Surface anesthesia application and preparation method thereof

Abstract

The invention provides a surface anesthesia application and a preparation method thereof, and belongs to the technical field of application. The surface anesthesia application is composed of a base material and anesthetic liquid, and the anesthetic liquid is prepared from, by mass, 0.5-10% of anesthetic, 0-1% of sodium hyaluronate, 0.1-10% of penetration enhancer, 0.1-1% of thickening agent, 0.01-0.5% of pH value regulator, 0.1-1% of preservative, 0-5% of emulsifier and the balance water. The surface anesthesia application prepared by the invention takes effect quickly, has a good anesthesia effect, reduces the dosage of anesthetics, and is convenient to use and low in cost.

Description

Technical Field

[0001] The present invention relates to the technical field of dressing, in particular to a surface anesthesia dressing and a preparation method thereof. Background Art

[0002] Surface anesthesia is a local anesthesia method commonly used in medical activities in clinical departments such as surgery and dermatology to solve the patient's pain or involuntary reactions during disease diagnosis and treatment.

[0003] The existing technology usually uses creams or gels containing anesthetic drugs to apply to the local skin, but has the following disadvantages:

[0004] (1) It takes a long time to take effect, the turnover rate of the operating table is low, and both doctors and patients have to wait for a long time. The anesthetic cream needs to be applied for 1 hour before the operation can begin.

[0005] (2) It is inconvenient to use. The application process is cumbersome. It needs to be covered with plastic wrap and then wiped off. The anesthetic cream needs to be spread little by little with a coating board. The process is cumbersome. After application, it needs to be covered with plastic film to help the drug penetrate and absorb. After a certain period of time, it needs to be manually wiped off little by little and washed off. The process is cumbersome.

[0006] (3) Uneven application of the ointment may cause skin burns. It is difficult to apply the ointment evenly by hand, and the thickness often varies greatly, resulting in a large disparity in the local dosage of the ointment. This not only causes different anesthetic effects in different parts of the body, but also often results in cases of ointment burns in clinical practice, causing serious troubles for both doctors and patients.

[0007] (4) The dosage is large and there are many adverse drug reactions, which poses certain safety risks. Summary of the Invention

[0008] In view of this, the object of the present invention is to provide a topical anesthesia patch with rapid onset, good anesthetic effect, low anesthetic dosage and low cost.

[0009] The present invention provides a surface anesthesia patch, which is composed of a base material and an anesthetic solution;

[0010] The ratio of the anesthetic solution to the substrate is 4 to 10 g / 100 cm 2 ;

[0011] The anesthetic solution comprises the following raw materials in percentage by mass:

[0012] Anesthetic drug 0.5-10%, sodium hyaluronate 0-1%, penetration enhancer 0.1-10%, thickener 0.1-1%, pH adjuster 0.01-0.5%, preservative 0.1-1%, emulsifier 0-5%, and the balance is water.

[0013] In the present invention, the anesthetic is the main ingredient that produces the anesthetic effect. Sodium hyaluronate has moisturizing, repairing, and healing effects. The penetration enhancer can promote skin absorption. The thickener is used to increase the consistency so that the product can adhere to the corresponding part of the skin and prevent it from falling off easily. The pH adjuster makes the anesthetic solution alkaline, which is conducive to the absorption of the anesthetic. The emulsifier's emulsification effect facilitates the dispersion of the anesthetic into an emulsion. The synergistic effect of the above ingredients enhances the anesthetic effect of the anesthetic solution.

[0014] Preferably, the anesthetic drugs are at least two of lidocaine, prilocaine, tetracaine, and lidocaine hydrochloride.

[0015] Preferably, the penetration enhancer is one or more of a surfactant penetration enhancer, an azone penetration enhancer, an alcohol penetration enhancer, a fatty acid penetration enhancer, and a terpene penetration enhancer.

[0016] More preferably, the surfactant-based penetration enhancer is at least one of Tween-80 and poloxamer; the azone-based penetration enhancer is lauryl azotocin. Ketone; the alcohol penetration enhancer is at least one of propylene glycol and glycerol; the fatty acid penetration enhancer is at least one of linoleic acid and isopropyl myristate; the terpene penetration enhancer is at least one of menthol and eucalyptus oil.

[0017] More preferably, the penetration enhancer is lauryl nitrogen One or more of ketone, glycerin, linoleic acid, propylene glycol, and eucalyptus oil.

[0018] Preferably, the thickener is hydroxyethyl cellulose or carbomer 940.

