CN112107591A - Liquid-solid composite lubricant in joints and preparation method thereof - Google Patents
Liquid-solid composite lubricant in joints and preparation method thereof Download PDFInfo
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- CN112107591A CN112107591A CN202010876445.1A CN202010876445A CN112107591A CN 112107591 A CN112107591 A CN 112107591A CN 202010876445 A CN202010876445 A CN 202010876445A CN 112107591 A CN112107591 A CN 112107591A
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- caryophyllene
- joint
- sodium hyaluronate
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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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
- A61K9/0012—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
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- 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
Abstract
The invention belongs to the technical field of biomedical engineering, and particularly relates to an intra-articular liquid-solid composite lubricant and a preparation method thereof, wherein the preparation method comprises the following steps: adding the caryophyllene into sodium hyaluronate to make the concentration be 20-50 mug/ml, and carrying out ultrasonic treatment for 0.5-2h at 15-60 ℃ to uniformly disperse the caryophyllene. The lubricant disclosed by the invention is safe and reliable, has a good cartilage injury resisting effect, forms a uniform lubricating film on the surface of a joint, effectively reduces the friction injury of the joint, increases the joint movement and recovers the knee joint function. Meanwhile, the caryophyllene can stably exist in the joint cavity in a living body for a long time, has super strong adsorbability and good biocompatibility, has adsorption and slow release effects on sodium hyaluronate, slows down the consumption of the sodium hyaluronate, and the sodium hyaluronate can protect articular cartilage and obviously reduce local symptoms of knee joints. The number of injections is significantly reduced. The original continuous injection once a week for 5 weeks is changed into the minimum one-time injection, so that the pain of multiple injections is relieved.
Description
Technical Field
The invention relates to the technical field of biomedical engineering, in particular to an intra-articular liquid-solid composite lubricant and a preparation method thereof.
Background
Osteoarthritis is also called degenerative arthritis, and is a chronic disease, the main pathological changes are degeneration of articular cartilage and secondary hyperosteogeny, and the osteoarthritis is often seen in middle-aged and elderly people, while women are more than men, and the osteoarthritis is better at load-bearing joints.
The treatment methods are more, and non-operative treatment is generally adopted in the early stage. The traditional treatment mainly comprises non-steroidal anti-inflammatory drugs (NASIDS), but the long-term administration of the traditional treatment easily causes damage to the stomach, intestine and kidney. At present, sodium hyaluronate injection in joint cavities is a common method for treating osteoarthritis, however, in the clinical practice process, people think that the natural joint synovial fluid cannot be completely replaced by the pure sodium hyaluronate injection treatment, and the knee joint gradually consumes the sodium hyaluronate in long-term use, so that the relapse is caused.
In order to improve the existing treatment method, the related clinical research proposes that acupuncture, traditional Chinese medicine manipulations and exercise training are combined with sodium hyaluronate intra-articular injection treatment to make up for the defect of pure sodium hyaluronate intra-articular injection treatment, which is the superposition of the number of treatment means, but the improvement on injection materials is not carried out. With the development of natural science and technology, related clinical researches propose that the injection material is improved to a certain extent by applying ozone or astragalus injection and sodium hyaluronate in intra-articular injection, but the friction reducing effect of the liquid lubricant is not obvious when the joint surface is loaded and extruded. Thus, liquid lubricants are not effective in reducing frictional cartilage damage under load conditions.
Disclosure of Invention
Based on the prior technical problem, the invention provides a preparation method of a liquid-solid composite lubricant in joints.
The invention provides a preparation method of a liquid-solid composite lubricant in joints, which comprises the following steps: adding the caryophyllene into sodium hyaluronate to enable the concentration to be 20-50 mu g/ml, and carrying out ultrasonic treatment for 0.5-2h at the temperature of 15-60 ℃ to enable the caryophyllene to be uniformly dispersed, wherein the outer surface of the caryophyllene is in a laminated shape, the purity of the caryophyllene is 99.9-99.999%, the particle size is 30-120 nm, and the molecular weight of the sodium hyaluronate is 50-220 ten thousand.
