A kind of toad oil cream and preparation method thereof

Abstract

The present invention provides a toad oil cream and a preparation method thereof, and relates to the field of medical technology. The cream comprises toad oil and a matrix, wherein the toad oil is prepared according to the method of Chinese invention patent application CN117126696 A, and the matrix comprises phase A, phase B and phase C, wherein the phase A comprises: cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethyl silicone oil and propylparaben, the phase B comprises: carbomer, glycerol, potassium lauryl phosphate, hyaluronic acid, methylparaben and water, and the phase C comprises the component triethanolamine. By optimizing the matrix, the cream obtained by the present invention has moderate hardness and softness, low cost, good coating property, uniformity and stability, and at the same time, the toad oil is turned into treasure.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a toad oil cream and a preparation method thereof. Background Art

[0002] At present, the main toads used as medicine are toad venom and toad skin. After collecting toad venom and peeling toad skin, toad bones, meat and internal organs become waste, resulting in a great waste of resources. Chinese invention patent application CN117126696A discloses a toad oil and its preparation method and application, using toad internal organs after collecting toad venom and peeling toad skin as raw materials, extracting and processing to make toad oil, turning waste into treasure; the toad oil obtained by the invention has obvious effects on skin diseases (inflammation, eczema, etc.), and according to its component analysis, the toad oil obtained by the invention also has anti-tumor function; the toad oil in the patent application is derived from the internal organs of toads, but it involves the preparation of toad oil, and does not involve information on making toad oil into an ointment for deep utilization.

[0003] Regarding creams, the research progress of cream preparation methods [J] (Nie Jihong, Wang Ping, Jia Ziyi La. Xinjiang Medicine, 2004, (06): 173-177) reviewed the optimization of cream bases and the emulsification methods of creams. The ideal cream should be uniform, delicate, stable and have appropriate viscosity, adhesion and spreadability.

[0004] In order to facilitate the clinical application of the above-mentioned toad oil, it is urgent to develop a toad oil ointment, which can turn toad oil into treasure while preparing an ointment that is uniform, delicate, stable and has suitable viscosity, adhesion and spreadability, while controlling the raw material cost of the ointment matrix. Summary of the invention

[0005] In view of the problems existing in the prior art, the present invention provides a toad oil cream and a preparation method and application thereof. Under the premise of controlling costs, a uniform, delicate, stable toad oil cream with suitable viscosity, adhesion and spreadability is obtained by optimizing the matrix. While turning toad oil into treasure, the toad resource utilization system is improved, and the toad oil is a breakthrough resource reserve for external use of traditional Chinese medicine to treat skin diseases.

[0006] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0007] The first object of the present invention is to provide a toad oil cream, comprising toad oil and a matrix, wherein the matrix comprises a phase A, a phase B and a phase C, wherein the phase A comprises the following components: cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone and propylparaben, the phase B comprises the following components: carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben and water, and the phase C comprises the component triethanolamine.

[0008] Preferably, the mass ratio of phase A, phase B and phase C is 10-20:50-70:0.1-0.5.

[0009] Preferably, the weight proportions of the components in phase A, phase B and phase C are as follows:

[0010] Phase A: 1.5-2.5 parts of cetostearyl alcohol, 1-5 parts of glyceryl monostearate, 6-10 parts of liquid paraffin, 1-3.5 parts of dimethicone, 0.05-0.15 parts of propylparaben;

[0011] Phase B: 0.05-0.15 parts of carbomer, 6-10 parts of glycerin, 1.5-2.5 parts of potassium lauryl phosphate, 0.5-1.5 parts of hyaluronic acid, 0.15-0.25 parts of methylparaben, 50-60 parts of water;

[0012] Phase C: 0.05-0.15 parts of triethanolamine.

[0013] Further preferably, the weight proportions of the components in phase A, phase B and phase C are as follows:

[0014] Phase A: 2 parts of cetostearyl alcohol, 1 part of glyceryl monostearate, 8 parts of liquid paraffin, 2 parts of dimethicone, 0.1 parts of propylparaben;

[0015] Phase B: 0.1 parts of carbomer, 7 parts of glycerin, 2 parts of potassium lauryl phosphate, 1 part of hyaluronic acid, 0.2 parts of methylparaben, 57 parts of water;

[0016] Phase C: 0.1 parts of triethanolamine.

