Flux core release agent and preparation method thereof

Abstract

The invention relates to the technical field of medicinal release agents, and particularly discloses a medicine core release agent and a preparation method thereof. The flux core release agent is prepared from the following raw materials in parts by weight: 160-165 parts of lauryl sodium sulfate; 55 to 60 parts of sodium p-toluenesulfonate; 300 to 310 parts of sodium alcohol ether sulphate; 1450 to 1550 parts of a wetting agent; and 4800 to 5200 parts of water. The preparation method comprises the following steps: taking 10-15% by weight of water, heating to 90-95 DEG C, adding lauryl sodium sulfate and p-toluenesulfonic acid, and uniformly mixing; cooling to 50-55 DEG C, adding sodium alcohol ether sulphate, and uniformly mixing; finally, adding the residual weight of water and glycerol at the temperature of 60-65 DEG C, and uniformly mixing; and cooling to obtain the flux core release agent. After the flux core release agent is applied, the peeling strength between a film structure formed by the flux core release agent and a flux core is not prone to large loss along with continuous proceeding of the demolding process, and the whole flux core release agent has excellent application stability durability.

Description

Technical Field

[0001] The present application relates to the technical field of pharmaceutical release agents, and more specifically, to a drug core release agent and a preparation method thereof. Background Art

[0002] A release agent is a functional substance between the mold and the finished product. It is used as an interface coating on the surfaces of two objects that are easy to adhere to each other. It can make the surfaces of the objects easy to detach, smooth and clean, and aims to improve the separation performance between the mold and the finished workpiece material.

[0003] In the production process of drug cores in the pharmaceutical industry, molds are needed to press the drug cores into shape, and demolding refers to the process of removing the pressed drug cores from the molds. During the demolding process, a release agent is used to prevent the tablets from sticking and making demolding difficult. In the production process of drug cores, the selection of release agents is a crucial link. Its main function is to reduce the friction between the mold and the drug core during the pressing and molding of the drug core, prevent the drug core from sticking to the mold, and ensure the smooth progress of the pressing process and the integrity of the product. Currently, the commonly used release agents are liquid paraffin, vegetable oil and glycerin, which will not contaminate the molded product during use.

[0004] Regarding the above-mentioned related technologies, the inventors believe that although the release agent can bring higher demoulding efficiency at the beginning of use and the obtained demoulding core product quality is also higher, as the demoulding process continues, the peeling strength between the film structure formed by the release agent and the core will increase, and excessively high peeling strength will make it difficult for the core to be removed from the mold, and it is easy to cause the core to be damaged or deformed during the demoulding process. Therefore, it is necessary to regularly reapply the release agent used on the mold. It can be seen that the application stability and durability of the release agent still needs to be improved.

[0005] Therefore, it is urgent to propose a solution to solve the above technical problems. Summary of the invention

[0006] In order to improve the application stability and durability of a core release agent, the present application provides a core release agent and a preparation method thereof.

[0007] In the first aspect, the present application provides a core release agent, which adopts the following technical solution: A core release agent is prepared from the following raw materials in parts by weight: 160-165 parts of sodium lauryl sulfate; 55-60 parts of sodium p-toluenesulfonate; 300-310 parts of fatty alcohol polyoxyethylene ether sodium sulfate; Wetting agent 1450-1550 parts; 4800-5200 parts of water.

[0008] By adopting the above technical solution, in the core release agent, the wetting agent contains at least any one of liquid paraffin, vegetable oil and glycerin, which can help the core release agent to have excellent surface wetting properties after use, so that it can enter tiny gaps more easily, and it can also help the core release agent to adhere to the mold surface more stably, and it has excellent lubrication properties, which is also more conducive to better core release effects. At the same time, sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate are also used in the core release agent. Sodium dodecyl sulfate has good emulsification, penetration and dispersion properties, which can reduce the surface tension of the core release agent and form a more uniform film after the core release agent is used; sodium p-toluenesulfonate has water-soluble, viscosity-reducing, dispersing and emulsifying properties, which can make the raw materials of each component fully mixed and form a stable joint, and make the film structure after the core release agent is used and the peel strength between the core is lower and more stable; sodium fatty alcohol polyoxyethylene ether sulfate is in various environments It can maintain good stability under all conditions and form a stable emulsion system after mixing with other raw materials. After the drug core release agent is applied, the drug core is easier to be separated from the mold. Moreover, after the mixed application of sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate, in addition to being able to stably exert their own effects, it can also bring excellent synergistic effects, so that after the drug core release agent is applied, during the continuous demoulding process, the loss of peeling strength between the film structure formed by the release agent and the drug core will be significantly reduced, thereby being able to bring about an excellent improvement in the stability and durability of the release agent application.

