Method and system for treating bone or joint

Abstract

Whole blood is mixed with one or more coagulators to produce coagulated blood which is then introduced into a site of bone or joint damage or disease and allowed to coagulate at the site. The aim is to promote healing or amelioration of a disease, disorder or lesion at the site, such as healing and regeneration-6623 of damaged bone, damaged joint, cartilage lesion, and the like.

Description

Technical Field

[0001] The present disclosure relates generally to the field of orthopedics and to formulations and methods for inducing a regenerative process in bones or joints. Background Art

[0002] Although bones have the ability to regenerate, occasionally there are injuries (e.g. bone injuries and joint wear) that do not heal and require medical intervention procedures. This is, for example, various complex bone injuries caused by disease or injury, where the body's natural repair mechanisms are unable to heal the injury, or joint damage due to mechanical wear or long-term infection (e.g. due to osteoarthritis or rheumatoid arthritis).

[0003] In cases of bone damage, a special procedure is often used to transplant bone grafts to replace bone lost due to disease, fractures, etc. The basic treatment principles include osteoconduction (used to guide the growth of natural bone), osteoinduction (used to promote undifferentiated cells to become active bone-forming cells), and osteogenesis (where the graft material includes living bone cells that aid in bone remodeling). While osteoconduction and osteoinduction may involve a variety of different grafts, osteogenesis occurs only in autologous graft tissue and allograft cellular bone matrix. Other bone graft materials include demineralized bone matrix (DMB), synthetic materials, minerals (such as hydroxyapatite), organic polysaccharide complexes (such as chitin, chitosan, and alginate), etc.

[0004] Joint injections (intra-articular injections) of therapeutic agents, such as anti-inflammatory agents, are a common treatment for inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis, gout, tendinitis, bursitis, carpal tunnel syndrome, and osteoarthritis. Joint injections also include lubricants such as hyaluronic acid, which are sometimes used to replace bursal fluid due to their high viscosity.

[0005] Wound dressings containing coagulants have been suggested for treating chronic wounds, see WO2010 / 086848, WO2019 / 058373, WO2019 / 150355, WO2019 / 058375 and WO2021 / 124317. The use of coagulated blood to treat various damaged tissues is disclosed in WO2022 / 168099, WO2022 / 180627 and WO2023 / 037373. Summary of the invention

[0006] The present disclosure provides a method for treating a disease, disorder or damage to a bone or joint.

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

[0008] The term "site" is used herein to refer to the site where a condition manifests (eg, an infected joint, a severed or fractured bone, a bone or joint site that has undergone surgery, etc.).

[0009] The term "blood" (interchangeably with "whole blood") is used herein to refer to whole blood, which is typically venous blood drawn from a subject.

[0010] The term "coagulated blood" is used herein to refer to whole blood that is still in a flowable state and is in the process of coagulation. Coagulated blood is typically whole blood mixed with one or more coagulants or anti-anti-coagulants (i.e., reagents that counteract or inhibit the effects of anticoagulants, which are mixed with whole blood to prevent it from coagulating when whole blood is drawn from a subject).

[0011] According to the present disclosure, whole blood is mixed with one or more coagulants, and the coagulated blood is then introduced into the site and allowed to coagulate at the site. One aspect of the present disclosure provides a method for treating a bone or joint disease or damage of a subject, wherein a mixture of whole blood and one or more coagulants is introduced into the site of the disease or damage so that the blood coagulates at the site. On the other hand, a system comprising elements is provided, including one or more devices and / or materials for performing the method. Yet another aspect of the present disclosure also provides an assembly and parts kit, which includes one or more elements of the system or elements required to perform the method.

[0012] The methods of the present disclosure promote healing or improvement of the 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 coagulants is introduced into the site and allowed to coagulate in situ. Typically, before the whole blood is introduced into the site, it is mixed with one or more coagulants that coagulate the blood, and before complete coagulation, the blood is still in a flowable state (i.e., in a liquid or partially coagulated state) and introduced into the site.

[0014] By some embodiments, the blood may be mixed with other agents such as bone substitutes or bone regeneration inducers, anti-inflammatory agents, disease modifiers, etc.

[0015] Some embodiments of the present disclosure will now be described in the following numbered paragraphs, and these embodiments will be referenced in subsequent paragraphs by reference numerals (in a format similar to the claims). These embodiments are intended to increase (but not limit) the disclosure herein:

[0016] 1. A method for treating a bone or joint disease or damage in a subject, comprising:

[0017] A mixture of whole blood and one or more coagulants is introduced to the site of disease or damage, and the blood is allowed to coagulate at the site.

