TWI569732B - Animal feed additive of plant origin - Google Patents
Animal feed additive of plant origin Download PDFInfo
- Publication number
- TWI569732B TWI569732B TW101112081A TW101112081A TWI569732B TW I569732 B TWI569732 B TW I569732B TW 101112081 A TW101112081 A TW 101112081A TW 101112081 A TW101112081 A TW 101112081A TW I569732 B TWI569732 B TW I569732B
- Authority
- TW
- Taiwan
- Prior art keywords
- feed additive
- feed
- copper
- zinc
- stabilizer
- Prior art date
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- 235000019730 animal feed additive Nutrition 0.000 title 1
- 239000000284 extract Substances 0.000 claims description 23
- 241000196324 Embryophyta Species 0.000 claims description 22
- 239000003674 animal food additive Substances 0.000 claims description 19
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 18
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Landscapes
- Fodder In General (AREA)
Description
本發明係關於一種飼料添加劑。 The present invention relates to a feed additive.
豬痢疾為一種在全球範圍內,以及在匈牙利廣泛分佈的疾病。除了無特定病源(Specific Pathogen Free,SPF)豬以外,此種疾病目前臨床上三分之一的家畜中存在,並且家畜中一更顯著的份額中為沒有症狀的感染。由於直接損失以及治療的高費用,此種疾病為在匈牙利以及其他主要養豬國家中經濟上最重要的問題之一。同時,在最近的幾十年內,對於醫藥、食品、保存以及化妝品行業中的天然、主要為植物源的物質之使用具有世界範圍的興趣。 Swine dysentery is a disease that is widespread on a global scale and in Hungary. In addition to the Specific Pathogen Free (SPF) pigs, the disease is currently present in one third of the clinically occurring livestock, and a more significant share of the livestock is an asymptomatic infection. Due to the direct loss and the high cost of treatment, this disease is one of the most economically important problems in Hungary and other major pig-raising countries. At the same time, in the last few decades, there has been worldwide interest in the use of natural, mainly plant-derived substances in the pharmaceutical, food, preservation and cosmetics industries.
此種疾病首先透過美國的威廷(Whiting)、道爾(Doyle)以及斯潘(Spray)描述(1921年)。在匈牙利,此種疾病的病理透過霍業里(Hegyeli)及希爾特(Hirt)(1942年),以及曼尼哥(Manninger)及考森特(Csontos)描述(1943),將其命名為傳染性的豬胃以及腸炎。雖然始終強調此疾病的傳染性,但是其病理上假定為幾種不同的微生物(病毒、弧形桿菌(弧菌)大腸菌、螺旋體、滴蟲等)。儘管此種疾病具有高的經濟影響力,但本病的病因僅在70年代初期才澄清。病原體由英國的泰勒(Taylor)及亞歷山大(Alexander)(1971年),以及美國的哈里斯(Harris)等(1972年)首先培養,並且闡明產生本疾病的病因作用。 The disease was first described by Whiting, Doyle, and Spray in the United States (1921). In Hungary, the pathology of this disease was named by Hegyeli and Hirt (1942), and by Manninger and Csontos (1943). Infectious pig stomach and enteritis. Although the infectivity of the disease has always been emphasized, it is pathologically assumed to be several different microorganisms (virus, arcabacter (Vibrio) coliform, spirochete, trichomoniasis, etc.). Despite the high economic impact of the disease, the cause of the disease was only clarified in the early 1970s. The pathogens were first cultivated by Taylor and Alexander (1971) in the United Kingdom, and Harris et al. (1972) in the United States, and clarified the etiology of the disease.
在最近的幾十年內,對於醫藥、食品、保存以及化妝品行業 中的使用天然、主要為植物源的物質的使用具有世界範圍的興趣。具有五百多種出版物討論這些物質的組成以及效能。 In the last few decades, for the pharmaceutical, food, preservation and cosmetics industries The use of natural, primarily plant-derived materials has a worldwide interest. There are more than 500 publications discussing the composition and efficacy of these substances.
此病原體係為豬痢疾短螺旋體(初期的小蛇菌,以前的密螺旋體),一種具有長、寬、不均勻螺旋的螺旋體。它能夠透過苯酚-品紅與吉姆薩(Giemsa)兩者染色,能夠在厭氧條件下在血液瓊脂上培養。包含介質的大觀霉素可用於其選擇性的培養。在有毒菌株之下以及圍繞有毒菌株,發生強烈的β-溶血。溶血素為一種具有細胞毒素特性的低分子量肽。基於自細胞壁中提取的脂多醣抗原,豬痢疾短螺旋體株可透過瓊脂凝膠沉澱(Agar Gel Precipitation,AGP)分析劃分為9個血清組。然而,在相同的血清組的菌株之間根據抗原結構具有進一步細微的差別。 The pathogen system is B. hyodysenteriae (initial B. catarrhalis , former Treponema pallidum ), a spirochete with long, wide, and uneven helix. It can be incubated on blood agar under anaerobic conditions by staining both phenol-magenta and Giemsa. The spectinomycin containing the medium can be used for its selective culture. Strong beta-hemolysis occurs under toxic strains and around toxic strains. Hemolysin is a low molecular weight peptide with cytotoxic properties. Based on the lipopolysaccharide antigen extracted from the cell wall, the B. hyodysenteriae strain can be divided into 9 serogroups by Agar Gel Precipitation (AGP) analysis. However, there are further subtle differences between the strains of the same serogroup depending on the antigen structure.
短螺旋體的抵抗力為低,它們在超過60℃且使用消毒劑時在幾分鐘內死亡,並且當乾燥時,在幾天內死亡,但在黏液,帶血的糞便中,它們在夏季存活至少一個星期,以及在冬天存活至長達兩個月。類似地,病原體在弱鹼性的糞料中可能存活幾個月。 Short spirals have low resistance, they die within a few minutes when using a disinfectant at temperatures above 60 ° C, and die within a few days when dry, but in mucus, bloody feces, they survive at least in summer Live for up to two months in a week and in the winter. Similarly, pathogens may survive for several months in weakly alkaline feces.
此病原體可移植於於豬農場生活的小鼠、大鼠以及狗的腸中。它能夠由大鼠排泄幾天、由狗排泄幾周、由小鼠排泄幾個月。 This pathogen can be transplanted into the intestines of mice, rats and dogs living on pig farms. It can be excreted by rats for several days, excreted by dogs for several weeks, and excreted by mice for several months.
