阅读说明：本技术 一种制备微粒状医药级羊毛醇的方法 (Method for preparing micro-particle medical grade lanonol ) 是由 单伟达 王丽虹 王子强 刘建刚 钱国平 邵振宝 郭建阳 于 2021-08-19 设计创作，主要内容包括：本发明提供了一种微粒状医药级羊毛醇的生产方法,所述微粒状医药级羊毛醇的粒径为0.2-2mm,所述方法为：将原料加入有机溶剂中完全溶解得到原料液；所述原料包括羊毛醇原料、羊毛甾醇、抗氧化剂；原料液与复合吸附剂搅拌混合吸附,吸附液快速真空蒸馏脱除溶剂,得膏状的医药级羊毛醇粗品；粗品进行三级分子蒸馏,收集二级轻相和三级轻相,混合后作为医药级羊毛醇的造粒前体；造粒前体加热熔融后,经冷却喷雾塔造粒固化成型,喷雾塔底部收集产品,得到微粒状的医药级羊毛醇产品。本发明首次制备了微粒状的医药级羊毛醇,产品质量稳定性高,极大便利了产品后续的运输及使用,满足大规模的医药级羊毛醇产品的生产需求以及市场的质量提升与实际使用需求。(The invention provides a production method of particulate pharmaceutical grade lanolin alcohol, wherein the particle size of the particulate pharmaceutical grade lanolin alcohol is 0.2-2mm, and the method comprises the following steps: adding the raw materials into an organic solvent to be completely dissolved to obtain a raw material solution; the raw materials comprise a lanosterol raw material, lanosterol and an antioxidant; stirring, mixing and adsorbing the raw material liquid and the composite adsorbent, and quickly distilling the adsorption liquid in vacuum to remove the solvent to obtain a pasty pharmaceutical grade lanonol crude product; carrying out three-stage molecular distillation on the crude product, collecting a second-stage light phase and a third-stage light phase, and mixing to obtain a granulation precursor of the pharmaceutical grade lanolin alcohol; and heating and melting the granulation precursor, granulating, solidifying and forming by a cooling spray tower, and collecting a product at the bottom of the spray tower to obtain a medical grade lanonol product in a micro-particle form. The invention prepares the medical grade lanonol in micro-particles for the first time, has high product quality stability, greatly facilitates the subsequent transportation and use of the product, and meets the production requirement of large-scale medical grade lanonol products and the quality improvement and actual use requirements of the market.)

1. A process for the production of particulate pharmaceutical grade lanolin alcohol, wherein the particulate pharmaceutical grade lanolin alcohol has a particle size of from 0.2 to 2mm, the process comprising the steps of:

(1) compounding raw materials: adding the raw materials into an organic solvent, heating, fully stirring and mixing to completely dissolve the materials to obtain a raw material solution; the raw materials comprise a lanosterol raw material, lanosterol and an antioxidant;

(2) adsorption by using a composite adsorbent: stirring, mixing and adsorbing the raw material liquid in the step (1) and a composite adsorbent, and then carrying out solid-liquid separation; sending the collected adsorption solution into a high vacuum system, and quickly vacuum distilling to remove the solvent to obtain a pasty pharmaceutical grade lanonol crude product;

(3) molecular distillation: performing three-stage molecular distillation on the crude pharmaceutical grade lanolin product obtained in the step (2), collecting a first-stage light phase as a byproduct, feeding a first-stage heavy phase into a second-stage molecular distillation system, feeding a second-stage heavy phase into a third-stage molecular distillation system, collecting a second-stage light phase and a third-stage light phase, and mixing the two phases to obtain a granulation precursor of the pharmaceutical grade lanolin alcohol;

(4) and (3) granulation and forming: and (4) heating and melting the granulation precursor of the pharmaceutical grade lanolin alcohol in the step (3), granulating, solidifying and forming by a cooling spray tower, and collecting a product at the bottom of the spray tower to obtain a particulate pharmaceutical grade lanolin alcohol product.

2. The method according to claim 1, wherein the raw material of lanosterol, lanosterol and antioxidant in the step (1) is mixed in a mass ratio of 1: 0.01-0.20: 0.0001 to 0.0010.

