CN102860416B - Composition containing silymarin or derivatives of silymarin and application of composition for protection of animal livers - Google Patents

Composition containing silymarin or derivatives of silymarin and application of composition for protection of animal livers Download PDF

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CN102860416B
CN102860416B CN201210236948.8A CN201210236948A CN102860416B CN 102860416 B CN102860416 B CN 102860416B CN 201210236948 A CN201210236948 A CN 201210236948A CN 102860416 B CN102860416 B CN 102860416B
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silymarin
derivative
composition
feed
animal
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萧培珍
张宝彤
叶元土
张波
裴双秀
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Sangpu Biochemical Tech Co Ltd Beijing
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Sangpu Biochemical Tech Co Ltd Beijing
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Abstract

The invention relates to a composition containing silymarin or a derivative of the silymarin and applications. The composition can be used for protecting animal livers. The invention also relates to a method for feeding animals and animal feed containing the silymarin or the derivative of the silymarin. The composition comprises, by weight, 0.01%-5% of the silymarin or the derivative of the silymarin, 5%-15% of white carbon black, 10%-30% of zeolite powder and 0.5%-1% of taurine. The derivative of the silymarin is silymarin succinate monoester or silymarin meglumine.

Description

The composition that contains silymarin or derivatives thereof and the liver purposes that watches for animals
The application is to applying date 2011.03.09; Application number 201110055418.9; Dividing an application of the application for a patent for invention of denomination of invention " the animal feed additive composition and the purposes that contain silymarin or derivatives thereof ".
Technical field
The composition that the present invention relates to a kind of adjusting animal physiological biochemistry that contains silymarin or derivatives thereof, also relates to it as the purposes of animal feed additive.
Background technology
China's animal farming industry has experienced the fast-developing phase, and the research of cultivated animals nutrition and disease is also more deep.The event that causes aquatic livestock enteron aisle, liver pancreas to sustain damage because of feed substances, disease etc. in breeding production process takes place frequently, and has affected the development of animal farming industry.
Milk thistle is the plant of composite family Silybum, formal name used at school Silybum marianum (L.) Gaertn.Originate in southern Europe, north African, within 1972, introduce China, as a kind of medicinal plant popularizing planting that protects the liver.Silymarin (Silymarin) is the active ingredient that the dry fruit of pale reddish brown milk thistle obtains through extracting, refining, its effective component is Herba Silybi mariani total flavones, main active is legalon (Silybin), Isosilybin (Isosilibinin), silydianin (Silidinain) and Silychristin (Siliehristin), and wherein the activity of legalon is the strongest and content is the highest.Silymarin can improve the effect of liver function, and acute, chronic hepatitis, cirrhosis and metabolism toxic liver injury are had to good curative effect; Also have hepatic cholagogic, anti peroxidation of lipid, radioresistance, antitumor, remove the functions such as free radical and anti-gastric-ulcer, be a kind of Antitumor Natural Products of high-efficiency low-toxicity, in pharmaceuticals industry, be used for the treatment of one of main medicine of liver diseases.
Summary of the invention
One of the object of the invention is to provide the composition of silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative for promoting the purposes of growth of animal.
Two of the object of the invention is to provide the composition of silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative for the protection of the purposes of animal's liver.
Three of the object of the invention is to provide the composition of silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative for improving the purposes of animal oxidation resistance, immune defense power and premunition.
Four of the object of the invention is to provide the composition of silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative for improving the purposes of meat quality and local flavor.
A kind of in described purposes can be used for producing animal feed, the composition that described animal feed comprises silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative, in animal feed, the weight ratio of silymarin or silymarin derivative is 0.0001 ‰~0.05 ‰, be preferably 0.0001 ‰~0.04 ‰, more preferably 0.0001 ‰~0.025 ‰; (when the composition that comprises containing silymarin when animal feed or the composition of containing silymarin derivative, in this feed, the weight ratio of silymarin or silymarin derivative is 0.0001 ‰~0.05 ‰, be preferably 0.0001 ‰~0.04 ‰, more preferably 0.0001 ‰~0.025 ‰; That is to say, no matter silymarin or silymarin derivative be with monomer or add in animal feed with the form of composition, and the weight ratio of finally controlling silymarin in feed or silymarin derivative is 0.0001 ‰~0.05 ‰.)
Described animal feed is selectable other raw materials such as wheat, corn, soybean, dregs of beans, wheat bran, fine rice bran, cotton dregs, the dish dregs of rice, digested tankage, meat meal tankage, fish meal, yeast, salt, calcium dihydrogen phosphate, mineral matter, vitamin, amino acid, zeolite powder, bentonite, soya-bean oil that comprise also, and other raw material in described animal feed can be needed select or design according to Animal nutrition by those skilled in the art; Or the standard animal feed/basic animal feed that comprises applicable growth of animal.
