CN109481739A - Bone joint lubricant and preparation method thereof - Google Patents
Bone joint lubricant and preparation method thereof Download PDFInfo
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- CN109481739A CN109481739A CN201811520963.9A CN201811520963A CN109481739A CN 109481739 A CN109481739 A CN 109481739A CN 201811520963 A CN201811520963 A CN 201811520963A CN 109481739 A CN109481739 A CN 109481739A
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- parts
- lubricant
- microgel
- joints
- bones
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- 239000000314 lubricant Substances 0.000 title claims abstract description 29
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 12
- 239000008367 deionised water Substances 0.000 claims abstract description 9
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 9
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 8
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 5
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 5
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims abstract description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 125000005385 peroxodisulfate group Chemical group 0.000 claims description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 239000004530 micro-emulsion Substances 0.000 claims description 5
- 239000000178 monomer Substances 0.000 claims description 5
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 4
- 229960001231 choline Drugs 0.000 claims description 4
- FIKFOOMAUXPBJM-UHFFFAOYSA-N hepta-2,5-dienediamide Chemical class NC(=O)C=CCC=CC(N)=O FIKFOOMAUXPBJM-UHFFFAOYSA-N 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 230000026731 phosphorylation Effects 0.000 claims description 4
- 238000006366 phosphorylation reaction Methods 0.000 claims description 4
- 239000003643 water by type Substances 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 150000004985 diamines Chemical class 0.000 claims 1
- 230000001050 lubricating effect Effects 0.000 abstract description 5
- 230000008093 supporting effect Effects 0.000 abstract description 3
- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 abstract 1
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 abstract 1
- 239000012935 ammoniumperoxodisulfate Substances 0.000 abstract 1
- 229920002635 polyurethane Polymers 0.000 abstract 1
- 239000004814 polyurethane Substances 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 229920002385 Sodium hyaluronate Polymers 0.000 description 14
- 229940010747 sodium hyaluronate Drugs 0.000 description 14
- 238000012360 testing method Methods 0.000 description 6
- 229920002946 poly[2-(methacryloxy)ethyl phosphorylcholine] polymer Polymers 0.000 description 5
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 210000000629 knee joint Anatomy 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000007863 gel particle Substances 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000012726 Water-in-Oil Emulsion Polymerization Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
Classifications
-
- 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
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L31/145—Hydrogels or hydrocolloids
-
- 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
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F230/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
- C08F230/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing phosphorus
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/452—Lubricants
-
- 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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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention provides a bone joint lubricant, which is microgel prepared from the following components in percentage by weight: 13-20 parts of 2-methacryloyloxyethyl phosphorylcholine; 6-10 parts of methylene bisacrylamide; 170-256 parts of Tween 80, 159-239 parts of Span 80, 2.4-3.7 parts of ammonium peroxodisulfate, 12-19 parts of tetramethylethylenediamine, 4000-6000 parts of deionized water and 5238-7858 parts of hexane. The bone joint lubricant prepared by the invention has good shear thinning property. The viscosity is higher without the action of force; under the action of force, the viscosity of the modified polyurethane can be reduced along with the increase of the shear rate. It is speculated that the microgel has good supporting effect when the patient is at rest, and has lower viscosity and lower friction when the patient walks, so that the microgel has more durable and stronger lubricating effect. The injectable microgel prepared by the method can be used as a new choice for interventional therapy of patients with early osteoarthritis.
Description
Technical field
The present invention relates to biomedical materials fields, and in particular to a kind of Bones and joints lubricant and preparation method thereof.
Background technique
Osteoarthritis is the common disease on Orthopedic Clinical, and knee joint is one of the position most often involved.Due to knee joint
It is the main weight-bearing joints of body, therefore knee joint osseous arthritis can lead to the more serious dysfunction of patient.Sodium hyaluronate is
The common selection for the treatment of early stage Osteoarthritis at present, but since it can be degraded in vivo by hyaluronidase quickly, so right
The lubricating action in joint is limited, and therapeutic effect is undesirable.
Therefore, one kind new high lubricating effect, good biocompatibility and not degradable joint lubrication agent are studied to treatment
Osteoarthritis is of great significance.
Summary of the invention
The object of the present invention is to provide a kind of Bones and joints lubricants and preparation method thereof.
The present invention provides a kind of Bones and joints lubricants, it is the microgel being prepared by the component of following weight ratio:
13~20 parts of 2- methylacryoyloxyethyl phosphorylation choline；6~10 parts of methylene-bisacrylamides；170~256
Part 80,159~239 parts of Tween, 80,2.4~3.7 parts of Span peroxo disulfate acid ammonium, 12~19 parts of tetramethylethylenediamines, 4000
~6000 parts of deionized waters, 5238~7858 parts of hexanes.
