Preparation method of compound menthol ointment

Abstract

The invention discloses a preparation method of a compound menthol ointment. The preparation method comprises the following steps: preparing menthol and / or camphor microcrystals: coating the microcrystals with a wall material to obtain microcapsules; and mixing the menthol with a matrix and other oil-soluble active ingredients to prepare the compound menthol ointment. Camphora and / or menthol crystal grains with the average particle size of 1-10 microns are obtained by adopting a solvent replacement recrystallization method, the microcapsule is prepared by taking the camphor and / or menthol crystal grains as a core material, and after the microcapsule is broken, the oil-soluble component or skin grease of an outer matrix slowly dissolves the crystal grains, so that the camphor and / or menthol component slowly contacts with air, the volatilization of the camphor and / or menthol component is slowed down, and the effect of improving the quality of the microcapsule is achieved. Therefore, the cool skin feeling effect is prolonged.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a method for preparing a compound menthol ointment. Background Art

[0002] Compound menthol ointment is an over-the-counter medicine used for nasal congestion caused by colds, insect bites, chapped skin, mild burns, abrasions, sunburn and skin itching. It usually contains ingredients such as menthol, camphor, eucalyptus oil, etc. that provide a cooling sensation on the skin, but these ingredients are highly volatile, so topical ointments or solutions containing such substances can only provide a short-term cooling sensation on the skin, and it is difficult to relieve itching and refresh the mind for a long time.

[0003] In view of this, the present invention is proposed. Summary of the invention

[0004] The invention provides a preparation method of a compound menthol ointment, aiming to prolong the skin feeling effect of cooling ingredients including camphor and menthol on the skin.

[0005] The present invention is achieved in that:

[0006] In a first aspect, the present invention provides a method for preparing a compound menthol ointment, comprising the following steps:

[0007] (1) preparing microcrystals: dissolving a cooling ingredient in ethanol to obtain an organic phase; adding the organic phase to pure water, standing for crystallization, and obtaining microcrystals after solid-liquid separation; the cooling ingredient comprises at least one of menthol and camphor;

[0008] (2) Preparation of microcapsules: dispersing microcrystals in an aqueous solution of a wall material, homogenizing, and spray drying to obtain microcapsules;

[0009] (3) preparing the matrix: heating and melting the matrix to obtain a matrix liquid;

[0010] (4) Preparation of compound menthol ointment: Add the oil-soluble active ingredient into the base liquid, stir evenly while keeping warm, add the microcapsules after cooling, stir evenly, can while hot, and obtain the compound menthol ointment after cooling.

[0011] In some embodiments of the present invention, the particle size of the microcrystals is 0.5 to 20 μm; preferably, the average particle size of the microcrystals is 1 to 10 μm.

[0012] In some embodiments of the present invention, the wall material includes a temperature sensitizer.

[0013] In some embodiments of the invention, the thermosensitizer is polyethylene glycol 1000 vitamin E succinate.

[0014] In some embodiments of the present invention, the wall material further comprises sodium starch octenyl succinate and maltodextrin; preferably, the viscosity of sodium starch octenyl succinate at 25° C. is 20 to 100 mPa·s.

[0015] In some embodiments of the present invention, the mass percentage of the wall material in the aqueous solution of the wall material is 10% to 30%.

[0016] In some embodiments of the present invention, the feed mass ratio of microcrystals to the wall material is 0.8 to 2:1.

[0017] In some embodiments of the present invention, the concentration of the cooling component in the organic phase is 0.2 to 0.3 g / mL.

[0018] In some embodiments of the present invention, the volume ratio of the organic phase to pure water is 1:8-12.

[0019] In some embodiments of the present invention, the solid-liquid separation is carried out by centrifugation or filter pressing.

[0020] In some embodiments of the present invention, the spray drying temperature is 30-55°C.

[0021] In some embodiments of the present invention, the base includes at least one of paraffin, ozokerite, petrolatum, zinc wax, and lanolin.

[0022] In some embodiments of the present invention, the oil-soluble active ingredient includes at least one of methyl salicylate, eucalyptus oil, turpentine oil, clove oil, rose essential oil, cinnamon oil, olive oil, thymol and silicone oil.

[0023] In a first aspect, the present invention provides a compound menthol ointment prepared by the preparation method of any embodiment.

[0024] A compound menthol ointment is composed of the following raw materials by weight based on a total weight of 1000g: 50-100g of menthol, 90-150g of camphor, 70-250g of wall material, 250-300g of oil-soluble active ingredients, and the rest of the matrix.