病原體在此種疾病的病因學中的作用透過此疾病在無特定病原體與普通的豬中均由人工成功地產生的事實所證明。為了理解發病機制與成功的保護,應強調無菌仔豬僅當短螺旋體引入至具有腸道內正常存在厭氧細菌的豬體內時成功地感染。這一點透過短螺旋體與正常的厭氧細菌,例如主要為類桿菌屬,以及後桿菌門之間的協同效應解釋。根據此假定,這些微生物提供短螺旋體 傳播的適合的微環境及基質。因此,除了在透過豬痢疾感染的豬腸物體中存在大量的短螺旋體之外,它不為偶然的,正常腸菌群的平衡之失調也是值得注意的。 The role of pathogens in the etiology of this disease is evidenced by the fact that the disease was successfully produced artificially in both specific pathogens and normal pigs. In order to understand the pathogenesis and successful protection, it should be emphasized that sterile piglets are successfully infected only when B. burgdorferi is introduced into pigs with normal anaerobic bacteria in the gut. This is explained by the synergistic effect between the short spirochetes and normal anaerobic bacteria, such as mainly Bacteroides, and the bacillus. According to this hypothesis, these microorganisms provide B. Suitable microenvironment and matrix for propagation. Therefore, it is not accidental except for the presence of a large number of short spirochetes in pig intestinal objects infected with swine dysentery, and the imbalance of the normal intestinal flora is also noteworthy.
在急性豬痢疾中,腸球菌與桿狀菌的數量在腸菌群中顯著減少,並且同時,類桿菌屬的細菌,後桿菌門,大腸桿菌以及某些大腸菌群的數量增加。在慢性情況中,梭狀芽胞桿菌的增加明顯。伴隨及剩餘菌群對主菌群之比例的增加導致生態平衡停止,以及代替地形成一有害性狀態。有害性菌群表示對宿主生物的負擔增加。在這種狀態下,飼料利用性劣化,產量下降,並且在更嚴重的情況下,動物可死亡。 In acute swine dysentery, the number of Enterococcus and Bacillus is significantly reduced in the intestinal flora, and at the same time, the number of Bacteroides, Bacillus, Escherichia coli and certain coliforms is increased. In chronic conditions, the increase in Clostridium is significant. An increase in the proportion of the accompanying and remaining flora to the main flora results in the cessation of ecological balance and the formation of a deleterious state instead. The harmful flora indicates an increased burden on the host organism. In this state, feed utilization is deteriorated, yield is lowered, and in more severe cases, animals can die.
需要開發適合於取代抗生素且有效競爭性的基於草藥的製品。 There is a need to develop herbal-based products that are suitable for replacing antibiotics and are highly competitive.
不同的藥用及醚性植物,以及由其製成的提取物自古代開始在本土文化中廣泛應用,其抗菌效果也長時間為人所知。 Different medicinal and etheric plants, as well as extracts made therefrom, have been widely used in native culture since ancient times, and their antibacterial effects have long been known.
在草藥提取物的情況下,它往往可以證明具有一些殺菌抑菌效果,以及「改善腸道菌群」,益生的效果。其中一個最普遍的這種化合物為,例如百里香油提取物,除了上面提到的積極效果,百里香油提取物還能夠根據初步實驗選擇性地抑制沙門氏菌。 In the case of herbal extracts, it can often prove to have some bactericidal and bacteriostatic effects, as well as "improving the intestinal flora" and probiotic effects. One of the most common such compounds is, for example, thyme oil extract. In addition to the positive effects mentioned above, the thyme oil extract is capable of selectively inhibiting Salmonella according to preliminary experiments.
產量增加的使用藥用植物的多數產品,包含植物本身,或者其一些提取物。問題在於藥用植物的藥物含量顯著變化的事實。這取決於產地、收穫時間,因此它們的使用從安全的觀點看為有問題的,但是至少它不能夠標準化。藥用植物源的藥物的進一步問題為食物中可能出現殘留藥物及風險。 Most products that use increased yields of medicinal plants, including the plants themselves, or some of their extracts. The problem is the fact that the drug content of medicinal plants varies significantly. This depends on the origin, harvest time, so their use is problematic from a safety point of view, but at least it cannot be standardized. A further problem with medicinal plant-derived drugs is the presence of residual drugs and risks in food.
麝香草(百里香)屬於唇形科家族,唇形目。它為一常年的半灌木,在五月與七月之間開花。它為地中海天生的,而不是匈牙利的地方性的,但是它可以培育。其有效成分主要為香精油,包含的香精油為大約1-2.5%。香精油的主要成分為大約出現為20-60%的麝香草酚,以及大約25%的香芹酚。 Thyme (thyme) belongs to the family of the Labiatae, the shape of the lip. It is a perennial semi-shrub that blooms between May and July. It is native to the Mediterranean, not Hungarian, but it can be nurtured. Its active ingredient is mainly essential oil, and the essential oil is about 1-2.5%. The main component of the essential oil is about 20-60% thymol, and about 25% carvacrol.
除香精油之外,百里香還包含其他物質中的類胡蘿蔔素、多酚、黃酮類似物等。麝香草酚與香芹酚的抗病毒、抗菌以及抗真菌的活性已知相比較於苯酚高出一個數量級,同時類胡蘿蔔素、多酚以及黃酮類化合物具有自由基清除劑以及抗氧化劑能力。 In addition to essential oils, thyme also contains carotenoids, polyphenols, flavonoids and the like in other substances. The antiviral, antibacterial and antifungal activities of thymol and carvacrol are known to be an order of magnitude higher than phenol, while carotenoids, polyphenols and flavonoids have free radical scavengers and antioxidant capacity.