Preferably, the intra-articular liquid-solid composite lubricant prepared by the above method.
The beneficial effects of the invention are as follows:
1. the lubricant disclosed by the invention is safe and reliable, has a good cartilage injury resisting effect, forms a uniform lubricating film on the surface of a joint, effectively reduces the friction injury of the joint, increases the joint movement and recovers the knee joint function. Meanwhile, the caryophyllene can stably exist in the joint cavity in a living body for a long time, has super strong adsorbability and good biocompatibility, has adsorption and slow release effects on sodium hyaluronate, slows down the consumption of the sodium hyaluronate, can protect articular cartilage, obviously reduces the local symptoms of knee joints, and obviously reduces the injection times. The original continuous injection once a week for 5 weeks is changed into the minimum one-time injection, so that the pain of multiple injections is relieved.
Drawings
FIG. 1 is a first day microscopic view of a method of preparing an intra-articular liquid-solid composite lubricant according to the present invention;
FIG. 2 is a second day microscopic view of a method of preparing an intra-articular liquid-solid composite lubricant according to the present invention;
FIG. 3 is a microscope photograph of a third day showing a method for preparing the intra-articular liquid-solid composite lubricant according to the present invention;
FIG. 4 is a fourth day microscopic observation of a method of preparing an intra-articular liquid-solid composite lubricant according to the present invention;
FIG. 5 is a microscope photograph of a fifth day of the method of preparing the intra-articular liquid-solid composite lubricant according to the present invention;
FIG. 6 is a microscope photograph of the sixth day of the present invention for the preparation of a liquid solid composite lubricant for use in joints.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Referring to fig. 1-6, a method for preparing a liquid-solid composite lubricant in a joint includes the following steps: adding the caryophyllene into sodium hyaluronate to enable the concentration to be 20-50 mu g/ml, and carrying out ultrasonic treatment for 0.5-2h at the temperature of 15-60 ℃ to enable the caryophyllene to be uniformly dispersed, wherein the outer surface of the caryophyllene is in a laminated shape, the purity of the caryophyllene is 99.9-99.999%, the particle size is 30-120 nm, and the molecular weight of the sodium hyaluronate is 50-220 ten thousand.
The first embodiment is as follows:
a preparation method of a liquid-solid composite lubricant in joints is characterized by comprising the following steps: the method comprises the following steps: preparing the caryophyllene by an improved Hummers method, wherein the caryophyllene is lamellar, the particle size is about 90nm, and the purity is 99.99%;
adding the caryophyllene into sodium hyaluronate with the molecular weight of 150 ten thousand to enable the concentration to be 30 mu g/ml, carrying out ultrasonic treatment for 0.5h at the temperature of 60 ℃ to enable the caryophyllene to be uniformly dispersed, and balancing a composite lubricant to 25 ℃ for later use;
male SD rats, weighing 200 ± 10g, purchased from shanchuan red laboratory animals science and technology limited, tianjin, with license number SCXK (jin) 2009-0001, production lot number: 20120617, selecting healthy male SD rats, anesthetizing with 0.3 g.kg body weight ip 10% chloral hydrate, loading 4% papain into 35% poloxamer carrier to prepare temperature sensitive in-situ gel controlled release agent, injecting from knee joint at both sides according to 0.05ml (1.6U)/joint dosage, acting at 50 deg.C for 2 hr, randomly extracting 3/10 rats for histopathological examination, rechecking the reliability and success rate of the method, obtaining molded articular cartilage slices,
1ml of the intra-articular liquid-solid composite lubricant prepared in the embodiment is extracted and injected into the knee joint of a mouse suffering from osteoarthritis, the gait of the mouse is still almost normal when observed 30 days after treatment, the knee joint cartilage of the mouse is taken as a pathological section, and the section shows that a large amount of caryophyllene is still adsorbed on the cartilage surface of the knee joint of the mouse.