[0025] The present invention has the following beneficial effects:

[0026] The present invention provides a method for preparing a compound menthol ointment, using a solvent replacement recrystallization method to obtain small-sized camphor and / or menthol crystals, using them as core materials to prepare microcapsules, and after the microcapsules are broken, the oil-soluble components of the external matrix or skin grease slowly dissolve the crystals, so that the camphor and / or menthol components slowly contact the air, which is conducive to slowing down their volatilization, thereby prolonging the cooling skin feeling effect. Further, the present invention adds a thermosensitive agent to the wall material of the microcapsule, and the addition of the thermosensitive agent is conducive to promoting the microcapsule to release camphor and / or menthol components at skin temperature, and the compound menthol ointment with different sustained-release effects is prepared by controlling the dosage of the thermosensitive agent. In addition, the present invention prepares sustained-release microcapsules from camphor and / or menthol, which is conducive to improving the accuracy of the feeding ratio of the two during the preparation process, and is conducive to improving the stability of product quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The optical microscope image of the menthol microcrystals (a) prepared in Example 1 and the physical image of the raw material menthol (b) are shown.

[0028] Figure 2 The release rates of menthol microcrystals and raw menthol at different times.

[0029] Figure 3 The release rates of menthol microcrystals and raw menthol at different temperatures. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0031] In the description of the embodiments of the present application, technical terms such as "first" and "second" are only used to distinguish different objects and cannot be understood as indicating or implying relative importance or implicitly indicating the number, specific order or primary and secondary relationship of the indicated technical features.

[0032] Reference to "embodiment" herein means that a particular feature, structure, or characteristic described in conjunction with the embodiment may be included in at least one embodiment of the present application. The appearance of the phrase in various locations in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments.

[0033] In the embodiment of the present application, the term "or / and" is only a description of the association relationship of associated objects, indicating that three relationships may exist. For example, A or / and B can represent three situations: A exists alone, A and B exist at the same time, and B exists alone.

[0034] In addition, the character “ / ” in this article generally indicates that the previous and next associated objects are in an “or” relationship.

[0035] In the embodiments of the present application, "multiple" means more than two (including two). Similarly, "multiple groups" means more than two groups (including two groups), and "multi-layer" means more than two layers (including two layers), unless otherwise clearly specified and limited.

[0036] In the embodiments of the present application, "at least one" means one or more than one.

[0037] In the embodiments of the present application, the orientations or positional relationships indicated by the technical terms "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", etc. are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the embodiments of the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed in a specific orientation, etc., and cannot be understood as limiting the embodiments of the present application. Those skilled in the art can understand the specific meanings of the above terms in the embodiments of the present application according to specific circumstances.

[0038] Sources of some raw materials:

[0039] Sodium starch octenylsuccinate, viscosity (25°C) 72 mPa·s, purchased from Deqing Sanfu Food Co., Ltd.

[0040] Maltodextrin, DE value 18-20, was purchased from Shandong Xiwang Sugar Co., Ltd.

[0041] Polyethylene glycol 1000 vitamin E succinate, melting point 34-38°C, was purchased from Wuhan Kemik Biopharmaceutical Technology Co., Ltd.

[0042] The following is a specific implementation method to further illustrate the solution of the present invention.

[0043] Example 1

[0044] A method for preparing a compound menthol ointment comprises the following steps:

[0045] (1) Menthol was dissolved in anhydrous ethanol to obtain a menthol organic phase with a concentration of 0.25 g / mL, and then the menthol organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain menthol microcrystals, the average particle size of which was measured to be 2.4 μm. The volume ratio of the menthol organic phase to pure water was 1:10.

[0046] Camphor was dissolved in anhydrous ethanol to obtain a camphor organic phase with a concentration of 0.3 g / mL, and then the camphor organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain camphor microcrystals with an average particle size of 1.4 μm. The volume ratio of the camphor organic phase to pure water was 1:10.

[0047] (2) Mixing menthol microcrystals and camphor microcrystals according to the formula and dispersing them in the aqueous solution of the wall material, homogenizing to obtain a suspension, and drying the suspension in a spray freeze dryer to obtain microcapsules.

[0048] The wall material is composed of sodium octenyl succinate starch, maltodextrin and polyethylene glycol 1000 vitamin E succinate in a mass ratio of 60:10:10; the mass percentage of the wall material in the aqueous solution of the wall material is 15%; the mass ratio of microcrystals to wall material is 1.4:1; and the spray drying temperature is 40°C.

