient autologous fluid fractions with activator.
Description of figures and table:
Fig. 1 - shows an outline of a system comprising a chamber (Al), an activator (A2) positioned inside said chamber, a cone with stabilizing rings on the outside of the chamber, and a screw cap location followed by a controller screw for moving fluid out of the chamber.
Fig. 1 also shows the stopper in side view (Bl) and top view (B2), the base of the stopper in side view (B3) and top view (B4), the cap of the tube in side view (B5) and top view (B6) and the stopper of the tube in top view (B7), both sides (B8-9) and bottom view (BIO) allowing processing in a closed system ensuring sterility of the procedure.
Fig. 2 - shows the average concentration of DKK-1 in platelet-rich plasma prepared according to the standard procedure used for this purpose in the Xerthra device and the preparation procedure of the patent claim, averaged over no less than 8 patients (SEM error bars, t-student test, p*<0.05).
Table 1. Concentration of pro- and anti-inflammatory factors in the plasma fraction isolated from the Xerthra device (TNF-a - tumor necrosis factor, BMP -2 - bone morphogenetic protein which is a growth factor belonging to the TNF- β protein superfamily, VEGF - vascular endothelial growth factor, IGFBP-1 - insulin-like growth factor binding protein type 1 , IL- 1β - interleukin 1β, IL-4 - interleukin 4, IL-6 - interleukin 6, IL-8 - interleukin 8, IL-10 - interleukin 10; ↓- levels below the detection of the assay) and after the preparation procedure with the activator system.
The invention is illustrated by the following example of implementation, which is not a limitation thereof.
Example 1
Peripheral blood of the patients was collected into the syringe with anticoagulant (sodium citrate in the amount of 10% of the volume of the target suspension). From the syringe the blood was transferred to the tube with activator, where it was mixed with the activator. After 10 minutes of incubation during which the blood was stirred for 1 minute at room temperature, the blood in the Activator tube was separated by 5 minutes centrifugation at an acceleration of 1200 G into a red blood cell fraction, an enriched platelet-rich plasma
fraction, and a platelet-poor plasma fraction. The different fractions were then transferred into syringes.
As a control, platelet-rich plasma was obtained using Tube.
In each case, the concentration of DKK-1 inhibitor in platelet-rich plasma was determined with an ELISA kit that allows the determination of DKK-1 protein in plasma, and the levels of selected cytokines and growth factors were determined using a multiplex panel for the assessment of growth factors, cytokines, and chemokines during a single analysis.
It is shown in fig. 2 that the level of DKK-1 in the platelet-rich plasma obtained in the Tube with activator was higher than that obtained in the Tube without the addition of activator. In doing so, there was no increase in pro-inflammatory cytokines above the detection level as shown in Table 1.
The platelet-rich preparation obtained in the Activator tube is safe in a manner analogous to plasma obtained in many other products, however it is enriched with DKK - 1, an inhibitor of the Wnt pathway.
Activator:
- Electrostatically charged material, preferably glass,
- borosilicate glass,
- in the form of spheres or oval shaped particles,
- diameter 0.1 - 10 mm.
- is between 1 and 10 % of the contents of the Tube.
The polycarbonate tube is cylindrical in shape (round body), tapering upwards to form a neck, around the circumference of which it has four stabilisers in the form of rings; at the lower end, the body of the tube has a thread into which a round stopper is inserted. The elements of the tube are the tube stopper, the base of the tube stopper and the tube cap. The stopper of the tube is pressed from the bottom into the centre of the tube. The base of the tube stopper is then placed in the middle of the stopper by pressing it in. The round cap is then screwed onto the thread, thereby closing the tube from below. At the end of the neck there is a stopper with a closure.
The entire single-chamber system for isolation and separation of patient autologous fluid fractions with activator (Activator tube) is a sterile system.
Sterilization is by radiation (e-beam or gamma).
Claims
1. A system for the isolation and separation of patient autologous fluid fractions, wherein it provides a cylindrical Tube made of polycarbonate that contains an activator that increases the level of an endogenous Wnt pathway inhibitor.
2. The system according to claim 1, wherein the separation of a fraction containing an increased level of an inhibitor of the Wnt pathway is possible despite the use of an anticoagulant.
3. The system according to claim 1, wherein the separation of a fraction containing an increased level of an inhibitor of the Wnt pathway is produced by centrifugal force.
4. The system according to claim 1, wherein the increase of the content of the Wnt- glucose inhibitor is carried out by means of contact with the activator for 1 to 15 minutes.
5. The system according to claim 1, wherein the activator is made of electrostatically charged material, preferably glass.
6. The system according to claim 5, wherein the glass is borosilicate.
7. The system according to claim 5, wherein the activator is in the form of balls or particles having a spherical or oval shape.
8. The system according to claim 5, wherein the balls or particles have diameters from 0.1 to 10 mm.
9. The system according to claim 5, wherein the activator constitutes from 1 to 10 % of the content of the Tube.
10. The system according to claim 1, wherein it is a sterile system.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL439627A PL439627A1 (en) | 2021-11-24 | 2021-11-24 | System containing an activator that increases the level of an endogenous Wnt pathway inhibitor |
| PLP.439627 | 2021-11-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023096509A1 true WO2023096509A1 (en) | 2023-06-01 |
Family
ID=85174033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/PL2022/000065 WO2023096509A1 (en) | 2021-11-24 | 2022-11-23 | A system containing an activator that increases the level of an endogenous inhibitor of the wnt pathway |
Country Status (2)
| Country | Link |
|---|---|
| PL (1) | PL439627A1 (en) |
| WO (1) | WO2023096509A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4049496A (en) * | 1976-05-27 | 1977-09-20 | Henry Philip D | Rapid separation of plasma creatine kinase isoenzymes |
| US20040120942A1 (en) * | 2002-12-23 | 2004-06-24 | Mcginnis Daniel | Device and process for the preparation of autologous thrombin serum |
| JP2014118362A (en) * | 2012-12-13 | 2014-06-30 | Jms Co Ltd | Method for preparing serum and serum |
| US20200345780A1 (en) * | 2008-08-22 | 2020-11-05 | Reapplix Aps | Multilayered blood product |
| WO2021199041A1 (en) * | 2020-03-30 | 2021-10-07 | Estar Technologies Ltd | System and a method for obtaining an improved plasma extract |
-
2021
- 2021-11-24 PL PL439627A patent/PL439627A1/en unknown
-
2022
- 2022-11-23 WO PCT/PL2022/000065 patent/WO2023096509A1/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4049496A (en) * | 1976-05-27 | 1977-09-20 | Henry Philip D | Rapid separation of plasma creatine kinase isoenzymes |
| US20040120942A1 (en) * | 2002-12-23 | 2004-06-24 | Mcginnis Daniel | Device and process for the preparation of autologous thrombin serum |
| US20200345780A1 (en) * | 2008-08-22 | 2020-11-05 | Reapplix Aps | Multilayered blood product |
| JP2014118362A (en) * | 2012-12-13 | 2014-06-30 | Jms Co Ltd | Method for preparing serum and serum |
| WO2021199041A1 (en) * | 2020-03-30 | 2021-10-07 | Estar Technologies Ltd | System and a method for obtaining an improved plasma extract |
Also Published As
| Publication number | Publication date |
|---|---|
| PL439627A1 (en) | 2023-05-29 |
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