[0009] Preferably, the weight ratio of the sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate is 20:29:152.

[0010] By adopting the above technical scheme, when the sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol sulfate in the above weight ratio are used in combination, the synergistic effect between each other is relatively excellent, so that the peel strength between the film structure formed by the release agent and the drug core is not prone to significant loss as the demolding process continues, and has a longer service life, thereby showing better application stability and durability.

[0011] Preferably, 8-15 parts by weight of a functional additive are added to the raw materials of the core release agent, and the functional additive is composed of hexaglycerol monooleate and sodium petroleum sulfonate in a weight ratio of (3-5):1.

[0012] By adopting the above technical scheme, hexaglycerol monooleate can improve the wettability and dispersibility of the release agent, and can inhibit the structural changes of the release agent during use, thereby improving the performance stability of the release agent; sodium petroleum sulfonate can reduce the liquid surface tension of the core release agent and reduce the interface formation, and has a promoting effect on the mixing and combining of the raw materials, so that the application performance of the release agent is further improved; and when hexaglycerol monooleate and sodium petroleum sulfonate are used as functional additives, the two can form a microstructure and microinterface regulation and enhancement system to ensure that the film structure formed by the application of the core release agent has more excellent stability during the continuous demolding process. At the same time, the functional additive also has an auxiliary synergistic effect on the compound system of sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol sulfate, thereby significantly improving the application stability and durability of the core release agent.

[0013] Preferably, the weight ratio of hexaglycerol monooleate to sodium petroleum sulfonate is 4.2:1.

[0014] By adopting the above technical scheme, when the functional additive composed of hexaglycerol monooleate and sodium petroleum sulfonate in the above weight ratio is used, the corresponding effect brought by the interaction between the two is better, and the application stability and durability of the obtained core release agent is also better.

[0015] Preferably, the wetting agent is one or a combination of liquid paraffin, vegetable oil and glycerin.

[0016] By adopting the above technical scheme, liquid paraffin has better fluidity and can form an isolation film on the surface of the mold; vegetable oil has good lubrication and isolation effects, and is more environmentally friendly and safe to use; glycerin can be extracted from glycerin residue, which is conducive to the comprehensive utilization of resources, and the molecular structure and viscosity of glycerin also help to improve the spreadability and demolding effect of the release agent; one or more of liquid paraffin, vegetable oil and glycerin are selected as wetting agents, which are all suitable for the excellent effects of the composite system of sodium dodecyl sulfate, sodium p-toluenesulfonate and fatty alcohol polyoxyethylene ether sodium sulfate, thereby obtaining a core release agent with stable application and excellent durability.

[0017] Preferably, the wetting agent consists of vegetable oil and glycerin in a weight ratio of 1:(4-6).

[0018] By adopting the above technical scheme, vegetable oil and glycerin are used as a wetting agent, which can make the drug core release agent more excellent in spreadability, thereby forming a more uniform film structure, and helping sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate to fully cooperate to produce corresponding effects; at the same time, the combination of vegetable oil and glycerin has certain advantages in cost control and environmental protection.

[0019] Preferably, the vegetable oil is modified before use, and the modification steps are as follows: S1, mixing oleic acid and acetic acid at a molar ratio of 1:(0.4-0.5), adding sulfuric acid as a catalyst, heating to 35-40°C, adding hydrogen peroxide in an amount of 1.2-1.6 times the amount of oleic acid, reacting at 55-65°C for 3.5-4h, heating under reflux for 50-70min, and standing for stratification; mixing the oil layer raw material after stratification with glycerol at a molar ratio of 1:(0.9-1.1), adding zinc oxide as a catalyst, reacting at 175-185°C for 3.5-4.5h, and obtaining a modifier; S2. Mix the vegetable oil raw material and the modifier in a weight ratio of (2.2-2.5):1, stir under nitrogen protection, and heat to 175-185°C. After reacting for 5.5-6.5 hours, cool down, mix with trimethylsilyl chloride in a molar ratio of (1.1-1.3):1, add anhydrous ether, react at 40-45°C for 2-3 hours, wash the product, evaporate the solvent, and vacuum dry to remove water to obtain modified vegetable oil.

