WO2004002451A1

WO2004002451A1 - Controllable released suppository used in milk-secreting channel

Info

Publication number: WO2004002451A1
Application number: PCT/CN2002/000449
Authority: WO
Inventors: Fang Chen; Xiaoguang Xiang; Guangping Jiang
Original assignee: Fang Chen; Xiaoguang Xiang; Guangping Jiang
Priority date: 2002-06-28
Filing date: 2002-06-28
Publication date: 2004-01-08
Also published as: AU2002318711A1; CN1226998C; CN1516577A

Abstract

The invention relates to a controllable released suppository useful in milk-secreting channel. Said suppository comprises the body of suppository with length of 10-70 mm and length-diameter ratio of 10-20:1, and a coating over the body of suppository. The body of suppository have 1-7 release layers, said each layer contains 50-95 wt% release base and 5-50 wt% a pharmaceutical active ingredient in basis of the total weight of release base and active ingredient. Said suppository can be used for treatment of mastitis during milk-secreting and weaning periods in animals, such as milk cows. It is also effective in treatment of contusion caused by injury or in preventing adhesion for the channel after stricturotomy.

Description

可控释型奶道栓技术领域 TECHNICAL FIELD

本发明涉及畜牧兽医领域，具体地涉及适用于奶牛等产奶动物的可控释型或缓释型奶道栓。背景技术 The invention relates to the field of animal husbandry and veterinary medicine, in particular to a controlled-release or slow-release milk canal suppository suitable for dairy animals such as cows. Background technique

奶牛等动物在 "泌乳期"、 "干奶"及 "干奶期"常常发生***炎，或者奶道因外伤引起内挫伤时常出现奶道粘连，严重的甚至引起奶道堵塞。此外，对奶道狭窄进行手术后容易发生奶道粘连。目前，国内外尚无有效的解决办法。 In cows and other animals, mastitis often occurs during the "lactation period", "dry milk" and "dry period", or the milk canal is often blocked due to internal contusion due to trauma, which can even lead to blockage of the milk canal. In addition, milk duct adhesions are prone to occur after surgery for milk duct stenosis. At present, there is no effective solution at home and abroad.

一种常用的解决方法是注射抗生素药物防治***炎，然而，这样必然使奶牛产生抗生素抗体，或者使奶牛的泌乳中含有抗生素残留物。 A common solution is to inject antibiotic drugs to prevent mastitis. However, this will inevitably cause cows to produce antibiotic antibodies, or the cow's lactation will contain antibiotic residues.

另一种方法是用机械扩张器防止奶道内挫伤时引起奶道粘连闭锁。然而，机械扩张常诱发***炎，这样势必影响牛奶产量，并使牛奶品质下降。 Another method is to use mechanical dilators to prevent the milk duct from being blocked and blocked in the milk duct. However, mechanical expansion often induces mastitis, which will definitely affect milk production and reduce milk quality.

另一种方法是口服给予以抗生素 (磺胺类)为主要成分的药物，但易产生抗生素残留，或者是口服黄连、蒲公英、银花等植物制剂，但效果不显著。 Another method is to orally administer antibiotics (sulfa drugs) as the main component, but it is easy to produce antibiotic residues, or oral preparations of Coptis chinensis, dandelion, silver flower, etc., but the effect is not significant.

此外，国外已有釆用奶道栓来进行***疾病护理的报道，但其奶道栓不含药物成分或含抗生素，且长度不超过 30mm，有时不能达到病变部位；只能起到物理隔离的护理作用，无法起有效的治疗效果。 In addition, foreign countries have reported using breast milk plugs for breast disease care, but the milk breast plugs do not contain pharmaceutical ingredients or antibiotics, and the length does not exceed 30 mm. Sometimes the lesions cannot be reached; only physical isolation can be achieved. Nursing effect, can not play an effective therapeutic effect.