Five of the object of the invention is to provide the animal feed of the composition of a kind of composition that comprises silymarin or silymarin derivative or containing silymarin or containing silymarin derivative, is used for promoting growth of animal.
Six of the object of the invention is to provide the animal feed of the composition of a kind of composition that comprises silymarin or silymarin derivative or containing silymarin or containing silymarin derivative, is used for the liver that watches for animals.
Seven of the object of the invention is to provide the animal feed of the composition of a kind of composition that comprises silymarin or silymarin derivative or containing silymarin or containing silymarin derivative, is used for improving animal oxidation resistance, immune defense power and premunition.
Eight of the object of the invention is to provide the animal feed of the composition of a kind of composition that comprises silymarin or silymarin derivative or containing silymarin or containing silymarin derivative, is used for improving meat quality and local flavor.
According to the animal feed described in described goal of the invention five to eight, the composition that comprises silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative, in animal feed, the weight ratio of silymarin or silymarin derivative is 0.0001 ‰~0.05 ‰, be preferably 0.0001 ‰~0.04 ‰, more preferably 0.0001 ‰~0.025 ‰; (when the composition that comprises containing silymarin when animal feed or the composition of containing silymarin derivative, in this feed, the weight ratio of silymarin or silymarin derivative is 0.0001 ‰~0.05 ‰, be preferably 0.0001 ‰~0.04 ‰, more preferably 0.0001 ‰~0.025 ‰; That is to say, no matter silymarin or silymarin derivative be with monomer or add in animal feed with the form of composition, and the weight ratio of finally controlling silymarin in feed or silymarin derivative is 0.0001 ‰~0.05 ‰.)
Described animal feed is selectable other raw materials such as wheat, corn, soybean, dregs of beans, wheat bran, fine rice bran, cotton dregs, the dish dregs of rice, digested tankage, meat meal tankage, fish meal, yeast, salt, calcium dihydrogen phosphate, mineral matter, vitamin, amino acid, zeolite powder, bentonite, soya-bean oil that comprise also, and other raw material in described animal feed can be needed select or design according to Animal nutrition by those skilled in the art; Or the standard animal feed/basic animal feed that comprises applicable growth of animal.
The animal feed of the composition that comprises silymarin or silymarin derivative or containing silymarin as the present invention or the composition of containing silymarin derivative when raising healthy animal, can promote growth of animal, the liver that watches for animals, improve animal oxidation resistance and immune defense power, improve animal disease resistant power and improve meat quality, local flavor.
The animal feed of the composition that comprises silymarin or silymarin derivative or containing silymarin as the present invention or the composition of containing silymarin derivative is for the culture-cycle of letting animals feed, when cultivating early stage and being growth period and fattening period mid-term, can preferentially promote growth of animal.While promoting growth of animal, in animal feed, silymarin or silymarin derivative weight ratio content are preferably 0.0001 ‰~0.025 ‰.
The animal feed of the composition that comprises silymarin or silymarin derivative or containing silymarin as the present invention or the composition of containing silymarin derivative is for letting animals feed during in liver damage or pathology, can priority protection and repair animal's liver.
The animal feed of the composition that comprises silymarin or silymarin derivative or containing silymarin as the present invention or the composition of containing silymarin derivative when health status declines, can preferentially improve animal oxidation resistance, immune defense power and resistance against diseases for letting animals feed.
The animal feed of the composition that comprises silymarin or silymarin derivative or containing silymarin as the present invention or the composition of containing silymarin derivative during for letting animals feed, can improve meat quality and local flavor.
Nine of the object of the invention is to provide a kind of letting animals feed and promotes growth of animal, and the liver that watches for animals improves animal oxidation resistance, immune defense power and premunition, improves the method for animal meat quality and local flavor, comprising:
(1) prepare silymarin or the composition of silymarin derivative or containing silymarin or the composition of containing silymarin derivative;
(2) prepare animal feed;
(3) adopt described animal feed to raise described animal.
Ten of the object of the invention is to provide a kind of composition of containing silymarin or the composition of containing silymarin derivative; can promote growth of animal; and/or the liver that watches for animals; and/or improve animal oxidation resistance, immune defense power; and/or improve animal disease resistant power, and/or improve meat quality, local flavor.
Usually, in feed, the weight ratio of silymarin or silymarin derivative is (when silymarin or silymarin derivative add in animal feed with the form of composition in 0.0001 ‰~0.05 ‰ scopes, effective content in silymarin in feed or silymarin derivative, lower same), show animal is had to obvious promotion growth.
The present invention's discovery, in feed, the weight ratio of silymarin or silymarin derivative is in 0.0001 ‰~0.025 ‰ scopes, shows animal is had to obvious promotion growth.
