CN116687835B - A long-acting sustained-release gel injectable into articular cavity and preparation method thereof - Google Patents
A long-acting sustained-release gel injectable into articular cavity and preparation method thereof Download PDFInfo
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- CN116687835B CN116687835B CN202310748307.9A CN202310748307A CN116687835B CN 116687835 B CN116687835 B CN 116687835B CN 202310748307 A CN202310748307 A CN 202310748307A CN 116687835 B CN116687835 B CN 116687835B
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
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- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种可关节腔注射的长效缓释凝胶及其制备方法；所述的凝胶包括如下质量分数的组分：非甾体类抗炎药0.05～2.0％、凝胶基质1.0～3.0％、稳定剂0.1～5.0％、缓冲剂0.05～1.0％、辅料0.5～1.5％以及余量水；凝胶的pH为7.0±0.5；方法：S1、将缓冲剂溶于水获得缓冲液；S2、将非甾体类抗炎药和稳定剂溶于缓冲液，得到溶解液；S3、向溶解液中加入辅料、凝胶基质并搅拌至其完全溶解呈凝胶状态，补足水；S4、经过滤或湿热灭菌后得到长效缓释凝胶。应用：将该凝胶用于骨关节疾病的治疗或改善关节症状。本发明的凝胶在快速缓解疼痛的同时能长期改善骨关节的润滑和保护程度，提供整体治疗效果。The present invention discloses a long-acting sustained-release gel that can be injected into the articular cavity and a preparation method thereof; the gel comprises the following components in mass fraction: 0.05-2.0% of nonsteroidal anti-inflammatory drugs, 1.0-3.0% of gel matrix, 0.1-5.0% of stabilizer, 0.05-1.0% of buffer, 0.5-1.5% of auxiliary materials and the balance of water; the pH of the gel is 7.0±0.5; the method is as follows: S1, dissolving the buffer in water to obtain a buffer solution; S2, dissolving the nonsteroidal anti-inflammatory drugs and stabilizers in the buffer solution to obtain a dissolved solution; S3, adding auxiliary materials and gel matrix to the dissolved solution and stirring until the solution is completely dissolved and in a gel state, and replenishing water; S4, filtering or wet heat sterilization to obtain a long-acting sustained-release gel. Application: The gel is used for the treatment of bone and joint diseases or improvement of joint symptoms. The gel of the present invention can improve the lubrication and protection of bone and joints for a long time while quickly relieving pain, providing an overall therapeutic effect.
Description
Technical Field
The invention relates to the field of pharmaceutical preparations, in particular to a long-acting slow-release gel capable of being injected into a joint cavity and a preparation method thereof.
Background
Ketorolac is a non-steroidal drug with potent analgesic activity. In order to improve the water solubility of ketorolac and meet the requirements of injection and oral administration, the ketorolac can rapidly act in body fluid and gastrointestinal tract, and the ketorolac tromethamine salt is generally prepared, and the structure of the ketorolac tromethamine salt is shown as a formula (I):
Injections (30 mg/time) and oral formulations (10 mg/time) of ketorolac tromethamine can be used to relieve moderate to severe postoperative pain, swelling and pain, and pain caused by other inflammation. In addition, it can also relieve acute renal colic, biliary colic, toothache, wound pain, cancer visceral pain, and various pains which can be relieved by morphine or pethidine. The main pharmacological actions of ketorolac are to achieve analgesic, anti-inflammatory, antipyretic and platelet aggregation inhibition by inhibiting prostaglandin synthesis.
Currently, ketorolac formulations marketed in china are tablets, capsules, injections and eye drops. In order to overcome the defect of frequent administration of ketorolac oral preparations, various preparation technologies are adopted to prepare the ketorolac into oral slow-release microcapsules, osmotic pump tablets, gastric floating tablets, pulse drug release systems and the like, so as to realize the long-acting analgesic effect of the ketorolac. The ketorolac tromethamine oral preparation has the problems of gastrointestinal side effects shared by non-steroidal medicines, weak pertinence in the aspect of treating local pain and the like, so that a novel ketorolac local preparation with various administration routes such as skin, eyes, nasal cavities, oral mucosa and the like is developed, and the pain of subcutaneous soft tissues, joints, oral cavities and the like can be treated. The novel ketorolac formulation is developed around long-acting and locally targeted analgesic purposes, thereby meeting different clinical analgesic requirements.
