WO2007082425A1 - Composition médicinale chinoise et sa méthode d'utilisation - Google Patents

Composition médicinale chinoise et sa méthode d'utilisation Download PDF

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Publication number
WO2007082425A1
WO2007082425A1 PCT/CN2006/002365 CN2006002365W WO2007082425A1 WO 2007082425 A1 WO2007082425 A1 WO 2007082425A1 CN 2006002365 W CN2006002365 W CN 2006002365W WO 2007082425 A1 WO2007082425 A1 WO 2007082425A1
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parts
chinese medicine
traditional chinese
pharmaceutical composition
medicine compound
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PCT/CN2006/002365
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English (en)
French (fr)
Inventor
Tong Liu
Yun Mo
Huaming Hu
Ling Tian
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Beijing Dabeinong Animal Health Science And Technology Co., Ltd.
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Publication of WO2007082425A1 publication Critical patent/WO2007082425A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/708—Rheum (rhubarb)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539—Scutellaria (skullcap)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718—Coptis (goldthread)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/756—Phellodendron, e.g. corktree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a traditional Chinese medicine compound pharmaceutical composition, a preparation method thereof, and the use of the composition for controlling aquatic animal diseases. Background technique
  • Ultrafine powder is a very fine powder with a particle size of less than 50 microns obtained by breaking the plant cell wall by using ultrafine pulverization technology. Its characteristics are: small particle size, uniform distribution and uniform quality, which is conducive to drug release and absorption. Bioavailability and pharmacodynamic activity, reducing dosage, saving herbs, and reducing costs.
  • the object of the present invention is to provide a traditional Chinese medicine compound pharmaceutical composition for preventing and treating aquatic animal diseases with high efficiency, low toxicity and environmental protection.
  • Another object of the present invention is to provide a method for preparing the traditional Chinese medicine compound pharmaceutical composition.
  • Still another object of the present invention is to provide a use of the traditional Chinese medicine compound pharmaceutical composition for the preparation of a medicament for controlling aquatic animal diseases.
  • the traditional Chinese medicine compound pharmaceutical composition provided by the invention is prepared from the raw materials of berberine, astragalus, rhubarb and cork in a certain weight ratio.
  • the preferred raw material weight ratio is 5-12 parts of Coptidis Rhizoma, 10-30 parts of Astragalus, 10-20 parts of Rhubarb, and 10-25 parts of Phellodendron.
  • the weight ratio of the raw materials is 8-10 parts of berberine, 25-30 parts of astragalus, 15-20 parts of rhubarb, and 15-20 parts of cork.
  • the traditional Chinese medicine compound pharmaceutical composition of the present invention is preferably in the form of a powder, and more preferably the powder has a particle diameter of 50 ⁇ m or less.
  • the present invention also relates to a method for preparing the above-mentioned traditional Chinese medicine compound pharmaceutical composition, which comprises superfinely pulverizing and mixing the above-mentioned ratios of berberine, scutellaria, rhubarb, and phellodendron, optionally in the form of a powder.
  • coptis, scutellaria, rhubarb, and xanthine are ultrafinely pulverized to less than 50 microns.
  • the present invention also provides the use of the traditional Chinese medicine compound pharmaceutical composition of the present invention for the preparation of a medicament for controlling diseases of aquatic animals.
  • the traditional Chinese medicine compound pharmaceutical composition of the present invention is especially useful for treating explosive bleeding diseases in aquatic animals, and diseases such as enteritis, rot disease, and erythroderma.
  • the preparation method of the traditional Chinese medicine compound pharmaceutical composition of the present invention is as follows -
  • the traditional Chinese medicine compound pharmaceutical composition prepared by the method has a particle diameter of 50 ⁇ m or less.
  • the invention exerts the combined effect of the traditional Chinese medicine compound preparation to treat the disease, has the curative effect and is effective, and is used for preventing and treating explosive hemorrhagic diseases of aquatic animals, as well as diseases such as enteritis, rot disease and red skin disease.
  • the present invention uses an ultrafine pulverization technique to increase the surface area of the drug particles, enhance the dissolution and absorption of the drug, thereby improving the efficacy of the drug. Compared with the powder prepared by the ordinary pulverization method, the dosage of the medicine is reduced, and the medicinal material resource is saved.
