A salicylic acid liniment and a preparation method thereof

Abstract

The application belongs to the technical field of salicylic acid preparation, and specifically provides a salicylic acid liniment and a preparation method thereof, and the preparation steps include the following: 60-80 parts of 75% alcohol, 5-10 parts of polysorbate, 5-20 parts of propylene glycol, 10-20 parts of an additive component and 0.5-1 part of rice bran extract are mixed, vacuum defoaming treatment is performed, then 2-5 parts of salicylic acid is added, and stirring is continued for 1-2 min to obtain the salicylic acid liniment; the preparation steps of the additive component include the following: a homogeneous liquid is taken, a surfactant is added, an enzymatic product is further added, stirring is performed, then a calcium agent is added, ultrasonic treatment is performed, and then standing is performed, and the additive component is obtained by storing at 2-8 DEG C in the dark; the salicylic acid liniment prepared by using the additive component has the advantages of mild low irritation and persistent antibacterial property.

Description

Technical Field

[0001] This application belongs to the field of salicylic acid preparation technology, and in particular relates to a salicylic acid liniment and its preparation method. Background Technology

[0002] Salicylic acid lotion is a classic topical dermatological preparation, with salicylic acid as its main active ingredient. Clinically, this preparation is used to treat various superficial skin infections. Its core pharmacological action lies in its strong inhibitory and bactericidal effects against pathogenic microorganisms, especially Gram-positive bacteria.

[0003] The main mechanism of action of salicylic acid topical ointments is as follows: After application, salicylic acid molecules penetrate the skin's stratum corneum barrier, reaching the infected lesions in the epidermis and even the dermis. Upon reaching the site of action, salicylic acid disrupts bacterial cell membranes, increasing their permeability and causing leakage of intracellular substances. Secondly, salicylic acid inhibits various bacterial enzyme systems, especially enzymes related to energy metabolism, thereby interfering with normal bacterial physiological activities and ultimately achieving antibacterial and anti-inflammatory effects. Through this process, it effectively eliminates pathogens, reduces inflammatory responses, and promotes recovery of the infected area.

[0004] However, while salicylic acid molecules exert their therapeutic effects, they also pose a certain degree of irritation to skin tissue. This irritation is mainly manifested in their direct effect on local capillaries and tiny nerve endings in the epidermis. When salicylic acid molecules penetrate the skin too quickly and form excessively high concentrations locally in a short period of time, they can significantly cause local stinging, burning, and itching sensations, severely affecting patient medication adherence and experience.

[0005] To alleviate this irritation, common formulation improvement strategies mainly fall into two categories: one is to introduce auxiliary analgesic or local anesthetic components (such as borneol, menthol, etc.) to numb nerve endings and mask discomfort; the other is to introduce sustained-release components to reduce the transdermal penetration rate of salicylic acid, thereby reducing the irritation of the topical application. However, both strategies have significant limitations: while introducing analgesic components provides comfort, it also introduces new potential allergens, which may trigger contact allergic reactions, complicating the formulation and increasing safety risks; while adding sustained-release components prolongs the residence time of salicylic acid molecules on the skin surface, leading to accelerated photodegradation of salicylic acid molecules themselves. Therefore, it is necessary to find a salicylic acid topical application and its preparation method that can reduce skin irritation during application of salicylic acid molecules, prolong the duration of the topical application, and reduce the photodegradation of salicylic acid. Summary of the Invention

[0006] To address the aforementioned issues and further reduce the skin irritation of salicylic acid liniments while prolonging the duration of their effect, this application provides a salicylic acid liniment and its preparation method.

[0007] This application first provides a method for preparing a salicylic acid liniment, the preparation steps of which include the following:

[0008] Take 60-80 parts of 75% alcohol, 5-10 parts of polysorbate, 5-20 parts of propylene glycol, 10-20 parts of additives and 0.5-1 parts of rice bran extract, and perform vacuum degassing treatment. Then add 2-5 parts of salicylic acid and continue stirring to obtain the final product.

[0009] The preparation steps of the added component include the following:

[0010] S01. Take flaxseed cake, crush and sieve it, then add water to disperse it into a suspension, then add proteolytic enzyme, carry out enzymatic hydrolysis, then quench the reaction, adjust the pH to 7, centrifuge and dialyze the supernatant to obtain the enzymatic hydrolysis product;

[0011] S02. Take the homogeneous liquid, add the surfactant, then add the enzymatic hydrolysis product, stir, then add the calcium agent, sonicate, let stand, and store at 2-8℃ in the dark to obtain the product.

