Plaster for surface anesthesia and preparation method thereof

Abstract

The invention relates to the technical field of anesthetic drugs, in particular to an application for surface anesthesia and a preparation method thereof. The patch for surface anesthesia comprises a base material layer, an anesthesia layer and an isolation layer which are arranged in sequence, the anesthesia layer is prepared from the following components in parts by weight: 5 to 10 parts of anesthetic, 1 to 3 parts of piceatannol, 0.5 to 2 parts of ligustralactone, 15 to 25 parts of polyvinyl alcohol, 1 to 5 parts of chitosan, 0.3 to 0.5 part of thickening agent, 5 to 10 parts of transdermal absorbent and 50 to 60 parts of purified water. The patch for surface anesthesia can be applied to the surface of skin, can quickly permeate into the skin, and has the characteristics of quick anesthesia effect, longer anesthesia duration and the like. In addition, the application also has the advantages of excellent antibacterial activity, high safety, simplicity and convenience in use and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of anesthetic drugs, and particularly relates to a patch for topical anesthesia and a preparation method thereof. Background Art

[0002] Almost all surgeries in clinical practice involve anesthetic means to relieve the pain of patients during the surgery. The anesthetic methods are divided into two types, one is general anesthesia, and the other is local anesthesia. General anesthesia, also known as GA, refers to the anesthetic drug being inhaled through the respiratory tract, injected intravenously or intramuscularly into the body, resulting in temporary inhibition of the central nervous system, manifested as loss of consciousness, disappearance of general pain sensation, amnesia, reflex inhibition, and skeletal muscle relaxation. Local anesthesia, also known as regional anesthesia, refers to applying the drug to a local part of the body in a state of clear consciousness of the human body to temporarily block the sensory nerve conduction function of a certain part of the body for the convenience of surgery, with the characteristics of being simple and easy to operate, safe, and having less impact on the physiological functions of patients. However, the traditional method of local anesthesia usually involves injecting local anesthetic drugs, which can easily cause fear in patients, resulting in non - cooperation of patients. On this basis, topical anesthesia has gradually attracted much attention in the technical field of anesthetic drugs.

[0003] Topical anesthesia refers to directly applying a local anesthetic to the surface of the human skin to block the conduction function of nerve endings through the skin to achieve the effect of local anesthesia. Anesthetic patches are widely used in topical anesthesia surgeries because they are convenient for application and cleaning. However, clinical practice has found that existing anesthetic patches have problems such as a long onset time of anesthesia and a short duration of anesthesia. Based on this, a new patch for topical anesthesia is needed to relieve the pain of patients. Summary of the Invention

[0004] In order to overcome the deficiencies of the prior art, the primary object of the present invention is to provide a patch for topical anesthesia, which has the characteristics of high safety, fast onset, and long duration of anesthesia.

[0005] Another object of the present invention is to provide a preparation method for a patch for topical anesthesia, with simple steps.

[0006] The object of the present invention is achieved by the following technical solutions: A patch for topical anesthesia, comprising a base material layer, an anesthetic layer, and a release layer arranged in sequence; the anesthetic layer is composed of the following components in parts by weight: 5 - 10 parts of anesthetic, 1 - 3 parts of piceatannol, 0.5 - 2 parts of ligustilide, 15 - 25 parts of polyvinyl alcohol, 1 - 5 parts of chitosan, 0.3 - 0.5 parts of thickening agent, 5 - 10 parts of transdermal absorbent, and 50 - 60 parts of purified water.

[0007] Further, the anesthetic is selected from one of procaine, butamben, dyclonine, bupivacaine, etidocaine, oxybuprocaine, pumocaine, and proxymetacaine.

[0008] Furthermore, the anesthetic is procaine.

[0009] Further, the transdermal absorbent is composed of the following raw materials in parts by weight: 15 - 25 parts of isopropanol and 5 - 10 parts of azone.

[0010] Further, the thickening agent is selected from one of carbomer, guar gum, and xanthan gum.

