WO2021209075A1 - 一种超细的高性能微晶纤维素产品及其制备方法 - Google Patents

一种超细的高性能微晶纤维素产品及其制备方法 Download PDF

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WO2021209075A1
WO2021209075A1 PCT/CN2021/099143 CN2021099143W WO2021209075A1 WO 2021209075 A1 WO2021209075 A1 WO 2021209075A1 CN 2021099143 W CN2021099143 W CN 2021099143W WO 2021209075 A1 WO2021209075 A1 WO 2021209075A1
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microcrystalline cellulose
shear
pulp
particle size
product
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PCT/CN2021/099143
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French (fr)
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尹丽敏
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牡丹江霖润药用辅料有限责任公司
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Priority to JP2022546694A priority Critical patent/JP2023524612A/ja
Priority to AU2021256240A priority patent/AU2021256240A1/en
Priority to EP21788975.7A priority patent/EP4137531A4/en
Publication of WO2021209075A1 publication Critical patent/WO2021209075A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
    • C08L1/02—Cellulose; Modified cellulose
    • C08L1/04—Oxycellulose; Hydrocellulose, e.g. microcrystalline cellulose
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
    • A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
    • A23L29/262—Cellulose; Derivatives thereof, e.g. ethers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A23L33/24—Cellulose or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B15/00—Preparation of other cellulose derivatives or modified cellulose, e.g. complexes
    • C08B15/02—Oxycellulose; Hydrocellulose; Cellulosehydrate, e.g. microcrystalline cellulose
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C08J3/122—Pulverisation by spraying
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2301/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2301/04—Oxycellulose; Hydrocellulose