[0020] By adopting the above technical scheme, in the process of sensitization of vegetable oil, by increasing the content of linoleic acid and oleic acid, reducing the double bond content in vegetable oil, and introducing silicone into the vegetable oil molecule, the oxidative stability of vegetable oil can be improved, and the obtained modified vegetable oil can also show better lubrication performance. When the obtained modified vegetable oil is applied to the core release agent, the core release agent can form a closer combination with other raw materials during the actual film-forming process, and the formed film structure can also maintain better stability as the demoulding process continues, further improving the application stability and durability of the core release agent.

[0021] In a second aspect, the present application provides a method for preparing a core release agent, using the following technical solution: A method for preparing a core release agent comprises the following steps: (1) preparing raw materials including sodium lauryl sulfate, sodium p-toluenesulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, a wetting agent and water according to a ratio; (2) Take 10-15% by weight of water, heat it to 90-95° C., add sodium dodecyl sulfate and p-toluenesulfonic acid, and mix them evenly; then cool it to 50-55° C., add sodium fatty alcohol polyoxyethylene ether sulfate, and mix them evenly; finally, add the remaining weight of water and wetting agent, the water temperature is 60-65° C., and mix them evenly; after cooling, the core release agent is obtained.

[0022] By adopting the above technical scheme, the above method is simple to operate and is convenient for large-scale industrial production; at the same time, the raw materials are used in an orderly manner, which not only makes it easy to control the quality during the process, but also enables sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate to be fully compounded after mixing, thereby obtaining a core release agent with stable quality and excellent quality.

[0023] In summary, this application has the following beneficial effects: 1. The present application uses sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate to mix and compound, so that after the drug core release agent is applied, the peel strength between the film structure formed and the drug core is not prone to significant loss as the demoulding process continues, and has a long service life, thereby being able to bring about an excellent improvement in the stability and durability of the application of the release agent; 2. The present application uses a functional additive composed of hexaglycerol monooleate and sodium petroleum sulfonate to form a microstructure and microinterface regulation and enhancement system in the mixed system of the drug core release agent, and to assist in enhancing the effect of the compound system between sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate, thereby significantly improving the application stability and durability of the drug core release agent; 3. In the present application, vegetable oil and glycerin are used as a wetting agent, and the vegetable oil is modified so that the drug core release agent forms a closer bond with other raw materials during the film-forming process, and the final film structure can maintain better stability as the demolding process continues, thereby further improving the stability and durability of the drug core release agent. DETAILED DESCRIPTION

[0024] The present application is further described in detail below in combination with preparation examples, embodiments and comparative examples.

[0025] Unless otherwise specified, the raw materials used in the preparation examples, embodiments and comparative examples of the present application are commercially available: Glycerol was purchased from Jinan Xinshuangyue Chemical Co., Ltd., Musim Mas, Indonesia, and was pharmaceutical grade; The vegetable oil was epoxidized soybean oil purchased from Shanghai Bangcheng Chemical Co., Ltd. and was of pharmaceutical grade.

[0026] Preparation examples of raw materials and / or intermediates Preparation Example 1 A modified vegetable oil is prepared by the following steps: S1, oleic acid and acetic acid are mixed at a molar ratio of 1:0.45, sulfuric acid is added as a catalyst, the temperature is raised to 37.5°C, hydrogen peroxide in an amount 1.4 times the amount of oleic acid is added, the mixture is reacted at 60°C for 3.75 hours, the mixture is heated under reflux for 60 minutes, and the mixture is allowed to stand for stratification; the oil layer raw material after stratification is mixed with glycerol at a molar ratio of 1:1, zinc oxide is added as a catalyst, the mixture is reacted at 180°C for 4 hours, and a modifier is obtained; S2. Mix the vegetable oil raw material and the modifier in a weight ratio of 2.35:1, stir under nitrogen protection, and heat to 180°C. After reacting for 6 hours, cool down, mix with trimethylsilyl chloride in a molar ratio of 1.2:1, add anhydrous ether, react at 42.5°C for 2.5 hours, wash the product with saturated sodium chloride solution, evaporate the solvent, and vacuum dry to remove water to obtain modified vegetable oil.

