CN111110845A - Novel shock wave treatment coupling agent with anti-inflammatory and analgesic effects and preparation method thereof - Google Patents
Novel shock wave treatment coupling agent with anti-inflammatory and analgesic effects and preparation method thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
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- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 5
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0047—Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- 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
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- 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]
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Abstract
The invention discloses a novel coupling agent with anti-inflammatory and analgesic effects for shock wave treatment, wherein the coupling agent adopts a drug-loaded hyaluronic acid nano microemulsion, and the loaded drug is a non-steroidal anti-inflammatory drug. Also discloses a preparation method of the novel coupling agent with the functions of diminishing inflammation and easing pain for shock wave treatment. The modified drug-loaded hyaluronic acid nano microemulsion is prepared by utilizing the characteristics of good transdermal absorption, moisture preservation and lubrication of hyaluronic acid, can be used as a coupling agent for in vitro shock waves, and can be matched with the shock waves, so that the transdermal absorption effect of anti-inflammatory drugs wrapped in the hyaluronic acid nano microemulsion is improved under the action of the shock wave energy, the anti-inflammatory effects of shock wave treatment and transdermal drug delivery treatment are obviously improved, the operation is simple, and the clinical curative effect is obvious.
Description
Technical Field
The invention relates to the field of medical coupling agents, in particular to a novel shock wave treatment coupling agent with anti-inflammatory and analgesic effects and a preparation method thereof.
Background
The External Shock Wave (ESW) is a sound wave that can transmit energy and has more characteristics than ultrasonic waves, and acts on human tissues through its mechanical effect, cavitation effect and thermal effect. When in treatment, the shock wave transmits the sound wave energy to target cells in a human body through the treatment probe and the couplant, and then the treatment probe is positioned and moved to act on a wider area where human body pain occurs.
The existing coupling agent has a lubricating effect, so that the friction between the probe surface and the skin is reduced; secondly, gaps between the treatment probe and the skin of the patient are filled, so that trace air in the gaps does not influence the penetration of sound waves; and thirdly, the acoustic impedance difference between the probe and the skin is reduced through the transition effect of the couplant, so that the reflection loss of the sound wave energy at the interface is reduced. But do not have a therapeutic effect.
Transdermal drug delivery can avoid many disadvantages caused by traditional methods such as oral drug delivery and intravenous injection, and has the advantages of increasing patient compliance, avoiding liver first pass effect, and maintaining stable and effective drug delivery concentration for a long time. However, the skin barrier function of the Stratum Corneum (SC) imposes strict requirements on the pharmaceutical formulation and the absorption rate of the drug is low.
The inventor creates a novel shock wave treatment coupling agent with anti-inflammatory and analgesic effects and a preparation method thereof on the basis of the prior art, so that the coupling agent also has anti-inflammatory treatment effects, can enhance the transdermal absorption effect of anti-inflammatory drugs while realizing shock wave treatment, and comprehensively improves the clinical treatment effect.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a novel coupling agent for shock wave treatment with anti-inflammatory and analgesic effects, so that the coupling agent has an anti-inflammatory treatment effect, can enhance the transdermal absorption effect of anti-inflammatory drugs while realizing shock wave treatment, and comprehensively improves the clinical curative effect.
In order to solve the technical problems, the invention provides a novel coupling agent with anti-inflammatory and analgesic effects for shock wave treatment, wherein the coupling agent adopts a drug-loaded hyaluronic acid nano microemulsion, and a non-steroidal anti-inflammatory drug is loaded in the drug-loaded hyaluronic acid nano microemulsion.
Further improved, the preparation method of the drug-loaded hyaluronic acid nano microemulsion comprises the following steps:
(1) respectively dissolving hyaluronic acid and N-N 'cyclohexyl carbodiimide in a phosphate buffer solution (pH is 7.3-7.4), mixing and stirring the solution for 2-5h to form an A solution, wherein the molar ratio of the hyaluronic acid to the N-N' cyclohexyl carbodiimide is 1: 1-1.2;
(2) preparing an acetone solution containing glycerol monostearate to form a solution B;
(3) dropwise adding the solution A into the solution B at the speed of 1 drop/second by using a peristaltic pump, reacting at the temperature of 32-38 ℃ for 10-14h with the molar ratio of the hyaluronic acid to the glycerol monostearate being 1:1-1.5, centrifuging to obtain a precipitate, dialyzing, purifying and freeze-drying to form HA-GMS powder;
(4) dissolving the HA-GMS powder and the non-steroidal anti-inflammatory drug in deionized water according to the mass ratio of 1:1-2 to form a solution C, sequentially dripping Tween-80 and D- α -tocopheryl polyethylene glycol 1000 succinate into the solution C, magnetically stirring until uniformly mixing, performing ultrasonic treatment for 20-40s to form a hyaluronic acid nano microsphere solution wrapping the non-steroidal anti-inflammatory drug, then slowly dripping a trehalose dispersing agent, continuously stirring for 20-40min, and performing low-temperature ultrasonic treatment for 3-7min to obtain the drug-loaded hyaluronic acid nano microemulsion.
