WO2020073800A1 - 一种过瘤胃氯化胆碱微胶囊及其制备方法 - Google Patents

一种过瘤胃氯化胆碱微胶囊及其制备方法 Download PDF

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WO2020073800A1
WO2020073800A1 PCT/CN2019/107649 CN2019107649W WO2020073800A1 WO 2020073800 A1 WO2020073800 A1 WO 2020073800A1 CN 2019107649 W CN2019107649 W CN 2019107649W WO 2020073800 A1 WO2020073800 A1 WO 2020073800A1
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choline chloride
rumen
passing
rice bran
film
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PCT/CN2019/107649
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English (en)
French (fr)
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徐二华
李浙烽
张倩云
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杭州康德权饲料有限公司
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Priority to JP2021513799A priority Critical patent/JP7018239B2/ja
Priority to EP19870132.8A priority patent/EP3841887B1/en
Publication of WO2020073800A1 publication Critical patent/WO2020073800A1/zh
Priority to US17/216,645 priority patent/US20210212341A1/en

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/105—Aliphatic or alicyclic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/158—Fatty acids; Fats; Products containing oils or fats
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/28—Silicates, e.g. perlites, zeolites or bentonites
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/20—Inorganic substances, e.g. oligoelements
    • A23K20/30—Oligoelements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/10—Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
    • A23K40/35—Making capsules specially adapted for ruminants

Definitions

  • the invention relates to the technical field of feed additives, in particular to a rumen-passing choline chloride microcapsule and a preparation method thereof.
  • Choline is a B vitamin and its chemical name is hydroxyethyl trimethylamine. It has many biological functions, including: phospholipid components, involved in the formation of lecithin and sphingomyelin, etc .; unstable methyl group donor; plays an important role in regulating liver fat metabolism; the main component of acetylcholine synthesis. At present, choline has been used as a feed additive for pigs, poultry full-price materials and ruminant concentrate. It is an indispensable additive. It not only has a significant effect on the growth, development and performance of livestock and poultry, but also can Enhance the physical and disease resistance of livestock and poultry.
  • Choline is a colorless liquid at room temperature, which is hygroscopic, alkaline and viscous.
  • Choline chloride is the hydrochloride salt of choline. The molecule has a polar tendency and is easy to absorb moisture in the air and deliquesce. Choline chloride is commonly used in the feed industry to replace choline. Compared with choline, choline chloride is more stable, its aqueous solution is neutral, and it has less stimulation on animal body tissues. However, the choline chloride crystal is very absorbent and easily agglomerates, which causes inconvenience to the processing, transportation and storage of feed.
  • Choline chloride has a destructive effect on other vitamins, especially in the presence of metal elements, it has a destructive effect on vitamins A, D3, E, K3, so it should not be mixed with vitamin premix, but it can be directly added to concentrated feed or compounded Go to the feed to minimize the chance of contacting choline chloride with other active ingredients.
  • Ruminants can synthesize choline to meet the needs of animals. Although choline is generally not lacking, when in pregnancy and lactation, choline in the body can not meet the needs of animals. Therefore, supplementing with sufficient choline can save the part of methionine consumed for the synthesis of choline, making more methionine available for milk production. At the same time, in the rumen of ruminants, choline will be degraded by ruminal microorganisms to acetaldehyde and trimethylamine, and further degraded to methane, with the animal belching. The degradation rate of choline is very high, and the degradation rate of choline chloride is as high as 98.6%, so it is often difficult for unprotected choline to pass through the rumen.
  • the invention patent with authorization announcement number CN101269051B discloses a rumen-passing choline chloride microcapsule and its preparation process.
  • the microcapsule contains choline chloride with a mass percentage of 35-45% as the main active ingredient as the core material.
  • Acrylic resin IV is used as the inner layer coating of the core material, and chitosan is used as the outer layer coating.
  • the quality of the inner and outer layer coatings is 3% to 5% of the core material.
  • the invention patent with authorization announcement number CN102630817B discloses a choline rumen microcapsule additive and a preparation method thereof.
  • the microcapsule additive includes a core and a surface layer wrapped on the surface of the core; the composition of the core is based on choline
  • the mixture of choline-based mixtures includes 83% -98.9% of choline chloride as the carrier, 1% -10% of polyacrylic resin IV and 0.1% -10% by weight percent Hypromellose.
  • the above documents provide a variety of processes for preparing rumen-choline chloride particles / microcapsules, the effective ingredients of the rumen-passing choline chloride particles / microcapsules prepared by the above process are low, or have been processed in the rumen.
  • the rumen rate is between 85% and 90% (24h), and the optimal release rate in the small intestine is less than 95%; and there is moisture absorption when placed for a long time, which is not easy to store for a long time.
  • the invention discloses a rumen-passing choline chloride microcapsule and a preparation method thereof.
  • the content of choline chloride in the rumen-passing choline chloride microcapsule can reach 75%, and the rumen-passing rate of the product (can reach 90 %) And the release rate (over 95%) are high, and can effectively deliver choline chloride to the small intestine and release it immediately, significantly improving the utilization efficiency of choline chloride for ruminants.
  • a rumen-passing choline chloride microcapsule comprising a core material composed of choline chloride and a carrier, an inner envelope and an outer envelope;
  • the raw material of the inner coating includes one or more vegetable fats with a melting point higher than 60 ° C;
  • the raw materials of the outer coating include rice bran wax, zinc oxide powder and film-forming materials; the film-forming materials are glucose phthalate, polyethylene glycol or sodium alginate;
  • the content of the rice bran wax is 5 to 10%, and the mass ratio of the rice bran wax, zinc oxide powder and film-forming material is 1 to 5: 0.1 to 1: 0.1 to 1.