[0049] (3) Heat the matrix to 100°C and stir to melt to obtain a matrix liquid, which is then kept warm for later use.

[0050] The matrix is ​​composed of solid paraffin, ozokerite and white vaseline in a mass ratio of 85:1:180.

[0051] (4) Adding the oil-soluble active ingredient to the matrix liquid of step (3), stirring evenly while keeping warm, cooling to 40-50° C., adding the microcapsules and stirring at 500 rpm for 30 seconds, canning while hot, and then rapidly cooling at 5° C. to obtain the compound menthol ointment.

[0052] The oil-soluble active ingredient is composed of methyl salicylate, eucalyptus oil and turpentine oil in a mass ratio of 90:50:2.

[0053] A compound menthol ointment, calculated on a total weight of 1000 g, is composed of the following raw materials by weight:

[0054] Menthol 80g, camphor 120g, wall material 143g, oil-soluble active ingredient 270g, matrix: the rest.

[0055] Example 2

[0056] A method for preparing a compound menthol ointment comprises the following steps:

[0057] (1) Menthol was dissolved in anhydrous ethanol to obtain a menthol organic phase with a concentration of 0.2 g / mL, and then the menthol organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain menthol microcrystals with an average particle size of 1.5 μm. The volume ratio of the menthol organic phase to pure water was 1:12.

[0058] Camphor was dissolved in anhydrous ethanol to obtain a camphor organic phase with a concentration of 0.2 g / mL, and then the camphor organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain camphor microcrystals with an average particle size of 1.6 μm. The volume ratio of the camphor organic phase to pure water was 1:8.

[0059] (2) Mixing menthol microcrystals and camphor microcrystals according to the formula and dispersing them in the aqueous solution of the wall material, homogenizing to obtain a suspension, and drying the suspension in a spray freeze dryer to obtain microcapsules.

[0060] The wall material is composed of sodium starch octenylsuccinate and maltodextrin in a mass ratio of 60:10; the mass percentage of the wall material in the aqueous solution of the wall material is 30%; the mass ratio of microcrystals to wall material is 0.8:1; and the spray drying temperature is 55°C.

[0061] (3) Heat the matrix to 100°C and stir to melt to obtain a matrix liquid, which is then kept warm for later use.

[0062] The matrix is ​​composed of solid paraffin, ozokerite and yellow vaseline in a mass ratio of 12:1:20.

[0063] (4) Adding the oil-soluble active ingredient to the matrix liquid of step (3), stirring evenly while keeping warm, cooling to 40-50° C., adding the microcapsules and stirring at 500 rpm for 30 seconds, canning while hot, and then rapidly cooling at 5° C. to obtain the compound menthol ointment.

[0064] Among them, the oil-soluble active ingredients are composed of methyl salicylate, eucalyptus oil, turpentine oil and silicone oil in a mass ratio of 90:50:2:5.

[0065] A compound menthol ointment, calculated on a total weight of 1000 g, is composed of the following raw materials by weight:

[0066] Menthol 50g, camphor 100g, wall material 187g, oil-soluble active ingredient 300g, matrix: the rest.

[0067] Example 3

[0068] A method for preparing a compound menthol ointment comprises the following steps:

[0069] (1) Menthol was dissolved in anhydrous ethanol to obtain a menthol organic phase with a concentration of 0.3 g / mL, and then the menthol organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain menthol microcrystals, the average particle size of which was measured to be 3.7 μm. The volume ratio of the menthol organic phase to pure water was 1:8.

[0070] Camphor was dissolved in anhydrous ethanol to obtain a camphor organic phase with a concentration of 0.3 g / mL, and then the camphor organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain camphor microcrystals with an average particle size of 1.1 μm. The volume ratio of the camphor organic phase to pure water was 1:12.

[0071] (2) Mixing menthol microcrystals and camphor microcrystals according to the formula and dispersing them in the aqueous solution of the wall material, homogenizing to obtain a suspension, and drying the suspension in a spray freeze dryer to obtain microcapsules.

[0072] The wall material is composed of sodium octenyl succinate starch, maltodextrin and polyethylene glycol 1000 vitamin E succinate in a mass ratio of 60:10:20; the mass percentage of the wall material in the aqueous solution of the wall material is 10%; the mass ratio of microcrystals to wall material is 2:1; and the spray drying temperature is 30°C.

[0073] (3) Heat the matrix to 100°C and stir to melt to obtain a matrix liquid, which is then kept warm for later use.

