An anesthetic preparation containing trimecaine and its preparation method

Abstract

The present invention belongs to the technical field of biomedicine, and particularly relates to an anesthetic preparation containing trimecaine and a preparation method thereof. The anesthetic preparation containing trimecaine comprises the following raw materials in parts by weight: 8-12 parts of trimecaine, 0.5-1 part of lindenenolide, 0.3-0.8 part of sodium phytate, 1-5 parts of schizophyllan oligosaccharide, 3-5 parts of 1,2-propanediol, 2-6 parts of sodium carboxymethylcellulose, 3-8 parts of Tween, and 60-70 parts of physiological saline. The combination of lindenenolide and trimecaine added in the anesthetic preparation of the present invention can improve the anesthetic effect and prolong the anesthetic time. Sodium phytate and schizophyllan oligosaccharide in the anesthetic preparation act synergistically to effectively improve the stability of the anesthetic preparation. Among them, due to the film-forming property of schizophyllan oligosaccharide, it can also improve the anesthetic efficacy of the anesthetic preparation to a certain extent. In addition, the anesthetic prepared by the present invention has no obvious irritation to the skin.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technologies, and particularly relates to an anesthetic preparation containing trimecaine and a preparation method thereof. Background Art

[0002] In the medical field, the research and application of anesthetic drugs have always been an important topic for improving the safety of surgeries and the comfort of patients. The most basic function of anesthetic preparations is to provide pain relief. During surgeries or certain special treatment processes, patients may experience severe pain. Anesthetic drugs can effectively relieve this pain by interfering with the pain signal conduction pathway, blocking the patient's ability to feel pain, and making them painless during the 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 also have extensive applications in the field of pain treatment, such as chronic pain management, cancer pain treatment, etc. In recent years, with the continuous progress of medical technologies, the types and properties of anesthetic drugs have also been continuously upgraded. Among them, anesthetic preparations containing trimecaine have received extensive attention due to their advantages such as rapid penetration, fast onset, long anesthetic duration, and no obvious irritation to the skin.

[0003] As a common ester local anesthetic drug, trimecaine is widely used in various surgical procedures and medical operations due to its rapid and effective analgesic effect. Its anesthetic mechanism is mainly to achieve local anesthesia by inhibiting nerve conduction. Currently, there are already various anesthetic preparations containing trimecaine on the market, but the existing trimecaine anesthetic preparations still have some deficiencies in preparation and application, such as unstable anesthetic effects, irritation to the skin, etc., which limit their effects in practical applications.

[0004] Linderane is a natural compound extracted from Lindera aggregata, which has various pharmacological activities. Research shows that linderane can inhibit the conduction of pain signals through various 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 affect 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 object of the present invention is to provide an anesthetic preparation containing trimecaine.

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

[0007] The objects of the present invention are achieved by the following technical solutions:

[0008] An anesthetic preparation containing trimecaine, comprising raw materials in the following parts by weight: 8-12 parts of trimecaine, 0.5-1 part of lindenenolide, 0.3-0.8 part of sodium phytate, 1-5 parts of schizophyllan oligosaccharide, 3-5 parts of 1,2-propanediol, 2-6 parts of sodium carboxymethylcellulose, 3-8 parts of Tween, and 60-70 parts of physiological saline.

[0009] Further, the anesthetic preparation containing trimecaine comprises raw materials in the following parts by weight: 10 parts of trimecaine, 0.75 part of lindenenolide, 0.5 part of sodium phytate, 3 parts of schizophyllan oligosaccharide, 4 parts of 1,2-propanediol, 4 parts of sodium carboxymethylcellulose, 5 parts of Tween, and 65 parts of physiological saline.

[0010] Further, the molecular weight of the schizophyllan oligosaccharide is 1-3 KD.

[0011] Further, the Tween is Tween-80 or Tween-60.

[0012] A preparation method of an anesthetic preparation containing trimecaine comprises the following steps:

[0013] (1) Weigh each component according to the above parts by weight. Take lindenenolide and add it to 1,2-propanediol, then add sodium carboxymethylcellulose and Tween, and stir and mix evenly to obtain a mixed solution A;

[0014] (2) Add trimecaine, sodium phytate, and schizophyllan oligosaccharide to the mixed solution A, heat and stir to obtain a mixed solution B;

[0015] (3) Cool the mixed solution B to room temperature, and then add physiological saline for vacuum homogenization to obtain the product.

[0016] Further, the heating temperature is 35-40 °C, and the stirring time is 3-7 min.