根據一些研究,即使在存在血液時,百里香油完全抑制革蘭氏陽性微生物的繁殖。其對單胞菌株的繁殖的抑製效果較弱,並且對其他革蘭氏陰性微生物,以及某些真菌的抑制作用較強。百里香精油與其不同的提取物對抗菌及抗真菌的影響進行了長期的研究。這些研究到目前為止已經清楚地證明其對廣泛變化的致病性以及食物腐壞微生物的有效性(多爾曼(Dorman)與迪安(Deans),2000年;帕斯誇(Pasqua)等人,2005年;Arnal-Schnebelen等人,2004年;安哥里尼(Angelini)等人,2006年)。 According to some studies, thyme oil completely inhibits the reproduction of Gram-positive microorganisms even in the presence of blood. It has a weak inhibitory effect on the reproduction of a single strain, and has a stronger inhibitory effect on other Gram-negative microorganisms, as well as certain fungi. The long-term study of the effects of thyme essential oil and its different extracts on antibacterial and antifungal properties. These studies have so far clearly demonstrated their effectiveness against a wide range of pathogenicity and food spoilage microorganisms (Dorman and Deans, 2000; Pasqua et al. , 2005; Arnal-Schnebelen et al., 2004; Angelini et al., 2006).
根據其中的一些研究,它對革蘭氏陽性菌的活動性相比較於對革蘭氏陰性菌更高(法拉格(Farag)等人,1989年;史密斯帕爾默(Smith-Palmer)等人,1998年;馬里諾(Marino)等人,1999年;卡勒巴(Kalemba),1999年),而其他的研究也發現抵抗革蘭陰性菌的效果(Penalver等人,2005年;Ashour等人,2005年;Oussalah等人,2006年)。其在離體條件下(對豬痢疾短螺發體) 產生作用。然而,沒有對百里香的反短螺旋體活性的資料。因為如此,我們研究抵抗豬痢疾的病原體的百里香之水提取物。 According to some of these studies, it is more active against Gram-positive bacteria than Gram-negative bacteria (Farag et al., 1989; Smith-Palmer et al.) , 1998; Marino et al., 1999; Kalemba, 1999), and other studies have also found resistance to Gram-negative bacteria (Penalver et al., 2005; Ashour et al. , 2005; Oussalah et al., 2006). It has an effect on ex vivo conditions (for porcine dysentery ). However, there is no data on the activity of thyme anti-B. Because of this, we studied extracts of thyme water against pathogens of swine dysentery.
在初步的實驗室研究中,驚訝地發現,在一些藥用植物的情況下,能夠看到幾個藥用植物的較佳提取物的協同效應。研究的組合物除了百里香提取物之外,還包含自洋槐(長角豆屬,長角果)的自然菌株的胚乳製備的粉狀物。此粉末物由高分子量的,由苷邊界連接的半乳糖與甘露糖單元組成的水膠體多醣,化學上描述為半乳甘露聚糖形成。此半乳甘露聚糖之含量係為至少75%。此種種子粉用於食品應用中,並且作為嬰兒配方的添加劑(E 410)。 In preliminary laboratory studies, it was surprisingly found that in the case of some medicinal plants, synergistic effects of preferred extracts of several medicinal plants can be seen. The composition of the study contained a powder prepared from the endosperm of a natural strain of artichoke (Cornus, silique) in addition to the thyme extract. This powder consists of a high molecular weight hydrocolloid polysaccharide consisting of galactose and mannose units linked by glycoside boundaries, chemically described as galactomannan. The galactomannan content is at least 75%. This seed powder is used in food applications and as an additive to infant formula (E 410).
百里香與洋槐種子的水提取物的組合物按照濃度依賴的方式,抑制豬痢疾短螺旋體,我們的瓊脂擴散試驗中稱為豬痢疾之病原體的活性。這表現出與其他具有不同微生物的結果很好的相關性(瑪格達(Magda)等人,2000年;EL-Astal等人,2004年;EL-Astal等人,2005年;Czapska等人,2006年)。 The composition of the water extract of thyme and artichoke seeds inhibits the activity of the pathogen known as swine dysentery in our agar diffusion test in a concentration-dependent manner. This shows a good correlation with other results with different microorganisms (Magda et al., 2000; EL-Astal et al., 2004; EL-Astal et al., 2005; Czapska et al., year 2006).
自1999年以來,歐盟禁止維吉尼亞黴素(Virginiamycin)、泰黴素(Tylosin)、史黴素(Spiramycin)以及桿菌肽(Bacitracin)的預防與增加量的使用。這個規則在2006年1月1日收緊,並且歐盟成員國完全禁止抗生素用於疾病預防以及產量提高的使用。本發明的方法具有特別重要的意義,因為百里香中存在的活性成分影響抗藥性微生物(尼爾森(Nelson)等人,1997年;赫希(Hersch)等人,2005年;弗里德曼(Friedman)等人,2006年;弗里德曼(Friedman)等人,2006年),因此,這些抗生素能夠按照需要被 取代(Onibala等人,2001年;Urbanczyk等人,2002年),並且能夠認為作為一產量提高的替代(德米爾(Demir)等人,2005年),並且使用它們,安全食品的生產條件具有環境意識的提高。 Since 1999, the EU has banned the use of prophylactic and increased amounts of Virginiamycin, Tylosin, Spiramycin, and Bacitracin. This rule was tightened on January 1, 2006, and EU member states completely banned the use of antibiotics for disease prevention and increased yield. The method of the invention is of particular importance because the active ingredients present in thyme affect drug resistant microorganisms (Nelson et al., 1997; Hersch et al., 2005; Friedman). Et al., 2006; Friedman et al., 2006), therefore, these antibiotics can be Replaced (Onibala et al., 2001; Urbanczyk et al., 2002) and can be considered as an alternative to yield increase (Demir et al., 2005), and using them, the production conditions of safe foods have an environment Increased consciousness.
本發明的產品根據以下的細節為新穎的,並且它們相比較於類似產品為具有創新的。 The products of the present invention are novel in light of the following details, and they are innovative compared to similar products.
- 首先,根據我們所知,在國際市場上沒有類似於開發的產品,抵抗上述豬疾病的具體、基於草藥、高效以及無抗生素的保護方法。 - First of all, as far as we know, there are no similar products developed in the international market, specific herbal, high-efficiency and antibiotic-free protection methods against the above-mentioned swine diseases.
- 該項目涉及產品中有效成分的發展,而非植物本身。 - The project involves the development of active ingredients in the product, not the plant itself.
- 該產品不包含一單一的藥用植物,而是包含適合於獲得目標的活性成分的適當的結合。 - The product does not contain a single medicinal plant, but rather a suitable combination of active ingredients suitable for obtaining the target.