[0074] The matrix is ​​composed of solid paraffin, liquid paraffin and white vaseline in a mass ratio of 1:3:16.

[0075] (4) Adding the oil-soluble active ingredient to the matrix liquid of step (3), stirring evenly while keeping warm, cooling to 40-50° C., adding the microcapsules and stirring at 500 rpm for 30 seconds, canning while hot, and then rapidly cooling at 5° C. to obtain the compound menthol ointment.

[0076] Among them, the oil-soluble active ingredients are composed of methyl salicylate, eucalyptus oil, clove oil and rose essential oil in a mass ratio of 80:60:1:2.

[0077] A compound menthol ointment, calculated on a total weight of 1000 g, is composed of the following raw materials by weight:

[0078] Menthol 100g, camphor 90g, wall material 95g, oil-soluble active ingredient 250g, matrix: the rest.

[0079] Example 4

[0080] The difference from Example 1 is that camphor microcrystals are not added in step (2).

[0081] A compound menthol ointment, calculated on a total weight of 1000 g, is composed of the following raw materials by weight:

[0082] Menthol 100g, wall material 71g, oil-soluble active ingredient 270g, matrix: the rest.

[0083] Example 5

[0084] The difference from Example 1 is that the wall material is composed of sodium starch octenylsuccinate and maltodextrin in a mass ratio of 60:10.

[0085] Example 6

[0086] The difference from Example 1 is that the mass ratio of microcrystals to wall materials is 0.8:1.

[0087] Example 7

[0088] The difference from Example 1 is that the mass ratio of microcrystals to wall materials is 2:1.

[0089] Example 8

[0090] The difference from Example 1 is that in the process of preparing microcapsules in step (2), menthol microcrystals with an average particle size of 2.4 μm are replaced by menthol microcrystals with an average particle size of 1.5 μm prepared in Example 2; and camphor microcrystals with an average particle size of 1.4 μm are replaced by camphor microcrystals with an average particle size of 1.1 μm prepared in Example 2.

[0091] Example 9

[0092] The difference from Example 1 is that in the process of preparing microcapsules in step (2), menthol microcrystals with an average particle size of 2.4 μm are replaced by menthol microcrystals with an average particle size of 3.7 μm prepared in Example 3; and camphor microcrystals with an average particle size of 1.4 μm are replaced by camphor microcrystals with an average particle size of 1.6 μm prepared in Example 2.

[0093] Comparative Example 1

[0094] A method for preparing a compound menthol ointment comprises the following steps:

[0095] (1) Menthol was dissolved in anhydrous ethanol to obtain a menthol organic phase with a concentration of 0.25 g / mL, and then the menthol organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain menthol microcrystals, the average particle size of which was measured to be 2.4 μm. The volume ratio of the menthol organic phase to pure water was 1:10.

[0096] Camphor was dissolved in anhydrous ethanol to obtain a camphor organic phase with a concentration of 0.3 g / mL, and then the camphor organic phase was added dropwise to pure water at a dropping speed of 2 mL / min. After the addition was completed, the mixture was allowed to stand at room temperature for 24 hours, and then filtered to obtain camphor microcrystals with an average particle size of 1.4 μm. The volume ratio of the camphor organic phase to pure water was 1:10.

[0097] (2) Heat the matrix to 100°C and stir to melt to obtain a matrix liquid, which is then kept warm for later use.

[0098] The matrix is ​​composed of solid paraffin, ozokerite and white vaseline in a mass ratio of 85:1:180.

[0099] (3) Adding the oil-soluble active ingredient to the matrix liquid of step (2), stirring evenly while keeping warm, cooling to 40-50° C., adding menthol microcrystals and camphor microcrystals, stirring at 500 rpm for 30 seconds, canning while hot, and then rapidly cooling at 5° C. to obtain a compound menthol ointment.

[0100] The oil-soluble active ingredient is composed of methyl salicylate, eucalyptus oil and turpentine oil in a mass ratio of 90:50:2.

[0101] A compound menthol ointment, calculated on a total weight of 1000 g, is composed of the following raw materials by weight:

[0102] Menthol microcrystals 80g, camphor microcrystals 120g, oil-soluble active ingredients 270g, matrix: the rest.

[0103] Comparative Example 2

[0104] A method for preparing a compound menthol ointment comprises the following steps:

[0105] (1) mixing menthol and camphor, stirring and mixing at 40° C. to melt, to obtain a eutectic solution of menthol and camphor, and keeping the mixture warm for later use;

[0106] (2) Heat the matrix to 100°C and stir to melt to obtain a matrix liquid, which is then kept warm for later use.