[0018] 2. The method according to embodiment 1, comprising:

[0019] drawing blood from the subject,

[0020] mixing the drawn blood with one or more coagulants to form the mixture, and

[0021] The mixture is introduced into the site.

[0022] 3. The method according to embodiment 2, wherein

[0023] The drawn blood is mixed with an anticoagulant, and the one or more coagulants include an anticoagulant, which is an agent that counteracts the anticoagulant effect of the anticoagulant.

[0024] 4. The method of embodiment 3, wherein the one or more solidifying agents comprises kaolin.

[0025] 5. A method according to any one of embodiments 1-4, wherein the one or more coagulants include a calcium salt of an organic acid (e.g., calcium gluconate).

[0026] 6. The method according to any one of claims 1 to 5, wherein the introducing is performed by injection.

[0027] 7. The method according to any one of embodiments 1-6, for treating bone lesions, the method comprising:

[0028] A bone-affecting agent is added to the mixture, wherein the bone-affecting agent has the effect of inducing one or more of the following: (i) bone regeneration process, (ii) improving damage or damage to bone tissue, and (iii) improving symptoms of bone disease or damage, and

[0029] The mixture is introduced into the site.

[0030] 8. The method according to embodiment 7, wherein the bone-affecting agent is a bone graft material.

[0031] 9. The method according to embodiment 8, wherein the bone transplant material is selected from materials having one or more bone regeneration effects, wherein the bone regeneration effects include osteoconduction, osteoinduction and osteogenesis.

[0032] 10. The method according to embodiment 9, wherein the bone graft material is selected from the group consisting of: bone tissue, demineralized bone matrix, synthetic materials, minerals and complex organic polysaccharides.

[0033] 11. The method according to any one of embodiments 1-6, for treating inflammatory joint disease, cartilage damage or cartilage injury.

[0034] 12. The method according to embodiment 11 comprises: adding a joint-affecting therapeutic agent to the mixture.

[0035] 13. The method according to embodiment 12, comprising:

[0036] A joint-affecting agent is added to the mixture, wherein the joint-affecting agent has the effect of inducing one or more of the following: (i) joint regeneration process, (ii) improving damage or damage to joint tissue, and (iii) improving symptoms of joint disease or damage, and

[0037] Introduce the mixture into the joint.

[0038] 14. The method according to any one of embodiments 11-13, for treating inflammatory joint diseases.

[0039] 15. The method of embodiment 14, comprising injecting the mixture into a joint.

[0040] 16. A system for treating a joint or bone injury or disease, comprising:

[0041] One or more devices or a combination of devices for drawing and collecting whole blood,

[0042] a container configured for mixing the whole blood with one or more coagulants, and

[0043] One or more devices for introducing the blood mixture to the site of disease or damage.

[0044] 17. The system of embodiment 16, comprising one or more coagulants.

[0045] 18. A system according to embodiment 17, wherein

[0046] The one or more devices for collecting the whole blood include an anticoagulant, and wherein

[0047] The one or more coagulants include an anticoagulant, which is an agent that counteracts the anticoagulant effect of the anticoagulant.

[0048] 19. The system of embodiment 18, wherein the anti-coagulant comprises kaolin.

[0049] 20. The system of any one of embodiments 16-19, wherein the one or more coagulants comprises a calcium salt of an organic acid (eg, calcium gluconate).

[0050] 21. The system of any one of embodiments 16-20, wherein the one or more coagulants are contained in the container.

[0051] 22. The system of any one of embodiments 16-21, comprising: a syringe for injecting blood from the container into the site of manifestation of the damage or disease.

[0052] 23. The system according to any one of embodiments 16-22, for use in treating a bone disease or damage, the system comprising:

[0053] A bone-affecting agent for mixing with whole blood, wherein the bone-affecting agent has the effect of inducing one or more of the following: (i) bone regeneration process, (ii) improving injury or damage of bone tissue, and (iii) improving symptoms of bone disease or injury.

[0054] 24. The system of embodiment 23, wherein the bone-affecting agent is in a bone graft material.

[0055] 25. A system according to embodiment 24, wherein the bone graft material is selected from materials having one or more bone regeneration effects, including osteoconduction, osteoinduction and osteogenesis.

[0056] 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 complex organic polysaccharides.

[0057] 27. The system according to any one of embodiments 16-22, for use in treating inflammatory joint disease, cartilage damage or cartilage injury.