  • the key of the present invention lies in the components of the inner envelope and the outer envelope.
  • the purity of the choline chloride used is not strictly required; of course, if the purity of the choline chloride used is ⁇ 99.5%, it is more conducive to improving The efficiency of ruminant utilization of choline chloride.
  • Various conventional carriers can be used as the carrier, for example: silica, corn starch, dextrin, etc.
  • the vegetable fat with a melting point higher than 60 ° C in the present invention refers to greater than or equal to 60 ° C.
  • Rice bran wax has good plasticity, which is beneficial to the formation of microcapsules; rice bran wax has a high melting point, can resist the degradation of rumen microorganisms and the mechanical pressure and temperature during the granulation process, and can delay the release or discharge of active substances.
  • Film-forming materials refer to materials such as glucose phthalate, polyethylene glycol and sodium alginate, which can prevent choline chloride from absorbing moisture and increase the rumen-passing rate of the active ingredient.
  • the combination of zinc oxide powder and rice bran wax can not only absorb moisture in the active ingredient during storage and application, but also maintain stability in the special environment of the rumen, and can be immediately in the small intestine after the microcapsules reach the small intestine. freed.
  • the particle size of the zinc oxide powder is 200-600 mesh; the particle size of the zinc oxide powder is small and the specific surface area is large, which can increase the contact surface area of the zinc oxide and the small intestinal fluid and accelerate the reaction of the zinc oxide powder and the small intestinal fluid ;
  • the particle size should be appropriate. If the zinc oxide powder is too fine, such as nano-zinc oxide, it is easy to cause the nano-zinc oxide to be dispersed in the rumen and small intestine and other organs, which is not conducive to the growth of cattle; The formed film is easily destroyed in the rumen, which affects the rumen-passing rate of the product. More preferably, the particle size of the zinc oxide powder is 300 to 500 mesh.
  • the effective content of the choline chloride is 20-75%.
  • the invention adopts specific inner and outer coating materials, so that the effective embedding content of choline chloride is significantly improved; even if the effective content of choline chloride is up to 75%, it will not cause the microcapsules to break, Furthermore, the utilization efficiency of choline chloride in ruminants is improved. More preferably, the effective content of the choline chloride is 30-75%. More preferably, the effective content of the choline chloride is 50-75%, and the microcapsules have the best stability at this effective content.
  • the carrier is silica.
  • the mass ratio of the choline chloride to the carrier is 1-2: 0.2-1.
  • Silica has good fluidity and adsorption, and can fully adsorb active substances.
  • the inner coating material needs to use vegetable fat whose melting point is higher than the rumen fermentation temperature, which is solid at normal temperature and does not melt in the rumen.
  • the raw material of the inner layer coating is at least one of carnauba wax, Xifeng wax or rice bran wax.
  • carnauba wax is more preferred, because the melting point of carnauba wax is 80-86 °C, and the hardness of carnauba wax is very high, which can maintain the hardness of the first coating particles , To prevent the rupture of microcapsules; Moreover, carnauba wax is non-toxic and harmless, and has the advantages of moisture resistance, oxidation resistance, good emulsification performance and good molding performance.
  • the content of the inner layer coating is 5-30% based on the mass percentage of the microcapsules. More preferably, the content of the inner layer envelope is 15-30% based on the mass percentage of the microcapsules.
  • the effective content of the choline chloride is 20-75%; the mass ratio of the choline chloride to the carrier is 1-2: 0.2-1; the inner layer package The content of the film is 5-30%; the rest is the outer coating.
  • the content of the rice bran wax is 5-10%
  • the content of zinc oxide powder is 1-10%
  • the film-forming material is glucose phthalate, the content is 1-10%.
  • Glucose phthalate is a carbohydrate derivative of phthalic acid. It is a coating material that is insoluble in water and lye and soluble in most enoic acids. It plays a film-forming role in the outer coating and helps The active substance is stable under alkaline conditions in the rumen, and is completely released after reaching the small intestine. It has been found through experiments that glucose phthalate is particularly suitable among various film-forming materials.
  • the components of the rumen-passing choline chloride microcapsules are: a core material composed of choline chloride and a carrier, an inner envelope and an outer envelope,
  • the raw material of the inner coating is one or more vegetable fats with a melting point higher than 60 ° C;
  • the raw material of the outer coating is rice bran wax, zinc oxide powder and film-forming material;
  • the film-forming material is glucose phthalate, polyethylene glycol or sodium alginate;
  • the content of the rice bran wax is 5 to 10%, and the mass ratio of the rice bran wax, zinc oxide powder and film-forming material is 1 to 5: 0.1 to 1: 0.1 to 1.
  • the rumen-passing choline chloride microcapsules include the following raw material components:
  • the raw material of the inner layer coating is one or more vegetable fats with a melting point higher than 60 ° C; the film-forming material is glucose phthalate, polyethylene glycol or sodium alginate.
  • the rumen-passing choline chloride microcapsules include the following raw material components:
  • the rumen-passing choline chloride microcapsules include the following raw material components:
  • the invention also provides a preparation method of the rumen-passing choline chloride microcapsules, which includes the following steps:
  • the organic solvent may be an organic solvent capable of dissolving fats such as absolute ethanol and isopropanol.
  • the organic solvent is recovered during the production process to avoid volatilization to the environment and does not affect the growth and production of animals, especially cattle.
  • the organic solvent is ethanol with a volume fraction of 75-85%.
  • the bottom spray coating can only be carried out after the rice bran wax, film-forming material and zinc oxide powder are dissolved with an organic solvent.
  • the bottom spray coating parameters are: flow rate 0.1-1L / min, inlet air temperature 50-90 °C, time 3-4h .