3. The method according to claim 1, wherein the raw materials of step (1) are a lanosterol raw material, lanosterol, an antioxidant and NF-grade cholesterol; the mass ratio of the lanosterol raw material to the lanosterol to the antioxidant to the NF-grade cholesterol is 1: 0.01-0.20: 0.0001 to 0.0010: 0 to 0.40, wherein 0 represents infinitely close to 0 but not 0.

4. The method of claim 1, wherein the organic solvent is one of hexane, heptane, isooctane, petroleum ether, or a mixture thereof.

5. The method according to claim 1, wherein the antioxidant is one or a mixture of natural tocopherol, dibutylhydroxytoluene, propyl gallate, butylhydroxyanisole, and tert-butylhydroquinone.

6. The method according to claim 1, wherein in the step (2), the composite adsorbent is a mixture of two or more of α -alumina, silica gel, and molecular sieve.

7. The method according to claim 1, wherein in the step (2), the vacuum distillation is performed at a temperature of 50-60 ℃ and an absolute pressure of 500-1000 pa for 0.5-2 hours.

8. The method as claimed in claim 1, wherein in the step (3), the temperature of the primary molecular distillation is 120-160 ℃, the vacuum pressure is 10-500Pa, the temperature of the secondary molecular distillation is 160-200 ℃, the vacuum pressure is 1-200Pa, the temperature of the tertiary molecular distillation is 200-250 ℃, and the vacuum pressure is 0.1-100 Pa.

9. The method according to claim 1, wherein in step (4), the heating and melting temperature of the granulated precursor of pharmaceutical grade lanolin alcohol is controlled to 80-100 ℃, the cooling air temperature of the cooling spray tower is controlled to 0-10 ℃, and the humidity inside the spray tower is controlled to 0-20%.

10. The method according to claim 1, wherein in step (4), the cooling spray tower; the spraying pressure is controlled to be 0.2-0.5 Mpa; the aperture of the nozzle is 0.2-0.5 mm, the rotating speed of the spray head is controlled to be 4000-8000 r/min, and the feeding rate is controlled to be 35-50 mL/min; the inner wall of the cooling spray tower cylinder body is coated with an anti-sticking coating which is made of polytetrafluoroethylene or fluorinated ethylene propylene, the inner wall of the cooling spray tower is cooled through a liquid refrigerant of a jacket, and the temperature range of the liquid refrigerant is-20-10 ℃.

Technical Field

The invention belongs to the field of pharmaceutical chemicals, mainly relates to a preparation method of pharmaceutical grade lanolin alcohol, and particularly relates to a preparation method of micro-granular pharmaceutical grade lanolin alcohol.

Background

The lanonol is obtained by saponifying natural lanolin and separating wool acid, and comprises higher fatty alcohol, sterol, triterpene alcohol, etc. At normal temperature, the lanonol is light yellow brown wax, the melting point is 40-85 ℃, the average carbon chain length is 25, and the lanonol is widely applied to various fields such as cosmetics, medical products, lubricants and the like at present.

The pharmaceutical grade lanonol product is an important class of lanonol products, is a yellowish or light brown hard paste lanonol product at normal temperature, and has excellent emulsifying and lubricating properties. Compared with the conventional daily chemical grade and cosmetic grade lanolin alcohol products, the pharmaceutical grade lanolin alcohol product has more outstanding characteristics of low chroma, low odor, high moisture retention and the like, has more strict requirements on indexes such as peroxide value, ash content and the like of the product, is mainly used in the fields of high-end face creams, sun-screening agents, infant skin care products, various medical ointment preparations and the like at present, and has relatively higher added value.

The medical grade lanolin alcohol product has the problems of easy oxidative deterioration, deep color, cholesterol agglomeration, crystallization separation, poor product uniformity and the like in the subsequent transportation and use process due to the high proportion of cholesterol (the cholesterol content index is more than or equal to 30%) and the complex and various easily-oxidized and discolored chemical group structures, and meanwhile, the product in the market is usually packaged and sold in the form of filling iron containers or plastic containers, and customers have great inconvenience in subsequent subpackaging, transportation, sale and use and measurement, so that the product quality requirements and use requirements of the customers in the market on the medical grade lanolin alcohol cannot be completely met.