  • the invention is a pure traditional Chinese medicine preparation, has small toxic and side effects, does not produce drug residues harmful to human health, is not easy to produce drug resistance, does not pollute the environment, and does not cause drug-induced diseases.
  • Figure 1 is a volume distribution curve of the particle size of the four yellow powder ultrafine powder. detailed description
  • Rhizoma Coptidis 9 parts of Rhizoma Coptidis, 27 parts of Astragalus, 18 parts of Rhubarb, 18 parts of Cork, drying thousands, ultra-fine pulverization, sieving, combined according to the required ratio, and evenly mixed into a powder, the particle size of the drug is controlled below 50 microns.
  • Rhizoma Coptidis 2 parts of Rhizoma Coptidis, 2 parts of Astragalus, 5 parts of Rhubarb, 3 parts of Cork, dried, superfinely pulverized, sieved, combined according to the required ratio, stirred to form a powder, and the particle size of the drug is controlled below 50 microns.
  • Rhizoma Coptidis 8 parts of Rhizoma Coptidis, 16 parts of Astragalus, 15 parts of Rhubarb, 19 parts of Cork, dried, superfinely pulverized, sieved, combined according to the required ratio, and stirred to form a powder.
  • the particle size of the drug is controlled below 50 microns.
  • the traditional Chinese medicine compound pharmaceutical composition is prepared as follows:
  • the average body weight was (0.98 ⁇ 0.25) g of P. vannamei. After 7 days of holding, the small and weak individuals were discarded, and the shrimps with the same size and size (average body weight (1.0 ⁇ 0.17) g ) were used for the experiment; Feed the basic bait during the feeding period. Each group was randomly selected for 30 measurements of body weight and used as the initial weight of the test shrimp. 150 pieces of P. vannamei were stocked in each tank.
  • A, B, and C are low, medium, and high drug dose groups, respectively, fed with IgG/kg, 2g/kg, and 4g/kg of Chinese herbal compound pharmaceutical composition, and fed continuously for seven days every half month.
  • the time was fed to the basal feed; the D group was the negative control group, and the basal feed was fed.
  • the water temperature, growth, and death were recorded, and the bottom bait, feces, and dead individuals were removed, and the water was changed according to the water quality 1/3 ⁇ : 1/2.
  • Each group was fed the corresponding bait twice a day, 9 am and 4 pm, respectively.
  • the amount of feed was basically finished within 2 hours.
  • the growth test was carried out for 60 days.
  • the experimental data were statistically processed, and the ANOVA analysis showed that the A, B, and C groups were significantly higher than the control group in terms of daily weight gain rate and survival rate. There was significant difference between group A and control group, P ⁇ 0.05. There was a significant difference between group B and group C, P ⁇ 0.01. There was significant difference between group B and group C, P ⁇ 0.05. The weight gain rate of sputum in group B was slightly higher than that in group C, and the survival rate was slightly lower than that in group C, but there was no significant difference between the two groups, P>0.05.
  • the therapeutic effect of Aeromonas hydrophila is observed by using the Chinese medicine compound pharmaceutical composition of Example 2 of the present invention for treating squid enteritis, and the pharmaceutical composition of the Chinese medicinal compound composition of Example 2 is lg/kg, 2.5 g /kg, 5 g / The g g , 7.5g/kg, lOg/k concentration is prepared as a medicine bait for feeding, and the powder of the same composition prepared by the conventional method is lg/kg, 2.5 g / kg, 5 g/kg, 7.5 g /k. g , lOg/kg concentration bait for comparison.
  • the cure rate of the traditional Chinese medicine compound preparation of the present invention is 85%, 100%, 100%, 100%, 100%, respectively, and the cure rates of the preparations prepared by the conventional method are 49% and 62%, respectively. 83%, 94% and 100%. Therefore, the effective dosage of the traditional Chinese medicine preparation prepared by the invention in the feed is 0.25%, which shows a better therapeutic effect on the squid enteritis produced by the conventional method.
  • test cells There are five test cells with an area of 180m 2 , numbered A, B, C, D, E.