In a further improvement, the non-steroidal anti-inflammatory drug adopts diclofenac sodium, ibuprofen, aspirin or indometacin.
The invention also provides a preparation method of the novel shock wave treatment couplant with the functions of diminishing inflammation and easing pain, and the preparation method of the shock wave couplant comprises the following steps:
(1) respectively dissolving hyaluronic acid and N-N 'cyclohexyl carbodiimide in a phosphate buffer solution (pH is 7.3-7.4), mixing and stirring the solution for 2-5h to form an A solution, wherein the molar ratio of the hyaluronic acid to the N-N' cyclohexyl carbodiimide is 1: 1-1.2;
(2) preparing an acetone solution containing glycerol monostearate to form a solution B;
(3) dropwise adding the solution A into the solution B at the speed of 1 drop/second by using a peristaltic pump, reacting at the temperature of 32-38 ℃ for 10-14h with the molar ratio of the hyaluronic acid to the glycerol monostearate being 1:1-1.5, centrifuging to obtain a precipitate, dialyzing, purifying and freeze-drying to form HA-GMS powder;
(4) dissolving the HA-GMS powder and the non-steroidal anti-inflammatory drug in deionized water according to the mass ratio of 1:1-2 to form a solution C, sequentially dripping Tween-80 and D- α -tocopheryl polyethylene glycol 1000 succinate into the solution C, magnetically stirring until uniformly mixing, performing ultrasonic treatment for 20-40s to form a hyaluronic acid nano microsphere solution wrapping the non-steroidal anti-inflammatory drug, then slowly dripping a trehalose dispersing agent, continuously stirring for 20-40min, and performing low-temperature ultrasonic treatment for 3-7min to obtain the shock wave coupling agent.
In a further improvement, the non-steroidal anti-inflammatory drug adopts diclofenac sodium, ibuprofen, aspirin or indometacin.
After adopting such design, the invention has at least the following advantages:
1. the hyaluronic acid is prepared into the drug-loaded nano microemulsion by utilizing the characteristics of good transdermal absorption, moisture preservation and lubrication of the hyaluronic acid, so that the hyaluronic acid not only can be used as a coupling agent for an in-vitro shock wave treatment probe, but also can be matched with shock waves, so that the transdermal absorption effect of anti-inflammatory drugs wrapped in the hyaluronic acid is improved under the action of the shock waves, the anti-inflammatory effects of shock wave treatment and transdermal drug delivery treatment are better realized, the operation is simple, and the curative effect is obvious.
2. According to the preparation method of the drug-loaded hyaluronic acid nano microemulsion, the hyaluronic acid is modified by the glycerol monostearate, so that the modified hyaluronic acid nano microemulsion with better stability and proper mechanical strength is obtained, the modified hyaluronic acid nano microemulsion can resist a certain shock wave effect, the hyaluronic acid nano microspheres are promoted to move towards deep tissues of a human body under the action of smaller shock waves, and when the shock waves are gradually increased, the nano microspheres can be mediated to break, so that the drug wrapped by the hyaluronic acid nano microemulsion is released in the deep tissues of the human body, the transdermal effect of the drug is improved, and the purpose of treating inflammation is achieved.
Drawings
The foregoing is only an overview of the technical solutions of the present invention, and in order to make the technical solutions of the present invention more clearly understood, the present invention is further described in detail below with reference to the accompanying drawings and the detailed description.
FIG. 1 is a particle size distribution diagram of a drug-loaded hyaluronic acid nano microemulsion in the novel coupling agent for shock wave treatment with anti-inflammatory and analgesic effects.