[0027] Note: In the above operation, the amount of sulfuric acid used as a catalyst is 3% of the mass of the mixture of oleic acid and acetic acid; the amount of zinc oxide used as a catalyst is 5% of the mass of the mixture of oil layer raw materials and glycerol; the ratio of anhydrous ether used and the mixture obtained by adding trimethylsilyl chloride is 1mL:12mg.

[0028] Preparation Example 2 A modified vegetable oil, which is different from Preparation Example 1 in that it is prepared by the following steps: S1, oleic acid and acetic acid are mixed at a molar ratio of 1:0.4, sulfuric acid is added as a catalyst, the temperature is raised to 35°C, hydrogen peroxide in an amount 1.2 times the amount of oleic acid is added, the mixture is reacted at 55°C for 4 hours, the mixture is heated under reflux for 50 minutes, and the mixture is allowed to stand for stratification; the oil layer raw material after stratification is mixed with glycerol at a molar ratio of 1:0.9, zinc oxide is added as a catalyst, the mixture is reacted at 175°C for 4.5 hours, and a modifier is obtained; S2. Mix the vegetable oil raw material and the modifier in a weight ratio of 2.2:1, stir under nitrogen protection, and heat to 175°C. After reacting for 6.5 hours, cool down, mix with trimethylsilyl chloride in a molar ratio of 1.1:1, add anhydrous ether, react at 40°C for 3 hours, wash the product with saturated sodium chloride solution, evaporate the solvent, and vacuum dry to remove water to obtain modified vegetable oil.

[0029] Preparation Example 3 A modified vegetable oil, which is different from Preparation Example 1 in that it is prepared by the following steps: S1, oleic acid and acetic acid are mixed at a molar ratio of 1:0.5, sulfuric acid is added as a catalyst, the temperature is raised to 40°C, hydrogen peroxide in an amount 1.2 times the amount of oleic acid is added, the mixture is reacted at 65°C for 3.5 hours, the mixture is heated under reflux for 50 minutes, and the mixture is allowed to stand for stratification; the oil layer raw material after stratification is mixed with glycerol at a molar ratio of 1:1.1, zinc oxide is added as a catalyst, the mixture is reacted at 185°C for 3.5 hours, and a modifier is obtained; S2. Mix the vegetable oil raw material and the modifier in a weight ratio of 2.5:1, stir under nitrogen protection, and heat to 185°C. After reacting for 5.5 hours, cool down, mix with trimethylsilyl chloride in a molar ratio of 1.3:1, add anhydrous ether, react at 45°C for 2 hours, wash the product with saturated sodium chloride solution, evaporate the solvent, and vacuum dry to remove water to obtain modified vegetable oil. Example

[0030] Example 1 A core release agent, the weight of raw materials used in its preparation is shown in Table 1, and it is prepared by the following steps: (1) preparing raw materials including sodium lauryl sulfate, sodium p-toluenesulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, a wetting agent and water according to a ratio; (2) Take 12.5% ​​by weight of water, heat it to 92.5° C., add sodium dodecyl sulfate and p-toluenesulfonic acid, stir at 135 r / min for 15 min to mix evenly; then cool to 52.5° C., add sodium fatty alcohol polyoxyethylene ether sulfate, stir at 135 r / min for 25 min to mix evenly; finally add the remaining weight of water and glycerin, the water temperature is 62.5° C., stir at 135 r / min for 25 min to mix evenly; after cooling to 37° C., the core release agent is obtained.

[0031] Note: The wetting agent used in the above operation is glycerol.

[0032] Example 2 A core release agent, which is different from Example 1 in that it is prepared by the following steps: (1) preparing raw materials including sodium lauryl sulfate, sodium p-toluenesulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, a wetting agent and water according to a ratio; (2) Take 10% by weight of water, heat it to 90° C., add sodium dodecyl sulfate and p-toluenesulfonic acid, stir at 135 r / min for 15 min to mix evenly; then cool to 50° C., add sodium fatty alcohol polyoxyethylene ether sulfate, stir at 135 r / min for 25 min to mix evenly; finally add the remaining weight of water and glycerin, the water temperature is 60° C., stir at 135 r / min for 25 min to mix evenly; after cooling to 37° C., the core release agent is obtained.