The composition of the composition of silymarin of the present invention or silymarin derivative or containing silymarin or containing silymarin derivative can be independent; or mix with standard feed/basal feed; in the growth of animal stage, feed continuously; effectively promote Physiological and Biochemical Metabolism process in animal body; regulate animal growth; can promote growth of animal; and/or the liver that watches for animals; and/or improve animal oxidation resistance, immune defense power; and/or improve animal disease resistant power, and/or improve meat quality, local flavor.
Silymarin (Silmyarin) refers to from catananche milk thistle [silybum marinaum (L) Gaenrt] fruit and seed and extracts a class flavanonol of gained and flavanolignan's constituents that phenyl propanoid derivative condensation forms.Mainly contain legalon, Isosilybin, Silychristin, four kinds of isomers of silydianin, wherein legalon content is the highest, and liver-protecting activity is also the highest.Legalon, 2,3-dihydro-3-(4-hydroxy 3-methoxybenzene base)-2-methylol-6-(3,5,7-trihydroxy-4-oxo chromene-2-yl) benzodioxane, is off-white color crystalline powder, odorless, mildly bitter flavor are puckery, have draw moist.Be soluble in acetone, ethyl acetate, methyl alcohol, ethanol, be slightly dissolved in chloroform, water-soluble hardly; Molecular formula: C 25h 22o 10, molecular weight: 482.44, fusing point: 164-174 ℃.Structural formula is as follows:
Silymarin preparation method can adopt art methods, as Xu Yong, and Ma Chengfang, Zhang Ronggui; " discussion of silymarin production technology "; Chinese Wild plant resources [J], the 4th phase in 1996; And Zhang Shihang, Wu Zhihang; " preparation of water-soluble legalon and preparation and quality standard "; Pharmacy circular [J], 1984, the 1 phases.The ethyl acetate method of mentioning in milk thistle and effective medicinal components research thereof, (1) remove oily milk thistle seed meal, with ethyl acetate hot reflux, extract 5 times, each 4h, merging extract, filtration, filtrate decompression concentrate, and obtain brown paste, with benzinum (60~90 ℃), grind soak degreasing 4 times, dry, obtain yellow powder.(2) add methyl alcohol hot reflux and dissolve, room temperature is placed, and centrifugal, crystallization is respectively washed 3 times with methyl alcohol and benzinum, dry, obtains off-white color crystalline powder, i.e. legalon.
Technique is shown in Figure of description 1.
Silymarin of the present invention can extract from plant milk thistle [silybum marinaum (L) Gaenrt], can be also to adopt art methods synthetic, or the commercial prod of directly buying from market.
Silymarin is mainly used in treating acute hepatitis, chronic hepatitis in human body pharmaceuticals industry, the effect such as cirrhosis and hepatic injury, antitumor, anti-inflammatory, reducing blood lipid, treatment glycosuria.Green Tea Extract activity, lipoid peroxidization resistant, the effect of lipotropism oxygenase, antitumor action, mainly as a kind of medicinal application of liver protecting.
Silymarin is insoluble in water and common organic solvents, finds that silymarin absorption difference, bioavilability when oral are low in research.Water-soluble research for silymarin derivative has more wide prospect.
Described silymarin derivative is legalon monomester succinate or silibinin meglumine.
Described silymarin derivative is legalon monomester succinate, be mainly that structure of modification is carried out in 23-position to the main component legalon 3 in silymarin, obtain having the derivative of carboxyl, to improve the Pharmacokinetic Characteristics of legalon, increase it and be water-solublely beneficial to its absorption.The preparation method of legalon monomester succinate can adopt art methods, as Zhu Lin, and Li Jinzhu, Bian Huimin, Qin Kai, Li Wei; " the synthetic and liver-protecting activity research of legalon monomester succinate "; Asia-Pacific traditional medicine [J], the 1st phase in 2009;
Synthetic method: the succinic anhydride of certain mol proportion, NaOH, oxolane are joined in round-bottomed flask, after stirring at room 1 hour, add legalon, continue stirring at room 3 hours, obtain turbid solution, silica gel mixed sample, volatilize after solvent, low temperature drying, with silica gel column chromatography separating purification, with CH 2cl 2-CH 3oH wash-out, collects cut, and pressure reducing and steaming solvent, obtains two products, dry, obtains respectively following two kinds of legalon monomester succinates and is: compound 1 is legalon-3,23-disuccinic acid monoesters, white solid, fusing point: 115~117 ℃, molecular formula is C 33h 30o 16, molecular weight is 682, structural formula is as follows:
Compound 2, is legalon-3-monomester succinate, white solid, fusing point: 169~172 ℃, molecular formula is C 29h 26o 13, molecular weight is 582, structural formula is as follows:
Above two kinds of compounds are carboxylic silybin derivant; therefore be easy to be made into the good sodium salt of solubility in water; and can be used as antiphlogistic; Zhu Lin etc. have carried out the research of anti-acute liver damage to it; take glutamic-pyruvic transaminase (ALT) level as detecting index; result demonstration, the sodium salt of two kinds of compounds all can reduce the Serum ALT value that carbon tetrachloride causes acute injury mouse, shows that it has protection and repair to impaired liver cell.