[0017] Preferably, the mass ratio of the toad oil to the matrix is ​​1:99-20:80.

[0018] Preferably, the weight ratio of the cetostearyl alcohol, the potassium lauryl phosphate and the hyaluronic acid is 3-5:3-5:1-3.

[0019] Preferably, the toad oil is prepared according to the method of Chinese invention patent application CN117126696 A, specifically, the toad oil preparation method comprises the following steps:

[0020] S1: crushing the toad viscera to obtain toad viscera paste;

[0021] S2: heating the minced toad viscera obtained in step S1 and then centrifuging and separating the mixture to obtain toad oil;

[0022] In the step S2, the heating method includes heating the toad viscera paste in water, heating with water, and heating with a weak alkali; the heating temperature is ≤95°C, preferably 65°C; the heating time is ≤60min, preferably 30min.

[0023] Further preferably, in the step S1, the particles are crushed to a size of ≤5 mm; in the step S2, a solvent is added when the toad viscera mince is heated in water, and the solvent is distilled water; NaCl is added for salting out when the toad viscera mince is heated in water, and the amount of NaCl added is within 2% of the mass of the toad viscera mince, and more preferably 1%.

[0024] More preferably, in step S2, the salting-out time is ≤20 min, preferably 10 min; the centrifugal rate is ≤10000 r / min, preferably 6000 r / min; and the centrifugal time is <30 min, preferably 15 min.

[0025] The second aspect of the present invention is to provide a method for preparing the toad oil cream according to the claim, comprising the following preparation steps:

[0026] (1) Mix cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone and propylparaben, and stir to obtain a phase A emulsion;

[0027] (2) Carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben and water are mixed and stirred to obtain a phase B emulsion;

[0028] (3) Add phase A to phase B, heat, homogenize, keep warm, add toad oil and triethanolamine, homogenize, and obtain.

[0029] Preferably, the stirring time in step (1) is 10-20 minutes, wherein 12 minutes is the best.

[0030] Preferably, the stirring time in step (2) is 10-20 minutes, with 15 minutes being the best.

[0031] Preferably, the heating temperature in step (3) is 85-100° C., with 85° C. being the best.

[0032] Preferably, the homogenization time in step (3) is 2-5 minutes, among which 3 minutes is the best.

[0033] Preferably, the insulation time in step (3) is 20-30 minutes, of which 25 minutes is the best.

[0034] Compared with the prior art, the present invention has the following beneficial effects: (1) the cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid in the cream matrix of the present invention have a great influence on the comprehensive score of the toad oil cream, including appearance, spreadability, cold stability, heat stability and centrifugal stability, and play a synergistic role in the comprehensive performance of the cream; (2) the cost of the cream matrix of the present invention is relatively low, and the cetostearyl alcohol, potassium lauryl phosphate and triethanolamine in the matrix of the present invention are used as emulsifiers; monostearate glyceryl is selected as the oil phase, liquid paraffin is used as the matrix, and dimethyl silicone oil is used to adjust the viscosity of the oil phase; carbomer is added to the aqueous phase to stabilize the system, and glycerol is added as a moisturizer; in order to prevent the cream from being stored during storage When mildew occurs, two preservatives, propylparaben and methylparaben, are added to make the preservative system more stable; the appearance of the cream is greatly improved by adding hyaluronic acid; although the prior art has matrices such as a165, caprylic / capric triglyceride, shea butter, sweet almond oil, propylene glycol, lubricant oil or amino acid moisturizer that can replace or supplement the matrix of corresponding properties in the present invention, the cost of the above raw material matrix is ​​relatively high. The prior art can achieve a good preparation effect on the basis of saving economic costs, which has the advantage; (3) By optimizing the matrix, the obtained toad oil cream has moderate hardness and softness, good coating properties, uniformity and stability, and at the same time, the toad oil is effectively utilized, turning waste into treasure and saving resources. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 Response surface and contour plots of the mutual influence of potassium lauryl phosphate addition and hyaluronic acid addition (B is the amount of potassium lauryl phosphate added, C is the amount of hyaluronic acid added);