Example two:
a preparation method of a liquid-solid composite lubricant in joints comprises the following steps: preparing caryophyllene by an Offeman method, wherein the caryophyllene is lamellar, the particle size is about 110nm, and the purity is 99.9%;
adding the caryophyllene into sodium hyaluronate with the molecular weight of 80 ten thousand to enable the concentration to be 50 mu g/ml, carrying out ultrasonic treatment for 1h at the temperature of 20 ℃ to enable the caryophyllene to be uniformly dispersed, and balancing the composite lubricant to 25 ℃ for later use;
male SD rats, weighing 200 ± 10g, purchased from shanchuan red laboratory animals science and technology limited, tianjin, with license number SCXK (jin) 2009-0001, production lot number: 20120617, selecting healthy male SD rats, anesthetizing with 0.3 g.kg body weight ip 10% chloral hydrate, loading 4% papain with 35% poloxamer carrier to prepare temperature-sensitive in-situ gel controlled release agent, injecting from knee joints at both sides according to 0.05ml (1.6U)/joint dose, acting at 50 deg.C for 2 hr, randomly extracting 3/10 rats for histopathological examination, and rechecking the reliability and success rate of the method;
1.5ml of the intra-articular liquid-solid composite lubricant prepared in the embodiment is extracted and injected into the knee joint of a mouse suffering from osteoarthritis, the gait of the mouse is still almost normal observed 60 days after treatment, the knee joint cartilage of the mouse is taken as a pathological section, and the section shows that a large amount of caryophyllene is still adsorbed on the cartilage surface of the knee joint of the mouse.
Example three:
a preparation method of a liquid-solid composite lubricant in joints comprises the following steps:
purchasing nontoxic caryophyllene, wherein the caryophyllene is lamellar, the particle size is about 120nm, and the purity is 99.999%;
adding the caryophyllene into sodium hyaluronate with the molecular weight of 220 ten thousand to enable the concentration to be 20 mu g/ml, carrying out ultrasonic treatment for 2 hours at the temperature of 15 ℃ to enable the caryophyllene to be uniformly dispersed, and balancing the composite lubricant to 25 ℃ for later use;
male SD rats, weighing 200 ± 10g, purchased from shanchuan red laboratory animals science and technology limited, tianjin, with license number SCXK (jin) 2009-0001, production lot number: 20120617, selecting healthy male SD rats, anesthetizing with 0.3 g.kg body weight ip 10% chloral hydrate, loading 4% papain with 35% poloxamer carrier to prepare temperature-sensitive in-situ gel controlled release agent, injecting from knee joints at both sides according to 0.05ml (1.6U)/joint dose, acting at 50 deg.C for 2 hr, randomly extracting 3/10 rats for histopathological examination, and rechecking the reliability and success rate of the method;
1ml of the intra-articular liquid-solid composite lubricant prepared in the embodiment is extracted and injected into the knee joint of a mouse suffering from osteoarthritis, the gait of the mouse is still almost normal when observed 90 days after treatment, the knee joint cartilage of the mouse is taken as a pathological section, and the section shows that a large amount of caryophyllene is still adsorbed on the cartilage surface of the knee joint of the mouse.
Example four:
a preparation method of a liquid-solid composite lubricant in joints comprises the following steps:
purchasing nontoxic caryophyllene, wherein the caryophyllene is lamellar, the particle size is about 30nm, and the purity is 99.99%;
adding the caryophyllene into sodium hyaluronate with the molecular weight of 50 ten thousand to enable the concentration to be 40 mu g/ml, carrying out ultrasonic treatment for 0.5h at the temperature of 40 ℃ to enable the caryophyllene to be uniformly dispersed, and balancing a composite lubricant to 30 ℃ for later use;
male SD rats, weighing 200 ± 10g, purchased from shanchuan red laboratory animals science and technology limited, tianjin, with license number SCXK (jin) 2009-0001, production lot number: 20120617. selecting healthy male SD rats, anesthetizing with 0.3 g.kg body weight ip 10% chloral hydrate, loading 4% papain with 35% poloxamer carrier to prepare temperature-sensitive in-situ gel controlled release agent, injecting from knee joints at both sides according to 0.05ml (1.6U)/joint dose, acting at 50 deg.C for 2 hr, randomly extracting 3/10 rats for histopathological examination, and rechecking the reliability and success rate of the method;
1.5ml of the intra-articular liquid-solid composite lubricant prepared in the embodiment is extracted and injected into the knee joint of a mouse suffering from osteoarthritis, the gait of the mouse is still almost normal when observed 60 days after treatment, the knee joint cartilage of the mouse is taken as a pathological section, and the section shows that a large amount of caryophyllene is still adsorbed on the cartilage surface of the knee joint of the mouse.