Described silymarin derivative is silibinin meglumine, has another name called Silybin Meglumine, and chemical name is:
2-(2,3-Dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-Isosorbide-5-Nitrae-benzodioxin-6-yl)-2,3-dihydro-3, the meglumine salt of 5,7-trihydroxy-4H-1-benzopyran-4-one.Molecular formula: C 32h 39o 15n, molecular weight: 677.66, this strain legalon and meglumine are combined into, and are yellow amorphous powder; Odorless almost, mildly bitter flavor band is puckery; Have draw moist.This product is dissolved in water, slightly molten in methyl alcohol or ethanol, slightly soluble in acetone, soluble,very slightly in chloroform.Structural formula is as follows:
Silibinin meglumine preparation method can adopt art methods, as (pharmacy practice magazine, 2008,26 (4): 274-277 such as Zhang Jing.) preparation of silibinin meglumine is with refining: legalon and absolute ethyl alcohol are joined in there-necked flask according to a certain percentage, add hot reflux it is dissolved, slightly lower the temperature, keep 80 ℃ standby.Separately get a certain amount of distilled water, add meglumine, be heated to 80 ℃ it is dissolved, slowly join in above-mentioned legalon solution, be heated to reflux, keep 10min.Stop adding thermal agitation, solution is chilled to room temperature, moves in-10 ℃ of refrigerators and places and spend the night, and filters, filter cake absolute ethyl alcohol and stirring 0.5h, filters, and uses absolute ethanol washing 1 time, in 40 ℃ of vacuum drying 12h, obtain product, wherein determine that the molar ratio of legalon and meglumine is 1.05 ﹕ 1.
With respect to legalon, silibinin meglumine has good water solubility, good absorbing; bioavilability is high, and directly Scavenger of ROS, protects liver plasma membrane; promote to be damaged liver cell synthetic DNA and structural proteins, the pharmacotoxicological effects such as immunological regulation and anti-hepatic fibrosis.The scholars such as nineteen ninety Lotteron have reported in Mouse Liver microsome, and silibinin meglumine can reduce CC1 4the external lipid peroxidation that metabolin causes and the peroxidation being caused separately by DPNH I.Zoopery shows: it is active that this product can increase hepatocellular microsomal enzyme, accelerates the detoxification ability of liver; Also can reduce the rat blood serum glutamic-pyruvic transaminase that carbon tetrachloride causes and increase effect; Also can stablize the cell membrane of various types of hepatic injuries that the hepatotoxic agents such as carbon tetrachloride, thioacetamide, mucronatine cause, and reach obvious liver protection.
The silymarin that composition of the present invention comprises percentage by weight 0.01%~5% or silymarin derivative, composition preferably comprises 0.01%~4% silymarin or described silymarin derivative, and composition more preferably comprises 0.01%~2.5% silymarin or described silymarin derivative.
Further, described composition also comprises, the white carbon of percentage by weight 5%~15%, and 10%~30% zeolite powder, for improving mobility and the homogeneity of composition.
Described composition also comprises the taurine of percentage by weight 0.5~1%; Taurine can strengthen liver to fatty trans-utilization, can improve palatability and the digestibility of feed, improves feed intake and the Feeding Velocity of animal, improves cultivated animals meat quality and local flavor, and body approaches nature build.
Taurine (Taurine, H 2nCH 2cH 2sO 3h), claiming again taurine, Taurine, is a kind of little molecule β-sulfur-containing amino acid, is the essential amino acid of cat.In higher mammal body, taurine can be that raw material is synthetic by methionine, cystine, cysteine.And aquatic livestock mainly comes via cystine metabolism by the methionine of ingesting; also can directly absorb by bait; taurine common form with free amino acid or little peptide in aquatic livestock body exists, and is nonprotein synthesizing amino acid, can not carry out metabolism as energy substance.The physiological function that it is main: participate in the synthetic and fatty metabolism of cholic acid, promote digesting and assimilating of fatty emulsification and lipid material (as liposoluble vitamin), liver is had to certain protective effect; Affect combination and the transhipment of calcium ion, maintain and regulate osmotic pressure; Especially can stimulate fish, shrimps to ingest, its sense of smell and the sense of taste are had to spread effect.
All the other compositions of described composition are maize cob meal, as carrier.