Definitions

  • the invention relates to the field of microcrystalline cellulose, in particular to an ultrafine high-performance microcrystalline cellulose product and a preparation method thereof.
  • Microcrystalline cellulose is a free-flowing fine powdery particle that is hydrolyzed by dilute acid from natural cellulose to the limit of polymerization (LODP). Its color is white or nearly white, odorless and tasteless, and its limit degree of polymerization (LODP) is usually 100-350; it is insoluble in water, dilute acids, organic solvents and oils, and partially dissolves and swells in dilute alkali solutions. Microcrystalline cellulose has stable properties under high temperature, high humidity, and strong light exposure, and is widely used in various industries such as medicine, food, daily chemicals, and light industry.
  • Microcrystalline cellulose is widely used in the pharmaceutical industry as a pharmaceutical excipient. It is mainly used as a binder, disintegrant and filler in the pharmaceutical industry. It is mainly used in the tableting process. It can be used not only for wet granulation but also for dry granulation and direct compression. It has good compression resistance. Plays the role of disintegration and lubrication, and is an important pharmaceutical excipient. Because of its unique porous structure, microcrystalline cellulose can also play a sustained role in drug release. Microcrystalline cellulose can be used as an important functional food base material-dietary fiber in the food industry. It is an ideal food additive and can be used as a fat substitute.
  • PH101 average particle size of 40-60 ⁇ m, bulk density of 0.26-0.32g/ml
  • PH102 average particle size of 70-100 ⁇ m, bulk density of 0.28- 0.33g/ml
  • PH103 average particle size of 45-75um, bulk density of 0.26-0.34g/ml
  • PH112 average particle size of 90-140um, bulk density of 0.28-0.37g/ml
  • higher density PH 301 average particle size is 40-60 ⁇ m, bulk density is 0.34-0.45g/ml
  • PH302 average particle size is 90-140um, bulk density is 0.35-0.50g/ml
  • small The particle size is PH105 (average particle size is 20-40 ⁇ m, bulk density is 0.2-0.3g/ml) and so on.
  • Microcrystalline cellulose products with different particle sizes or densities have different application properties.
  • the smaller the particle size of microcrystalline cellulose the better it is to mix with other ingredients such as medicines. It is suitable for materials with small particle sizes and Mix materials with low active ingredient content to improve the uniformity of the content.
  • the traditional small particle size microcrystalline cellulose also has a unique advantage.
  • the smaller the particle size the higher the tablet strength performance.
  • the smaller the particle size the worse the fluidity, which is not conducive to the process of direct compression and other preparations, which greatly limits its application in medicines and foods.
  • microcrystalline cellulose products with small particle diameters can be produced by dry powder grinding, sieving or ball milling, especially in the presence of grinding aids.
  • Chinese invention patent CN101481424B discloses that microcrystalline cellulose 60 Co- ⁇ is irradiated to degrade and ultrafine, and then mechanically pulverized or/and chemically degraded to obtain ultrafine microcrystalline cellulose with a particle size of ⁇ 10 ⁇ m.
  • the density of microcrystalline cellulose products produced by these methods has not been significantly increased.
  • Commercially available small particle size microcrystalline cellulose products generally have an average particle size D50 of about 15-30 ⁇ m, and a bulk density of 0.2-0.3 g/ml. Therefore, the smaller the particle size, the worse the fluidity of the product. Greatly restrict its application in industry.
  • Chinese invention patent CN109666078A discloses a method for preparing microcrystalline cellulose by acid hydrolysis after high-shear mechanical pretreatment.
  • the high-shear mechanical force cuts off the fiber, which improves the accessibility of the acid liquid to the cellulose, increases the rate at which the acid liquid penetrates into the cellulose, and increases the acid liquid to the amorphous area of the cellulose.
  • Hydrolysis rate reduce the amount of chemicals or shorten the reaction time.
  • the microcrystalline cellulose prepared by this method has no increase in density, and the average particle size of the microcrystalline cellulose product is still above 38.7 ⁇ m.
  • Chinese invention patent CN110229239A discloses a high bulk density microcrystalline cellulose and its production process.
  • the filter cake obtained by acid hydrolysis is kneaded by a kneader and spray dried.
  • the bulk density of the microcrystalline cellulose product obtained is 0.6-0.65g/cm 3 , however, the product particle size is also larger, with an average particle size D50 of 45-50 ⁇ m.
  • Chinese invention patents CN103726378A, CN103526624A, and CN1671743A also respectively disclose methods for preparing microcrystalline cellulose.
  • the particle size range and bulk density of the microcrystalline cellulose products produced by these methods are not within the scope of the present invention, for example, the particle size is above 25 ⁇ m, or the bulk density is much lower than 0.5 g/ml.
  • the present invention provides a microcrystalline cellulose product with ultra-fine particle size and extremely high density and a manufacturing method thereof, so that it has better performance and wider application. field.
  • the present invention provides a microcrystalline cellulose particle, which is characterized in that its average particle size D50 is 1-25 ⁇ m, and the bulk density is 0.50-0.80 g/ml; preferably, the average particle size D50 of the microcrystalline cellulose particle It is 1-25 ⁇ m, and the bulk density is 0.52-0.75 g/ml; more preferably, the average particle size D50 of the microcrystalline cellulose particles is 10-20 ⁇ m, and the bulk density is 0.55-0.75 g/ml.
  • the above-mentioned microcrystalline cellulose particles are made of ordinary microcrystalline cellulose through high-shear mechanical action, and the solid content of ordinary microcrystalline cellulose during high-shear mechanical action is 15%-60%; wherein, more preferably, the solid content of ordinary microcrystalline cellulose during high-shear mechanical action is 30%-50%.
  • the above-mentioned microcrystalline cellulose particles wherein the high-shear mechanical action is to use a high-shear equipment with a torque greater than 20 Newton ⁇ m; more preferably, the high-shear mechanical
  • the function is to use high-shear equipment with a torque greater than 50 Newton ⁇ m.
  • the high-shearing equipment is preferably a high-strength and high-shearing screw extrusion equipment, such as a screw extruder, a screw extruder, a screw kneader, or a screw extrusion kneader.