Patent CN109568167s describes a method for preparing lanolin alcohol, but the cholesterol content of lanolin alcohol prepared by this technique is low (usually, the cholesterol content is less than or equal to 10%), the melting point is low, and the cloth pelletizer equipment used in the method occupies a large area, the cooling efficiency is low, the product particles are easy to stick to the conveyor belt and other particles, the product manufacturing is unstable and the efficiency is low. In addition, the method has low precision of regulating and controlling the particle size of the product, and is not suitable for manufacturing particle products.

Disclosure of Invention

The invention aims to provide a method for efficiently preparing micro-particle medical grade lanolin alcohol, which improves the quality stability of products and simultaneously quickly solidifies, granulates and shapes, thereby meeting the actual production and market requirements of the medical grade lanolin alcohol market.

In order to achieve the purpose, the invention adopts the technical scheme that: a process for the production of particulate pharmaceutical grade lanolin alcohol having a particle size of 0.2 to 2mm, said process comprising the steps of:

(1) compounding raw materials: adding the raw materials into an organic solvent, heating, fully stirring and mixing to completely dissolve the materials to obtain a raw material solution; the raw materials comprise a lanosterol raw material, lanosterol and an antioxidant;

(2) adsorption by using a composite adsorbent: stirring, mixing and adsorbing the raw material liquid in the step (1) and a composite adsorbent, and then carrying out solid-liquid separation; sending the collected adsorption solution into a high vacuum system, and quickly vacuum distilling to remove the solvent to obtain a pasty pharmaceutical grade lanonol crude product;

(3) molecular distillation: performing three-stage molecular distillation on the crude pharmaceutical grade lanolin product obtained in the step (2), collecting a first-stage light phase as a byproduct, feeding a first-stage heavy phase into a second-stage molecular distillation system, feeding a second-stage heavy phase into a third-stage molecular distillation system, collecting a second-stage light phase and a third-stage light phase, and mixing the two phases to obtain a granulation precursor of the pharmaceutical grade lanolin alcohol;

(4) and (3) granulation and forming: and (4) heating and melting the granulation precursor of the pharmaceutical grade lanolin alcohol in the step (3), granulating, solidifying and forming by a cooling spray tower, and collecting a product at the bottom of the spray tower to obtain a particulate pharmaceutical grade lanolin alcohol product.

In the step (1), the ratio of the raw material of the lanonol, the lanosterol and the antioxidant is 1: 0.01-0.20: 0.0001 to 0.0010, preferably 1: 0.01-0.1: 0.0003 to 0.0006, more preferably 1: 0.04-0.05: 0.0005.

Further, NF-grade cholesterol can be added into the raw materials in the step (1) in a certain proportion, so that the yield of the product is improved, namely the raw materials are a lanosterol raw material, lanosterol, an antioxidant and NF-grade cholesterol;

when the raw material contains NF-grade cholesterol, the mass ratio of the raw material of the lanonol, the lanosterol, the antioxidant and the NF-grade cholesterol in the step (1) is 1: 0.01-0.20: 0.0001 to 0.0010: 0-0.40, wherein 0 represents infinitely close to 0 but not 0, and the preferable ingredient mass ratio is 1: 0.01-0.1: 0.0003 to 0.0006: 0.20 to 0.40.

The purity of cholesterol in the NF-grade cholesterol is not less than 95%.

The raw material of the lanonol is one or a mixture of daily chemical grade lanonol and cosmetic grade lanonol, and the standard is as the following table 1:

TABLE 1

The main indexes of the pharmaceutical grade lanonol are as follows: the cholesterol content is more than or equal to 30 percent, the melting point is more than or equal to 56 ℃, the Gardner chroma is less than or equal to 10, the acid value is less than or equal to 2mg KOH/g, the peroxide value is less than or equal to 15meq/kg, and the hydroxyl value range is 120-180 mgKOH/g.

The applicant researches and discovers that the melting point and the subsequent curing, granulating and forming speed of a pharmaceutical grade lanosterol product can be effectively improved by adding lanosterol in a certain proportion during raw material compounding.

