Preparation method of ultra-high-purity nanoscale octacosanol dispersion

Abstract

The invention belongs to the technical field of high-carbon fatty alcohol mixture extraction processes. The invention particularly relates to a preparation method of an ultra-high-purity nanoscale octacosanol dispersion. The device specifically comprises (1) a subcritical pressure composite liquefied gas leaching, filtering and separating integrated device, and (2) a vacuum integrated device for extracting milky white cane wax; (3) refining octacosanol through cooperation of high-vacuum secondary distillation and multi-time recrystallization of a composite solvent; (4) performing superfine nanometer grinding; according to the invention, the combined extraction method is adopted for the first time in China, and the nanoscale octacosanol dispersion with the particle size median value D50 being less than or equal to 0.07 mu m and the purity being 99.5% is obtained from the sugarcane by-product through refining extraction; compared with other known methods, the method for extracting the high-purity nanoscale octacosanol through the combined extraction method has the advantages of being simple in process, short in reaction time and high in yield, purity and mesh number.

Description

Technical Field

[0001] The invention belongs to the technical field of high-carbon fatty alcohol mixture extraction process methods, and specifically relates to a method for preparing an ultra-high-purity nano-scale octacosanol dispersion. Background Art

[0002] According to conventional technical knowledge in this field, higher fatty alcohols are also called policosanols, and their sources include rice bran wax, insect wax, wheat germ oil, and sugarcane wax. Their carbon chain length is generally an even number of 22 to 34, and they are a general term for mixed long-chain fatty alcohols. Their main components range from 22-carbon fatty alkanols to 36-carbon fatty alkanols, as shown in Table 1. Table 1

[0003] According to industry consensus, the current status of octacosanol extraction technology research at home and abroad is as follows: The 24-34 carbon higher alkanols contained in Cuban Policosanol account for more than 90% of the weight of the extract, of which the purity of octacosanol is 60%-70%; Claim (5) of Chinese Patent CN105237339B - A method for extracting octacosanol using sugar factory mixed juice scum as raw material, takes crystals 3, repeats the above crystallization operation step (4), that is, performs multiple recrystallization operations at 20°C, and obtains crystals 4, the yield of crystals 4 is 1.00%-2.00%, and the purity of octacosanol in the obtained crystals 4 is 68.00%-80.00%; Therefore, 98% policosanol with a purity of 60% has become a hot-selling specification in the market. The octacosanol claimed in the market is only a conceptual summary. It is not pure octacosanol, but a mixture of some higher fatty alcohols with low extraction rate and more impurities in the extraction. The reason is mostly due to the limitations of extraction technology by manufacturers. The above purity can only be used for health care functions such as anti-fatigue and improving human body functions, thus limiting its further development in the fields of food and medicine; Based on the common knowledge in the industry, different purity and octacosanol have different effects in different fields. Since the higher the purity of octacosanol, the stronger its activity and the greater its polarity, if you want to achieve the effects of effectively lowering lipids, preventing cardiovascular diseases, improving hypoxia tolerance and preventing osteoporosis, the purity must be at least 90%. Therefore, purity determines the physiological activity of a drug;

[0004] Therefore, how to prepare ultra-high purity nano-scale octacosanol at low cost is currently the focus of research by scientists from various countries and a technical fortress that has not been overcome so far. Summary of the invention

[0005] At present, most countries use a single extraction method to study the extraction of octacosanol, and cross-comparison and integrated compounding of various extraction processes are rare; there are still certain limitations in industrial application; Therefore, the study of integrating and compounding multiple extraction processes to nano-purify ultra-high purity octacosanol has great application value. This application proposes a method for preparing an ultra-high purity nano-scale octacosanol dispersion to extract a nano-scale octacosanol dispersion with an octacosanol purity of 99.5% and a median particle size D50≦0.07μm. This aspect has not been reported yet; it was the first case before our company's application.

[0006] In order to achieve the above object, a method for preparing an ultra-high purity nano-scale octacosanol dispersion comprises the following process steps: Step 1: Extract milky white sugarcane wax using subcritical composite liquefied gas extraction, filtration and separation integrated device Put the sugarcane byproduct crushed to 2000 mesh into the leaching reaction tank of the integrated device, start the pressure pump, press the composite liquefied gas into the reaction tank, the mass volume ratio of the sugarcane byproduct to the composite liquefied gas is 1:3.5-5, adjust the pressure to 3.75-4.05MPa, and after the room temperature treatment time is 28-35min, transfer the solvent containing the sugarcane wax to the separator for filtration, separate the desolvated milky white sugarcane wax in the separator, and the composite liquefied gas after the sugarcane wax is separated is compressed and cooled by the recovery device and recycled; The sugarcane by-product is any one of bagasse, sugarcane filter mud, coarse sugarcane husk and dry sugarcane silk; The composite liquefied gas is any one of propane, butane, and mixed hexane; Step 2: Ultrafine grinding, microwave, ultrasonic wave and ultra-high pressure vacuum integrated device to enhance the extraction of high-grade fatty alcohol mixture The sugarcane wax obtained in step 1 is mixed with an ethanol solution with a concentration of 50-70%, and 0.15-0.8% organic acid is added to the total weight of the feed liquid at a feed-liquid ratio of 1:12-20 g / mL, and placed in an ultrafine grinding-microwave-ultrasonic-ultrahigh pressure vacuum integrated device for treatment, the microwave function is started, the microwave power range is set to 350w-400w, and the microwave frequency is 2400-2500MHz for microwave treatment for 2 minutes, and then the microwave function is turned off; food-grade 99.9999% ultrapure nitrogen is input, the ultrahigh pressure function is started, and the extraction is carried out at a pressure of 200-600MPa, the pressure increase rate is 50MPa / s, and the pressure is maintained for 2-8min after the pressure increase is completed, and then the pressure is relieved, and the pressure relief rate is 100MPa / s, and then the ultrahigh pressure function is turned off; at the 5th to 11th minute of the total treatment time, the grinding is started; Grinding function and microwave function: the grinding function adopts a linear speed of 16m / s, adjusts the pressure to 0.4-0.6MPa, and the grinding treatment time is 39-47min. The microwave function performs intermittent treatment, that is, microwave treatment for 2min, then standing for 3min, microwave treatment for 1min, and then standing for 3min to complete a cycle. This cycle is repeated 4 times. At the 21st to 24th minute of the total treatment time, the ultrasonic function is started, the ultrasonic frequency is set to 20KHz-40KHz, the ultrasonic power is 1.2Kw-3Kw, the ultrasonic treatment time is 25-30min, and then the ultrasonic function is turned off; the total treatment time is 49-51min; the precipitate is discarded, the upper layer liquid is poured out for suction filtration, cooled and precipitated, and a submicron-level high-grade fatty alcohol mixture with a median particle size D50≦0.361μm is obtained; and the solution is recovered at the same time; The organic acid is any one of succinic acid, tartaric acid, citric acid, malic acid, acetic acid and lactic acid, and the pH value is 3 to 3.86; The method for detecting the median particle size is to use a laser particle size analyzer to perform wet particle size detection. For third-party detection, see Document 1 - Median Particle Size "Test Report"; The ultrafine grinding-microwave-ultrasonic-ultrahigh pressure vacuum integrated device adopts the TG2022-13 ultrafine grinding-microwave-ultrasonic-ultrahigh pressure vacuum integrated device manufactured by Shandong Warner Intelligent Equipment Co., Ltd. under the technical authorization of Guangzhou Lvhui New Materials Research Institute Co., Ltd. Step 3: High vacuum secondary distillation and multiple recrystallizations of composite solvents to synergistically refine octacosanol: ①High vacuum secondary distillation: The higher fatty alcohol mixture obtained in step 2 is placed in a closed kettle and heated to 115-125° C.; the heat preservation and vacuum systems are turned on, and a fatty alcohol mixture of C28 alcohol or higher is obtained by secondary distillation at a vacuum degree of 11-12 Pa and a distillation temperature of 220-240° C.; ②Multiple recrystallization process flow: Add the fatty alcohol mixture above C28 alcohol obtained in ① into cyclohexane-anhydrous ethanol composite solvent, with a crystallization temperature of 35°C and a solid-liquid ratio of 1:5.5-6.5, stir until uniform, let stand, and filter to obtain a filtrate. After standing, recover the lower residual liquid, repeat recrystallization of the upper filtrate twice, and obtain a crystal of octacosanol with a purity of 99.5% by filtering; The volume ratio of the cyclohexane-anhydrous ethanol composite solvent is 1:3.5-4.5; Step 4: Ultrafine nano-grinding: Put 20-30 parts of the octacosanol crystals obtained in step 3②, 1-2 parts of a dispersant, 4-10 parts of anhydrous ethanol, and 58-75 parts of deionized water into a device for superfine nano-grinding of plant fiber powder by pressure-variable cavitation high-speed three-vortex-microwave composite, and perform superfine nano-grinding to a median particle size of D50≦0.07 μm, then desolventize, and spray freeze-dry to obtain a nano-scale octacosanol dispersion with a purity of 99.5% and a D50≦0.07 μm; The method for detecting the median particle size is to use a laser particle size analyzer to perform wet particle size detection. For third-party detection, see Document 2 - Particle Size Median "Test Report"; The purity detection method is to use gas chromatography for detection and measurement. The third-party detection can be found in the certificate document 3 - Octacosanol Purity "Test Report".

[0007] The subcritical composite liquefied gas extraction, filtration and separation integrated device described in step 1 is composed of an extraction reaction tank, a separator and a recovery device.

[0008] The dispersant described in step 4 is any one of polyethylene glycol monomethyl ether 2000, polyethylene glycol 2000, and polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or a composite of two of the two.

[0009] The nanometer-scale octacosanol dispersion described in step 4 is used in the fields of aerospace, special food, special functional beverage, health care product, raw material medicine and medicine as required.

[0010] Beneficial Effects How to quickly, efficiently, economically and environmentally friendly extract octacosanol from sugarcane wax sources, and produce large quantities of high-quality such substances on an industrial and large scale, the problems that should be solved in production are the focus of our research. The research of this application starts from the following aspects.

[0011] First, extract milky white sugarcane wax using a subcritical composite liquefied gas extraction, filtration and separation integrated device (1) Current status of sugarcane wax production ① Both at home and abroad, sugarcane wax has been extracted and produced from sugarcane filter mud for a period of time. Due to the traditional sugar making method, the filter mud contains too many ineffective impurities and is "very dirty". The traditional extraction method is difficult to purify and refine, the yield of effective ingredients is not high, the solvent consumption is large, and the cost is high. Therefore, there has been no large-scale production for many years; ② According to literature reports, the traditional extraction methods of sugarcane wax are generally solvent extraction and supercritical CO2 extraction. The two methods each have their own advantages and disadvantages. The disadvantage of the former is that the solvent consumption is large and it pollutes the environment, but the equipment requirements are not high and it is suitable for large-scale industrial production. The latter is not solvent-based, which can simplify the process, simple process, and easy operation, but the one-time investment in equipment is large.

[0012] (2) This application uses subcritical pressure composite liquefied gas leaching to extract milky white sugarcane wax The present application has found and verified the effects of various solvent extraction methods on cane wax extraction through experimental research, see Table 2 Table 2 The experiment in Table 2 shows that hexane is a very good extraction solvent, which is manifested in: the yield of sugarcane wax is relatively high, and milky white sugarcane wax can be obtained by one-step extraction, and the steps of soaking and decolorization can be omitted; the present application is based on the fact that alkanes with relatively small carbon atoms will have a better effect on the extraction of sugarcane wax, and any composite liquefied gas of propane, butane, and mixed hexane is used as a liquefied leaching agent; at this time, the pressure only needs to be 3.75 to 4.05 MPa, therefore, the present application proposes the use of a subcritical composite liquefied gas leaching filtration-separation integrated device, and an leaching separation integrated process.