  • the high shear force equipment can be continuous or intermittent, and can also be divided into multiple stages, multiple or repeated processing methods.
  • a method for preparing the aforementioned microcrystalline cellulose particles which includes the step of passing ordinary microcrystalline cellulose through the high shear force mechanical action of a high shear force device, and said Ordinary microcrystalline cellulose has a solid content of 15%-60% during high-shear mechanical action; among them, more preferably, ordinary microcrystalline cellulose has a solid content of 30% during high-shear mechanical action -50%; wherein the high shear force mechanical action is to use a high shear force equipment with a torque greater than 20 Newton ⁇ m; more preferably, the high shear force mechanical action is to use a torque greater than 50 Newton ⁇ m High shear equipment.
  • the "ordinary microcrystalline cellulose” mentioned above refers to a microcrystalline cellulose product with an average particle size D50 and/or bulk density that is different from the average particle size D50 and bulk density of the present invention, and its average particle size D50 exceeds 25 ⁇ m and/or bulk density is lower than 0.50g/ml.
  • the raw materials for preparing microcrystalline cellulose are microcrystalline cellulose products prepared by conventional methods in the art.
  • natural cellulose pulp undergoes a conventional hydrolysis method (for example, it can be made from cellulose
  • the pulp is filtered through acid hydrolysis at a temperature of 110-170°C and an acid concentration of 0.03-0.35mol/L to prepare a filter cake) or electron beam radiation (for example, by electron beam radiation, with a radiation dose of 0.2Mrad-10Mrad)
  • a conventional hydrolysis method for example, it can be made from cellulose
  • the pulp is filtered through acid hydrolysis at a temperature of 110-170°C and an acid concentration of 0.03-0.35mol/L to prepare a filter cake
  • electron beam radiation for example, by electron beam radiation, with a radiation dose of 0.2Mrad-10Mrad
  • the material source of the natural cellulose pulp is not particularly limited, and it may be a material commonly used in the field for the production of microcrystalline cellulose, such as including but not limited to the following raw materials or pulp: wood pulp, hemp pulp, bamboo pulp, cotton, cotton linters, straw, reed, straw pulp, bagasse, algae, bacteria and microorganisms, etc.
  • the existing commercially available microcrystalline cellulose products include but are not limited to microcrystalline cellulose products coded as PH101, PH102, PH112, PH301, PH302, PH105 or PH103.
  • the material processed by the high-shearing device further optionally includes the steps of dilution and dispersion, drying, sieving and/or fine grinding to obtain the microcrystalline cellulose particles.
  • microcrystalline cellulose particles as an auxiliary material or carrier in the pharmaceutical, health care, food, industrial, light industry, daily chemical, petroleum, personal care, agricultural chemical and other industries is provided the use of.
  • particles can also be understood as “powders” and the like, which refer to granular or powdered particles with an average particle size D50 of 1-25 ⁇ m and a bulk density of 0.50-0.80 g/ml Microcrystalline cellulose products.
  • the high-shearing force device used in the present invention can reduce the particle size of particles through mechanical actions such as extremely high shearing force, pressure or frictional force.
  • the present invention does not use solid grinding aids and grinding agents, nor does it use water-soluble grinding aids such as salts during the high shear process.
  • the high shear force device of the present invention can be a continuous or intermittent device, and can also be processed repeatedly in multiple times. Under normal circumstances, if screw devices such as extruders, kneaders, and extruders are used, the torque should be >20 Newton ⁇ m.
  • the torque used in the embodiment of the present invention can be >50 Newton ⁇ m, and the control torque is between 50-150. Between Newton meters. In the actual extrusion operation, the torque is a variable. At the beginning, the torque is low, for example, about 50 Newton ⁇ m, the later the torque will increase, the torque reaches more than 100 Newton ⁇ m, the resulting microcrystalline cellulose product All can reach the particle size and density range of the present invention.
  • the solid content of the material is generally between 15-60%, preferably between 30-50%. If the processed material is hydrolyzed microcrystalline cellulose filter cake, if the solid content is too high, you can add an appropriate amount of water before or during processing until it reaches the appropriate solid content; if the solid content is too low, perform high-shear processing Before or during the process, the material can be dehydrated.
  • the dehydration method can be centrifugation, filtration, pressing, infrared radiation, hot air blowing, air blowing, etc., or a combination thereof. It can also be obtained by adding microcrystalline cellulose dry powder or high solid content.
  • the hydrolyzed microcrystalline cellulose filter cake makes the final mixture reach a suitable solid content.
  • the processed material is the existing microcrystalline cellulose powder
  • an appropriate amount of water can be added before or during processing until the appropriate solid content is reached.
  • the solid microcrystalline cellulose powder can be factory-made microcrystalline cellulose powder or existing products on the market, such as but not limited to PH101, PH102, PH112, PH301, PH302, PH105, PH103, etc.
  • the method of the present invention reduces the particle size while significantly increasing the density of microcrystalline cellulose by controlling the steps of high-shearing mechanical action, so as to obtain A high-performance microcrystalline cellulose product with small particle size and high density.
  • the material processed by the high-shear device can be further diluted and dispersed according to an appropriate amount of water, and the general solid content during the dispersion process can be controlled at 1%-25%.
  • the dispersing device used includes, but is not limited to, any high-shear dispersing device, such as a high-shear mixer, a homogenizer, and a homogenizing pump.
  • the diluted and dispersed materials can be further dried, and the drying can be spray drying, fluidized bed drying, airflow drying, flash drying, etc. According to needs, the dried material can be further sieved or finely ground.
  • any pulp and source can be used.