[0036] Figure 2 Response surface and contour map of the mutual influence of the addition amount of cetostearyl alcohol and hyaluronic acid (A is the addition amount of cetostearyl alcohol, C is the addition amount of hyaluronic acid);

[0037] Figure 3 Response surface and contour diagram of the mutual influence of the addition amount of cetostearyl alcohol and potassium lauryl phosphate (A is the addition amount of cetostearyl alcohol, B is the addition amount of potassium lauryl phosphate);

[0038] Figure 4 Properties of the toad oil ointment prepared in Example 1 of the present application. DETAILED DESCRIPTION

[0039] It is worth noting that the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0040] The viscera of Chinese giant toad were obtained from Xichang Fuhua Jinchan Biotechnology Co., Ltd. Toad oil was prepared according to the method of Example 1 of Chinese invention patent application CN117126696 A, specifically: S1: Put the toad viscera into a meat grinder and mince it into toad viscera paste with a particle size of ≤5mm; S2: Take 30g of toad viscera paste and put it into a conical flask, place it in a constant temperature water bath at 80℃ and heat it for 45min, take it out and place it at room temperature, centrifuge it at 6000r / min for 15min, and separate toad oil. Triethanolamine (batch number 20230502) was purchased from Chengdu Huayi Pharmaceutical Excipient Manufacturing Co., Ltd. Glycerol (batch number 20230301) and dimethyl silicone oil (batch number 20230502) were purchased from Jiangxi Puyisheng Pharmaceutical Co., Ltd. Sodium hyaluronate (hyaluronic acid) (batch number 23072401-E) was purchased from Shandong Anhua Biopharmaceutical Co., Ltd. Potassium lauryl phosphate (batch number 119511001090) was purchased from Shandong Yousuo Chemical Technology Co., Ltd. Cetostearyl alcohol (batch number 20230502) and glyceryl monostearate (batch number YF20230201) were purchased from Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd. Liquid paraffin (batch number 20230301) was purchased from Tianjin Damao Chemical Reagent Factory. Propylparaben and methylparaben were purchased from Jiangsu Zhenghong Biotechnology Co., Ltd. Carbomer U20 was purchased from Guangzhou Shengda Biotechnology Co., Ltd. Water was Wahaha purified water.

[0041] Experimental Example 1 Optimization of cream matrix formulation by Box-Behnken response surface methodology

[0042] 1. Determination of key factors

[0043] In the matrix, cetostearyl alcohol, potassium lauryl phosphate and triethanolamine were used as emulsifiers; monostearate glyceryl was selected as the oil phase, liquid paraffin was used as the matrix, and dimethyl silicone oil was used to adjust the viscosity of the oil phase; carbomer was added to the water phase to stabilize the system, and glycerol was added as a moisturizer; in order to prevent the cream from mildewing during storage, two preservatives, propylparaben and methylparaben, were added to make the preservative system more stable; hyaluronic acid was added to promote the absorption of toad oil and improve the efficacy of the drug. In the process of preparing toad oil cream, it was found that the amount of cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid had a great influence on the quality of toad oil cream. Therefore, the comprehensive evaluation index of toad oil cream was used as the response value (dependent variable), and the three factors that had the greatest impact on the quality of toad oil cream, namely, the amount of cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid, were selected as independent variables. Using Design-Expert 13 software, a three-factor three-level test (see Table 1) was conducted to optimize the prescription of toad oil cream.

[0044] Table 1 Response surface experimental factors and levels

[0045]

[0046] 2. Comprehensive evaluation indexes of toad oil cream

[0047] 2.1 Appearance

[0048] If the cream is glossy, uniform and delicate, without bubbles, of appropriate hardness and softness, and has no oil droplets on the surface, it is scored as 16-20 points; if it is smooth, relatively delicate, with a small amount of bubbles, and a small amount of oil droplets on the surface, it is scored as 11-15 points; if it is dull, slightly rough, and has oil droplets on the surface, it is scored as 6-10 points; if it is dull and matte, rough, with a large number of bubbles, and a large number of oil droplets on the surface, it is scored as 0-5 points.