[0011] Further, the molecular weight of the chitosan is 15 - 30 kDa.

[0012] Further, the base material layer is a medical polyurethane film; the isolation layer is a release paper.

[0013] The preparation method of the above surface anesthetic patch includes the following steps: (1) According to the above parts - by - weight ratio, add polyvinyl alcohol and chitosan to purified water, heat and stir, then add the thickening agent and the transdermal absorbent, and mix evenly to obtain a gel matrix; add the anesthetic, piceatannol, and ligustilide to the gel matrix and mix evenly to obtain a gel; (2) Coat the gel from step (1) on the base material layer to form an anesthetic layer; cover the isolation layer on the anesthetic layer, and perform irradiation sterilization to obtain the product.

[0014] Further, the temperature of the heating and stirring in step (1) is 60 - 80°C.

[0015] Further, the thickness of the anesthetic layer in step (1) is 0.8 - 1.5 mm.

[0016] Further, the irradiation time in step (2) is 20 - 30 min.

[0017] The present invention has the following effects compared with the prior art: 1. The present invention provides a surface anesthetic patch with a base material layer, an anesthetic layer, and an isolation layer arranged in sequence. The anesthetic layer includes components such as the anesthetic procaine, piceatannol, and ligustilide. Detection of the anesthetic effect of the surface anesthetic patch shows that the combined use of procaine, piceatannol, and ligustilide can enhance the anesthetic effect and the anesthetic duration of the patch.

[0018] 2. The surface anesthetic patch of the present invention can be applied to the skin surface, can quickly penetrate the skin, and has the characteristics of fast anesthetic onset and long anesthetic duration. In addition, the patch also has excellent antibacterial properties and is simple and convenient to use.

[0019] 3. The preparation method of the topical anesthetic patch of the present invention has simple steps, is easy to operate and is easy to mass-produce. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 It is a schematic structural diagram of the topical anesthetic patch obtained in Example 1 of the present invention; Reference numerals: 1, base material layer; 2, anesthetic layer; 3, isolation layer. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0021] The present invention will be further described in detail below in conjunction with embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field. The test methods without specific experimental conditions in the following examples are usually carried out according to conventional experimental conditions or according to the experimental conditions recommended by the manufacturer. Unless otherwise specified, the reagents and raw materials used in the present invention can be obtained through commercial channels.

[0022] Embodiment Embodiment 1 This embodiment provides a topical anesthetic patch, which includes a base material layer 1, an anesthetic layer 2 and an isolation layer 3 arranged in sequence. For the schematic structural diagram, see Figure 1 ; The anesthetic layer 2 is composed of the following components in parts by weight: 8 parts of procaine, 2 parts of piceatannol, 1 part of ligustilide, 20 parts of polyvinyl alcohol, 2 parts of chitosan, 0.4 part of carbomer, 7 parts of transdermal absorption agent, and 53 parts of purified water; wherein the base material layer 1 is a medical polyurethane film, the isolation layer 3 is a release paper, and the transdermal absorption agent is composed of the following raw materials in parts by weight: 20 parts of isopropanol, 6 parts of azone; the molecular weight of chitosan is 25 kDa.

[0023] This embodiment also provides a preparation method of the above-mentioned topical anesthetic patch, and the specific preparation process is as follows: (1) According to the above-mentioned weight ratio, add polyvinyl alcohol and chitosan to purified water, heat to 70 °C and stir until dissolved. After cooling to room temperature, slowly add carbomer and transdermal absorption agent in sequence under stirring, and mix evenly to obtain a gel matrix; slowly add procaine, piceatannol and ligustilide to the gel matrix under stirring conditions, and stir evenly to obtain a gel; (2) Uniformly coat the gel matrix obtained in step (1) on the medical polyurethane film to form an anesthetic layer 2 with a thickness of 1 mm, cover the release paper on the anesthetic layer 2, and irradiate and sterilize for 25 min to obtain.

