CN103169823B - Veterinary drug composition, application, preparation and preparation method for preventing and treating mycotoxin poisoning - Google Patents
Veterinary drug composition, application, preparation and preparation method for preventing and treating mycotoxin poisoning Download PDFInfo
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- CN103169823B CN103169823B CN201310136059.9A CN201310136059A CN103169823B CN 103169823 B CN103169823 B CN 103169823B CN 201310136059 A CN201310136059 A CN 201310136059A CN 103169823 B CN103169823 B CN 103169823B
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Abstract
Description
技术领域technical field
本发明涉及一种兽药组合物、制剂及其制备方法,具体涉及一种防治霉菌毒素中毒的兽药组合物、制剂及其制备方法。The invention relates to a veterinary drug composition, a preparation and a preparation method thereof, in particular to a veterinary drug composition, a preparation and a preparation method thereof for preventing and treating mycotoxin poisoning.
背景技术Background technique
霉菌是丝状真菌的统称,它们往往能形成分枝繁茂的菌丝体,但又不像蘑菇那样产生大型的子实体;其大致按属性可分为曲霉菌(Asperquillus)、青霉菌(Penicillium)、镰孢霉菌(Fusarum)等。霉菌毒素则是霉菌在谷物、食品和饲料上生长繁殖过程中产生的代谢产物,例如镰刀菌毒素和黄曲霉毒素。霉菌毒素通常是小分子物质,分子量常常在几百到几千道尔顿,并且其没有抗性,属于热稳定性物质,不会因简单加热而受到破坏,从而常常引起畜禽或人体出现霉菌毒素中毒现象。Mold is a general term for filamentous fungi, which tend to form branched and luxuriant mycelia, but do not produce large fruiting bodies like mushrooms; they can be roughly divided into Asperquillus (Asperquillus), Penicillium (Penicillium) , Fusarum (Fusarum), etc. Mycotoxins are metabolites produced during the growth and reproduction of molds on grains, food and feed, such as fusarium toxins and aflatoxins. Mycotoxins are usually small molecular substances with a molecular weight of several hundred to several thousand Daltons, and they have no resistance and are thermally stable substances that will not be destroyed by simple heating, which often cause mold in livestock, poultry or humans Toxin poisoning phenomenon.
一种霉菌可以产生多种霉菌毒素,而同一种霉菌毒素也可以由几种霉菌产生。到目前为止,已分离出几十种被公认为对畜禽和人体健康有危害的霉菌毒素;在饲料产品中常见的且对养殖业造成严重损害的霉菌毒素有黄曲霉毒素(aflatoxins,AF)、单端孢菌毒素(trichothecenes)(包括呕吐毒素和T-2毒素)、玉米赤霉烯酮(zearalenone,ZEN)、赭曲霉毒素A(ochratoxin,OT)、烟曲霉毒素(fumonisins,FUM)和麦角毒素(ergotoxin,ERG)等。One mold can produce multiple mycotoxins, and the same mycotoxin can also be produced by several molds. So far, dozens of mycotoxins that are recognized as harmful to livestock and human health have been isolated; the mycotoxins that are common in feed products and cause serious damage to the breeding industry include aflatoxins (AF) , trichothecenes (including vomitoxin and T-2 toxin), zearalenone (ZEN), ochratoxin A (ochratoxin, OT), fumonisins (fumonisins, FUM) and Ergot toxin (ergotoxin, ERG) and so on.
上述几种霉菌毒素普遍存在于饲料及饲料原料中,对畜禽养殖和人体健康常常会造成严重的危害,并且带来巨大的经济损失。由于在畜禽养殖过程中,畜禽对饲料的摄取是连续的,霉菌毒素会不断被累计,即使是单一重量的饲料中的霉菌毒素仅仅是微量组分,但通过一段时间的蓄积作用同样可达到致病或致死量。The above-mentioned mycotoxins are commonly found in feed and feed materials, which often cause serious harm to livestock and poultry breeding and human health, and bring huge economic losses. Since the intake of feed by livestock and poultry is continuous during the breeding process of livestock and poultry, mycotoxins will continue to accumulate. Even if the mycotoxins in a single weight of feed are only trace components, they can also be accumulated after a period of time. reach pathogenic or lethal doses.
现有除去动物饲料中的霉菌毒素的方法中一般为使用传统的霉菌毒素吸附剂或者是生物脱霉剂;前者吸附剂虽然可以吸附部分的霉菌毒素,但其还会吸附饲料中的营养物质;而后者生物脱霉剂则由于自身稳定性较差,不耐热不耐酸等原因较难得到推广。The existing methods for removing mycotoxins in animal feed generally use traditional mycotoxin adsorbents or biological mold removers; although the former adsorbent can adsorb part of mycotoxins, it can also adsorb nutrients in the feed; The latter biological mold remover is difficult to be popularized due to poor self-stability, heat resistance and acid resistance.