  • Each sputum is about 250 grams, a total of 5,000, divided into five sputum pools, 1000 stocks per pool; 50 samples were randomly selected before stocking.
  • the farm is regularly disinfected.
  • a pool is a negative control group, and the basic feed is always fed;
  • B pool and C pool are low dose drug groups, according to 2 g /k g
  • the traditional Chinese medicine compound pharmaceutical composition is fed, and the D pool and the E pool are high-dose medicine groups, which are fed according to the 4 g/kg Chinese medicine compound pharmaceutical composition bait, and fed continuously for seven days every half month, and the rest of the time is cast.
  • Feed the basic feed; the feed amount of each pool is consistent.
  • the water quality was regularly checked during the test, and the pools for disinfection and application of biological agents were consistent. The test was carried out for a total of 90 days.
  • Enteritis, erythroderma, rot disease, and bacterial sepsis are common bacterial diseases in grass carp culture.
  • the intensive ponds of the main grass-raising fish in Hubei Xinzhou, Xiaogan, Hunchun, Wuxue, Huangmei, Jingzhou, Xianyu, Jiangxia and other areas were randomly selected, ranging from 2 to 30 mu, and the water depth was 1 to 2 m. Feed grass fish commodity bait.
  • a total of 105 ponds with different degrees of bacterial diseases such as enteritis, erythroderma, rot disease, and bacterial sepsis were selected for therapeutic trials.
  • Example 4 has significant preventive and therapeutic effects on common bacterial diseases of aquatic animals such as enteritis, red skin, rotten sputum, bacterial sepsis, and its therapeutic efficiency is significantly better than that of traditional Chinese medicine compound combination.
  • Crude powder and ciprofloxacin hydrochloride Crude powder and ciprofloxacin hydrochloride.