[0013] This application has found and verified through experimental research: ① When the leaching time increased from 15min to 28-35min, the yield of sugarcane wax increased from 1% to 1.6%, which was a significant increase, indicating that the extraction of sugarcane wax was ongoing during this period; while when the leaching time increased from 28-35min to 60min, the yield of sugarcane wax only increased from 1.6% to 1.65%, which was a small increase, indicating that after 28-35min of leaching, the reaction was basically completed. Extending the reaction time had little effect on the yield of sugarcane wax; Using the subcritical composite liquefied gas pressure leaching method of the present application, the leaching time for extracting sugarcane wax is only 28 to 35 minutes. Compared with the extraction time of 2 to 5 hours in Patent 200710175801.1 (a method for extracting sugarcane wax from sugarcane filter mud by subcritical pressure pulse), the leaching time of the present application is greatly shortened; compared with the traditional solvent leaching method, the present application greatly improves the leaching efficiency.

[0014] ② Using the subcritical composite liquefied gas extraction, filtration and separation integrated device of the present application, milky white sugarcane wax is extracted. When the mass volume ratio of sugarcane by-products and composite liquefied gas increases from 1:1 to 1:3.5-5, the yield of sugarcane wax increases from 0.9% to 1.6%, indicating that when the composite liquefied gas, that is, the amount of solvent is too small, the extraction of sugarcane wax is incomplete; and when the mass volume ratio of sugarcane by-products and composite liquefied gas increases from 1:3.5-5 to 1:6, the yield of sugarcane wax does not change much, indicating that the amount of solvent is sufficient to extract the sugarcane wax, and the liquid-solid ratio has no effect on the yield of sugarcane wax, so there is no need to increase the amount of composite liquefied gas.

[0015] ③ Compared with the traditional solvent extraction method of cane wax, the method of extracting milky white cane wax using the subcritical composite liquefied gas leaching filtration-separation integrated device of the present application has a greatly reduced leaching solid-liquid ratio from 1:6 to 1:3.5-5, which saves leaching liquid and thus saves production costs; The extraction time of the method of the present application is short, and the entire extraction process can be completed in 28 to 35 minutes; the extraction temperature is low, which avoids the denaturation of the sugarcane wax due to high-temperature melting during the extraction process; and the operation under normal temperature and low pressure makes the output high in quality ratio and easy to industrialize on a large scale; the yield of sugarcane wax is relatively high, and milky white sugarcane wax can be obtained by one-step extraction, which can save the soaking and decolorization steps of the current traditional process; therefore, a new way with commercial value is created for the extraction and purification of sugarcane wax.

[0016] The extraction results of sugarcane wax from sugarcane byproducts in different forms in this application are shown in Table 3 Table 3 Bagasse in different forms Sugarcane wax production (g) Sugarcane wax yield (%) Solvent recovery rate (%) Ordinary bagasse 0.623 2.492 68.1 Sugarcane filter mud 0.489 1.956 72.8 Sugarcane peel 0.786 3.144 75.2 Dried sugarcane shreds 1.062 4.248 69.8

[0017] The present application determines that the optimal process for extracting milky white sugarcane wax using a subcritical composite liquefied gas extraction, filtration and separation integrated device is as follows: 2000 mesh dry sugarcane silk, a mass volume ratio of sugarcane by-products to composite liquefied gas of 1:3.5-5, adjusting the pressure to 3.75-4.05 MPa, and processing time of 28-35 min; using this optimal process for repeatability verification tests, the extraction results have good stability and will not have a significant impact on the structure of the sugarcane wax.

[0018] second, According to the literature [Food and Oils - Study on the Preparation of High-Purity Octacosanol from Rice Bran Wax - Zhejiang Institute of Grain Science]: There are two main preparation methods for preparing fatty alcohols from rice bran wax. One method is to hydrolyze the wax ester to make the fatty alcohol free, which is convenient for extraction. There are many methods of hydrolysis, such as high-pressure hydrolysis, acid or alkali decomposition, and enzymatic decomposition in recent years. According to the industry's well-known knowledge in this field, the current research on the extraction of higher fatty alcohols from sugarcane wax at home and abroad: ⑴ The existing processes have the following disadvantages: long reaction time, complex process flow, cumbersome operation, low product yield, high cost, and the addition of a large amount of strong acid and alkali, which increases the amount of sewage discharged and causes serious environmental pollution, which increases the environmental pressure of enterprises. ⑵ The temperature and pressure control deviation of the extraction equipment is large, especially in terms of accuracy, and the stability is also poor. The performance of the high-pressure pump is poor, and blockage or leakage often occurs, which places high requirements on the equipment; ⑶ The equipment investment is large, the extraction kettle cannot continuously operate the solid material, the equipment energy consumption is large during the operation, and it is difficult to industrialize production; Therefore, as stated in the public literature: There is no domestic enterprise that uses the above method to process the production of higher fatty alcohol mixtures extracted from sugarcane wax and corresponding products on a large scale, and industrialization has certain difficulties.

[0019] This application pioneered the use of ultrafine grinding-microwave-ultrasound-ultra-high pressure vacuum integrated device, combined with 50-70% ethanol solution and organic acid to enhance the hydrolysis reaction effect. The combined dynamic extraction method was used as a new auxiliary method to obtain a submicron-level white high-grade fatty alcohol mixture with a median particle size of D50 = 0.361 μm. These efforts can be divided into the following six strategies.

[0020] ⒈ This application uses 50-70% ethanol solution as the solvent for the hydrolysis of sugarcane wax Water is the medium of sugarcane wax hydrolysis reaction and also one of the reactants. Sugarcane wax molecules need the participation of water molecules to undergo hydrolysis reaction. Ethanol has solubility for most plant secondary metabolites, and its extraction principle is to separate the substances to be extracted by utilizing its affinity and solubility for the extracted substances. Based on general chemical principles, during the sugarcane wax hydrolysis reaction, the addition of ethanol solution can adjust the dissolution and dispersion of the reaction system, increase the flexibility and controllability of the reaction, have a certain catalytic effect, and promote the hydrolysis reaction, thereby increasing the reaction rate and conversion rate, making the reaction more efficient.

[0021] ⑴ The melting point range of cane wax is 84°C, the melting point of higher fatty alcohols is 81-83°C, and the boiling point of ethanol is 78°C; due to the solubility of wax esters and alcohols, the temperature must be increased to make them in a completely molten state, and the reaction temperature is limited by the boiling point of the solvent. The boiling point of a 50-70% ethanol aqueous solution will increase as the ethanol concentration decreases. Specifically, the higher the ethanol concentration, the lower the boiling point. The boiling point of a 50-70% ethanol aqueous solution in actual operation is about 85-90°C. These data show that the boiling point range of a 50-70% ethanol aqueous solution is similar to the melting point range of cane wax, and the reaction system is uniform, which is conducive to the occurrence of the reaction. Therefore, this makes the 50-70% ethanol solution in this application an effective solvent for separating higher fatty alcohols from cane wax; (2) The higher the ethanol concentration, the higher the extraction rate of the ingredients; however, too high an ethanol concentration will affect the air-liquid surface tension of the substance, causing the substance to be unable to dissolve and diffuse smoothly, and instead reducing the extraction effect. The concentration of the 50-70% ethanol solution in this application can avoid this effect to a certain extent and ensure the extraction effect; it has a certain solubility for the active ingredients in sugarcane wax, which helps to extract the required higher fatty alcohols; ⑶ The 50-70% ethanol solution of the present application can remove a large amount of impurities such as colloids and vitamins in higher fatty alcohols; and the ethanol solution used can be recycled and reused, thereby reducing costs, being cheap and clean.

[0022] ⒉ This application uses weak acid composite ultra-high pressure double modification technology for sugarcane wax hydrolysis ⑴ Use weak acid as a catalyst to reduce the activation energy of sugarcane wax hydrolysis reaction and gently promote the reaction process In general, under the appropriate acid type and acidity, the activity of the catalyst usually increases with the increase of acidity, either linearly or nonlinearly. Under acidic conditions, the hydrolysis of ester groups usually involves acid catalysts, such as strong acids or weak acids, and the difference in acid hydrolysis lies in the degree of reaction and the number of products. In addition, strong acids can make the ester hydrolysis reaction faster, but excessive acidity may lead to incomplete reaction or the production of by-products. At the same time, it is also necessary to pay attention to its strong corrosiveness, which has a greater impact on the environment. The ester hydrolysis rate under weak acid conditions is slower than that of strong acids, but weak acids can accelerate the speed at which hydrolysis reaches equilibrium and play a catalytic role; they can reduce the activation energy of the sugarcane wax hydrolysis reaction under mild conditions and promote the hydrolysis reaction. The degree of reaction is affected by many factors, such as temperature and concentration. These differences make strong and weak acid conditions have an important influence on the selection and control of ester hydrolysis reactions.

[0023] The pH value of the organic acid used in this application is 3 to 3.86, which replaces the strong acid (such as sulfuric acid with a pH value of about -1.265) or strong alkali in traditional technology and is used for interfacial reaction to achieve the acid decomposition effect of the sugarcane wax in this application; according to the "National Food Safety Standard for the Use of Food Additives" (GB 2760-2024), they are all clearly included in the category of food additives and will not remain.

[0024] (2) Ultra-high pressure hydrolysis treatment of this application According to common knowledge in the industry: when other conditions are exactly the same, the density of a fluid reflects its solubility to a considerable extent, and the concentration of solute dissolved in the fluid increases with the increase of fluid density. Fluid density increases with the increase of pressure, and a slight change in pressure can lead to a sharp change in fluid density.

[0025] Based on the characteristics of ultra-high pressure, pressure is an important factor in ultra-high pressure hydrolysis extraction. Increasing the pressure can increase the penetration of the solvent, thereby shortening the time required for the hydrolysis process. The present application has discovered and verified through experimental research that the ultra-high pressure hydrolysis treatment technology of the present application has many unique advantages compared with other traditional technologies, which are specifically manifested in the following aspects.

[0026] ①Short hydrolysis time and high extraction yield: In the pressure-increasing and pressure-holding stages of the ultra-high pressure treatment of the present application, the ultra-high pressure difference allows the solvent to quickly penetrate into the sugarcane wax, and the hydrolyzed extract is quickly dissolved in the solvent; in the pressure-releasing stage, the pressure is rapidly reduced from the ultra-high pressure of several hundred MPa to normal pressure within a few seconds. The shorter the pressure-releasing time, the stronger the impact force generated by the fluid in the material while diffusing outward, and the stronger the turbulent effect caused. The ultra-high reverse pressure difference provides ultra-high mass transfer power for the extraction components dissolved in the solvent to diffuse from the inside of the sugarcane wax to the outside. Under the action of the reverse pressure, the fluid and the hydrolyzate matrix structure become loose, and structural changes such as the extraction components and the solvent are fully contacted. The solvent that has dissolved the extraction components is quickly transferred to the outside of the sugarcane wax under the high osmotic pressure difference, thereby achieving the purpose of extraction; the larger the effective specific surface area of ​​a certain mass of the sugarcane wax matrix, the smaller the mass transfer resistance of the extraction components to diffuse, the more sufficient the contact with the solvent will be, and the higher the hydrolysis efficiency will be; the extraction components can quickly diffuse out of the sugarcane wax, so the ultra-high pressure hydrolysis treatment can significantly shorten the hydrolysis extraction time; The hydrolysis extraction yield of the ultra-high pressure treatment of the present application is increased by 25% compared with the traditional ethanol reflux extraction method, but the hydrolysis extraction time of the present application is 2 to 10 minutes, which is 1.1 to 5.6% of the ethanol reflux extraction time of 180 minutes.

[0027] ②Low solvent consumption: The ultra-high pressure treatment of the present application is carried out under completely closed conditions, without volatilization and consumption of solvents, and the diffusion of the extraction components from the sugarcane wax to the surrounding solvent is not simply provided by the concentration gradient to provide mass transfer power, but mainly by the pressure difference, which can significantly reduce the consumption of solvents.

[0028] ③High extraction efficiency: The pressure of the ultra-high pressure treatment in this application is 200-600MPa. Due to the high pressure, the solvent can penetrate into the sugarcane wax in a very short time and quickly reach a dissolution equilibrium, which greatly accelerates the solvent infiltration process and the solute diffusion process, thereby increasing the mass transfer rate of hydrolysis; the hydrolyzate can be completely extracted in a very short time, so the time required for hydrolysis can be significantly shortened, thereby improving the extraction efficiency.