[0033] Example 3 A core release agent, which is different from Example 1 in that it is prepared by the following steps: (1) preparing raw materials including sodium lauryl sulfate, sodium p-toluenesulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, a wetting agent and water according to a ratio; (2) Take 15% by weight of water, heat it to 95°C, add sodium dodecyl sulfate and p-toluenesulfonic acid, stir at 135 r / min for 15 min to mix evenly; then cool to 55°C, add sodium fatty alcohol polyoxyethylene ether sulfate, stir at 135 r / min for 25 min to mix evenly; finally add the remaining weight of water and wetting agent, the water temperature is 65°C, stir at 135 r / min for 25 min to mix evenly; after cooling to 37°C, the core release agent is obtained.

[0034] Embodiment 4-6 A core release agent, which is different from Example 1 in that the weights of the raw materials used in its preparation are shown in Table 1.

[0035] Table 1 Raw materials used in the preparation of Examples 1, 4-6 and their corresponding weights (kg / portion) raw material Example 1 Example 4 Example 5 Example 6 Sodium Lauryl Sulfate 162 162.5 160 165 Sodium p-toluenesulfonate 58 55 50 60 Fatty alcohol polyoxyethylene ether sodium sulfate 304 305 300 310 Wetting Agents 1500 1500 1450 1550 water 5000 5000 4800 5200 Example 7 A medicine core release agent, which is different from Example 1 in that the wetting agent consists of vegetable oil and glycerin in a weight ratio of 1:5, and the vegetable oil is epoxidized soybean oil.

[0036] Example 8 A medicine core release agent, which is different from Example 1 in that the wetting agent consists of vegetable oil and glycerin in a weight ratio of 1:4, and the vegetable oil is epoxidized soybean oil.

[0037] Example 9 A medicine core release agent, which is different from Example 1 in that the wetting agent consists of vegetable oil and glycerin in a weight ratio of 1:6, and the vegetable oil is epoxidized soybean oil.

[0038] Example 10 A medicine core release agent, which is different from Example 1 in that the wetting agent is vegetable oil, and the vegetable oil is epoxidized soybean oil.

[0039] Embodiment 11 A core release agent, which is different from Example 7 in that the vegetable oil is replaced by modified vegetable oil, and the modified vegetable oil is obtained from Preparation Example 1.

[0040] Example 12 A core release agent, which is different from Example 7 in that the vegetable oil is replaced by modified vegetable oil, and the modified vegetable oil is obtained from Preparation Example 2.

[0041] Embodiment 13 A core release agent, which is different from Example 7 in that the vegetable oil is replaced by modified vegetable oil, and the modified vegetable oil is obtained from Preparation Example 3.

[0042] Embodiment 14 A core release agent is different from Example 1 in that 11.5 parts by weight of a functional additive are also added to the raw material, the functional additive is composed of hexaglycerol monooleate and sodium petroleum sulfonate in a weight ratio of 4.2:1, and the functional additive is added together with the wetting agent.

[0043] Embodiment 15 A core release agent, which is different from Example 14 in that the weight parts of the functional auxiliary agent added are 8 parts.

[0044] Example 16 A core release agent, which is different from Example 14 in that the weight portion of the functional auxiliary agent added is 15 parts.

[0045] Embodiment 17 A core release agent, which is different from Example 14 in that the functional additive is composed of hexaglycerol monooleate and sodium petroleum sulfonate in a weight ratio of 4:1.

[0046] Embodiment 18 A core release agent, which is different from Example 14 in that the functional additive is composed of hexaglycerol monooleate and sodium petroleum sulfonate in a weight ratio of 3:1.

[0047] Embodiment 19 A core release agent, which is different from Example 14 in that the functional additive is composed of hexaglycerol monooleate and sodium petroleum sulfonate in a weight ratio of 5:1.

[0048] Embodiment 20 A core release agent, which is different from Example 14 in that hexaglycerol monooleate is not used in the functional auxiliary agent.

[0049] Embodiment 21 A core release agent, which is different from Example 14 in that sodium petroleum sulfonate is not used in the functional additive.