现有另外一种方法为采用中药复方来防止霉菌毒素引起的病变。现有防治霉菌毒素中毒的中药复方一般为采用保肝和对肝功有恢复作用的中药组合物,其防治机理为:其中的药效成分被畜禽吸收后与畜禽已吸收进血液的霉菌毒素结合,然后将毒素运入肝脏解毒后再排出体外;中药复方可将已吸收入体内的霉菌毒素进行清除,同时其药效成分还可以有效的对抗霉菌毒素等引起的肝脏损伤等病变。但是,到目前为止,仍没有可以有效对霉菌毒素的中毒现象明显缓解或防治作用的中药复方,尤其是黄曲霉毒素导致的中毒现象。Another existing method is to use traditional Chinese medicine compound to prevent the lesions caused by mycotoxins. The existing traditional Chinese medicine compound for the prevention and treatment of mycotoxin poisoning is generally a traditional Chinese medicine composition that protects the liver and restores liver function. The toxins are combined, and then the toxins are transported into the liver for detoxification and then excreted from the body; the Chinese medicine compound can remove the mycotoxins that have been absorbed into the body, and its medicinal ingredients can also effectively fight against liver damage and other diseases caused by mycotoxins. However, so far, there is still no traditional Chinese medicine compound that can effectively alleviate or prevent mycotoxin poisoning, especially the poisoning caused by aflatoxin.
黄曲霉毒素是目前引起畜禽霉菌毒素致病的重要原因之一,其毒性往往较其他的霉菌毒素较大;同时,黄曲霉毒素致病的机理为直接对畜禽的肝脏产生实质的病理损伤,表现为生长性能降低、消化能力下降、肝酶指标升高、氧化应激升高等,甚至可能导致肝硬化或肝癌变。因此,黄曲霉毒素对于畜禽养殖业的威胁相对其他霉菌毒素而言较大。Aflatoxin is one of the important causes of mycotoxins in livestock and poultry at present, and its toxicity is often greater than other mycotoxins; at the same time, the pathogenic mechanism of aflatoxin is to directly cause substantial pathological damage to the liver of livestock and poultry , manifested as decreased growth performance, decreased digestive capacity, increased liver enzymes, increased oxidative stress, etc., and may even lead to liver cirrhosis or liver cancer. Therefore, aflatoxins pose a greater threat to the livestock and poultry industry than other mycotoxins.
发明内容Contents of the invention
有鉴于此,本发明提供一种防治霉菌毒素的兽药组合物,其可以有效改善或逆转动物霉菌毒素中毒引起的病理损伤,降低动物霉菌毒素后的死亡率,从而起到有效防治动物霉菌毒素中毒的作用。In view of this, the present invention provides a veterinary drug composition for preventing and treating mycotoxins, which can effectively improve or reverse the pathological damage caused by mycotoxin poisoning in animals, reduce the mortality rate of animals after mycotoxins, and thus effectively prevent and treat mycotoxin poisoning in animals role.
为解决以上技术问题,本发明的技术方案是采用一种防治霉菌毒素中毒的兽药组合物,所述防治霉菌毒素中毒的兽药组合物由下述中药材制备而成,各原料按重量份数计:In order to solve the above technical problems, the technical solution of the present invention is to adopt a veterinary drug composition for preventing and treating mycotoxin poisoning. The veterinary drug composition for preventing and treating mycotoxin poisoning is prepared from the following Chinese medicinal materials, and each raw material is calculated in parts by weight :
柴胡 5-8重量份;Bupleurum 5-8 parts by weight;
黄芩 3-6重量份;Scutellaria baicalensis 3-6 parts by weight;
黄芪 4-7重量份;Astragalus 4-7 parts by weight;
泽泻 5-8重量份;和Alisma 5-8 parts by weight; and
五味子 4-6重量份。Schisandra 4-6 parts by weight.
优选的,所述防治霉菌毒素中毒的兽药组合物由下述中药材制备而成,各原料按重量份数计:Preferably, the veterinary drug composition for preventing and treating mycotoxin poisoning is prepared from the following Chinese medicinal materials, and each raw material is calculated in parts by weight:
柴胡 6-7重量份;Bupleurum 6-7 parts by weight;
黄芩 4-5重量份;Scutellaria baicalensis 4-5 parts by weight;
黄芪 5-6重量份;Astragalus 5-6 parts by weight;
泽泻 6-7重量份;和Alisma 6-7 parts by weight; and
五味子 5-6重量份。Schisandra 5-6 parts by weight.
本发明与现有技术相比,其详细说明如下:Compared with the prior art, the present invention is described in detail as follows:
本发明所采用的技术方案为防治霉菌毒素中毒的兽药组合物,其由下述中药材制备而成,各原料按重量份数计:The technical solution adopted in the present invention is a veterinary drug composition for preventing and treating mycotoxin poisoning, which is prepared from the following Chinese medicinal materials, and each raw material is counted in parts by weight:
柴胡 5-8重量份;Bupleurum 5-8 parts by weight;
黄芩 3-6重量份;Scutellaria baicalensis 3-6 parts by weight;
黄芪 4-7重量份;Astragalus 4-7 parts by weight;
泽泻 5-8重量份;和Alisma 5-8 parts by weight; and
五味子 4-6重量份。Schisandra 4-6 parts by weight.
本发明主要采用将前述五种中药材作为原料来制备成防治霉菌毒素的兽药组合物,主要中药原料为柴胡、黄芩、黄芪、泽泻和五味子。The present invention mainly uses the aforementioned five kinds of Chinese medicinal materials as raw materials to prepare a veterinary drug composition for preventing and treating mycotoxins, and the main raw materials of Chinese medicinal materials are Bupleuri, Scutellaria baicalensis, Radix Astragali, Alisma and Schisandra.