- 尋求與使用的活性成分之間的協同作用。 - Seek synergy with the active ingredients used.
- 自草藥提取物中清除殘餘物質成分,因此開發的產品從食品安全的立場看無風險。 - The removal of residual constituents from herbal extracts, so the products developed are risk free from a food safety standpoint.
- 草藥提取物的效率透過化學過程提高。微量元素甘氨酸螯合化合物的穩定作用增強草藥的活性成分。 - The efficiency of herbal extracts is enhanced by chemical processes. The stabilizing effect of the trace element glycine chelate compound enhances the active ingredient of the herb.
- 微量元素甘氨酸螯合物在人類藥用產品中發現,但這些廠家不是競爭對手,因為它們不是獸醫市場的生產者。 - Trace element glycine chelate is found in human pharmaceutical products, but these manufacturers are not competitors because they are not producers of the veterinary market.
- (藥用)植物產品主要用於動物飼料中的香味增強。Ayurvet公司為印度最大的飼料添加劑產品的生產商 之一。它具有幾種藥用植物產品,但這些並非用於這裡所述的豬疾病的預防,因此不是這個項目的產品的競爭對手。Ruchamax與Yakrifit為基於草藥的反芻動物的增產產品。在匈牙利(SzIEÁOTK)具有它們的測試資訊,但是觀測值沒有優勢。Uperliv與Ayucee為對家禽開發的藥用植物的混合物。 - (Medicinal) plant products are mainly used for aroma enhancement in animal feed. Ayurvet is the largest producer of feed additive products in India one. It has several medicinal plant products, but these are not used for the prevention of swine diseases as described here and are therefore not competitors of the products of this project. Ruchamax and Yakrifit are products for the production of herbal-based ruminants. In Hungary (SzIEÁOTK) they have their test information, but the observations have no advantage. Uperliv and Ayucee are mixtures of medicinal plants developed for poultry.
印度公司Kamdhenu飼料的對抗腹瀉的藥用植物產品(Diakam)用於改善一般症狀。它對疾病沒有特別的效果。在歐洲沒有使用這些產品的經驗。 The medicinal plant product (Diakam) against diarrhea from the Indian company Kamdhenu is used to improve general symptoms. It has no special effect on the disease. There is no experience in using these products in Europe.
超濾為一種長期用於發酵工業中的分離技術。當目標為去除一具有已知大小,例如大於10千道爾頓(kDa)但是小於100千道爾頓(kDa)的分子時,超濾用於過濾或分離的具有分子量為1000千道爾頓(kDa)或更小的分子濃度。具有兩種主要類型的膜過濾:薄膜與中空纖維過濾。在膜過濾期間,提取物使用一給定的壓力通過具有一給定孔徑尺寸的膜板,因此其為一傳統的過濾技術。中空纖維過濾在毛細管中執行,其中該毛細管具有一具有給定千道爾頓(kDa)的截止值的表面。過濾的液體在這些穿孔的毛細管中循環,直至去除較小分子量材料的大部分,並且濃縮物保持於這些毛細管中。此種技術的一個新穎使用為藥用植物提取物的濃縮。水狀與/或異丙醇提取物的小於100千道爾頓(kDa)的分子大小的片段在1千道爾頓(kDa)的截止毛細管中循環,用 以濃縮它,由此產生藥用植物提取物的濃縮版本。 Ultrafiltration is a long-term separation technique used in the fermentation industry. When the target is to remove a molecule of known size, for example greater than 10 kilodaltons (kDa) but less than 100 kilodaltons (kDa), ultrafiltration is used for filtration or separation with a molecular weight of 1000 kilodaltons. Molecular concentration of (kDa) or less. There are two main types of membrane filtration: membrane and hollow fiber filtration. During membrane filtration, the extract passes through a membrane having a given pore size using a given pressure, thus it is a conventional filtration technique. Hollow fiber filtration is performed in a capillary having a surface having a cutoff value of a given kilodalton (kDa). The filtered liquid circulates in these perforated capillaries until most of the smaller molecular weight material is removed and the concentrate remains in these capillaries. One novel use of this technique is the concentration of medicinal plant extracts. A molecular size fragment of less than 100 kilodaltons (kDa) of aqueous and/or isopropanol extract is circulated in a 1 kilodalton (kDa) cut-off capillary. To concentrate it, thereby producing a concentrated version of the medicinal plant extract.
礦物質在活體的生理及生化作業中起到多種與基本的作用。其中,這些礦物質為酶成分(鋅、銅、錳、鎂、鐵),(鐵、錳、鋅、銅、鎂、鉀)以及維生素(Co),它們在不同的保護機制中具有特殊作用(銅、鋅、鐵、硒),參與造血功能(銅、鐵),繁殖(磷、銅、鉀、錳、鋅、鎂),促進核酸與蛋白質的合成。 Minerals play a variety of and fundamental roles in the physiological and biochemical operations of living organisms. Among them, these minerals are enzyme components (zinc, copper, manganese, magnesium, iron), (iron, manganese, zinc, copper, magnesium, potassium) and vitamins (Co), which have special effects in different protection mechanisms ( Copper, zinc, iron, selenium), participate in hematopoietic function (copper, iron), reproduction (phosphorus, copper, potassium, manganese, zinc, magnesium), promote the synthesis of nucleic acids and proteins.
飼料植物的微量元素含量取決於幾個因素(例如氣候、應用的農業技術、環境污染等),並且具有很大差異。然而,繁育高產的牲畜需要一增加及平衡的礦物質(包含微量元素)的補充。該要求幾乎通過飼料完全滿足,主要向提供飼料中混合不同的礦物鹽。 The trace element content of the feed plants depends on several factors (eg climate, applied agricultural technology, environmental pollution, etc.) and varies widely. However, breeding high-yielding livestock requires an addition and balance of minerals (including trace elements). This requirement is almost completely met by the feed, mainly by mixing different mineral salts into the feed.
這些生產預混料的工廠使用無機形式的微量元素,儘管事實上這些元素在植物中主要以有機化合物存在,並且在過去的10-15年的科研表明使用有機化合物的微量元素相比較於無機形式具有確實的優勢。 These premixed plants use trace elements in inorganic form, despite the fact that these elements are mainly organic compounds in plants, and studies over the past 10-15 years have shown that trace elements using organic compounds are compared to inorganic forms. Has a definite advantage.