[0012] Furthermore, in step S01, the water dispersion is set to a solid-liquid ratio of 1:(20-30).

[0013] Furthermore, in step S01, the proteolytic enzyme is added to the system at a ratio of 1 / 140 to 1 / 120 of the suspension mass;

[0014] The enzymatic hydrolysis reaction is set at a temperature of 48-50℃ and the pH value is adjusted to 7.7-8.2.

[0015] Furthermore, in step S01, the centrifugation speed is set to 3000-5000 rpm; the dialysis is performed using a dialysis bag with a molecular weight cutoff of 500 Da.

[0016] Furthermore, in step S02, the homogeneous liquid is prepared by mixing water and glycerol in a volume ratio of (6-8):1;

[0017] The surfactant is at least one of sodium lauroyl amphoteric acid, cocamidopropyl betaine, and cocoyl monoethanolamine.

[0018] The calcium agent is at least one of calcium gluconate and calcium carbonate.

[0019] Furthermore, in step S02, the mass-to-volume ratio of the homogeneous liquid, the enzymatic hydrolysis product, and the calcium agent is (35-45) mL:(0.32-0.36) g:(0.1-0.2) g.

[0020] This application also provides a salicylic acid liniment, prepared using the above-described preparation method.

[0021] Compared with the prior art, this application has the following beneficial effects:

[0022] 1. This application describes a method for treating flaxseed meal with proteolytic enzymes to obtain enzymatically hydrolyzed peptides with hydrophilic / hydrophobic end groups. The enzymatically hydrolyzed peptides are then treated in a homogeneous liquid. The hydrophilic ends of the peptide chains interact with the aqueous phase, while the hydrophobic ends form hydrophobic associations between molecules, self-assembling to form primary micelles. These micelles are then subjected to directional non-covalent interactions such as inter-chain hydrogen bonds and electrostatic attraction. The primary micelles further grow in a directional manner to obtain peptide nanofibers. The added calcium salt dissolves in the aqueous phase, and the ionized Ca... 2+ It can form a dimer structure by binding with the free carboxyl groups of the peptide side chain through ionic bonds, which plays a bridging role, promotes the entanglement between peptide fibers, and obtains a more stable three-dimensional skeleton of peptide fibers.

[0023] 2. When a salicylic acid liniment is prepared using the additive components of this application as raw materials, the transdermal migration of salicylic acid molecules is inhibited by the three-dimensional framework and the attraction of the framework hydrogen bond network, the skin penetration is reduced, the irritation of the liniment is reduced, and the duration of action is increased. Furthermore, the flaxseed peptides obtained by enzymatic hydrolysis of flaxseed cake can scavenge oxidative hydroxyl free radicals generated by light, inhibit the reactive binding failure of salicylic acid with hydroxyl free radicals, and further improve the utilization efficiency of the active components of the liniment. Attached Figure Description

[0024] Figure 1 The results show the relative antibacterial activity of salicylic acid liniment in Examples 1-3 and Control Groups 1-3 of this application.

[0025] Figure 2 Radar graphs showing the irritation test results of salicylic acid liniment in Examples 1-3 and Control Groups 1-3 of this application.

[0026] Figure 3 Radar graphs showing the durability test of salicylic acid liniment in Examples 1-3 and Control Groups 1-3 of this application.

[0027] Figure 4 Radar graphs showing the texture test of salicylic acid liniment in Examples 1-3 and Control Groups 1-3 of this application. Detailed Implementation

[0028] To make the inventive objectives, technical solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with embodiments. Obviously, the described embodiments are merely some, not all, of the embodiments described herein. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0030] When using “including,” “having,” and “contains” as described herein, the intention is to cover non-exclusive inclusion, unless an explicit qualifying term such as “only,” “consisting of,” etc., is used, in which case another component may be added.

[0031] The terms "preferred," "more preferably," "better," and "even better" used in this application refer to embodiments of this application that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this application. That is, in this application, "preferred," "more preferably," "better," and "even better" are merely descriptions of implementations or embodiments with better effects, but do not constitute a limitation on the scope of protection of this application.

[0032] In this application, terms such as "further," "even more," and "particularly" are used for descriptive purposes and indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0033] In this application, "at least one" means one or more, such as one, two, or more. "Multiple" or "several" means at least two, such as two, three, etc., and "multi-layered" means at least two layers, such as two layers, three layers, etc., unless otherwise explicitly specified. In the description of this application, "several" means at least one, such as one, two, etc., unless otherwise explicitly specified.