[0017] Further, the pressure of the vacuum homogenization is 20-40 MPa, and the time is 3-5 min.

[0018] Furthermore, the anesthetic preparation containing trimecaine is an anesthetic preparation for external application.

[0019] The present invention has the following effects compared with the prior art:

[0020] 1. The present invention provides an anesthetic preparation containing trimecaine, and lindenenolide, sodium phytate and schizophyllan oligosaccharide are further added to the formulation. The combination of lindenenolide and trimecaine can enhance the anesthetic effect and prolong the anesthetic time. Sodium phytate and schizophyllan oligosaccharide can act synergistically to effectively improve the stability of the anesthetic preparation. Among them, due to the film-forming property of schizophyllan oligosaccharide, it can also improve the anesthetic efficacy of the anesthetic preparation to a certain extent. In addition, the anesthetic preparation prepared by the present invention has no obvious irritation to the skin.

[0021] 2. The present invention provides a preparation method of an anesthetic preparation containing trimecaine. This method is simple and efficient, can be used for industrial production, and has broad application prospects in the medical field. Specific Embodiments

[0022] The present invention will be further described in detail below with reference to the 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 embodiments 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.

[0023] Example 1

[0024] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 part of lindenenolide, 0.5 part of sodium phytate, 3 parts of schizophyllan oligosaccharide (molecular weight 2KD), 4 parts of 1,2 - propanediol, 4 parts of sodium carboxymethylcellulose, 5 parts of Tween - 80, and 65 parts of physiological saline.

[0025] A preparation method of an anesthetic preparation containing trimecaine, comprising the following steps:

[0026] (1) Weigh each component according to the above parts by weight. Add lindenenolide into 1,2 - propanediol, and then add sodium carboxymethylcellulose and Tween - 80, and stir and mix evenly to form a mixed solution A;

[0027] (2) Add trimecaine, sodium phytate and schizophyllan oligosaccharide to the mixed solution A, and stir at 40 °C for 5 min to obtain a solution B;

[0028] (3) Cool the mixed solution B to room temperature, and then add physiological saline and carry out vacuum homogenization (40 MPa, 5 min) to obtain the product.

[0029] Example 2

[0030] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 8 parts of trimecaine, 0.5 part of lindenenolide, 0.3 part of sodium phytate, 1 part of schizophyllan oligosaccharide (molecular weight 1KD), 3 parts of 1,2 - propanediol, 2 parts of sodium carboxymethylcellulose, 3 parts of Tween - 60, and 60 parts of normal saline.

[0031] A preparation method of an anesthetic preparation containing trimecaine, comprising the following steps:

[0032] (1) Weigh each component according to the above parts by weight. Add lindenenolide into 1,2 - propanediol, and then add sodium carboxymethylcellulose and Tween - 60, and stir and mix evenly to form mixture A;

[0033] (2) Add trimecaine, sodium phytate, and schizophyllan oligosaccharide to mixture A, and stir at 40 °C for 3 min to obtain solution B;

[0034] (3) Cool mixture B to room temperature, and then add normal saline and carry out vacuum homogenization (20 MPa, 5 min) to obtain the product.

[0035] Example 3

[0036] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 12 parts of trimecaine, 1 part of lindenenolide, 0.8 part of sodium phytate, 5 parts of schizophyllan oligosaccharide (molecular weight 3KD), 5 parts of 1,2 - propanediol, 6 parts of sodium carboxymethylcellulose, 8 parts of Tween - 80, and 70 parts of normal saline.

[0037] A preparation method of an anesthetic preparation containing trimecaine, comprising the following steps:

[0038] (1) Weigh each component according to the above parts by weight. Add lindenenolide into 1,2 - propanediol, and then add sodium carboxymethylcellulose and Tween - 80, and stir and mix evenly to form mixture A;

[0039] (2) Add trimecaine, sodium phytate, and schizophyllan oligosaccharide to mixture A, and stir at 40 °C for 7 min to obtain solution B;

[0040] (3) Cool mixture B to room temperature, and then add normal saline and carry out vacuum homogenization (30 MPa, 3 min) to obtain the product.

[0041] Comparative Example 1

[0042] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 10 parts of trimecaine, 0.5 part of sodium phytate, 3 parts of schizophyllan oligosaccharide (molecular weight 2KD), 4 parts of 1,2 - propanediol, 4 parts of sodium carboxymethylcellulose, 5 parts of Tween - 80, and 65 parts of normal saline. The rest is the same as in Example 1.