含有金屬的有機複合體係為生物系統中的主要化合物形式之一。金屬離子在這些複合體中佔據中心位置,並且離子、分子、天然有機化合物(氨基酸、多肽、蛋白質、碳水化合物等),即為附加於其的配體。當該金屬離子附加至一配體的兩個或兩個以上的原子時,某些離子與有機化合物之間的化學反應產生螯合物。具有金屬-配體相互作用的螯合化合物對於有機體最重要,因為在 這些複合體中金屬的活性相比較於離子形式高105-107倍。 Metal-containing organic composite systems are one of the major compound forms in biological systems. Metal ions occupy a central position in these complexes, and ions, molecules, natural organic compounds (amino acids, polypeptides, proteins, carbohydrates, etc.) are ligands attached thereto. When the metal ion is attached to two or more atoms of a ligand, a chemical reaction between certain ions and the organic compound produces a chelate. Chelating compounds with metal-ligand interactions are most important for organisms because The activity of the metals in these complexes is 105-107 times higher than the ionic form.
在大多數微量元素的情況下,形成以下的螯合物:使用氨基酸、蛋白質、有機酸等形成複合體,其中蛋白質(氨基酸)微量元素複合體為基本的。最近獲得可喜的成果-與品種、年齡以及使用無關-在更高效的微量元素供應中,主要使用硒、鉻、鋅、銅、錳以及鐵。 In the case of most trace elements, the following chelate is formed: a complex is formed using an amino acid, a protein, an organic acid, or the like, wherein the protein (amino acid) trace element complex is basic. Recently, gratifying results have been obtained - irrespective of breed, age and use - in the more efficient supply of trace elements, mainly selenium, chromium, zinc, copper, manganese and iron.
同時,有機形式提供的甘氨酸銅及鋅不僅利用較好,而且令人驚訝的對微生物具有抑製作用。微量元素有機甘氨酸銅及鋅螯合物的作用機制中的一重要因素為,這些螯合物能夠抑制飼料中革蘭氏陰性病原體或兼性病原體的擴散,因此腸菌群的有用成員,例如雙歧桿菌與乳酸桿菌,可佔上風。有機結合微量元素甘氨酸組合物與藥用植物的混合物可有效地用於恢復腸菌群的平衡,用於腸菌群的生產以及用於對抗對動物健康具有風險的兼致病微生物體。 At the same time, copper and zinc glycinate provided by the organic form not only utilizes better, but also surprisingly inhibits microorganisms. An important factor in the mechanism of action of trace element organic glycine copper and zinc chelate is that these chelate compounds can inhibit the spread of Gram-negative or facultative pathogens in feed, so useful members of the intestinal flora, such as double Bacillus and Lactobacillus can prevail. The mixture of the organically combined trace element glycine composition and the medicinal plant can be effectively used to restore the balance of the intestinal flora, for the production of the intestinal flora and for combating pathogenic microorganisms at risk to animal health.
此外,微量元素管理的一基本問題為如何防止在吸收前,金屬離子與腸菌群中的其他成分的相互作用,這一點可透過提供顆粒狀配方獲得。 In addition, a fundamental problem in the management of trace elements is how to prevent the interaction of metal ions with other components in the intestinal flora prior to absorption, which can be obtained by providing a granular formulation.
對於在粒化期間使用的擠出與成球狀步驟的理想擠出物的物理性質,透過自藥用植物提取物中準備的糊之濕度,微量元素甘氨酸及添加劑,以及其中包含的輔助材料的比例確定。一些添加劑使用於食品與製藥行業中,例如微晶纖維素(一纖維素的結晶形式),或者聚乙烯吡咯烷酮(Σ-PVP)以及PVP及CMC。它們通常用作載體,對於造粒乳化及賦形。結合及包圍有濕度,致使 其顆粒膨脹,從而粒子之間的空間為細菌提供了理想的環境。CMC由於在食品工業以及其他行業中的高黏度性能,因此受到使用。它沒有毒性,不會引起過敏,不在地面中累積。透過吸收水分,它可以用作顆粒中的黏合劑。PVP提供高持水能力,因為它可以吸收自身重量的40%。由於顆粒在滾圓期間,受到顯著的物理衝擊,因此顆粒的適當凝聚力與蓄水能力非常重要。高黏度聚合物吸收水分是必要的,用以避免水的沉澱,以及從而避免在工藝步驟中顆粒的黏附。一個完全同質的「塊」具有普遍的濕粉的一致性,因此它不像每天感覺的糊料。 The physical properties of the desired extrudate for the extrusion and spheroidal steps used during granulation, through the moisture of the paste prepared from the medicinal plant extract, the trace elements glycine and additives, and the auxiliary materials contained therein The ratio is determined. Some additives are used in the food and pharmaceutical industries, such as microcrystalline cellulose (a crystalline form of cellulose), or polyvinylpyrrolidone (Σ-PVP) and PVP and CMC. They are commonly used as carriers for granulation emulsification and shaping. Combine and enclose humidity, causing The particles expand and the space between the particles provides the ideal environment for the bacteria. CMC is used because of its high viscosity properties in the food industry and other industries. It is non-toxic, does not cause allergies, and does not accumulate in the ground. By absorbing moisture, it can be used as a binder in the granules. PVP provides high water holding capacity because it absorbs 40% of its own weight. Since the particles are subjected to significant physical impact during spheronization, proper cohesion and water storage capacity of the particles are very important. It is necessary for the high viscosity polymer to absorb moisture to avoid precipitation of the water and thereby avoid adhesion of the particles during the process steps. A completely homogeneous "block" has a common consistency of wet powder, so it doesn't look like a paste every day.
產生的糊料利用壓力擠壓而擠出:透過填充至一管中受壓縮,以及該擠出物在一預定的每分鐘轉數下施壓至一螺桿擠出機中的羅線中,然後收集。 The resulting paste is extruded by pressure extrusion: compressed by filling into a tube, and the extrudate is pressed into a spiral in a screw extruder at a predetermined number of revolutions per minute, and then collect.