[0024] Embodiment 2 This embodiment provides a topical anesthetic patch, which includes a substrate layer 1, an anesthetic layer 2, and a release layer 3 arranged in sequence; the anesthetic layer 2 is composed of the following components in parts by weight: 5 parts of procaine, 1 part of piceatannol, 0.5 part of ligustilide, 15 parts of polyvinyl alcohol, 1 part of chitosan, 0.3 part of guar gum, 5 parts of a transdermal absorbent, and 50 parts of purified water; wherein the substrate layer 1 is a medical polyurethane film, the release layer 3 is a release paper, and the transdermal absorbent is composed of the following raw materials in parts by weight: 15 parts of isopropanol and 5 parts of azone; the molecular weight of chitosan is 15 kDa.

[0025] This embodiment also provides a preparation method of the above-mentioned topical anesthetic patch, and the specific preparation process is as follows: (1) According to the above-mentioned weight ratio, add polyvinyl alcohol and chitosan to purified water, heat to 60 °C and stir until dissolved, and after cooling to room temperature, slowly add guar gum and the transdermal absorbent in sequence under stirring, and mix evenly to obtain a gel matrix; slowly add procaine, piceatannol, and ligustilide to the gel matrix under stirring conditions, and stir evenly to obtain a gel; (2) Uniformly coat the gel matrix obtained in step (1) on the medical polyurethane film to form an anesthetic layer 2 with a thickness of 0.8 mm, cover the release paper on the anesthetic layer 2, and irradiate and sterilize for 20 min to obtain the product.

[0026] Example 3 This embodiment provides a topical anesthetic patch, which includes a substrate layer 1, an anesthetic layer 2, and a release layer 3 arranged in sequence; the anesthetic layer 2 is composed of the following components in parts by weight: 10 parts of procaine, 3 parts of piceatannol, 2 parts of ligustilide, 25 parts of polyvinyl alcohol, 5 parts of chitosan, 0.5 part of xanthan gum, 10 parts of a transdermal absorbent, and 60 parts of purified water; wherein the substrate layer 1 is a medical polyurethane film, the release layer 3 is a release paper, and the transdermal absorbent is composed of the following raw materials in parts by weight: 25 parts of isopropanol and 10 parts of azone; the molecular weight of chitosan is 30 kDa.

[0027] This embodiment also provides a preparation method of the above-mentioned topical anesthetic patch, and the specific preparation process is as follows: (1) According to the above-mentioned weight ratio, add polyvinyl alcohol and chitosan to purified water, heat to 80 °C and stir until dissolved, and after cooling to room temperature, slowly add xanthan gum and the transdermal absorbent in sequence under stirring, and mix evenly to obtain a gel matrix; slowly add procaine, piceatannol, and ligustilide to the gel matrix under stirring conditions, and stir evenly to obtain a gel; (2) Uniformly coat the gel matrix obtained in step (1) on the medical polyurethane film to form an anesthetic layer 2 with a thickness of 1.5 mm, cover the release paper on the anesthetic layer 2, and irradiate and sterilize for 30 min to obtain the product.

[0028] Comparative Example Comparative Example 1 Comparative Example 1 provides a patch, which includes a substrate layer 1, an anesthetic layer 2, and a release layer 3 arranged in sequence; the anesthetic layer 2 is composed of the following components in parts by weight: 8 parts of procaine, 1 part of ligustilide, 20 parts of polyvinyl alcohol, 2 parts of chitosan, 0.4 part of carbomer, 7 parts of a transdermal absorption enhancer, and 53 parts of purified water; wherein the substrate layer 1 is a medical polyurethane film, the release layer 3 is a release paper, and the transdermal absorption enhancer is composed of the following raw materials in parts by weight: 20 parts of isopropanol and 6 parts of azone; the molecular weight of chitosan is 25 kDa.

[0029] This comparative example also provides a preparation method of the above patch, which is specifically the same as that of Example 1.

