WO2017204688A2 - Système pour obtenir un sérum autologue - Google Patents

Système pour obtenir un sérum autologue Download PDF

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Publication number
WO2017204688A2
WO2017204688A2 PCT/RU2017/000330 RU2017000330W WO2017204688A2 WO 2017204688 A2 WO2017204688 A2 WO 2017204688A2 RU 2017000330 W RU2017000330 W RU 2017000330W WO 2017204688 A2 WO2017204688 A2 WO 2017204688A2
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WO
WIPO (PCT)
Prior art keywords
syringe
autologous serum
solid
coated
human
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PCT/RU2017/000330
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English (en)
Russian (ru)
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WO2017204688A3 (fr
Inventor
Артем Витальевич ДЫДЫКИН
Янина Иозавна ЗУЕВА
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Individual
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Publication of WO2017204688A2 publication Critical patent/WO2017204688A2/fr
Publication of WO2017204688A3 publication Critical patent/WO2017204688A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor

Definitions

  • the invention relates to medicine, namely to a system for producing autologous serum with a high content of IL-1 RA, growth factors and a reduced content of proinflammatory cytokines and other proinflammatory factors and can be used to obtain autologous plasma preparations in various variants that are actively used in medicine for the treatment of a wide range of diseases.
  • IL-1 and TNF-a are currently considered the most significant.
  • drugs that block these cytokines remicade, adalimumab
  • IL-1 RA interleukin 1 antagonist IL-1
  • blood serum autologous concentrated serum - ACS
  • the main objective of the study is to find ways to stimulate the release of anti-inflammatory cytokines from blood cells in high concentrations and remove the resulting pro-inflammatory cytokines (and other factors). In this case, it is supposed to stimulate the release of cytokines with inert, easily removable components or media.
  • Autologous plasma preparations involves the introduction of autologous conditioned serum (ACS) with an increased content of interleukin 1 receptor antagonist (IL-1 RA) into the affected joint, place of enthesopathy, or into the inflamed tendon.
  • ACS autologous conditioned serum
  • IL-1 RA interleukin 1 receptor antagonist
  • a study on back pain conducted by Bochum University (Becker et al., 2007) compared autologous plasma therapy with corticosteroids with epidural perineural administration. No specific side effects were observed.
  • Autologous plasma therapy is recognized internationally as a highly effective, innovative method of local therapy; The advantages of this method are described in specialized medical journals.
  • a known apparatus for producing therapeutically active proteins in the blood including a tube containing silica-coated granules. After collecting the blood, the tube is incubated under aseptic conditions at 37 ° C for 24 hours. After incubation, each tube is centrifuged (3500 rpm, 10 min) and the top layer, being plasma or serum, is transferred to a sterile syringe and injected back to the patient.
  • an interleukin-1 receptor antagonist or a therapeutically effective protein selected as the closest analogue to the patented solution (US N & 2010125236, 05.20.2010).
  • Blood is obtained from the patient using a conventional syringe, and then injected into a double Luer centrifuge tube.
  • the centrifuge tube is equipped with silanized coated balls.
  • the tube is then incubated and centrifuged. After incubation and centrifugation of serum containing therapeutically active autologous proteins, such as IL-1RA, the resulting plasma is introduced back into the patient's body.
  • the technical result of the proposed technical solution is a significant decrease in the concentration of the pro-inflammatory cytokine IL- ⁇ (possibly additional TNF- ⁇ , IL-6, MMP), as a result, increasing the effectiveness of the therapeutic effect of autologous concentrated serum.
  • the claimed technical result is achieved by using the design of a multicomponent system to obtain autologous serum with a high content of IL-1 RA and with a reduced content of pro-inflammatory cytokines, including one syringe (syringe 1), the inner walls of which are coated with a solid-phase polymer sorbent with monoclonal antibodies fixed to it IL- ⁇ (possibly in addition to TNF- ⁇ , IL-6), in addition to the walls, the solid-phase polymer sorbent can be located on an additional structure (sponge, mesh, system e tubes) inside a syringe containing glass balls with a diameter of 2.5 to 3.5 mm mm, occupying up to 40% of the total volume of the syringe, and 3-6 syringes (syringe 2), the inner walls of which are coated with a solid-phase polymer sorbent with fixed human IL- ⁇ (possibly additionally TNF-a, IL-6), and a sterile adapter for transferring
  • OR possibly IL-6, TNF- ⁇
  • TNF- ⁇ which is formed upon receipt of autologous serum or which is initially in human blood in high concentration, binds to a specific protein (monoclonal antibody) during of this reaction
  • the monoclonal antibody - IL-1 complex remains fixed on the solid-phase sorbent (possibly an additional monoclonal antibody - TNF-a, monoclonal antibody - IL-6), and the autologous serum in the syringe is free and contains a significantly reduced amount of IL- ⁇ (possibly IL-6, TNF-a).