在擠壓期間,糊料在一高壓下壓縮且恢復為長絲線的形狀,如果糊料具有適當的長度、強度以及稠度,則該長絲線可在一滾圓機中成為珠粒狀。在滾圓過程期間,擠出物受到高物理衝擊,以及不正確結合的水分沉澱於擠出物或顆粒的表面上。在此種情況下,成粒狀的顆粒黏合在一起,並且其尺寸可達到5-6毫米(mm)的直徑。滾圓在一具有方格圖案的凹槽的金屬板上執行,並且在高迴轉下旋轉,稀糊細線根據凹槽的密度裁剪,然後根據迴轉數滾圓。由於在滾圓期間透過連續的空氣噴射形成一殼,因此顆粒硬化,並且它們的結構得到維持。 During extrusion, the paste is compressed at a high pressure and restored to the shape of a filament, and if the paste has an appropriate length, strength, and consistency, the filament can be in the form of beads in a spheronizer. During the spheronization process, the extrudate is subjected to high physical impact, and incorrectly bound moisture precipitates on the surface of the extrudate or granule. In this case, the granulated particles are bonded together and are sized to a diameter of 5 to 6 millimeters (mm). The spheronization is performed on a metal plate having a groove of a checkered pattern, and is rotated under high rotation, the thin paste line is cut according to the density of the groove, and then rounded according to the number of revolutions. Since a shell is formed by continuous air jet during spheronization, the particles harden and their structure is maintained.
對於在離體實驗中,準備該藥物的一冷(25℃)水提取物。測量該植物樣本的細粉三克,以及在室溫下使用100毫升的蒸餾水搖晃1小時,然後在不同的分子量截止(1 kDa、10 kD、100 kDa、500 kDa)超濾膜柱(KOCH/Romicon WF2,中空纖維)下過濾幾次,然後使用號數為2005/89與2005/94的濾液以準備系列稀釋,直至濃度為1:20000。 For the in vitro experiment, a cold (25 ° C) water extract of the drug was prepared. Three grams of the fine powder of the plant sample was measured, and shaken with 100 ml of distilled water at room temperature for 1 hour, and then subjected to different molecular weight cutoff (1 kDa, 10 kD, 100 kDa, 500 kDa) ultrafiltration membrane column (KOCH/ Filter under Romicon WF2, hollow fiber) several times, then use the filtrates numbered 2005/89 and 2005/94 to prepare serial dilutions until the concentration is 1:20000.
對於在離體實驗中,準備該藥物的一冷(25℃)水提取物。測量該植物樣本的細粉三克,以及在室溫下使用100毫升的蒸餾水搖晃1小時,然後通過100 kDa的柱過濾,然後通過1 kDa的柱濃縮,然後自該濃縮的提取物中準備系列的稀釋直至濃度為1:20 000。 For the in vitro experiment, a cold (25 ° C) water extract of the drug was prepared. Three grams of the fine powder of the plant sample was measured, and shaken with 100 ml of distilled water at room temperature for 1 hour, then filtered through a 100 kDa column, then concentrated through a 1 kDa column, and then a series was prepared from the concentrated extract. Dilute until the concentration is 1:20 000.
洋槐種子粗粉在40℃下,在水溶液中提取2小時,然後透過添加20%的異丙醇進一步提取,該提取物如實例1中所述通過100 kDa的柱過濾,然後通過1 kDa的柱濃縮,然後自該濃縮的提取物中準備一系列稀釋直至濃度為1:20 000。 The artichoke seed meal was extracted in aqueous solution at 40 ° C for 2 hours and then further extracted by adding 20% isopropanol. The extract was filtered through a 100 kDa column as described in Example 1, and then passed through a 1 kDa column. Concentrate and then prepare a series of dilutions from the concentrated extract until the concentration is 1:20 000.
研究來自該濃縮的異丙醇-水部份的該沉澱的提取物。 The precipitated extract from the concentrated isopropanol-water fraction was studied.
對表現出豬痢疾臨床症狀的生長肥育豬隔離的豬痢疾短螺旋體(Brachyspira hyodysenteriae)巴塔(Bata)變種菌株執行抗菌 效果的研究,然後在5個不同的農場隔離的豬痢疾短螺旋體菌株進一步包含於該研究中。根據廣為所之的瓊脂擴散協定,測試菌擴散至血液瓊脂培養基上,然後在無菌條件下在瓊脂平板中切割井。待研究的這些提取物移液至這些井中,然後在35℃下孵育24-48小時。在一活性樣品的情況下,圍繞瓊脂井的測試菌死亡,並且抑制區能夠以較小或較大的環之形式觀察到。抗菌活性能夠自抑制區的直徑測量中推斷出。 Antibacterial activity of Brachyspira hyodysenteriae Bata strains isolated from growing and finishing pigs exhibiting clinical signs of swine dysentery A study of the effects and then isolation of B. hyodysenteriae strains on 5 different farms was further included in the study. According to the widely accepted agar diffusion protocol, the test bacteria were spread onto blood agar medium, and then the well was cut in agar plates under aseptic conditions. The extracts to be studied were pipetted into these wells and then incubated at 35 ° C for 24-48 hours. In the case of an active sample, the test bacteria surrounding the agar well died and the zone of inhibition was observed in the form of a smaller or larger loop. Antibacterial activity can be inferred from the measurement of the diameter of the zone of inhibition.