[0107] The matrix is ​​composed of solid paraffin, ozokerite and white vaseline in a mass ratio of 85:1:180.

[0108] (3) adding the oil-soluble active ingredient into the matrix liquid of step (2), stirring evenly while keeping warm, cooling to 40-50° C., adding menthol and camphor eutectic solution and stirring at 500 rpm for 30 seconds, canning while hot, and then rapidly cooling at 5° C. to obtain a compound menthol ointment.

[0109] The oil-soluble active ingredient is composed of methyl salicylate, eucalyptus oil and turpentine oil in a mass ratio of 90:50:2.

[0110] A compound menthol ointment, calculated on a total weight of 1000 g, is composed of the following raw materials by weight:

[0111] Menthol microcrystals 80g, camphor microcrystals 120g, oil-soluble active ingredients 270g, matrix: the rest.

[0112] The physical properties of the products of the embodiments and comparative examples were tested using the following test methods:

[0113] (1) Average particle size of microcrystals: The particle size of microcrystals is tested in accordance with GB / T 19077.1. The average particle size refers to the number average particle size of microcrystals.

[0114] (2) Microscope test: The morphology of menthol microcrystals and camphor microcrystals was observed using an optical microscope.

[0115] Figure 1 The optical microscopic image of menthol microcrystals (1a) and the actual image of menthol raw material without recrystallization (1b) are shown. The large-particle menthol raw material is recrystallized into micron-sized menthol microcrystals by the method of the present invention, which is conducive to being dispersed in the ointment as tiny solid particles after being coated to obtain microcapsules.

[0116] (3) Sustained-release performance of microcapsules: A concentration standard curve of L-1-methyl-4-isopropylcyclohexanol-3 (chemical name of menthol) was established by GC-MS gas spectrometry. Then, the menthol microcapsules or uncoated menthol prepared in each specific embodiment were placed in an oven at 40±2°C and heated for a period of time (t=0 min, 0.5 min, 1 min, 3 min, 5 min, 10 min). The microcapsules were taken out and ground and dissolved with methanol. The microcapsules were then diluted and analyzed by GC-MS. The residual amount of menthol was calculated based on the concentration standard curve and the sample amount. The sustained-release performance was evaluated by the release rate. The release rate at t=1-the residual amount of menthol at t / the residual amount of menthol at 0.

[0117] Figure 2 It is the release rate of different menthol-containing samples at different times. As can be seen from the figure, compared with the uncoated menthol, the release amount of the coated microcapsules over time is lower, that is, the release is relatively slow, indicating that the microcapsules are beneficial to slow down the volatilization of menthol, thereby prolonging its medicinal effect and the cooling feeling. In addition, from Examples 1, 6 and 7, the mass ratio of microcrystals to wall materials has an impact on the sustained release performance. The more wall materials are used, the better the sustained release performance is, which can be regulated according to actual needs; from Examples 1, 8 and 9, the average particle size of the microcrystals has an impact on the sustained release performance. The larger the average particle size of the microcrystals, the better the sustained release performance is.

[0118] (4) Thermosensitive performance of microcapsules: A concentration standard curve of L-1-methyl-4-isopropylcyclohexanol-3 (chemical name of menthol) was established using GC-MS. Then, menthol microcapsules or uncoated menthol were placed in an oven at different temperatures (T = 20°C, 30°C, 40°C, 50°C) and heated for 0.5 min. The microcapsules were taken out and ground and dissolved with methanol. The microcapsules were then diluted and analyzed by GC-MS. The residual amount of menthol was calculated based on the concentration standard curve and the sample amount. The sustained release was evaluated by the release rate. The release rate at temperature T = 1 - the residual amount of menthol at temperature T ÷ the residual amount of menthol at 20°C.

[0119] Figure 3 is the release rate of different samples at different temperatures. It can be seen from the figure that the wall materials of Examples 2 and 5 do not contain the thermosensitive agent polyethylene glycol 1000 vitamin E succinate, while the wall materials of Examples 1 and 3 contain the thermosensitive agent. Therefore, when the temperature of Examples 1 and 3 rises from 30°C to 40°C, the growth rate of the release rate is relatively large, indicating that the addition of the thermosensitive agent increases the temperature sensitivity of the wall material, allowing the microcapsule to quickly release menthol at 30-40°C. The thermosensitive agent polyethylene glycol 1000 vitamin E succinate has a melting point of 37-41°C and has good water solubility. As a component of the wall material, it can provide good temperature responsiveness for the microcapsule.