[0030] Comparative Example 2 Comparative Example 2 provides a patch, which includes a substrate layer 1, an anesthetic layer 2, and a release layer 3 arranged in sequence; the anesthetic layer 2 is composed of the following components in parts by weight: 8 parts of procaine, 2 parts of piceatannol, 20 parts of polyvinyl alcohol, 2 parts of chitosan, 0.4 part of carbomer, 7 parts of a transdermal absorption enhancer, and 53 parts of purified water; wherein the substrate layer 1 is a medical polyurethane film, the release layer 3 is a release paper, and the transdermal absorption enhancer is composed of the following raw materials in parts by weight: 20 parts of isopropanol and 6 parts of azone; the molecular weight of chitosan is 25 kDa.

[0031] This comparative example also provides a preparation method of the above patch, which is specifically the same as that of Example 1.

[0032] Comparative Example 3 Comparative Example 3 provides a patch, which includes a substrate layer 1, an anesthetic layer 2, and a release layer 3 arranged in sequence; the anesthetic layer 2 is composed of the following components in parts by weight: 8 parts of procaine, 20 parts of polyvinyl alcohol, 2 parts of chitosan, 0.4 part of carbomer, 7 parts of a transdermal absorption enhancer, and 53 parts of purified water; wherein the substrate layer 1 is a medical polyurethane film, the release layer 3 is a release paper, and the transdermal absorption enhancer is composed of the following raw materials in parts by weight: 20 parts of isopropanol and 6 parts of azone; the molecular weight of chitosan is 25 kDa.

[0033] This comparative example also provides a preparation method of the above patch, which is specifically the same as that of Example 1.

[0034] Test Example Test Example 1 The drug effects of the patches obtained in Examples 1 - 3 and Comparative Examples 1 - 3 were detected as follows: Test subjects: A total of 60 SD rats were randomly divided into groups of Examples 1 - 3 and Comparative Examples 1 - 3.

[0035] Test process: Rats in each group were induced and maintained under anesthesia by inhaling 3% isoflurane, and then about 6×6 cm of the back in the thoracic and lumbar segments was shaved with an electric hair clipper. 2For the hair, disinfect the bare skin with alcohol. Apply the products obtained in Examples 1 - 3 and Comparative Examples 1 - 3 onto the surface of the bare skin of each group of rats respectively. Divide the drug - administration site on the back into 6 equal parts. At 10 min, 30 min, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, and 5.5 h after drug administration, use a 15 g Vonfrey + needle to prick the skin at the marked points, with the penetration depth about 1 mm. Observe whether there is a pain response in each group of rats and score the pain response. The pain - scoring method is as follows: Randomly prick the skin 6 times at the 6 - equal - part drug - administration site. If there are no pain responses such as skin wrinkles or avoidance in all 6 pricks, it is complete analgesia, recorded as 6; if there are no pain responses such as skin wrinkles or avoidance in 3 - 5 pricks, it is effective analgesia, recorded as 3 - 5; if there are no pain responses such as skin wrinkles or avoidance in 0 - 2 pricks, it is ineffective analgesia, recorded as 0 - 2. The test results are shown in Table 1.

[0036] Table 1 As can be seen from Table 1, the patch obtained in the present invention can take effect in 10 min, and the anesthesia duration is about 5 h, with the characteristics of fast onset of anesthesia and relatively long anesthesia duration.

[0037] Compared with Examples 1 - 3, the patches obtained in Comparative Examples 1 - 3 can also take effect in 10 min, but their anesthesia durations are significantly shortened. Among them, in Comparative Example 3, both paclitaxel and ligustilide are omitted, and the obtained patch has the shortest anesthesia duration. The anesthetic effect of the patch obtained in Comparative Example 1 where paclitaxel is omitted is better than that of Comparative Examples 2 and 3. This may be because ligustilide has a certain analgesic effect. The above experimental results also show that the combination of procaine with paclitaxel and ligustilide effectively increases the anesthesia duration of the patch.