因此，本领域迫切需要开发有效解决上述问题的新技术。发明内容 Therefore, there is an urgent need in the art to develop new technologies that effectively solve the above problems. Summary of the Invention

本发明的目的就是提供一种可控释型奶道栓，该奶道栓可防治奶牛等经济动物在 "泌乳期" "干奶期"过程中的***炎，并可有效治疗和 /或预防 (1)因外伤引起的奶道内挫伤所造成的奶道粘连，以及 (2)因奶道狭窄进行手术后的奶道粘连。本发明提供了一种可控释型奶道栓，包括： The purpose of the present invention is to provide a controllable release milkway plug, which can prevent and treat mastitis of economic animals such as cows during the "lactation period" and "drying period", and can effectively treat and / or prevent (1) Adhesion to the milk duct due to intratraumatic contusion due to trauma, and (2) Adhesion to the milk duct after surgery due to a narrowed milk duct. The present invention provides a controllable-release milk canal suppository, including:

(a)柱状栓体，其长度为 10— 70毫米，其长径比为 10— 20 : 1； (a) a cylindrical plug with a length of 10-70 mm and an aspect ratio of 10-20: 1;

(b)位于栓体外部的外壳层，所述外壳层为包裹层；确认本 (c)位于栓体内部的 1一 7层释放层，所述各释放层含有 50— 95重量％释放基质和 5— 50重量％的药物活性成分，按各层的缓释基质和药物活性成分的总重在一优选例中，所述的栓体的横截面为圆形、椭圆形、卵形、多边形、或其组合，且直径为 l _ 5mm。 (b) a shell layer located on the outside of the bolt body, the shell layer being a wrapping layer; (c) One to seven release layers located inside the plug body, each release layer containing 50-95% by weight of a release matrix and 5-50% by weight of a pharmaceutically active ingredient, and each layer of the sustained-release matrix and the pharmaceutically active ingredient In a preferred example, the cross section of the plug body is circular, oval, oval, polygonal, or a combination thereof, and has a diameter of 1-5 mm.

在一优选例中，所述的药物活性成分包括天然植物的提取物。更佳地，所述的植物提取物是选自下列植物的提取物：黄连、蒲公英、板蓝根、血竭、银花、连翘、瓜萎、丝瓜络、芙蓉叶、或其混合物。 In a preferred example, the pharmaceutically active ingredients include natural plant extracts. More preferably, the plant extract is an extract selected from the following plants: Coptis chinensis, dandelion, isatis root, blood exhaustion, silver flower, forsythia, melon wilt, loofah, hibiscus leaf, or a mixture thereof.

在另一优选例中，所述的释放基质选自下组：硬脂酸、甘油、明胶、甘油明胶基质、可可豆脂基质、香果脂基质、石蜡基质、蜂蜡基质、或其混合物。 In another preferred example, the release matrix is selected from the group consisting of stearic acid, glycerin, gelatin, glycerin gelatin matrix, cocoa butter matrix, fragrant butter matrix, paraffin matrix, beeswax matrix, or a mixture thereof.

在另一优选例中，栓体的长度为 30— 60mm，直径为 2.5— 3.5mm。 In another preferred example, the length of the plug body is 30-60 mm and the diameter is 2.5-3.5 mm.

在另一优选例中，各释放层含有 60— 90重量％释放基质和 10— 40重量％的药物活性成分，按释放基质和药物活性成分的总重量计。 In another preferred example, each release layer contains 60-90% by weight of a release matrix and 10-40% by weight of a pharmaceutically active ingredient, based on the total weight of the release matrix and the pharmaceutically active ingredient.

在另一优选例中，在栓体的一端设置有直径大于栓体直径的凸台型的栓帽，且在栓体的另一端设置有锥头。 In another preferred example, a boss-type plug cap having a diameter larger than the diameter of the plug body is provided at one end of the plug body, and a cone head is provided at the other end of the plug body.

在另一优选例中，在栓体内部有 2层释放层，位于外侧的释放层的释放速度大于位于内侧的释放层。 In another preferred example, there are two release layers inside the plug body, and the release speed of the release layer located on the outside is faster than the release layer located on the inside.

在另一优选例中，所述的外壳层为胶囊包裹层。附图说明 In another preferred example, the shell layer is a capsule coating layer. BRIEF DESCRIPTION OF THE DRAWINGS

图 1是本发明的一种优选可控释型奶道栓的外型示意图； FIG. 1 is a schematic diagram of a preferred controllable-release milk duct plug of the present invention;

图 2是图 1中的 A— A的截面示意图。具体实施方式 FIG. 2 is a schematic cross-sectional view taken along A-A in FIG. 1. detailed description