FIG. 2 is an electron microscope scanning form diagram of the drug-loaded hyaluronic acid nano microemulsion in the novel coupling agent for shock wave treatment with anti-inflammatory and analgesic effects.
FIG. 3 is a graph showing the results of the detection of the osmotic drugs in the experimental group and the control group at different time points in the examples of the results of the novel coupling agent for shock wave therapy with anti-inflammatory and analgesic effects of the present invention.
Detailed Description
Example 1
First, a phosphate buffer solution (i.e., PBS solution) having a pH of 7.4 was prepared, 37.932mg of Hyaluronic Acid (HA) and 20.633mg of N-N' cyclohexylcarbodiimide (EDC) were dissolved in 90ml of PBS solution, respectively, and mixed and stirred by a magnetic stirrer at a speed of 100rpm for 3 hours to form a solution a.
53.7mg of D- α -Glycerol Monostearate (GMS) was dissolved in 10ml of acetone and stirred until completely dissolved to form a solution B.
And dropwise adding the solution A into the solution B by using a peristaltic pump at the speed of 1 drop/second, enabling the molar ratio of HA to GMS to be 1:1.5, stirring and reacting at 35 ℃ for 10h to finally form 100ml of system solution, then centrifuging at 12000rpm for 10min, taking the precipitate for dialysis, intercepting substances with the molecular weight of 8000-10000, and freeze-drying after purification to form HA-GMS powder, namely hyaluronic acid powder modified by D- α -glycerol monostearate.
Then, 2.0mg of HA-GMS powder and 2.0mg of diclofenac sodium drug are dissolved in 70ml of deionized water to form a solution C, 1.5g of Tween-80 and 0.75g of D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) are sequentially dripped into the solution C, magnetic stirring is carried out at 100rpm until the solution C is uniformly mixed, ultrasonic processing is carried out for 30s to form a hyaluronic acid nano microsphere solution wrapping the diclofenac sodium, then 0.5mmol of trehalose solution is slowly dripped into a reaction system, stirring is carried out continuously for 30min, ultrasonic processing is carried out at 4 ℃ for 5min, and the drug-loaded hyaluronic acid nano microemulsion, namely the novel coupling agent 1 for shock wave treatment with the anti-inflammatory and analgesic effects is obtained.
Example 2
First, a phosphate buffer solution (i.e., PBS solution) having a pH of 7.3 was prepared, 56.898mg of Hyaluronic Acid (HA) and 30.949mg of N-N' cyclohexylcarbodiimide (EDC) were dissolved in 90ml of PBS solution, respectively, and mixed and stirred by a magnetic stirrer at a speed of 100rpm for 5 hours to form a solution a.
53.7mg of D- α -Glycerol Monostearate (GMS) was dissolved in 10ml of acetone and stirred until completely dissolved to form a solution B.
And dropwise adding the solution A into the solution B by using a peristaltic pump at the speed of 1 drop/second, enabling the molar ratio of HA to GMS to be 1:1, stirring and reacting at 32 ℃ for 10h to finally form 100ml of system solution, then centrifuging at 12000rpm for 10min, taking the precipitate for dialysis, intercepting substances with molecular weight of 8000-10000, purifying and freeze-drying to form HA-GMS powder, namely hyaluronic acid powder modified by D- α -glyceryl monostearate.
And then, dissolving 1.0mg of HA-GMS powder and 1.5mg of diclofenac sodium drug in 70ml of deionized water to form a solution C, sequentially dripping 1.5g of Tween-80 and 0.75g of D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) into the solution C, magnetically stirring at 100rpm until uniformly mixing, performing ultrasonic treatment for 30s to form a hyaluronic acid nano microsphere solution wrapping the diclofenac sodium, slowly dripping 0.5mmol of trehalose solution into a reaction system, continuously stirring for 30min, and performing ultrasonic treatment for 5min at 4 ℃ to obtain the drug-loaded hyaluronic acid nano microemulsion, namely the novel shock wave treatment coupling agent 2 with the anti-inflammatory and analgesic effects.
Example 3
First, a phosphate buffer solution (i.e., PBS solution) having a pH of 7.4 was prepared, 18.966mg of Hyaluronic Acid (HA) and 12.379mg of N-N' cyclohexylcarbodiimide (EDC) were dissolved in 90ml of PBS solution, respectively, and the solution was mixed and stirred by a magnetic stirrer at a speed of 100rpm for 2 hours to form a solution a.