Further, the organic solvent compounded by the raw materials is one or a mixture of hexane, heptane, isooctane and petroleum ether, and the more preferable organic solvent is petroleum ether with a boiling range of 60-90 ℃.

The volume dosage of the organic solvent is 15-25L/kg, preferably 20L/kg, calculated by the mass of the lanonol raw material.

In the step (1), the mixture is generally heated to 50-55 ℃ and stirred to be mixed, so that the materials are completely dissolved.

The antioxidant is one or mixture of natural tocopherol (VE), dibutyl hydroxy toluene (BHT), Propyl Gallate (PG), Butyl Hydroxy Anisol (BHA), and tert-butyl hydroquinone (TBHQ), preferably alpha-tocopherol or dibutyl hydroxy toluene. The use of the antioxidant enables the pharmaceutical grade lanonol to play a certain protection role when the molecular distillation temperature is higher, reduces the peroxide value of the product, and can delay the oxidation of the product in production, transportation and storage and improve the subsequent stability of the product.

In the step (2), a composite adsorbent adsorption process is adopted, and the liquid phase adsorption of the composite adsorbent can adsorb and remove a large amount of lanonol with active groups and other polar impurities, remove the active alcohol molecules which are easy to oxidize and discolor, and improve the product indexes of the prepared pharmaceutical grade lanonol product, such as chromaticity, peroxide value, hydroxyl value and the like.

Further, the composite adsorbent is a mixture of two or more of alpha-alumina, silica gel and a molecular sieve, the mass of the used adsorbent is 0.5-5%, preferably 2-3% of the total mass of the raw materials in the step (1), the adsorption temperature ranges from 30 ℃ to 50 ℃, and the adsorption time is 1-3 hours.

In the step (2), the vacuum distillation is carried out for 0.5-2 hours under the conditions that the temperature is 50-60 ℃ and the absolute pressure is 500-1000 pa.

In the step (3) of the present invention, the temperature of the primary molecular distillation is 160 ℃ and the vacuum pressure is 10-500Pa, and more preferably the distillation temperature is 125 ℃ and the vacuum pressure is 200 Pa. Further, the temperature of the secondary molecular distillation is 160-200 ℃, the vacuum pressure is 1-200Pa, and the more preferable distillation temperature is 160-170 ℃, and the vacuum pressure is 10-50 Pa. Further, the temperature of the three-stage molecular distillation is 200-250 ℃, the vacuum pressure is 0.1-100Pa, and the more preferable distillation temperature is 200-210 ℃, and the vacuum pressure is 0.1-20 Pa.

For the molecular distillation section process, on one hand, the yield and the purification effect of the product are improved to a certain extent by increasing the distillation temperature, but the oxidative decomposition of the sterol in a distiller and the oxidative discoloration of long-chain fatty alcohol are easily caused by the overhigh distillation temperature; on the other hand, the yield of the product can be greatly improved by maintaining lower vacuum pressure in the molecular distillation, but the removal and separation effects on colored groups, peroxy groups and the like are greatly reduced. Therefore, in the multistage molecular distillation process, the synergistic optimization of main process parameters such as molecular distillation temperature, vacuum degree and the like is a key factor influencing the production and quality of the pharmaceutical grade lanolin alcohol product, and the lanolin alcohol with higher melting point and higher cholesterol content can be obtained by the three-stage molecular distillation process, so that the indexes of the melting point and the cholesterol content in the pharmaceutical grade lanolin alcohol are achieved.

Further, the condensation temperature of the light phase in the molecular distillation is controlled between 70 and 100 ℃, and the film scraping rotating speed of the molecular distillation is controlled between 20 and 60 rpm; further, in the molecular distillation, the condensation temperature of a light phase of a primary molecular distillation system is 70-75 ℃, and the rotating speed of a film scraping is 30-40 rpm; the condensation temperature of the light phase of the secondary molecular distillation system is 80-85 ℃, and the rotating speed of a film scraping is 40-50 rpm; the condensation temperature of the light phase of the three-stage molecular distillation system is 95-100 ℃, and the rotating speed of the film scraping is 50-60 rpm.