本发明人经过广泛而深入的研究，将天然植物药与可控释剂型相结合，并采用特定的栓剂形式，可以有效地防治***炎或治疗奶道内挫伤，并减少或消除牛奶中抗生素残留。在此基础上完成了本发明。如本文所用，栓体的 "直径"指横截面中所能容纳的最大圆的直径。如本文所用，栓体的 "长径比"指栓体长度与栓体直径的比值。如图 1所示，奶道栓的栓体 1为柱体，栓体的形状为圆柱、棱柱等长径比较大的细长柱体。通常，本发明可控释型奶道栓的柱状栓体长度为 10— 70毫米，较佳地 30— 60毫米，更佳地 40— 60毫米；其长径比为 10— 20: 1。栓体的直径通常为 1— 5mm，较佳地为 2— 4mm，更佳地为 2.5— 3.5mm。 After extensive and intensive research, the present inventors combined natural plant medicines with controlled-release dosage forms and adopted specific suppository forms, which could effectively prevent mastitis or treat contusions in the milk canal, and reduce or eliminate antibiotic residues in milk. The present invention has been completed on this basis. As used herein, the "diameter" of the plug body refers to the diameter of the largest circle that can be accommodated in cross section. As used herein, the "aspect ratio" of a plug body refers to the ratio of the length of the plug body to the diameter of the plug body. As shown in FIG. 1, the plug body 1 of the lactation plug is a cylinder, and the shape of the plug body is a slender column with a relatively large diameter such as a cylinder or a prism. Generally, the length of the cylindrical plug of the controlled-release milk duct plug of the present invention is 10-70 mm, preferably 30-60 mm, and more preferably 40-60 mm; and its aspect ratio is 10-20: 1. The diameter of the plug body is usually 1-5 mm, preferably 2-4 mm, and more preferably 2.5-3.5 mm.

为了便于使用，在栓体的一端设置可有直径大于栓体直径的凸台型的栓帽 2, 在栓体的另一端设置有锥头 3，栓帽便于手工操作，而圆锥型的锥头便于将栓剂***奶道内。栓帽的直径通常约为 5— 7mm。 For the convenience of use, one end of the bolt body is provided with a boss-type bolt cap 2 having a diameter larger than the diameter of the bolt body, and the other end of the bolt body is provided with a cone head 3, the bolt cap is convenient for manual operation, and the cone-shaped cone head Easy to insert suppositories into the milk canal. The diameter of the bolt cap is usually about 5-7mm.

本发明的可控释型奶道栓具有位于栓体内部的 1一 7层 (较佳地 2— 4层：)可控释层，所述各释放层含有 50— 95重量％缓释基质和 5— 50重量％的药物活性成分，按释放基质和药物活性成分的总重量计。各释放层的释放基质和药物活性成分的种类和 /或含量不同，从而提供不同的药物活性成分，或者以不同的释放速度提供活性成分。 The controllable-release milk duct plug of the present invention has 1-7 layers (preferably 2-4 layers) in the body of the controllable release layer. Each of the release layers contains 50-95% by weight of a sustained-release matrix and 5-50% by weight of the pharmaceutically active ingredient, based on the total weight of the release matrix and the pharmaceutically active ingredient. The types and / or contents of the release matrix and the pharmaceutically active ingredient of each release layer are different, so as to provide different pharmaceutically active ingredients, or to provide the active ingredients at different release rates.

如图 1所示，在一优选例中，可控释型奶道栓含有外壳层 7，以及位于外壳层之内的快速释放层 4、中速释放层 5和慢速释放层 6。快速释放层的作用在于能快速释放特定的药物，促进药物吸收。而中速和慢速释放层是在 2— 4天，以及 3— 8天内缓慢释放药物。 As shown in FIG. 1, in a preferred example, the controlled-release milk duct plug includes a shell layer 7, and a quick-release layer 4, a medium-speed release layer 5, and a slow-release layer 6 located within the shell layer. The role of the quick release layer is to be able to release specific drugs quickly and promote drug absorption. The medium and slow release layers release drugs slowly in 2-4 days and 3-8 days.