  • These raw materials or pulps include but are not limited to wood pulp, hemp pulp, bamboo pulp, cotton, cotton short Wool, straw, reed, straw pulp, bagasse, algae, bacteria and microorganisms, etc.
  • the ultra-fine high-density microcrystalline cellulose product manufactured by the present invention can be applied to any known application fields of microcrystalline cellulose, and can also be applied to any potential or emerging application fields. These fields include pharmaceuticals, health products, Food, industry, light industry, daily chemical, petroleum, personal care, agricultural chemistry and other industries. In the pharmaceutical field, its application can be used as, but not limited to, adhesives, disintegrants, excipients, taste masking agents, dispersants, adsorbents, etc.
  • the product of the present invention can be used in any formulation process, including but not limited to wet granulation, dry granulation, direct compression, extrusion spheronization, spray drying, pellets, microtablets, coatings, liquid formulations , Creams and creams, injections, sprays, etc.
  • Medicinal applications also include traditional Chinese medicine, Chinese patent medicine and so on.
  • the application of the fine microcrystalline cellulose powder of the present invention in the food field is also extremely wide. For example, it can be applied to various dairy products, milk beverages, solid beverages, coffee and tea beverages, carbonated beverages, meat products, jams, condiments, soups, frozen foods, yogurt, fermented milk, cheese, biscuits, and so on.
  • ultrafine microcrystalline cellulose of the present invention can also be used in some new fields.
  • ultrafine microcrystalline cellulose can be used as a carrier of flavor substances, pigments or other nutrients due to its unique delicate taste and taste masking or taste adjustment function, and is especially suitable for tableting candies.
  • These superior functions add Its very good fluidity greatly improves the quality and performance of tableted candies, and can also reduce or replace the use of sugar alcohols.
  • examples of other applications include, but are not limited to, as an embedding agent, as an excipient for active microorganisms in spray drying or tableting.
  • the microcrystalline cellulose product of the present invention has a small particle size and high bulk density at the same time, and enhances the fluidity and compressibility of the product, so that it has a wider range of applications; in particular, the product of the present invention
  • the microcrystalline cellulose product has a unique particle morphology, which is spherical or quasi-spherical particles, while the existing microcrystalline cellulose on the market is a fibrous product segment by segment, and there are no spherical particles; moreover, the microcrystalline cellulose of the present invention
  • the angle of repose of the cellulose product is also smaller than that of the microcrystalline cellulose product UF-702, which has the smallest angle of repose on the market.
  • microcrystalline cellulose product of the present invention not only has good fluidity and strong compressibility properties, and is very suitable for the tableting process, but also has a small particle size, spherical or approximately spherical fine shape, which gives the product a good taste and fineness. , And masking peculiar smell, etc., suitable for medicine and food molding.
  • Figure 1 The particle structure of the product of Example 1 under a 32x optical microscope
  • Figure 2 The particle structure of the product of Example 1 under a 63X optical microscope
  • Figure 3 Particle structure diagram of AVICEL PH101 products on the market under a 32x optical microscope
  • the particle size, density, angle of repose and microscopic measurement of the present invention are as follows:
  • Particle size distribution measured by Malvern 2000 laser particle size analyzer.
  • the method of measuring the tap density Place the measuring cylinder containing the material for measuring the loose density on the tap, vibrate 500 times, read the volume V (ml), and convert it to density m/v (g/ml) ).
  • Optical microscope Take a small amount of microcrystalline cellulose powder on the glass slide, add a small amount of absolute ethanol to make the dispersion more uniform, and then place it under the microscope to observe, adjust the appropriate magnification, and make the picture clearer through fine-tuning.
  • the torque is a variable.
  • the torque is low, for example, about 50 Newton ⁇ m, and the torque will increase later, generally reaching 100-150 Newton ⁇ m, and reaching the equipment when it exceeds 150 Newton ⁇ m The limit.
  • the torque reaches 100 Newton ⁇ m or more, the prepared microcrystalline cellulose product can reach the particle size and density range of the present invention.
  • the microcrystalline cellulose particle product prepared above has a loose density of 0.670g/ml, a tap density of 0.807g/ml, and a particle size distribution: D10 of 8.721 ⁇ m, D50 of 19.776 ⁇ m, D90 is 48.369 ⁇ m; the angle of repose is 27.8°.
  • microcrystalline cellulose particle products prepared above were observed the particle morphology under an optical microscope at 32x and 63x respectively. The results are shown in Figure 1 and Figure 2. It can be seen that the product has a unique particle morphology, which is spherical or quasi-spherical. particle.
  • Vivapur PH102 microcrystalline cellulose powder Take the commercially available Vivapur PH102 microcrystalline cellulose powder with a limit polymerization degree of 225.
  • the bulk density is 0.32g/ml
  • the tap density is 0.44g/ml
  • the particle size distribution D10 is 29.623 ⁇ m.
  • D50 is 104.997 ⁇ m
  • D90 is 227.668 ⁇ m.
  • the microcrystalline cellulose product prepared above has a bulk density of 0.598g/ml, a tap density of 0.738g/ml, a particle size distribution of D10 of 8.629 ⁇ m, D50 of 18.649 ⁇ m, and D90 of 36.61 ⁇ m.
  • the microcrystalline cellulose product prepared above has a bulk density of 0.624g/ml, a tap density of 0.811g/ml, a particle size distribution D10 of 5.613 ⁇ m, D50 of 12.221 ⁇ m, and D90 of 31.201 ⁇ m.
  • the microcrystalline cellulose product prepared above has a bulk density of 0.619g/ml, a tap density of 0.774g/ml, a particle size distribution D10 of 6.665 ⁇ m, D50 of 14.447 ⁇ m, and D90 of 30.297 ⁇ m.
  • the loose density of the microcrystalline cellulose particles prepared above is 0.600g/ml
  • the tap density is 0.730g/ml
  • the particle size distribution: D10 is 8.773 ⁇ m
  • D50 is 21.459 ⁇ m
  • D90 is 48.528 ⁇ m
  • the angle of repose is 30.5°.
  • the particle size and density of the microcrystalline cellulose particles prepared above have a loose density of 0.487g/ml, a tap density of 0.574g/ml, and a particle size distribution: D10 is 11.598 ⁇ m, D50 is 37.001 ⁇ m, and D90 is 87.476 ⁇ m.