Hyaluronic Acid (HA) is an anionic non-sulfate glycosaminoglycan, comprising N-acetyl-D-glucosamine (GlcNAc) and gluconic acid (GlcA) linked by 1, 4-glycosidic bonds to form a repeating unit, and the repeating units are linked by β -1, 3-glycosidic bonds to form a linear backbone. Hyaluronic acid is widely present in mammalian tissues, including connective, epithelial and nervous tissues, and its main biological functions include modulation of tissue fluid viscoelasticity, such as joint synovial fluid and ocular vitreous fluid. Hyaluronic acid has received extensive attention and research in the medical field due to its good hydrophilicity, biocompatibility and non-immunogenicity, for example, by treating arthritis as a supplementary synovial fluid to improve pain and function, as a filler for ophthalmic surgery, and in wound dressings, and as a drug delivery material for targeted administration or drug solubilization. In addition, hyaluronic Acid (HA) HAs also been widely used in the food and cosmetic fields. At present, a plurality of HA products are marketed for treating osteoarthritis at home.
Chitin, known by the chemical name poly-1, 4-beta-N-acetyl-D-glucosamine, is widely found in the exoskeletons of crustaceans and fungal cell walls. Chitosan (Chitosan) is the most important derivative of chitin, and is produced by deacetylation of chitin, and its chemical name is poly-1, 4-beta-D-glucosamine, and since there are a large number of exposed amino and hydroxyl groups, chitosan readily forms strong hydrogen bonds in or between molecules, which makes it difficult to dissolve in water or conventional organic solvents, and N-acylation is a common modification strategy to enhance its water solubility. Medical chitosan (for intra-articular injection) is the only polymer polysaccharide available for osteoarthritis treatment (Libao, national mechanical injection 20173130026) which is currently used in the market except sodium hyaluronate. In addition, polymers such as heparin precursors (Heparosan), pentosan Polysulfate (PPS), human lubricin (lubricin) or polyvinyl alcohol are also increasingly entering clinical trials for the treatment of arthritis, but these are also very promising therapeutic drugs or materials, although no products are yet marketed.
The polyalcohol such as mannitol, sorbitol and the like has high-density hydroxyl in the molecular structure, is easy to dissolve in water and has low toxicity, and is often used as a food additive. Therefore, the polyalcohol is used as a heat sterilization stabilizer of carboxymethyl chitin preparation, the molecular structure of carboxymethyl chitin can be stabilized through the hydrogen bond action formed between the polyalcohol and the carboxymethyl chitin preparation, and the integrity of molecular chains is protected to ensure that the carboxymethyl chitin is resistant to high-temperature degradation. Clinical treatment proves that ketorolac can effectively relieve pain caused by acute gouty arthritis, and some researches prove that the knee joint injection cavity ketorolac is effective in treating knee osteoarthritis. The long-acting gel product of ketorolac can play a role in rapidly relieving pain while continuously maintaining long-term lubrication, is a better choice for treating osteoarthritis, but the product is not seen to be marketed at present.
Disclosure of Invention
The invention aims to solve the problems in the background technology and provides a long-acting slow-release gel capable of being injected into a joint cavity and a preparation method thereof.
The invention is realized by the following technical scheme:
the long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
0.05-2.0wt% of non-steroidal anti-inflammatory agent, 1.0-3.0wt% of gel matrix, 0.1-5.0wt% of stabilizer, 0.05-1.0wt% of buffer and the balance of water, wherein the pH of the long-acting slow-release gel is 7.0+/-0.5, and the osmotic pressure is 280-380 mOsm/kg.
Specifically, the long-acting slow-release gel developed by the invention is suitable for injection of joint cavities, can be used for treating bone joint diseases, can improve the lubrication and protection degree of bone joints for a long time while rapidly relieving pain, and provides an overall treatment effect.
Further, a long-acting sustained-release gel capable of being injected into joint cavities is characterized in that the nonsteroidal anti-inflammatory drug is ketorolac tromethamine.