在本发明中，通过对药栓结构中每一层主要基质成分配方的调整，实现对药物释放时间与量的调整。一个优选的 3层的可控释型奶道栓的配方如下： In the present invention, by adjusting the formulation of the main matrix components in each layer of the drug suppository structure, adjustment of the time and amount of drug release is achieved. A preferred 3-layer controlled release milkway suppository is formulated as follows:

快速释放层，基质配方：按基质的总重量计，硬脂酸 80%、甘油 10%、可可豆脂 10%，释放时间约 30分钟； Quick-release layer, matrix formula: based on the total weight of the matrix, stearic acid 80%, glycerol 10%, cocoa butter 10%, release time is about 30 minutes;

中速释放层，基质配方：按基质的总重量计，硬脂酸 60%、甘油 10%、明胶 30%，释放时间约 3天； Medium release layer, matrix formulation: based on the total weight of the matrix, 60% stearic acid, 10% glycerol, 30% gelatin, release time is about 3 days;

慢速释放层，基质配方：按基质的总重量计，硬脂酸 50%、甘油 2%、明胶 40%, 石蜡 6%，吐温 2%，释放时间约 8天。 Slow release layer, matrix formulation: Based on the total weight of the matrix, 50% stearic acid, 2% glycerol, 40% gelatin, 6% paraffin, 2% Tween, and release time is about 8 days.

适用于本发明的植物没有特别限制，可以是任何含有杀菌或抑菌成分的植物。代表性的植物包括黄连、蒲公英、板蓝根、血竭、银花、连翘、瓜萎、丝瓜络、芙蓉叶等，它们可以单独使用或混合使用。优选的植物包括黄连、蒲公英、板蓝根、血竭等。黄连为毛茛科植物黄连属植物的干燥根茎。主要成分包括小檗碱、黄连碱、甲基黄连碱等多种生物碱，以及阿魏酸等物质。黄连对痢疾杆菌，伤寒杆、大肠杆菌、绿脓杆菌、葡萄球菌、溶血性链球菌、肺炎双球菌等有抑制作用。对流感病毒、钩端螺旋体、阿米巴原虫及皮肤真菌亦有抑制作用，同时能增强奶牛白细胞的吞噬能力。 The plant suitable for the present invention is not particularly limited, and may be any plant containing a fungicidal or bacteriostatic component. Representative plants include Coptis chinensis, dandelion, isatis root, blood exhaustion, silver flower, forsythia, melon wilt, loofah, hibiscus leaf, etc., which can be used alone or in combination. Preferred plants include Coptis chinensis, dandelion, isatis root, blood exhaustion and the like. Pistacia is a dried rhizome of the ranunculus family Pistacia. The main ingredients include berberine, berberine, methyl berberine and other alkaloids, as well as ferulic acid and other substances. Coptis chinensis inhibits dysentery bacillus, typhoid bacillus, E. coli, Pseudomonas aeruginosa, staphylococcus, hemolytic streptococcus, pneumococcus, and the like. It also has inhibitory effects on influenza virus, Leptospira, amoebia and skin fungi, and can enhance the phagocytic ability of cow white blood cells.

蒲公英为菊科植物。主要成分包括：三萜醇，留醇、苦素、咖啡酸、菊糖、果胶、胆碱等。蒲公英对金黄色葡萄球菌和多种皮肤真菌有抑制作用。 Dandelions are plants in the family Asteraceae. The main ingredients include: triterpene alcohol, sterol, picrin, caffeic acid, inulin, pectin, and choline. Dandelion inhibits Staphylococcus aureus and various skin fungi.

可用于本发明的制备植物提取物的方法没有特别限制，可以是常规的各种提取法，例如水煮法。即将药材与足量水一起煮数小时，然后过滤即可。也可使用其他提取法，如萃取法。 The method for preparing a plant extract that can be used in the present invention is not particularly limited, and may be various conventional extraction methods, such as a boiling method. That is, the medicinal materials are boiled with a sufficient amount of water for several hours, and then filtered. Other extraction methods, such as extraction methods, can also be used.

一种特别有用的药物优选成分是含 8— 15重量份 (较佳地约 12份：)黄连提取物、 4一 8重量份 (较佳地约 6份)蒲公英提取物、 1一 2重量份 (较佳地约 14份)板蓝根提取物、和 0.2— 1重量份 (较佳地约 0.6份)血竭提取物的混合物。 A particularly useful pharmaceutical preferred ingredient is 8-15 parts by weight (preferably about 12 parts): Coptis chinensis extract, 4 to 8 parts by weight (preferably about 6 parts) dandelion extract, 1 to 2 parts by weight (Preferably about 14 parts) a mixture of isatis root extract and 0.2-1 part by weight (preferably about 0.6 parts) of the blood exhaustion extract.

此外，在本发明的药物活性成分还可包括抗生素、抗氧化剂、稳定剂等额外的添加剂。 In addition, the pharmaceutically active ingredient of the present invention may include additional additives such as antibiotics, antioxidants, and stabilizers.