[0050] Comparative Example Comparative Example 1 A core release agent, which is different from Example 1 in that sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate are not used in the raw materials.

[0051] Comparative Example 2 A core release agent, which is different from Example 1 in that sodium lauryl sulfate and sodium fatty alcohol polyoxyethylene ether sulfate are not used in the raw materials.

[0052] Comparative Example 3 A core release agent, which is different from Example 1 in that sodium dodecyl sulfate and sodium p-toluenesulfonate are not used in the raw materials.

[0053] Comparative Example 4 A core release agent, which is different from Example 1 in that sodium lauryl sulfate is not used in the raw materials.

[0054] Comparative Example 5 A core release agent, which is different from Example 1 in that sodium p-toluenesulfonate is not used in the raw materials.

[0055] Comparative Example 6 A core release agent, which is different from Example 1 in that fatty alcohol polyoxyethylene ether sodium sulfate is not used in the raw materials.

[0056] Comparative Example 7 A core release agent, which is different from Example 1 in that sodium lauryl sulfate, sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate are not used in the raw materials.

[0057] Comparative Example 8 A core release agent, which is different from Example 14 in that sodium lauryl sulfate, sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate are not used in the raw materials.

[0058] Performance test test samples: The core release agent obtained in Example 1-21 was used as test sample 1-21, and the core release agent obtained in Comparative Example 1-8 was used as control sample 1-8.

[0059] Test method: Taking the preparation method of a contraceptive implant core disclosed in patent publication number CN113413358A as an example, a finished core with a length of 43 mm, a diameter of 2.1±0.01 mm, and a weight of 150 mg was prepared according to the method described in Example 1 in the specification; during the preparation process, a core release agent was sprayed on the surface of the mold at a spraying amount of 0.25 ml / m 2, and after the finished drug core is molded, the peel strength tester is used to accurately measure the peeling force between the drug core and the substrate, and the obtained peel strength is recorded as the initial peel strength; at the same time, in the preparation of the finished drug core, after 20 demouldings, the peel strength tester is used again to accurately measure the peeling force between the drug core and the substrate, and the obtained peel strength is recorded as the peel strength after application; finally, the peel strength growth rate is calculated, the peel strength growth rate = (peel strength after application-initial peel strength) / initial peel strength, the greater the peel strength growth rate, the worse the application stability and durability of the drug core release agent. After completing the test samples 1-21 and control samples 1-8 in turn according to the above method, the test results are recorded in Table 2 accordingly.

[0060] Table 2 Test results of test samples 1-21 and control samples 1-8 It can be seen from Examples 1-3 and Comparative Examples 1-7 and Table 2 that in the core release agent of the present application, by using sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate, the peel strength growth rate obtained in the test can be significantly reduced, thereby significantly improving the application stability and durability of the release agent; and if, on the basis of containing a wetting agent, only one or two of sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate are used, it is found that although the peel strength growth rate can be reduced, the effect is extremely limited, and the effects are only simply superimposed on each other. Only when the three raw materials are compounded and used, can a compounding improvement effect of 1+1>2 be brought about, and a core release agent with stable and durable application can be obtained.

[0061] Combining Example 1 and Examples 4-6 with Table 2, it can be seen that when the weight ratio of sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate is 20:29:152, the corresponding effect of the three is relatively excellent, so that the peel strength between the film structure formed by the release agent and the drug core is not prone to significant loss as the demolding process continues, and the peel strength growth rate obtained by the test is also low.

[0062] Combining Example 1 and Example 7-10 with Table 2, it can be seen that the use of vegetable oil and glycerol as a wetting agent has a lower peel strength growth rate than using vegetable oil or glycerol alone as a wetting agent, indicating that the mixed system of vegetable oil and glycerol is more suitable for sodium lauryl sulfate, sodium p-toluenesulfonate and sodium polyoxyethylene fatty alcohol ether sulfate to fully cooperate and exert excellent corresponding effects. Combining Examples 11-13 with Table 2, it can be seen that modifying the vegetable oil can improve the stability and durability of the core release agent after application, and the peel strength growth rate obtained by the test has also been further reduced.