[0019] Preferably, the pH regulator is one or more of sodium hydroxide, potassium hydroxide, ammonia water, and ethanolamine.

[0020] Preferably, the preservative is one or more of phenoxyethanol, potassium sorbate, methylparaben, and parahydroxybenzoate; and the emulsifier is polyoxyethylene 40 hydrogenated castor oil.

[0021] Preferably, the substrate is a woven or non-woven fabric made of cotton, linen, silk or chemical fiber material.

[0022] Another object of the present invention is to provide a method for preparing a topical anesthesia patch, the method comprising the following steps:

[0023] (1) Weigh the raw materials in proportion, mix them evenly, and stir them at 70-90°C for 30-60 minutes until they are uniform, to obtain an anesthetic solution;

[0024] (2) Immersing the substrate in the anesthetic solution, loading the anesthetic solution on the substrate, and encapsulating the substrate for more than 24 hours to obtain the surface anesthesia patch.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] (1) It takes effect quickly, shortening the anesthesia application time from 60 minutes to 20 minutes, saving the waiting time of both doctors and patients and improving the utilization rate of doctors and operating beds.

[0027] (2) The anesthetic effect is good, and the anesthetic is evenly distributed throughout the target area, avoiding problems such as unsatisfactory local anesthesia effect and skin burns caused by uneven application of anesthetic cream.

[0028] (3) The amount of anesthetic used is reduced. Under the premise of ensuring the anesthetic effect, the amount of anesthetic used is only 31.47% of the anesthetic cream, thereby reducing the toxic and side effects of anesthetics.

[0029] (4) Easy to use. The numbing process has been changed from being tedious and complicated to being extremely simple. Only one application is needed, which greatly reduces the workload of medical staff.

[0030] (5) Low cost. The production cost after mass production is about 1 / 2 of that of anesthetic paste. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is the lidocaine average cumulative release per unit area-time square root curve (n=6);

[0032] Figure 2 is the average cumulative release of prilocaine per unit area-time square root curve (n=6);

[0033] Figure 3 The curve is the average cumulative release amount of sodium hyaluronate per unit area-square root of time (n=6). DETAILED DESCRIPTION

[0034] A topical anesthesia patch, comprising a base material and an anesthetic solution;

[0035] The ratio of the anesthetic solution to the substrate is 4.7 g / 100 cm 2 .

[0036] The anesthetic solution comprises the following raw materials in percentage by mass:

[0037] The composition comprises 0.5-10% anesthetic, 0-1% sodium hyaluronate, 0.1-10% penetration enhancer, 0.1-1% thickener, 0.01-0.5% pH adjuster, 0.1-1% preservative, 0-5% emulsifier, and the balance is water, wherein water is the solvent and sodium hyaluronate is the active ingredient.

[0038] Preferably, the anesthetic drugs are at least two of lidocaine, prilocaine, tetracaine, and lidocaine hydrochloride.

[0039] In a specific embodiment of the present invention, the substrate is a woven or non-woven fabric made of cotton, linen, silk or chemical fiber material. The substrate is a non-woven fabric with a size of 24 cm×22 cm.

[0040] The preparation method of the topical anesthesia patch of the present invention comprises the following steps:

[0041] (1) Weigh the raw materials in proportion, mix them evenly, and stir them at 75°C for 60 minutes until they are uniform to obtain an anesthetic solution;

[0042] (2) Immersing the substrate in the anesthetic solution, loading the anesthetic solution on the substrate, and encapsulating the substrate for more than 24 hours to obtain the surface anesthesia patch.

[0043] In a specific embodiment of the present invention, the anesthetic drug is an oil phase component, the thickener, pH adjuster, and preservative are all aqueous phase components, and the penetration enhancer comprises different components of the oil phase and aqueous phase. During the preparation process, the oil phase and aqueous phase of the above components should be mixed separately, and then the oil phase should be poured into the aqueous phase, mixed, and heated with stirring.

[0044] In a specific embodiment of the present invention, the anesthetic drug needs to be dissolved in a water bath at 50° C. to form a low-melting eutectic mixture and then mixed with an oil phase penetration enhancer to obtain an oil phase.

[0045] In a specific embodiment of the present invention, homogenization is performed twice during the heating and stirring process, with a stirring speed of 38 r / min and each time for 5 minutes.

[0046] The present invention will be further described below with reference to the embodiments.

[0047] Example 1

[0048] A topical anesthesia patch, wherein the raw material composition of the anesthetic solution is as shown in Table 1.