The byproducts of the first-level light phase and the third-level heavy phase are mixed and collected, and can be prepared into a daily chemical grade or cosmetic grade lanolin alcohol product through subsequent processing treatment, so that the utilization rate of the raw materials is further improved.

In the step (4), the heating and melting temperature of the granulation precursor of the pharmaceutical grade lanolin alcohol is controlled to be 80-100 ℃, the temperature of cooling air of a cooling spray tower is controlled to be 0-10 ℃, and the humidity inside the spray tower is controlled to be 0-20%, preferably 5-10%. The low-temperature and low-humidity environment in the cooling spray tower can effectively accelerate the cooling, solidification and molding of the lanolin alcohol drops, prevent the product from softening by water absorption, and obviously improve the phenomenon of powder accumulation and material accumulation in the tower wall.

Further, in the cooling spray tower; the spraying pressure is controlled at 0.2-0.5 MPa. The aperture of the nozzle is 0.2-0.5 mm, the rotating speed of the spray head is controlled at 4000-8000 r/min, and the feeding rate is controlled at 35-50 mL/min.

Further, an anti-sticking coating is coated on the inner wall of the cooling spray tower cylinder body, the anti-sticking coating is made of polytetrafluoroethylene or fluorinated ethylene propylene, the inner wall of the cooling spray tower is cooled through a liquid refrigerant of a jacket, and the temperature of the liquid refrigerant ranges from minus 20 ℃ to 10 ℃, and is preferably from minus 15 ℃ to minus 5 ℃. In the preparation process, the low-temperature anti-sticking coating can effectively reduce the generation of the wall hanging phenomenon of molten liquid drops, remarkably improve the yield of granular products, and effectively control the particle size distribution of the products by adjusting the parameters such as the feeding rate, the spraying pressure, the rotating speed of a nozzle, the aperture of the nozzle and the like.

In conclusion, the invention takes the lanosterol and the lanosterol as main compound raw materials, and produces and prepares the fine-grained medical grade lanosterol product by the steps of raw material compounding, adsorption, molecular distillation, granulation and molding and the like under the protection of trace antioxidant. Compared with the prior art, the method has the beneficial effects that:

(1) the medicinal grade lanonol in micro-particles is prepared for the first time, the product has good color and luster, light smell and less impurities, the particle uniformity and color stability of the product are high, and the stability of each index of the product is high.

(2) Compared with the traditional steel belt granulation, the equipment for cooling and spraying granulation has small occupied area, reduces the selection limit on site space, and the cooling and spraying granulator not only can quickly realize the quick solidification and forming of the lanonol through the forced air cooling circulation effect, but also can generate spherical particles which reduce the contact area between the particles compared with hemispherical particles, obviously reduce the phenomenon of adhesion between the particles and greatly improve the qualification rate and the yield of products; the particle size of the product can be quickly adjusted by adjusting the process parameters such as the feeding speed, the feeding pressure, the rotating speed of the nozzle, the spraying aperture and the like, and different requirements of the market are met. Compared with a traditional cloth granulator, the particle diameter of the product is 4-10mm, and the cooling sprayer is used for granulation, so that the particle size is greatly reduced, the particle size is 0.2-2mm, about one order of magnitude is reduced, the reduction of the particle size facilitates the use and packaging of downstream customers, the metering and mixing are more accurate, the melting and dissolving rates of small-particle-size products are further enhanced, and the mixing and compounding efficiency of users is further improved.

(3) The coupling process of composite adsorption and three-stage molecular distillation is adopted, the qualification rate of products and the use stability of the products are improved, and meanwhile, the pharmaceutical grade lanolin alcohol is produced and prepared by taking the daily chemical grade lanolin alcohol with low additional value as a raw material, so that the additional value and the competitiveness of the products are further improved.

In summary, the preparation method provided by the invention is simple and convenient to operate, mild in process conditions, high in production efficiency, low in production cost, and high in product quality stability, greatly facilitates subsequent transportation and use of products, and meets the production requirements of large-scale pharmaceutical grade lanolin alcohol products and the requirements of market quality improvement and actual use.

Detailed Description

The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto:

example 1

(1) 1000g daily chemical grade lanonol (cholesterol content: 7.5%), 40g lanosterol and 0.5g alpha-tocopherol are dissolved in 20L petroleum ether solvent (boiling range is 60-90 ℃), heated and stirred at 55 ℃ to fully dissolve the materials, and a mixed raw material solution is prepared.

