CN109498852B - Biodegradable material for treating orthopedic diseases and application thereof - Google Patents
Biodegradable material for treating orthopedic diseases and application thereof Download PDFInfo
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- CN109498852B CN109498852B CN201811635473.3A CN201811635473A CN109498852B CN 109498852 B CN109498852 B CN 109498852B CN 201811635473 A CN201811635473 A CN 201811635473A CN 109498852 B CN109498852 B CN 109498852B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
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Abstract
The invention discloses a biodegradable material for treating osteoarthritis and application thereof, wherein the biodegradable material is a solid or semisolid molding material formed after being injected into subchondral bone of the osteoarthritis. The degradable biomaterial is injected into the bone under the articular cartilage of the bone, so that a favorable environment is created for repairing and regenerating the damaged bone tissue, and the effects of relieving joint pain, protecting the articular cartilage, improving the motion function and the like are achieved. The biological material is safe and nontoxic, has good biocompatibility, can be used for treating osteoarthritis quickly and effectively, and has small wound. The invention takes the subchondral bone as a target site, fundamentally relieves the symptoms of pain and the like of a patient, improves the joint function and prevents the disease from developing to a more serious direction.
Description
Technical Field
The invention belongs to the field of medical instruments, and particularly relates to a biodegradable material for treating orthopedic diseases (such as osteoarthritis and bone marrow edema) and application thereof.
Background
Osteoarthritis (OA) is a chronic damage to the articular cartilage and surrounding tissues, characterized by pain, stiffness and loss of joint function, a degenerative disease that severely affects the quality of life of patients. Osteoarthritis is the most common joint disease, and recent statistics show that there are 3.55 million people with arthritis worldwide. By 2015, more than 1.2 million arthritis patients in continental china have had an incidence of about 13% and over 50% in the 60-75 year old population.
The pathological features of OA include degenerative destruction of articular cartilage, subchondral bone sclerosis, bone marrow edema (BML) in subchondral bone region, cystic degeneration, osteoproliferation at joint margins to form osteophytes, synovial lesions, contracture of joint capsule, ligament relaxation, muscle atrophy, etc., as shown in fig. 1.
At present, the treatment of OA at home and abroad mainly comprises drug treatment (oral drugs and joint cavity injection drugs) and operation treatment. But the curative effect of the existing various clinical schemes is not ideal.
The current clinical OA treatment drugs can only be used for symptom relief, and do not directly change the course of osteoarthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs for relieving pain and improving joint function of OA patients, but the NSAIDs have higher cardiovascular and cerebrovascular risks after long-term administration. Opioid analgesics may be used in individuals who are not effective or resistant to NSAIDs treatment, but opioid drugs have a relatively high incidence of adverse effects and addiction, suggesting prudent use. In addition, the use of hyaluronic acid, chitosan for medical purposes, etc. for intraluminal injection is also contemplated, but its role in cartilage protection and slowing of disease progression is still controversial. Although these medications, which aim to relieve pain and protect cartilage, temporarily relieve the clinical symptoms of the patient, slow down the further degeneration of cartilage to some extent, and do not prevent the disease from progressing to a more serious state.
The surgical treatment of OA comprises articular cartilage repair, arthroscopic cleaning operation, osteotomy, joint fusion and artificial joint replacement, and is suitable for patients who have no effect of non-surgical treatment and influence normal life. However, surgical treatment such as joint replacement is expensive, abrasion and looseness can occur after long-term activity, revision is required, postoperative thrombosis can occur, and catastrophic complications such as amputation caused by infection after replacement can occur.
Aiming at the current situations that the existing oral drugs can only relieve symptoms, the effect of joint cavity injection drugs in the disease relieving process is disputed, the operation treatment cost is high, the infection risk is high and the like, the osteoarthritis still lacks a quick and effective treatment method with small wound.
Disclosure of Invention
The degradable biological material is injected into the subchondral bone of the osteoarticular bone and the bone marrow edema of the subchondral bone in a minimally invasive way, so that the aims of relieving the joint pain caused by osteoarthritis, improving the joint function, protecting the articular cartilage and improving the motion function are achieved, and the condition of the disease is prevented from developing to a more serious direction.
The invention aims to provide a biodegradable material for treating osteoarthritis and application thereof.
The technical scheme adopted by the invention is as follows:
the application of the injection-molded biodegradable material in the preparation of medical instruments, medical materials or/and medicines for treating or assisting in treating orthopedic diseases; the orthopedic diseases comprise osteoarthritis and bone marrow edema.