根据中兽医学理论,从辨证论治的角度分析,畜禽霉菌毒素中毒可以辩证为湿热下注肝胆。湿热郁结于肝胆,致使肝气不疏,胆汁分泌排泄失常,脾胃运化功能减弱,即而出现食欲不振。根据中医理论,其治疗原则为疏肝解郁,清热利湿。因此可采用此类中药材进行配置。According to the theory of traditional Chinese veterinary medicine, from the perspective of syndrome differentiation and treatment, mycotoxin poisoning in livestock and poultry can be diagnosed as damp heat beating the liver and gallbladder. Damp heat stagnates in the liver and gallbladder, resulting in poor liver qi, abnormal bile secretion and excretion, weakened spleen and stomach transportation and transformation, and loss of appetite. According to the theory of traditional Chinese medicine, its treatment principle is to soothe the liver and relieve stagnation, clear away heat and dampness. Therefore, such Chinese medicinal materials can be used for configuration.
本发明人以大量的中药材做研究,发现本发明所述的中药原料组分以及含量所制备出的组合物可以很好的防治动物霉菌毒素中毒现象,尤其是黄曲霉毒素的中毒现象。The inventors conducted research on a large number of Chinese medicinal materials, and found that the composition prepared from the raw material components and contents of the traditional Chinese medicine described in the present invention can effectively prevent and treat mycotoxin poisoning in animals, especially aflatoxin poisoning.
本发明中所使用的中药柴胡,入肝胆经,性善疏泄;黄芩,入胆经,长于清热燥湿;泽泻,利水渗湿;黄芪,益气健脾;五味子,敛汗涩精。该五种中药原料共同制备而成的组合物可以对动物霉菌毒素中毒现象起到较为明显的防治作用(实际效果可参见后续具体实施例部分)。The traditional Chinese medicine Bupleurum used in the present invention enters the liver and gallbladder meridian and is good at dredging diarrhea; Scutellaria baicalensis enters the gallbladder meridian and is good at clearing away heat and dampness; The composition prepared by the five kinds of traditional Chinese medicine raw materials can play a relatively obvious preventive effect on animal mycotoxin poisoning (for the actual effect, please refer to the subsequent specific examples).
上述中药配方中的原料以及各原料的重量份数均为在大量的实验基础上获取的,即使原料与本发明相同,但各原料的重量份数若与本发明不相同,则其所得到的药效结果就不够理想。The raw materials in the above-mentioned Chinese medicine formula and the parts by weight of each raw material are all obtained on the basis of a large number of experiments. Even if the raw materials are the same as the present invention, if the parts by weight of each raw material are different from the present invention, the obtained The drug effect result is just not ideal enough.
进一步的,本发明优选采用所述防治霉菌毒素中毒的兽药组合物由下述中药材制备,各中药材按重量份计:Further, the present invention preferably adopts the veterinary drug composition for preventing and treating mycotoxin poisoning to be prepared from the following Chinese medicinal materials, and each Chinese medicinal material is calculated in parts by weight:
柴胡 6-7重量份;Bupleurum 6-7 parts by weight;
黄芩 4-5重量份;Scutellaria baicalensis 4-5 parts by weight;
黄芪 5-6重量份;Astragalus 5-6 parts by weight;
泽泻 6-7重量份;和Alisma 6-7 parts by weight; and
五味子 5-6重量份。Schisandra 5-6 parts by weight.
从后文具体实施例部分可以看出本发明进一步优选的实施方式可对防治霉菌毒素中毒的药效有一定的提高。It can be seen from the following specific examples that further preferred embodiments of the present invention can improve the efficacy of preventing and treating mycotoxin poisoning.
本发明的第二个目的在于提供一种前述的兽药组合物在制备预防或治疗畜禽霉菌毒素中毒的药品上的应用。The second object of the present invention is to provide the application of the aforementioned veterinary drug composition in the preparation of medicines for the prevention or treatment of mycotoxin poisoning in livestock and poultry.
本发明前述的兽药组合物可以用于制备预防或治疗畜禽霉菌毒素中毒的药品,该药品属于兽药,从下文的具体实施例部分可以得知,本发明的兽药组合物对于预防或治疗畜禽霉菌毒素中毒具有较好的药效效果。The aforementioned veterinary drug composition of the present invention can be used to prepare medicines for preventing or treating mycotoxin poisoning of livestock and poultry. Mycotoxin poisoning has good efficacy.
进一步的,本发明优选采用前述应用中可优选采用霉菌毒素为黄曲霉毒素。黄曲霉毒素目前是畜禽霉菌毒素中毒的首要原因,并且,从下文实施例部分可以得知,本发明的兽药组合物制备药品时其对于防治黄曲霉毒素中毒的药效数据优于其他霉菌毒素的药效数据。Further, the present invention preferably adopts aflatoxin as mycotoxin in the aforementioned applications. Aflatoxin is currently the primary cause of mycotoxin poisoning in livestock and poultry, and, as can be seen from the examples below, the veterinary drug composition of the present invention has better drug efficacy data for preventing and treating aflatoxin poisoning than other mycotoxins efficacy data.
本发明的第三个目的在于提供一种用于防治霉菌毒素中毒的兽药制剂,所述兽药制剂包含有前述任一种的兽药组合物。将前述任一种兽药组合物制备成兽药制剂时,其制备方法可以采用现有中药兽药制剂的常规方法,同时,其剂型也可以采用现有兽药制剂的常规制剂。The third object of the present invention is to provide a veterinary drug preparation for preventing and treating mycotoxin poisoning, said veterinary drug preparation comprising any one of the aforementioned veterinary drug compositions. When preparing any of the aforementioned veterinary drug compositions into veterinary drug preparations, the preparation method can adopt conventional methods of existing traditional Chinese medicine veterinary drug preparations, and meanwhile, its dosage form can also adopt conventional preparations of existing veterinary drug preparations.