[0120] (5) Skin feel test: A human test was conducted. 20 volunteers aged 18 to 45 years who met the test requirements were selected as test subjects (10 males and 10 females). 0.020±0.005 g of the sample was applied to the flexor side of the forearm and evenly applied back and forth with the index finger in two movements over a circular area with a radius of 2 cm. The cooling sensation of the different samples after 0 h and 1 h was felt and ranked. The sample with the most cooling sensation was numbered 1. The average of the numbers was used to obtain the score of the sample at 0 h or 1 h. The results are listed in Table 1.

[0121] Table 1

[0122] project Example 1 Example 4 Example 5 Comparative Example 1 Comparative Example 2 0h Cooling feeling 3 4.4 4.6 1.8 1.2 1h cooling sensation 1.2 2.9 1.9 4.2 4.8

[0123] As can be seen from the table, over time, the ranking of cooling sensation changes greatly. At 0h, Comparative Example 1 and Comparative Example 2 can give skin a stronger cooling sensation, but as time goes by, due to the volatilization of cooling ingredients camphor and menthol, the cooling sensation gradually weakens, and since Examples 1 and 5 are obtained by coating sustained-release microcapsules, the cooling ingredients are continuously released, so after 1h, Example 1 and Example 5 become the two strongest samples of cooling sensation. The above description shows that the preparation method provided by the present invention can prolong the drug effect of menthol ointment. In addition, since Example 4 does not add camphor microcapsules, the cooling ingredients are reduced, so the cooling sensation is poorer than 1.

[0124] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing a compound menthol ointment, characterized in that: The steps include: (1) preparing microcrystals: dissolving a cooling ingredient in ethanol to obtain an organic phase; adding the organic phase to pure water, standing for crystallization, and obtaining microcrystals after solid-liquid separation; the cooling ingredient comprises at least one of menthol and camphor; (2) preparing microcapsules: dispersing the microcrystals in an aqueous solution of a wall material, homogenizing, and then spray drying to obtain microcapsules; (3) preparing the matrix: heating and melting the matrix to obtain a matrix liquid; (4) Preparation of compound menthol ointment: adding the oil-soluble active ingredient into the matrix liquid, stirring evenly while keeping warm, adding the microcapsules after cooling, stirring evenly, canning while hot, and obtaining the compound menthol ointment after cooling.

2. The method for preparing the compound menthol ointment according to claim 1, characterized in that: The particle size of the microcrystals is 0.5 to 20 μm, and the average particle size is 1 to 10 μm.

3. The method for preparing the compound menthol ointment according to claim 1 or 2, characterized in that: The wall material includes a temperature sensitive agent.

4. The method for preparing the compound menthol ointment according to claim 3, characterized in that: The thermosensitive agent is polyethylene glycol 1000 vitamin E succinate.

5. The method for preparing the compound menthol ointment according to claim 1, 2 or 4, characterized in that: The wall material comprises sodium starch octenylsuccinate and maltodextrin.

6. The method for preparing the compound menthol ointment according to claim 1, characterized in that: The mass percentage of the wall material in the aqueous solution of the wall material is 10% to 30%; And / or, the feed mass ratio of the microcrystals to the wall material is 0.8 to 2:1; And / or, the concentration of the cooling component in the organic phase is 0.2-0.3 g / mL. And / or, the volume ratio of the organic phase to pure water is 1:8-12.

7. The method for preparing the compound menthol ointment according to claim 1, characterized in that: The solid-liquid separation method is centrifugation or filter press; And / or, the spray drying temperature is 30-55°C.

8. The method for preparing the compound menthol ointment according to claim 1, characterized in that: The matrix comprises at least one of paraffin, ozokerite, vaseline, zinc wax and lanolin; And / or, the oil-soluble active ingredient includes at least one of methyl salicylate, eucalyptus oil, turpentine oil, clove oil, rose essential oil, cinnamon oil, olive oil, thymol and silicone oil.

9. A compound menthol ointment, characterized in that: The invention is prepared by the preparation method according to any one of claims 1 to 8.

10. The compound menthol ointment according to claim 9, characterized in that: Based on a total weight of 1000 g, the compound menthol ointment is composed of the following raw materials by weight: 50-100 g of menthol, 90-150 g of camphor, 70-250 g of wall material, 250-300 g of oil-soluble active ingredients, and the rest of the matrix.

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