[0029] ④Low energy consumption: In the ultra-high pressure treatment process of the present application, fluid is used as mass transfer, and when the fluid is compressed, less energy is consumed, and the energy consumed is only about 1% of the reflux extraction. After deducting the influence of various factors during actual operation, at least 80% of energy can be saved; there is no energy consumption or energy transfer in the pressure maintenance and pressure relief processes.

[0030] ⑤Extraction at room temperature: During the ultra-high pressure treatment process of the present application, the solution generates less heat when being compressed and can basically be maintained at room temperature. At the same time, since the ultra-high pressure of the present application uses fluid static pressure, the pressure transmission is completed instantly, and the pressure in any direction and position in the container is equal. Therefore, the ultra-high pressure treatment of the present application has a uniform effect on the material, avoiding local uneven heating in the traditional high temperature and high pressure method or hot reflux method extraction process, causing structural changes and losses of target components, thereby ensuring that the hydrolyzed extract has higher biological activity.

[0031] The present application has analyzed and verified through orthogonal test that: when the extraction pressure is greater than 600MPa, as the pressure increases, the extraction rate decreases instead. The optimal process of ultra-high pressure treatment of the present application is: input food-grade 99.9999% ultra-pure nitrogen, extract at a pressure of 450-600MPa, the pressure increase rate is 50MPa / s, and the pressure is maintained for 3-5 minutes after the pressure increase is completed, and then the pressure is released; this optimal process is used to carry out repeatability verification tests, and the hydrolysis extraction results are more stable.

[0032] ⒊ This application adopts intermittent microwave treatment, using microwaves for rapid and selective heating Temperature mainly affects the extraction effect through density and volatility of solute. The temperature has both positive and negative effects on the dissolution of solute. On the one hand, when other conditions remain constant: when the acid decomposition temperature is low, the reaction rate decreases, resulting in incomplete acid decomposition reaction, prolonged reaction time, and slow growth of acid decomposition rate; the solubility of the higher fatty alcohol mixture is relatively poor and the quality is poor. On the other hand, the increase in temperature increases the volatility of the extracted components, thereby increasing the solubility; when the temperature gradually reaches the melting point of sugarcane wax and higher fatty alcohols, the melted higher fatty alcohol molecules can more fully contact with the molecules of ethanol solution with a concentration of 50-70%. According to the principle of like dissolves like, the growth rate of the yield of the higher fatty alcohol mixture is accelerated.

[0033] Microwaves have light-like, wave-like, high-frequency, thermal and non-thermal biological effects; this determines that organic samples in microwave extraction environments have the following characteristics: 1. Instantaneous temperature generation and short extraction time; 2. Uniform heating; 3. Selective heating, which can improve the extraction effect through appropriate solvents; 4. Accompanied by biological effects;

[0034] The present application is based on the fact that microwave radiation can rapidly heat up, microwave power increases, temperature rises, molecular motion speeds up, and effective substances can be extracted quickly and efficiently, which is beneficial to extraction; the present application has undergone a large number of preliminary tests: (1) The electromagnetic field generated by microwaves causes the 50-70% ethanol solution used in this application to rotate at high speed into an excited state, thereby strengthening the driving force of the extraction component; the released energy is transferred to other substance molecules, accelerating their thermal motion, accelerating the diffusion rate of the extracted part to the extraction solvent interface, and shortening the time for the molecules of the extraction component to diffuse from the inside of the material to the extraction solvent interface, thereby increasing the extraction rate several times; ⑵ By using intermittent microwave treatment, the extraction medium can be captured and dissolved under appropriate temperature conditions, while also reducing the extraction temperature to maximize the quality of the extraction; using the heating effect of microwave energy to accelerate the dissolution of components in the material by the solvent can improve the extraction efficiency and have better selectivity; microwave-assisted method can shorten the extraction time, promote the dissolution of effective substances, and significantly improve the extraction efficiency.

[0035] Temperature is an important factor affecting the hydrolysis reaction rate of sugarcane wax. Properly increasing the temperature can increase the speed of molecular movement, making the collision between sugarcane wax molecules and water molecules more frequent, thereby accelerating the hydrolysis reaction. Accelerate the hydrolysis rate of sugarcane wax. However, too high a temperature may result in a product that is no longer the desired product. This application has been analyzed and verified through orthogonal experiments: when the microwave power is 350-380w, the temperature of the 50-70% ethanol solution is 86.90-92.62, which is slightly higher than the melting point of sugarcane wax and higher fatty alcohols, and is similar to the boiling point of the 50-70% ethanol solution; when the microwave power is 375w, the extraction reaches its peak. The optimal process of the intermittent microwave method of the present application is determined as follows: the microwave frequency is 2500MHz, and the microwave power is 375w for intermittent treatment, that is, the microwave is first treated for 2min, then allowed to stand for 3min, the microwave is treated for 1min, and then allowed to stand for 3min. After 4 cycles, the microwave treatment time is a total of 14min. Among them, the microwave power and extraction time have a highly significant effect on the extraction rate. This optimal process is used for repeatability verification tests, and the auxiliary extraction results are more stable and will not have a significant effect on the higher fatty alcohol mixture.

[0036] ⒋ This application uses ultrasonic treatment to utilize the effect of ultrasonic cavitation on the side effects of sugarcane wax As an elastic wave, ultrasound can generate powerful energy through vibration, giving the medium point a great speed and acceleration, causing the extract and sugarcane wax to oscillate continuously, which helps the diffusion of solutes. Ultrasonic waves penetrate deeper into sugarcane wax than electromagnetic waves and stay longer, which can accelerate the entry of effective ingredients in sugarcane wax into the solvent and increase the extraction rate of effective ingredients. Compared with traditional stirring technology, ultrasonic cavitation can more easily achieve uniform mixing of media, eliminate local concentration unevenness, increase reaction speed, stimulate the formation of new phases, shear the agglomerates, and cause strong mutual collision and aggregation between molecules, causing significant changes in the surface morphology, surface composition and reaction activity of the reactants. It improves local heat and mass transfer between solid-liquid interfaces, thereby improving reaction efficiency.

[0037] The reason for the ultrasonic enhancement of the acid decomposition reaction in this application is that its strong emulsification and cavitation effects enhance the interaction between the alcohol and wax phases, which greatly increases the reaction interface and strongly mixes the two phases to form a highly dispersed emulsion, shortening the induction period, and promoting uniform mixing of the two phases, reducing concentration polarization, and thus accelerating the reaction. On the other hand, in the acid decomposition reaction, the application of ultrasound depends on the effect of its sound wave energy generation, which significantly improves the leaching rate and product purity, and shortens the reaction time. Therefore, the use of ultrasound to assist the acid decomposition reaction can accelerate the reaction rate and improve the conversion rate; The present application analyzes and verifies through orthogonal experiments that: as the ultrasonic power increases, the cavitation effect accelerates the seepage of the target product; compared with the water bath extraction, the extraction rate is improved to a certain extent, and the liquid-solid ratio is reduced, shortening the extraction time; in industrialization, the pressure on subsequent processing steps is reduced; considering the extraction efficiency, the optimal process conditions of the ultrasonic method of the present application are determined as follows: the ultrasonic frequency is 30KHz, the ultrasonic power is 2.3Kw, and the extraction time is 30min; this optimal process is used to carry out repeatability verification tests, and the extraction results are stable.

[0038] ⒌ This application adopts intermittent microwave treatment-ultrasonic time difference overlapping treatment synergistic reaction / extraction: When processing the sample, the cane wax is first subjected to intermittent microwave treatment, which first produces a thermal effect inside it, increases the internal pressure, and causes the active compounds to dissolve; then the time-difference overlapping ultrasound produces mechanical vibrations inside the cane wax, destroying its stable structure; and the synergistic effect of the two treatments greatly improves the extraction efficiency of the mixture of higher fatty alcohols in cane wax; during the extraction process, the yield of the mixture of higher fatty alcohols in cane wax increases rapidly; a reasonable explanation for this phenomenon may be that the solvent absorbs microwave energy in the early stage of extraction and accumulates heat energy that raises the temperature, making the difference in concentration inside and outside the cane wax accelerate the extraction of higher fatty alcohols in the cane wax. The dissolution of the mixture promotes its entry into the solvent; as the extraction time increases, higher temperatures accelerate molecular motion and change the conductivity of the extraction solvent and the material. The target has a higher solubility in the extraction solvent at a higher temperature, while the surface tension and viscosity become smaller, which will enhance sample preparation and penetration into the matrix; on the other hand, temperature also affects the cavitation threshold of ultrasound; a high threshold can improve the cavitation effect of sound waves, promote the formation of cavitation nuclei, expand the contact area between the solvent and the material, and promote the penetration of the solvent into the extract; these two effects accelerate the diffusion of the extract solute in the extraction solvent; as a result, the maximum yield is gradually achieved.

[0039] Experimental studies have found and verified that, compared with other known methods, the intermittent microwave-ultrasonic time difference overlapping treatment synergistic reaction / extraction of the high-grade fatty alcohol mixture in sugarcane wax of the present application has a very good effect.

[0040] 1. Comparison with traditional microwave extraction method: Under the same conditions of ethanol concentration, extraction time, solid-liquid ratio and extraction temperature, the results showed that the strong microwave effect of the traditional microwave extraction method would destroy the structure of the higher fatty alcohol mixture, causing the higher fatty alcohol mixture to degrade, and the yield would decrease instead; the intermittent microwave-ultrasonic time difference overlapping treatment synergistic reaction / extraction of the present application increased the extraction rate by about 9.5% compared with microwave alone.

[0041] (Ⅱ)Comparison with traditional ultrasonic extraction method: When the ethanol concentration, extraction time, solid-liquid ratio and extraction temperature are the same, the results show that the traditional ultrasonic power is too strong, which will form a sound screen on the surface of the sugarcane wax, thereby affecting the extraction of the higher fatty alcohol mixture; the intermittent microwave-ultrasonic time difference overlapping treatment synergistic reaction / extraction of the present application increases the extraction rate by about 14% compared with the single action of ultrasound.

[0042] ㈢This difference in the above comparison is attributed to the huge instantaneous energy generated by the strong vibration and cavitation of the ultrasound of the present application and the impact caused by the heating caused by the intermittent microwave, which causes the high-level fatty alcohol mixture in the cane wax to be quickly dissolved into the solvent without a penetration process; on the other hand, the 50-70% concentration ethanol solution of the present application can effectively absorb microwave energy and cause effective heating of the cane wax; therefore, the extract is allowed to be released into the solvent during the intermittent microwave-ultrasonic time difference overlapping treatment of the present application, and the release of the extract is accelerated, thereby improving the extraction rate of the high-level fatty alcohol mixture in the cane wax.

[0043] 6. This application adopts ultra-fine grinding: According to the literature "J. Ugelstad, Adv. Colloid Interface Sci": The excellent properties of ultrafine powders are mainly manifested in surface effects and volume effects: as the particle size decreases, the surface energy of ultrafine powders increases, and the catalytic, adsorption and other effects associated with the surface characteristics will be significantly enhanced; the single particle of ultrafine powder is small in size and has a small number of atoms. Its properties are different from the thermal and chemical reactions of bulk materials and large particle materials containing "infinite" atoms. Due to the significant reduction in particle size, narrow particle size distribution, and uniform particle size distribution, ultrafine powders exhibit surface effects, small size effects, quantum size effects, and macroscopic quantum tunneling effects that bulk materials do not have, thus having special physical and chemical properties that general particles do not have, such as high surface activity, large specific surface area, large adsorption, fast dissolution rate, fast chemical reaction rate, and unique electromagnetic, mechanical and chemical macroscopic properties. The ultrafine grinding process is not only a process of particle size reduction, but also accompanied by varying degrees of changes in the crystal structure and physical and chemical properties of the crushed material. Moreover, as the material becomes finer, when it reaches the "ultrafine powder" level, the above changes will be more obvious due to the long crushing time and high crushing intensity, which will affect the application of ultrafine powder. The change in the physical and chemical properties of the material itself is another characteristic of the ultrafine crushing process.