Further, aforementioned Bones and joints lubricant is the microgel being prepared by the component of following weight ratio:
16.4 parts of 2- methylacryoyloxyethyl phosphorylation choline, 7.7 parts of methylene-bisacrylamides, 221.8 parts of Tween
80,198.8 parts of Span, 80,3.012 parts of peroxo disulfate acid ammoniums, 15.5 parts of tetramethylethylenediamines, 5000 parts of deionized waters, 6548
Part hexane.
Further, the partial size of particle is 4~10 μm in the microgel.
The present invention also provides a kind of methods for preparing Bones and joints lubricant above-mentioned, it includes the following steps:
(1) each component of weight proportion is weighed；
(2) 2- methylacryoyloxyethyl phosphocholine and methylene-bisacrylamide are dissolved in deionized water, are formed
Water phase；Tween 80 and Span 80 are dissolved in hexane, oily phase is formed, water phase and oil is mixed, are vigorously stirred, after ultrasound
Obtain micro emulsion；
(3) purification for argon flask is used at normal temperature, after so that micro emulsion is deaerated, is separately added into peroxo disulfate acid ammonium and tetramethyl
The emulsion of acquisition is stirred at room temperature overnight by base ethylenediamine；
(4) after n-hexane evaporation, polymeric micro-gel is washed with deionized water and tetrahydrofuran, to remove extra monomer
With surfactant to get.
Further, in the step (2), being vigorously stirred the time is 5min.
Further, in the step (2), ultrasonic time 30min.
The present invention also provides application of the Bones and joints lubricant above-mentioned in the lubricant of preparation treatment Osteoarthritis.
Further, the Osteoarthritis is early stage Osteoarthritis.
Bones and joints lubricant prepared by the present invention has good shear thinning behavior.Viscosity is higher under the action of not stressing；
Under the action of stress, viscosity can be reduced with the increase of shear rate.Microgel tool in patient at rest can be speculated accordingly
There is good supporting role, and have lower viscosity in patient's walking, reduce friction, to have more longlasting, more potent
Lubricating action.The syringeability microgel of the method preparation can be used as one kind of early stage osteoarthritis patient's Clinical intervention
New selection.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, modification, replacement or the change of more other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Detailed description of the invention
Fig. 1 is the diagram of polymeric micro-gel polymerization process of the present invention.
Fig. 2 is the optical microscope picture of polymeric micro-gel suspension of the present invention.
Fig. 3 is the particle diameter distribution of polymeric micro-gel of the present invention.
Fig. 4 is the shear thinning behavior in polymeric micro-gel suspension of the present invention, sodium hyaluronate suspension and deionized water.
Specific embodiment
The preparation method of the Bones and joints lubricant of the present invention of experimental example 1
It is ampholytic monomer with 2- methylacryoyloxyethyl phosphocholine (MPC), methylene-bisacrylamide (MBA) is to hand over
Join agent, peroxo disulfate acid ammonium (APS) is polymerization initiator, tetramethylethylenediamine (TMEDA) is catalyst.The synthesis of microgel exists
It is carried out in the water phase of water-in-oil emulsion, as shown in Figure 1.
16.4mg ampholytic monomer and 7.7mg crosslinking agent are dissolved in 5mL deionized water, water phase is formed；By 0.2mL's
The Span 80 of Tween 80 and 0.2mL is dissolved in the hexane of 10mL, forms oily phase.Water phase and oil are mixed in 100mL flask
In, it is vigorously stirred 5min, and ultrasound 30min, forms micro emulsion.Purification for argon flask is used at normal temperature, so that solution is deaerated, so
It is separately added into the TMEDA of APS and 0.02mL that 0.06mL concentration is 0.22mol/L afterwards.The emulsion of acquisition is stirred at room temperature
Overnight.After n-hexane is evaporated, washed polymeric micro-gel (PMPC) each 3 times with water and tetrahydrofuran respectively, with remove monomer and
Surfactant is to get Bones and joints lubricant of the present invention.
The preparation of 1 sodium hyaluronate suspension of comparative example
Crosslinking agent using divinyl sulfone (DVS) as sodium hyaluronate.
Using the NaOH solution of 0.1mol/L as raw material, 3% (w/v) NaCl is added and is made molten under conditions of being stirred continuously
Liquid；Hyaluronic Acid sodium powder is added in the solution and is prepared into the suspension that sodium hyaluronate concentration is 2% (w/v), the DVS added is to glass
Sour sodium is crosslinked, and sodium hyaluronate suspension is obtained.Wherein the mass ratio of sodium hyaluronate and DVS are 100:1.
Beneficial effects of the present invention are proved with the mode of test example below:
The pattern of the Bones and joints lubricant of the present invention of test example 1
1, test method
The joint lubrication agent being prepared is centrifuged 10min under the revolving speed of 3000rpm, collects micro-gel particles, is utilized
Optical microscopy obtains image, carries out image procossing using Image J, and measure micro-gel particles diameter, and statistic diameters point
Cloth.