[0043] Comparative Example 2

[0044] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 part of lindenenolide, 3.5 parts of schizophyllan oligosaccharide (molecular weight 2KD), 4 parts of 1,2-propanediol, 4 parts of sodium carboxymethylcellulose, 5 parts of Tween-80, and 65 parts of normal saline. The rest is the same as in Example 1.

[0045] Comparative Example 3

[0046] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 part of lindenenolide, 3.5 parts of sodium phytate, 4 parts of 1,2-propanediol, 4 parts of sodium carboxymethylcellulose, 5 parts of Tween-80, and 65 parts of normal saline. The rest is the same as in Example 1.

[0047] Comparative Example 4

[0048] An anesthetic preparation containing trimecaine, comprising the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 part of lindenenolide, 0.5 part of sodium phytate, 3 parts of schizophyllan oligosaccharide (molecular weight 10kD), 4 parts of 1,2-propanediol, 4 parts of sodium carboxymethylcellulose, 5 parts of Tween-80, and 65 parts of normal saline.

[0049] Test Example 1

[0050] Skin irritation test

[0051] Test animals: SPF guinea pigs at 6 weeks of age were selected for skin irritation experiments, and then placed in an environment of 25°C and a relative humidity of 60%, with 12h of light and 12h of darkness alternating. The guinea pigs were subjected to an adaptation test for one week, during which they drank and ate normally every day.

[0052] Test method: Ninety guinea pigs were randomly divided into a negative control group, a positive control group, Example 1-3 groups, and Comparative Example 1-4 groups, with 10 guinea pigs in each group. On the 0th day, 7th day, and 14th day, anesthetic preparations (0.5 mL) of Examples 1-3 and Comparative Examples 1-4 in equal amounts were applied to the depilated area of 3 cm * 3 cm on the left side of the guinea pigs' backs. The positive control group was applied with an equal amount of 2,4-dinitrochlorobenzene (concentration 2.5%), and the negative control group was applied with an equal amount of sterile physiological saline. The administration site was covered with 2 layers of gauze and 1 layer of cellophane, fixed with a sterile bandage, and the drug was washed off with water after 6 h. On the 14th day after sensitization with the last administration of the test substance, a challenge contact experiment was conducted (the area of 3 cm * 3 cm on the right side of the animal's back was depilated before the experiment). The negative control group was applied with an equal amount of sterile physiological saline, the positive control group was applied with an equal amount of acetone solution of 2,4-dinitrochlorobenzene (concentration 2.5%), and the Example 1-3 groups and Comparative Example 1-4 groups were applied with the corresponding products. After 6 h, the test substance was removed with water, and the skin allergic reaction could be observed and compared. Then, it was observed again at 48 h.

[0053] Specifically, scoring was carried out according to the skin irritation test response 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.

[0054] Table 1 Skin irritation test response scoring table

[0055]

[0056] Table 2 Skin irritation intensity evaluation criteria

[0057]

[0058] Table 3 Evaluation of skin irritation intensity of samples in Example 1-3 and Comparative Example 1-4 groups

[0059]

[0060] From the experimental data in Table 3, it can be seen that the anesthetic preparations of Examples 1-3 of the present invention showed no adverse phenomena such as erythema and edema after use and had no irritation to the skin.

[0061] Test Example 2

[0062] In order to verify the stability of the anesthetic preparations of Examples 1-3 and Comparative Examples 1-4, the anesthetic preparations of each group were placed under the conditions of 40 °C ± 2 °C and 75% ± 5%, and the changes in the appearance and the labeled content of trimecaine of the samples were observed at the 0th, 1st, 2nd, 3rd, and 6th months. The results are shown in Table 4.

[0063] Table 4

[0064]

[0065] As can be seen from the test results in Table 4, when the samples of Examples 1-3 were placed under accelerated conditions, the labeled content of trimecaine and the changes in the appearance properties of the anesthetic preparation all met the requirements.

[0066] After the samples of Comparative Examples 1-4 were placed under accelerated conditions for 6 months, varying degrees of changes occurred in the trimecaine content and the appearance properties of the anesthetic preparation. Among them, sodium phytate was omitted in Comparative Example 2, and Schizophyllan oligosaccharide was omitted in Comparative Example 3. After 6 months, the content of trimecaine decreased and layering occurred in both cases, indicating that Schizophyllan oligosaccharide and sodium phytate can act synergistically to improve the stability of the anesthetic preparation. In Comparative Example 4, the molecular weight of Schizophyllan oligosaccharide was changed. After 6 months of accelerated testing, the stability of the sample was also inferior to that of Example 1, indicating that the molecular weight of Schizophyllan oligosaccharide also has a certain influence on the stability of the anesthetic preparation. The difference between Comparative Example 1 and Examples 1-3 was not obvious.