[0044] Since the force mode of the grinding method of the present application is high-acceleration impact + shearing, the material is compressed, torn and crushed under the action of the bidirectional composite force. The magnitude of the grinding force is not affected by the mass of the material, and the material with small mass is also subjected to a large force; under the action of the external exciting force, the grinding medium sometimes disperses and sometimes gathers in a throwing motion; the grinding medium itself rotates in the same direction, and the grinding medium group revolves; the inner and outer layers of grinding media constantly exchange positions, and the grinding media constantly collide, squeeze and shear the material, so that the material is squeezed and cut, and the particles are continuously ground from large to small; in the grinding process, the larger particles are subjected to force first and are broken first.

[0045] According to the Brownian motion theory and the osmotic diffusion motion principle proposed by Einstein based on the principle of molecular kinetic theory, the present application has found and verified through experimental research that when the material is subjected to the combined action of strong forward extrusion force and tangential shear force, as the processing time increases, the particle size becomes smaller, the specific surface area of ​​the material increases, and the mass transfer area per unit volume of the material increases. A smaller particle size can provide a higher specific surface area. The increase in specific surface area accelerates the diffusion and mass transfer of the higher fatty alcohol mixture in the sugarcane wax, thereby shortening the mass transfer path and shortening the operation time, and improving the mass transfer efficiency; The present application finally grinds the material to a median particle size of D50≦0.361μm, and the extraction rate increases almost linearly with the grinding particle size. The smaller the particle size of the raw material, the faster the extraction rate. The measurement results show that the dissolution amount is 40% higher than that of traditional air flow grinding, and the extraction amount of higher fatty alcohols is significantly increased, and its specific surface area is much larger than the former. There are also obvious differences in electron microscope observation.

[0046] The optimal ultrafine grinding process of this application is determined as: using a linear speed of 16 m / s, adjusting the pressure to 0.4-0.6 MPa, and grinding for 39-47 min to obtain an extract with a median particle size D50≦0.361 μm; using this optimal process for repeatability verification tests, the processing results have good stability and will not have a significant impact on the higher fatty alcohol mixture.

[0047] In contrast, in traditional SC-CO2 extraction, although the diffusion rate of SC-CO2 is much faster than that of general liquids, it also has the same characteristics as general solvent extraction. The particle size of the raw material has a greater impact on the extraction process. Since the extraction process is controlled by the diffusion rate, the extraction yield is low within a certain period of time. In order to achieve a certain recovery rate, the extraction time must be extended. It is usually economically not feasible to increase the recovery rate by extending the extraction time. When the raw material particles are very large, it is difficult for CO2 to fully contact with the higher fatty alcohols contained in the particles, and the extraction rate is very slow, and the extraction amount is also very small.

[0048] In summary, this application: ① Using 50-70% ethanol solution as the solvent for the hydrolysis of sugarcane wax, the boiling point of the solvent is increased, the solvent properties of the reaction system are adjusted, the flexibility and controllability of the reaction are increased, and the reaction is promoted, thereby increasing the reaction rate and conversion rate, making the reaction more efficient and playing a catalytic role; using ultrafine grinding to force the material and the solvent to move against each other through mechanical means, so that the effective ingredients of the material are always in a higher concentration gradient (countercurrent extraction mechanism), stirring during the preparation process helps to accelerate the dissolution of sugarcane wax, and the submicron particle size accelerates the diffusion and mass transfer of the high-grade fatty alcohol mixture in the sugarcane wax, thereby shortening the mass transfer path and improving the mass transfer efficiency, thereby shortening the operation time and greatly increasing the release rate and amount of the effective ingredients extracted; using weak acid composite ultra-high pressure double modification technology: weak acid reduces the hydrolysis reaction of sugarcane wax under mild conditions The activation energy of the reaction, the speed of reaching balanced hydrolysis, the catalytic effect of promoting the hydrolysis reaction, and the acceleration of molecular movement under high pressure system promote the movement of chemical equilibrium, and the solvent penetration and solute dissolution quickly reach equilibrium; the thermal effect and non-thermal effect (biological effect) of microwaves are used for rapid and selective heating; the oscillation, dispersion and cavitation of ultrasound are used to greatly accelerate the solvent infiltration process and the solute diffusion process; a variety of action modes are combined to make the effects on each point of the sample consistent, thereby reducing the binding force between the target and the sample matrix, accelerating the target from the solid phase into the solvent, thereby increasing the mass transfer rate of the effective ingredients. In a very short time, the effective ingredients can be completely extracted, realizing efficient and rapid sample processing, and having the advantages of short extraction time, high yield of advanced fatty alcohol mixture, low energy consumption, and no need for external heating.

[0049] ② Although the effects of weak acid and strong acid are different, this application is cross-integrated according to the characteristics of each component module and system configuration, and the mechanical and thermal effects such as high pressure and strong shock waves generated by each synergistic combination are combined to create an extreme physical and chemical condition microenvironment, increase the contact frequency and energy between the reactants, make the structure of sugarcane wax loose, reduce the crystallinity, and weaken the hydrogen bonding effect between sugarcane wax molecules; accelerate the chemical reaction of sugarcane wax, including side reactions such as oxidation and hydrolysis. The cavitation effect and the hydroxyl radicals produced help to accelerate chemical reactions, effectively increase the activation energy of reactant molecules, promote effective collisions between molecules, improve mass transfer and improve reaction efficiency, affect the reaction balance, and promote the acid decomposition reaction to be more thorough and improve the reaction efficiency. Thereby compensating for the low degree of ionization of weak acids to a certain extent. The ideal decomposition effect can be achieved at a lower acidity, thereby reducing the intensity of acidolysis. Therefore, the combined action of the synergistic combination of this application makes sugarcane wax more prone to side reactions than the traditional strong acid reaction treatment. This effect indicates that the synergistic combination of the present application to assist the acid decomposition reaction can reduce the demand for acidity, so that higher reaction efficiency and extraction rate can be achieved at lower acidity, allowing the reaction to proceed under milder conditions.

[0050] ③ This application is the first in China and abroad to combine dynamic ultrafine grinding-microwave-ultrasound-ultrahigh pressure functions, cooperate with 50-70% ethanol solution and organic acid to strengthen the hydrolysis reaction effect, extract a new generation of multifunctional combination and multiple modification technology of advanced fatty alcohol mixture, replace the traditional saponification and solvent extraction and refining process, avoid the use of toxic solvents, and control solvent residues, environmental pollution and energy consumption to the maximum extent, so that consumers do not need to worry about excessive use of chemical substances in the production process. At the same time, from the perspective of sustainable development, it solves the shortcomings of traditional processing technology such as high energy consumption and serious environmental pollution, which is of great significance for environmental protection. Literature review shows that there are no related reports at home and abroad using similar technologies of this application. This application effectively fills the gap in this aspect and is a pioneering research technology. It can also be widely used in the development of other products with larger scales and deeper depths, and further expand the development of this application in other fields and other industrial production. Provide a basis and technical support, with huge economic potential.

[0051] ④ This application uses several extraction methods together, which not only combines the advantages of various methods, improves the extraction efficiency, but also avoids the disadvantages of using a single method, and makes up for its shortcomings. It significantly improves the extraction and yield of the effective components of the high-grade fatty alcohol mixture in sugarcane wax, shortens the extraction time, realizes the continuous extraction operation, and improves the production efficiency; it is a relatively cutting-edge extraction method, which is more economical than the traditional extraction method. It has the advantages of energy saving, less pollution, high efficiency, low cost and high extraction rate. See Table 4 Table 4 Compared with the present application, the traditional process has a long reaction time, and after the reaction, an alkaline solution needs to be added to react to make the high-carbon fatty alcohol easy to separate. Therefore, the reaction steps and reaction time are increased, and the reaction time is 4-10 times that of the present application, which reduces the production efficiency; the addition of a large amount of alkali and toxic carcinogenic solvents such as benzene and dichloromethane increases the amount of sewage discharge, resulting in increased environmental pressure on enterprises. The present application can avoid these problems; it not only shortens the reaction time, reduces the auxiliary agent and dosage, but also simplifies the operation, the yield is also improved, and the reaction conditions are milder; considering the ecological benefits and social benefits, the present application has more application prospects.

[0052] Third, the present invention uses high vacuum secondary distillation and multiple recrystallization of composite solvents to synergistically refine octacosanol Octacosanol and its higher alcohol homologues are substances with high boiling points and high freezing points. They are difficult to separate by a single general method (such as recrystallization, including melt crystallization). Even with today's very advanced molecular distillation technology, 6 to 7 distillations are required to achieve a purity of 60%, and the production cost is very high. Higher fatty alcohols have many components, and the purity of fatty alcohols with a carbon number higher or lower than 28 accounts for a large proportion. Choosing the best distillation method and crystallization temperature is extremely critical to improving the purity of octacosanol. Therefore, the present application is the first to propose the use of high vacuum secondary distillation and multiple recrystallizations with composite solvents to synergistically refine octacosanol.

[0053] (1) The high vacuum secondary distillation used in the present application is to obtain a fatty alcohol mixture of C28 alcohol or above by high vacuum secondary distillation under the conditions of system insulation and high vacuum: High vacuum distillation refers to the distillation separation process carried out under a relatively high vacuum degree of 1.33 to 266.6 Pa. It has the characteristics of effectively lowering the boiling point and having a low risk of decomposition and polymerization. It can remove low molecular substances in the material and can selectively evaporate the target product and remove other unnecessary components.

[0054] The purpose of the high vacuum secondary distillation in this application is to separate low-carbon chain alcohols of C26 and below and collect components containing more C28 alcohols and above. It also serves the purpose of removing impurities and improving the quality of mixed alcohols.

[0055] This application experimental study found and verified: Table 5 contains the data on various higher fatty alcohols with the most biologically active components, ranging from 22-carbon fatty alkanols to 36-carbon fatty alkanols. Table 5;

[0056] project Tetracosanol Hexacosanol Octacosanol Triacontanol Dotriacontanol Molecular weight 354.66 382.71 410.77 438.82 466.87 Melting point(℃) 75.5 79.3 83.2 86.5 88.5 Boiling point(℃) 166(10Pa) 178(10Pa) 190(10Pa) 200(10Pa) 211(10Pa)

[0057] The composition of octacosanol after two-stage high vacuum distillation is shown in Table 6. Table 6

[0058]

[0059] From the various data in the higher fatty alcohol mixture in Table 5, it can be seen that fatty alcohols with less than 26 carbon atoms can be effectively separated at 180°C; from the data in Table 6, it can be seen that when the distillation temperature is 160-200°C, no distillate is collected, and the composition of the residue C28 is similar to that of the raw material; when the distillation temperature exceeds 210°C, light components begin to distill out, and when the distillation temperature is 220-240°C, the purity of C28 can reach up to 85.33 after secondary high vacuum distillation. At this time, the fatty alcohols with less than C26 in the raw material are separated with the light components, and the C28 component in the residual heavy component is enriched; when the temperature continues to rise to above 250°C, the material in the distillation tower begins to coke, the color becomes darker, and the components begin to decompose due to the high heating temperature.

[0060] Therefore, the optimal process conditions of the high vacuum secondary distillation method are determined as follows: at a vacuum degree of 11-12 Pa and a distillation temperature of 220-240°C, a fatty alcohol mixture above C28 alcohol is obtained by secondary distillation; this optimal process is used for repeatability verification tests, and the distillation results are stable.

[0061] ⑵ This application uses a composite solvent for multiple recrystallization to separate the mixture of higher fatty alcohols of C30 and above to obtain octacosanol with a purity of up to 99.5%: Crystallization technology is based on the difference in solubility of the purified substance and impurities in the solvent, so that the purified substance is crystallized from the supersaturated solution system, and all or most of the other unnecessary components are left in the mother liquor to achieve the purpose of purification; the extraction and purification of octacosanol is to utilize its solubility difference in organic solvents and its different dependence on temperature, and finally separate it from higher fatty alcohols; the correct selection of solvents and crystallization conditions (including liquid-to-solid ratio, crystallization temperature, and number of recrystallizations) is the key issue in separation and purification by recrystallization, which has a great influence on the results.