进一步的,本发明优选采用所述兽药制剂的剂型为颗粒剂。颗粒制剂不仅具有中药口服液分散度大、吸收快、作用缓和、毒副作用低的特点,其药物稳定性较高。另外,颗粒制剂在使用时可以兑水或拌入动物饲料,便于规模化养殖场群体给药。而且与口服液相比,颗粒制剂便于生产和贮运;因此,本发明优选采用所述兽药制剂的剂型为颗粒剂。Further, the present invention preferably adopts the dosage form of the veterinary drug preparation as granules. Granular preparations not only have the characteristics of large dispersion, fast absorption, moderate action, and low toxic and side effects of traditional Chinese medicine oral liquid, but also have high drug stability. In addition, the granule preparation can be mixed with water or mixed with animal feed during use, which is convenient for group administration in large-scale farms. Moreover, compared with the oral liquid, the granule preparation is convenient for production, storage and transportation; therefore, the preferred dosage form of the veterinary preparation in the present invention is a granule.
本发明的第四个目的在于提供一种前述的防治霉菌毒素中毒的兽药制剂的制备方法,包含有以下步骤:The fourth object of the present invention is to provide a method for preparing the aforementioned veterinary drug preparation for preventing and treating mycotoxin poisoning, which includes the following steps:
1)将柴胡、黄芩、黄芪、五味子加重量为15-25倍的水,煎煮0.8-1h,过滤得水煎液,所得水煎液浓缩至相对密度为1.21-1.25;1) Add 15-25 times the weight of Bupleurum, Scutellaria, Astragalus, and Schisandra to water, decoct for 0.8-1 hour, filter to obtain a decoction, and concentrate the obtained decoction to a relative density of 1.21-1.25;
2)将泽泻用乙醇浸泡2-3h,收集6-8倍量的渗漉液,流速为4-5mL/min;浓缩至相对密度为1.01-1.05;2) Soak Alisma alisma in ethanol for 2-3 hours, collect 6-8 times the percolation liquid at a flow rate of 4-5mL/min; concentrate to a relative density of 1.01-1.05;
3)合并1)和2)所得浓缩液,得浸膏;3) Combine the concentrate obtained in 1) and 2) to obtain the extract;
4)将3)所得浸膏与糖按照1L/1kg的体积/质量比为1:3-4的比例混合、过筛、干燥得所述防治霉菌毒素中毒的兽药制剂,所述制剂的剂型为颗粒剂。4) Mix the extract obtained in 3) with sugar according to the volume/mass ratio of 1L/1kg of 1:3-4, sieve, and dry to obtain the veterinary drug preparation for preventing and treating mycotoxin poisoning. The dosage form of the preparation is Granules.
本发明采用上述步骤来制备所述剂型为颗粒剂的兽药制剂,上述制备方法对于所得的兽药制剂可以有效而充分的提取出各中药材中的药效成分,从而提高制剂的药效作用。The present invention adopts the above-mentioned steps to prepare the veterinary drug preparation in the form of granules. The above-mentioned preparation method can effectively and fully extract the medicinal ingredients in each Chinese medicinal material from the obtained veterinary drug preparation, thereby improving the medicinal effect of the preparation.
所述渗漉液为采用中药常规提取中的渗漉法得到,溶剂为乙醇。The percolation liquid is obtained by adopting the percolation method in conventional extraction of traditional Chinese medicine, and the solvent is ethanol.
进一步的,本发明优选采用所述步骤1)中煎煮分为两次进行,每次0.8-1h,过滤后合并两次滤液得水煎液。Further, in the present invention, the decoction in the step 1) is preferably divided into two times, each time for 0.8-1 h, and the two filtrates are combined after filtration to obtain a water decoction.
进一步的,本发明优选采用所述步骤2)中泽泻为用75%的乙醇浸泡。Further, in the present invention, it is preferred to soak Alisma in step 2) with 75% ethanol.
进一步的,本发明优选采用所述制备方法包含有以下步骤:Further, the present invention preferably adopts the preparation method comprising the following steps:
1)将柴胡、黄芩、黄芪、五味子加重量为20倍的水,煎煮两次,每次0.8-1h,过滤得水煎液,所得水煎液浓缩至相对密度为1.21-1.25;1) Add Bupleurum, Scutellaria, Radix Astragali, and Schisandra to 20 times the weight of water, decoct twice for 0.8-1 hour each time, filter to obtain decoction, and concentrate the obtained decoction to a relative density of 1.21-1.25;
2)将泽泻用75%乙醇浸泡3h,收集8倍量的渗漉液,流速为4-5mL/min;浓缩至相对密度为1.01-1.05;2) Soak Alisma alisma in 75% ethanol for 3 hours, collect 8 times the percolation liquid at a flow rate of 4-5mL/min; concentrate to a relative density of 1.01-1.05;
3)合并1)和2)所得浓缩液,得浸膏;3) Combine the concentrate obtained in 1) and 2) to obtain the extract;
4)将3)所得浸膏与糖按照1L/1kg的体积/质量比为1:4的比例混合、过筛、干燥得所述防治霉菌毒素中毒的兽药制剂,所述制剂的剂型为颗粒剂。4) Mix the extract obtained in 3) with sugar at a volume/mass ratio of 1L/1kg of 1:4, sieve, and dry to obtain the veterinary drug preparation for preventing and treating mycotoxin poisoning, and the dosage form of the preparation is granules .
具体实施方式Detailed ways
为了使本领域的技术人员更好地理解本发明的技术方案,下面结合具体实施例对本发明作进一步的详细说明。In order to enable those skilled in the art to better understand the technical solutions of the present invention, the present invention will be further described in detail below in conjunction with specific examples.