(2) Mixing the prepared raw material liquid with 30g of composite adsorbent (activated alumina and silica gel, mass ratio is 1:1), stirring and adsorbing at 45 ℃ for 1h, carrying out solid-liquid separation, and rapidly removing the collected adsorption liquid solvent in vacuum (distillation temperature: 55 ℃, distillation absolute pressure: 500-600 Pa, distillation time: 1 h) to obtain a crude product A of pharmaceutical grade lanolin alcohol.

(3) Feeding the crude product A of the pharmaceutical grade lanonol into a primary molecular distiller, wherein the distillation temperature is 120 ℃, the system pressure is 100Pa, the condensation temperature of a light phase is 72 ℃, and the film scraping rotation speed is 40rpm, and respectively collecting a primary distilled light phase and a heavy phase; feeding the primary molecular distillation heavy phase into secondary molecular distillation, wherein the distillation temperature is 170 ℃, the system pressure is 50Pa, the light phase condensation temperature is 81 ℃, the film scraping rotation speed is 40rpm, and respectively collecting a secondary distillation light phase and a secondary distillation heavy phase; and (3) feeding the second-stage molecular distillation heavy phase into third-stage molecular distillation, wherein the distillation temperature is 215 ℃, the system pressure is 20Pa, the condensation temperature of the light phase is 95 ℃, the film scraping rotating speed is 60rpm, and respectively collecting the third-stage distillation light phase and the third-stage distillation heavy phase. The collected secondary and tertiary light phases are mixed as a granulation precursor for pharmaceutical grade lanolin alcohol.

(4) Melting the granulation precursor (the melting temperature is 90 ℃), conveying the granulation precursor to a nozzle at the top of a cooling spray tower, controlling the temperature of cooling air to be 5 ℃, the air humidity to be 10%, controlling the temperature of a jacket liquid refrigerant to be-5 ℃, controlling the anti-sticking coating coated on the inner wall of the tower to be polytetrafluoroethylene, controlling the pressure of the nozzle to be 0.5Mpa, controlling the aperture of the nozzle to be 0.2mm, controlling the rotating speed of a spray head to be 8000r/min and the feeding rate to be 35ml/min, obtaining 179g of a fine-grained medical-grade lanolin alcohol product, controlling the yield to be 17.2%, controlling 85% of the product to pass through a 50-mesh sieve, controlling 10% of the rest 15% to pass through a 30-mesh sieve, controlling 3% to pass through a 20-mesh sieve and controlling 2% to pass through a 10-mesh sieve. The main physical and chemical indexes are detected as follows: the cholesterol content is 30.5 percent, the melting point is 67 ℃, the Gardner color is 8.9, the acid value is 0.2mgKOH/g, the peroxide value is 2.3meq/kg, the hydroxyl value is 141mgKOH/g, and the quality of the product meets the related index requirements of European pharmacopoeia and United states pharmacopoeia.

Example 2

(1) 1000g daily chemical grade lanonol (cholesterol content: 7.5%), 40g lanosterol and 0.5g alpha-tocopherol are dissolved in 20L petroleum ether solvent, heated and stirred at 55 ℃ to fully dissolve the materials, and a mixed raw material solution is prepared.

(2) Mixing the prepared raw material liquid with 30g of composite adsorbent (activated alumina and molecular sieve, mass ratio is 1:1), stirring and adsorbing at 45 ℃ for 1h, then carrying out solid-liquid separation, collecting the adsorption liquid, and quickly evaporating the solvent in vacuum (distillation temperature: 50 ℃, distillation absolute pressure: 500-600 Pa, distillation time: 1 h) to obtain a crude product B of pharmaceutical grade lanolin alcohol.