  • the present invention has the following beneficial effects:
  • the present invention uses rice bran wax, zinc oxide powder and film-forming materials as outer coating materials, which not only significantly improves the rumen-passing rate of rumen-passing choline chloride microcapsules in rumen and the small intestine The release rate also reduces the hygroscopicity of the product during storage and use, thereby effectively improving the efficiency of ruminant use of choline chloride.
  • the present invention cooperates with suitable inner coating materials to further promote the increase of rumen-passing rate and release rate, as well as the reduction of hygroscopicity.
  • the product prepared by adopting specific inner and outer coating materials and matching with the corresponding process conditions can significantly increase the effective content of choline chloride in rumen-passing choline chloride products, thereby improving rumination The efficiency of animal use of choline chloride.
  • the particle size of the zinc oxide powder used in the following examples is 400 mesh, and the following materials are all conventional commercial products.
  • a rumen-passing choline chloride microcapsule the raw material composition is as follows: choline chloride 25%; silica 25%; carnauba wax 30%; rice bran wax 10%; glucose phthalate 5%; zinc oxide powder 5%.
  • the rumen pass rate and intestinal juice dissolution rate of the product of this example were measured by the nylon bag degradation method, and the anti-moisture absorption effect of the product was investigated by observation method.
  • the degradation time it is divided into 6 treatments, which are 2h, 4h, 6h, 12h, 24h and 48h respectively.
  • the non-ruminal treatment is used as the control group (0h), each treatment is repeated 2 times, each time point is repeated Two parallel sample bags, each bag sample is 5g, and the remaining content of choline chloride at each time point is determined.
  • the dissolution of intestinal fluid was measured by freeze-dried powder method (FDI) of dairy cow intestinal fluid.
  • FDI freeze-dried powder method
  • the degradation rate showed a gradual increase trend with the extension of the treatment time.
  • %, 1.40%, 1.20% and 1.00% significantly lower than the 48h treated samples, indicating that the microencapsulated coating effectively relieved the release of choline chloride in the rumen and played a role in rumen protection, but in After 48h, the degradation rate has been significantly improved, which also suggests that in the subsequent different digestion stages, the coated choline chloride will be gradually released for the animal to make full use of absorption.
  • the rumen-passing rate of choline chloride was all above 98%, and the rumen-passing rate of choline chloride was 48.50% when treated for 48 hours. Judging from the physiological characteristics of dairy cows, the time for the rumen to pass through the rumen generally does not exceed 48h, which suggests that the rumen-passing effect of the rumen-passed choline chloride used in this study can fully meet the physiological requirements of dairy cows.
  • the product opening is placed indoors. After 24 hours, the product does not block and the fluidity is not affected.
  • a rumen-passing choline chloride microcapsule the raw material composition is as follows: choline chloride 50%; silica 25%; carnauba wax 15%; rice bran wax 5%; phthalate glucose 2.5%; zinc oxide powder 2.5%.
  • the product After testing, the product has a rumen-passing rate of 96.43% in 24 hours and a release rate of 94.33% in the intestine at 6 hours. It does not absorb moisture after 24 hours of exposure and has good fluidity.
  • a rumen-passing choline chloride microcapsule the raw material composition is as follows: choline chloride 75%; silica 10%; carnauba wax 5%; rice bran wax 5%; phthalate glucose 2.5%; zinc oxide powder 2.5%.
  • the product After testing, the product has a rumen-passing rate of 95.90% in 24 hours and a release rate of 94.95% in the intestine at 6 hours. It does not absorb moisture after 24 hours of exposure and has good fluidity.
  • the rice bran wax is 125 kg and the phthalate glucose is 75 kg.
  • the remaining raw materials and production process are the same as in Example 1.
  • the product has been tested for a rumen-passing rate of 79.33% at 24 hours and a release rate of 72.35% at 6 hours in the intestine. It does not absorb moisture after 24 hours of open exposure and has good fluidity.
  • the product has been tested for a rumen pass rate of 70.07% at 24 hours and a release rate of 85.00% at 6 hours in the intestine. It does not absorb moisture after 24 hours of open exposure and has good fluidity.
  • the rumen-fat powder was used instead of rice bran wax (the dosage is still 100kg), except for zinc oxide powder of 50kg and glucose phthalate of 50kg.
  • the remaining raw materials and production process are the same as in Example 1. .
  • the product has been tested for a rumen-passing rate of 75.37% at 24 hours and a release rate of 94.86% at 6 hours in the intestine. It does not absorb moisture after 24 hours of exposure and has good fluidity.
  • the raw material of the outer layer coating uses hydrogenated palm oil instead of rice bran wax (the dosage is still 100 kg), the zinc oxide powder is 50 kg, and the phthalic acid glucose is 50 kg.
  • the remaining raw materials and production processes are the same as in Example 1.
  • the product has been tested for a rumen pass rate of 82.65% for 24 hours and a release rate of 94.75% for 6 hours in the intestine. It does not absorb moisture after 24 hours of exposure and has good fluidity.
  • the product has been tested for a rumen-passing rate of 95.32% at 24 hours and a 95.47% release rate at 6 hours in the intestine. After 24 hours of open exposure, the product has a hygroscopic phenomenon, particles stick, and poor fluidity.
  • the product has been tested to have a rumen-passing rate of 94.73% at 24 hours and a release rate of 93.53% at 6 hours in the intestine. After 24 hours of open exposure, there is moisture absorption, particles sticking, and poor fluidity.
  • a rumen-passing choline chloride microcapsule the raw material composition is as follows: choline chloride 50%; silica 10%; carnauba wax 5%; rice bran wax 10%; glucose phthalate 5%; zinc oxide powder 20%.
