Methods and systems for bone or joint treatment

Abstract

Whole blood is mixed with one or more clotting agents to produce a coagulated blood that is then injected into a site of bone or joint trauma or disease and allowed to clot at the site. The purpose is to promote healing or recovery at the site of disease, injury, or trauma. For example, healing and regeneration of damaged bones, damaged joints, cartilage damage, etc.

Description

[Technical Field]

[0001] FIELD OF THE DISCLOSURE The present disclosure is generally in the field of orthopedics and relates to formulations and methods for inducing bone or joint regeneration processes. [Background technology]

[0002] Although the skeleton has the ability to regenerate, there are occasional injuries, such as bone injuries and joint wear, that do not heal and require medical intervention, such as various complex bone injuries caused by disease or trauma, where the body's natural repair mechanisms are unable to heal the injury, or damage to the joint as a result of mechanical wear or prolonged infection, for example, as a result of osteoarthritis or rheumatoid arthritis.

[0003] In cases of bone injury, a specific treatment often used is the implantation of bone grafts to replace bone lost due to disease, fracture, etc. The underlying therapeutic principles include osteoconductivity (to induce natural bone growth), osteoinductivity (to promote undifferentiated cells to become active osteoblasts), and osteogenicity (when the graft material contains living bone cells that contribute to bone remodeling). While osteoconductivity and osteoinductivity can be associated with a variety of different grafts, osteogenicity occurs only in autograft tissue and allograft cellular bone matrix. Other bone graft materials include demineralized bone matrix (DMB), synthetic materials, minerals (such as hydroxyapatite), organic polysaccharide compounds (such as chitin, chitosan, and alginate), and others.

[0004] Intra-articular injections of therapeutic agents, such as anti-inflammatory drugs, are a common treatment for inflammatory joint diseases, such as those in rheumatoid arthritis, psoriatic arthritis, gout, tendonitis, bursitis, carpal tunnel syndrome, and osteoarthritis. Joint injections sometimes also include a lubricant, such as hyaluronic acid, which is used to replace bursal fluid due to its high viscosity.

[0005] Wound dressings containing blood clotting agents have been proposed for the treatment of chronic wounds (see WO2010 / 086848, WO2019 / 058373, WO2019 / 150355, WO2019 / 058375, and WO2021 / 124317). The use of coagulated blood for the treatment of various damaged tissues is disclosed in WO2022 / 168099, WO2022 / 180627, and WO2023 / 037373. Summary of the Invention [Problem to be solved by the invention]

[0006] The present disclosure provides methods for treating bone or joint diseases, disorders or trauma. [Means for solving the problem]

[0007] The term "condition" is used herein to refer collectively to a disease, disorder or injury.

[0008] The term "site" is used herein to denote the location where a disease manifests itself, e.g., an infected joint, the location of a severed or fractured bone, or the location of a bone or joint that undergoes a surgical procedure.

[0009] The term "blood" is used herein to refer to whole blood, typically venous blood drawn from a subject undergoing medical treatment.

[0010] The term "coagulating blood" is used herein to refer to whole blood that is still flowable and is in the process of clotting. Coagulating blood is typically whole blood that has been mixed with one or more coagulants or anti-anticoagulants (i.e., agents that counteract or inhibit the action of anticoagulants that are mixed with the whole blood to prevent it from clotting when it is drawn from a subject).

[0011] According to the present disclosure, whole blood is mixed with one or more clotting agents, and the clotted blood is then administered to the site and allowed to clot at the site. One aspect of the present disclosure provides a method for treating bone or joint disease or injury in a subject, in which a mixture of whole blood and one or more clotting agents is administered to the site of disease or injury and the blood is allowed to clot at the site. Another aspect provides a system including elements, including one or more devices and / or materials, for carrying out the method. A further aspect of the present disclosure also provides an assembly or kit of parts including one or more of the elements of the system or the elements necessary to carry out the method.

[0012] The disclosed methods promote healing or remission of such conditions, for example, healing and regeneration of damaged bones, damaged joints, cartilage damage, and the like.

[0013] According to the present disclosure, a mixture of whole blood and one or more clotting agents is introduced to the site and allowed to clot in situ. Typically, the whole blood is mixed with one or more clotting agents that cause the blood to clot prior to its introduction to the site, and it is introduced to the site while the blood is still flowable (i.e., liquid or partially coagulated) before it has fully clotted.

[0014] The blood may, in some embodiments, be mixed with other drugs, such as bone substitute or bone regeneration-inducing drugs, anti-inflammatory drugs, disease-modifying drugs, and the like.

