Anesthetic preparation containing trimethylcaine and preparation method thereof

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a trimethylcaine-containing anesthetic preparation and a preparation method thereof. The anesthetic preparation containing the trimethylcaine is prepared from the following raw materials in parts by weight: 8 to 12 parts of the trimethylcaine, 0.5 to 1 part of linderane, 0.3 to 0.8 part of sodium phytate, 1 to 5 parts of schizophyllum oligomerization polysaccharide, 3 to 5 parts of 1, 2-propylene glycol, 2 to 6 parts of sodium carboxymethyl cellulose, 3 to 8 parts of Tween and 60 to 70 parts of normal saline. According to the anesthetic preparation disclosed by the invention, the linderane and the trimethylcaine which are added into the anesthetic preparation are matched, so that the anesthetic effect can be improved, and the anesthetic time can be prolonged. The sodium phytate and the schizophyllum oligomerization polysaccharide in the anesthetic preparation have a synergistic effect, so that the stability of the anesthetic preparation is effectively improved, and the schizophyllum oligomerization polysaccharide has a film-forming property, so that the anesthetic effect of the anesthetic preparation can be improved to a certain extent. In addition, the anesthetic prepared by the invention has no obvious irritation to the skin.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to an anesthetic preparation containing trimecaine and a preparation method thereof. Background Art

[0002] In the medical field, the research and development and application of anesthetic drugs have always been an important topic to improve surgical safety and patient comfort. The most basic function of anesthetic preparations is to provide pain relief. During surgery or certain special treatments, patients may experience severe pain. Anesthetic drugs can effectively relieve this pain by interfering with the pain conduction pathway, blocking the patient's ability to feel pain, and making them feel no pain during surgery or treatment. Anesthetic drugs can also be used for postoperative pain management, reducing the patient's pain and discomfort, and promoting the patient's rapid recovery. In addition, anesthetic preparations are also widely used in the field of pain treatment, such as chronic pain management, cancer pain treatment, etc. In recent years, with the continuous advancement of medical technology, the types and performance of anesthetic drugs have also been continuously upgraded. Among them, anesthetic preparations containing trimecaine have received widespread attention due to their advantages such as rapid penetration, rapid onset, long duration of anesthesia, and no obvious irritation to the skin.

[0003] As a common ester local anesthetic, trimethocaine is widely used in various surgical operations and medical procedures due to its rapid and effective analgesic effect. Its anesthetic mechanism is mainly to achieve the purpose of local anesthesia by inhibiting nerve conduction. At present, there are many anesthetic preparations containing trimethocaine on the market, but the existing trimethocaine anesthetic preparations still have some shortcomings in preparation and application, such as unstable anesthetic effect and irritation to the skin, which limit its effect in practical application.

[0004] Lindera aggregata is a natural compound extracted from Lindera aggregata with multiple pharmacological activities. Studies have shown that lindera aggregata can inhibit the conduction of pain signals through multiple pathways, thereby effectively reducing the pain of patients. In addition, traditional anesthetic preparations often have problems such as uneven drug dispersion and poor stability during the preparation process, which affects the efficacy and safety of the drugs. Therefore, it is of great significance to develop an efficient, stable and safe anesthetic preparation. Summary of the invention

[0005] In order to overcome the deficiencies of the prior art, the primary purpose of the present invention is to provide an anesthetic preparation containing trimecaine.

[0006] Another object of the present invention is to provide a method for preparing an anesthetic preparation containing trimecaine.

[0007] The purpose of the present invention is achieved through the following technical solutions: An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 8-12 parts of trimecaine, 0.5-1 parts of lindera lactone, 0.3-0.8 parts of sodium phytate, 1-5 parts of oligomeric schizophyllan polysaccharide, 3-5 parts of 1,2-propylene glycol, 2-6 parts of sodium carboxymethyl cellulose, 3-8 parts of Tween and 60-70 parts of normal saline.

[0008] Furthermore, the anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.75 parts of lindera ether lactone, 0.5 parts of sodium phytate, 3 parts of oligomeric schizophyllan polysaccharide, 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween, and 65 parts of normal saline.

[0009] Furthermore, the molecular weight of the oligomeric Schizophyllan polysaccharide is 1-3KD.

[0010] Furthermore, the Tween is Tween-80 or Tween-60.