[0062] Although the structures of octacosanol and triacontanol are very similar, it is extremely important to determine the appropriate solvent for separation and purification. In addition to physical and chemical properties, other issues should also be considered comprehensively. First, the selected solvent has a large solubility for the substance to be removed, and the target substance has a certain solubility but it should not be too large. Its solubility will change significantly with changes in external conditions. Secondly, the selected solvent should be easy to recover, safe to operate, and less polluting. Try to choose low-toxic or non-toxic ones to reduce harm to operators. Therefore, simplifying the process, reducing the use of toxic reagents, reducing solvent consumption, and improving purification efficiency are the research focuses of solvent recrystallization purification.

[0063] The present application uses a composite solvent for multiple recrystallizations, the purpose of which is to separate and remove higher alkanols higher than carbon 28 in the crystals, so as to further improve the purity of octacosanol and obtain octacosanol with a purity of up to 99.5%; for this purpose, the selection of the recrystallization solvent type, solvent ratio, material-liquid ratio, crystallization temperature, and the research on the material-liquid ratio and crystallization times during the recrystallization process are aimed at achieving better separation and purification of octacosanol in higher fatty alcohols. The present application analyzes and verifies through orthogonal experiments: ①Through the single solvent screening experiment, n-butyl ketone, cyclohexane and n-hexane have better purification performance for octacosanol.

[0064] ② According to the principle of multi-solvent selection, the solvent ratio of cyclohexane-anhydrous ethanol was tested. The results showed that when the volume ratio of the two was 1:4, the purification effect of octacosanol was the best.

[0065] ③ When the material-liquid ratio is too large, it is difficult for the purified substance to form crystals and precipitate; when the material-liquid ratio is too small, due to the excessive proportion of the solvent, the system is not easy to form a saturated state at the same temperature, so that a large amount of the purified substance is dissolved in the solvent, and the separation and purification effect is not good, and no purification effect is achieved; through experiments, the results show that when the material-liquid ratio is 1:6, the crystals contain the most octacosanol.

[0066] ④ In order to further maximize the purity of octacosanol, three recrystallizations were performed using a binary solvent; a fatty alcohol mixture of C28 alcohol or above obtained by secondary distillation in the present application was selected as a raw material, and three crystallizations were performed at 35°C. The purity of octacosanol in the products of each stage was determined by gas chromatography. The results are shown in Table 7. The purity of octacosanol in the recrystallized sample is shown in Table 7. Table 7

[0067] Crystallization times / times Crystal weight / g Purity of octacosanol in crystals / % 0 100.00 85.33 1 70.01 99.31 2 60.10 99.48 3 52.81 99.5

[0068] It can be seen from Table 7 that after the purity of octacosanol of 85.33 was recrystallized three times, the purity of octacosanol in the crystals increased from 85.33 to 99.5%; therefore, by multiple crystallizations at 35°C, higher alkanols higher than octaconic acid in the crystals can be effectively separated and removed; it is unnecessary to crystallize more times, which will result in a waste of solvent and a low recovery rate.

[0069] ⑤ The optimal process conditions determined in this application are: cyclohexane-anhydrous ethanol (the volume ratio of cyclohexane: anhydrous ethanol is 1:4) composite solvent, crystallization temperature 35°C, solid-liquid ratio 1:6, stirring until uniform, standing, filtering, and obtaining a filtrate. After standing, the lower residual liquid is recovered, and the upper filtrate is recrystallized twice, and a crystal of octacosanol with a purity of 99.5% is obtained by filtering; this optimal process is used for a repeatability verification test, and a product of octacosanol with a higher purity is obtained, and the distillation result has good stability.

[0070] Fourth, ultrafine nano-grinding to a particle size median of D50 = 0.07 μm to obtain a nano-scale octacosanol dispersion From the perspective of pharmacological principles, the dissolution rate of a drug is proportional to the specific surface area of ​​the drug particles, while the specific surface area is inversely proportional to the particle size; the smaller the particle size, the better the effect; the solubility of octacosanol is closely related to its particle size. When the particles become smaller, the interaction between the particles and the solvent increases, the solubility increases, and reducing the particle size becomes the preferred method for increasing the solubility of octacosanol; based on the above principle, the present application adopts changing the physical state of octacosanol, which is a method worthy of active exploration to improve the effect and develop new products; among them, changing the unit size (volume) of octacosanol is one of the most effective methods.

[0071] The present application adopts a device for ultrafine nano-grinding plant fiber powder using pressure-variable cavitation high-speed three-vortex-microwave composite ultrafine nano-grinding to obtain a nano-scale octacosanol dispersion with a median particle size D50=0.07 μm. According to the Noyes-Whitney and Friendly Ostwald equations, its surface area is greatly increased, thereby significantly increasing its solubility and dissolution rate. In addition, the nano-scale octacosanol dispersion is easily absorbed, and also benefits from its bioadhesion effect: increasing gastrointestinal retention time and coexistence of multiple absorption mechanisms; therefore, the nano-scale octacosanol dispersion prepared by the nanotechnology of the present application can greatly improve the bioavailability of drugs and reduce local irritation; The present application has discovered and verified through experimental research that after adopting this technology, the surface area of ​​the octacosanol dispersion obtained in the present application is increased, and the dispersibility, adsorption capacity, surface activity, etc. have undergone comprehensive changes; these characteristics can significantly improve the solubility, absorption rate and bioavailability of the nano-scale octacosanol dispersion obtained in the present application, and it has good dispersibility and adhesion, which is conducive to the easy absorption of the effective ingredients.

[0072] ① The solubility is greatly increased. The release rate and amount of the effective ingredients of the nano-scale octacosanol dispersion obtained in the present application are greatly increased. The amount of the effective ingredients of octacosanol absorbed by the human body per unit time is much higher than that of the octacosanol powder or crystals without deep processing and grinding made by the traditional processing technology. Although the properties and purity of the main chemical components have not changed significantly, 30-50% of octacosanol can be saved, that is, the same effect can be achieved, and even the efficacy can be improved; thus, the dosage of octacosanol is greatly reduced, the waste of raw material resources is saved, the cost is saved, and the rational utilization of octacosanol resources is promoted.

[0073] ② The specific surface area is increased, the porosity is increased, the particles are more uniform and fine, and the particle size distribution is narrower; the nano-scale octacosanol dispersion obtained in the present application is easier to disperse and dissolve in the gastrointestinal fluid, and the contact area with the gastrointestinal mucosa is increased, the adhesion is enhanced, and the residence time of octacosanol in the digestive tract is prolonged, so that the absorption of the active ingredients is more sufficient and complete, which greatly improves the bioavailability and efficacy of octacosanol.

[0074] ③ The distribution of each active ingredient is uniform, and the solubility is significantly increased. Compared with the octacosanol powder or crystals produced by traditional processing technology without deep processing and grinding, the uniformity of the nano-scale octacosanol dispersion obtained in this application is improved, and it provides a basis for confirming that octacosanol forms a "solid emulsion" structure during ultrafine grinding.

[0075] ④ According to the principles of physics, the pharmacodynamic material basis contained in the nano-scale octacosanol dispersion with a median particle size D50 = 0.07 μm obtained in the present application will not undergo significant changes in molecular structure compared with the octacosanol powder or crystals that have not been processed and ground by traditional processing technology, that is, its biologically active ingredients or active chemical composition will not be destroyed, so the pharmacological and pharmacological mechanisms of the octacosanol dispersion obtained in the present application will not be changed, and will not pose a threat to drug safety.

[0076] ⑤ The nano-scale octacosanol dispersion obtained in this application has special physical and chemical properties that the octacosanol powder or crystals made by traditional processing technology without deep processing and grinding do not have, such as very significant dispersibility, adsorption, solubility, chemical reactivity, etc. This is a major advantage of this technology! Therefore, this technology will have a very wide range of applications in the fields of food, medicine, etc.

[0077] ⑥ The optimal process conditions determined in this application are: 20-30 parts of the above-obtained octacosanol crystals, 1-2 parts of dispersant, and 68-79 parts of deionized water are placed in a device for ultrafine nano-grinding of plant fiber powder by pressure-variable cavitation high-speed three-vortex-microwave composite ultrafine nano-grinding, and ultrafine nano-grinding to a median particle size D50 = 0.07 μm to obtain a nano-scale octacosanol dispersion with a median particle size D50 = 0.07 μm and a purity of 99.5%; this optimal process was used to carry out a repeatability verification test, and the results were stable.

[0078] The octacosanols claimed on the market are all octacosanol powders or crystals made by traditional processing technology. These octacosanol powders or crystals that have not been deeply processed have large particle sizes (D50=47μm). When entering the gastrointestinal tract or directly acting on the pathological site, octacosanol is a large molecular fat-soluble substance, which will produce a strong hydrophobic effect under the action of water molecules in body fluids; a considerable number of effective ingredients are excreted from the body before they can be absorbed in time, and often fail to reach an effective therapeutic concentration, and the effect is slow, which is what people often call "slow onset and low intensity of action", resulting in waste; in addition, some octacosanols often have insufficient particle sizes and may even produce local irritation, affecting clinical applications.

[0079] The present application proposes a method for preparing an ultra-high purity nano-scale octacosanol dispersion for the first time, which has the following advantages, innovations, and industrial applicability compared with other known methods.

[0080] ① The invention is the first in China to adopt the preparation method of the present application to extract octacosanol from sugarcane by-products, and has achieved satisfactory results. After refined extraction, a nano-scale octacosanol dispersion with a median particle size of D50≦0.07 μm and a purity of 99.5% is obtained (the bagasse powder currently sold on the market has a minimum particle size of D50=19 μm for German technology and D50=10 μm for Chinese technology), which not only maintains the therapeutic effect of octacosanol, but also can be added or subtracted dialectically, thereby improving the bioavailability of octacosanol; it has very important practical significance and practical value for improving the efficacy, quality, bioavailability, reducing the waste and loss of octacosanol resources, and improving social and economic benefits.

[0081] ② Compared with other known methods, the preparation method proposed in the present application for extracting high-purity nano-scale octacosanol dispersion has the advantages of simple process, short reaction time, high yield and purity; the application of the technology of the present application in the field of octacosanol not only has the characteristics of "resource-saving and environmentally friendly", but also effectively improves the processing performance of octacosanol, improves the uniformity of octacosanol, and improves the batch-to-batch stability of octacosanol, thereby ensuring the consistency of the efficacy of octacosanol batches; accelerates the dissolution of the active ingredients of octacosanol, improves the dissolution rate, and increases the absorption speed and degree, thereby improving the effect intensity and onset speed of octacosanol, breaking the long-standing mindset of "octacosanol has a slow onset and low intensity of action"; reduces the dosage of medication, saves octacosanol, is conducive to alleviating the shortage of octacosanol resources, and is conducive to the sustainable development of octacosanol and other advantages, truly achieving "limited resources, extreme utilization".

[0082] ③This application has great potential for developing new dosage forms of octacosanol: First, during the ultra-high pressure treatment of the present application, viruses at 200-300MPa are generally inactivated; molds and yeasts at 300-400MPa are inactivated; bacteria and pathogens at 300-600MPa are inactivated; spores can be inactivated after several treatments at 600Mpa; since most of the bacteria in the solution have been inactivated, the stability of the extract is significantly improved compared with conventional extraction methods, and the clarity is good and the shelf life is extended; generally, the boiled extract becomes turbid and precipitates after 4 days; while the high-pressure extract has no obvious changes after 40 days; this provides extremely favorable conditions for the preservation of the extract, subsequent separation and purification, and even the direct use of the extract; it also indicates that the ultra-high pressure treatment extraction technology of the present application may make a difference in improving the stability of Chinese medicine injections.