Furthermore, the long-acting slow-release gel capable of being injected into the joint cavity is characterized in that the gel matrix is extracted naturally or biologically fermented or chemically synthesized, and the gel matrix can be any one or a combination of two or more of crosslinked sodium hyaluronate, non-crosslinked sodium hyaluronate, medical chitosan, heparin precursor (Heparosan), pentosan Polysulfate (PPS), human lubricin (lubricin) or polyvinyl alcohol.
Furthermore, the long-acting sustained-release gel capable of being injected into the joint cavity is characterized in that the molecular weight of sodium hyaluronate is 100-10000 kD, and the molecular weight of medical use couple Ding Tangfen is 100-1000 kD.
Furthermore, the long-acting slow-release gel capable of being injected into the joint cavity is characterized in that the stabilizer is sorbitol, mannitol or meglumine. The stabilizer is a polyol stabilizer.
Further, the long-acting slow release gel capable of being injected into joint cavities is characterized in that the buffering agent is selected from one or a mixture of more of phosphate, borate or citrate.
The preparation method of the long-acting slow-release gel capable of being injected into the joint cavity is characterized by comprising the following specific steps of:
s1, dissolving the buffer in water to obtain a buffer solution;
S2, dissolving the nonsteroidal anti-inflammatory drug and the stabilizer in the buffer solution to obtain a dissolution solution;
S3, adding the gel matrix into the dissolution liquid, stirring until the gel matrix is completely dissolved to form a gel state, supplementing water, and regulating the pH value of the system to 7.0+/-0.5;
S4, filtering or wet-heat sterilizing to obtain the long-acting slow-release gel capable of being injected into the joint cavity.
The preparation method of the long-acting slow-release gel capable of being injected into the joint cavity is characterized by comprising the following specific steps of:
s1, dissolving the buffer in water to obtain a buffer solution;
S2, adding the gel matrix into the buffer solution, and stirring until the gel matrix is completely dissolved to obtain a gel system;
s3, adding the non-steroidal anti-inflammatory drug and a stabilizer into the gel system, supplementing water, and regulating the pH value of the system to 7.0+/-0.5;
S4, filtering or wet-heat sterilizing to obtain the long-acting slow-release gel capable of being injected into the joint cavity.
The long-acting slow-release gel capable of being injected into the joint cavity can be used for treating bone joint diseases or improving joint symptoms. Wherein the bone joint disease can comprise knee joint, hip joint, shoulder joint, ankle joint, finger joint injury, osteoarthritis, rheumatoid arthritis, etc.
The invention has the beneficial effects that:
(1) The invention relates to ketorolac tromethamine which is prepared into long-acting slow-release gel capable of being injected into joint cavities for the first time and used for treating osteoarthritis, and aims to reduce the irritation of medicines, reduce systemic adverse reactions, increase the curative effect and the medication safety, and simultaneously have good biocompatibility and in-vivo degradability. Wherein, ketorolac tromethamine adopted in the invention is COX1/2 nonsteroidal anti-inflammatory drug, and can avoid causing gastrointestinal adverse reaction of the digestive tract and toxicity of the liver and the kidney through local administration of the joint cavity. Meanwhile, the long-acting slow-release gel provided by the invention can be injected through the joint cavity, and the joint cavity is a relatively closed space and is relatively safe after local administration, so that the long-acting slow-release gel has higher medicinal safety.
(2) The long-acting slow-release gel capable of being injected into the joint cavity can quickly relieve pain, improve lubrication and protection degree of bone joints for a long time and provide an overall treatment effect. Wherein, the lubrication and protection are mainly the viscoelastic supplement performance of gel, and the medicine release carrier can improve the overall treatment effect of arthritis.
Detailed Description
The technical solutions of the present invention will be clearly and completely described below in conjunction with specific embodiments, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. The following description of at least one exemplary embodiment is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The device comprises viscotester IQ Air parts of a rotor, P35/Ti-01150939 parts of a rotor, 25 ℃ of temperature and 0.1-100/s of shear rate.