[0034] When a numerical range is disclosed herein, the range is considered continuous and includes the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to integers, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are incorporated.

[0035] Unless otherwise specified, all steps in this application may be performed sequentially or randomly. For example, the method comprising steps (a) and (b) indicates that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, the mention that the method may also include step (c) indicates that step (c) may be added to the method in any order; for example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc. Unless otherwise stated, singular terms may include plural forms and should not be construed as having a quantity of one.

[0036] In this application, "above" or "below" includes the number itself. For example, "below 1" includes 1.

[0037] In this application, room temperature refers to 0~40℃, including but not limited to 10~40℃, or further to 20~30℃.

[0038] The present application will be further illustrated by the following examples, but these examples do not limit the scope of the present application.

[0039] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in this application, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments whose manufacturers are not specified are conventional products that can be purchased commercially. In addition to the specific methods, equipment, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description in this application, any prior art methods, equipment, and materials similar to or equivalent to those described, used, or made by the methods, equipment, and materials in the embodiments of this application may be used to implement this application.

[0040] The raw material formulations of salicylic acid liniments in Examples 1-3 and Control Groups 1-3 of this application are shown in Table 1.

[0041] Table 1. Raw material formulations of salicylic acid liniments in Examples 1-3 and Control Groups 1-3

[0042]

[0043] The preparation steps for salicylic acid liniment are as follows:

[0044] Mix 75% alcohol, polysorbate, propylene glycol, additives and rice bran extract, stir for 5 minutes, then degas under vacuum for 20 minutes, then add salicylic acid and continue stirring for 2 minutes to obtain the final product.

[0045] Preparation Example 1

[0046] Take 500g of flaxseed cake (homemade), grind it for 1 hour and then pass it through a 100-mesh sieve. Then, control the solid-liquid ratio at 1:20 and add water to disperse it to obtain a suspension. Then, add proteolytic enzyme (model: Protamex 1.6, supplied by Novogene) at a dosage of 1 / 120 (g / g) of the suspension mass. Adjust the temperature to 48℃ and the pH value to 7.7. Perform enzymatic hydrolysis in a constant temperature shaking water bath for 2 hours. Then, rapidly raise the temperature to 90℃ to quench the enzymatic hydrolysis reaction. Then, readjust the pH value to 7 and cool at room temperature. Then, centrifuge at 3000rpm for 30 minutes. Take the supernatant and filter it using a dialysis bag with a molecular weight cutoff of 500Da. Then, store it at -80℃ to obtain the enzymatic hydrolysis product.

[0047] Preparation Example 2

[0048] Take 500g of flaxseed cake (homemade), grind it for 1.5h and then pass it through a 100-mesh sieve. Then, control the solid-liquid ratio at 1:30 and add water to disperse it to obtain a suspension. Then, add proteolytic enzyme (model: Protamex 1.6, supplied by Novogene) at a dosage of 1 / 130 (g / g) of the suspension. Adjust the temperature to 50℃ and the pH to 7.9. Perform enzymatic hydrolysis in a constant temperature shaking water bath for 3h. Then, rapidly raise the temperature to 95℃ to quench the enzymatic hydrolysis reaction. Then, readjust the pH to 7 and cool at room temperature. Then, centrifuge at 4000rpm for 25min. Take the supernatant and filter it using a dialysis bag with a molecular weight cutoff of 500Da. Then, store it at -80℃ to obtain the enzymatic hydrolysis product.

[0049] Preparation Example 3

[0050] Take 500g of flaxseed cake (homemade), grind it for 2 hours and then pass it through a 100-mesh sieve. Then, control the solid-liquid ratio at 1:30 and add water to disperse it to obtain a suspension. Then, add proteolytic enzyme (model: Protamex 1.6, supplied by Novogene) at a dosage of 1 / 140 (g / g) of the suspension. Adjust the temperature to 50℃ and the pH to 8.2. Perform enzymatic hydrolysis in a constant temperature shaking water bath for 3 hours. Then, rapidly raise the temperature to 95℃ to quench the enzymatic hydrolysis reaction. Then, readjust the pH to 7 and cool at room temperature. Then, centrifuge at 5000rpm for 30 minutes. Take the supernatant and filter it using a dialysis bag with a molecular weight cutoff of 500Da. Then, store it at -80℃ to obtain the enzymatic hydrolysis product.