[0011] A method for preparing an anesthetic preparation containing trimecaine comprises the following steps: (1) Weighing the components according to the above weight proportions, adding lindera lactone to 1,2-propylene glycol, then adding sodium carboxymethyl cellulose and Tween, and stirring to obtain a mixed solution A; (2) adding trimecaine, sodium phytate and oligomeric schizophyllan to the mixed solution A, heating and stirring to obtain a mixed solution B; (3) Cool the mixed solution B to room temperature, then add physiological saline and homogenize under vacuum to obtain the product.

[0012] Furthermore, the heating temperature is 35-40° C., and the stirring time is 3-7 min.

[0013] Furthermore, the vacuum homogenization pressure is 20-40 MPa and the time is 3-5 min.

[0014] Furthermore, the anesthetic preparation containing trimecaine is an anesthetic preparation for patch application.

[0015] The present invention has the following effects compared with the prior art: 1. The present invention provides an anesthetic preparation containing trimethocaine, wherein lindera lactone, sodium phytate and oligomeric schizophyllan polysaccharide are further added to the formula, and the combination of lindera lactone and trimethocaine can enhance the anesthetic effect and prolong the anesthesia time. Sodium phytate and oligomeric schizophyllan polysaccharide can act synergistically to effectively improve the stability of the anesthetic preparation, wherein the oligomeric schizophyllan polysaccharide can enhance the anesthetic efficacy of the anesthetic preparation to a certain extent due to its film-forming property. In addition, the anesthetic preparation prepared by the present invention has no obvious irritation to the skin.

[0016] 2. The present invention provides a method for preparing an anesthetic preparation containing trimecaine. The method is simple and efficient, can be used for industrial production, and has broad application prospects in the medical field. DETAILED DESCRIPTION

[0017] The present invention will be described in further detail below in conjunction with the examples, 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 art. The test methods for which specific experimental conditions are not specified 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 commercially.

[0018] Example 1 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 parts of lindera lactone, 0.5 parts of sodium phytate, 3 parts of oligomeric schizophyllan polysaccharide (molecular weight 2KD), 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween-80, and 65 parts of normal saline.

[0019] A method for preparing an anesthetic preparation containing trimecaine comprises the following steps: (1) Weighing the components according to the above weight proportions, adding lindera lactone to 1,2-propylene glycol, and then adding sodium carboxymethyl cellulose and Tween-80, stirring and mixing to form a mixed solution A; (2) adding trimethocaine, sodium phytate and oligomeric schizophyllan to the mixed solution A, stirring at 40° C. for 5 min to obtain solution B; (3) Cool the mixed solution B to room temperature, then add physiological saline and homogenize under vacuum (40 MPa, 5 min).

[0020] Example 2 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 8 parts of trimecaine, 0.5 parts of lindera lactone, 0.3 parts of sodium phytate, 1 part of oligomeric schizophyllan (molecular weight 1KD), 3 parts of 1,2-propylene glycol, 2 parts of sodium carboxymethyl cellulose, 3 parts of Tween-60, and 60 parts of normal saline.

[0021] A method for preparing an anesthetic preparation containing trimecaine comprises the following steps: (1) Weighing the components according to the above weight proportions, adding lindera lactone to 1,2-propylene glycol, and then adding sodium carboxymethyl cellulose and Tween-60, stirring and mixing to form a mixed solution A; (2) adding trimethocaine, sodium phytate and oligomeric schizophyllan to the mixed solution A, and stirring at 40° C. for 3 min to obtain solution B; (3) Cool the mixed solution B to room temperature, then add physiological saline and homogenize under vacuum (20 MPa, 5 min).

[0022] Example 3 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 12 parts of trimecaine, 1 part of lindera ether lactone, 0.8 parts of sodium phytate, 5 parts of oligomeric schizophyllan polysaccharide (molecular weight 3KD), 5 parts of 1,2-propylene glycol, 6 parts of sodium carboxymethyl cellulose, 8 parts of Tween-80, and 70 parts of normal saline.

[0023] A method for preparing an anesthetic preparation containing trimecaine comprises the following steps: (1) Weighing the components according to the above weight proportions, adding lindera lactone to 1,2-propylene glycol, and then adding sodium carboxymethyl cellulose and Tween-80, stirring and mixing to form a mixed solution A; (2) adding trimethocaine, sodium phytate and oligomeric schizophyllan to the mixed solution A, and stirring at 40° C. for 7 min to obtain solution B; (3) Cool the mixed solution B to room temperature, then add physiological saline and homogenize under vacuum (30 MPa, 3 min).