豬痢疾短螺旋體的分離及其瓊脂擴散試驗:豬痢疾短螺發體菌株自在匈牙利的不同地區飼養的,表現出豬痢疾的臨床症狀的生長肥育的豬中隔離。在屠宰場出血之後,表現出臨床體徵的豬的結腸圈系住且在六小時內運送至實驗室。在打開結腸部分之後,該樣本作為結腸黏膜的刮樣提供。在任何情況下,在刮痕器上的黏膜刮屑在供給有10%的去纖維蛋白牛血與400微克/毫升的大觀黴素(Sigma-Aldrich公司的Kft)作為抑製劑的新鮮準備的TSA瓊脂(Scharlau微生物)的表面散布。在孕育之後,培養物在嚴格的厭氧條件下在+42℃孵育96小時。厭氧條件透過使用厭氧氣體生成包(Oxoid公司,Gas Generating Kit,厭氧系統BR0038B)以及厭氧培養罐(Oxoid公司,厭氧罐)獲得。確定初級及此級的生化特性與識別分離株透過標準技術(奎恩(Quinn)等人,1994年)執行。在識別之後且直至在試驗中使用,這些菌株以懸浮形式儲存於在-80℃下冷凍的具有無菌甘油的TSB液中(Scharlau微生物)。 Isolation of B. hyodysenteriae and agar diffusion test: B. gingivalis strains were isolated from pigs that were raised in different regions of Hungary and showed growth symptoms of swine dysentery. After hemorrhage at the slaughterhouse, the colonic colon of the pig showing clinical signs was tied and transported to the laboratory within six hours. After opening the colon portion, the sample is provided as a scraping of the colonic mucosa. In any case, the mucous shavings on the scraper were freshly prepared TSA supplied with 10% defibrinated bovine blood and 400 μg/ml of spectinomycin (Sigma-Aldrich Kft) as an inhibitor. The surface of agar (Scharlau microorganisms) is scattered. After inoculation, the cultures were incubated at +42 °C for 96 hours under stringent anaerobic conditions. Anaerobic conditions were obtained by using an anaerobic gas generating package (Oxoid, Gas Generating Kit, anaerobic system BR0038B) and an anaerobic culture tank (Oxoid, anaerobic tank). Determining the biochemical properties of the primary and secondary levels and identifying isolates was performed by standard techniques (Quinn et al., 1994). After identification and until use in the assay, these strains were stored in suspension in TSB with sterile glycerol (Scharlau Microorganisms) frozen at -80 °C.
這些株預先在-25℃下冷凍儲存。自解凍的細菌塊中,在血瓊脂上(改良的胰蛋白大豆瓊脂培養基,輔以5-10%的去纖維蛋白牛血)準備預先培養物。自顯著很好地溶血的預培養的瓊脂平板上,切離8-10個,幾乎相同的大小(±5%的差別)的瓊脂塊移植物,然後使用直徑大約5毫米(mm)的玻璃棒分佈至直徑為90毫米(mm)的新鮮配製的瓊脂平板上。該面板以覆蓋形式乾燥5分鐘。 These strains were previously stored frozen at -25 °C. Pre-cultures were prepared on blood agar (modified tryptic soy agar medium supplemented with 5-10% defibrin bovine blood) from the thawed bacterial mass. On a pre-cultured agar plate that was significantly well hemolyzed, cut 8-10 agar block grafts of almost the same size (±5% difference) and then use a glass rod approximately 5 mm (mm) in diameter. Distributed onto freshly prepared agar plates with a diameter of 90 mm (mm). The panel was dried in a cover form for 5 minutes.
根據實驗室中的開發順序,該移植的面板使用瓊脂盤切割設備在中間打孔。這些5毫米(mm)直徑的全體放置於距離面板之邊緣至少40毫米,用以允許容易評估圍繞敏感單離體的較大抑菌區。因此,形成於90毫米(mm)直徑的培養面板上的全體僅包含一個樣本。在應用一定濃度的百里香提取物之後,這些面板在15分鐘之內放置於一浮空器中(Oxoid公司的厭氧包及罐),並且在無氧氣體環境中在37℃下孵育4-5天。 The transplanted panels were perforated in the middle using an agar disc cutting device according to the development sequence in the laboratory. These 5 mm (mm) diameters are placed at least 40 mm from the edge of the panel to allow easy evaluation of the larger bacteriostatic zone surrounding the sensitive single body. Therefore, the entirety of the culture panel formed on a 90 mm (mm) diameter contains only one sample. After applying a certain concentration of thyme extract, the panels were placed in an aerostat (Oxoid anaerobic bag and canister) within 15 minutes and incubated at 37 ° C in an oxygen-free atmosphere for 4-5 day.
研究的菌株根據圍繞面板全體的溶血抑制環的直徑尺寸分類,用以確定其對於水溶百里香藥物提取物的給定濃度的敏感性。 The strains studied were classified according to the diameter size of the hemolysis suppression ring surrounding the panel as a whole to determine its sensitivity to a given concentration of the water-soluble thyme drug extract.
標記敏感度(S)(抑制環的直徑>25毫米(mm)),表明細菌對於一定濃度的離體敏感且死去。 Marker sensitivity (S) (suppression ring diameter > 25 mm (mm)) indicates that the bacteria are sensitive to a certain concentration and die.
適度敏感(M)的結果(抑制環的直徑為15-25毫米(mm))表示給定濃度的離體效果為不可靠。 The result of moderate sensitivity (M) (the diameter of the suppression ring is 15-25 mm (mm)) indicates that the ex vivo effect at a given concentration is unreliable.
標記抗藥,不敏感(R)(10毫米(mm)或一類似的敏感直徑)表示離體的無效性。 Marking resistance, insensitivity (R) (10 mm (mm) or a similar sensitive diameter) indicates ineffectiveness in vitro.
結果總結於表1,2以及3中
在本實例中,百里香-與實例1及2一樣使用超濾濃縮的洋槐種子藥用植物提取物,按照1:1的比例混合,並且與地面菊苣以及100 ppm的含鋅微量元素甘氨酸摻鋅單甘氨酸與/或雙甘氨酸鋅與/或二甘氨酸鋅穩定劑混合在一起,並且在90℃進入且在60℃排出的空氣溫度下乾燥噴霧。 In this example, thyme - as in Examples 1 and 2, an ultrafiltration-concentrated artichoke seed medicinal plant extract was mixed in a ratio of 1:1 and mixed with ground chicory and 100 ppm zinc-containing trace element glycine. Glycine is mixed with zinc bisglycinate and/or zinc bisglycinate stabilizer and is sprayed at 90 ° C and dried at a temperature of 60 ° C.
在本實例中,百里香-與實例1及2一樣使用超濾濃縮的洋槐種子藥用植物提取物,按照1:1的比例混合,並且與地面玉米芯以及15 ppm的含銅單甘氨酸銅與/或雙甘氨酸銅與/或二甘氨酸銅穩定劑混合在一起,並且在70℃進入且在50℃排出的空氣溫度下在流化床上乾燥。 In this example, thyme - as in Examples 1 and 2, an ultrafiltration-concentrated artichoke seed medicinal plant extract was mixed in a 1:1 ratio with ground corn cob and 15 ppm copper-containing monoglycine copper and / Or copper bisglycine and/or copper bisglycinate stabilizer are mixed together and dried at 70 ° C and dried on a fluid bed at an air temperature of 50 ° C.