  • s Syringe 1 is essentially a tube that acts as a syringe due to vacuum and a double-sided needle.
  • the volume of the syringe, the walls of which are coated with an antibody to I L-1 b (possibly in addition to IL-6, TNF- ⁇ ), is from 20 to 60 ml.
  • the most likely use of monoclonal murine antibodies obtained by hybridoma technology is also possible to use other types of genetically engineered monoclonal antibodies.
  • the volume of the syringe, the walls of which are internally coated with human IL- ⁇ (possibly optionally IL-6, TNF- ⁇ ), suitable for in vivo use for 15 elimination of murine monoclonal antibodies, is 5-10 ml.
  • the sterile adapter is a polymer tube with a diameter of up to 4 mm and a length of 40 to 100 mm, which can also be coated from the inside with either monoclonal antibodies or human IL-1, depending on the need.
  • the adapter makes it possible to make multiple passages 20 of the plasma, thus stimulating the binding of pro-inflammatory cytokines to fixed antibodies.
  • FIG. 2 is a top view of the syringe of FIG. 1.
  • FIG. 3 embodiments of the syringe with an additional porous structure.
  • FIG. 4 is a top view of a syringe sector with an additional porous structure.
  • FIG. 5 is a flow diagram of a process for producing plasma using two syringes.
  • FIG. 6 is a flowchart of a plasma production process using an adapter and two syringes.
  • FIG. 7 is a flowchart of a plasma production process using a three-component syringe.
  • the system includes a syringe 1 (pos. 1), the inner walls of which are coated with a solid-phase polymer sorbent (pos. 2) with monoclonal antibodies to IL- ⁇ ⁇ fixed on it (possibly in addition to TNF- ⁇ , IL-b).
  • the solid-phase polymer sorbent can be located on an additional structure (sponge, mesh, tube system) (pos. 4) inside the syringe 1.
  • Syringe 1 contains glass balls (pos. 3) with a diameter of 2.5 to 3.5 mm mm, occupying up to 40% of the total volume of the syringe, and 3-6 syringes (syringe 2),
  • Blood is obtained from the patient using a conventional syringe and injected into syringe 1 (item 1), it is possible to introduce not only blood, but also other autologous fluids, plasma, and platelet-rich plasma into syringe 1.
  • Syringe 1 is then incubated. Incubation is carried out on a rack specially designed for this purpose (with the 25th possibility of giving the syringe 1 additional rocking movements or certain cycles of spatial position with a change in the angle of inclination to the horizon from 90 to 30 degrees), at a temperature of 36.5 - 37 degrees C for 2- 24 hours.
  • a sterile adapter (pos. 5, 7) is inserted into syringe 1, through which the obtained serum is transferred from syringe 1 to syringe 2 (pos. 6).
  • the movement can be carried out in several modes, with a change in the speed parameters and a possible change in the direction of flow. The most likely use of the regime at low speed, providing the transition of serum from syringe 1 to syringe 2 within 5-15 minutes.
  • System consisting of syringes 3 (pos. 8). The system combines in one syringe all the essential details of the plasma production process, with a high content of IL-1RA, with a low content of pro-inflammatory cytokines.
  • the system consists of a vacuum tube, which is transformed into a syringe, with a volume of 5-10 ml, containing glass balls with a diameter of 2.5 to 3.5 mm mm, occupying up to 30-40% of the total volume of the syringe and piston, consisting of many capillaries coated inside solid-phase sorbent with antibodies to IL-1 fixed on it (possibly in addition to IL-6, fno a).
  • the syringe has a piston lock in position 2 (key 10).
  • the claimed system can be implemented in the following processes for the production of autologous serum.
  • syringe 1 (item 1) and syringe 2 (item 6).
  • Blood is centrifuged in syringe 1 (any modification is possible), then the resulting plasma is collected in syringe 2 using a universal adapter with double-sided needles (item 5).
  • pro-inflammatory cytokines bind to antibodies and are fixed on the polymer (syringe 1), and antibody residues are removed in syringe 2 using IL-1.
  • b cytokines bind to antibodies and are fixed on the polymer (syringe 1), and antibody residues are removed in syringe 2 using IL-1.
  • the process can be intensified by the passage of blood through an adapter (pos. 7), which is internally coated with antibodies to proinflammatory cytokines (IL-1) (it is possible to place fixed IL-1 on the inner surface of the adapter).
  • IL-1 proinflammatory cytokines
  • Blood is centrifuged in the syringe 3 (pos. 8) (the piston is in position 1 (pos. 9)). Then the piston is transferred from position 1 (pos. 9) to position 2 (pos. 10) using a needle, which is inserted into the tube. The resulting plasma slowly passes through the piston capillaries, the inner surface of which is covered with monoclonal antibodies to IL-1 (possibly TNF, IL-6). Pro-inflammatory cytokines (IL-1, possibly TNF, IL-6) bind to antibodies and are fixed on the polymer. The piston moves with the needle to the latch. With the same needle, the plasma is drawn into a syringe (universal), which is injected.
  • IL-1 possibly TNF, IL-6