[0063] It can be seen from Example 1 and Example 14-19 and Table 2 that the use of a functional additive composed of hexaglycerol monooleate and sodium petroleum sulfonate can significantly improve the application stability and durability of the core release agent, and the peel strength growth rate obtained by testing is also significantly reduced, wherein when the weight ratio of hexaglycerol monooleate and sodium petroleum sulfonate is 4.2: 1, the corresponding improvement effect brought by the application of the functional additive is better. It can be seen from Example 20-21 and Table 2 that if any one of hexaglycerol monooleate and sodium petroleum sulfonate is added and used alone, the corresponding improvement effect brought is limited, and is far less than the excellent effect brought by the compounding of the two. It can be seen from Comparative Examples 7-8 and Table 2 that if sodium lauryl sulfate, sodium p-toluenesulfonate and sodium sulfate of fatty alcohol polyoxyethylene ether are not used in the raw materials, it is found that the improvement effect brought by the functional additive will be greatly discounted, indicating that the compounding system formed by the two has the effect of mutual assistance and enhancement, and thus a core release agent with excellent application stability and durability can be obtained.

[0064] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make modifications to the present embodiment without any creative contribution as needed, but such modifications are protected by the patent law as long as they are within the scope of the claims of the present application.

Claims

1. A core release agent, characterized in that: Made from the following raw materials in parts by weight: 160-165 parts of sodium lauryl sulfate; 55-60 parts of sodium p-toluenesulfonate; 300-310 parts of fatty alcohol polyoxyethylene ether sodium sulfate; Wetting agent 1450-1550 parts; 4800-5200 parts of water.

2. The core release agent according to claim 1, characterized in that: The weight ratio of the sodium dodecyl sulfate, sodium p-toluenesulfonate and sodium fatty alcohol polyoxyethylene ether sulfate is 20:29:

152.

3. The core release agent according to claim 1, characterized in that: The raw materials of the core release agent are further added with 8-15 parts by weight of a functional auxiliary agent, wherein the functional auxiliary agent is composed of hexaglycerol monooleate and sodium petroleum sulfonate in a weight ratio of (3-5):

1.

4. The core release agent according to claim 3, characterized in that: The weight ratio of hexaglycerol monooleate to sodium petroleum sulfonate is 4.2:

1.

5. The core release agent according to claim 1, characterized in that: The wetting agent is one or a combination of liquid paraffin, vegetable oil and glycerin.

6. The core release agent according to claim 1, characterized in that: The wetting agent is composed of vegetable oil and glycerin in a weight ratio of 1: (4-6).

7. The core release agent according to claim 6, characterized in that: The vegetable oil is modified before use, and the modification steps are as follows: S1. Mix oleic acid and acetic acid in a molar ratio of 1:(0.4-0.5), add sulfuric acid as a catalyst, heat to 35-40°C, add hydrogen peroxide in an amount 1.2-1.6 times the amount of oleic acid, react at 55-65°C for 3.5-4h, heat under reflux for 50-70min, and stand for stratification; mix the oil layer raw material after stratification with glycerol in a molar ratio of 1:(0.9-1.1), add zinc oxide as a catalyst, react at 175-185°C for 3.5-4.5h, and obtain a modifier; S2. Mix the vegetable oil raw material and the modifier in a weight ratio of (2.2-2.5):1, stir under nitrogen protection, and heat to 175-185°C. After reacting for 5.5-6.5 hours, cool down, mix with trimethylsilyl chloride in a molar ratio of (1.1-1.3):1, add anhydrous ether, react at 40-45°C for 2-3 hours, wash the product, evaporate the solvent, and vacuum dry to remove water to obtain modified vegetable oil.

8. The method for preparing the core release agent according to claim 1, characterized in that: The following steps are involved: (1) preparing raw materials including sodium lauryl sulfate, sodium p-toluenesulfonate, sodium fatty alcohol polyoxyethylene ether sulfate, a wetting agent and water according to a ratio; (2) Take 10-15% by weight of water, heat it to 90-95°C, add sodium dodecyl sulfate and p-toluenesulfonic acid, and mix them evenly; then cool it to 50-55°C, add sodium fatty alcohol polyoxyethylene ether sulfate, and mix them evenly; finally, add the remaining weight of water and wetting agent, the water temperature is 60-65°C, and mix them evenly; after cooling, the core release agent is obtained.

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