The injection-molded biodegradable material is applied to the preparation of medical instruments, medical materials or/and medicines for relieving pain of orthopedic diseases, protecting or treating articular cartilage or/and improving joint functions; the orthopedic diseases comprise osteoarthritis and bone marrow edema.
The application of the injection-molded biodegradable material in preparing medical devices or/and medicines for treating or assisting in treating the bone marrow edema of the subchondral bone.
The application of the injection-molded biodegradable material in the preparation of medical devices or/and medicines for treating, assisting in treating or protecting subchondral bone in osteoarthritis.
Preferably, the treatment of subchondral bone in osteoarthritis comprises decreasing the bone volume fraction of subchondral bone, increasing the trabecular resolution of subchondral bone, increasing trabecular pattern factor.
Preferably, the injection molded biodegradable material is injected into subchondral bone of osteoarthritis to form a solid or semi-solid shaped biodegradable material; the solid or semi-solid shaped form includes, but is not limited to, a flocculent, a milky, a paste, a gel.
Preferably, the injection-molded biodegradable material consists of a material A and a material B;
the material A is selected from at least one of glycolide-lactide copolymer, poly (lactic acid-glycolic acid) copolymer, polylactic acid, polylactic-co-glycolic acid, polyethylene glycol copolymer and polyethyleneimine degradable copolymer;
the material B is at least one of N-methyl pyrrolidone, 1, 2-propylene glycol carbonate and glyceryl triacetate.
Preferably, the mass ratio of the material A to the material B is 5-50: 50 to 95.
Preferably, the material A and the material B are mixed to form clear liquid; the mixture is injected into subchondral bone of osteoarthritis to form a solid or semi-solid shape.
Preferably, the solid or semi-solid shaped form includes, but is not limited to, a flocculent, a milky, a paste, a gel.
The invention has the beneficial effects that:
(1) the degradable biomaterial is injected into the bone under the articular cartilage, and the degradable biomaterial forms white flocculent, milky, pasty and gelatinous solid or semisolid molding shape when meeting body fluid after injection, thereby creating favorable environment for repairing and regenerating damaged bone tissues, and further achieving the effects of relieving joint pain, protecting articular cartilage, improving motion function and the like.
(2) The degradable biological material used in the invention is safe and nontoxic, and has good biocompatibility and biodegradability. The traditional Chinese medicine composition is quick and effective in treating osteoarthritis and has small wound.
(3) The invention takes the subchondral bone as a target site, fundamentally relieves the symptoms of pain and the like of a patient, improves the joint function and prevents the disease from developing to a more serious direction.
Drawings
FIG. 1 is a schematic representation of osteoarthritis leading to cartilage wear, subchondral bone sclerosis, bone marrow edema, osteophyte formation, and joint capsule thickening;
FIG. 2 is an injection-molded biodegradable material for the treatment of osteoarthritis prepared in example 1;
FIG. 3 shows that the biodegradable material prepared in example 1 is in milky suspension after being injected into a body fluid environment;
FIG. 4 shows the results of safranin fast green staining (A) and OARSI-Modified Mankin scoring (B) of osteoarthritic cartilage specimens of rats in each group;
FIG. 5 Micro-CT examination of various groups of rats, (A) bone volume fraction of subchondral bone (BV/TV); (B) subchondral bone trabecular resolution (tb.sp); (C) is trabecular bone pattern factor (tb.pf).
Detailed Description
The present invention will be further described with reference to the following examples.
Example 1 preparation of an injection-molded biodegradable Material for the treatment of osteoarthritis
Glycolide-lactide copolymer (PLGA) and N-methylpyrrolidone (NMP) were precisely weighed at a weight ratio of 10: 90, respectively; transferring N-methylpyrrolidone (NMP) into a stainless steel liquid preparation tank, stirring at a low speed (200-400 rpm) by using a stirring paddle, slowly adding PLGA powder, dispersing, and fully dissolving to obtain a relatively stable solution system; the solution system was then sterile filtered using a 0.22 μm sterile filter. And after filtering, filling to obtain the biodegradable material for injection molding for treating osteoarthritis. Storing in dark and room temperature.
The product needs technical detection, which includes observation, identification and determination of molecular weight, and meanwhile, heavy metals, solvent residues, moisture, sterility, bacterial endotoxin, biological properties, physical and mechanical properties and the like are detected to ensure the safety and stability of the product.