[0049] 2.2 Coating properties

[0050] Take an appropriate amount of toad oil cream and apply it on the glassware. If it is easy to spread, delicate, uniform and non-sticky, it will be scored as 16-20 points; if it is slightly poor in spreadability, not easy to spread, and slightly sticky after application, it will be scored as 11-15 points; if it is difficult to spread, poor in uniformity, and sticky after application, it will be scored as 6-10 points; if it is difficult to spread, uneven, and has a strong oily feeling after application, it will be scored as 0-5 points.

[0051] 2.3 Cold resistance and stability

[0052] Take 2g of toad oil cream and place it in a centrifuge tube. Put it in a -20 ℃ refrigerator for 24 hours, then take it out and restore it to room temperature for observation. If it is uniform and without stratification, it will be scored as 16-20 points; if it is uneven in appearance and slightly stratified, it will be scored as 11-15 points; if it is obviously stratified, it will be scored as 6-10 points; and if it is severely stratified, it will be scored as 0-5 points.

[0053] 2.4 Heat stability

[0054] Take 2g of toad oil cream and put it in a centrifuge tube, store it in a 45℃ constant temperature box for 24 hours, then take it out and restore it to room temperature for observation. If it is uniform and without stratification, it will be scored as 16-20 points; if it is uneven in appearance and slightly stratified, it will be scored as 11-15 points; if it is obviously stratified, it will be scored as 6-10 points; and if it is severely stratified, it will be scored as 0-5 points.

[0055] 2.5 Centrifugal stability

[0056] Take 2g of toad oil cream and put it in a centrifuge tube. After centrifugation at 4500r for 20 min, if it is uniform and without stratification, it will be scored as 16-20 points; if it is uneven in appearance and slightly stratified, it will be scored as 11-15 points; if it is obviously stratified, it will be scored as 6-10 points; and if it is severely stratified, it will be scored as 0-5 points.

[0057] 3. Results

[0058] 3.1 Overall Rating

[0059] The results obtained with cetostearyl alcohol, potassium lauryl phosphate and hyaluronic acid as independent variables and comprehensive evaluation index as dependent variable are shown in Table 2. Among them, the comprehensive evaluation index scores obtained in Experiments 1, 2 and 10 were relatively high.

[0060] Table 2 Response surface experiment results

[0061]

[0062] 3.2 Model Building

[0063] Design-Expert 13 software was used to perform regression fitting on the dependent variable data of toad oil cream, and a binary polynomial regression equation with comprehensive evaluation index as the response value was obtained: Y=79-0.5A-0.375B-1.13C-0.25AB+0.75AC-1.25A 2 -3B 2 -6C 2 (A is the amount of cetostearyl alcohol added, B is the amount of potassium lauryl phosphate added, and C is the amount of hyaluronic acid added). The results of variance analysis of the regression model of toad oil cream are shown in Table 3.

[0064] Table 3 Analysis of variance of regression model

[0065]

[0066] As shown in Table 3, the P value of the model is less than 0.01, indicating that the model is significant, and the P value of the lack-of-fit term is 0.1423, indicating that the lack-of-fit term is not significant, indicating that the model has a good fit. 2 =0.9428, indicating that the actual value and the predicted value have a good correlation, so the model can be used to optimize the preparation process of toad oil cream. From the F value, we can see that the order of influence of the three independent variables on the comprehensive evaluation index of toad oil cream is: hyaluronic acid>cetostearyl alcohol>potassium lauryl phosphate.

[0067] 3.3 Response surface optimization, prediction, and optimal prescription verification

[0068] Design-Expert 13 software was used to make two-dimensional contour lines and three-dimensional effect surface diagrams of the interaction between various factors on the comprehensive evaluation index of toad oil cream, see Figure 1-3 Using the Numerical function of Design-Expert 13 software, the predicted optimal prescription combination of toad oil cream is: 2g of cetostearyl alcohol, 2g of potassium lauryl phosphate, and 1g of hyaluronic acid.