  • Example 5 The particle size of the Chinese herbal compound composition was 50 ⁇ m or less by a laser particle size detector (MALVERN VALIDATION INITIATIVE), of which 50% (volume parts) reached 12.30 ⁇ m or less, and 90% reached 27.26 ⁇ m or less. .
  • the results are shown in Figure 1, Table 4. Particle size distribution of four yellow powder ultrafine powder
  • the volume (%) column indicates the volume fraction of the ultrafine powder contained in the particle size range.

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Description

一种中药组合物及其制备方法和用途
技术领域
本发明涉及一种中药复方药物组合物及其制备方法， 以及该组合物用于防治水产 动物疾病的用途。 背景技术
与防治畜禽疾病的药物相比， 批准用于水产动物疾病防治的药物较少， 而且大部 分是毒性比较大的药物。 由于缺乏有效的药物， 加上滥用药品， 致使氯霉素、 孔雀石 绿等水产动物药物残留事件频繁发生，严重影响了我国水产动物产品的出口贸易和我 . 国的声誉， 危害了公众健康， 破坏了生态环境。 随着"无公害食品行动计划 "在全国范 围内的推进， 水产用中草药制剂作为一类 "三效 "(髙效、速效、长效)、 "三小 "(毒性小、 副作用小、 用量小)、 不危害人类健康、 不破坏水域生态环境的植物源渔药在水产动 物健康养殖中逐渐得到关注。
兽医临床上中药以散剂为最常用剂型， 普通中药散剂存在"粗、 大、 黑"的问题。 由于普通中药散剂粒径较粗， 降低了其利用率， 影响了药效的发挥， 通常使用剂量较 大。 即使进行萃取提纯， 但也存在工艺复杂、 投资大、 成本高、 有机溶剂污染、 有效 成分损失、 资源浪费等问题。超微粉是利用超微粉碎技术打破植物细胞壁而得到的粒 度小于 50微米的极细粉， 其特点是： 粉末粒径小， 分布均勾、 质量均一， 有利于药 物的释放和吸收， 提髙药物的生物利用度和药效学活性， 减少剂量、 节省药材、 降低 成本。
按中医原理， 黄连、 黄柏清热燥湿， 泻火解毒， 黄芩清热解毒， 止血， 大黄凉血 解毒， 泻热通肠， 混合配制而成的中药复方制剂具有抗菌消炎、 清热止血、 燥湿、 抗 病毒等多种功能； 适宜防治水产动物爆发性出血病， 以及肠炎、 烂鳃病、 赤皮病等疾 病。 W 发明内容
本发明的目的在于，提供一种高效低毒绿色环保的防治水产动物疾病的中药复方 药物组合物。
本发明的另一目的还在于， 提供该中药复方药物组合物的制备方法。
本发明的再一目的在于，提供该中药复方药物组合物在制备防治水产动物疾病药 物的用途。
本发明所提供的一种中药复方药物组合物， 是由黄连、 黄芩、 大黄、 黄柏原料按 一定的重量配比而制成。
它含有下述重量配比的原料：黄连 2-15份、黄芩 2-30份、大黄 5-25份、黄柏 3-35 份。
优选的原料重量配比是：黄连 5-12份、黄芩 10-30份、大黄 10-20份、黄柏 10-25 份。
更优选的原料重量配比是:黄连 8-10份、黄芩 25-30份、大黄 15-20份、黄柏 15-20 份。
本发明的中药复方药物组合物优选是散剂的形式， 更优选散剂的粒经为 50微米 以下。
本发明还涉及上述中药复方药物组合物的制备方法， 包括将上述配比的黄连、黄 芩、 大黄、 和黄柏超微粉碎， 并混合， 任选制成散剂的形式。
优选地， 将黄连、 黄芩、 大黄、 和黄桕超微粉碎至 50微米以下。
本发明还提供了本发明的中药复方药物组合物在制备用于防治水产动物疾病的 药物的应用。 本发明的中药复方药物组合物尤其用于治疗水产动物的爆发性出血病， 以及肠炎、 烂鳃病、 赤皮病等疾病。
具体地， 本发明的中药复方药物组合物的制备方法如下-
( 1 )称取下列中药材为原料： 黄连 2-15份、 黄苓 2-30份、 大黄 5-25份、 黄柏 3-35份。
(2 ) 将各组分洗净烘干， 经超微粉碎后按所需比例组合， 搅拌均匀制成散剂即 得。 (3) 由该方法制成的中药复方药物组合物粒径在 50微米以下。
本发明的优点和积极效果在于：