对照例1Comparative example 1
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
柴胡 1份Bupleurum 1 part
黄芩 15份Scutellaria baicalensis 15 parts
对照例2Comparative example 2
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例3Comparative example 3
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例4Comparative example 4
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例5Comparative example 5
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例6Comparative example 6
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例7Comparative example 7
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例8Comparative example 8
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例9Comparative example 9
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例10Comparative example 10
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例11Comparative Example 11
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例12Comparative example 12
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
对照例13Comparative example 13
按照以下重量份数称取各原料:Take each raw material according to the following parts by weight:
将各对照例1-13分别按照以下制备方法制备出相应的防治霉菌毒素中毒的兽药组合物,各制备方法的步骤如下:Each of Comparative Examples 1-13 was prepared according to the following preparation methods to prepare corresponding veterinary drug compositions for the prevention and treatment of mycotoxin poisoning. The steps of each preparation method are as follows:
方法(1):method 1):
将对照例1-10中所述的各中药简单粉碎并混合得兽药组合物。Simply pulverize and mix the traditional Chinese medicines described in Comparative Examples 1-10 to obtain a veterinary drug composition.
方法(2):Method (2):
1)将对照例7-13中所述的柴胡、黄芩、黄芪、五味子加入重量为15-25倍的水,煎煮0.8-1h,过滤得水煎液,所得水煎液浓缩至相对密度为1.21-1.25;1) Add bupleurum, scutellaria baicalensis, astragalus, and schisandra described in Comparative Example 7-13 to 15-25 times the weight of water, decoct for 0.8-1 hour, filter to obtain a decoction, and concentrate the obtained decoction to a relative density 1.21-1.25;
2)将泽泻用60%乙醇浸泡2-3h,收集6-8倍量的渗漉液,流速为4-5mL/min;所得渗漉液浓缩至相对密度为1.01-1.05;2) Soak Alisma alisma in 60% ethanol for 2-3 hours, collect 6-8 times the amount of percolate, and the flow rate is 4-5mL/min; the obtained percolate is concentrated to a relative density of 1.01-1.05;
3)合并1)和2)所得浓缩液,得浸膏;3) Combine the concentrate obtained in 1) and 2) to obtain the extract;
4)将3)所得浸膏与糖按照体积/质量比1:3-4的比例混合、过筛、干燥得所述防治霉菌毒素的兽药制剂,所述制剂的剂型为颗粒剂。4) Mix the extract obtained in 3) with sugar at a volume/mass ratio of 1:3-4, sieve, and dry to obtain the veterinary drug preparation for preventing and treating mycotoxins, and the preparation is in the form of granules.
方法(3):Method (3):
1)将对照例7、9、11、13中所述的柴胡、黄芩、黄芪、五味子加入重量为20倍的水,煎煮两次,每次0.8-1h,过滤并合并两次水煎液,所得水煎液浓缩至相对密度为1.21-1.25;1) Add the bupleurum, baicalin, astragalus, and schisandra described in Comparative Examples 7, 9, 11, and 13 to 20 times the weight of water, decoct twice, each time for 0.8-1h, filter and combine twice to decoct in water liquid, and the obtained decoction is concentrated to a relative density of 1.21-1.25;
2)将泽泻用75%乙醇浸泡3h,收集8倍量的渗漉液,流速为4-5mL/min;所得渗漉液浓缩至相对密度为1.01-1.05;2) Soak Alisma alisma in 75% ethanol for 3 hours, collect 8 times the amount of percolate at a flow rate of 4-5mL/min; the obtained percolate is concentrated to a relative density of 1.01-1.05;
3)合并1)和2)所得浓缩液,得浸膏;3) Combine the concentrate obtained in 1) and 2) to obtain the extract;
4)将3)所得浸膏与糖按照体积/质量比1:4的比例混合、过筛、干燥得所述防治霉菌毒素的兽药制剂,所述制剂的剂型为颗粒剂。4) Mix the extract obtained in 3) with sugar at a volume/mass ratio of 1:4, sieve, and dry to obtain the veterinary drug preparation for preventing and treating mycotoxins, and the preparation is in the form of granules.
实施例1——按照方法(1)分别制备出的对照例1-10的兽药组合物的药效试验Example 1——Efficacy test of the veterinary drug compositions of Comparative Examples 1-10 prepared according to method (1)
实验方法:experimental method:
1.1基础日粮参考美国NRC(1994)肉用仔鸡营养需要配合成试验饲粮,配方及主要营养指标见表一。1.1 The basal ration was formulated with reference to the nutritional requirements of broiler chicks from the American NRC (1994). The formula and main nutritional indicators are shown in Table 1.
表一试验基础日粮组成和营养指标Table 1 Experimental basal diet composition and nutritional indicators
多维微量元素:1500IU维生素A,200IU维生素D3,10mg维生素E,0.5mg维生素K,4mg维生素Bz,10mg d-泛酸,25mg维生素B6,25mg烟酸,800mg氯化胆碱,0.15mg生物素,60mg Mn,40mg Zn,80mg Fe,8.0mg Cu,0.35mgI,0.15mg Se。Multidimensional trace elements: 1500IU vitamin A, 200IU vitamin D3, 10mg vitamin E, 0.5mg vitamin K, 4mg vitamin Bz, 10mg d-pantothenic acid, 25mg vitamin B6, 25mg niacin, 800mg choline chloride, 0.15mg biotin, 60mg Mn, 40mg Zn, 80mg Fe, 8.0mg Cu, 0.35mgI, 0.15mg Se.