[0024] Comparative Example 1 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.5 parts of sodium phytate, 3 parts of oligomeric schizophyllan (molecular weight 2KD), 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween-80, and 65 parts of physiological saline. The rest is the same as in Example 1.

[0025] Comparative Example 2 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 parts of lindera lactone, 3.5 parts of oligomeric schizophyllan (molecular weight 2KD), 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween-80, and 65 parts of physiological saline. The rest is the same as in Example 1.

[0026] Comparative Example 3 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 parts of lindera lactone, 3.5 parts of sodium phytate, 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween-80, and 65 parts of normal saline. The rest is the same as in Example 1.

[0027] Comparative Example 4 An anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 parts of lindera lactone, 0.5 parts of sodium phytate, 3 parts of oligomeric schizophyllan (molecular weight of 10 kD), 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween-80, and 65 parts of normal saline.

[0028] Test Example 1 Skin irritation test Experimental animals: 6-week-old SPF guinea pigs were selected for skin irritation test. They were then placed in an environment of 25°C and 60% relative humidity with alternating 12h light and 12h darkness. The guinea pigs were subjected to the adaptation test for one week, during which they drank water and ate normally every day.

[0029] Test method: 90 guinea pigs were randomly divided into negative control group, positive control group, Example 1-3 group, and Comparative Example 1-4 group, with 10 in each group. On the 0th day, 7th day, and 14th day, the same amount of anesthetic preparations (0.5 mL) of Example 1-3 and Comparative Example 1-4 were applied to the 3cm*3cm hair removal area on the left side of the back of the guinea pigs, respectively. The positive control group was coated with the same amount of 2,4-dinitrochlorobenzene (concentration of 2.5%), and the negative control group was coated with the same amount of sterile saline. The administration site was covered with 2 layers of gauze and 1 layer of cellophane, fixed with a sterile bandage, and washed off with clean water after 6 hours. On the 14th day after the last administration of the test substance, an irritation contact experiment was carried out (the 3cm*3cm area on the right side of the back of the animal was depilated before the experiment), the negative control group was coated with the same amount of sterile saline, the positive control group was coated with the same amount of 2,4-dinitrochlorobenzene acetone solution (concentration of 2.5%), and the Example 1~3 group and the Comparative Example 1-4 group were coated with the corresponding products. After 6 hours, remove the test substance with clean water and observe and compare the skin allergic reaction, and then observe again after 48 hours.

[0030] Specifically, the scores were scored according to the skin irritation test reaction scoring table in Table 1, and the skin irritation intensity was evaluated according to the evaluation criteria in Table 2. The final experimental results were recorded in Table 3.

[0031] Table 1 Skin irritation test reaction score table Table 2 Evaluation criteria for skin irritation intensity Table 3 Evaluation of skin irritation intensity of samples in each group of Examples 1-3 and Comparative Examples 1-4 It can be seen from the experimental data in Table 3 that the anesthetic preparations of Examples 1-3 of the present invention did not cause adverse phenomena such as erythema and edema after use and had no irritation to the skin.

[0032] Test Example 2 In order to verify the stability of the anesthetic preparations of Examples 1-3 and Comparative Examples 1-4, each group of anesthetic preparations was placed under the conditions of 40°C±2°C and 75%±5%, and the changes in the appearance properties of the samples and the labeled content of trimecaine were observed at 0, 1, 2, 3, and 6 months. The results are shown in Table 4.

[0033] Table 4 It can be seen from the test results in Table 4 that when the samples of Examples 1-3 are placed under accelerated conditions, the changes in the labeled content of trimecaine and the appearance properties of the anesthetic preparations are in compliance with regulations.

[0034] After the samples of Comparative Examples 1-4 were placed under accelerated conditions for 6 months, the trimecaine content of the samples and the appearance of the anesthetic preparations changed to varying degrees. Among them, sodium phytate was omitted in Comparative Example 2, and oligomeric schizophyllan polysaccharides were omitted in Comparative Example 3. After 6 months, the content of trimecaine decreased and stratification occurred, indicating that oligomeric schizophyllan polysaccharides and sodium phytate can work synergistically to improve the stability of the anesthetic preparation. Comparative Example 4 changed the molecular weight of oligomeric schizophyllan polysaccharides. After 6 months of accelerated testing, the stability of the samples was not as good as that of Example 1, indicating that the molecular weight of oligomeric schizophyllan polysaccharides also has a certain effect on the stability of the anesthetic preparation. The difference between Comparative Example 1 and Examples 1-3 is not obvious.