[0058] 28. The system of embodiment 27, comprising: a joint-affecting therapeutic agent for addition to whole blood.

[0059] 29. A system according to embodiment 28, wherein

[0060] The joint-affecting agent has the effect of inducing one or more of the following: (i) joint regeneration process, (ii) improving damage or injury to joint tissue, and (iii) improving symptoms of joint disease or injury.

[0061] 30. The system according to any one of embodiments 27-29, for use in treating inflammatory joint diseases.

[0062] 31. An assembly or kit of parts comprising one or more elements as defined in any one of embodiments 16-30. DETAILED DESCRIPTION

[0063] Methods for treating a joint or bone disorder in a subject according to the present disclosure include introducing a mixture of whole blood and one or more coagulants into a site of disease or damage and allowing the blood to coagulate at the site.

[0064] The term "blood mixture" will be used to refer to a mixture of blood with one or more coagulants and optionally with other agents (e.g., agents that themselves have therapeutic effects, including anti-inflammatory drugs, antibiotics or other antibacterial drugs, drugs with disease-modifying effects, etc.).

[0065] The term "mixing container" will be used herein to refer to the container in which the blood is mixed with other reagents.

[0066] The blood mixture is introduced to the treatment site so that the coagulation process starts in vitro (i.e., outside the patient's body) and is completed in vivo (i.e., the treatment site). The blood mixture is usually introduced to the treatment site in a liquid or semi-gel pre-coagulated state, and the coagulation process is completed at the site so that the preparation is completely coagulated in situ at the site.

[0067] Typically, the rate of solidification can be controlled (eg, by the nature or concentration of one or more solidifying agents).

[0068] One or more coagulants can include a single agent or a combination of agents that induce blood coagulation.Anticoagulants are agents that counteract anticoagulants, which are mixed with blood after blood is drawn to inhibit its coagulation.When blood (usually venous blood) is drawn into a blood collection tube (such as a vacuum blood collection tube), it will coagulate rapidly in the absence of an anticoagulant.In order to avoid blood coagulation, the drawn blood is usually mixed with an anticoagulant (such as sodium citrate, anticoagulant citrate dextrose, solution A (Anticoagulant Citrate Dextrose, Solution A, ACD-A), heparin, oxalate, EGTA or EDTA) to keep it flowing.Before blood is introduced into the site, in order to induce a coagulation reaction, an anticoagulant (i.e., an agent that counteracts the coagulation inhibition of coagulation (such as a calcium salt of an organic acid (such as calcium gluconate))) can be mixed into the blood.

[0069] In addition, or in the alternative, one or more coagulants may include agents (such as kaolin, glass powder, diatomaceous earth powder, ellagic acid, silicon dioxide powder) that accelerate the coagulation cascade, increase the firmness of the formed blood coagulant, etc. It will be understood that the teachings of the present disclosure are not limited to any particular coagulant or combination of coagulants.

[0070] By way of example, the one or more solidifying agents include kaolin and calcium gluconate.

[0071] The blood may be mixed with one or more coagulants in a dedicated mixing container, which may be configured for this purpose. The mixing container may sometimes be the same container in which the drawn blood is collected. The mixing container may also be a device (e.g., the barrel of a syringe) for transferring the blood to the site.

[0072] One or more coagulants may be pre-included in the mixing container. Alternatively, one or more coagulants may be introduced before, simultaneously with, or after the blood is introduced into the container. By another alternative, at least one of the one or more coagulants may be included in the container, and at least another of the one or more coagulants may be introduced before or after the blood is introduced into the container.

[0073] According to the embodiments of the present disclosure, the blood is autologous blood drawn from the subject. The blood can be used immediately after being drawn, or can be stored for a period of time under appropriate conditions until it is used.

[0074] The blood mixture may be introduced into the site by injection. Alternatively, by other embodiments, or for example, in the case of an open fracture site, the blood mixture may be pasted to the site.

[0075] By one embodiment of treating a bone disorder according to the present disclosure, the blood mixture is combined with a bone-affecting agent, which can be an agent that has the effect of inducing one or more of the following: (i) bone regeneration process, (ii) improving damage or damage to bone tissue, and (iii) improving symptoms of bone disease or damage. An example of a bone-affecting agent is a bone transplant material (e.g., a material having one or more bone regeneration effects, including osteoconduction, osteoinduction, and osteogenesis). Specific examples of such bone transplant materials are bone tissue (from a donor or a deceased person), demineralized bone matrix, synthetic materials, minerals, and complex organic polysaccharides. By some embodiments, the blood mixture with the bone-affecting agent can also include an anti-inflammatory agent, an antimicrobial agent (e.g., an antibiotic), and the like.