1.2动物分组即饲养实验1.2 Animal grouping is feeding experiment
选择羽1日龄健康肉鸡,购自四川正大养殖场,按饲养试验要求采用2x2因子完全随机设计分为12组,分别标记为T1、T2、T3、T4、T5、T6、T7、T8、T9、T10、T11、T12共12个实验组,每组设3个重复,每个重复公母各半;基础日粮饲喂至7日龄,剔除弱小。Select 1-day-old healthy broiler chickens, purchased from Sichuan Zhengda Farm, and divide them into 12 groups according to the requirements of the feeding experiment using a 2x2 factor completely random design, labeled as T1, T2, T3, T4, T5, T6, T7, T8, T9 , T10, T11, T12, a total of 12 experimental groups, each group set up 3 replicates, each replicate male and female half and half; the basic diet was fed to 7 days old, and the weak ones were eliminated.
T12组:8-27日龄均采用基础日粮(不含黄曲霉毒素B1)喂养,T12组作为空白对照组;T12 group: 8-27 days old were fed with basic diet (excluding aflatoxin B1), and T12 group was used as the blank control group;
T1-T10组:8-21日龄采用含赭曲霉毒素A50μg/kg的基础日粮统一喂养,22日龄-27日龄又改为基础日粮(不含赭曲霉毒素A),并且开始投服药物,T1-T10分别按照对照例1-10所得的兽药组合物进行每日一次灌胃给药;Groups T1-T10: 8-21 days of age were uniformly fed with basal diet containing ochratoxin A 50 μg/kg; Taking the medicine, T1-T10 were administered by intragastric administration once a day according to the veterinary drug composition obtained in Comparative Example 1-10 respectively;
T11组:8-21日龄采用含赭曲霉毒素A50μg/kg的基础日粮统一喂养,22日龄-27日龄仅改为基础日粮(不含赭曲霉毒素A)喂养。Group T11: From 8 to 21 days old, the basal diet containing ochratoxin A 50 μg/kg was uniformly fed, and from 22 days to 27 days, only the basal diet (without ochratoxin A) was fed.
上述T1-T12组均按常规进行鸡瘟、鸡病毒性肝炎、禽流感等疫苗接种。采用地面平养,自由采食和饮水,24h光照,试验期27d(1~27日龄)。The above-mentioned T1-T12 groups were routinely vaccinated against fowl plague, chicken viral hepatitis, and avian influenza. Raised on the ground, free access to food and water, 24h of light, the test period of 27d (1 to 27 days old).
赭曲霉毒素A的产生是用赭曲霉菌种2471(CICC编号,购自中国工业微生物菌种保藏中心)按Marquardt等的方法发酵而成。玉米和饲粮中赭曲霉毒素A采用高效液相色谱法进行测定。Ochratoxin A is produced by fermenting Ochratoxin 2471 (CICC code, purchased from China Industrial Microorganism Collection Center) according to the method of Marquardt et al. Ochratoxin A in corn and feed was determined by high performance liquid chromatography.
1.3屠宰试验和样品采集1.3 Slaughter test and sample collection
饲养试验结束后,于21、23、25、27日龄分别采样,做动态治疗观察。每组选体重相近的肉鸡,给水不给料,禁食12h,称重。颈静脉真空无抗凝剂采血管采血,自然析出血清,分装于Eppendof管,-20℃冰箱保存。并立即取部分肝脏组织于流式细胞仪做肝细胞凋亡分析,另取部分肝脏组织固定于10%中性甲醛中,做病理组织切片。After the feeding experiment, samples were taken at 21, 23, 25, and 27 days of age for dynamic treatment observation. Broilers with similar body weight were selected for each group, given water but no feed, fasted for 12 hours, and weighed. Vacuum blood collection tubes without anticoagulant in the jugular vein, the serum was naturally precipitated, divided into Eppendof tubes, and stored in a -20°C refrigerator. Immediately take part of the liver tissue for analysis of hepatic cell apoptosis by flow cytometry, and another part of the liver tissue is fixed in 10% neutral formaldehyde for pathological tissue sectioning.
1.4血清生化指标分析1.4 Analysis of serum biochemical indicators
谷丙转氨酶(GPT)、谷草转氨酶(GOT)、碱性磷酸酶(AKP)、谷胱甘肽-S转移酶(GST)、用南京建成生物工程研究所提供的试剂盒在Bio-rad680酶标仪和紫外分光光度计测定。Alanine aminotransferase (GPT), aspartate aminotransferase (GOT), alkaline phosphatase (AKP), glutathione-S transferase (GST), using the kit provided by Nanjing Jiancheng Bioengineering Institute in Bio-rad680 enzyme labeling instrument and UV spectrophotometer.
1.5血清抗氧化指标的测定1.5 Determination of serum antioxidant indexes
超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)采用南京建成生物工程研究所提供的试剂盒在Bio-rad680酶标仪和紫外分光光度计测定。Superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) were tested on Bio-rad680 microplate reader and ultraviolet spectrometer using kits provided by Nanjing Jiancheng Bioengineering Institute. Photometer measurement.
1.6数据处理1.6 Data processing
试验数据处理和分析采用SPSS(17.0)中的一般线性模式(General Linear ModelsProcedure)方差分析,差异显著时采用Duncan氏方法对各组间平均数进行多重比较,P<0.05表示差异显著,结果以表示。Experimental data processing and analysis adopted the general linear model (General Linear Models Procedure) analysis of variance in SPSS (17.0). When the difference was significant, Duncan's method was used to carry out multiple comparisons between the means of each group. P<0.05 indicated that the difference was significant. express.