The preparation method of described composition is:
1) composite formula Raw is pulverized, crossed 80 mesh standard sieves, standby;
The silymarin that described composition comprises percentage by weight 0.01%~5% or silymarin derivative,
Described composition also comprises, the white carbon of percentage by weight 5%~15%, and 10%~30% zeolite powder,
Described composition also comprises the taurine of percentage by weight 0.5~1%,
All the other compositions of described composition are maize cob meal;
2) by formula, take respectively each raw material in composition, standby;
3) each raw material in composite formula is added in mixer and is mixed, mixture homogeneity reaches more than 95%, and the coefficient of variation≤5% is prepared into composition.Described composition can be used for preparing feed or cultivated animals.
Said composition is with respect to the functional advantage of single silymarin or silymarin derivative:
1) said composition has better mobility, improves the mixture homogeneity of composition in feed, easy to operation, and has effectively avoided the loss of activity or the reduction that cause in transportation, storage process.
2) said composition activity is preserved in storage process.
3) said composition can not cause to the animal by its nursing obvious side effect (as the injury to stomach, enteron aisle, stimulate stomach lining and intestinal mucosa, affect animal appetite).
4) said composition can also improve feed intake and the Feeding Velocity of animal, makes animal have certain hobby and dependence to said composition, improves the speed of growth of animal and reduces the waste causing slowly because of Feeding Velocity; Improve cultivated animals meat quality and local flavor, body approaches nature build.
5) addition of said composition in feed is in containing silymarin or silymarin derivative weight ratio; when 0.0001 ‰~0.05 ‰ scope; have obvious growth-promoting effect, using dosage and cost are low, and the protection of liver and reparation are had to good effect.
6) said composition can facilitate easily and mixes with any standard feed/basal feed, make said composition can be extensive, simple and effective Di plant apply.
7) when there is health problem (as hepatic injury) in animal, feeding animals after said composition can being mixed with standard feed/basal feed; Also can be by the independent feeding animals of said composition.
Animal of the present invention includes but not limited to aquatic livestock, as fish, shrimp, crab etc., also comprises poultry, fowl, ruminant etc., and all can cultivated animals.
Standard feed/the basal feed of the applicable growth of animal of the composition that can comprise silymarin or silymarin derivative or containing silymarin by direct mixing or the composition of containing silymarin derivative is implemented the present invention; Or, can be by previously prepared/purchase silymarin or the composition of silymarin derivative or previously prepared containing silymarin or composition of containing silymarin derivative, again the composition of the composition of silymarin or silymarin derivative or containing silymarin or containing silymarin derivative is mixed with standard feed/basal feed, thereby implement the present invention.
The derivative of silymarin or silymarin is used for a long time in feed, can effectively repair the damaging action of feed substances to parenchymatous organ's tissues such as enteron aisle, liver pancreases, and health watches for animals.Make the animal can be under healthy state; especially relate to that feed substances is digested and assimilated, the function of intestinal canal of immune defense just can be brought into play its effect effectively; for liver pancreas, as the physiological function at metabolism center, can access normal performance; thereby demonstrate effective promotion growth, improve feed efficiency, ensure that cultivated animals is healthy, the effect of parenchymatous organ's tissue health such as protection enteron aisle and liver pancreas, can substitute antibiotics etc. the effect of medicine in feed.It is mainly the wound repair effect to animal organ's tissue, the normal physiological health of Dependent Animals has been given play to the maximum growth potentiality of animal body self, best defending and fighting against diseases ability, rather than as drug use, the Modern Concepts and the trend that meet green feed additive exploitation, safeguard animal health, produce the animal product of edible safety.
The present invention has the following advantages: (1) silymarin is (being containing 0.1~50g silymarin or silymarin derivative in feed per ton) within the scope of lower additive capacity, can bring into play more effective effect; Show good growth promoting function, improve animal growth rate and reduce feed coefficient, the effective dosage ranges of growth-promoting effect is very little, has made up prior art not enough; Cost is low, and effect is remarkable.(2) animal's liver is had to good adjusting, protection and repair, pathologic liver is had to good therapeutic action; (3) improve oxidation resistance and the immune defense power of animal, the toxic action of the generation of reduction MDA to animal, strengthens animal physique and improves the anti-copingability of animal, reduces outburst and the harm of Animal diseases; Solved the not resistance to transportation problem of animal; (4) improve animal disease resistant power and improve animal meat quality and local flavor, making cultivated animals more approach natural quality; (5) silymarin is a Plant Extracts, substitute antibiotics and short long class medicine are applied in aquatic feeds completely, ensureing the edible safety of aquaculture product, safeguard that cultivated animals is healthy, is a kind of novel environment friendly, safe, green feed addictive; (6) raw materials enjoy stable sources, production technology is simple, adds cost low, can improve production performance and culture benefit, has good social benefit and ecological benefits.