[0083] Second, the research and improvement of new dosage forms of octacosanol should be developed in the direction of high efficiency, rapid effect, long-term effect, low toxicity, easy to carry, convenient to take and easy to store; to achieve small dosage, high absorption rate and bioavailability, and long-term maintenance of the necessary concentration of octacosanol in the body, such as micropills, dripping pills, granules, injections, sustained-release preparations, controlled-release preparations, targeted preparations, and new dosage forms and technologies such as granulation and tableting of octacosanol whole powder without excipients; according to the provisions of Part II of the 2005 edition of the Chinese Pharmacopoeia: the dispersed phase of the intravenous emulsion injection 90% of the particle size of the spheroids should be below 1 μm, and there should be no spheroids larger than 5 μm; the technology of the nano-scale octacosanol dispersion with a purity of 99.5% and a median particle size D50≦0.07 μm in the present application, the nano system contains only nano-scale octacosanol and a small amount of stabilizer; as a "non-specific technology" for improving the bioavailability of poorly soluble drugs, it can be applied to most drugs with poor solubility problems; therefore, the requirements of the above conditions can be met, providing a material basis for the development of new dosage forms for octacosanol.

[0084] ④ Generally speaking, the harder and more brittle the material is, the easier it is to grind and pulverize it; however, natural plants have extremely obvious toughness, stickiness, and heat sensitivity, making them more difficult to make into powders. It is difficult to completely superfine the materials described in this application using ordinary superfine grinding methods. According to reports, the highest mesh number of tough, sticky, heat-sensitive and natural plant fiber materials currently sold on the market is D50=19μm≈800 mesh for German technology and D50=10μm≈1600 mesh for Chinese technology (laboratory scale). In the process of preparing micropowders, as described in the literature [Process and Equipment-Principles and Applications of Superfine Grinding Technology]: Superfine grinding of tough, sticky, heat-sensitive and fibrous materials has always been a difficulty in the process of preparing micropowders. As described in the literature [Powder Technology - New Field of High-Function Materials - Preparation and Application of Ultrafine Polymer Powders]: Due to its thermal sensitivity and viscoelasticity, polymer materials are generally difficult to be fined by crushing or grinding like inorganic materials, so ultrafine processing is difficult. It is very difficult to produce polymer microspheres with a particle size of 1-10 microns. Therefore, the ultra-fine grinding of tough, sticky, heat-sensitive and natural plant fiber materials has always been a difficult point in the industry's production research and is currently the focus of research by scientists from various countries.

[0085] The ultrafine grinding-microwave treatment and ultrafine nano-grinding described in this application are all made by using the Chinese patent authorization 202310979633.0 (authorization announcement date: April 9, 2024, authorization announcement number: CN116943840B) and PCT / CN2024 / 110213 (August 6, 2024) "A device for high-speed three-vortex-microwave composite ultrafine nano-grinding plant fiber powder by pressure-variable cavitation". Both are invented by the applicant company, similar to the above-mentioned submicron and nano-level ultra-low particle size median and technology of this application, which has not been reported yet, and is the first case before the applicant company.

[0086] ⑤ The technical research of the present application on the preparation of nano-scale octacosanol dispersion with a huge specific surface area and a median particle size of D50 = 0.07 μm and a purity of 99.5% has not been reported before, and it is the first case before the present application company; the technology of nano-scale ultra-high purity octacosanol dispersion in the present application is a pioneering research technology; it is not only refreshing, but also provides a solid theoretical reference and new research ideas for better development of a new generation of multifunctional natural organic plant material extraction research. It will become the production concept of multifunctional sub-micro / nano-scale materials in the future, and will receive more and more attention from the society; it has important practical significance for enriching the development of a new generation of functional multifunctional sub-micro / nano-scale natural organic plant material extraction and technology in my country; therefore, the present application will have extremely broad and practical value.

[0087] ⑥ The introduction of the technology of this application into the field of octacosanol will bring a profound revolution to the reform and modernization of octacosanol dosage forms, enriching the content of traditional extraction and bringing new vitality to the production and application of octacosanol, becoming a new growth point for the octacosanol industry.

[0088] This application can significantly improve the dissolution and yield of active ingredients, shorten the extraction time, realize continuous operation of extraction, improve production efficiency, and maintain excellent performance while being non-toxic, harmless, pollution-free, safe, and residue-free, reducing costs. In the future, the extraction and separation of active ingredients in natural products will become a very promising research direction. It has extremely important application value for solving technical problems that cannot be solved by a single method and improving separation efficiency. It lays a theoretical foundation for further obtaining optimal extraction conditions. It has good economic significance and can also promote the technical development of deep processing of agricultural products.

[0089] The octacosanol extracts of the present application can all be extracted from sugarcane by-products, and the raw materials are abundant, readily available and renewable; there is no carbon emission, and can be used in aerospace, special food, special functional beverages, health products, raw materials, medicines and other fields, with a wide product coverage.

[0090] The production process of the preparation method of the present application is highly continuous and stable, the production process is safe and has no environmental pollution, is suitable for industrial-scale production, and is energy-saving and environmentally friendly; the solid waste is mainly plant fiber, which is non-toxic; it is dried into powder and applied to high value-added products such as composite materials, bioplastics, plant fiber molding and other applications. DETAILED DESCRIPTION

[0091] The present application is further described in detail below through examples. These examples are only used to illustrate the present application and do not limit the scope of the present application.

[0092] Example 1 A method for preparing an ultra-high purity nano-scale octacosanol dispersion comprises the following process steps: Step 1: Extract milky white sugarcane wax using subcritical composite liquefied gas extraction, filtration and separation integrated device Put the dried sugarcane shreds crushed to 2000 mesh into the leaching reaction tank of the integrated device, start the pressure pump, press the composite liquefied gas mixed with hexane into the reaction tank, the mass volume ratio of the dried sugarcane shreds to the composite liquefied gas mixed with hexane is 1:5, adjust the pressure to 4.05MPa, and after treating at room temperature for 30 minutes, transfer the solvent containing the sugarcane wax into the separator for filtration, and separate the desolvated milky white sugarcane wax in the separator; the composite liquefied gas after separating the sugarcane wax is compressed and cooled by the recovery device and then recycled for recycling; Step 2: Ultrafine grinding, microwave, ultrasonic wave and ultra-high pressure vacuum integrated device to enhance the extraction of high-grade fatty alcohol mixture The sugarcane wax obtained in step 1 is mixed with 70% ethanol solution, 0.8% tartaric acid is added to the total weight of the feed liquid, and the feed liquid ratio is 1:20g / mL, and the ultrafine grinding-microwave-ultrasonic-ultra-high pressure vacuum integrated device is placed for treatment, the microwave function is started, the microwave power range is set to 370w, and the microwave frequency is set to 2500MHz for microwave treatment for 2 minutes, and then the microwave function is turned off; food-grade 99.9999% ultra-pure nitrogen is input, the ultra-high pressure function is started, and the extraction is carried out at a pressure of 600MPa, and the pressure increase rate is 50MPa / s. After the pressure increase is completed, the pressure is maintained for 3min, and then the pressure is released, and the pressure release rate is 100MPa / s, and then the ultra-high pressure function is turned off; at the 6th minute of the total processing time, the grinding function is started Energy and microwave function: the grinding function adopts a linear speed of 16m / s, adjusts the pressure to 0.6MPa, and the grinding treatment time is 46min. The microwave function performs intermittent treatment, that is, microwave treatment for 2min, then standing for 3min, microwave treatment for 1min, and then standing for 3min to complete a cycle. This cycle is repeated 4 times. At the 21st minute of the total treatment time, the ultrasonic function is started, the ultrasonic frequency is set to 30KHz, the ultrasonic power is set to 2.3Kw, the ultrasonic treatment time is 30min, and then the ultrasonic function is turned off; the total treatment time is 51min; the precipitate is discarded, the upper layer liquid is poured out, filtered, cooled and precipitated, and a submicron-level high-grade fatty alcohol mixture with a median particle size D50≦0.361μm is obtained; the solution is recovered at the same time; Step 3: High vacuum secondary distillation and multiple recrystallizations of composite solvents to synergistically refine octacosanol ①High vacuum secondary distillation: The higher fatty alcohol mixture obtained in step 2 is placed in a closed kettle and heated to 125° C. The heat preservation and vacuum systems are turned on, and a fatty alcohol mixture of C28 alcohol and above is obtained by secondary distillation at a vacuum degree of 12 Pa and a distillation temperature of 240° C. ②Multiple recrystallization process flow: Add the fatty alcohol mixture above C28 alcohol obtained in ① into cyclohexane-anhydrous ethanol composite solvent, with a crystallization temperature of 35°C and a solid-liquid ratio of 1:6, stir until uniform, let stand, and filter to obtain a filtrate. After standing, recover the lower residual liquid, repeat recrystallization of the upper filtrate twice, and obtain a crystal of octacosanol with a purity of 99.5% by filtering; The volume ratio of the cyclohexane-anhydrous ethanol composite solvent is 1:4; Step 4: Ultrafine Nano-grinding 30 parts of the octacosanol crystals obtained in step 3②, 1 part of polyethylene glycol monomethyl ether 2000, 1 part of polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, 10 parts of anhydrous ethanol, and 58 parts of deionized water are placed in a device for superfine nano-grinding of plant fiber powder by pressure-variable cavitation high-speed three-vortex-microwave composite ultrafine nano-grinding, and ultrafine nano-grinding to a median particle size D50 = 0.07 μm, followed by desolventizing, and spray freeze drying to obtain a nano-scale octacosanol dispersion with a median particle size D50 = 0.07 μm and a purity of 99.5%; The nanometer-scale octacosanol dispersion obtained in step 4 can be used in the field of raw materials medicine as needed.

[0093] Example 2 A method for preparing an ultra-high purity nano-scale octacosanol dispersion comprises the following process steps: Step 1: Extract milky white sugarcane wax using subcritical composite liquefied gas extraction, filtration and separation integrated device Put the crude sugarcane peel crushed to 2000 mesh into the leaching reaction tank of the integrated device, start the pressure pump, press the composite liquefied gas mixed with hexane into the reaction tank, the mass volume ratio of the crude sugarcane peel to the composite liquefied gas mixed with hexane is 1:4.5, adjust the pressure to 4.05MPa, and after the room temperature treatment time is 28min, transfer the solvent containing the sugarcane wax into the separator for filtration, separate the desolvated milky white sugarcane wax in the separator, and the composite liquefied gas after the sugarcane wax is separated is compressed and cooled by the recovery device for recycling; Step 2: Ultrafine grinding, microwave, ultrasonic wave and ultra-high pressure vacuum integrated device to enhance the extraction of high-grade fatty alcohol mixture The sugarcane wax obtained in step 1 is mixed with 60% ethanol solution, 0.48% acetic acid is added to the total weight of the feed liquid, and the feed liquid ratio is 1:16g / mL, and the ultrafine grinding-microwave-ultrasonic-ultra-high pressure vacuum integrated device is placed for treatment, the microwave function is started, the microwave power range is set to 370w, the microwave frequency is 2450MHz, and the microwave treatment is carried out for 2 minutes, and then the microwave function is turned off; input food grade 99.9999% ultra-pure nitrogen, start the ultra-high pressure function, extract at a pressure of 450MPa, the pressure increase rate is 50MPa / s, and the pressure is maintained for 5min after the pressure increase is completed, and then the pressure is released, and the pressure release rate is 100MPa / s, and then the ultra-high pressure function is turned off; at the 8th minute of the total treatment time, the grinding is started Function and microwave function: the grinding function adopts a linear speed of 16m / s, adjusts the pressure to 0.5MPa, and the grinding treatment time is 43min. The microwave function performs intermittent treatment, that is, microwave treatment for 2min, then standing for 3min, microwave treatment for 1min, and then standing for 3min to complete a cycle. This cycle is repeated 4 times. At the 22nd minute of the total treatment time, the ultrasonic function is started, the ultrasonic frequency is set to 20KHz, the ultrasonic power is 2Kw, the ultrasonic treatment time is 28min, and then the ultrasonic function is turned off; the total treatment time is 50min; the precipitate is discarded, the upper layer liquid is poured out, filtered, cooled and precipitated, and a submicron-level high-grade fatty alcohol mixture with a median particle size D50≦0.361μm is obtained; the solution is recovered at the same time; Step 3: High vacuum secondary distillation and multiple recrystallizations of composite solvents to synergistically refine octacosanol ①High vacuum secondary distillation: The higher fatty alcohol mixture obtained in step 2 is placed in a closed kettle and heated to 120° C. The heat preservation and vacuum systems are turned on, and a fatty alcohol mixture of C28 alcohol and above is obtained by secondary distillation at a vacuum degree of 11.5 Pa and a distillation temperature of 230° C.; ②Multiple recrystallization process flow: The fatty alcohol mixture above C28 alcohol obtained in ① is added into cyclohexane-anhydrous ethanol composite solvent, the crystallization temperature is 35°C, the solid-liquid ratio is 1:6.5, stirred until uniform, allowed to stand, and filtered to obtain a filtrate. After standing, the lower residual liquid is recovered, and the upper filtrate is recrystallized twice to obtain a crystal of octacosanol with a purity of 99.4% by filtering; the volume ratio of the cyclohexane-anhydrous ethanol composite solvent is 1:4.5; Step 4: Ultrafine Nano-grinding 26 parts of the octacosanol crystals obtained in step 3②, 0.75 parts of polyethylene glycol 2000, 0.75 parts of polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, 7 parts of anhydrous ethanol, and 65.5 parts of deionized water are placed in a device for compressive cavitation high-speed three-vortex-microwave composite ultrafine nano-grinding of plant fiber powder, ultrafine nano-grinding to a median particle size D50 = 0.075 μm, then desolventizing, spray freeze drying, and obtaining a nano-scale octacosanol dispersion with a median particle size D50 = 0.075 μm and a purity of 99.4%; The nanometer-scale octacosanol dispersion obtained in step 4 can be used in the fields of aerospace and special food as required.