(3) Feeding the crude product B of the pharmaceutical grade lanonol into a primary molecular distiller, wherein the distillation temperature is 120 ℃, the system pressure is 200Pa, the condensation temperature of a light phase is 70 ℃, and the film scraping rotation speed is 40rpm, and respectively collecting a primary distilled light phase and a heavy phase; sending the primary molecular distillation heavy phase into secondary molecular distillation, wherein the distillation temperature is 165 ℃, the system pressure is 20Pa, the light phase condensation temperature is 80 ℃, the film scraping rotation speed is 40rpm, and respectively collecting the secondary distillation light phase and the heavy phase; and (3) feeding the secondary molecular distillation heavy phase into a tertiary molecular distillation, wherein the distillation temperature is 200 ℃, the system pressure is 10Pa, the condensation temperature of the light phase is 95 ℃, the film scraping rotating speed is 60rpm, and collecting the tertiary distillation light phase and the tertiary distillation heavy phase respectively. The collected secondary and tertiary light phases are mixed as a granulation precursor for pharmaceutical grade lanolin alcohol.

(4) Melting the granulation precursor (the melting temperature is 90 ℃), conveying the granulation precursor to a nozzle at the top of a cooling spray tower, controlling the temperature of cooling air to be 5 ℃, the air humidity to be 10%, controlling the temperature of a jacket liquid refrigerant to be-5 ℃, controlling the anti-sticking coating coated on the inner wall of the tower to be polytetrafluoroethylene, controlling the pressure of the nozzle to be 0.4Mpa, controlling the aperture of the nozzle to be 0.2mm, controlling the rotating speed of a spray head to be 8000r/min and the feeding rate to be 40ml/min, obtaining 224g of a fine-particle medical-grade lanolin alcohol product, controlling the yield to be 21.5%, controlling 85% of the product to pass through a 30-mesh sieve, controlling 11% of the rest 15% to pass through a 20-mesh sieve, and controlling 4% to pass through a 10-mesh sieve. The main physical and chemical indexes are detected as follows: the cholesterol content is 32 percent, the melting point is 68 ℃, the Gardner color is 7.8, the acid value is 0.3mgKOH/g, the peroxide value is 2.5meq/kg, the hydroxyl value is 144mgKOH/g, and the quality of the product meets the related index requirements of European pharmacopoeia and United states pharmacopoeia. Compared with example 1, after the distillation temperature and pressure of molecular distillation are improved, the yield of the product is improved, and the chroma is reduced.

Example 3

(1) 1200g of cosmetic grade lanonol (cholesterol content: 9.7%), 20g of lanosterol and 0.7g of dibutyl hydroxytoluene are dissolved in 20L of petroleum ether solvent, and the mixture is heated and stirred at 50 ℃ to fully dissolve the materials to prepare a raw material solution.

(2) Mixing the compounded raw material liquid with 50g of composite adsorbent (molecular sieve and silica gel, mass ratio is 1:1), stirring and adsorbing at 50 ℃ for 1h, then carrying out solid-liquid separation, quickly vacuum evaporating the collected adsorption liquid for solvent (distillation temperature: 60 ℃, distillation absolute pressure: 600-700 Pa, distillation time: 0.5 h) to obtain a crude product C of pharmaceutical grade lanolin alcohol.

(3) Feeding the crude product C into a primary molecular distiller, distilling at 120 deg.C under system pressure of 100Pa, condensing at 70 deg.C, and rotating at 40rpm to collect primary distilled light phase and heavy phase; sending the primary molecular distillation heavy phase into secondary molecular distillation, wherein the distillation temperature is 165 ℃, the system pressure is 10Pa, the light phase condensation temperature is 80 ℃, the film scraping rotation speed is 40rpm, and respectively collecting the secondary distillation light phase and the heavy phase; and (3) feeding the second-stage molecular distillation heavy phase into third-stage molecular distillation, wherein the distillation temperature is 200 ℃, the system pressure is 1.5Pa, the condensation temperature of the light phase is 95 ℃, the film scraping rotating speed is 60rpm, collecting the third-stage distillation light phase and the heavy phase respectively, and mixing the collected second-stage light phase and the third-stage light phase to be used as a granulation precursor of the pharmaceutical-grade lanolin alcohol.