[0069] The numerical function of Design-Expert 13 software was used to predict the optimal formula combination of toad oil cream: 1.77 g cetostearyl alcohol, 1.95 g potassium lauryl phosphate, and 0.93 g hyaluronic acid. The comprehensive evaluation index under this formula condition was 79.12 points. Combined with actual operation, 2 g cetostearyl alcohol, 2 g potassium lauryl phosphate, and 1 g hyaluronic acid were selected for three experiments to calculate the deviation of the comprehensive evaluation index. The deviation values ​​of the measured value and the predicted value were 0.15%, 3.6%, and 1.11%, respectively, indicating that the model predicted by the software is reliable, indicating that Design-Expert 13 software can accurately predict the optimal ratio of the toad oil cream formula for the design of the cream formula.

[0070] Example 1

[0071] Composition: 2 g cetostearyl alcohol, 1 g glyceryl monostearate, 8 g liquid paraffin, 2 g dimethicone, 0.1 g propylparaben, 0.1 g carbomer, 7 g glycerin, 2 g potassium lauryl phosphate, 1 g hyaluronic acid, 0.2 g methylparaben, 57 g water, 0.1 g triethanolamine, 9 g toad oil.

[0072] Preparation method: (1) Mix cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone and propylparaben, and stir for 12 minutes to obtain phase A emulsion; (2) Mix carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben and water, and stir for 15 minutes to obtain phase B emulsion; (3) Add phase A to phase B, heat to 85°C until completely dissolved, homogenize for 3 minutes, keep warm for 25 minutes, add toad oil and triethanolamine, and homogenize for 3 minutes.

[0073] Example 2

[0074] Ingredients: 1.5 g cetostearyl alcohol, 1 g glyceryl monostearate, 6 g liquid paraffin, 1 g dimethicone, 0.05 g propylparaben, 0.05 g carbomer, 6 g glycerin, 1.5 g potassium lauryl phosphate, 0.5 g hyaluronic acid, 0.15 g methylparaben, 50 g water, 0.05 g triethanolamine, 2 g toad oil.

[0075] The preparation method is the same as that of Example 1.

[0076] Example 3

[0077] 2.5 g cetostearyl alcohol, 5 g glyceryl monostearate, 10 g liquid paraffin, 3.5 g dimethicone, 0.15 g propylparaben, 0.15 g carbomer, 10 g glycerin, 2.5 g potassium lauryl phosphate, 1.5 g hyaluronic acid, 0.25 g methylparaben, 60 g water, 0.15 g triethanolamine, 18 g toad oil.

[0078] The preparation method is the same as Example 1.

[0079] Comparative Example 1

[0080] Composition: 2 g glyceryl stearate, 1 g glyceryl monostearate, 8 g liquid paraffin, 2 g dimethicone, 0.1 g propylparaben, 0.1 g carbomer, 7 g glycerin, 2 g potassium lauryl phosphate, 1 g hyaluronic acid, 0.2 g methylparaben, 57 g water, 0.1 g triethanolamine, 9 g toad oil.

[0081] The difference from Example 1 is that cetostearyl alcohol is replaced by an equal amount of glyceryl stearate.

[0082] The preparation method is the same as Example 1.

[0083] Comparative Example 2

[0084] 2 g cetostearyl alcohol, 1 g glyceryl monostearate, 8 g liquid paraffin, 2 g dimethicone, 0.1 g propylparaben, 0.1 g carbomer, 7 g glycerin, 3 g potassium lauryl phosphate, 0.2 g methylparaben, 57 g water, 0.1 g triethanolamine, 9 g toad oil.

[0085] The difference from Example 1 is that hyaluronic acid is replaced by an equal amount of potassium lauryl phosphate.

[0086] The preparation method is the same as Example 1.

[0087] Comparative Example 3

[0088] 2 g cetostearyl alcohol, 1 g glyceryl monostearate, 8 g liquid paraffin, 2 g dimethicone, 0.1 g propylparaben, 0.1 g carbomer, 7 g glycerin, 3 g hyaluronic acid, 0.2 g methylparaben, 57 g water, 0.1 g triethanolamine, 9 g toad oil.