[0094] Example 3 A method for preparing an ultra-high purity nano-scale octacosanol dispersion comprises the following process steps: Step 1: Extract milky white sugarcane wax using subcritical composite liquefied gas extraction, filtration and separation integrated device Put the bagasse crushed to 2000 mesh into the leaching reaction tank of the integrated device, start the pressure pump, press the composite liquefied gas propane and butane into the reaction tank, the mass volume ratio of bagasse to composite liquefied gas propane and butane is 1:3.5, adjust the pressure to 3.75MPa, after the processing time is 35min, transfer the solvent containing the sugarcane wax into the separator for filtration, separate the desolvated milky white sugarcane wax in the separator, and the composite liquefied gas after the sugarcane wax is separated is compressed and cooled by the recovery device and recycled; Step 2: Ultrafine grinding, microwave, ultrasonic wave and ultra-high pressure vacuum integrated device to enhance the extraction of high-grade fatty alcohol mixture The sugarcane wax obtained in step 1 is mixed with 50% ethanol solution, 0.15% citric acid is added to the total weight of the feed liquid, and the feed liquid ratio is 1:12g / mL, and the ultrafine grinding-microwave-ultrasonic-ultra-high pressure vacuum integrated device is placed for treatment, the microwave function is started, the microwave power range is set to 360w, and the microwave frequency is set to 2400MHz for microwave treatment for 2 minutes, and then the microwave function is turned off; food-grade 99.9999% ultra-pure nitrogen is input, the ultra-high pressure function is started, and the extraction is carried out at a pressure of 200MPa, and the pressure increase rate is 50MPa / s. After the pressure increase is completed, the pressure is maintained for 8min, and then the pressure is released, and the pressure release rate is 100MPa / s, and then the ultra-high pressure function is turned off; at the 11th minute of the total processing time, the grinding function is started Energy and microwave function: the grinding function adopts a linear speed of 16m / s, the pressure is adjusted to 0.4MPa, the grinding treatment time is 39min, and the microwave function performs intermittent treatment, that is, microwave treatment for 2min, then standing for 3min, microwave treatment for 1min, and then standing for 3min to complete a cycle, and this cycle is repeated 4 times. At the 21st minute of the total treatment time, the ultrasonic function is started, the ultrasonic frequency is set to 30KHz, the ultrasonic power is 1.2Kw, the ultrasonic treatment time is 25min, and then the ultrasonic function is turned off; the total treatment time is 49min; the precipitate is discarded, the upper layer liquid is poured out, filtered, cooled and precipitated, and a submicron-level high-grade fatty alcohol mixture with a median particle size D50≦0.361μm is obtained; and the solution is recovered at the same time; Step 3: High vacuum secondary distillation and multiple recrystallizations of composite solvents to synergistically refine octacosanol ①High vacuum secondary distillation: The higher fatty alcohol mixture obtained in step 2 is put into a closed kettle and heated to 115°C; the heat preservation and vacuum system are turned on, and a fatty alcohol mixture above C28 alcohol is obtained by secondary distillation at a vacuum degree of 11Pa and a distillation temperature of 220°C; ② Multiple recrystallization process flow: The fatty alcohol mixture above C28 alcohol obtained in ① is added into cyclohexane-anhydrous ethanol composite solvent, the crystallization temperature is 35°C, the solid-liquid ratio is 1:5.5, stirred until uniform, allowed to stand, and filtered to obtain a filtrate. After standing, the lower residual liquid is recovered, and the upper filtrate is recrystallized twice to obtain a crystal of octacosanol with a purity of 99.3% by filtering; the volume ratio of the cyclohexane-anhydrous ethanol composite solvent is 1:3.5; Step 4: Ultrafine Nano-grinding 20 parts of the octacosanol crystals obtained in step 3②, 1 part of polyethylene glycol monomethyl ether 2000, 4 parts of anhydrous ethanol, and 75 parts of deionized water are placed in a device for superfine nano-grinding of plant fiber powder by pressure-variable cavitation high-speed three-vortex-microwave composite, and the superfine nano-grinding is performed to a particle size median value D50 = 0.08 μm, followed by desolventization, spray freeze drying, and a nano-scale octacosanol dispersion with a particle size median value D50 = 0.08 μm and a purity of 99.3% is obtained; The nanometer-scale octacosanol dispersion obtained in step 4 can be used in the field of special functional beverages as required.

[0095] Due to the influence of the hypoxic environment in the plateau, the physical labor capacity of people from the plains will be significantly affected when they move to a plateau above 3,000 meters. Therefore, seeking measures to improve the human body's ability to work in the plateau is an important part of plateau medical research. At present, there are no very effective measures in this regard at home and abroad.

[0096] The present application has discovered and verified through experimental research that the nano-scale octacosanol dispersion obtained according to the above Example 1 has an effect on improving the labor capacity of plateau operations.

[0097] ⑴Evaluation method: Twenty healthy male youths who had lived at a plateau above 3700m for more than one year were selected and randomly divided into a nano-octacosanol dispersion group obtained in this example and a control (starch) group by a double-blind method, 10 in each group; 10 mg was taken every day for 30 consecutive days. After taking octacosanol for one month, the subjects sat quietly on a bicycle and started exercising after entering a quiet state. The exercise load started from 30w and increased by 30w every 3min, and stopped when the exercise load reached 90w for 3min.

[0098] ⑵The detection indicators are as follows: ① Changes in heart rate before and after taking the medicine Table 8

[0099]

[0100] The heart rate of the nano-octacosanol dispersion group obtained in Example 1 was significantly lower than that before taking the medicine; while there was basically no significant change in the control (starch) group, as shown in Table 8.

[0101] ② Changes in blood oxygen saturation before and after taking the medicine The blood oxygen saturation of the nano-octacosanol dispersion group obtained in Example 1 was significantly higher than that before taking the medicine; while the control (starch) group had almost no change, as shown in Table 9. Table 9

[0102]

[0103] ③ Changes in hemoglobin purity before and after taking the medicine Table 10

[0104]

[0105] The hemoglobin concentration of the nano-octacosanol dispersion group obtained in Example 1 was significantly reduced compared to before taking the medicine; while the hemoglobin concentration of the control (starch) group was almost unchanged, as shown in Table 10.

[0106] ⑶Results: After taking the medicine for one month, the resting and cycling heart rates of the subjects in the nano-octacosanol dispersion group obtained in Example 1 were significantly reduced, the hemoglobin concentration was reduced, and the blood oxygen saturation during cycling was significantly increased, while there was no such change in the control (starch) group.

[0107] ⑷ This application has found and verified through experimental research: ① After taking octacosanol, the heart rate of the nano-octacosanol dispersion group obtained in Example 1 was significantly reduced regardless of whether it was quiet or during weight-bearing exercise, while the control group had no such effect, indicating that the nano-octacosanol dispersion obtained in Example 1 of the present application can improve the efficiency of the body's work and the heart reserve capacity in a plateau environment, thereby improving the body's labor capacity in a plateau environment.

[0108] ② After taking the nano-octacosanol dispersion obtained in Example 1 of the present application, the blood oxygen saturation during 90W exercise can be improved, indicating that the nano-octacosanol dispersion obtained in Example 1 of the present application can increase the amount of oxygenated hemoglobin in arterial blood after exercise, increase the oxygen reserve in the blood, and thus improve the labor capacity of the human body at high altitudes.

[0109] ③ After people who live in plateaus take the nano-sized octacosanol dispersion obtained in Example 1 of the present application, the amount of hemoglobin can be reduced, which helps to reduce blood viscosity, reduce the burden on the heart, and improve the body's labor capacity.

[0110] ④ In the mouse experiment, it was also found that the nano-scale octacosanol dispersion obtained in Example 1 of the present application can reduce the hemoglobin amount and red blood cell count of hypoxic mice, and at the same time prolong the survival time of mice under closed hypoxic conditions after injection of isoproterenol; experiments have shown that octacosanol can reduce the oxygen consumption of the brain under hypoxic conditions and improve the anaerobic respiration metabolic capacity of myocardial cells under hypoxic conditions. Therefore, it can protect the heart and brain from serious damage caused by hypoxia in a short period of time; octacosanol can effectively increase the energy supply time of animals, especially in the anaerobic respiration process caused by insufficient oxygen supply in a short period of time, to provide a certain energy demand for the brain, so as to improve the ability to tolerate hypoxia.

[0111] ⑤ The nano-scale octacosanol dispersion obtained in Example 1 of the present application can enhance plateau labor capacity and reduce erythrocytosis caused by plateau hypoxia.

[0112] It is well known that under weightlessness, a series of physiological and biochemical changes occur in astronauts' bodies, such as increased blood viscosity, elevated blood lipids and loss of bone calcium.

[0113] The present application has discovered and verified through experimental research the influence of the nano-scale octacosanol dispersion obtained according to the above Example 2 on the biological effect of weightlessness in tail-suspended simulated weightlessness rats.

[0114] (1) Evaluation method: In this experiment, rats were randomly divided into 3 groups: a control group (hereinafter referred to as Group A), a tail suspension group (hereinafter referred to as Group B) and a tail suspension group plus the nano-octacosanol dispersion obtained in Example 2 (hereinafter referred to as Group C); each group had 8 rats, and the supply amount was 25 mg / kg body weight per rat per day, and the experimental period was 14 days; at the end of the experiment, blood and tissue samples were collected after the rats were fasted for 12 hours; heart blood was collected by cardiac puncture, trunk blood was collected after decapitation, the thymus and spleen were removed and weighed, and the left hind limb femur was separated and removed; the weight of the immune organs, the fluidity of the red blood cell membrane and the biomechanical properties of the femur were observed.

[0115] (2) The test indicators are as follows: ①Thymus and spleen weight The weight of the thymus and spleen of rats in group B was significantly lower than that of rats in group A, but the weight of the thymus of rats in group C was 0.37 g, which was significantly higher than 0.24 g of rats in group B. The results showed that the nano-octacosanol dispersion group obtained in Example 2 of this application can inhibit thymus atrophy caused by suspension simulated weightlessness. The thymus and spleen are important immune organs of the body, which suggests that the nano-octacosanol dispersion group obtained in Example 2 of the present application has a certain protective effect on the decline of immune function caused by suspension simulated weightlessness.