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  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne la médecine humaine et notamment un système pour obtenir un sérum autologue présentant une teneur élevée en IL-1 RA et en facteurs de croissance, et une teneur réduite en cytokine anti-inflammatoire et d'autres facteurs anti-inflammatoires, et peut être utilisée pour obtenir des préparations de plasma autologue dans différentes variantes utilisées activement en médecine humaine pour traiter un large spectre d'affections. Le résultat de la solution technique proposée consiste à réduire sensiblement la concentration de la cytokine inflammatoire IL-1β ce qui a pour conséquence une meilleure efficacité thérapeutique du sérum autologue concentré. Le système pour obtenir un sérum autologue à teneur plus éleveé en IL-1RA comprend une première seringue, les parois internes de laquelle sont recouvertes d'un sorbant polymérique en phase solide comportant des anticorps monoclonaux contre IL-1β qui y sont fixés, qui comprend des billes de verre ayant un diamètre de 2,5 à 3,5 mm occupant jusqu'à 40 % du volume global de la seringue, et au moins une seringue dont les parois internes sont recouvertes d'un sorbant polymérique en phase solide sur lequel sont fixées des IL-1β humaines, ainsi qu'un raccord stérile réalisé de manière à permettre le transfert du sérum autologue de la seringue avec des anticorps dans la seringue avec des IL-1β humaines.
PCT/RU2017/000330 2016-05-24 2017-05-22 Système pour obtenir un sérum autologue Ceased WO2017204688A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2016120010A RU2617537C1 (ru) 2016-05-24 2016-05-24 Система для получения аутологичной сыворотки
RU2016120010 2016-05-24

Publications (2)

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WO2017204688A2 true WO2017204688A2 (fr) 2017-11-30
WO2017204688A3 WO2017204688A3 (fr) 2018-03-01

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PCT/RU2017/000330 Ceased WO2017204688A2 (fr) 2016-05-24 2017-05-22 Système pour obtenir un sérum autologue

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RU (1) RU2617537C1 (fr)
WO (1) WO2017204688A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118483410A (zh) * 2024-07-15 2024-08-13 烟台大学 一种免疫检测装置及基于该装置的免疫检测方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8460227B2 (en) * 2008-11-17 2013-06-11 Arthrex, Inc. Cytokine concentration system
US9241977B2 (en) * 2013-03-01 2016-01-26 Arthrex, Inc. Enhanced anabolic cytokine production and delivery system

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118483410A (zh) * 2024-07-15 2024-08-13 烟台大学 一种免疫检测装置及基于该装置的免疫检测方法
CN118483410B (zh) * 2024-07-15 2024-10-18 烟台大学 一种免疫检测装置及基于该装置的免疫检测方法

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WO2017204688A3 (fr) 2018-03-01
RU2617537C1 (ru) 2017-04-25

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