[0049] Table 1

[0050]

[0051] A topical anesthesia experiment was conducted on five volunteers. The topical anesthesia patch was applied to the inner forearm of the hand, and the anesthetic effect was recorded at different times. The following symbols were used for recording:

[0052] —: No numbness

[0053] +: There is numbness, but the tingling sensation is obvious;

[0054] ++: The needle prick is painful but tolerable;

[0055] +++: Acupuncture is basically painless and surgery can be performed.

[0056] The results are shown in Table 2.

[0057] Table 2

[0058]

[0059] *: There was a tingling and burning sensation on the local skin at 80 minutes for No. 1 and 60 minutes for No. 2.

[0060] Conclusion: The surface anesthesia has an ideal effect and takes effect quickly.

[0061] Example 2

[0062] A topical anesthesia patch, wherein the raw material composition of the anesthetic solution is as shown in Table 3.

[0063] Table 3

[0064]

[0065]

[0066] The topical anesthesia patch was subjected to a topical anesthesia experiment according to the method of Example 1. The results are shown in Table 4.

[0067] Table 4

[0068]

[0069] Conclusion: The surface anesthesia has an ideal effect and takes effect quickly.

[0070] Example 3

[0071] A topical anesthesia patch, wherein the raw material composition of the anesthetic solution is as shown in Table 5.

[0072] Table 5

[0073]

[0074]

[0075] The topical anesthesia patch was subjected to a topical anesthesia experiment according to the method of Example 1. The results are shown in Table 6.

[0076] Table 6

[0077]

[0078] Conclusion: The surface anesthesia has an ideal effect and takes effect quickly.

[0079] The drug content in Example 3 is: lidocaine 22 mg / g, prilocaine 22 mg / g, and sodium hyaluronate 1 mg / g.

[0080] Comparative Example 1

[0081] A topical anesthesia patch, wherein the raw material composition of the anesthetic solution is as shown in Table 7.

[0082] Table 7

[0083]

[0084] The topical anesthesia patch was subjected to a topical anesthesia experiment according to the method of Example 1. The results are shown in Table 8.

[0085] Table 8

[0086]

[0087]

[0088] Conclusion: The surface anesthesia effect was not achieved.

[0089] Comparative Example 2

[0090] A topical anesthesia patch, wherein the raw material composition of the anesthetic solution is as shown in Table 9.

[0091] Table 9

[0092]

[0093] The topical anesthesia patch was subjected to a topical anesthesia experiment according to the method of Example 1. The results are shown in Table 10.

[0094] Table 10

[0095]

[0096] Conclusion: There is a certain surface anesthetic effect, but it is not ideal.

[0097] Comparative Example 3

[0098] A topical anesthesia patch, wherein the raw material composition of the anesthetic solution is as shown in Table 11.

[0099] Table 11

[0100]

[0101]

[0102] The topical anesthesia patch was subjected to a topical anesthesia experiment according to the method of Example 1. The results are shown in Table 12.

[0103] Table 12

[0104]

[0105] Conclusion: There is a certain surface anesthetic effect, but it is not ideal.

[0106] Comparative Example 4

[0107] Compared with the existing numbing cream (drug name Lidocaine cream, trade name Enna, 1g cream contains lidocaine 25mg, prilocaine 25mg), the dosage of the numbing cream according to the instructions is 1.5g / 10cm 2 , the drug content of lidocaine and prilocaine is calculated as 25 mg / g each, and the equivalent dosage is lidocaine 37.5 mg / 10 cm 2 , prilocaine 37.5mg / 10cm 2 The present invention uses the same concentration (2.5% each of lidocaine and prilocaine, which is equivalent to 25 mg / g each of lidocaine and prilocaine) and the mask-shaped specifications (oval, non-woven fabric size 24 cm × 22 cm, area 528 cm 2 ) Conventional immersion volume is 25g, per 10cm 2 The amount of immersion liquid is 0.47g, which is equivalent to the dosage of lidocaine and prilocaine, 11.8mg / 10cm 2 , compared with 37.5mg / 10cm of anesthetic cream 2 , which is only 31.47% of the drug content in the numbing ointment, significantly reducing the dosage of the drug and reducing the adverse reactions of the drug.