适用于本发明可控释型奶道栓的释放基质没有特别限制，可以是本领域常用的缓释基质，代表性的例子包括 (但并不限于)：硬脂酸、甘油、明胶、甘油明胶基质、可可豆脂基质、香果脂基质、石腊基质，或其混合物。 The release matrix suitable for the controlled-release type milk canal suppository of the present invention is not particularly limited, and may be a slow-release matrix commonly used in the art. Representative examples include (but are not limited to): stearic acid, glycerin, gelatin, glycerin gelatin Base, cocoa butter base, meringue base, paraffin base, or mixtures thereof.

适用于本发明可控释型奶道栓的外壳材料没有特别限制，可以是本领域常用的明胶类材料，一种优选的外壳层材料为胶囊包裹层 (明胶 +钛白粉)。这些胶囊包裹层材料可方便地从市场上 (如成都昊太胶囊材料厂 (成都，中国)等)购得。 The shell material suitable for the controlled-release type milk duct plug of the present invention is not particularly limited, and may be a gelatin-based material commonly used in the art. One preferred shell layer material is a capsule coating layer (gelatin + titanium dioxide). These capsule coating materials can be easily purchased from the market (such as Chengdu Haotai Capsule Material Factory (Chengdu, China), etc.).

制造本发明可控释型奶道栓的技术没有特别限制，可以常用栓剂领域的常规技术。以 3层的可控释型奶道栓为例，一种制备过程如下： The technique for manufacturing the controlled-release type milk canal suppository of the present invention is not particularly limited, and conventional techniques in the field of suppositories can be used. Taking a 3-layer controlled release milkway suppository as an example, a preparation process is as follows:

(a)将慢速释放基质加热熔化，加入适量药物，迅速搅拌均匀，注入 1#栓模，冷却、出模，得到慢速释放层的栓体部分 1 ; (a) The slow-release matrix is heated and melted, an appropriate amount of drug is added, and the mixture is quickly stirred and uniformly injected into the # 1 plug mold, cooled and ejected to obtain the plug body portion 1 of the slow-release layer;

(b)将中速释放基质加热熔化，加入适量药物，迅速搅拌均匀，注入 2#栓模， ***前面工序已得到的栓体部分 1，冷却、出模，得到栓体部分 2; (b) The medium-speed release matrix is heated and melted, an appropriate amount of drug is added, and the mixture is stirred quickly, injected into the # 2 plug mold, inserted into the plug body portion 1 obtained in the previous process, and cooled and ejected to obtain the plug body portion 2;

(c)将快速释放基质水浴溶化，加入适量药物，迅速搅拌均匀，注入 3#栓模， ***前工序已经得到的栓体部分 2，冷却、出模，得到栓体部分 3 ; (d) 将包裹层基质加热熔化。 ***栓体部分 3，缓慢取出，冷却，即得到多层可控释型奶道栓。 (c) Melt the quick-release matrix water bath, add an appropriate amount of drug, stir quickly, inject into the # 3 plug mold, insert the plug body part 2 obtained in the previous step, and cool and exit the mold to obtain the plug body part 3; (d) Heat the cladding substrate to melt. Insert the plug body part 3, take it out slowly, and cool to obtain a multi-layer controlled release milkway plug.

本发明可控释型奶道栓的使用很方便。当奶牛发生***炎、干奶期及出现奶道内挫伤时，将可控释型奶道栓缓缓置入奶道即可。栓内药物有效成分在奶道内持续释放，奶道栓将全部自行在奶道内溶融和溶解。可控释型奶道栓含有天然植物药，故能有效抑制和杀灭奶道内有害病菌，同时也能有效阻止外部病菌的侵入。再加上可控释给药，能保证药物有效地发挥作用，根据不同的治疗需要持续给药的目的，故有效解决了 "泌乳期" 、 "干奶"及 "干奶期"***炎的防治，及奶道粘连导致挤奶困难等难题。本发明的优点在于： The controllable-release milk duct plug of the present invention is convenient to use. When cows develop mastitis, dry periods, and bruises in the milk canal, place a controlled release milk canal plug into the milk canal. The active ingredients in the suppository are continuously released in the milk duct, and all the milk duct plugs will melt and dissolve in the milk duct by themselves. The controlled release milkway suppository contains natural plant medicines, so it can effectively inhibit and kill harmful bacteria in the milkway, and can also effectively prevent the invasion of external bacteria. Coupled with controlled-release drug delivery, it can ensure that the drug effectively functions. According to the purpose of continuous treatment according to different treatment needs, it effectively solves the problems of "lactation", "dry milk" and "dry milk" mastitis. Prevention and treatment, and milking difficulties such as milking difficulties. The advantages of the present invention are:

(1) 操作简便，快捷，实用。 (1) The operation is simple, fast and practical.