[0051] Example 1

[0052] In this embodiment, the preparation steps of the added component are as follows:

[0053] Take 30 mL of pure water and 5 mL of glycerol, stir to obtain a homogeneous liquid, then slowly add 0.005 g of sodium lauroamphoacetate, vacuum degassing for 10 min, then add 0.32 g of enzymatic hydrolysis product, adjust the magnetic stirring speed to 100 rpm and stir for 5 min, then add 0.1 g of calcium carbonate to the system, sonicate for 5 min and let stand for 1 h, then transfer to a low temperature chamber and store at 2℃ in the dark to obtain the added component.

[0054] In this embodiment, the enzymatic hydrolysis product was prepared in Preparation Example 1.

[0055] Example 2

[0056] In this embodiment, the preparation steps of the added component are as follows:

[0057] Take 35 mL of pure water and 5 mL of glycerol, stir to obtain a homogeneous liquid, then slowly add 0.008 g of cocamidopropyl betaine, vacuum degassing for 12 min, then add 0.35 g of enzymatic hydrolysis product, adjust the magnetic stirring speed to 100 rpm and stir for 10 min, then add 0.15 g of calcium gluconate to the system, sonicate for 5 min and let stand for 1 h, then transfer to a low temperature chamber and store at 2℃ in the dark to obtain the added component.

[0058] In this embodiment, the enzymatic hydrolysis product was prepared in Preparation Example 2.

[0059] Example 3

[0060] In this embodiment, the preparation steps of the added component are as follows:

[0061] Take 40 mL of pure water and 5 mL of glycerol, stir to obtain a homogeneous liquid, then slowly add 0.01 g of cocoyl monoethanolamine, vacuum degassing for 20 min, then add 0.36 g of enzymatic hydrolysis product, adjust the magnetic stirring speed to 200 rpm and stir for 20 min, then add 0.2 g of calcium carbonate to the system, sonicate for 10 min and let stand for 2 h, then transfer to a low temperature chamber and store at 8 °C in the dark to obtain the added component;

[0062] In this embodiment, the enzymatic hydrolysis product was prepared as described in Preparation Example 3.

[0063] Control group 1

[0064] The difference between this control group and Example 1 is that the preparation steps for the added components are as follows:

[0065] Take 60 mL of pure water and 10 mL of glycerol, stir to obtain a homogeneous liquid, then slowly add 0.005 g of sodium lauroamphoacetate, vacuum degassing for 10 min, then add 0.32 g of enzymatic hydrolysis product, adjust the magnetic stirring speed to 100 rpm and stir for 5 min, then add 0.1 g of calcium carbonate to the system, sonicate for 5 min and let stand for 1 h, then transfer to a low temperature chamber and store at 2℃ in the dark to obtain the added component.

[0066] The remaining steps are the same as in Example 1.

[0067] Control group 2

[0068] The difference between this control group and Example 1 is that an equal amount of sodium gluconate was used instead of calcium to prepare the additive component.

[0069] The remaining steps are the same as in Example 1.

[0070] Control group 3

[0071] The raw material formula used in this control group is shown in Table 1, and the remaining steps are the same as in Example 1.

[0072] Performance testing

[0073] 1. Antibacterial test

[0074] Preparation of culture medium for bacterial strains:

[0075] Using a streak loop, pneumococcus, Staphylococcus aureus, and Enterococcus faecalis were inoculated onto the surface of nutrient agar medium and incubated at 35°C for 20 hours for later use.

[0076] Test filter paper preparation:

[0077] Light-protected group: Under sterile light-protected conditions, the salicylic acid liniment of Examples 1-3 and Control Groups 1-3 was evenly applied to both sides of the filter paper. Excess liniment was scraped off with tweezers to obtain test filter paper A. The test group is represented by ⊘.

[0078] Irradiation group: Take filter paper A and place it in a UV light environment. Set the vertical distance between the filter paper and the UV lamp to 50cm. The UV lamp power is 30W. Irradiate for 10min to obtain test filter paper B. The test group is represented by ⊗.

[0079] Take three filter paper pieces A from each of Examples 1-3 and Control Groups 1-3 and attach them to the surface of the bacterial culture medium. Use tweezers to gently press the filter paper pieces flat, ensuring that the spacing between the filter paper pieces is not less than 50 mm and the distance from the center of the paper piece to the edge of the culture dish is not less than 25 mm. After the filter paper pieces are treated, place them in a 35°C constant temperature incubator and incubate in the dark for 24 hours within 15 minutes. Then measure the diameter (mm) of the inhibition zone of each group to obtain the average value of the inhibition zone. Similarly, take filter paper pieces B for testing. Evaluate the antibacterial performance of each group of liniments based on the size of the inhibition zone.