Example 1
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
0.75wt% of non-steroidal anti-inflammatory drugs, 2.0wt% of gel matrix, 4.0wt% of stabilizing agents, 0.65wt% of buffering agents and the balance of water, wherein the pH value of the long-acting slow-release gel is 6.8-7.4, the osmotic pressure is 280-350 mOsm/kg, and the shear viscosity is more than 3Pas;
The non-steroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is a mixture of sodium hyaluronate and medical chitosan in a mass ratio of 1:1, the stabilizer is sorbitol, and the buffer is phosphate.
The preparation method of the long-acting slow-release gel capable of being injected into the joint cavity comprises the following steps:
s1, dissolving phosphate in water to obtain a phosphate buffer solution;
S2, dissolving ketorolac tromethamine and sorbitol in a phosphate buffer solution, and stirring for 1-3 hours at 5-50 ℃ to obtain a solution;
S3, adding a gel matrix (sodium hyaluronate and medical chitosan) into the dissolution liquid, stirring for 1-10 hours at 5-50 ℃, supplementing water when the dissolution liquid is completely dissolved into a gel state, and regulating the pH value of the system to be 6.8-7.4;
S4, filtering or wet-heat sterilizing to obtain the long-acting slow-release gel capable of being injected into the joint cavity.
The long-acting slow-release gel can be injected through joint cavities for treating bone joint diseases or improving joint symptoms. Wherein the bone joint disease can comprise knee joint, hip joint, shoulder joint, ankle joint, finger joint injury, osteoarthritis, rheumatoid arthritis, etc.
Example 2
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
1.5wt% of non-steroidal anti-inflammatory drugs, 1.5wt% of gel matrix, 4.0wt% of stabilizing agent, 0.65wt% of buffering agent and the balance of water, wherein the pH value of the long-acting slow-release gel is 7.0+/-0.5, the osmotic pressure is 280-380 mOsm/kg, and the shear viscosity is more than 3Pas;
the non-steroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is a mixture of sodium hyaluronate and medical chitosan in a mass ratio of 1:1, the stabilizer is sorbitol, and the buffer is borate.
Example 3
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
0.75wt% of non-steroidal anti-inflammatory drugs, 1.0wt% of gel matrix, 1.0wt% of stabilizing agent, 0.85wt% of buffering agent and the balance of water, wherein the pH value of the long-acting slow-release gel is 7.0+/-0.5, the osmotic pressure is 280-330 mOsm/kg, and the shear viscosity is more than 8Pas;
Wherein the nonsteroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is sodium hyaluronate, the stabilizer is sorbitol, and the buffer is phosphate.
Example 4
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
0.375wt% of non-steroidal anti-inflammatory drug, 2.0wt% of gel matrix, 4.0wt% of stabilizer, 0.45wt% of buffer and the balance of water, wherein the pH of the long-acting slow-release gel is 7.0+/-0.5, the osmotic pressure is 280-360 mOsm/kg, and the shear viscosity is more than 0.5Pas;
wherein the nonsteroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is medical chitosan, the stabilizer is sorbitol, and the buffer is phosphate.
Example 5
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
0.05wt% of non-steroidal anti-inflammatory drug, 1.0wt% of gel matrix, 0.1wt% of stabilizer, 0.05wt% of buffer and the balance of water, wherein the pH of the long-acting slow-release gel is 7.0+/-0.5;
The non-steroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is non-crosslinked sodium hyaluronate with the molecular weight of 100-10000 kD, the stabilizer is mannitol, and the buffer is a mixture of phosphate and borate.
The preparation method of the long-acting slow-release gel capable of being injected into the joint cavity comprises the following steps:
s1, dissolving phosphate and borate in water to obtain a buffer solution;
S2, adding non-crosslinked sodium hyaluronate into the buffer solution, and stirring for 1-10 hours at 5-50 ℃ until the non-crosslinked sodium hyaluronate is completely dissolved, so as to obtain a gel system;
S3, adding ketorolac tromethamine and mannitol into the gel system, supplementing water, and regulating the pH value of the system to 7.0+/-0.5;
S4, filtering or wet-heat sterilizing to obtain the long-acting slow-release gel capable of being injected into the joint cavity.