[0015] Embodiment Several embodiments of the present disclosure are described herein in the following numbered paragraphs and are referred to by that number reference in the subsequent paragraphs (in a format similar to that of the claims). These embodiments are intended to add to (but not limit) the present disclosure:

[0016] 1. A method for treating a bone or joint disease or injury in a subject, comprising: It involves injecting a mixture of whole blood and one or more clotting agents into the site of disease or trauma and allowing the blood to clot at the site.

[0017] 2. The method of embodiment 1, comprising: Drawing blood from the subject; mixing the collected blood with one or more coagulants, thereby forming said mixture; and injecting the mixture into said area. Includes.

[0018] 3. The method of embodiment 2, comprising: The drawn blood is mixed with one or more anticoagulants, including an anti-anticoagulant, which is a drug that counteracts the anticoagulant effect of an anticoagulant.

[0019] 4. The method of embodiment 3, wherein the one or more coagulants comprises kaolin.

[0020] 5. The method of any one of embodiments 1-4, wherein the one or more coagulants comprises a calcium salt of an organic acid (eg, calcium gluconate).

[0021] 6. The method of any one of claims 1 to 5, wherein said administering is by injection.

[0022] 7. The method of any one of embodiments 1-6 for treating bone trauma, adding a bone-acting drug to the mixture, the drug having the effect of inducing one or more of: (i) bone regeneration processes; (ii) repairing damage or trauma to bone tissue; and (iii) repairing symptoms of bone disease or injury; and injecting said mixture into said area; Includes.

[0023] 8. The method of embodiment 7, wherein said bone-acting agent is a bone graft material.

[0024] 9. The method of embodiment 8, wherein the bone graft material is selected from materials having one or more bone regenerating effects, including osteoconductive, osteoinductive, and osteogenic properties.

[0025] 10. The method of embodiment 9, wherein the bone graft material is selected from the group consisting of bone tissue, demineralized bone matrix, synthetic materials, minerals, and organic polysaccharide compounds.

[0026] 11. The method of any one of embodiments 1-6 for the treatment of inflammatory joint disease, cartilage trauma or cartilage damage.

[0027] 12. The method of embodiment 11, comprising adding an arthritis-acting therapeutic agent to the mixture.

[0028] 13. The method of embodiment 12, further comprising: adding a joint-acting therapeutic agent to the mixture, the agent having the effect of inducing one or more of: (i) joint regeneration processes; (ii) repairing damage or trauma to joint tissue; and (iii) repairing symptoms of joint disease or injury; and injecting said mixture into a joint. Includes.

[0029] 14. The method of any one of embodiments 11-13 for the treatment of inflammatory joint diseases.

[0030] 15. The method of embodiment 14, comprising injecting the mixture into a joint.

[0031] 16. A system for treating joint or bone injury or disease, comprising: one or more devices or combinations of devices for drawing and collecting whole blood; a container configured for mixing whole blood with one or more clotting agents; and One or more devices for administering the blood mixture to the site of disease or trauma. Includes.

[0032] 17. The system of embodiment 16, comprising one or more coagulants.

[0033] 18. The system of embodiment 17, the one or more devices for collecting whole blood contain an anticoagulant; and The one or more coagulation agents include anticoagulants, which are agents that counteract the anticoagulant effect of anticoagulants.

[0034] 19. The system of embodiment 18, wherein the anticoagulant comprises kaolin.

[0035] 20. The system of any one of embodiments 16-19, wherein the one or more coagulants include a calcium salt of an organic acid (e.g., calcium gluconate).

[0036] 21. The system of any one of embodiments 16-20, wherein the one or more coagulants are contained within the container.

[0037] 22. The system of any one of embodiments 16-21, including a syringe for injecting blood from said container to said site of injury or disease manifestation.

[0038] 23. The system of any one of embodiments 16-22 for the treatment of bone diseases or trauma, A bone-acting drug for mixing with whole blood, said drug having the effect of inducing one or more of: (i) bone regeneration processes; (ii) repairing damage or trauma to bone tissue; and (iii) repairing symptoms of bone disease or injury.

[0039] 24. The system of embodiment 23, wherein the bone-acting agent is a bone graft material.

[0040] 25. The system of embodiment 24, wherein the bone graft material is selected from materials having one or more bone regenerating effects, including osteoconductivity, osteoinduction, and osteogenicity.

[0041] 26. The system of embodiment 25, wherein the bone graft material is selected from the group consisting of bone tissue, demineralized bone matrix, synthetic materials, minerals, and organic polysaccharide compounds.

[0042] 27. The system of any one of embodiments 16-22 for the treatment of inflammatory joint diseases, cartilage trauma or cartilage damage.

[0043] 28. The system of embodiment 27, comprising an indirect acting therapeutic agent for addition to whole blood.