[0067] Test Example 3

[0068] 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 conducted, and the specific steps were as follows:

[0069] Test animals: Balb / c mice

[0070] The mice were placed in a plastic box such that the ventral side of the distal end of their tails, approximately 5 to 6 cm from the tip, was exactly above a circular opening with a diameter of 0.5 cm, and an infrared radiation lamp was arranged below the circular opening. The light source was used to irradiate the tail skin of the mice, and the baseline latency (3-5) seconds of the mice was calculated. Mice that were too sensitive or too dull were discarded. Subsequently, equal amounts of the anesthetic preparations of Examples 1-3 and Comparative Examples 1-4 were respectively applied to the tails of the mice, and the tail-flick latency at 10 min, 30 min, 1 h, 3 h, and 5 h after administration was recorded. To prevent damage to the tail tissues of the mice, the cut-off time was set to 10 seconds. The maximum possible effect (MPE%) at different time points was calculated, and the maximum possible effect was obtained according to the following formula:

[0071] Maximum possible effect (MPE) = (tail-flick latency - baseline latency) / (cut-off time - baseline latency) × 100%. The results are shown in Table 5.

[0072] Table 5

[0073]

[0074] As can be seen from Table 5, the anesthetic preparations described in Examples 1-3 are outstanding in terms of maximum anesthetic efficacy and anesthetic time, having a better anesthetic effect, a fast onset of anesthesia, and a longer anesthetic duration. In Comparative Example 1, lindenenolide was omitted, and the maximum possible effect decreased to 68.15% after 5 h, with a significant decrease in the anesthetic effect, indicating that the combination of lindenenolide and trimecaine added to the formulation can effectively enhance the anesthetic efficacy and prolong the anesthetic duration. In Comparative Example 3, schizophyllan oligosaccharide was omitted, and the maximum possible effect decreased to 79.66% after 5 h. This may be because schizophyllan oligosaccharide has a certain film-forming property, and after application, it can form a uniform thin film on the skin surface, reducing the loss of the active ingredients of the anesthetic preparation, and to a certain extent, it can also enhance its anesthetic efficacy and anesthetic time.

[0075] 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 with specific implementation schemes above. On the basis of the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not make the essence of the corresponding technical solutions deviate from the scope of the present invention claimed.

Claims

1. An anesthetic preparation containing trimecaine, characterized in that, It comprises the following raw materials in parts by weight: 8-12 parts of trimecaine, 0.5-1 part of lindenenolide, 0.3-0.8 part of sodium phytate, 1-5 parts of schizophyllan oligosaccharide, 3-5 parts of 1,2-propanediol, 2-6 parts of sodium carboxymethyl cellulose, 3-8 parts of Tween, and 60-70 parts of normal saline; the molecular weight of the schizophyllan oligosaccharide is 1-3 KD.

2. The anesthetic preparation containing trimecaine according to claim 1, characterized in that, It comprises the following raw materials in parts by weight: 10 parts of trimecaine, 0.7 part of lindenenolide, 0.5 part of sodium phytate, 3 parts of schizophyllan oligosaccharide, 4 parts of 1,2-propanediol, 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 Tween is Tween-80 or Tween-60.

4. The preparation method of the anesthetic preparation containing trimecaine according to claim 1, characterized in that, It comprises the following steps: (1) Weigh each component according to the parts by weight described in Claim 1. Take lindenenolide and add it to 1,2-propanediol, then add sodium carboxymethyl cellulose and Tween, and stir and mix evenly to obtain mixture A; (2) Add trimecaine, sodium phytate, and schizophyllan oligosaccharide to mixture A, heat and stir to obtain mixture B; (3) Cool mixture B to room temperature, then add normal saline and homogenize under vacuum to obtain the product.

5. The preparation method of the anesthetic preparation containing trimecaine according to claim 4, characterized in that, The temperature of the heating and stirring is 35-40 °C, and the time is 3-7 min.

6. The preparation method of the anesthetic preparation containing trimecaine according to claim 4, characterized in that, The pressure of the vacuum homogenization is 20-40 MPa, and the time is 3-5 min.

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