  • the product has been tested for a rumen-passing rate of 85.17% at 24 hours and a 96.65% release rate at 6 hours in the intestine. After 24 hours of open exposure, the product has moisture absorption, particle adhesion, and poor fluidity.
  • This example is the same as Example 1 except that Xifeng wax is used instead of carnauba wax in the inner coating raw material.
  • the product After testing, the product has a rumen-passing rate of 90.11% at 24 hours and a release rate of 94.97% at 6 hours in the intestine. After 24 hours of open exposure, it does not absorb moisture and has good fluidity.
  • This example is the same as Example 1 except that rice bran wax is used instead of carnauba wax in the inner coating raw material.
  • the product has been tested for a rumen-passing rate of 92.97% at 24 hours and a release rate of 90.45% in the intestine at 6 hours. It does not absorb moisture after 24 hours of exposure and has good fluidity.
  • Example 3 On the basis of Example 1, the types and amounts of raw materials were adjusted to obtain the following example cases and results (Table 3):

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Abstract

一种过瘤胃氯化胆碱微胶囊及其制备方法，该微胶囊包括由氯化胆碱和载体组成的芯材、内层包膜和外层包膜，内层包膜的原料包括一种或一种以上熔点高于60℃的植物脂肪；所述外层包膜的原料包括米糠蜡、氧化锌粉末和成膜材料；所述成膜材料为邻苯二甲酸葡萄糖、聚乙二醇或海藻酸钠；所述米糠蜡的含量为5-10%，米糠蜡、氧化锌粉末和成膜材料的质量比为1-5: 0.1-1: 0.1-1。采用米糠蜡、氧化锌粉末和成膜材料作为外层包膜的原料，不仅显著提高了过瘤胃氯化胆碱微胶囊在反刍动物瘤胃中的过瘤胃率和在小肠中的释放率，还降低了产品在存放和使用过程中的吸湿性，从而有效提高了反刍动物对氯化胆碱的利用效率。

Description

一种过瘤胃氯化胆碱微胶囊及其制备方法 技术领域
本发明涉及饲料添加剂技术领域，尤其涉及一种过瘤胃氯化胆碱微胶囊及其制备方法。
背景技术
胆碱是一种B族维生素，化学名称为羟乙基三甲胺。其生物学功能较多，包括：磷脂组成部分，参与组成卵磷脂和鞘磷脂等；不稳定的甲基基团供体；调节肝脏脂肪代谢中起重要作用；合成乙酰胆碱的主要成分。目前胆碱作为一种饲料添加剂已被用于猪、禽全价料及反刍动物精料，是一种必不可少的添加物质，不仅对畜禽的生长、发育、性能提高具有显著效果，还可以增强畜禽的体质和抗病能力。
胆碱常温下为无色液体，具有吸湿性、吸碱性和粘滞性。氯化胆碱是胆碱的盐酸盐，分子具有极性倾向，极易吸收空气中的水分而潮解。饲料工业中常用氯化胆碱来替代胆碱，与胆碱相比，氯化胆碱稳定性更高，其水溶液呈中性，对动物体组织刺激较小。但氯化胆碱晶体吸水性很强易结块，给饲料的加工、运输和贮存带来不便。氯化胆碱对其他维生素有破坏作用，尤其是在金属元素存在时，对维生素A、D3、E、K3有破坏作用，所以不宜与维生素预混料相混，但可以直接加入浓缩饲料或配合饲料中去，以尽量减少氯化胆碱与其他活性成分的接触机会。
反刍动物体内能合成胆碱，以满足动物的需要。尽管胆碱一般是不会缺乏的，但是当处于妊娠和泌乳期时，体内的胆碱则无法满足动物的需要。因此，补充充足的胆碱可以节省用于合成胆碱所消耗蛋氨酸部分，使得更多的蛋氨酸可用于产奶需要。同时在反刍动物瘤胃内，胆碱会被瘤胃微生物降解为乙醛和三甲胺，并进一步降解为甲烷，随动物嗳气排出。胆碱的降解率很高，其中氯化胆碱的降解率高达98.6％，因此未保护的氯化胆碱常常难以通过瘤胃。
授权公告号为CN101269051B的发明专利公开了一种过瘤胃氯化胆碱微胶囊及其制备工艺，该微胶囊以含有质量百分比为35～45％氯化胆碱为主要的有效成份作为芯材，以丙烯酸树脂IV作为芯材的内层包衣，壳聚糖作为外层包衣，所述内、外层包衣质量均为芯材质量的3～5％。