(2) 直接对病变部分进行治疗，缩短治疗周期，提高治疗效果。 (2) Directly treat the diseased part, shorten the treatment cycle and improve the treatment effect.

(3) 成本低廉。 (3) Low cost.

(4) 有效成分均系天然植物的提取物，无毒副作用，无残留。 (4) The active ingredients are all natural plant extracts, with no toxic side effects and no residue.

(5) 减少或消除抗生素的使用。 (5) Reduce or eliminate the use of antibiotics.

下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。实施例 1 The present invention is further described below with reference to specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. Example 1

植物提取物的制备 Preparation of plant extracts

黄连素按本领域常规的酸性乙醇法提取小檗碱的方式制备。简而言之，取黄连粗粉（过三号筛）适量 0.1%HC1乙醇（85%) 液渗滤，用 HC1乙醇液渗滤至无色，收集渗滤液。减压回收乙醇，得浓缩液，再加适量稀 HC1溶液溶解，冷置过夜。过滤，收集滤液，残渣用水洗，收集洗液，并与滤液合并，放出沉淀，过滤得沉淀物（小檗碱）。将沉淀物用氯仿及氨水进行精制，挥去氯仿得高纯度黄连素生物碱。 Berberine is prepared in the manner of extracting berberine by the acidic ethanol method conventional in the art. In brief, take the Coptis chinensis powder (passed through the No. 3 sieve) and diafiltration with an appropriate amount of 0.1% HC1 ethanol (85%), diafiltration with HC1 ethanol solution to colorless, and collect the leachate. The ethanol was recovered under reduced pressure to obtain a concentrated solution, and an appropriate amount of a dilute HC1 solution was added to dissolve the solution. Filter, collect the filtrate, wash the residue with water, collect the washings, combine with the filtrate, release the precipitate, and filter to obtain a precipitate (berberine). The precipitate was refined with chloroform and ammonia, and chloroform was evaporated to obtain a high-purity Berberine alkaloid.

蒲公英、板蓝根、血竭按渗漉法提取浸膏的方式制备。简而言之，取蒲公英 1000g,粉碎粗粉，加 7倍量的 75%乙醇作溶剂，浸渍 48小时后，以每分钟 l〜3ml 的速度渗漉，收集初漉液，另器保存，继续渗漉，待有效成份完全漉出，收集续漉液，在 60°C减压回收乙醇，提取物浓缩至浸膏状适量，低温干燥，研细，过六号筛，即得蒲公英浸膏。板蓝根、血竭浸膏提取方式与蒲公英相同。 Dandelion, isatis root, and blood exhaustion were prepared by the method of extracting extracts by infiltration method. In short, take 1000g of dandelion, pulverize the coarse powder, add 7 times the amount of 75% ethanol as a solvent, and soak for 48 hours, then l ~ 3ml Percolate at a rapid rate, collect the initial solution, store it in another device, and continue to infiltrate until the effective ingredients are completely decanted. Collect the subsequent solution, recover the ethanol under reduced pressure at 60 ° C, concentrate the extract to the appropriate amount of extract, and dry at low temperature After sieving, pass through the No. 6 sieve to get dandelion extract. Banlangen and Xuejie extract are extracted in the same way as dandelion.

使用时，根据各种治疗要求，将上述植物提取物按适当的比例配置即可。一种特别优选的活性成分是混合以下物质而得的混合物： 12份黄连提取物、 6份蒲公英提取物、 14份板蓝根提取物、和 0.6份血竭提取物的混合物。实施例 2 When in use, the above-mentioned plant extract may be arranged in an appropriate ratio according to various treatment requirements. A particularly preferred active ingredient is a mixture obtained by mixing 12 parts of Coptis chinensis extract, 6 parts of dandelion extract, 14 parts of isatis root extract, and 0.6 parts of blood exhaustion extract. Example 2

可控释型奶道栓 1 Controlled release teat plug 1

栓体长 60毫米，横截面为圆形，直径 3毫米。 The body is 60 mm long, circular in cross section, and 3 mm in diameter.