Accompanying drawing explanation
Fig. 1 is silymarin reparation technology figure.
The specific embodiment
Embodiment 1
Silymarin is purchased from Xi'an App Chem-Bio (Tech) Co., Ltd., trade name: milk thistle extract, and wherein silymarin content 83.5%, and legalon and Isosilybin total amount are 30%, are yellow powder shape thing.
The preparation method of silymarin: get milk thistle seed after mechanical disintegration, with oil press oil expression, seed expelleers oily powder must deoil, get seed meal 500g, each with 1000ml ethyl acetate heating and refluxing extraction 4h, totally 5 times, combined ethyl acetate extract, recovered under reduced pressure ethyl acetate, concentrate is brown paste, with benzinum (60~90 ℃ of boiling ranges), grinds soak degreasing 4 times, dry, fling to remaining benzinum, obtain yellow powder shape thing 32g.
Get 32g yellow powder shape material, be dissolved in 64ml methyl alcohol, reflux a moment, in room temperature, place 2, centrifugal, crystallization methanol wash 3 times, mother liquor is crystallization again, to obtain altogether white powder material 4g, is legalon.
Embodiment 2
Silymarin derivative---the preparation method of legalon monomester succinate:
In 50ml round-bottomed flask, add succinic anhydride 0.3g (3mmol), NaOH 0.04g (1mmol), oxolane 30ml, after stirring at room 1h, add legalon 0.24g (0.5mmol), continue stirring at room 3 hours, obtain turbid solution, silica gel mixed sample, volatilize after solvent, low temperature drying, with (100~200 order) silica gel column chromatography separating purification, with CH 2cl 2-CH 3oH (80:1~40:1) gradient elution, silica gel (GF 254) thin-layer chromatography detection, with CHCl 3-CH 3oH-CH 3cOOH (20:1:0.5) is solvent, under uviol lamp 254nm, detects.Collect cut, pressure reducing and steaming solvent, obtains two products, dry, obtains respectively 0.15g legalon-3,23-disuccinic acid monoesters and 0.12g legalon-3-monomester succinate, and productive rate is respectively 51.8% and 35.3%.
Embodiment 3
The preparation method of silymarin derivative---silibinin meglumine:
In the round-bottomed flask of 250ml, add legalon 15g, then add absolute ethyl alcohol 155ml, be heated to 80 ℃, legalon is dissolved, and remain on 80 ℃ standby; Separately take meglumine 6.0g, be placed in beaker, add 6ml water, be heated to 80 ℃ of dissolvings, meglumine solution is added in legalon absolute ethyl alcohol, add hot reflux 10min, after having reacted, move in-10 ℃ of refrigerators and place 15h, filter, filter cake stirs 0.5h with the making beating of 30ml absolute ethyl alcohol respectively, filters, with 10ml absolute ethanol washing 1 time, in 40 ℃ of vacuum drying 12h.
Through ultraviolet spectrometer, detect and obtain silymarin meglumine content higher than 96%, high efficiency liquid phase detects silibinin meglumine content 89%.Gross mass yield is about 72.1%.Obtain silibinin meglumine 15.5g.
Embodiment 4
The preparation method of the composition of containing silymarin or silymarin derivative:
1) by composite formula Raw: white carbon, zeolite powder, maize cob meal, silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) are pulverized, cross 80 mesh standard sieves, standby;
2) by formula, take respectively white carbon 50g, zeolite powder 200g, maize cob meal 740g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 10g, standby;
3) by white carbon, zeolite powder, maize cob meal, silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine), be added in the small-sized mixer of stainless steel (Central-South pharmaceutical machine production) and mix, mixture homogeneity reaches more than 95%, and the coefficient of variation≤5% is prepared into composition.Described composition can be used for preparing feed or cultivated animals.In animal feed, the addition of composition is 0.1%.
Embodiment 5
The preparation method of the composition of containing silymarin or silymarin derivative:
1) by composite formula Raw: white carbon, zeolite powder, maize cob meal, silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine), taurine are pulverized, cross 80 mesh standard sieves, standby;
2) by formula, take respectively white carbon 50g, zeolite powder 200g, maize cob meal 735g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 10g, taurine 5g, standby;
3) by white carbon; zeolite powder; maize cob meal; silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine); taurine, is added in the small-sized mixer of stainless steel (Central-South pharmaceutical machine production) and mixes, and mixture homogeneity reaches more than 95%; the coefficient of variation≤5%, is prepared into composition.Described composition can be used for preparing feed or cultivated animals.In animal feed, the addition of composition is 0.1%.