( 1 ) 本发明发挥中药复方制剂的组合效应治疗疾病， 疗效确切， 见效快， 用于 防治水产动物爆发性出血病， 以及肠炎、 烂鳃病、 赤皮病等疾病。
(2)本发明釆用超微粉碎技术，增大药物颗粒的表面积，增强药物的溶出和吸收， 从而提高药物疗效。 与普通粉碎方法制备的粉剂相比， 药物使用剂量减少， 节省药材 资源。
(3) 本发明为纯中药制剂， 毒副作用小、 不会产生危害人类健康的药物残留、 不易产生耐药性、 不污染环境、 不引发药源性疾病。
( 4 ) 在防治水产动物病害过程中， 除了兼有药物性和营养性外， 还具有提高水 产动物生产性能和饲料利用率的功效。 附图说明
下面结合附图和具体实施方式对本发明作进一步的详细说明。
图 1为四黄粉超微粉剂粒径的体积分布曲线。 具体实施方式
实施例 1
黄连 9份， 黄芩 27份， 大黄 18份， 黄柏 18份， 烘千， 超微粉碎， 过筛， 按所 需比例组合， 搅拌均匀制成散剂即得， 药物粒径控制在 50微米以下。
实施例 2
黄连 2份， 黄芩 2份， 大黄 5份， 黄柏 3份， 烘干， 超微粉碎， 过筛， 按所需比 例组合， 搅拌均匀制成散剂即得， 药物粒径控制在 50微米以下。
实施例 3
黄连 8份， 黄芩 16份， 大黄 15份， 黄柏 19份， 烘干， 超微粉碎， 过筛， 按所 需比例组合， 搅拌均匀制成散剂即得， 药物粒径控制在 50微米以下。 黄连 I5份， 黄芩 30份， 大黄 25份， 黄柏 35份， 烘干， 超微粉碎， 过筛， 按所 需比例组合， 搅拌均匀制成散剂即得， 药物粒径控制在 50微米以下。
实施例 5
该中药复方药物组合物按照如下方法制备取得：
( 1 ) 称取下列中药材为原料： 黄连 9份、 黄芩 27份、 大黄 18份、 黄柏 18份。
(2 ) 将各组分洗净烘干， 经超微粉碎后按所需比例组合， 搅拌均匀制成散剂即 得。
(3 ) 药物粒径控制在 50微米以下。 观察例
观察例 1
釆用本发明实施例 1对南美白对虾生长促进作用的观察
150cmx80cmx80cm的玻璃缸 12口， 每口缸装水 800L, 并用纱窗布罩住， 防止 虾跳出。试验期间水温为 20~28°C，整个养殖过程以充气泵连续充氧。试验前对室内 环境、 玻璃缸、 工具进行彻底消毒。
购平均体重为 (0.98±0.25)g南美白对虾， 暂养 7天后， 弃去小、 弱的个体， 将大 小规格基本一致 （平均体重为 (1.0±0.17)g) 的虾用于实验； 暂养期间投喂基础饵料。 每组随机抽取 30尾测量体重， 并将其作为试验虾的初始重量。 每口缸放养南美白对 虾 150只。
设八、 B、 C、 D四组， 每组又设 3个平行。 A、 B、 C分别是低、 中、 高药物剂 量组， 分别以 lg/kg、 2g/kg, 4g/kg的中药复方药物组合物药饵投喂， 每半个月连续 投喂七天， 其余时间投喂基础饲料； D组为阴性对照组， 投喂基础饲料。 试验期间每 天记录水温和生长、 死亡情况， 清除水底残饵、 粪便以及死亡个体， 并视水质情况换 水 1/3〜： 1/2。 各组每天投喂相应饵料两次， 上午 9时和下午 4时各一次， 投饵量以 2 小时内基本吃完为准。 生长试验进行了 60天。
经过 60天的养殖， 生长试验结束时， 对照组和各中药复方药物组合物试验组南 美白对虾的促生长作用结果见表 1。 表 1 中药复方药物组合物药饵对南美白对虾的生长和存活率的促进作用
Figure imgf000006_0001
对试验数据进行统计处理， 经 ANOVA分析检验， 在日增重率、存活率两个指标 上， A、 B、 C组明显高于对照组。 A组与对照组有显著差异， P<0.05; B、 C组与 对照组有极显著差异， P<0.01 ; B、 C组与 A组有显著差异， P<0.05。 B组的曰增 重率略高于 C组， 存活率略低于 C组， 但这两组之间无显著差异， P>0.05。
观察例 2
对嗜水气单胞菌病的治疗效果观察 采用本发明实施例 2中药复方药物组合物治疗鲤鱼肠炎，将实施例 2中药复方药 物组合物药物按照 lg/kg、 2.5g/kg、 5g/kg、 7.5g/kg, lOg/k 浓度制成药饵料进行投喂 治疗， 并与常规方法制成的相同组分的散剂 lg/kg、 2.5g/kg、 5g/kg, 7.5g/kg、 lOg/kg 浓度药饵进行对比。试验结果表明在 360小时内， 本发明的中药复方制剂的治愈率分 别是 85%、 100%、 100%、 100%、 100%,常规方法制作的制剂的治愈率分别是 49%、 62%、 83%、 94%和 100%。 因此， 本发明制作的中药复方制剂在饲料中的有效使用 剂量为 0.25%， 比常规方法制作的对鲤鱼肠炎表现出更好的治疗作用。