[0044] 29. The system of embodiment 28, The joint acting drug has the effect of inducing one or more of: (i) the process of joint regeneration; (ii) repairing damage or trauma to joint tissue; and (iii) repairing symptoms of joint disease or damage.

[0045] 30. The system of any one of embodiments 27-29, for use in treating inflammatory joint diseases.

[0046] 31. An assembly or kit of parts comprising one or more of the elements defined in any one of embodiments 16-30. DETAILED DESCRIPTION OF THE INVENTION

[0047] A method for treating a joint or bone disease in a subject according to the present disclosure includes administering a mixture of whole blood and one or more clotting agents to the site of disease or trauma and allowing the blood to clot at the site.

[0048] The term "blood mixture" is used to refer to a mixture of blood with one or more coagulants, and optionally with other drugs, such as drugs that have a therapeutic effect in their own right, including anti-inflammatory drugs, antibiotics or other antimicrobial drugs, drugs with disease-modifying effects, and others.

[0049] The term "mixing vessel" is used herein to denote a vessel in which blood is mixed with other agents.

[0050] The blood mixture is introduced to the treatment site such that the clotting process is initiated ex vivo, i.e., outside the patient's body, and completed in vivo, i.e., at the treatment site. The blood mixture is typically introduced to the treatment site in a liquid or semi-jelly pre-clotting state, and the clotting process is completed at the site such that the mixture clots completely in vivo at the site.

[0051] Typically, the rate of coagulation can be controlled, for example, by the nature or concentration of one or more coagulation agents.

[0052] The one or more coagulants may include a single agent or a combination of agents that induce blood clotting. An anticoagulant is an agent that counteracts the anticoagulant that is mixed with blood after collection to inhibit clotting. If blood (usually venous blood) is collected in a blood collection tube, e.g., a vacutainer, without an anticoagulant, it will immediately clot. To prevent clotting, the collected blood is typically mixed with sodium citrate, ACD-A (anticoagulant citrate dextrose, solution A), heparin, oxalate, EGTA, or EDTA, so that it remains flowable. Before the blood is introduced into the site, an anticoagulant, i.e., an agent that counteracts the anticoagulant effect of clotting, such as a calcium salt of an organic acid, e.g., calcium gluconate, may be mixed into the blood to induce a clotting reaction.

[0053] Additionally or alternatively, one or more clotting agents may include agents that promote the blood clotting cascade and increase the hardness of the formed blood clot, such as kaolin, glass powder, celite powder, ellagic acid, silica powder, etc. As will be appreciated, the teachings of the present disclosure are not limited to any particular clotting agent or combination of clotting agents.

[0054] According to one embodiment, the one or more coagulants include kaolin and calcium gluconate.

[0055] The blood may be mixed with one or more coagulants in a dedicated mixing vessel, which may be configured for that purpose. The mixing vessel may sometimes be the same vessel in which the drawn blood is collected. The mixing vessel may also be the device used to transfer the blood to the site, such as the cylinder of a syringe.

[0056] The mixing vessel may already contain one or more clotting agents therein. Alternatively, one or more clotting agents may be added before, together with, or after the blood is added to the vessel. According to yet another alternative, at least one of the one or more clotting agents may be contained within the vessel, and at least one other of the one or more clotting agents may be added before or after the blood is added to the vessel.

[0057] According to one embodiment of the present disclosure, the blood is autologous blood drawn from the subject. The blood may be used immediately after it is drawn or may be stored under appropriate conditions for a period of time until use.

[0058] The blood mixture may be injected into the site. Alternatively, according to other embodiments, or for example in the case of an open fracture site, the blood mixture may be applied to the site.

[0059] According to one embodiment of treating bone diseases according to the present disclosure, the blood mixture is combined with a bone-acting drug, which may be an agent having the effect of inducing one or more of the following: (i) bone regeneration processes; (ii) repairing damage or trauma to bone tissue; and (iii) repairing symptoms of bone disease or injury. An example of a bone-acting drug is a bone graft material, e.g., a material having one or more bone regeneration effects, including osteoconductivity, osteoinduction, and osteogenicity. Specific examples of such bone graft materials are bone tissue (from donors or cadavers), demineralized bone matrix, synthetic materials, minerals, and organic polysaccharide compounds. According to some embodiments, the blood mixture with the bone-acting drug may also include anti-inflammatory drugs, antimicrobial drugs (e.g., antibiotics), and others.

[0060] According to another embodiment, the mixture is used for treating joint conditions, including, for example, inflammatory joint disease, cartilage trauma, or cartilage damage. According to some embodiments, a joint-acting therapeutic agent can be added to the mixture. Such a joint-acting therapeutic agent can be a drug that has the effect of inducing one or more of the following: (i) joint regeneration processes, (ii) repairing damage or trauma to joint tissue, and (iii) alleviating symptoms of joint disease or damage. According to some embodiments, the blood mixture with the joint-acting therapeutic agent can also include anti-inflammatory agents, antibacterial agents (e.g., antibiotics), and others.