Example 6
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
2.0wt% of non-steroidal anti-inflammatory drugs, 1.2wt% of gel matrix, 5.0wt% of stabilizing agent, 1.0wt% of buffering agent and the balance of water, wherein the pH value of the long-acting slow-release gel is 7.0+/-0.5;
the non-steroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is crosslinked sodium hyaluronate, the stabilizer is meglumine, and the buffer is citrate.
Comparative example 1
The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
0.75wt% of non-steroidal anti-inflammatory drug, 1.0wt% of gel matrix, 0.85wt% of buffer and the balance of water, wherein the pH of the long-acting slow-release gel is 7.0+/-0.5;
wherein the nonsteroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is sodium hyaluronate, the buffer is phosphate, and the auxiliary material is sodium chloride.
Comparative example 1 was different from example 3 in that no sorbitol stabilizer was added in comparative example 1, and the rest was the same as example 3.
The addition of sorbitol stabilizer in the invention also has the function of regulating osmotic pressure.
The above-described preferred embodiments of the present invention are only for illustrating the present invention, and are not to be construed as limiting the present invention. Obvious changes and modifications of the invention, which are introduced by the technical solution of the present invention, are still within the scope of the present invention.
Claims (3)
1. The long-acting slow-release gel capable of being injected into joint cavities is characterized by comprising the following components:
1.5wt% of non-steroidal anti-inflammatory drugs, 1.5wt% of gel matrix, 4.0wt% of stabilizing agent, 0.65wt% of buffering agent and the balance of water, wherein the pH value of the long-acting slow-release gel is 7.0+/-0.5, and the osmotic pressure is 280-380 mOsm/kg;
The non-steroidal anti-inflammatory drug is ketorolac tromethamine, the gel matrix is a mixture of sodium hyaluronate and medical chitosan in a mass ratio of 1:1, the stabilizer is sorbitol, and the buffer is borate;
the molecular weight of the sodium hyaluronate is 100-10000 kD, and the molecular weight of the medical sodium hyaluronate is 100-1000 kD.
2. A method of preparing a long-acting slow-release gel for intra-articular injection according to claim 1, wherein the method is used for preparing a long-acting slow-release gel for intra-articular injection according to claim 1, the method comprising the steps of:
s1, dissolving the buffer in water to obtain a buffer solution;
S2, dissolving the nonsteroidal anti-inflammatory drug and the stabilizer in the buffer solution to obtain a dissolution solution;
S3, adding the gel matrix into the dissolution liquid, stirring until the gel matrix is completely dissolved to form a gel state, supplementing water, and regulating the pH value of the system to 7.0+/-0.5;
S4, filtering or wet-heat sterilizing to obtain the long-acting slow-release gel capable of being injected into the joint cavity.
3. A method of preparing a long-acting slow-release gel for intra-articular injection according to claim 1, wherein the method is used for preparing a long-acting slow-release gel for intra-articular injection according to claim 1, the method comprising the steps of:
s1, dissolving the buffer in water to obtain a buffer solution;
S2, adding the gel matrix into the buffer solution, and stirring until the gel matrix is completely dissolved to obtain a gel system;
s3, adding the non-steroidal anti-inflammatory drug and a stabilizer into the gel system, supplementing water, and regulating the pH value of the system to 7.0+/-0.5;
S4, filtering or wet-heat sterilizing to obtain the long-acting slow-release gel capable of being injected into the joint cavity.
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| KR20180128121A (en) * | 2017-05-22 | 2018-12-03 | 동국제약 주식회사 | Pharmaceutical composition comprising hyaluronic acid and non-steroidal anti-inflammatory drug and preparation method thereof |
| CN114432240A (en) * | 2022-03-04 | 2022-05-06 | 郑州市中心医院 | Stable non-irritating ketorolac tromethamine injection and preparation method thereof |
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| KR20180128121A (en) * | 2017-05-22 | 2018-12-03 | 동국제약 주식회사 | Pharmaceutical composition comprising hyaluronic acid and non-steroidal anti-inflammatory drug and preparation method thereof |
| CN114432240A (en) * | 2022-03-04 | 2022-05-06 | 郑州市中心医院 | Stable non-irritating ketorolac tromethamine injection and preparation method thereof |
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