(4) And melting the granulation precursor at 95 ℃ to form a liquid state, and conveying the liquid state to a melting cooling spray tower for cooling, solidifying and granulating. The temperature of cooling air is 5 ℃, the air humidity is 5%, the temperature of jacket cooling refrigerants is-15 ℃, an anti-sticking coating coated on the inner wall of the tower consists of polytetrafluoroethylene, the pressure of a nozzle is 0.2Mpa, the aperture of the nozzle is 0.5mm, the rotating speed of a nozzle is 4000r/min, the feeding rate is 50ml/min, 317g of a medical grade lanolin alcohol product of 95% micro particles passing through 10 meshes is obtained, the yield is 25.90%, and main physical and chemical indexes are detected: the cholesterol content is 32 percent, the melting point is 73 ℃, the Gardner chroma is 7.2, the acid value is 0.3mgKOH/g, the peroxide value is 1.3meq/kg, the hydroxyl value is 151mgKOH/g, and the quality of the product meets the related index requirements of European pharmacopoeia and United states pharmacopoeia.

Example 4

(1) 1000g of daily chemical grade lanolin alcohol (cholesterol content: 7.5%), 350g of NF grade cholesterol raw material (cholesterol content: 96%), 40g of lanosterol and 0.5g of alpha-tocopherol are dissolved in 20L of petroleum ether solvent, and the mixture is heated and stirred at 55 ℃ to fully dissolve the materials to prepare a mixed raw material solution.

(2) Mixing the prepared raw material liquid with 50g of composite adsorbent (activated alumina and molecular sieve, mass ratio is 1:1), stirring and adsorbing at 50 ℃ for 1h, then carrying out solid-liquid separation, collecting the adsorption liquid, and quickly evaporating the solvent in vacuum (distillation temperature: 60 ℃, distillation absolute pressure: 500-600 Pa, distillation time: 1 h) to obtain a crude product D of pharmaceutical grade lanolin alcohol.

(3) Feeding the crude product D of the pharmaceutical grade lanonol into a primary molecular distiller, wherein the distillation temperature is 120 ℃, the system pressure is 150Pa, the condensation temperature of a light phase is 70 ℃, and the film scraping rotation speed is 40rpm, and respectively collecting a primary distilled light phase and a heavy phase; feeding the primary molecular distillation heavy phase into secondary molecular distillation, wherein the distillation temperature is 170 ℃, the system pressure is 30Pa, the light phase condensation temperature is 80 ℃, the film scraping rotation speed is 40rpm, and respectively collecting a secondary distillation light phase and a secondary distillation heavy phase; and (3) feeding the secondary molecular distillation heavy phase into a tertiary molecular distillation, wherein the distillation temperature is 200 ℃, the system pressure is 10Pa, the condensation temperature of the light phase is 95 ℃, the film scraping rotating speed is 60rpm, and collecting the tertiary distillation light phase and the tertiary distillation heavy phase respectively. The collected secondary and tertiary light phases are mixed as a granulation precursor for pharmaceutical grade lanolin alcohol.

(4) Melting the granulation precursor (the melting temperature is 95 ℃), conveying the granulation precursor to a nozzle at the top of a cooling spray tower, controlling the temperature of cooling air to be 5 ℃, the air humidity to be 5%, controlling the temperature of a jacket liquid refrigerant to be-15 ℃, controlling the anti-sticking coating coated on the inner wall of the tower to be polytetrafluoroethylene, controlling the pressure of the nozzle to be 0.3Mpa, controlling the aperture of the nozzle to be 0.4mm, controlling the rotating speed of a spray head to be 6000r/min and the feeding rate to be 44ml/min, obtaining 954g of a fine-grained medical grade lanolin alcohol product, controlling the yield to be 68.6%, enabling 90% of the product to pass through a 20-mesh sieve, and enabling 7% of the rest 10% of the product to pass through a 10-mesh sieve and enabling 3% of the product to pass through an 8-mesh sieve. The main physical and chemical indexes are detected as follows: the cholesterol content is 31 percent, the melting point is 68 ℃, the Gardner color is 7.8, the acid value is 0.3mgKOH/g, the peroxide value is 2.0meq/kg, the hydroxyl value is 145mgKOH/g, and the quality of the product meets the related index requirements of European pharmacopoeia and United states pharmacopoeia. Compared with the examples 1, 2 and 3, the yield of the product is greatly improved by adding the cholesterol raw material.