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Abstract

一种超细的高性能微晶纤维素产品及其制备方法，该微晶纤维素产品平均粒径D50为1-25μm，松散密度为0.50-0.80g/ml，其普通微晶纤维素通过高剪切力设备在高剪切力机械作用下制得的。该微晶纤维素产品具有低粒径和高密度，具有球形或类球形粒子的独特的粒子形态，具有流动性好、可压性强、良好口感和细腻度等特点，其可在食品、医药、化工等多种领域广泛应用。

Description

[根据细则26改正24.06.2021]　一种超细的高性能微晶纤维素产品及其制备方法 技术领域
本发明涉及微晶纤维素领域，具体涉及一种超细的高性能微晶纤维素产品及其制备方法。
背景技术
微晶纤维素是从天然的纤维素经稀酸水解至极限聚合度(LODP)的可自由流动的细微粉末状颗粒。其颜色为白色或近白色,无臭、无味,极限聚合度(LODP)通常在100-350；不溶于水、稀酸、有机溶剂和油脂,在稀碱溶液中部分溶解、润胀。微晶纤维素在高温、高湿、强光照射情况下性质稳定，被广泛应用于医药、食品、日化以及轻工等各种行业。
微晶纤维素作为药用辅料被广泛应用于医药行业中。其在医药行业主要是作为粘合剂、崩解剂和填充剂，主要用于压片工艺中，不仅可以用于湿法制粒也可以用于干法制粒和直接压片，抗压性好，起到崩解和润滑的作用，是一种重要的药用辅料。微晶纤维素因为其独特的多孔结构，还可以起到对药物的缓释作用。微晶纤维素在食品行业中可作为重要的功能性食品基料-膳食纤维，是一种理想的食品添加剂，并可以作为脂肪的替代品。
市场上微晶纤维素产品有很多型号，常规的如PH101(平均粒径为40-60μm,松散密度为0.26-0.32g/ml)，PH102(平均粒径为70-100μm，松散密度为0.28-0.33g/ml)，PH103(平均粒径为45-75um，松散密度为0.26-0.34g/ml)，PH112(平均粒径为90-140um，松散密度为0.28-0.37g/ml)；也有特殊型号如密度更高的PH 301(平均粒径为40-60μm，松散密度为0.34-0.45g/ml)，PH302(平均粒径为90-140um，松散密度为0.35-0.50g/ml)；小粒径的PH105(平均粒径为20-40μm，松散密度为0.2-0.3g/ml)等。
下表引证自日本旭化成ASAHI产品手册，是目前市场上常见微晶纤维素产品包装上标示的产品参数：
Figure PCTCN2021099143-appb-000001
Figure PCTCN2021099143-appb-000002
粒径或密度不同的微晶纤维素产品，其应用性能也不同，一般来说，微晶纤维素的粒径越小，越有利于与药物等其他成分混合均匀，适用于小粒径物料及活性成分含量低的物料混合，提高含量的均匀性。传统的小粒径的微晶纤维素还有一个独特的优点，粒径越小压片强度性能越高。但粒径越小其流动性往往越差，不利于直接压片和其他制剂的工艺，大大限制了其在药品和食品中的应用。
传统上制造小粒径的微晶纤维素产品可以通过干粉研磨、筛分或球磨尤其是在有助磨剂的情况下制得。中国发明专利CN101481424B公开通过对微晶纤维素 60Co-γ辐照降解和超细处理，然后进行机械粉碎或/和化学降解，制得粒径<10μm的超细微晶纤维素。但这些方法制得的微晶纤维素产品的密度并没有显著提高。市售的小粒径微晶纤维素产品一般平均粒径D50在15-30μm左右，松散密度一般为0.2-0.3g/ml，因此存在粒径越小、产品的流动性越差的问题，这极大限制了其在工业中的应用。
中国发明专利CN109666078A公开了一种通过高剪切机械预处理后酸水解制备微晶纤维素的方法。在预处理过程中高剪切机械作用力切断纤维，提高了酸液对纤维素的可及度，增加了酸液渗透进入纤维素内部的速度，增大了酸液对纤维素无定形区的酸水解速率，减少化学品用量或缩短反应时间。该方法制得的微晶纤维素在密度上没有提高，而且微晶纤维素产品的平均粒径仍然是38.7μm以上。
中国发明专利CN110229239A公开了一种高堆积密度的微晶纤维素及其生产 工艺，酸水解制得的滤饼经捏合机捏合，并喷雾干燥，其所制得的微晶纤维素产品堆积密度为0.6-0.65g/cm 3，然而，其产品粒径也较大，平均粒径D50达到45-50μm。
中国发明专利CN103726378A、CN103526624A、CN1671743A还分别公开了制备微晶纤维素的方法。然而这些方法所制得的微晶纤维素产品，粒径范围和松散密度都不在本发明范围之中，比如粒径在25μm以上，或松散密度远低于0.5g/ml。
发明内容
为克服现有技术微晶纤维素类产品存在的缺陷，本发明提供一种超细粒径的极高密度的微晶纤维素产品及其制造方法，使其具有更好性能，更广泛的应用领域。
本发明技术方案如下：
本发明提供了一种微晶纤维素颗粒，其特征在于其平均粒径D50为1-25μm，松散密度0.50-0.80g/ml；作为优选地，所述的微晶纤维素颗粒平均粒径D50为1-25μm，松散密度0.52-0.75g/ml；更优选地，所述的微晶纤维素颗粒平均粒径D50为10-20μm，松散密度0.55-0.75g/ml。
优选地，上述所述的微晶纤维素颗粒，其是普通微晶纤维素通过高剪切力机械作用而制得，并且普通微晶纤维素在进行高剪切力机械作用中其固含量为15％-60％；其中，更优选地，普通微晶纤维素在进行高剪切力机械作用中其固含量为30％-50％。
优选地，上述所述的微晶纤维素颗粒，其中所述的高剪切力机械作用是使用扭矩大于20牛顿·米的高剪切力设备；更优选地，所述的高剪切力机械作用是使用扭矩大于50牛顿·米的高剪切力设备。所述的高剪切力设备，优选为高强度高剪切力的螺杆挤压设备，例如为螺杆挤压机、螺杆挤出机、螺杆捏合机或螺杆挤出捏合机等。所述的高剪切力设备可以为连续的或者间歇的，也可以分多段的，多次的或者重复的加工等方式。
作为本发明另一目的，还提供一种制备上述所述的微晶纤维素颗粒的方法，其包括普通微晶纤维素通过高剪切力设备的高剪切力机械作用的步骤，并且所述 普通微晶纤维素在进行高剪切力机械作用中其固含量为15％-60％；其中，更优选地，普通微晶纤维素在进行高剪切力机械作用中其固含量为30％-50％；其中所述的高剪切力机械作用是使用扭矩大于20牛顿·米的高剪切力设备；更优选地，所述的高剪切力机械作用是使用扭矩大于50牛顿·米的高剪切力设备。