[0076] By another embodiment, the mixture is used to treat joint conditions (e.g., including inflammatory joint diseases, cartilage damage, or cartilage injury). By some embodiments, a joint-affecting therapeutic agent can be added to the mixture. Such a joint-affecting agent can be an agent that has the effect of inducing one or more of the following: (i) joint regeneration processes, (ii) improving damage or damage to joint tissue, and (iii) improving symptoms of joint disease or damage. By some embodiments, the blood mixture with the joint-affecting therapeutic agent can also include an anti-inflammatory agent, an antimicrobial agent (e.g., an antibiotic), etc.

[0077] Another aspect of the present disclosure provides a system for performing the method. The system of the present disclosure includes one or more devices or a combination of devices for extracting and collecting blood; a mixing container; and the system includes one or more devices for introducing the blood mixture to the site.

[0078] The one or more devices or combination of devices used to draw and collect blood can be standard blood drawing and collection devices routinely used in laboratory practice (e.g., a vacuum tube system consisting of a venipuncture needle, a tube holder that can be connected directly to the needle or connected by a connecting tube, and a vacuum tube). However, the present disclosure is not limited to any particular device or combination of devices for blood drawing and collection.

[0079] The mixing container may be the same as or different from the blood collection device or device used to introduce the blood mixture to the site. By some embodiments, the blood collection container (typically a blood collection tube) may also serve as the mixing container. By other embodiments, the mixing container is a dedicated container configured specifically for this purpose. By another embodiment, the mixing container is the same as the mixing container used to transfer the blood mixture to the site, thereby achieving this dual purpose.

[0080] The system may further comprise the one or more coagulants. The one or more coagulants may be contained within the mixing container or in a separate container to be added to the mixing container before, simultaneously with, or after the blood is introduced into the container.

[0081] The one or more devices used to introduce the blood mixture into the site may be a syringe or any other device or combination of devices used for this purpose.

[0082] The system may also include bone-affecting agents or joint-affecting agents, therapeutic drugs, etc. in combination with the mixture depending on the intended use.

[0083] Additional aspects of the present disclosure also provide an assembly or a kit of parts comprising one or more elements used in the above method or included by the system.

Claims

1. A system for treating joint or bone damage or disease, comprising: One or more devices or a combination of devices for drawing and collecting whole blood, a container configured for mixing the whole blood with one or more coagulants, and One or more devices for introducing the blood mixture to the site of disease or damage.

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

3. The system according to claim 2, wherein The one or more devices for collecting the whole blood include an anticoagulant, and wherein The one or more coagulants include an anticoagulant, which is an agent that counteracts the anticoagulant effect of the anticoagulant.

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

5. A system according to any one of claims 1 to 4 for treating bone disease or damage, the system comprising: A bone-affecting agent for mixing with whole blood, the bone-affecting agent having the effect of inducing one or more of the following: (i) bone regeneration process, (ii) improving damage or injury to bone tissue, and (iii) improving symptoms of bone disease or injury 6. The system according to any one of claims 1 to 4, for use in the treatment of inflammatory joint diseases, cartilage damage or cartilage injury.

7. The system according to claim 6 comprises a joint-affecting therapeutic agent for addition to the whole blood, wherein the joint-affecting agent has the effect of inducing one or more of the following: (i) joint regeneration process, (ii) improving injury or damage to joint tissue, and (iii) improving symptoms of disease or injury to the joint.

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

9. A method for treating a bone or joint disease or damage in a subject, comprising: A mixture of whole blood and one or more coagulants is introduced to the site of disease or damage, and the blood is allowed to coagulate at the site.

10. The method according to claim 9, comprising: drawing blood from the subject, mixing the drawn blood with one or more coagulants to form the mixture, and The mixture is introduced into the site.

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

12. The method according to any one of claims 9 to 11 for treating bone lesions, the method comprising: A bone-affecting agent is added to the mixture, wherein the bone-affecting agent has the effect of inducing one or more of the following: (i) bone regeneration process, (ii) improving damage or damage to bone tissue, and (iii) improving symptoms of bone disease or damage, and The mixture is introduced into the site.

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

14. The method according to claim 13, comprising: A joint-affecting agent is added to the mixture, wherein the joint-affecting agent has the effect of inducing one or more of the following: (i) joint regeneration process, (ii) improving damage or damage to joint tissue, and (iii) improving symptoms of joint disease or damage, and Introduce the mixture into the joint.

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