Embodiment 6
The formula of animal basal feed: according to air dry matter weight percent meter, comprise fish meal 1-30%, dregs of beans 5-30%, dish dregs of rice 5-30%, digested tankage (or meat meal tankage) 2-10%, wheat (and/or corn) 5-20%, wheat bran 5-20%, fine rice bran 5-25%, soya-bean oil (and/or rape oil, and/or lard) 1-3%, zeolite powder 1-2%, bentonite 1-2%, B B-complex 0.1%, composite mineral matter 0.8%, calcium dihydrogen phosphate 1.8-2.2%, all the other are cotton dregs, and total amount is 100%.
The animal feed of the composition that comprises silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative: add the composition of silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) or containing silymarin or the composition of containing silymarin derivative (being legalon monomester succinate or silibinin meglumine) in above-mentioned animal basal feed, addition is controlled at and makes the content of silymarin in feed or silymarin derivative (being legalon monomester succinate or silibinin meglumine) is 0.0001 ‰~0.05 ‰.Preparation method is for respectively each raw material being pulverized, and crosses 40 mesh sieves, according to aforementioned proportion weigh, mixing, modified, granulation, cooling, air-dry, obtain described animal feed.
Described B B-complex and composite mineral matter are this area typical additives, and its formula variation does not affect final result of the test in the present invention.The B B-complex of addressing in the present invention with composite mineral matter with implication is identical herein.
The conventional B B-complex of the present invention is to contain in every kg B B-complex, vitamin A: 100~4,000,000 IU, neo dohyfral D3: 50~2,000,000 IU, vitamin E: 30~120g, prokayvit: 2~15g, vitamin B1: 5~20g, vitamin B2: 5~20g, pyridoxamine: 2~30g, B12:0~1g, nicotinic acid: 5~60g, pantothenic acid: 5~60g, folic acid: 0.5~10g, biotin: 0~0.15g, inositol: 30~200g, vitamin C: 50~200g, surplus is corn protein powder; Preferably in feed, B B-complex addition is 0.1%.For example one of described composite vitamin formula contains in every kg B B-complex, in vitamin, vitamin A: 2,000,000 IU, neo dohyfral D3: 1,000,000 IU, vitamin E: 60g, prokayvit: 5g, vitamin B1: 10g, vitamin B2: 10g, pyridoxamine: 20g, B12:0.1g, nicotinic acid: 30g, pantothenic acid: 20g, folic acid: 5g, biotin: 0.1g, inositol: 100g, vitamin C phosphoric ester (35% content): 300g, surplus is corn protein powder, in feed, this B B-complex addition is 0.1%.
The conventional composite mineral matter of the present invention is that in every kg composite mineral matter, constituent content is, ferro element 10~30g, copper 0.2~1g, manganese element 3~8g, zinc element 6~20g, I 0.02~0.1g, cobalt element 0.001~0.12g, selenium element 0.01~0.08g, magnesium elements 10~30g, surplus is zeolite powder, and in feed, composite mineral matter addition is preferably 0.8%~1%.For example one of described composite mineral matter formula is that in every kg composite mineral matter, constituent content is, ferro element 18.75g, copper 0.4375g, manganese element 3.75g, zinc element 15g, I 0.0813g, cobalt element 0.00875g, selenium element 0.0625g, magnesium elements 22.5g, surplus is that zeolite powder is supplied, and in feed, this composite mineral matter addition is 0.8%.
One of formula of concrete animal basal feed is: according to air dry matter weight percent meter, and fish meal 4%, dregs of beans 10%, cotton dregs 20%, the dish dregs of rice 20%, meat meal tankage 3%, wheat 15%, wheat bran 5%, fine rice bran 15%, zeolite powder 2%, bentonite 1%, soya-bean oil 2%, calcium dihydrogen phosphate 2%, B B-complex 0.1%, composite mineral matter 0.8%.In this basal feed, add the composition of silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) or containing silymarin or the composition of containing silymarin derivative (being legalon monomester succinate or silibinin meglumine), addition is controlled at and makes the content of silymarin in feed or silymarin derivative (being legalon monomester succinate or silibinin meglumine) is 0.01 ‰, and feed per ton is containing 10g silymarin.According to above-mentioned formula rate weigh, mixing, modified, granulation, cooling, air-dry, described in obtaining, comprise the animal feed of the composition of silymarin or silymarin derivative or containing silymarin or the composition of containing silymarin derivative.
Embodiment 7
Grass carp basal feed formula is, with air dry matter weight percent meter: fish meal 4%, dregs of beans 8%, the dish dregs of rice 22%, imported meat and bone meal 3%, wheat 15%, wheat bran 8%, fine rice bran 10%, zeolite powder 1%, bentonite 2%, calcium dihydrogen phosphate 2%, soya-bean oil 2%, B B-complex 0.1%, composite mineral matter 0.8%, all the other are cotton dregs, total amount is 100%.