上述所述的“普通微晶纤维素”，是指平均粒径D50和/或松散密度上区别于本发明所述平均粒径D50和松散密度的微晶纤维素产品，其平均粒径D50超过25μm和/或松散密度低于0.50g/ml。例如，现有技术中制备微晶纤维素的原材料按本领域中常规的方法所制得的微晶纤维素产品，如作为例子，天然纤维素浆粕经常规的水解法(例如可以由纤维素纸浆通过温度为110-170℃、酸浓度0.03-0.35mol/L的酸水解洗涤过滤而制得的滤饼)或电子束辐射法(例如通过电子束辐射，其辐射剂量为0.2Mrad-10Mrad制得的微晶纤维素)等所制得的微晶纤维素滤饼或半成品，或者是现有的市售的微晶纤维素产品。其中，所述的天然纤维素浆粕的材料来源没有特别限制，可以是本领域中常用的用于生产微晶纤维素的材料，例如包括但不限于下列原料或纸浆：木浆、麻浆、竹浆、棉花、棉短绒、秸秆、芦苇、草浆、甘蔗渣、水藻、细菌微生物等。所述现有的市售的微晶纤维素产品，例如包括但不限于代号为PH101，PH102，PH112、PH301、PH302、PH105或PH103等微晶纤维素产品。
上述所述的方法，其中，经过高剪切力装置加工后的物料还进一步任选地包括稀释分散、干燥、筛分和/或精磨的步骤制得所述的微晶纤维素颗粒。
作为本发明另一目的，提供了上述所述的微晶纤维素颗粒作为辅料或载体在制药、保健品、食品、工业、轻工、日化、石油、个人护理、农业化学等行业中的应用的用途。
本发明的微晶纤维素颗粒，其中“颗粒”也可被理解为“粉末”等，是指具有平均粒径D50为1-25μm，松散密度0.50-0.80g/ml的颗粒状或粉末状的微晶纤维素产品。
本发明所使用的高剪切力的装置，可以通过极高的剪切力和压力或者摩擦力等机械作用，降低粒子的粒径大小。不同于传统的精细微晶纤维素制造方法，本发明在高剪切过程中不使用固体助磨剂和研磨剂，也不使用盐类等水溶性的助磨剂。
本发明所述的高剪切力装置，可以为连续的或者间歇的装置，也可以分多次反复的加工。在通常情况下，如果使用挤压机、捏合机、挤出机等螺杆装置，其扭矩应该>20牛顿·米，本发明实施例中所用扭矩可以>50牛顿·米，控制扭矩在50-150牛顿·米之间。在实际挤出操作中，扭矩是一个变量，一开始扭矩低，例如为50牛顿·米左右，越往后扭矩会升高，扭矩达到100牛顿·米以上，所制得的微晶纤维素产品都可以达到本发明所述的粒径和密度范围。
在本发明所使用的高剪切力机械加工中，物料的固含量一般在15-60％之间，优选为30-50％之间。如果所加工的材料为水解微晶纤维素滤饼，若固含量过高，可在加工前或加工过程中添加适量的水直至到合适的固含量；若固含量过低，在高剪切加工前或者过程中，可以对物料进行脱水处理，脱水方式可以为离心、过滤、压榨、红外辐射、热吹风、吹风等方式或者其组合来取得，也可以通过添加微晶纤维素干粉或者高固含量的水解微晶纤维素滤饼使最终混合物达到合适的固含量。如果所加工的材料为现有的微晶纤维素粉末，则可在加工前或加工过程中添加适量的水直至达到合适的固含量。固体微晶纤维素粉末可以为工厂自制的微晶纤维素粉末也可以为市场上现有的产品，例如但不限于PH101，PH102，PH112、PH301、PH302、PH105、PH103等。
与传统的研磨等方法制备微晶纤维素产品不同，本发明方法通过控制高剪切力机械作用的步骤，在降低粒径的同时对微晶纤维素的密度有显著的提高，以制得具有小粒径和高密度的高性能微晶纤维素产品。
在本发明中，经过高剪切装置加工后的物料，可以进一步按照合适的水量进行稀释和分散，分散过程中一般固含量可以控制在1％-25％。所用的分散装置包括但不限于任何高剪切力的分散装置，如高剪切搅拌器、均质机、均质泵等。
稀释分散后的物料可以进一步干燥，干燥可以采用喷雾干燥、流化床干燥、气流干燥、闪蒸干燥等方式。根据需要，干燥后的物料可以选择进一步筛分或精磨。
本发明若使用纤维素原料或纤维素纸浆来制备水解微晶纤维素滤饼，任何纸浆及来源都可以应用，这些原料或纸浆包括但不限于木浆、麻浆、竹浆、棉花、棉短绒、秸秆、芦苇、草浆、甘蔗渣、水藻、细菌微生物等。
本发明所制造的超细的高密度微晶纤维素产品可应用于任何已知的微晶纤 维素应用领域，也可以应用于任何潜在的或新兴的应用领域，这些领域包括制药、保健品、食品、工业、轻工、日化、石油、个人护理、农业化学等行业中。在制药领域中，其应用可作为，但不限于粘合剂、崩解剂、赋型剂、掩味剂、分散剂、吸附剂等等。本发明的产品可使用于任何制剂工艺中，包括但不限于湿法造粒、干法造粒、直接压片、挤压滚圆、喷雾干燥、微丸、微片、包衣涂层、液体制剂、乳膏和乳霜、注射剂、喷剂等等。药用的应用也包括中药、中成药等。本发明的精细微晶纤维素粉末在食品领域中的应用也极为广泛。举例来说，可以应用于各种乳制品、乳饮料、固体饮料、咖啡茶饮、碳酸饮料、肉制品、果酱、调味品、汤料、冷冻食品、酸奶、发酵乳、奶酪、饼干等等。除了这些传统的食品应用外，本发明的超细微晶纤维素还可以应用于一些新型的领域中。例如，超细微晶纤维素因其特有的细腻的口感以及掩味或味觉的调节功能，可以作为风味物质、色素或其他营养物质的载体，尤其适用于压片糖果中，这些优越的功能加上其非常好的流动性，极大提高压片糖果的品质和性能，也可以降低或取代糖醇的使用。此外其他应用的例子包括但不限于，作为包埋剂，在喷雾干燥或者压片成型中作为活性微生物的赋型剂。
本发明的微晶纤维素产品，其具有小的粒径，同时具有高的松散密度，增强产品的流动性、可压性等性能，使其具有更广泛的应用领域；特别是，本发明的微晶纤维素产品具有独特的粒子形态，是球形或类球形的粒子，而市场上的现有微晶纤维素都是一段一段的纤维状产品，不存在球形粒子；并且，本发明的微晶纤维素产品的休止角，也小于目前市场上休止角最小的微晶纤维素产品UF-702。本发明的微晶纤维素产品不仅具有好的流动性和可压性强的性能，非常适用于压片工艺，而且粒径小，球形或近似球形的微细形态，赋予产品良好的口感和细腻度，以及掩蔽异味等，适用于药品和食品成型。
附图说明
图1：实施例1产品在32倍光学显微镜下的粒子结构图
图2：实施例1产品在63倍光学显微镜下的粒子结构图
图3：市场上AVICEL PH101产品在32倍光学显微镜下的粒子结构图
具体实施方式
以下实施例是为了解释和说明本发明的内容，实施例的内容不应被理解为对本发明保护范围构成限制。
本发明的所述粒径、密度、休止角以及显微镜测定，按如下方法：
1、粒径分布：采用马尔文2000型激光粒度测定仪测定。
2、松散密度的测定方法：取微晶纤维素粉末，加入到干燥的100ml的量筒中至100ml刻度，使粉体自然下沉，顶部呈水平状态，读取粉体体积V(ml)，将粉体全部倒出称量重量m(g)，松散密度＝m/v(g/ml)。