[0116] ② Red blood cell membrane fluidity The fluidity of erythrocyte membrane is usually expressed by the fluorescence polarization degree P value of erythrocyte membrane. The larger the P value, the smaller the hydrocarbon chain activity, the smaller the membrane fluidity, and the greater the blood microviscosity; conversely, the greater the membrane fluidity, the lower the blood microviscosity. After 14 days of suspension, the average P values ​​of erythrocyte membrane of rats in groups B and C were 0.30 and 0.27, respectively, which were significantly higher than 0.25 of rats in group A. The blood viscosity of rats in group C tended to decrease compared with that of rats in group B.

[0117] ③ Femoral biomechanical parameters Table 11 Mechanical parameters of femoral three-point bending test (average values) Mechanical parameters Group A Group B Group C Maximum load 4145 5030 8034 Elastic limit load 2780 3700 5529 Maximum deflection 0.80 0.85 1.19 Elastic limit deflection 0.45 0.48 0.50 Table 11 shows the biomechanical values ​​of the femur obtained by the three-point bending test. After 14 days of tail suspension, the maximum load and elastic limit load of the femur of the rats in group C were significantly higher than those in groups A and B. The results show that the nano-octacosanol dispersion group obtained in Example 2 of the present application can significantly counteract the decline in biomechanical properties of the femur of suspended rats. Table 12 Biomechanical properties of rat femur (average value)

[0118] Mechanical properties Group A Group B Group C Maximum stress 960 1150 1250 Elastic stress 645 840 939 Tensile stress 926 1020 1349 Elastic modulus 451 500 617 Deformation potential 3052 4393 6080 Table 12 shows the biomechanical properties of the femur calculated from the biomechanical and geometric parameters of the femur. The results show that the nano-scale octacosanol dispersion group obtained by Example 2 of the present application can significantly improve the biomechanical properties of the femur of suspended rats.

[0119] In summary, the experiments show that the nano-octacosanol dispersion group obtained in Example 2 of the present application has the following functions on tail-suspended rats: ① significantly increase the weight of the thymus; ② improve the fluidity of the red blood cell membrane of simulated weightlessness rats; ③ significantly improve the biomechanical properties of the femur; the nano-octacosanol dispersion obtained in Example 2 of the present application can effectively counteract certain adverse effects of tail-suspended rats; during the entire experimental process, no side effects of octacosanol were observed; this indicates a series of physiological and biochemical changes that occur in the bodies of astronauts under weightlessness, and they can be taken by taking health drinks or foods added with the nano-octacosanol dispersion obtained in Example 2 of the present application, and their ability to improve exercise endurance, lower blood lipids, improve blood viscosity, improve hypoxia endurance and prevent osteoporosis may become a health drink or food ingredient for astronauts.

[0120] The present application has discovered and verified through experimental research the effect of the nano-scale octacosanol dispersion obtained according to the above Example 3 on improving exercise, body endurance and adaptability to exercise load.

[0121] (1) Evaluation method: In this experiment, rats were randomly divided into 3 groups: a control group (hereinafter referred to as Group A), a group of octacosanol with a purity of 80% in the conventional market (hereinafter referred to as Group B), and a group of nano-scale octacosanol dispersion obtained in Example 3 (hereinafter referred to as Group C); each group had 8 rats. ① Pole climbing test and weighted swimming test: 25 days after oral administration, 30 minutes after the last administration, the trained and screened mice were placed on the upper end of a vertically suspended smooth glass rod with a length of 110 mm and a diameter of 7 mm, so that their muscles were in a static tension state. The time from the beginning of the climbing of the pole to the muscle fatigue and the inability to hold the glass rod and fall to the ground was recorded. This was repeated 3 times. The test was terminated after the third fall, and the accumulated time of 3 times was taken as the pole climbing time (s). Each group continued to receive oral administration for 5 days. 30 minutes after the last administration, a lead wire was used to load 5% of their body weight at the base of their tails. The mice were placed in a swimming box with a diameter of 150 mm, a water depth of 30 mm, and a water temperature of (25±0.5)℃. The time from the beginning of swimming to the death of the mice was recorded as the swimming time (min); ② Determination of related indicators: 25 days after intragastric administration, 30 minutes after administration, a lead wire weight of 2% of the mouse's body weight was placed at the base of its tail. The mouse was allowed to swim in 30°C water for 60 minutes, then taken out and the weight was removed. After 15 minutes of rest, blood was collected from the supraorbital venous plexus, and the blood lactate (BLA) content was determined using the p-hydroxybiphenyl colorimetric method. Mice in each group were given the drug by gavage for 5 days. 30 minutes after the last administration, they were put into 30℃ water to swim for 90 minutes and then taken out. Blood was collected from the supraorbital venous plexus and serum urea nitrogen (BUN) was determined by kit method. Then the animals were immediately killed, the liver was taken out, rinsed with 0.9% NaCl solution, dried with filter paper, and the liver glycogen content (LG) was determined by anthrone method.

[0122] (2) The test index results are as follows: ①Effect on exercise endurance (Table 13) Table 13 Effect of octacosanol extract on endurance of mice Group Dosage (mg / Kg / d) Climbing time(s) Swimming time (min) Group A 0 43.8±25.9 11.0±4.2 Group B 20 46.3±24.1 14.4±5.9 Group C 20 81.9±29.4 16.0±9.0 The climbing pole time and swimming time of mice in each test group were longer than those in the blank control group, indicating that the octacosanol extract can improve the exercise endurance of mice. ②Effects on biochemical indicators after swimming (Table 14) Table 14 Effects of octacosanol extract on some biochemical indices of swimming mice After 25 days of gavage, mice swam with weights, only group C had significantly lower blood lactate than the control group, indicating that the effect may be related to the purity and dosage of the test substance. The liver glycogen content of group C was significantly increased compared with groups A and B, and there was no significant change in group B, indicating that the use of the nano-scale octacosanol dispersion group obtained in Example 3 can improve the glycogen accumulation capacity of animals. The serum urea nitrogen levels of mice injected with the drug for 30 days were measured after swimming. The levels were significantly lower in each administration group than in group A, and the difference between group C and group A was extremely significant, indicating that the nano-octacosanol dispersion obtained in Example 3 can reduce serum urea nitrogen, improve body endurance and adaptability to exercise load.

[0123] All of the above descriptions of specific exemplary embodiments of the present application are for the purpose of explanation and illustration; these descriptions are not intended to limit the present application to the precise form disclosed, and it is obvious that many changes and variations can be made based on the above teachings; the purpose of selecting and describing the exemplary embodiments is to explain the specific principles of the present application and its practical application, so that technical personnel in the field can implement and utilize various different exemplary embodiments of the present application and various different selections and changes; or to make equivalent substitutions for some of the technical features therein; and these modifications or substitutions, and other conceivable alternative means, are all within the scope of protection of the present application, and do not deviate the essence of the corresponding technical solution from the spirit and scope of the technical solution of each embodiment of the present application.

Claims

1. A method for preparing an ultra-high purity nano-scale octacosanol dispersion, characterized in that: The process steps include: Step 1: Extract milky white sugarcane wax using subcritical composite liquefied gas extraction, filtration and separation integrated device Put the sugarcane byproduct crushed to 2000 mesh into the leaching reaction tank of the integrated device, start the pressure pump, press the composite liquefied gas into the reaction tank, the mass volume ratio of the sugarcane byproduct to the composite liquefied gas is 1:3.5-5, adjust the pressure to 3.75-4.05MPa, and after the room temperature treatment time is 28-35min, transfer the solvent containing the sugarcane wax to the separator for filtration, separate the desolvated milky white sugarcane wax in the separator, and the composite liquefied gas after the sugarcane wax is separated is compressed and cooled by the recovery device and recycled; The sugarcane by-product is any one of bagasse, sugarcane filter mud, coarse sugarcane husk and dry sugarcane silk; The composite liquefied gas is any one of propane, butane, and mixed hexane; Step 2: Ultrafine grinding, microwave, ultrasonic wave and ultra-high pressure vacuum integrated device to enhance the extraction of high-grade fatty alcohol mixture The sugarcane wax obtained in step 1 is mixed with an ethanol solution with a concentration of 50-70%, and 0.15-0.8% organic acid is added to the total weight of the feed liquid at a feed-liquid ratio of 1:12-20 g / mL, and placed in an ultrafine grinding-microwave-ultrasonic-ultrahigh pressure vacuum integrated device for treatment, the microwave function is started, the microwave power range is set to 350w-400w, and the microwave frequency is 2400-2500MHz for microwave treatment for 2 minutes, and then the microwave function is turned off; food-grade 99.9999% ultrapure nitrogen is input, the ultrahigh pressure function is started, and the extraction is carried out at a pressure of 200-600MPa, the pressure increase rate is 50MPa / s, and the pressure is maintained for 2-8min after the pressure increase is completed, and then the pressure is relieved, and the pressure relief rate is 100MPa / s, and then the ultrahigh pressure function is turned off; at the 5th to 11th minute of the total treatment time, the grinding is started; Grinding function and microwave function: the grinding function adopts a linear speed of 16m / s, adjusts the pressure to 0.4-0.6MPa, and the grinding treatment time is 39-47min. The microwave function performs intermittent treatment, that is, microwave treatment for 2min, then standing for 3min, microwave treatment for 1min, and then standing for 3min to complete a cycle, and this cycle is repeated 4 times; at the 21st to 24th minute of the total treatment time, start the ultrasonic function, set the ultrasonic frequency to 20KHz-40KHz, the ultrasonic power to 1.2Kw-3Kw, the ultrasonic treatment time to 25-30min, and then turn off the ultrasonic function; the total treatment time is 49-51min; discard the precipitate, pour out the upper liquid for suction filtration, cool and precipitate, and obtain a submicron-level high-grade fatty alcohol mixture with a median particle size D50≦0.361μm; and recover the solution at the same time; The organic acid is any one of succinic acid, tartaric acid, citric acid, malic acid, acetic acid and lactic acid, and the pH value is 3 to 3.86; Step 3: High vacuum secondary distillation and multiple recrystallizations of composite solvents to synergistically refine octacosanol ①High vacuum secondary distillation: The higher fatty alcohol mixture obtained in step 2 is placed in a closed kettle and heated to 115-125° C.; the heat preservation and vacuum systems are turned on, and a fatty alcohol mixture of C28 alcohol or higher is obtained by secondary distillation at a vacuum degree of 11-12 Pa and a distillation temperature of 220-240° C.; ②Multiple recrystallization process flow: Add the fatty alcohol mixture above C28 alcohol obtained in ① into cyclohexane-anhydrous ethanol composite solvent, with a crystallization temperature of 35°C and a solid-liquid ratio of 1:5.5-6.5, stir until uniform, let stand, and filter to obtain a filtrate. After standing, recover the lower residual liquid, repeat recrystallization of the upper filtrate twice, and obtain a crystal of octacosanol with a purity of 99.5% by filtering; The volume ratio of the cyclohexane-anhydrous ethanol composite solvent is 1:3.5-4.5; Step 4: Ultrafine Nano-grinding 20-30 parts of the octacosanol crystals obtained in step 3②, 1-2 parts of a dispersant, 4-10 parts of anhydrous ethanol, and 58-75 parts of deionized water are placed in a device for compressive cavitation high-speed three-vortex-microwave composite ultrafine nano-grinding of plant fiber powder, ultrafine nano-grinding to a median particle size D50≦0.07μm, then desolventizing, spray freeze drying, and obtaining a nano-scale octacosanol dispersion with a median particle size D50≦0.07μm and a purity of 99.5%.

2. The method for preparing an ultra-high purity nano-scale octacosanol dispersion according to claim 1, characterized in that: The subcritical composite liquefied gas extraction, filtration and separation integrated device described in step 1 is composed of an extraction reaction tank, a separator and a recovery device.

3. The method for preparing an ultra-high purity nano-scale octacosanol dispersion according to claim 1, characterized in that: The dispersant described in step 4 is any one of polyethylene glycol monomethyl ether 2000, polyethylene glycol 2000, and polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or a composite of two of the two.

4. The method for preparing an ultra-high purity nano-scale octacosanol dispersion according to claim 1, characterized in that: The nanometer-scale octacosanol dispersion described in step 4 is used in the fields of aerospace, special food, special functional beverage, health care product, raw material medicine and medicine as required.

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