2, test result
The present invention is prepared for a kind of transparent microgel, microgel optical imagery and partial size using water-in-oil emulsion polymerization
Distribution is as shown in Figures 2 and 3.By Fig. 2 and Fig. 3 it is found that the partial size of particle is mainly distributed on 4~10 μm in microgel.
The rheology analysis of the Bones and joints lubricant of the present invention of test example 2
1, test method
Using DV-II rheometer (Brookfield, Middleboro, MA) measure Bones and joints lubricant viscosity of the present invention and
The relationship of shear rate, using comparative example 1 prepare sodium hyaluronate suspension and deionized water as compare.
2, test result
The rheological property of Bones and joints lubricant of the present invention, control group sodium hyaluronate suspension and deionized water is as shown in Figure 4.
As shown in Figure 4, shear thinning behavior is presented in Bones and joints lubricant and sodium hyaluronate suspension of the present invention, i.e., with the increasing of shear rate
Add, viscosity reduces.At low shear rates, the viscosity of PMPC microgel prepared by the present invention is apparently higher than sodium hyaluronate suspension
The viscosity of liquid；And at high shear rates, the viscosity of sodium hyaluronate suspension is concentrated as in 142.7 ± 4.9cP, PMPC microgel
Suspension becomes 125.7 ± 4.0cP, and sodium hyaluronate suspension viscosity ratio PMPC microgel is high by 13% (p=0.003, ANOVA), and
The concentration ratio PMPC microgel suspension of the sodium hyaluronate suspension of 2% mass ratio (w/v) is 35 times low after crosslinking.Test result table
Bright, Bones and joints lubricant prepared by the present invention has good shear thinning behavior.
To sum up, Bones and joints lubricant prepared by the present invention has good shear thinning behavior.Viscosity under the action of not stressing
It is higher；Under the action of stress, viscosity can be reduced with the increase of shear rate.The microgel can be speculated in patient at rest accordingly
When there is good supporting role, and have lower viscosity in patient's walking, reduce friction, to have more longlasting, more
Potent lubricating action.The syringeability microgel of the method preparation can be used as early stage osteoarthritis patient's Clinical intervention
A kind of new selection.
Claims (8)
1. a kind of Bones and joints lubricant, it is characterised in that: it is the microgel being prepared by the component of following weight ratio:
13~20 parts of 2- methylacryoyloxyethyl phosphorylation choline；6~10 parts of methylene-bisacrylamides；170~256 parts
80,159~239 parts of Tween, 80,2.4~3.7 parts of Span peroxo disulfate acid ammonium, 12~19 parts of tetramethylethylenediamines, 4000~
6000 parts of deionized waters, 5238~7858 parts of hexanes.
2. Bones and joints lubricant according to claim 1, it is characterised in that: it be by following weight ratio component preparation and
At microgel:
16.4 parts of 2- methylacryoyloxyethyl phosphorylation choline, 7.7 parts of methylene-bisacrylamides, 221.8 parts of Tween 80,
198.8 parts of Span, 80,3.012 parts of peroxo disulfate acid ammoniums, 15.5 parts of tetramethylethylenediamines, 5000 parts of deionized waters, 6548 parts oneself
Alkane.
3. Bones and joints lubricant according to claim 1 or 2, it is characterised in that: the partial size of particle is 4 in the microgel
~10 μm.
4. a kind of method for preparing Bones and joints lubricant described in claims 1 to 3 any one, it is characterised in that: it includes
Following steps:
(1) each component of weight proportion is weighed；
(2) 2- methylacryoyloxyethyl phosphocholine and methylene-bisacrylamide are dissolved in deionized water, form water phase；
Tween 80 and Span 80 are dissolved in hexane, oily phase is formed, water phase and oil is mixed, are vigorously stirred, micro emulsion is obtained after ultrasound
Shape liquid；
(3) purification for argon flask is used at normal temperature, after so that micro emulsion is deaerated, is separately added into peroxo disulfate acid ammonium and tetramethyl second
The emulsion of acquisition is stirred at room temperature overnight by diamines；
(4) after n-hexane evaporation, polymeric micro-gel is washed with deionized water and tetrahydrofuran, to remove extra monomer and table
Face activating agent to get.
5. according to the method described in claim 4, it is characterized by: being vigorously stirred the time is 5min in the step (2).
6. according to the method described in claim 4, it is characterized by: in the step (2), ultrasonic time 30min.
7. Bones and joints lubricant described in claims 1 to 3 any one is in the lubricant of preparation treatment Osteoarthritis
Using.
8. application according to claim 7, it is characterised in that: the Osteoarthritis is early stage Osteoarthritis.
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