本栓剂的外壳层为常用的胶囊包裹层 (主要成分为明胶加少量钛白粉)，在栓剂内部有三层释放层，由外至内分别是- 第 1层，含实施例 1中制备的植物提取物 30%，其余为快速释放层基质（基质配方：按基质的总重量计，硬脂酸 80%、甘油 10%、可可豆脂 10%，释放时间约 30分钟。） The outer shell layer of this suppository is a commonly used capsule coating layer (the main component is gelatin plus a small amount of titanium dioxide), and there are three release layers inside the suppository, from the outside to the inside, respectively-the first layer containing the plant extract prepared in Example 30% of the content, the rest is a fast-release layer matrix (matrix formula: based on the total weight of the matrix, 80% stearic acid, 10% glycerol, 10% cocoa butter, release time is about 30 minutes.)

第 2层，含实施例 1中制备的植物提取物 25%，其余为中速释放层基质（基质配方：按基质的总重量计，硬脂酸 60%、甘油 10%、明胶 30%，释放时间约 3 天。） The second layer contains 25% of the plant extract prepared in Example 1, and the rest is a medium-release layer matrix (matrix formula: based on the total weight of the matrix, stearic acid 60%, glycerol 10%, gelatin 30%, release It takes about 3 days.)

第 3层，含实施例 1中制备的植物提取物 35%，其余为慢速释放层基质（基质配方：按基质的总重量计，硬脂酸 50%、甘油 2%、明胶 40%，石蜡 6%，吐温 2%，释放时间约 8天。）实施例 3 The third layer contains 35% of the plant extract prepared in Example 1, and the rest is a slow-release layer matrix (matrix formula: based on the total weight of the matrix, 50% stearic acid, 2% glycerol, 40% gelatin, paraffin 6%, Tween 2%, release time is about 8 days.) Example 3

可控释型奶道栓 1 Controlled release teat plug 1

栓剂的形状如图 1。栓体长度为 55毫米，横截面为圆形，直径 3.5毫米。本栓剂的外壳层为常用的胶囊包裹层 (主要成分为明胶加少量钛白粉)，在栓剂内部有二层释放层，由外至内分别是： The suppository shape is shown in Figure 1. The plug has a length of 55 mm, a circular cross-section, and a diameter of 3.5 mm. The outer layer of the suppository is a commonly used capsule coating layer (the main component is gelatin plus a small amount of titanium dioxide). There are two release layers inside the suppository, from the outside to the inside:

第 1层，含实施例 1中制备的植物提取物 30%，其余为中速缓放基质（按基质的总重量计，硬脂酸 60%、甘油 10%、明胶 30%，释放时间约 3天。）第 2层，含实施例 1中制备的植物提取物 15%，其余为慢速释放基质（按基质的总重量计，硬脂酸 50%、甘油 2%、明胶 40%，石蜡 6%，吐温 2%，释放时间约 8天。）实施例 4 The first layer contains 30% of the plant extract prepared in Example 1, and the rest is a medium-speed slow release matrix (based on the total weight of the matrix, stearic acid 60%, glycerol 10%, gelatin 30%, and the release time is about 3 Days.) The second layer contains 15% of the plant extract prepared in Example 1, and the rest is a slow-release matrix (based on the total weight of the matrix, 50% stearic acid, 2% glycerol, 40% gelatin, 6% paraffin, spit The temperature is 2%, and the release time is about 8 days.) Example 4

可控释型奶道栓 3— 8 Controlled release milk duct plugs 3— 8

按与实施例 3相同方式制备奶道栓，不同点仅在于改变栓体的长度和直径。 A milk duct plug was prepared in the same manner as in Example 3 except that the length and diameter of the plug body were changed.

实施例 5

Example 5

动物试验 Animal test

当奶牛干奶时，挤尽最后一手乳汁后或有奶道内挫伤时，将实施例 2-4中制备的各可控释型奶道栓缓缓置入奶道。 When the cow is dry, after the last hand of milk is squeezed out or when there is a bruise in the milk duct, the controllable release milk duct plugs prepared in Examples 2-4 are slowly placed into the milk duct.