[0080] According to the formula: Relative activity = Diameter of inhibition zone in the light-exposed group / Diameter of inhibition zone in the dark-exposed group × 100%;

[0081] The relative antibacterial activity of each group of salicylic acid liniments was calculated. The antibacterial performance and relative activity test results of salicylic acid liniments in Examples 1-3 and Control Groups 1-3 are shown in Table 2 and 3, respectively. Figure 1 As shown.

[0082] Table 2. Results of antibacterial performance tests of salicylic acid liniments in Examples 1-3 and Control Groups 1-3

[0083]

[0084] Analysis of Examples 1-3 and Control Groups 1-3, combined with Table 2 and Figure 1 It can be concluded that the antibacterial performance of the salicylic acid liniment in the examples and the control group was similar against the three Gram-positive bacteria under the light-protected test conditions, but there was a significant difference in antibacterial performance under light exposure. From the light exposure test results, the relative activity value of salicylic acid in control group 3 (without added components) was only 45%, far lower than the lowest level in the examples and control groups 1-2, indicating that the salicylic acid molecules in control group 3 exhibited severe photolysis. Since the liniment raw materials lack substances that can inhibit and absorb hydroxyl free radicals, the salicylic acid molecules directly react with free radicals and lose their antibacterial effect. It can be expected that the efficacy of this group of salicylic acid liniments in treating skin infections will be greatly reduced under light exposure.

[0085] 2. Sensory characteristics evaluation

[0086] Volunteers meeting the inclusion criteria were randomly selected from the factory area for salicylic acid liniment skin testing; the total sample size was 20. The evaluation indicators and results are shown in Table 3. Figure 2-4 As shown:

[0087] Table 3. Sensory characteristic evaluation indicators and test results of Examples 1-3 and Control Groups 1-3

[0088]

[0089] Examples 1-3 and control groups 1-3 were taken and compared with Table 3 and Figure 2-4It can be concluded that the salicylic acid liniment prepared using the embodiment scheme is superior to the control group scheme, exhibiting mild, low-irritation, and easy-to-apply sensory characteristics, and can exert a longer-lasting effect.

[0090] Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method for preparing a salicylic acid liniment, characterized in that, The preparation steps include the following: Take 60-80 parts of 75% alcohol, 5-10 parts of polysorbate, 5-20 parts of propylene glycol, 10-20 parts of additives and 0.5-1 parts of rice bran extract, and perform vacuum degassing treatment. Then add 2-5 parts of salicylic acid and continue stirring to obtain the final product. The preparation steps of the added component include the following: S01. Take flaxseed cake, crush and sieve it, then add water to disperse it into a suspension, then add proteolytic enzyme, carry out the enzymatic hydrolysis reaction, then quench the reaction, adjust the pH to 7, centrifuge and dialyze the supernatant to obtain the enzymatic hydrolysis product; the proteolytic enzyme model is Protamex 1.6, supplied by Novogene Co., Ltd. S02. Take the homogeneous liquid, add the surfactant, then add the enzymatic hydrolysis product, stir, then add the calcium agent, sonicate, let stand, and store at 2-8℃ in the dark to obtain the product; the homogeneous liquid is made by mixing water and glycerol in a volume ratio of (6-8):1; the calcium agent is at least one of calcium gluconate and calcium carbonate; the mass-volume ratio of the homogeneous liquid, enzymatic hydrolysis product and calcium agent used is (35-45) mL:(0.32-0.36) g:(0.1-0.2) g.

2. The method for preparing a salicylic acid liniment according to claim 1, characterized in that, In step S01, water is added to disperse the solid-liquid ratio to 1:(20-30).

3. The method for preparing a salicylic acid liniment according to claim 1, characterized in that, In step S01, the proteolytic enzyme is added to the system at a ratio of 1 / 140 to 1 / 120 of the suspension mass.

4. The method for preparing a salicylic acid liniment according to claim 1, characterized in that, In step S01, the enzymatic hydrolysis reaction is set at a temperature of 48-50℃ and the pH value is adjusted to 7.7-8.

2.

5. The method for preparing a salicylic acid liniment according to claim 1, characterized in that, In step S01, the centrifugation speed is set to 3000-5000 rpm; the dialysis is performed using a dialysis bag with a molecular weight cutoff of 500 Da.

6. The method for preparing a salicylic acid liniment according to claim 1, characterized in that, In step S02, the surfactant is at least one of sodium lauroamphoacetate, cocamidopropyl betaine, and cocoyl monoethanolamine.

7. A salicylic acid liniment, characterized in that, It is prepared by any one of the preparation methods described in claims 1-6.

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