授权公告号为CN102630817B的发明专利公开了一种胆碱过瘤胃微胶囊添加剂及其制备方法，该微胶囊添加剂包括内核以及包裹在所述内核表面的表面层；所述内核的成分为基于胆碱的混合物，所述基于胆碱的混合物按其重量百分比计包括 83％～98.9％的二氧化硅为载体的氯化胆碱、1％～10％的聚丙烯酸树脂Ⅳ号和0.1％～10％的羟丙甲纤维素。
虽然，上述文献提供了多种制备过瘤胃氯化胆碱颗粒/微囊的工艺，但是，上述工艺制得的过瘤胃氯化胆碱颗粒/微囊的有效成分低，或者在瘤胃中的过瘤胃率在85％～90％之间(24h)，在小肠中的最佳释放率低于95％；并且长时间放置时有吸潮现象，不易长时间存放。
因此，有必要进一步深入研究提供一种生产更为方便、过瘤胃效果更佳的氯化胆碱包膜技术，为行业提供一种有效成分高，过瘤胃效果好，应用过程不吸潮，到达肠道能够迅速释放的组分安全的包膜氯化胆碱产品。
发明内容
本发明公开了一种过瘤胃氯化胆碱微胶囊及其制备方法，该过瘤胃氯化胆碱微胶囊中氯化胆碱的含量可达到75％，且产品的过瘤胃率(可以达到90％以上)和释放率(达到95％以上)均较高，能将氯化胆碱有效输送到小肠中并立即释放，显著提高反刍动物对氯化胆碱的利用效率。
具体技术方案如下：
一种过瘤胃氯化胆碱微胶囊，包括由氯化胆碱和载体组成的芯材、内层包膜和外层包膜；
所述内层包膜的原料包括一种或一种以上熔点高于60℃的植物脂肪；
所述外层包膜的原料包括米糠蜡、氧化锌粉末和成膜材料；所述成膜材料为邻苯二甲酸葡萄糖、聚乙二醇或海藻酸钠；
以微胶囊的质量百分数计，所述米糠蜡的含量为5～10％，米糠蜡、氧化锌粉末和成膜材料的质量比为1～5：0.1～1：0.1～1。
本发明的关键在于内层包膜和外城包膜的组分，所用氯化胆碱的纯度不做严格要求；当然，若所用的氯化胆碱的纯度≥99.5％，则更有利于提高反刍动物对氯化胆碱的利用效率。载体可以采用多种常规载体，例如：二氧化硅，玉米淀粉，糊精等。本发明所述的熔点高于60℃的植物脂肪是指大于等于60℃。
米糠蜡具有良好的可塑性，有利于微胶囊的成型；米糠蜡熔点较高，能够抵抗瘤胃微生物的降解及制粒加工过程中的机械压力和温度的破坏，同时能延缓活性物质的释放或排出。成膜材料是指如邻苯二甲酸葡萄糖、聚乙二醇和海藻酸钠等，能够防止氯化胆碱吸潮，提高有效成分的过瘤胃率的材料。
经试验发现，氧化锌粉末与米糠蜡之间形成紧密的薄膜，氧化锌粉末嵌入至米糠蜡形成的薄膜内；氧化锌粉末在碱性环境的瘤胃中能够保持稳定，有利于帮助米糠蜡减小所受到的机械损伤，抵抗瘤胃微生物的降解，进而提高外层包膜在瘤胃中的稳定 性；而到达小肠后，氧化锌粉末与酸性的小肠液迅速反应，使米糠蜡形成的薄膜表面形成无数细孔，促使有效成分氯化胆碱的快速释放。所以，氧化锌粉末与米糠蜡的合用，既能有效成分在存放和应用过程中不吸潮，且在瘤胃这种特殊的环境中保持稳定，又能待微胶囊到达小肠后，在小肠中立即释放。
当外层包膜原料中缺少氧化锌时，不仅过瘤胃氯化胆碱微胶囊的过瘤胃率会受到影响，而且肠液溶出率也会受到影响。
进一步地，所述氧化锌粉末的粒径为200～600目；氧化锌粉末的粒径小，比表面积大，可提高氧化锌与小肠液的接触表面积，加快了氧化锌粉末与小肠液的反应；但是，粒径应当适宜，若氧化锌粉末过细，如纳米氧化锌则容易造成纳米氧化锌弥散于瘤胃和小肠等器官中，不利于牛的生长；若过粗，则氧化锌粉末与米糠蜡形成的薄膜在瘤胃中容易被破坏，影响产品的过瘤胃率。更优选，氧化锌粉末的粒径为300～500目。
进一步地，以微胶囊的质量百分数计，所述氯化胆碱的有效含量为20～75％。本发明因采用了特定的内、外层包膜原料，使得氯化胆碱的有效包埋含量得到显著提高；即便氯化胆碱的有效含量高达75％，也不会造成微胶囊的破裂，进而提高了反刍动物对氯化胆碱的利用效率。更优选，所述氯化胆碱的有效含量为30～75％。更优选，所述氯化胆碱的有效含量为50～75％，该有效含量下微胶囊稳定性最佳。
作为优选，所述载体为二氧化硅。作为优选，所述氯化胆碱与载体质量比为1～2：0.2～1。二氧化硅具有较好的流动性和吸附性，能充分吸附活性物质。
内层包膜材料需采用熔点高于瘤胃发酵温度，常温下为固态且在瘤胃内不熔化的植物脂肪。作为优选，所述内层包膜的原料为巴西棕榈蜡、西峰蜡或米糠蜡中的至少一种。
为确保内层包膜有一定的硬度，更优选巴西棕榈蜡，其原因是：巴西棕榈蜡的熔点在80-86℃，同时巴西棕榈蜡硬度非常高，可以保持第一次包膜颗粒的硬度，防止微胶囊的破裂；而且，巴西棕榈蜡无毒无害，且具有防潮、防氧化、乳化性能良好和成型性能良好的优点。
作为优选，以微胶囊的质量百分数计，所述内层包膜的含量为5～30％。更优选，以微胶囊的质量百分数计，所述内层包膜的含量为15-30％。
作为优选，以微胶囊的质量百分数计，所述氯化胆碱的有效含量为20～75％；所述氯化胆碱与载体质量比为1～2：0.2～1；所述内层包膜的含量为5～30％；其余为外层包膜。
作为优选，所述米糠蜡的含量为5～10％，氧化锌粉末的含量为1～10％，成膜材料为邻苯二甲酸葡萄糖，含量为1～10％。
邻苯二甲酸葡萄糖属于邻苯二甲酸的糖类衍生物，是一种不溶于水和碱液，溶于 多数烯酸的包膜材料，在外层包膜中起到膜成膜作用，有助于活性物质在瘤胃碱性条件下稳定，到达小肠后完全释放。经试验发现，在多种成膜材料中，邻苯二甲酸葡萄糖尤为适合。