3、振实密度的测定方法：将测定松散密度的上述装有物料的量筒放置在振实仪上，振动500次，读取体积V(ml)，并换算成密度m/v(g/ml)。
4、休止角的测定方法：采用固定圆锥法测定，将微晶纤维素粉末通过漏斗注入到具有固定直径的圆盘中心上，圆盘半径为r,直到粉体堆积层斜边的物料沿圆盘边缘自动流出为止，停止注入，测定粉体堆积成的圆锥体的高度h,计算休止角θ＝arctan(h/r)。
5、光学显微镜：取少量微晶纤维素粉末放在载玻片上，加少量无水乙醇，使其分散更均匀，然后放置在显微镜下观察，调整合适倍数，并通过微调使画面更加清晰。
在实际挤出操作中，扭矩是一个变量，一开始扭矩低，例如为50牛顿·米左右，越往后扭矩会升高，一般达到100-150牛顿·米，超过150牛顿·米就达到设备的极限。扭矩达到100牛顿·米以上，所制得的微晶纤维素产品都可以达到本发明所述的粒径和密度范围。
实施例1
取市场上的木浆纤维素纸浆，经高温酸水解(水解温度115-170℃，酸浓度0.03-0.35mol/L)1-2小时，制得水解微晶纤维素，经过过滤并水洗至pH至4-5，并将滤饼固含量提高到40％。将此固含量的滤饼通过高剪切力挤压装置(带有高剪切力浆片的连续挤压机)挤出3遍，并控制挤压装置的扭矩在50-150牛顿·米之间，在挤压机的夹层中，通入冷却水冷却。挤压后的物料经加水稀释并搅拌后，中和至pH为5-8，再喷雾干燥而制得本发明的微晶纤维素产品。
经粒径、密度和休止角测定，上述制得的微晶纤维素颗粒产品，其松散密度 为0.670g/ml，振实密度0.807g/ml，粒径分布：D10为8.721μm，D50为19.776μm，D90为48.369μm；休止角为27.8°。
上述制得的微晶纤维素颗粒产品，分别在32倍和63倍的光学显微镜下观察粒子形态，结果如图1和图2所示，可见产品具有独特的粒子形态，是球形或类球形的粒子。
作为比较，取市场上最具代表性的AVICEL PH101微晶纤维素产品在32倍光学显微镜下观察形态，结果如图3所示，可见其呈一段一段的纤维状。
实施例2
取市售的Vivapur PH102微晶纤维素粉，其极限聚合度为225，经粒径和密度测定，松散密度为0.32g/ml，振实密度为0.44g/ml，粒径分布D10为29.623μm，D50为104.997μm，D90为227.668μm。
称取Vivapur PH102微晶纤维素粉500g，加水500g混合均匀后至物料固含量为50％，将此固含量的滤饼通过高剪切力挤压装置挤出3遍，并控制挤压装置的扭矩在50-150牛顿·米之间，在挤压机的夹层中，通入冷却水冷却。挤压后的物料经加水稀释并搅拌后，中和至pH为5-8，再由喷雾干燥而制得本发明的微晶纤维素产品。
经粒径和密度测定，上述制得的微晶纤维素产品，其松散密度为0.598g/ml，振实密度为0.738g/ml，粒径分布D10为8.629μm，D50为18.649μm，D90为36.61μm。
实施例3
取市场上的竹子制得的纤维素纸浆，经高温酸水解(水解温度115-170℃，酸浓度0.03-0.35mol/L)1-2小时，制得水解微晶纤维素，经过过滤并水洗至pH至4-5，将此滤饼经水稀释，中和至pH为5-8，再由喷雾干燥而制得的传统微晶纤维素产品，经测定，此微晶纤维素粉末松散密度为0.440g/ml，振实密度0.575g/ml，粒径分布D50为39.01μm。
取上述制得的竹浆微晶纤维素滤饼，固含量控制在40％，通过高剪切力挤压装置挤出3遍，并控制挤压装置的扭矩在50-150牛顿·米之间，在挤压机的夹层 中，通入冷却水冷却。挤压后的物料经加水稀释并搅拌后，中和至pH为5-8，再由喷雾干燥而制得本发明的微晶纤维素产品。
经粒径和密度测定，上述制得的微晶纤维素产品，其松散密度为0.624g/ml，振实密度为0.811g/ml，粒径分布D10为5.613μm，D50为12.221μm，D90为31.201μm。
实施例4
取市场上的麻纤维制得的纤维素纸浆，经高温酸水解(水解温度115-170℃，酸浓度0.03-0.35mol/L)1-2小时，制得水解微晶纤维素，经过过滤并水洗至pH至4-5，将此滤饼经水稀释，中和至pH为5-8，再由喷雾干燥而制得的传统微晶纤维素产品，经测定，此微晶纤维素粉末松散密度为0.388g/ml，振实密度0.561g/ml，粒径分布D50为36.7μm。
取上述制得的麻浆微晶纤维素滤饼，固含量控制在40％，通过高剪切力挤压装置挤出3遍，并控制挤压装置的扭矩在50-150牛顿·米之间，在挤压机的夹层中，通入冷却水冷却。挤压后的物料经加水稀释并搅拌后，中和至pH为5-8，再由喷雾干燥而制得本发明的微晶纤维素产品。
经粒径和密度测定，上述制得的微晶纤维素产品，其松散密度为0.619g/ml，振实密度为0.774g/ml，粒径分布D10为6.665μm，D50为14.447μm，D90为30.297μm。
实施例5
取市场上的木浆纤维素纸浆，经高温酸水解(水解温度115-170℃，酸浓度0.03-0.35mol/L)1-2小时，制得水解微晶纤维素，经过过滤并水洗至pH至4-5，并将滤饼固含量提高到42％。将此固含量的滤饼通过高剪切力挤压装置(带有高剪切力浆片的连续挤压机)挤出3遍，并控制挤压装置的扭矩在50-150牛顿·米之间，在挤压机的夹层中，通入冷却水冷却。挤压后的物料经加水稀释并搅拌后，中和至pH为5-8，再喷雾干燥而制得本发明的微晶纤维素产品。
经粒径、密度、休止角测定，上述制得的微晶纤维素颗粒，其松散密度为0.600g/ml，振实密度0.730g/ml，粒径分布：D10为8.773μm，D50为21.459 μm，D90为48.528μm；休止角为30.5°。
对比例
取市场上的木浆纤维素纸浆，经高温酸水解(水解温度115-170℃，酸浓度0.03-0.35mol/L)1-2小时，制得水解微晶纤维素，经过过滤并水洗至pH至4-5，并将滤饼固含量提高到35％。将此固含量的滤饼通过高剪切力挤压装置(带有高剪切力浆片的连续挤压机)挤出3遍，并控制挤压装置的扭矩在14-20牛顿·米之间，随着挤出过程中水分的挥发，扭矩会逐渐升高，通过加适量水使扭矩保持在20牛顿·米以下。在挤压机的夹层中，通入冷却水冷却。挤压后的物料经加水稀释并搅拌后，中和至pH为5-8，再喷雾干燥而制得本发明的微晶纤维素产品。
经粒径和密度测定，上述制得的微晶纤维素颗粒，其松散密度为0.487g/ml，振实密度0.574g/ml，粒径分布：D10为11.598μm，D50为37.001μm，D90为87.476μm。