2结果2 results
2.1血清生化指标2.1 Serum biochemical indicators
表二——碱性磷酸酶测定数据Table 2 - Alkaline Phosphatase Determination Data
注:同一竖排肩标*表示与1-T11组比较差异显著(P<0.05);同一竖排肩标**表示与1-T11组比较差异极显著(P<0.01)。Note: The same vertical shoulder mark * means significant difference compared with 1-T11 group (P<0.05); the same vertical shoulder mark ** means extremely significant difference compared with 1-T11 group (P<0.01).
表三—超氧化物歧化酶测定数据Table 3 - Determination data of superoxide dismutase
注:同一竖排肩标*表示与1-T11组比较差异显著(P<0.05);同一竖排肩标**表示与1-T11组比较差异极显著(P<0.01)。Note: The same vertical shoulder mark * means significant difference compared with 1-T11 group (P<0.05); the same vertical shoulder mark ** means extremely significant difference compared with 1-T11 group (P<0.01).
从上表二和表三的测定数据可以看出,对照例1-6按照制备方法(1)制备所得的防治霉菌毒素的兽药组合物的药效数据明显低于本发明实施方式对照例7-10按照制备方法(1)制备所得的防治霉菌毒素的兽药组合物的药效数据。From the measurement data in Table 2 and Table 3 above, it can be seen that the efficacy data of the veterinary drug composition for preventing and treating mycotoxins prepared by Comparative Example 1-6 according to the preparation method (1) is significantly lower than that of Comparative Example 7- 10 Pharmacodynamic data of the veterinary drug composition for preventing and treating mycotoxins prepared according to the preparation method (1).
实施例2——按照方法(2)分别制备出的对照例7-13的兽药制剂的药效试验Example 2—Efficacy test of the veterinary drug preparations of Comparative Examples 7-13 prepared according to method (2)
实施例2的实验方法以及步骤同实施例1,仅将实验毒素换成黄曲霉毒素B1,实验对象换成樱桃谷商品肉鸭,购自四川绵阳樱桃谷鸭种业公司,从而进行相同的药效试验,各实验组分别标记为2-T1、2-T2、2-T3、2-T4、2-T5、2-T6、2-T7、2-T8、2-T9,其中,2-T1——2-T7为分别采用对照例7-13所制得的兽药制剂的实验组,其饲养方法同实施例1中1-T1——1-T10;2-T8为空白对照组,其饲养方法同实施例1中1-T12,2-T9为中毒实验组,其饲养方法同实施例1中的1-T11。所测定结果举例如下:The experimental method and steps of Example 2 are the same as in Example 1, only the experimental toxin is replaced by aflatoxin B1, and the experimental object is replaced by Cherry Valley commercial meat duck, purchased from Sichuan Mianyang Cherry Valley Duck Seed Industry Company, so as to carry out the same medicine Effect test, each experimental group is marked as 2-T1, 2-T2, 2-T3, 2-T4, 2-T5, 2-T6, 2-T7, 2-T8, 2-T9, among them, 2-T1 ——2-T7 is the experimental group that adopts the veterinary drug preparation that control example 7-13 makes respectively, and its feeding method is the same as 1-T1——1-T10 in embodiment 1; 2-T8 is the blank control group, and its feeding method The method is the same as that of 1-T12 in Example 1, and 2-T9 is the poisoning experiment group, and the feeding method is the same as that of 1-T11 in Example 1. Examples of measured results are as follows:
表四—谷丙转氨酶的测定数据Table 4 - Determination data of alanine aminotransferase
注:同一竖排肩标*表示与2-T9组比较差异显著(P<0.05);同一竖排肩标**表示与2-T9组比较差异极显著(P<0.01)。Note: The same vertical shoulder mark * means significant difference compared with 2-T9 group (P<0.05); the same vertical shoulder mark ** means extremely significant difference compared with 2-T9 group (P<0.01).
黄曲霉毒素的产生是用黄曲霉菌种2219(CICC编号,购自中国工业微生物菌种保藏中心)按Odette L.Shotwell等的方法发酵而成。玉米和饲粮中黄曲霉毒素B1采用高效液相色谱法进行测定。The production of aflatoxin is formed by fermentation of Aspergillus flavus strain 2219 (CICC number, purchased from China Industrial Microorganism Collection Center) according to the method of Odette L. Aflatoxin B1 in corn and feed was determined by high performance liquid chromatography.
从上表四中可以看出,对照例7-13按照制备方法(2)制备所得的兽药制剂对于防治霉菌毒素——黄曲霉毒素的药效测定结果中,对照例11-13明显高于对照例7-10。It can be seen from Table 4 above that in the results of the determination of the efficacy of the veterinary drug preparations prepared according to the preparation method (2) of Comparative Examples 7-13 for the prevention and treatment of mycotoxins - aflatoxins, Comparative Examples 11-13 were significantly higher than those of the Control Example 7-10.