结果，奶牛顺利完成干奶，无任何炎症发生。奶牛有内挫伤的奶道正常愈合，奶道通畅，奶道无粘连。应理解，在阅读了本发明的上述讲授内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。 As a result, the cows finished the dry milk without any inflammation. Cows with internal bruises heal normally, the milk canals are smooth, and the milk canals are non-adhesive. It should be understood that after reading the above-mentioned teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims appended to this application.

Claims

权利要求书 Claim

1.一种可控释型奶道栓，其特征在于，包括： A controllable release milkway suppository, comprising:

(a)柱状栓体，其长度为 10— 70毫米，其长径比为 10— 20: 1； (a) a cylindrical plug with a length of 10-70 mm and an aspect ratio of 10-20: 1;

(b)位于栓体外部的外壳层，所述外壳层为包裹层； (b) a shell layer located outside the plug body, the shell layer being a wrapping layer;

(c)位于栓体内部的 1一 7层释放层，所述各释放层含有 50— 95重量％释放基质和 5— 50重量％的药物活性成分，按各层的缓释基质和药物活性成分的总重 (c) One to seven release layers located inside the plug body, each release layer containing 50-95% by weight of a release matrix and 5-50% by weight of a pharmaceutically active ingredient, and each layer of the sustained-release matrix and the pharmaceutically active ingredient Total weight

2.如权利要求 1所述的奶道栓，其特征在于，所述的栓体的横截面为圆形、椭圆形、卵形、多边形、或其组合，且直径为 1一 5mm。 The milk plug according to claim 1, wherein a cross section of the plug body is circular, oval, oval, polygonal, or a combination thereof, and has a diameter of 1 to 5 mm.

3.如权利要求 1所述的奶道栓，其特征在于，所述的药物活性成分包括天然植物的提取物。 The teat plug according to claim 1, wherein the pharmaceutically active ingredient comprises an extract of a natural plant.

4.如权利要求 3所述的奶道栓，其特征在于，所述的植物提取物是选自下列植物的提取物：黄连、蒲公英、板蓝根、血竭、银花、连翘、瓜萎、丝瓜络、芙蓉叶、或其混合物。 The milk canal suppository according to claim 3, wherein the plant extract is an extract selected from the following plants: Coptis chinensis, dandelion, isatis root, blood exhaustion, silver flower, forsythia, melon, Loofah, hibiscus leaves, or a mixture thereof.

5.如权利要求 1所述的奶道栓，其特征在于，所述的释放基质选自下组：硬脂酸、甘油、明胶、甘油明胶基质、可可豆脂基质、香果脂基质、石蜡基质、蜂蜡基质、或其混合物。 The milk canal suppository according to claim 1, wherein the release matrix is selected from the group consisting of stearic acid, glycerin, gelatin, glycerin gelatin matrix, cocoa butter matrix, vanillin matrix, and paraffin wax. Matrix, beeswax matrix, or mixtures thereof.

6.如权利要求 1所述的奶道栓，其特征在于，栓体的长度为 30— 60mm，直径为 2.5— 3.5mm。 The milk plug according to claim 1, wherein the plug body has a length of 30-60 mm and a diameter of 2.5-3.5 mm.

7.如权利要求 1所述的奶道栓，其特征在于，各释放层含有 60— 90重量％释放基质和 10— 40重量％的药物活性成分，按释放基质和药物活性成分的总重 The lactation suppository according to claim 1, wherein each release layer contains 60-90% by weight of a release matrix and 10-40% by weight of a pharmaceutically active ingredient, based on the total weight of the release matrix and the pharmaceutically active ingredient

8.如权利要求 1所述的奶道栓，其特征在于，在栓体的一端设置有直径大于栓体直径的凸台型的栓帽，且在栓体的另一端设置有锥头。 The teat plug according to claim 1, wherein a plug-type plug cap having a diameter larger than that of the plug body is provided at one end of the plug body, and a tapered head is provided at the other end of the plug body.

9.如权利要求 1所述的奶'道栓，其特征在于，在栓体内部有 2层释放层，位于外侧的释放层的释放速度大于位于内侧的释放层。 9. The milk plug according to claim 1, wherein there are two release layers inside the plug body, and the release speed of the release layer located outside is faster than the release layer located inside.

10.如权利要求 1所述的奶道栓，其特征在于，所述的外壳层为胶囊包裹层。 The teat plug according to claim 1, wherein the outer shell layer is a capsule encapsulating layer.