作为优选，所述过瘤胃氯化胆碱微胶囊的组分为：由氯化胆碱和载体组成的芯材、内层包膜和外层包膜，
所述内层包膜的原料为一种或一种以上熔点高于60℃的植物脂肪；
所述外层包膜的原料为米糠蜡、氧化锌粉末和成膜材料；所述成膜材料为邻苯二甲酸葡萄糖、聚乙二醇或海藻酸钠；
以微胶囊的质量百分数计，所述米糠蜡的含量为5～10％，米糠蜡、氧化锌粉末和成膜材料的质量比为1～5：0.1～1：0.1～1。
作为优选，所述过瘤胃氯化胆碱微胶囊，以质量百分数计，包括以下原料组分：
Figure PCTCN2019107649-appb-000001
所述内层包膜的原料为一种或一种以上熔点高于60℃的植物脂肪；所述成膜材料为邻苯二甲酸葡萄糖、聚乙二醇或海藻酸钠。
作为优选，所述过瘤胃氯化胆碱微胶囊，以质量百分数计，包括以下原料组分：
Figure PCTCN2019107649-appb-000002
进一步优选，所述过瘤胃氯化胆碱微胶囊，以质量百分数计，包括以下原料组分：
Figure PCTCN2019107649-appb-000003
或者，
Figure PCTCN2019107649-appb-000004
或者，
Figure PCTCN2019107649-appb-000005
本发明还提供了所述过瘤胃氯化胆碱微胶囊的制备方法，包括以下步骤：
(1)将氯化胆碱与载体进行混合，再与液态的内层包膜原料混合，搅拌均匀后，利用冷冻喷雾干燥法进行制粒，得到一级包膜颗粒；
(2)把米糠蜡、成膜材料溶解于有机溶剂中，再加入氧化锌粉末形成混合溶液，对一级包膜颗粒进行底喷包衣，得到过瘤胃氯化胆碱微胶囊。
所述有机溶剂可以是无水乙醇、异丙醇等能够溶解脂肪类的有机溶剂，生产过程有机溶剂经过回收，避免挥发到环境中，且不会影响动物特别是牛的生长和生产。具体地，所述有机溶剂为体积分数75-85％的乙醇。采用有机溶剂将米糠蜡、成膜材料和氧化锌粉末溶解后才能够进行底喷包衣，底喷包衣参数为：流速0.1-1L/min，进风温度50-90℃，时间3-4h。
与现有技术相比，本发明具有以下有益效果：
(1)本发明采用米糠蜡、氧化锌粉末和成膜材料作为外层包膜的原料，不仅显著提高了过瘤胃氯化胆碱微胶囊在反刍动物瘤胃中的过瘤胃率和在小肠中的释放率，还降低了产品在存放和使用过程中的吸湿性，从而有效提高了提高反刍动物对氯化胆碱的利用效率。
(2)本发明在采用特定外层包膜原料的基础上，配合适宜的内层包膜原料，进一步促进了产品过瘤胃率和释放率的提升，以及吸湿性的降低。
(3)本发明通过采用特定的内、外层包膜原料，并配合相应工艺条件制备获得的产品可显著提高了过瘤胃氯化胆碱产品中氯化胆碱的有效含量，进而提高了反刍动物对氯化胆碱的利用效率。
具体实施方式
下面结合具体实施例对本发明作进一步描述，以下列举的仅是本发明的具体实施例，但本发明的保护范围不仅限于此。
下列实施例中采用的氧化锌粉末粒径为400目，以下材料均为常规市售产品。
实施例1
一种过瘤胃氯化胆碱微胶囊，原料组成如下：氯化胆碱25％；二氧化硅25％；巴西棕榈蜡30％；米糠蜡10％；邻苯二甲酸葡萄糖5％；氧化锌粉末5％。
具体制备工艺如下：
(1)取250kg氯化胆碱，粉碎后，与250kg二氧化硅混合均匀，得到混合物I；
(2)取300kg巴西棕榈蜡置于反应釜内熔化，并在高于其熔点20℃的温度下进行保温；再将熔化后的巴西棕榈蜡与混合物I进行混合，充分搅拌均匀，喷入冷冻室进行低温(8℃)冷冻干燥，得到一级包膜颗粒；
(3)将100kg米糠蜡、50kg邻苯二甲酸葡萄糖溶于500L的75％(体积分数)乙醇溶液中，再加入50kg氧化锌粉末，得到混合溶液II；再将一级包膜颗粒置于旋流流化床中，同时喷入混合溶液II，得到的产品过20目分析筛后，即得氯化胆碱有效含量为25％(质量分数)的过瘤胃氯化胆碱。
采用尼龙袋降解法测定本实施例产品的过瘤胃率、肠液溶出率，采用观察法考察产品的防吸潮效果。
试验内容：
按照降解时间分为6个处理，分别为2h、4h、6h、12h、24h和48h，以未经瘤胃处理的为对照组(0h)，每个处理2个重复，每个重复每个时间点2个平行样品袋，每袋样品为5g，测定各时间点的氯化胆碱剩余含量。同时采用奶牛小肠液冻干粉法(FDI)测定肠液中的溶出度。取适量的FDI置于含有30ml缓冲液的酶解管中；称取5g样品置于小尼龙袋后，再放入酶解管中；将酶解管放在39℃恒温水浴摇床上振荡；分别在培养到0，2，4，6，12，24，48h时取出测定。测定不同时间点样品的氯化胆碱含量，测定方法参照中华人民共和国化工行业标准《饲料添加剂——氯化胆碱》(HB2941-1999)规定检测。在外界室温条件下放置，分别12，24h取样，用观察法考察产品的防吸潮性能。
试验结果：
表1过瘤胃氯化胆碱过瘤胃率
Figure PCTCN2019107649-appb-000006
Figure PCTCN2019107649-appb-000007
由表1可见，经过瘤胃处理后，随着处理时间的延长，降解率呈现逐渐升高趋势，在瘤胃处理48h时损失达到14.40％，其他各处理时间点的干重损失分别为0.40％、1.40％、1.40％、1.20％和1.00％，明显低于48h处理样品，表明微囊化包被处理后，有效缓解了氯化胆碱在瘤胃内的释放，起到了过瘤胃保护的作用，但在48h后降解率有了明显的提高，也提示了在后续的不同消化阶段，包被氯化胆碱将逐步释放，供动物充分利用吸收。瘤胃处理24h以内，氯化胆碱的过瘤胃率均在98％以上，处理48h时氯化胆碱的过瘤胃率为85.50％。从奶牛生理特点来看，精料过瘤胃的时间一般不超过48h，由此提示本研究中采用的过瘤胃氯化胆碱的过瘤胃效果完全可以达到奶牛的生理要求。