21.48mg of D- α -Glyceryl Monostearate (GMS) was dissolved in 10ml of acetone and stirred until completely dissolved to form a solution B.
And dropwise adding the solution A into the solution B by using a peristaltic pump at the speed of 1 drop/second, enabling the molar ratio of HA to GMS to be 1:1.2, stirring and reacting at 32 ℃ for 10h to finally form 100ml of system solution, then centrifuging at 12000rpm for 10min, taking the precipitate for dialysis, intercepting substances with the molecular weight of 8000-10000, and freeze-drying after purification to form HA-GMS powder, namely hyaluronic acid powder modified by D- α -glycerol monostearate.
And then, dissolving 0.75mg of HA-GMS powder and 0.9mg of ibuprofen medicament in 70ml of deionized water to form a solution C, sequentially dripping 1.5g of Tween-80 and 0.75g of D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) into the solution C, magnetically stirring at 100rpm until uniformly mixing, performing ultrasonic treatment for 30s to form a hyaluronic acid nano microsphere shell solution wrapping the ibuprofen, slowly dripping 0.5mmol of trehalose solution into a reaction system, continuously stirring for 30min, and performing ultrasonic treatment for 5min at 4 ℃ to obtain the drug-loaded hyaluronic acid nano microemulsion, namely the novel coupling agent 3 for shock wave treatment with the anti-inflammatory and analgesic effects.
Of course, the non-steroidal anti-inflammatory drugs in the present application may also be aspirin, indomethacin, or other drugs of the enzexamine class.
Results example 1
For the sample shock wave coupling agents 1, 2 and 3 prepared in the above examples, the particle size and distribution of the hyaluronic acid nano microemulsion were measured by a laser particle sizer (DLS, Brookhaven Instrument-Omni, USA), and the morphology of the sample was characterized by a Scanning Electron Microscope (SEM), and as a result, the average particle size of the sample loaded with the hyaluronic acid nano microemulsion was 650nm, as shown in fig. 1 and 2.
Results example 2
Transdermal test: an in vitro skin permeation test was performed on the sample shock wave coupling agent 1 prepared in example one using a Franz transdermal diffusion apparatus. The specific operation is as follows:
c57BL/6 mice (purchased from Beijing encyclopedia) 6, 2% sodium pentobarbital (300. mu.l/100 g) were anesthetized by intraperitoneal injection and then decapitated, hair was removed from the back of the mice with an electric razor, and the exposed skin was carefully cut with scissors. Wiping the corium layer of skin with cotton ball stained with normal saline, removing subcutaneous tissue, washing with normal saline, wiping to dry, and placing in-20 deg.C refrigerator for use.
The prepared skin was randomly divided into control and experimental groups of 3 specimens each and fixed between a supply chamber and a receiving chamber of a Franz diffusion cell with the skin surface facing the supply chamber and the effective permeation area for supply of 3.164cm2. A volume of 12ml of PBS solution (PH 7.4) was added to the receiving chamber so that the liquid surface was in close contact with the skin. The experiment was carried out using a circulating water bath to maintain the temperature at 37 ℃ and stirring at 200 rpm.
4ml (concentration: 0.5mg/ml) of the sample prepared in example one was taken by a pipette, and added to each supply chamber separately, and sealed with a wrap film to prevent evaporation of the sample. At this time, the experimental group (ESW group) uses an external diffused shock wave therapeutic apparatus to perform shock wave intervention on the supply chamber on the side wall of the supply chamber in the direction perpendicular to the skin, and the shock wave intervention parameters are (1000s, 6 Hz); the control group (Ctrl group) did not employ in vitro shock wave interference.
The results of sampling 50. mu.l of the receiving chamber solution at predetermined times (1.0, 2.0, 3.0, 6.0, and 12.0 hours), diluting the sampled sample with PBS solution, filtering the diluted sample through filter paper, measuring the absorption of the drug in the solution by an ultraviolet spectrophotometer, and calculating the amount of drug accumulated through the skin over time and the maximum value of drug permeation through the skin are shown in FIG. 3.
And (4) conclusion: the diclofenac sodium accumulation and penetration amount of the experimental group (using shock wave intervention) is obviously higher than that of the control group (not using shock wave intervention), which shows that the in vitro shock wave has very good permeation promoting effect on percutaneous absorption of the drug-loaded hyaluronic acid nano microemulsion.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the present invention in any way, and it will be apparent to those skilled in the art that the above description of the present invention can be applied to various modifications, equivalent variations or modifications without departing from the spirit and scope of the present invention.