[0108] In the embodiments of the present application, the amount of lidocaine added is 2.0%, 2.2% or 2.5%, and the amount of prilocaine added is 2.0%, 2.2% or 2.5%, which is less than or equal to 2.5%, which is lower than or equal to the concentration of the anesthetic cream in the prior art. The dosage of the anesthetic cream in the prior art is 1.5-2g / 10cm 2 When the medicine is applied, it takes at least 2 hours to take effect. The product prepared in this application has a good anesthetic effect in 20 to 40 minutes, with a small amount of medicine per unit area and a fast onset of effect.

[0109] Experiment 1

[0110] Three batches of anesthetic solutions were prepared according to the ratio and method of Example 3, respectively designated as T1, T2, and T3, to investigate the cumulative release amount and release rate of lidocaine, prilocaine, and sodium hyaluronate.

[0111] The specific test method is:

[0112] (1) Experimental conditions:

[0113] An in vitro release test was performed using a Franz diffusion cell with an inner diameter of 1.5 cm and a receiving cell volume of 12 mL. A 0.45 μm polyethersulfone microporous filter membrane (purchased from Tianjin Keyilong Experimental Equipment Co., Ltd.) was used as the isolation membrane, the drug loading was 1 mL, and the receiving solution was PBS buffer. The temperature was set at 32°C, the rotation speed was 600 rpm, and the sampling time points were 0.5, 1, 2, 3, 4, and 6 h.

[0114] (2) Isolation film treatment:

[0115] The isolation membrane was cut into round pieces with a diameter of 3 cm, and then placed in a receiving solution (PBS buffer) and ultrasonicated for 10 minutes to remove the air in the membrane pores, and then soaked for 30 minutes for use.

[0116] (3) Drug application and sampling:

[0117] Place the treated artificial membrane in a diffusion cell apparatus and place a 1.4 cm diameter blank patch. Use a pipette to transfer 1 mL of anesthetic solution into the supply cell. After application, fill the receiving cell with degassed receiving solution. Place the receiving cell in a 32°C heating block and stir continuously with an electromagnetic stirrer at 600 rpm. Remove all receiving solution and replenish with an equal amount of constant-temperature receiving solution at 0.5, 1, 2, 3, 4, and 6 hours. Store the receiving solution at room temperature to obtain the test receiving solution. Terminate the test at the sixth hour, and remove the isolation membrane.

[0118] (4) Collection and extraction of residual preparations on the isolation membrane:

[0119] Place the isolation membrane containing the anesthetic solution in a 50 mL EP tube, add 15 mL PBS buffer, vortex mix, transfer the solution in the 50 mL EP tube to a 50 mL volumetric flask, continue to add 15 mL PBS buffer and vortex extract, extract 3 times in total, then adjust the volume to the scale with PBS buffer, shake well and filter with a 0.45 μm polyethersulfone needle filter, discard 1 mL of the initial filtrate, take the subsequent filtrate, and obtain the collection liquid of the residual preparation of the isolation membrane to be tested.

[0120] (5) Collect the residual drugs on the surface of the receiving liquid to be tested in step (3) and the residual preparation collected from the isolation membrane to be tested in step (4), determine the drug concentration therein, and calculate the percentage of the total content of lidocaine and prilocaine in the receiving liquid and the remaining preparation to the dosage, that is, the recovery rate. The material balance is required to be controlled between 85% and 115%.

[0121] Content test method: Pipette 1 mL of the receiving solution to be tested in step (3) or the collection solution of the residual preparation of the isolation membrane to be tested in step (4) into a 50 mL volumetric flask, dilute to volume with PBS buffer, shake well, and filter with a 0.45 μm polyethersulfone needle filter. Discard 1 mL of the initial filtrate and take the subsequent filtrate to obtain the sample to be tested.

[0122] (6) Sample determination:

[0123] The concentrations of lidocaine and prilocaine in the above-mentioned test samples were determined by LC-MS / MS.

[0124] Chromatographic conditions:

[0125] Octadecylsilane bonded silica gel was used as the filler; phosphate buffer (1.3 ml of 1 mol / L sodium dihydrogen phosphate solution and 32.5 ml of 0.5 mol / L sodium dihydrogen phosphate solution were diluted with water to 1000 ml and shaken well)-acetonitrile (50:50) (pH adjusted to 8.0 with phosphoric acid) was used as the mobile phase; the detection wavelength was 254 nm; and the injection volume was 20 μl.