[0038] Test Example 2 Detect the antibacterial performance and cytotoxicity of the patches obtained in Examples 1 - 3 as follows: Experimental bacteria: Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922.

[0039] Experimental process: Inoculate the activated Staphylococcus aureus and Escherichia coli onto an ordinary broth culture medium agar plate, culture at 37 °C for 24 h, appropriately dilute the bacteria with nutrient broth (10 8 CFU / mL), then add the patches obtained in Examples 1 - 3 respectively, incubate at room temperature for 1.5 h, take 50 μL respectively and coat them on the plate, culture in an inverted position at 37 °C for 24 h, observe the colony growth situation and count the number of colonies. Use sterile water instead of the patch as the blank control group, set 3 parallel tests for each group. The antibacterial rate = (total number of colonies in the blank control group - total number of colonies in the test group) / total number of colonies in the blank control group × 100%. The results are shown in Table 2.

[0040] Table 2 As can be seen from Table 2, the patch obtained by the present invention has excellent antibacterial properties and is applicable in clinical practice.

[0041] In summary, the patch for topical anesthesia provided by the present invention can be applied to the skin surface, and can also quickly penetrate the skin, with the characteristics of fast onset of anesthesia and long duration of anesthesia. Moreover, the patch for topical anesthesia of the present invention also has excellent antibacterial properties, high safety, and is simple and convenient to use.

[0042] The above embodiments are only the preferred embodiments of the present invention, and the scope of protection of the present invention cannot be limited thereby. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention belong to the scope of protection required by the present invention.

Claims

1. A patch for surface anesthesia, characterized in that, It includes a substrate layer, an anesthetic layer, and a release layer arranged in sequence; the anesthetic layer is composed of the following components in parts by weight: 5-10 parts of anesthetic, 1-3 parts of paclitaxel, 0.5-2 parts of ligustilide, 15-25 parts of polyvinyl alcohol, 1-5 parts of chitosan, 0.3-0.5 parts of thickening agent, 5-10 parts of transdermal absorbent, and 50-60 parts of purified water.

2. The topical anesthetic patch according to claim 1, wherein The anesthetic is selected from one of procaine, butamben, dyclonine, bupivacaine, etidocaine, oxybuprocaine, promoxine, and proxymetacaine.

3. The topical anesthetic patch according to claim 1, wherein The transdermal absorbent is composed of the following raw materials in parts by weight: 15-25 parts of isopropanol and 5-10 parts of azone.

4. The topical anesthetic patch according to claim 1, characterized in that, The thickening agent is selected from one of carbomer, guar gum, and xanthan gum.

5. The surface anesthesia patch according to claim 1, wherein The molecular weight of the chitosan is 15-30 kDa.

6. The topical anesthetic patch according to claim 1, wherein, The substrate layer is a medical polyurethane film; the release layer is release paper.

7. The preparation method of the topical anesthetic patch according to any one of claims 1 to 6, characterized in that, It includes the following steps: (1) According to the above parts-by-weight ratio, add polyvinyl alcohol and chitosan to purified water, heat and stir, then add the thickening agent and the transdermal absorbent, and mix evenly to obtain a gel matrix; add the anesthetic, paclitaxel, and ligustilide to the gel matrix and mix evenly to obtain a gel; (2) Coat the gel in step (1) on the substrate layer to form an anesthetic layer; cover the release layer on the anesthetic layer, and perform irradiation sterilization to obtain the product.

8. The preparation method of the topical anesthetic patch according to claim 7, characterized in that, The temperature of the heating and stirring in step (1) is 60-80 °C.

9. The preparation method of the topical anesthetic patch according to claim 7, characterized in that, The thickness of the anesthetic layer in step (2) is 0.8-1.5 mm.

10. The preparation method of the topical anesthetic patch according to claim 7, characterized in that, The irradiation time in step (2) is 20-30 min.

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