观察例 3
釆用本发明实施例 3对提高中华鳖生产性能效果的观察
面积 180m2的供试蹩池五个， 编号 A、 B、 C、 D、 E。 每只鳖约 250克， 共 5000 只， 分养于五个鳖池， 每池放养 1000只； 放养前随机抽取 50只测量体重。 养殖场定 期消毒。
A池为阴性对照组， 一直投喂基础饲料； B池和 C池为低剂量药物组， 按 2g/kg 的中药复方药物组合物药饵投喂， D池和 E池为高剂量药物组， 按 4g/kg的中药复方 药物组合物药饵分别投喂， 每半个月连续投喂七天， 其余时间投喂基础饲料； 各池的 饵料投喂量保持一致。试验期间定期检测水质， 消毒以及施用生物制剂等操作各池均 保持一致。 试验共进行了 90天。
经过 90天的饲养， 将各池的鳖起捕， 随机抽取 50只称重， 试验结果见表 2。 中药复方药物组合物药饵对中华鳖的生长和抗病力的促进作用
Figure imgf000007_0001
经 ANOVA分析检验， 在日增重率、 存活率两个指标上， B、 C、 D、 E池明显 高于 A池， 有极显著差异， P<0.01 ; 而 B、 C、 D、 E池之间无显著差异， P>0.05。 观察例 4
采用本发明实施例 4对草鱼常见细菌性疾病的预防和治疗作用研究
肠炎病、 赤皮病、 烂鳃病、 细菌性败血症为草鱼养殖过程中常见的细菌性疾病。 随机选取湖北新洲、 孝感、 蕲春、 武穴、 黄梅、 荆州、 仙祧、 江夏等地区的主养 草鱼的精养池塘， 面积为 2〜30亩不等， 水深为 1〜2米； 投喂草鱼商品饵料。 选择 不同程度发生了肠炎病、 赤皮病、 烂鳃病、 细菌性败血症等细菌性疾病的池塘共 105 口进行治疗试验。 分别以 2g/kg的实施例 4中药复方药物组合物、 2g/kg中药复方组 合物粗粉药饵连续投喂 6天、 以 1.5g/kg的盐酸环丙沙星粉药饵连续投喂 4天的方法 进行疾病治疗。 每天记录养殖情况和发病情况。
对于不同程度暴发了肠炎病、 赤皮病、 烂鳃病、 细菌性败血症等疾病的池塘， 治 疗效果详见表 3。 药物对草鱼细菌性疾病的治疗结果
Figure imgf000008_0001
表 3结果表明， 实施例 4中药复方组合物对肠炎、 赤皮、 烂鳃、 细菌性败血症等 水产动物常见细菌性疾病有显著的预防和治疗作用，而且其治疗有效率明显好于中药 复方组合物粗粉和盐酸环丙沙星。
观察例 5 经激光粒度检测仪 （MALVERN VALIDATION INITIATIVE) 检测， 中药复方 组合物的粒径在 50微米以下， 其中有 50% (体积份数） 达到了 12.30微米以下， 有 90 %达到了 27.26微米以下。 结果见图 1、 表 4。 四黄粉超微粉剂的粒径分布
Figure imgf000009_0001
注： 体积 （％) 栏表示的是该粒径范围内所含超微粉剂的体积份数

Claims

权 利 要 求
1、一种中药复方药物组合物，其特征在于由下述重量配比的原料制成：黄连 2-15 份、 黄芩 2-30份、 大黄 5-25份、 黄柏 3-35份。
2、 权利要求 1所述的中药复方药物组合物， 其特征在于由下述重量配比的原料 制成： 黄连 5-12份、 黄苓 10-30份、 大黄 10-20份、 黄柏 10-25份。
3、 权利要求 1所述的中药复方药物组合物， 其特征在于由下述重量配比的原料 制成： 黄连 8-10份、 黄芩 25-30份、 大黄 15-20份、 黄柏 15-20份。
4、 权利要求 1-3 中任一项所述的中药复方药物组合物， 其特征在于它是散剂的 形式。
5、 权利要求 1所述的中药复方药物组合物， 其特征在于所述散剂的粒经为 50微 米以下。
6、 权利要求 1-5 中任一项所述的中药复方药物组合物的制备方法， 包括将权利 要求 1-4中任一项所限定的配比的黄连、 黄芩、 大黄、 和黄柏超微粉碎， 并混合， 任 选制成散剂的形式。
7、权利要求 5所述的制备方法制成的中药复方药物组合物， 其特征在于将黄连、 黄苓、 大黄、 和黄柏超微粉碎至 50微米以下。
8、 权利要求 1-4 中任一项所述的中药复方药物组合物在制备用于防治水产动物 疾病的药物的应用。
9、 权利要求 8所述的应用， 其中所述水产动物疾病为爆发性出血病， 以及肠炎、 烂鳃病、 赤皮病。
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