粒化系統化的準備 Preparation for granulation systemization
微晶纖維素(JRS-Vivapur®),以下簡稱為Vivapur。它為一使用於食品與製藥行業的添加劑,一纖維素的結晶形式。 Microcrystalline cellulose (JRS-Vivapur®), hereinafter referred to as Vivapur. It is an additive used in the food and pharmaceutical industries, a crystalline form of cellulose.
羧甲基纖維素納鹽(Σ-CMC),以下簡稱為CMC。CMC由於其在食品工業,以及其他行業中的高黏度特性受到使用。通過吸收水,它能夠用作顆粒化的黏合劑。 Carboxymethylcellulose nano salt (Σ-CMC), hereinafter referred to as CMC. CMC is used for its high viscosity properties in the food industry and other industries. By absorbing water, it can be used as a granulated binder.
聚乙烯基吡咯烷酮,(Σ-PVP),以下簡稱為PVP。對於適當的凝聚力與顆粒的蓄水能力是重要的。 Polyvinylpyrrolidone , (Σ-PVP), hereinafter referred to as PVP. It is important for proper cohesion and the water storage capacity of the particles.
對於纖維素吸收濕氣需要一小時的均質化,用以膨脹以及形成正確的微晶構造,以及因此為細胞生存提供理想的環境。攪拌設備以產生均勻的糊料:Kendwood,英國。 The absorption of moisture by cellulose requires one hour of homogenization to swell and form the correct crystallite structure, and thus provide the ideal environment for cell survival. Stir the equipment to produce a uniform paste: Kendwood, UK.
粒化(擠出-滾圓)較佳地在一4M-8擠出(Pro-C-Ept)設備中進行。擠出在35℃下發生。擠出的參數:40 rpm,慢螺旋轉轉及壓縮。擠出機篩分尺寸:1.0毫米(mm)。滾圓的參數:3.25毫 米(mm)的溝槽板,1400 rpm,允許達到期望的粒度(1-2毫米(mm))。 Granulation (extrusion-spheronization) is preferably carried out in a 4M-8 extrusion (Pro-C-Ept) apparatus. Extrusion occurred at 35 °C. Extrusion parameters: 40 rpm, slow spiral rotation and compression. Extruder sieve size: 1.0 mm (mm). Rounding parameters: 3.25 milli Millimeter (mm) fluted plate, 1400 rpm, allows the desired particle size (1-2 millimeters (mm)) to be achieved.
顆粒如在實例5中所述在流化床上乾燥。 The granules were dried on a fluidized bed as described in Example 5.
根據實例1及2的藥用植物提取物的1:1比例混合物,在類似於上述實例4、5以及6用於乾燥及粒化組合物技術的離體實驗完成之後,為用於實地測試(Dysantic 1、2、3以及4)準備的劑型變化,以及賦形劑成分的功效在豬痢疾短螺旋體菌株上的不同稀釋中進行了測試(表6)。 A 1:1 ratio mixture of medicinal plant extracts according to Examples 1 and 2 was used for field testing after completion of ex vivo experiments similar to the above Examples 4, 5 and 6 for drying and granulating composition techniques ( The dosage form changes prepared for Dysantic 1, 2, 3 and 4 ), as well as the efficacy of the excipient ingredients, were tested in different dilutions on B. hyodysenteriae strains (Table 6).
該豬痢疾短螺發體菌株對於Dysantic樣本混合物的兩種稀釋在離體中出現敏感(S),而賦形劑成分證明單獨為無效的。 The short spiral hair hyodysenteriae strain for both Dysantic mixture was diluted sample appears sensitive (S) in vitro, and excipient ingredients as proved ineffective alone.
在初步實驗條件下,在兩種情況下進行實驗性餵養以生長豬。對照組與實驗組均包含100頭生長肥育用豬。後者組接收實驗組合物,如實驗室試驗確定的5公斤/噸的飼料劑量。在第一項研究中,對照組在其飼料中接收預防劑量的Getroxel(karbadox)(表7)。在第二項研究中,僅執行受到痢疾的豬之個體的治療(表8)。研究的參數:治療數、損失的發生、平均屠宰體重、以及飼料利用率。 Under the initial experimental conditions, experimental feeding was carried out in two cases to grow pigs. Both the control group and the experimental group contained 100 pigs for growth and finishing. The latter group received the experimental composition, such as a 5 kg/ton feed dose as determined by laboratory tests. In the first study, the control group received a prophylactic dose of Getroxel (karbadox) in its diet (Table 7). In the second study, only individuals with dysentery pigs were treated (Table 8). Parameters studied: number of treatments, loss occurrence, average slaughter weight, and feed utilization.
在第一個實驗中(表7),在相同長度的育肥時間之後,實驗組中的屠宰體重相比較於對照組平均高出2.8公斤,即2.6%,並且用以產生1公斤活畜重量必需的飼料量更小0.2公斤,這意味著在飼料利用率上增加6%。第二次(表8),在相同長度的育肥時間之後,實驗組中的屠宰體重相比較於對照組平均高4公斤,即3.8%,並且用以產生1公斤活畜重量必需的飼料量更低0.27公斤,即飼料利用率相比較於對照的動物減少9%。相比較於對照組(2),在對照組中對於豬痢疾的治療具有十倍以上(21)。 In the first experiment (Table 7), after the same length of fattening time, the slaughter weight in the experimental group was 2.8 kg higher than the control group, or 2.6%, and was used to produce 1 kg of live animal weight. The amount of feed is 0.2 kg smaller, which means an increase of 6% in feed utilization. The second time (Table 8), after the same length of fattening time, the slaughter weight in the experimental group was 4 kg higher than the control group, ie 3.8%, and the amount of feed necessary to produce 1 kg of live animal weight was more The low 0.27 kg, ie the feed utilization rate was reduced by 9% compared to the control animals. Compared with the control group (2), the treatment of swine dysentery in the control group was more than ten times (21) .
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| Title |
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| 甯紅梅等人,不同水準有機硒銅鋅對肉雞胴體及肉品質的影響,湖北農業科學,Vol.50 No.18,2011/09/20,page 3970-3974 * |
| 郭芳彬,畜禽的優質飼料-洋槐葉,農村實用技術與資訊,1994/02/15,page 23 * |
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