Claims (5)
1. The novel coupling agent with the effects of diminishing inflammation and easing pain for shock wave treatment is characterized in that the coupling agent adopts a drug-loaded hyaluronic acid nano microemulsion, and the drug-loaded hyaluronic acid nano microemulsion is loaded with a non-steroidal anti-inflammatory drug.
2. The novel couplant with anti-inflammatory and analgesic effects for shock wave therapy as claimed in claim 1, wherein the preparation method of the drug-loaded hyaluronic acid nano microemulsion is as follows:
(1) respectively dissolving hyaluronic acid and N-N 'cyclohexyl carbodiimide in a phosphate buffer solution (pH is 7.3-7.4), mixing and stirring the solution for 2-5h to form an A solution, wherein the molar ratio of the hyaluronic acid to the N-N' cyclohexyl carbodiimide is 1: 1-1.2;
(2) preparing an acetone solution containing glycerol monostearate to form a solution B;
(3) dropwise adding the solution A into the solution B at the speed of 1 drop/second by using a peristaltic pump, reacting at the temperature of 32-38 ℃ for 10-14h with the molar ratio of the hyaluronic acid to the glycerol monostearate being 1:1-1.5, centrifuging to obtain a precipitate, dialyzing, purifying and freeze-drying to form HA-GMS powder;
(4) dissolving the HA-GMS powder and the non-steroidal anti-inflammatory drug in deionized water according to the mass ratio of 1:1-2 to form a solution C, sequentially dripping Tween-80 and D- α -tocopheryl polyethylene glycol 1000 succinate into the solution C, magnetically stirring until uniformly mixing, performing ultrasonic treatment for 20-40s to form a hyaluronic acid nano microsphere solution wrapping the non-steroidal anti-inflammatory drug, then slowly dripping a trehalose dispersing agent, continuously stirring for 20-40min, and performing low-temperature ultrasonic treatment for 3-7min to obtain the drug-loaded hyaluronic acid nano microemulsion.
3. The novel couplant for shock wave therapy with anti-inflammatory and analgesic effects as claimed in claim 1 or 2, wherein the NSAID is diclofenac sodium, ibuprofen, aspirin or indomethacin.
4. A preparation method of a novel shock wave treatment couplant with anti-inflammatory and analgesic effects is characterized by comprising the following steps:
(1) respectively dissolving hyaluronic acid and N-N 'cyclohexyl carbodiimide in a phosphate buffer solution (pH is 7.3-7.4), mixing and stirring the solution for 2-5h to form an A solution, wherein the molar ratio of the hyaluronic acid to the N-N' cyclohexyl carbodiimide is 1: 1-1.2;
(2) preparing an acetone solution containing glycerol monostearate to form a solution B;
(3) dropwise adding the solution A into the solution B at the speed of 1 drop/second by using a peristaltic pump, reacting at the temperature of 32-38 ℃ for 10-14h with the molar ratio of the hyaluronic acid to the glycerol monostearate being 1:1-1.5, centrifuging to obtain a precipitate, dialyzing, purifying and freeze-drying to form HA-GMS powder;
(4) dissolving the HA-GMS powder and the non-steroidal anti-inflammatory drug in deionized water according to the mass ratio of 1:1-2 to form a solution C, sequentially dripping Tween-80 and D- α -tocopheryl polyethylene glycol 1000 succinate into the solution C, magnetically stirring until uniformly mixing, performing ultrasonic treatment for 20-40s to form a hyaluronic acid nano microsphere solution wrapping the non-steroidal anti-inflammatory drug, then slowly dripping a trehalose dispersing agent, continuously stirring for 20-40min, and performing low-temperature ultrasonic treatment for 3-7min to obtain the shock wave coupling agent.
5. The method for preparing the novel couplant for shock wave therapy with anti-inflammatory and analgesic effects as claimed in claim 4, wherein the non-steroidal anti-inflammatory drug is diclofenac sodium, ibuprofen, aspirin or indomethacin.
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| CN115317506A (en) * | 2022-07-29 | 2022-11-11 | 复旦大学附属中山医院 | Application of hyaluronic acid as or in preparation of photocoupler for skin phototherapy beauty |
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