[0061] Another aspect of the present disclosure provides a system for carrying out the method, the system of the present disclosure including one or more devices or a combination of devices for drawing and collecting blood, a mixing container, and one or more devices for administering the blood mixture to the site.

[0062] The one or more devices or combination of devices for drawing and collecting blood can be standard blood collection and collection devices routinely used in laboratory practice, such as a vacuum tube system consisting of a venipuncture needle, a tube holder that can be connected to the needle directly or through a connecting tube, and a vacuum tube, etc. However, the present disclosure is not limited to any particular device or combination of devices for drawing and collecting blood.

[0063] The mixing container can be the same as or different from the blood collection device or the device for introducing the blood mixture to the site. According to some embodiments, a blood collection container, typically a blood collection tube, can also be used as the mixing container. According to other embodiments, the mixing container is a dedicated container specifically configured for that purpose. According to yet other embodiments, the mixing container is the same as that used to transfer the blood mixture to the site, thus serving this dual purpose.

[0064] The system may also include one or more clotting agents, which may be contained within the mixing vessel or may be contained in a separate vessel to be added to the vessel before, together with, or after the blood is introduced into the mixing vessel.

[0065] The one or more devices for introducing the blood mixture into the site may be a syringe or any other device or combination of devices useful for that purpose.

[0066] The system may also include bone- or joint-acting drugs, therapeutic agents, etc. for use in combination with the mixture, subject to intended use.

[0067] Also provided by a further aspect of the present disclosure are assemblies or kits of parts including one or more of the elements for use in the aforementioned methods or included by the systems.

Claims

1. 1. A system for treating joint or bone injury or disease, comprising: one or more devices or combinations of devices for drawing and collecting whole blood; a container configured to mix the whole blood with one or more coagulants; one or more devices for administering said blood mixture to a site of disease or trauma; Including, the system.

2. The system of claim 1 , comprising one or more coagulants.

3. the one or more devices for collecting the whole blood contain an anticoagulant; and the one or more coagulation agents include an anticoagulant, which is an agent that counteracts the anticoagulant effect of the anticoagulant; The system of claim 2 .

4. The system of any one of claims 1 to 3, wherein the one or more coagulants are contained within the container.

5. For the treatment of bone disease or trauma, a bone-acting drug for mixing with the whole blood, the drug having the effect of inducing one or more of: (i) bone regeneration processes; (ii) repairing damage or trauma to the bone tissue; and (iii) repairing symptoms of disease or damage to the bone. The system according to any one of claims 1 to 4.

6. The system according to any one of claims 1 to 4 for the treatment of inflammatory joint diseases, cartilage trauma or cartilage damage.

7. 7. The system of claim 6, comprising a joint-acting therapeutic agent for addition to the whole blood, the joint-acting agent having the effect of inducing one or more of: (i) a joint regeneration process; (ii) repairing damage or trauma to the joint tissue; and (iii) repairing symptoms of disease or damage to the joint.

8. An assembly or kit of parts comprising one or more of the elements defined in any one of claims 1 to 7.

9. 1. A method for treating bone or joint disease or injury in a subject, comprising: A method comprising administering a mixture of whole blood and one or more clotting agents to a site of disease or trauma and allowing the blood to clot at the site.

10. Drawing blood from the subject; mixing the collected blood with one or more coagulants, thereby forming the mixture; injecting the mixture into the site; 10. The method of claim 9, comprising:

11. 11. The method of claim 10, wherein the drawn blood is mixed with an anticoagulant, and the one or more coagulants include an anti-anticoagulant, an agent that counteracts the anticoagulant effect of the anticoagulant.

12. For the treatment of bone trauma, adding a bone-acting drug to the mixture, the drug having the effect of inducing one or more of: (i) bone regeneration processes; (ii) repairing damage or trauma to the bone tissue; and (iii) repairing symptoms of bone disease or injury; administering the mixture to the site; The method according to any one of claims 9 to 11, comprising:

13. The method according to any one of claims 9 to 11 for treating inflammatory joint diseases, cartilage trauma or cartilage damage.

14. adding a joint-acting therapeutic agent to the mixture, the agent having the effect of inducing one or more of: (i) joint regeneration processes; (ii) repairing damage or trauma to the joint tissue; and (iii) repairing symptoms of disease or injury to the joint; injecting said mixture into said joint; 14. The method of claim 13, comprising:

15. 15. The method according to claim 13 or claim 14 for the treatment of inflammatory joint diseases.

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