表2过瘤胃氯化胆碱肠液溶出率
Figure PCTCN2019107649-appb-000008
由表2可见，经过肠液处理后，随着处理时间的延长，过瘤胃氯化胆碱干重迅速下降，到4h以内过瘤胃氯化胆碱的达到80％以上，6h以后基本均被肠液所分解，无明显差异。从肠液处理的溶出率来看，过瘤胃氯化胆碱的消化溶出趋势与干重下降趋势一致，随着处理时间的延长，过瘤胃保护的氯化胆碱迅速分解溶出，供动物营养所需。以上结果表明：过瘤胃处理的氯化胆碱不影响氯化胆碱在肠道中的释放和奶牛对氯化胆碱的营养需求。在肠液中处理4h的溶出率为83.10％，6h的溶出率为94.23％。表明本研究采用的过瘤胃氯化胆碱在肠道中4-6h可释放90％以上，完全可以满足奶牛对氯化胆碱的消化吸收要求。
产品敞口放置在室内，经过24h后，产品不发生粘连现象，流动性不受影响。
实施例2
一种过瘤胃氯化胆碱微胶囊，原料组成如下：氯化胆碱50％；二氧化硅25％；巴西棕榈蜡15％；米糠蜡5％；邻苯二甲酸葡萄糖2.5％；氧化锌粉末2.5％。
具体制备工艺如下：
(1)取500kg氯化胆碱，粉碎后，与250kg二氧化硅混合均匀，得到混合物I；
(2)取150kg巴西棕榈蜡置于反应釜内熔化，并在高于其熔点20℃的温度下进行保温；再将熔化后的巴西棕榈蜡与混合物I进行混合，充分搅拌均匀，喷入冷冻室进行低温(8℃)冷冻干燥，得到一级包膜颗粒；
(3)将50kg米糠蜡、25kg邻苯二甲酸葡萄糖溶于500L的75％(体积分数)乙醇溶液中，再加入25kg氧化锌粉末，得到混合溶液II；再将一级包膜颗粒置于旋流流化床中，同时喷入混合溶液II，得到的产品过20目分析筛后，即得氯化胆碱有效含量为50％(质量分数)的过瘤胃氯化胆碱。
该产品经检测，24小时的过瘤胃率为96.43％，在肠道6小时的释放率为94.33％，经过24小时敞口放置后不吸潮，流动性好。
实施例3
一种过瘤胃氯化胆碱微胶囊，原料组成如下：氯化胆碱75％；二氧化硅10％；巴西棕榈蜡5％；米糠蜡5％；邻苯二甲酸葡萄糖2.5％；氧化锌粉末2.5％。
具体制备工艺如下：
(1)取750kg氯化胆碱，粉碎后，与100kg二氧化硅混合均匀，得到混合物I；
(2)取50kg巴西棕榈蜡置于反应釜内熔化，并在高于其熔点20℃的温度下进行保温；再将熔化后的巴西棕榈蜡与混合物I进行混合，充分搅拌均匀，喷入冷冻室进行低温(8℃)冷冻干燥，得到一级包膜颗粒；
(3)将50kg米糠蜡、25kg邻苯二甲酸葡萄糖溶于500L的75％(体积分数)乙醇溶液中，再加入25kg氧化锌粉末，得到混合溶液II；再将一级包膜颗粒置于旋流流化床中，同时喷入混合溶液II，得到的产品过20目分析筛后，即得氯化胆碱有效含量为75％(质量分数)的过瘤胃氯化胆碱。
该产品经检测，24小时的过瘤胃率为95.90％，在肠道6小时的释放率为94.95％，经过24小时敞口放置后不吸潮，流动性好。
对比例1
本对比例除外层包膜原料中缺少氧化锌粉末，米糠蜡为125kg，邻苯二甲酸葡萄糖为75kg外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为79.33％，在肠道6小时的释放率为72.35％，经过24小时敞口放置后不吸潮，流动性好。
对比例2
本对比例除外层包膜原料中缺少米糠蜡，氧化锌为100kg，邻苯二甲酸葡萄糖为100kg外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为70.07％，在肠道6小时的释放率为85.00％，经过24小时敞口放置后不吸潮，流动性好。
对比例3
本对比例除外层包膜原料中采用过瘤胃脂肪粉替代米糠蜡(用量仍为100kg)，氧化锌粉末为50kg，邻苯二甲酸葡萄糖为50kg外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为75.37％，在肠道6小时的释放率为94.86％，经过24小时敞口放置后不吸潮，流动性好。
对比例4
本对比例除外层包膜原料中采用氢化棕榈油替代米糠蜡(用量仍为100kg)，氧化锌粉末为50kg，邻苯二甲酸葡萄糖为50kg外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为82.65％，在肠道6小时的释放率为94.75％，经过24小时敞口放置后不吸潮，流动性好。
实施例4
本实施例除外层包膜原料中使用聚乙二醇替代邻苯二甲酸葡萄糖外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为95.32％，在肠道6小时的释放率为95.47％，经过24小时敞口放置后有吸潮现象，颗粒粘连，流动性差。
实施例5
本实施例除外层包膜原料中使用海藻酸钠替代邻苯二甲酸葡萄糖外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为94.73％，在肠道6小时的释放率为93.53％，经过24小时敞口放置后有吸潮现象，颗粒粘连，流动性差。
对比例5
一种过瘤胃氯化胆碱微胶囊，原料组成如下：氯化胆碱50％；二氧化硅10％；巴西棕榈蜡5％；米糠蜡10％；邻苯二甲酸葡萄糖5％；氧化锌粉末20％。