[0126] The cumulative release amount per unit area at time t, Q, is calculated according to formula (1):

[0127]

[0128] The dose consumption is calculated according to formula (2):

[0129] Dose consumption (%) = cumulative release amount Q in the receiving solution over 6 hours 6h ·S / drug content (2)

[0130] Where: Q is the cumulative release per unit area per time t (μg·cm -2 ), V is the volume of the solution in the receiving cell, Cn is the measured concentration of the nth sample, and S is the effective release area;

[0131] The drug content of the drug is the total value of the cumulative release amount in the receiving liquid and the content in the collected liquid of the residual preparation of the isolation membrane to be tested.

[0132] The amount of drug released per unit area (μg·cm -2 ) versus the square root of time should produce a straight line. The slope (regression) of this line represents the in vitro release rate of the formulation (lidocaine and prilocaine).

[0133] (7) Experimental results:

[0134] Cumulative release amount and in vitro release rate:

[0135] The amount of drug released per unit area (μg·cm -2 ) is plotted against the square root of time to generate a straight line. The slope of the linear regression equation is the release rate of the preparation (μg·cm -2 ·h -1 / 2 ), lidocaine average cumulative release per unit area-time square root curve (n = 6) as shown Figure 1The average cumulative release of prilocaine per unit area-time square root curve (n=6) is as follows Figure 2 The average cumulative release of sodium hyaluronate per unit area-time square root curve (n=6) is as follows Figure 3 The cumulative release of lidocaine per unit area (Q) and the release rate between each cup (μg·cm) in T1, T2, and T3 preparations -2 ·h -1 / 2 ) data, see Table 13; Prilocaine cumulative release per unit area (Q) and release rate between each cup (μg·cm -2 ·h -1 / 2 ) data, see Table 14; cumulative release of sodium hyaluronate per unit area (Q) and release rate between each cup (μg·cm -2 ·h -1 / 2 ) data, see Table 15.

[0136] Table 13

[0137]

[0138]

[0139] Table 14

[0140]

[0141]

[0142] Table 15

[0143]

[0144]

[0145] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A topical anesthesia patch, characterized in that: It is composed of base material and anesthetic solution; The ratio of the anesthetic solution to the substrate is 4 to 10 g / 100 cm 2 ; The anesthetic solution comprises the following raw materials in percentage by mass: Anesthetic drug 0.5-10%, sodium hyaluronate 0-1%, penetration enhancer 0.1-10%, thickener 0.1-1%, pH adjuster 0.01-0.5%, preservative 0.1-1%, emulsifier 0-5%, and the balance is water.

2. The topical anesthesia patch according to claim 1, characterized in that: The anesthetic drugs are at least two of lidocaine, prilocaine, tetracaine, and lidocaine hydrochloride.

3. The topical anesthesia patch according to claim 1, characterized in that: The penetration enhancer is one or more of a surfactant penetration enhancer, an azone penetration enhancer, an alcohol penetration enhancer, a fatty acid penetration enhancer, and a terpene penetration enhancer.

4. The topical anesthesia patch according to claim 3, characterized in that: The surfactant penetration enhancer is at least one of Tween-80 and poloxamer; the azone penetration enhancer is lauryl azotocin. Ketone; the alcohol penetration enhancer is at least one of propylene glycol and glycerol; the fatty acid penetration enhancer is at least one of linoleic acid and isopropyl myristate; the terpene penetration enhancer is at least one of menthol and eucalyptus oil.

5. The topical anesthesia patch according to claim 4, characterized in that: The penetration enhancer is lauryl nitrogen One or more of ketone, glycerin, linoleic acid, propylene glycol, and eucalyptus oil.

6. The topical anesthesia patch according to claim 1, characterized in that: The thickener is hydroxyethyl cellulose or carbomer 940.

7. The topical anesthesia patch according to claim 1, characterized in that: The pH regulator is one or more of sodium hydroxide, potassium hydroxide, ammonia water, and ethanolamine.

8. The topical anesthesia patch according to claim 1, characterized in that: The preservative is one or more of phenoxyethanol, potassium sorbate, methylparaben, and parahydroxybenzoate; and the emulsifier is polyoxyethylene 40 hydrogenated castor oil.

9. The topical anesthesia patch according to claim 1, characterized in that: The substrate is a woven or non-woven fabric made of cotton, linen, silk or chemical fiber material.

10. A method for preparing the topical anesthesia patch according to claim 1, characterized in that: The following steps are involved: (1) Weigh the raw materials in proportion, mix them evenly, and stir them at 70-90°C for 30-60 minutes until they are uniform, to obtain an anesthetic solution; (2) Immersing the substrate in the anesthetic solution, loading the anesthetic solution on the substrate, and encapsulating the substrate for more than 24 hours to obtain the surface anesthesia patch.

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