[0035] Test Example 3 In order to verify the anesthetic effects of the anesthetic preparations of Examples 1-3 and Comparative Examples 1-4 of the present invention, a radiant heat tail-flick latency test was used to conduct the test, and the specific steps are as follows: Experimental animals: Balb / c mice Place the mouse in a plastic box so that the ventral side of the tail about 5 to 6 cm distal to the mouse is just above a circular opening with a diameter of 0.5 cm, and an infrared radiation bulb is placed below the circular opening. Irradiate the mouse's tail skin with a light source, calculate the mouse's baseline latency (3-5) seconds, and discard mice that are too sensitive or dull. Then, take equal amounts of the anesthetic preparations of Examples 1-3 and Comparative Examples 1-4 and apply them to the mouse's tail, and record the tail-flick latency 10 min, 30 min, 1 h, 3 h, and 5 h after administration. To prevent damage to the mouse's tail tissue, the cutoff time is set to 10 seconds. Calculate the maximum possible effect (MPE%) at different time points. The maximum possible effect is obtained according to the following formula: Maximum possible effect (MPE) = (tail-flick latency - baseline latency) / (cutoff time - baseline latency) × 100%. See Table 5 for the results.

[0036] Table 5 As shown in Table 5, the anesthetic preparations described in Examples 1-3 are outstanding in terms of maximum anesthesia efficacy and anesthesia time, with better anesthetic effect, fast anesthesia onset, and longer anesthesia duration. Comparative Example 1 omits lindera lactone, and the maximum possible effect drops to 68.15% after 5h, and the anesthetic effect drops significantly, indicating that the lindera lactone and trimethocaine added in the formula can effectively improve the anesthetic efficacy and extend the anesthesia lasting time. Comparative Example 3 omits oligomeric schizophyllum polysaccharide, and its maximum possible effect drops to 79.66% after 5h, which may be because oligomeric schizophyllum polysaccharide has certain film-forming properties, and a uniform thin film can be formed on the skin surface after application, reducing the loss of the active ingredients of the anesthetic preparation, and to a certain extent, its anesthetic efficacy and anesthesia time can also be improved.

[0037] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. On the basis of the present invention, some modifications or replacements may be made thereto, but these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of protection claimed by the present invention.

Claims

1. An anesthetic preparation containing trimecaine, characterized in that: The invention comprises the following raw materials in parts by weight: 8-12 parts of trimecaine, 0.5-1 parts of lindera ether lactone, 0.3-0.8 parts of sodium phytate, 1-5 parts of oligomeric schizophyllan polysaccharide, 3-5 parts of 1,2-propylene glycol, 2-6 parts of sodium carboxymethyl cellulose, 3-8 parts of Tween and 60-70 parts of physiological saline.

2. The anesthetic preparation containing trimecaine according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 parts of lindera ether lactone, 0.5 parts of sodium phytate, 3 parts of oligomeric schizophyllan polysaccharide, 4 parts of 1,2-propylene glycol, 4 parts of sodium carboxymethyl cellulose, 5 parts of Tween and 65 parts of normal saline.

3. The anesthetic preparation containing trimecaine according to claim 1, characterized in that: The molecular weight of the oligomeric schizophyllan polysaccharide is 1-3KD.

4. The anesthetic preparation containing trimecaine according to claim 1, characterized in that: The Tween is Tween-80 or Tween-60.

5. The method for preparing the anesthetic preparation containing trimecaine according to claim 1, characterized in that: The steps include: (1) Weigh the components according to the weight proportions of claim 1, add lindera lactone to 1,2-propylene glycol, then add sodium carboxymethyl cellulose and Tween, and stir to obtain a mixed solution A; (2) adding trimecaine, sodium phytate and oligomeric schizophyllan to the mixed solution A, heating and stirring to obtain a mixed solution B; (3) Cool the mixed solution B to room temperature, then add physiological saline and homogenize under vacuum to obtain the product.

6. The method for preparing the anesthetic preparation containing trimecaine according to claim 5, characterized in that: The heating and stirring is performed at a temperature of 35-40° C. and for a time of 3-7 minutes.

7. The method for preparing the anesthetic preparation containing trimecaine according to claim 6, characterized in that: The vacuum homogenization pressure is 20-40 MPa and the time is 3-5 min.

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