The injection molded biodegradable material prepared in this example is shown in fig. 2, which is a clear transparent solution. When the clear solution is injected into body fluid environment, it is in milky suspension and contains flocculent precipitate, as shown in figure 3.
Example 2 preparation of an injection-molded biodegradable Material for the treatment of osteoarthritis
Except that the weight ratio of glycolide-lactide copolymer (PLGA) to N-methylpyrrolidone (NMP) was 5: 95; the other preparation processes are the same as in example 1.
Example 3 preparation of an injection-molded biodegradable Material for the treatment of osteoarthritis
Except that the weight ratio of glycolide-lactide copolymer (PLGA) to N-methylpyrrolidone (NMP) was 50: 50; the other preparation processes are the same as in example 1.
EXAMPLE 4 preparation of injection-molded biodegradable Material for the treatment of osteoarthritis
Except that the weight ratio of glycolide-lactide copolymer (PLGA) to N-methylpyrrolidone (NMP) was 30: 70; the other preparation processes are the same as in example 1.
EXAMPLE 5 preparation of injection-molded biodegradable Material for the treatment of osteoarthritis
Except that glycolide lactide copolymer (PLGA) and N-methylpyrrolidone (NMP) were replaced with a 30: the preparation process was the same as in example 1 except for the poly (lactic-co-glycolic acid) copolymer of 70 and 1, 2-propanediol carbonate.
EXAMPLE 6 preparation of injection-molded biodegradable Material for the treatment of osteoarthritis
Except that glycolide lactide copolymer (PLGA) and N-methylpyrrolidone (NMP) were replaced with a 30: the preparation process was the same as in example 1 except for the polylactic acid-glycolic acid copolymer (70) and triacetin.
Example 7 preparation of injection-molded biodegradable Material for the treatment of osteoarthritis
Except that glycolide lactide copolymer (PLGA) and N-methylpyrrolidone (NMP) were replaced with a 30: the procedure of example 1 was followed except for the preparation of 70 g of polyethyleneimine and N-methylpyrrolidone.
EXAMPLE 8 preparation of an injection-molded biodegradable Material for the treatment of osteoarthritis
Except that the glycolide lactide copolymer (PLGA) and N-methylpyrrolidone (NMP) were replaced with a 15: 15: the preparation process was the same as in example 1 except for the polylactic acid of 70, the polyethylene glycol copolymer and N-methylpyrrolidone.
Example 9 use of the biodegradable materials prepared in the examples of the invention in the treatment of osteoarthritis
The method comprises the following steps: 12 SD rats were randomly divided into 3 groups, i.e., sham (sham), model, treatment, wherein model and treatment rats used anterior cruciate ligament resection (ACLT), a classical model of osteoarthritis. Treatment groups 5. mu.l of the biodegradable material prepared in the examples of the present invention (as in example 1) was injected into subchondral bone area (including the edematous area of subchondral bone marrow) of osteoarthritis after rat molding. After 12 weeks, all groups of rats are taken to study the structures of cartilage and subchondral bone from a microscopic level under Micro-CT scanning, the pathological changes of the subchondral bone are analyzed, meanwhile, the cartilage is taken to carry out OARSI-Modified manufacturing scoring of safranine fast green staining, the damage degree of the cartilage is evaluated, and the improvement condition of the subchondral bone is judged.
As a result:
(1) fast green safranin staining and OARSI-Modified Mankin scoring results
The results of safranin fast green staining and OARSI-Modified Mankin scoring are shown in FIG. 4, and by safranin fast green staining of cartilage specimens, it was found that the cartilage surface of rats in the Osteoarthritis (OA) model group had obvious cracks and gradually extended to the deep part of articular cartilage, and the chondrocytes were irregularly arranged and disordered. In contrast, the chondrocytes in the treated group were relatively well aligned and the structure was relatively intact (fig. 4A). The extent of destruction of articular cartilage was quantified by OARSI-modified Mankin score and it was found that the OA model group score was significantly higher than the treatment and sham groups, indicating that articular cartilage was destroyed in OA, statistically different from both the other groups (p <0.05) and not between the treatment and sham groups (fig. 4B). The above results indicate that in osteoarthritis, articular cartilage can be significantly protected by injecting the injection-molded biodegradable material prepared according to the example of the present invention through subchondral bone.