Claims (10)

  1. 一种微晶纤维素颗粒，其特征在于其平均粒径D50为1-25μm，松散密度0.50-0.80g/ml。
  2. 根据权利要求1所述的微晶纤维素颗粒，其是普通微晶纤维素通过高剪切力机械作用而制得，并且普通微晶纤维素在进行高剪切力机械作用中其固含量为15％-60％。
  3. 根据权利要求2所述的微晶纤维素颗粒，其中所述的高剪切力机械作用是使用扭矩大于20牛顿·米的高剪切力设备。
  4. 根据权利要求3所述的微晶纤维素颗粒，其中所述的高剪切力设备为高强度高剪切力的螺杆挤压设备，优选为螺杆挤压机、螺杆挤出机、螺杆捏合机或螺杆挤出捏合机。
  5. 一种制备权利要求1-4所述的微晶纤维素颗粒的方法，其包括普通微晶纤维素通过高剪切力设备的高剪切力机械作用的步骤，并且所述普通微晶纤维素在进行高剪切力机械作用中其固含量为15％-60％。
  6. 根据权利要求5所述的方法，其中所述的普通微晶纤维素是天然纤维素浆粕经水解法或电子束辐射法制得的微晶纤维素半成品，或者是现有的微晶纤维素粉末产品。
  7. 根据权利要求6所述的方法，其中所述的天然纤维素浆粕的材料来源包括但不限于下列原料或纸浆：木浆、麻浆、竹浆、棉花、棉短绒、秸秆、芦苇、草浆、甘蔗渣、水藻、细菌微生物等。
  8. 根据权利要求6所述的方法，其中所述的现有的微晶纤维素粉末产品包括但不限于代号为PH101，PH102，PH112、PH301、PH302、PH105或PH103的微晶纤维素。
  9. 根据权利要求5-8所述的方法，其中，经过高剪切力装置加工后的物料还进一步任选地包括稀释分散、干燥、筛分和/或精磨的步骤制得所述的微晶纤维素颗粒。
  10. 权利要求1-4所述的微晶纤维素颗粒作为辅料或载体在制药、保健品、食品、工业、轻工、日化、石油、个人护理、农业化学等行业中的应用。
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230011081A1 (en) * 2021-07-08 2023-01-12 Korea Institute Of Science And Technology Cellulose composite material, 3d printing material and 3d printing structure including the same, and method of manufacturing the 3d printing structure using the same
WO2024004466A1 (ja) * 2022-07-01 2024-01-04 フタムラ化学株式会社 未修飾セルロースビーズ及びその製造方法
JP7411852B1 (ja) 2023-03-29 2024-01-11 日本製紙株式会社 アニオン変性セルロースナノファイバー含有粉末

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111333875B (zh) * 2020-04-13 2023-02-07 牡丹江霖润药用辅料有限责任公司 一种超细的高性能微晶纤维素产品及其制备方法
FI20215507A1 (en) * 2021-04-30 2022-10-31 Andritz Oy System and method for producing microcrystalline cellulose
FI20215509A1 (en) * 2021-04-30 2022-10-31 Andritz Oy Microcrystalline cellulose product

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1671743A (zh) 2002-07-26 2005-09-21 Fmc有限公司 微晶纤维素的制造
CN101481424A (zh) 2009-02-06 2009-07-15 北京大学 一种超细微晶纤维素及其制备方法
CN103526624A (zh) 2013-10-22 2014-01-22 湖州市菱湖新望化学有限公司 一种微晶纤维素生产方法及其反应设备
CN103726378A (zh) 2013-12-26 2014-04-16 湖北葛店人福药用辅料有限责任公司 低温下制备微晶纤维素的方法
CN109666078A (zh) 2019-02-25 2019-04-23 陕西科技大学 一种高剪切机械预处理后酸水解制备微晶纤维素的方法
CN110229239A (zh) 2019-07-30 2019-09-13 珠海市东辰制药有限公司 一种高堆积密度的微晶纤维素及其生产工艺
EP3622966A1 (en) * 2018-09-17 2020-03-18 Omya International AG High performance excipient comprising co-processed microcrystalline cellulose and surface-reacted calcium carbonate
WO2020058252A1 (en) * 2018-09-17 2020-03-26 Omya International Ag High performance excipient comprising co-processed microcrystalline cellulose and surface-reacted calcium carbonate
CN111333875A (zh) * 2020-04-13 2020-06-26 牡丹江霖润药用辅料有限责任公司 一种超细的高性能微晶纤维素产品及其制备方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3094234B2 (ja) * 1992-09-22 2000-10-03 エフ エム シー コーポレーション 微晶質セルロース生成物及びその製造法
JP2011209221A (ja) * 2010-03-30 2011-10-20 Rikkyo Gakuin セルロース粒子の製造方法
CN102727393A (zh) * 2012-07-10 2012-10-17 中国国旅贸易有限责任公司 一种超细微晶纤维素爽身粉及其制备方法
CN103265711A (zh) * 2013-06-03 2013-08-28 徐季亮 胶态级微晶纤维素(mcc)的制备方法
CN106062055A (zh) * 2014-03-12 2016-10-26 富士胶片株式会社 纤维素多孔质粒子的制造方法及纤维素多孔质粒子
CN105688223B (zh) * 2016-01-26 2018-11-23 珠海市东辰制药有限公司 一种小粒径微晶纤维素丸芯的制备工艺

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1671743A (zh) 2002-07-26 2005-09-21 Fmc有限公司 微晶纤维素的制造
CN101481424A (zh) 2009-02-06 2009-07-15 北京大学 一种超细微晶纤维素及其制备方法
CN103526624A (zh) 2013-10-22 2014-01-22 湖州市菱湖新望化学有限公司 一种微晶纤维素生产方法及其反应设备
CN103726378A (zh) 2013-12-26 2014-04-16 湖北葛店人福药用辅料有限责任公司 低温下制备微晶纤维素的方法
EP3622966A1 (en) * 2018-09-17 2020-03-18 Omya International AG High performance excipient comprising co-processed microcrystalline cellulose and surface-reacted calcium carbonate
WO2020058252A1 (en) * 2018-09-17 2020-03-26 Omya International Ag High performance excipient comprising co-processed microcrystalline cellulose and surface-reacted calcium carbonate
CN109666078A (zh) 2019-02-25 2019-04-23 陕西科技大学 一种高剪切机械预处理后酸水解制备微晶纤维素的方法
CN110229239A (zh) 2019-07-30 2019-09-13 珠海市东辰制药有限公司 一种高堆积密度的微晶纤维素及其生产工艺
CN111333875A (zh) * 2020-04-13 2020-06-26 牡丹江霖润药用辅料有限责任公司 一种超细的高性能微晶纤维素产品及其制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4137531A4

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230011081A1 (en) * 2021-07-08 2023-01-12 Korea Institute Of Science And Technology Cellulose composite material, 3d printing material and 3d printing structure including the same, and method of manufacturing the 3d printing structure using the same
WO2024004466A1 (ja) * 2022-07-01 2024-01-04 フタムラ化学株式会社 未修飾セルロースビーズ及びその製造方法
JP7448590B2 (ja) 2022-07-01 2024-03-12 フタムラ化学株式会社 Ｉｉ型未修飾セルロースビーズ及びその製造方法
JP7411852B1 (ja) 2023-03-29 2024-01-11 日本製紙株式会社 アニオン変性セルロースナノファイバー含有粉末

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