实施例3——按照方法(3)分别制备出的对照例7、9、11、13的兽药制剂的药效试验Example 3—Efficacy test of the veterinary drug preparations of Comparative Examples 7, 9, 11, and 13 prepared according to method (3)
实施例3的实验方法以及步骤同实施例1,将实验毒素分别设置成黄曲霉毒素B1和赭曲霉毒素A,实验对象换成樱桃谷商品肉鸭,购自四川绵阳樱桃谷鸭种业公司,从而进行相同的药效试验;各实验组分别标记为黄曲霉毒素B1实验组:3-T1、3-T2、3-T3、3-T4、3-T5、3-T6和赭曲霉毒素A实验组:4-T1、4-T2、4-T3、4-T4、4-T5、4-T6;其中,3-T1——3-T4和4-T1——4-T4为分别采用对照例7、9、11、13所制得的兽药制剂的实验组,其饲养方法同实施例1中1-T1——1-T10;3-T5和4-T5为空白对照组,其饲养方法同实施例1中1-T12;3-T6和4-T6为中毒实验组,其饲养方法同实施例1中的1-T11。所测定结果举例如下:The experimental method and steps of Example 3 are the same as those in Example 1. The experimental toxins were set to aflatoxin B1 and ochratoxin A respectively, and the experimental subjects were changed to Cherry Valley commercial meat ducks, which were purchased from Sichuan Mianyang Cherry Valley Duck Seed Company. To carry out the same drug efficacy test; each experimental group is marked as aflatoxin B1 experimental group: 3-T1, 3-T2, 3-T3, 3-T4, 3-T5, 3-T6 and ochratoxin A experiment Groups: 4-T1, 4-T2, 4-T3, 4-T4, 4-T5, 4-T6; among them, 3-T1——3-T4 and 4-T1——4-T4 are the control examples respectively 7, 9, 11, and 13 prepared experimental groups of veterinary drug preparations, the feeding method is the same as that of 1-T1——1-T10 in Example 1; 3-T5 and 4-T5 are blank control groups, and the feeding method is the same as In Example 1, 1-T12; 3-T6 and 4-T6 are poisoning experimental groups, and the feeding method is the same as that of 1-T11 in Example 1. Examples of measured results are as follows:
黄曲霉毒素B1实验组:Aflatoxin B1 experimental group:
表五——谷丙转氨酶测定数据Table 5 - Determination data of alanine aminotransferase
注:同一竖排肩标*表示与3-T6组比较差异显著(P<0.05);同一竖排肩标**表示与3-T6组比较差异极显著(P<0.01)。Note: The same vertical shoulder mark * means significant difference compared with 3-T6 group (P<0.05); the same vertical shoulder mark ** means extremely significant difference compared with 3-T6 group (P<0.01).
赭曲霉毒素A实验组:Ochratoxin A experimental group:
表六——谷丙转氨酶测定数据Table 6 - Determination data of alanine aminotransferase
注:同一竖排肩标*表示与4-T6组比较差异显著(P<0.05);同一竖排肩标**表示与4-T6组比较差异极显著(P<0.01)。Note: The same vertical shoulder mark * means significant difference compared with 4-T6 group (P<0.05); the same vertical shoulder mark ** means extremely significant difference compared with 4-T6 group (P<0.01).
从上表五和表六中可以看出,本发明的兽药组合物和兽药制剂对于黄曲霉毒素的防治效果优于其他的霉菌毒素。It can be seen from Table 5 and Table 6 that the veterinary drug composition and veterinary drug preparation of the present invention have better control effects on aflatoxin than other mycotoxins.
以上仅是本发明的优选实施方式,应当指出的是,上述优选实施方式不应视为对本发明的限制,本发明的保护范围应当以权利要求所限定的范围为准。对于本技术领域的普通技术人员来说,在不脱离本发明的精神和范围内,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。The above are only preferred implementations of the present invention, and it should be noted that the above preferred implementations should not be regarded as limiting the present invention, and the scope of protection of the present invention should be based on the scope defined in the claims. For those skilled in the art, without departing from the spirit and scope of the present invention, some improvements and modifications can also be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.
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WO1998050056A1 (en) * | 1997-05-06 | 1998-11-12 | Kemin Industries, Inc. | Anti-fungal protein extracts from seeds of marigold |
CN1256967C (en) * | 2003-01-30 | 2006-05-24 | 王晓 | Health-preserving liver-protecting drug and method for making same |
CN1537598A (en) * | 2003-04-20 | 2004-10-20 | 毛友昌 | Traditional Chinese medicine Conghuang bushen granule for tonifying kidney, and its prepn. method |
CN1264503C (en) * | 2003-05-29 | 2006-07-19 | 北京汉典中西药研究开发中心 | Preparnig method for xiao Chaihu effervescent preparation and quality controlling method thereof |
CN101297889B (en) * | 2007-08-31 | 2010-09-01 | 天津生机集团有限公司 | Chinese medicine preparation for treating foot-and-mouth disease and preparation method thereof |
CN101342275B (en) * | 2008-08-25 | 2010-11-10 | 河北农业大学 | A kind of medicine for preventing and treating chicken aspergillosis |
CN101703608A (en) * | 2008-12-03 | 2010-05-12 | 泰安市山农大药业有限公司 | Composition for preventing and treating chicken aspergillosis |
CN103006870A (en) * | 2011-09-26 | 2013-04-03 | 董根荣 | Oral liquid for controlling avian aspergillosis and preparation method thereof |
CN102716214B (en) * | 2012-06-29 | 2013-11-27 | 河南中亚神鹏动物药业有限公司 | Veterinary medicine composition for preventing and treating mycotoxin pathopoiesia |
CN103169823B (en) * | 2013-04-18 | 2014-09-24 | 四川农业大学 | Veterinary drug composition, application, preparation and preparation method for preventing and treating mycotoxin poisoning |
-
2013
- 2013-04-18 CN CN201310136059.9A patent/CN103169823B/en not_active Expired - Fee Related
- 2013-07-24 WO PCT/CN2013/079981 patent/WO2014169542A1/en active Application Filing
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CN103169823A (en) | 2013-06-26 |
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