(2) Micro-CT examination result
The results of Micro-CT examination of rats in each group are shown in fig. 5, and the reconstruction of subchondral bone of animals in sham group, OA model group and treatment group by Micro-CT shows that in the OA model of rat knee joint with anterior cruciate ligament cut (ACLT), the bone volume fraction (BV/TV) of subchondral bone in OA model group is increased (fig. 5A), the degree of separation of subchondral bone trabecular bone (tb.sp) is decreased (fig. 5B), the bone trabecular pattern factor (tb.pf) is decreased (fig. 5C) compared with animals in treatment group and sham group, and the difference between model group and other two groups is statistically significant (p < 0.05). No significant statistical differences were found in the above test indices (P > 0.05) between the treatment and sham groups. The above results demonstrate that the injection of the biodegradable material prepared by the example of the present invention into subchondral bone can improve the subchondral bone abnormality caused by osteoarthritis, remarkably protect and treat the subchondral bone in osteoarthritis.
In conclusion, the degradable biomaterial is injected into the bone under the articular cartilage, and the degradable biomaterial forms white flocculent, milky, pasty and gelatinous solid or semisolid molding shape when meeting body fluid after injection, so that a favorable environment is created for repairing and regenerating damaged bone tissues, and the effects of relieving joint pain, protecting the articular cartilage, improving the motion function and the like are achieved. The biological material of the invention is safe and nontoxic, and has good biocompatibility and biodegradability. The traditional Chinese medicine composition is quick and effective in treating osteoarthritis and has little wound. The degradable biological material is injected by manufacturing the subchondral bone injection channel, and the specific injection part is the subchondral bone of a joint (such as a knee joint, a hip joint and other moving joints); the invention takes the subchondral bone as a target site, fundamentally relieves the symptoms of pain and the like of a patient, improves the joint function and prevents the disease from developing to a more serious direction. The invention adopts a minimally invasive injection mode, has convenient injection and small wound, and can normally carry out daily activities without the need of bed rest of patients after injection.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (6)
1. The application of the biodegradable material formed by injection molding in the preparation of medical instruments or/and medicines for treating or assisting in treating orthopedic diseases; the orthopedic diseases comprise osteoarthritis and bone marrow edema; the biodegradable material consists of a material A and a material B; the material A is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polyethylene glycol copolymer and polyethyleneimine degradable copolymer; the material B is at least one selected from 1, 2-propylene glycol carbonate and glyceryl triacetate; the mass ratio of the material A to the material B is 5-30: 70-95; the mixture of the material A and the material B is clear liquid; the mixture is injected into subchondral bone to form a solid or semi-solid shape.
2. The application of a biodegradable material formed by injection molding in the preparation of medical instruments or/and medicines for relieving pain of orthopedic diseases, protecting or treating articular cartilage or/and improving joint functions; the orthopedic diseases comprise osteoarthritis and bone marrow edema; the biodegradable material consists of a material A and a material B; the material A is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polyethylene glycol copolymer and polyethyleneimine degradable copolymer; the material B is at least one of 1, 2-propylene glycol carbonate and glyceryl triacetate; the mass ratio of the material A to the material B is 5-30: 70-95; the mixture of the material A and the material B is clear liquid; the mixture is injected into subchondral bone to form a solid or semi-solid shape.
3. The application of a biodegradable material formed by injection in the preparation of medical devices or/and medicines for treating or assisting in treating the bone marrow edema of subchondral bone; the biodegradable material consists of a material A and a material B; the material A is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polyethylene glycol copolymer and polyethyleneimine degradable copolymer; the material B is at least one of 1, 2-propylene glycol carbonate and glyceryl triacetate; the mass ratio of the material A to the material B is 5-30: 70-95, wherein a mixture obtained by mixing the material A and the material B is a clear liquid; the mixture is injected into subchondral bone to form a solid or semi-solid shape.
4. The application of the biodegradable material formed by injection in the preparation of medical devices or/and medicines for treating, assisting in treating or protecting subchondral bone in osteoarthritis; the biodegradable material consists of a material A and a material B; the material A is selected from at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polyethylene glycol copolymer and polyethyleneimine degradable copolymer; the material B is at least one selected from 1, 2-propylene glycol carbonate and glyceryl triacetate; the mass ratio of the material A to the material B is 5-30: 70-95; the mixture of the material A and the material B is clear liquid; the mixture is injected into subchondral bone to form a solid or semi-solid shape.
5. The use of claim 4, wherein the treatment of subchondral bone in osteoarthritis comprises decreasing bone volume fraction of subchondral bone, increasing subchondral bone trabecular separation, increasing trabecular bone pattern factor.
6. Use according to any one of claims 1 to 5, wherein the solid or semi-solid shaped form includes, but is not limited to, a flocculent, a milky, a paste, a gel.
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