Experiments prove that the caryophyllene in the liquid solid composite lubricant for joints can not be extruded out of the joint surface under the load condition and can be effectively attached to the joint surface to play a lubricating effect.
After the liquid solid composite lubricant in the joint is balanced to 25-30 ℃, the liquid solid composite lubricant is extracted and injected into the joint cavity under the aseptic condition, the caryophyllene has super-strong adsorbability, can be adsorbed on the joint surface for a long time after being injected into the joint, is not reduced along with the metabolism of the liquid lubricant, and plays a role in lubricating bone joints. The absorption and slow release effects of the caryophyllene on the sodium hyaluronate slow down the consumption of the sodium hyaluronate, prolong the injection period of patients, or reduce the injection times within a certain time. The compound lubricant is used, the injection period is 1 month and 1 time, and 1-3 times are a treatment course.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (2)
1. A preparation method of a liquid-solid composite lubricant in joints is characterized by comprising the following steps: the method comprises the following steps: adding the caryophyllene into sodium hyaluronate to enable the concentration to be 20-50 mu g/ml, and carrying out ultrasonic treatment for 0.5-2h at the temperature of 15-60 ℃ to enable the caryophyllene to be uniformly dispersed, wherein the outer surface of the caryophyllene is in a laminated shape, the purity of the caryophyllene is 99.9-99.999%, the particle size is 30-120 nm, and the molecular weight of the sodium hyaluronate is 50-220 ten thousand.
2. An intra-articular liquid-solid composite lubricant prepared by the process of claim 1.
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| CN202010876445.1A CN112107591A (en) | 2020-08-27 | 2020-08-27 | Liquid-solid composite lubricant in joints and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103534205A (en) * | 2011-03-15 | 2014-01-22 | 绝世环球有限责任公司 | Facile synthesis of graphene, graphene derivatives and abrasive nanoparticles, and their various uses, including as tribologically-beneficial lubricant additives |
| CN104383607B (en) * | 2014-11-21 | 2016-06-08 | 天津中医药大学第一附属医院 | A kind of intraarticular liquid solid compounded lubricant and preparation method |
| CN106565405A (en) * | 2016-11-09 | 2017-04-19 | 天津大学 | Preparation method for hydrated nanometer corannulene with controllable particle size |
| CN107141243A (en) * | 2017-06-27 | 2017-09-08 | 厦门大学 | The nitrogenous cyclosubstituted bowl alkene molecule of one five yuan of class and derivative and its preparation and application |
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2020
- 2020-08-27 CN CN202010876445.1A patent/CN112107591A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103534205A (en) * | 2011-03-15 | 2014-01-22 | 绝世环球有限责任公司 | Facile synthesis of graphene, graphene derivatives and abrasive nanoparticles, and their various uses, including as tribologically-beneficial lubricant additives |
| CN104383607B (en) * | 2014-11-21 | 2016-06-08 | 天津中医药大学第一附属医院 | A kind of intraarticular liquid solid compounded lubricant and preparation method |
| CN106565405A (en) * | 2016-11-09 | 2017-04-19 | 天津大学 | Preparation method for hydrated nanometer corannulene with controllable particle size |
| CN107141243A (en) * | 2017-06-27 | 2017-09-08 | 厦门大学 | The nitrogenous cyclosubstituted bowl alkene molecule of one five yuan of class and derivative and its preparation and application |
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