[0089] The difference from Example 1 is that potassium lauryl phosphate is replaced by an equal amount of hyaluronic acid.

[0090] The preparation method is the same as Example 1.

[0091] Comparative Example 4

[0092] 2 g cetostearyl alcohol, 1 g glyceryl monostearate, 8 g liquid paraffin, 2 g dimethicone, 0.1 g propylparaben, 0.1 g carbomer, 7 g glycerin, 2 g octadecyltrimethylammonium chloride, 1 g hyaluronic acid, 0.2 g methylparaben, 57 g water, 0.1 g triethanolamine, 9 g toad oil.

[0093] The difference from Example 1 is that potassium lauryl phosphate is replaced by an equal amount of octadecyltrimethylammonium chloride.

[0094] The preparation method is the same as that of Example 1.

[0095] With reference to the requirement of the Chinese Pharmacopoeia that creams should be uniform, fine, have appropriate viscosity, and be easy to apply, the creams of Example 1 and Comparative Examples 1-4 were scored. The evaluation criteria were based on "2. Comprehensive evaluation index of toad oil cream" in the above Experimental Example 1, and the scoring results are shown in Table 4.

[0096] Table 4: Scoring results of creams of Examples 1-3 and Comparative Examples 1-4

[0097]

[0098] The creams obtained in Examples 1-3 of the present application have moderate hardness and softness, good coating properties, uniformity and stability, and the comprehensive scores are all above 80 points. Figure 4 .

[0099] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A toad oil cream, comprising toad oil and a matrix, characterized in that: The matrix composition and weight parts are as follows: 2 parts of cetostearyl alcohol, 1 part of glyceryl monostearate, 8 parts of liquid paraffin, 2 parts of dimethicone, 0.1 parts of propylparaben, 0.1 parts of carbomer, 7 parts of glycerin, 2 parts of potassium lauryl phosphate, 1 part of hyaluronic acid, 0.2 parts of methylparaben, 57 parts of water, 0.1 parts of triethanolamine; or 1.5 parts of cetostearyl alcohol, 1 part of glyceryl monostearate, 6 parts of liquid paraffin, 1 part of dimethicone, 0.05 parts of propylparaben, 0.05 parts of carbomer, 6 parts of glycerin, 1.5 parts of potassium lauryl phosphate, 0.5 parts of hyaluronic acid, 0.15 parts of methylparaben, 50 parts of water, 0.05 parts of triethanolamine; or 2.5 parts of cetostearyl alcohol, 5 parts of glyceryl monostearate, 10 parts of liquid paraffin, 3.5 parts of dimethicone, 0.15 parts of propylparaben, 0.15 parts of carbomer, 10 parts of glycerin, 2.5 parts of potassium lauryl phosphate, 1.5 parts of hyaluronic acid, 0.25 parts of methylparaben, 60 parts of water, and 0.15 parts of triethanolamine.

2. The toad oil ointment according to claim 1, characterized in that The mass ratio of the toad oil to the matrix is ​​1:99-20:

80.

3. A method for preparing the toad oil cream according to any one of claims 1-2, characterized in that: The preparation method comprises the following steps: (1) Mix cetostearyl alcohol, glyceryl monostearate, liquid paraffin, dimethicone and propylparaben, and stir to obtain a phase A emulsion; (2) Carbomer, glycerin, potassium lauryl phosphate, hyaluronic acid, methylparaben and water are mixed and stirred to obtain a phase B emulsion; (3) Add phase A to phase B, heat, homogenize, keep warm, add toad oil and triethanolamine, homogenize, and obtain.

4. The preparation method according to claim 3, characterized in that: The stirring time in steps (1) and (2) is 10-20 minutes.

5. The preparation method according to claim 3, characterized in that: The heating temperature in step (3) is 85-100°C.

6. The preparation method according to claim 3, characterized in that: The homogenization time in step (3) is 2-5 minutes, and the insulation time is 20-30 minutes.

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