具体制备工艺如下：
(1)取500kg氯化胆碱，粉碎后，与100kg二氧化硅混合均匀，得到混合物I；
(2)取50kg巴西棕榈蜡置于反应釜内熔化，并在高于其熔点20℃的温度下进行保温；再将熔化后的巴西棕榈蜡与混合物I进行混合，充分搅拌均匀，喷入冷冻室进行低温(8℃)冷冻干燥，得到一级包膜颗粒；
(3)将100kg米糠蜡、50kg邻苯二甲酸葡萄糖溶于500L的75％(体积分数)乙醇溶液中，再加入200kg氧化锌粉末，得到混合溶液II；再将一级包膜颗粒置于旋流流化床中，同时喷入混合溶液II，得到的产品过20目分析筛后，即得氯化胆碱有效含量为50％(质量分数)的过瘤胃氯化胆碱。
该产品经检测，24小时的过瘤胃率为85.17％，在肠道6小时的释放率为96.65％，经过24小时敞口放置后有吸潮现象，颗粒粘连，流动性差。
实施例6
本实施例除内层包膜原料中使用西峰蜡替代巴西棕榈蜡外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为90.11％，在肠道6小时的释放率为94.97％，经过24小时敞口放置后不吸潮，流动性好。
实施例7
本实施例除内层包膜原料中使用米糠蜡替代巴西棕榈蜡外，其余原料及生产工艺均与实施例1相同。
该产品经检测，24小时的过瘤胃率为92.97％，在肠道6小时的释放率为90.45％，经过24小时敞口放置后不吸潮，流动性好。
实施例8～10
在实施例1的基础上，调整原料类型和用量，得到如下实施例案例和结果(表3)：
表3
Figure PCTCN2019107649-appb-000009
Figure PCTCN2019107649-appb-000010

Claims (13)

  1. 一种过瘤胃氯化胆碱微胶囊，包括由氯化胆碱和载体组成的芯材、内层包膜和外层包膜，其特征在于：
    所述内层包膜的原料包括一种或一种以上熔点高于60℃的植物脂肪；
    所述外层包膜的原料包括米糠蜡、氧化锌粉末和成膜材料；所述成膜材料为邻苯二甲酸葡萄糖、聚乙二醇或海藻酸钠；
    以微胶囊的质量百分数计，所述米糠蜡的含量为5～10％，米糠蜡、氧化锌粉末和成膜材料的质量比为1～5:0.1～1:0.1～1。
  2. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，以微胶囊的质量百分数计，所述氯化胆碱的有效含量为20～75％。
  3. 如权利要求2所述的过瘤胃氯化胆碱微胶囊，其特征在于，所述载体为二氧化硅；所述氯化胆碱与载体质量比为1～2:0.2～1。
  4. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，所述内层包膜的原料为：巴西棕榈蜡、西峰蜡或米糠蜡中的至少一种。
  5. 如权利要求4所述的过瘤胃氯化胆碱微胶囊，其特征在于，以微胶囊的质量百分数计，所述内层包膜的含量为5～30％。
  6. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，以微胶囊的质量百分数计，所述氯化胆碱的有效含量为20～75％；所述氯化胆碱与载体质量比为1～2：0.2～1；所述内层包膜的含量为5～30％；其余为外层包膜。
  7. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，所述米糠蜡的含量为5～10％，氧化锌粉末的含量为1～10％，成膜材料为邻苯二甲酸葡萄糖，含量为1～10％。
  8. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，所述氧化锌粉末的粒径为200～600目。
  9. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，以质量百分数计，包括以下原料组分：
    Figure PCTCN2019107649-appb-100001
    所述内层包膜的原料为一种或一种以上熔点高于60℃的植物脂肪；所述成膜材料 为邻苯二甲酸葡萄糖、聚乙二醇或海藻酸钠。
  10. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，以质量百分数计，包括以下原料组分：
    Figure PCTCN2019107649-appb-100002
  11. 如权利要求1所述的过瘤胃氯化胆碱微胶囊，其特征在于，以质量百分数计，包括以下原料组分：
    Figure PCTCN2019107649-appb-100003
  12. 如权利要求1～11任一项所述的过瘤胃氯化胆碱微胶囊的制备方法，其特征在于，包括以下步骤：
    (1)将氯化胆碱与载体进行混合，再与液态的内层包膜原料混合，搅拌均匀后，利用冷冻喷雾干燥法进行制粒，得到一级包膜颗粒；
    (2)把米糠蜡、成膜材料溶解于有机溶剂中，再加入氧化锌粉末形成混合溶液，对一级包膜颗粒进行底喷包衣，得到过瘤胃氯化胆碱微胶囊。
  13. 如权利要求12所述的制备方法，其特征在于，步骤(2)中，所述底喷包衣的流速为0.1-1L/min，进风温度为50-90℃，时间为3-4h。
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