Group design:
Four groups of various dose silymarins will be added respectively in above-mentioned grass carp basal feed, make the weight ratio content of silymarin in feed be respectively 0.0001 ‰, 0.01 ‰, 0.025 ‰, 0.04 ‰, 0.05 ‰, corresponding gradient is respectively 0.1g/t feed (representing with " S0.1 ", lower same), 10g/t feed (S10), 25g/t feed (S25), 40g/t feed (S40), 50g/t feed (S50); The not blank group C of containing silymarin is set simultaneously, positive controls D1[is the VBT (50% content) that adds weight ratio 0.2 ‰ in above-mentioned grass carp basal feed], positive controls D2 (being to add the quinocetone of weight ratio 0.1 ‰ in above-mentioned grass carp basal feed).
Utilize above-mentioned 7 groups of feeds to carry out culture experiment to grass carp, the culture experiment cycle is 2 months, puts every tail grass carp average weight specification in a suitable place to breed and be 41g left and right, every group establish 3 parallel, each parallel cultivation 98 tail grass carp.
Data processing: test data is all with " mean+SD " expression, and result is carried out variance analysis by One-way ANOVA process in SPSS12.0 version statistical software, and carries out DuncanShi multiple ratio, and P<0.05 is significant difference.
Cultivation result is as follows:
(1) impact on fish bulk-growth
Result shows that each group of silymarin (is S0.1, S10, S25, S40, S50, lower with) rate of body weight gain and specific growth rate higher than blank group C, feed coefficient is lower than blank group C, between two groups, there is significant difference (P<0.05), show to add the speed of growth that silymarin can improve fish, fish are had to growth promoting function.Along with the increase of silymarin addition, between each group of silymarin, compared with blank group C, aspect rate of body weight gain, improving 7%~20%, specific growth rate has improved 5.3%~13.2%, and feed coefficient has reduced by 5.5%~11%.
S0.1 group and S10 group are compared with positive controls D1 and positive controls D2 respectively, and rate of body weight gain, specific growth rate and feed coefficient all have significant difference (P<0.05).
S25 group, S40 group and S50 group are compared with positive controls D1 and positive controls D2 respectively, difference (P>0.05) that between rate of body weight gain, specific growth rate and feed coefficient group, there are no significant, but along with the increase of silymarin addition, the rate of body weight gain of S25 group and S40 group, specific growth rate are respectively higher than positive controls D1 and positive controls D2.S50 group to the specific growth rate of fish body and rate of body weight gain lower than positive controls D1 and positive controls D2.
Experimental result shows that in feed, silymarin content has significant growth-promoting effect to fish body within the scope of 0.1~50g/t.Compare with similar additive, in feed, silymarin content can meet or exceed positive controls D1 and positive controls D2 at 0.1~40g/t growth result.Result of the test is in Table one.
Table one: the impact on fish bulk-growth index
Indicate: in subscript, different letter representatives have significant difference, and same letter represents there was no significant difference, and significance is α=0.05.
(2) impact on fish body liver function
When transaminase is the decomposition of catalytic amino acid oxidase, transamination, to the enzyme of 2-ketoacid, is mainly present in liver cell under normal circumstances, and the content in serum is also very low.On human medical, using serum transaminase vigor size as liver function one of normal important indicator whether.Measure transaminase activity, result shows: silymarin is respectively organized serum glutamic oxalacetic transaminase activity and compared with positive controls D2 with blank group C, positive controls D1 respectively, all has significant difference (P < 0.05) between group.
Silymarin is respectively organized serum glutamic pyruvic transminase activity and is compared with positive controls D2 with blank group C, there was no significant difference between group (P > 0.05), has significant difference (P < 0.05) with positive controls D1.Glutamic-oxalacetic transaminease activity/gpt activity (AST/ALT) ratio, each group of silymarin is all lower than blank group C, simultaneously also lower than positive controls D1 and positive controls D2.
Show that silymarin has regulating action for liver, it is effective to the protection of liver pancreas that regulating effect is used widely commodity to protect the liver type additive than existing market.Result of the test is in Table two.
Table two: the impact on fish body liver function index
Group Glutamic-oxalacetic transaminease AST (U/mL) Glutamic-pyruvic transaminase ALT (U/mL) AST/ALT
Blank group C 41.44±1.35 a 63.23±4.03 a 0.66
Positive controls D1 56.47±8.78 b 71.30±1.92 b 0.79
Positive controls D2 37.44±3.38 a 65.13±3.54 a 0.57
S0.1 25.83±2.76 c 64.07±1.55 a 0.40
S10 20.47±2.20 c 62.18±1.25 a 0.33
S25 20.75±1.66 c 63.19±0.51 a 0.33
S40 27.40±1.58 c 64.07±0.51 a 0.43
S50 22.82±1.46 c 60.59±1.51 a 0.38
Indicate: in subscript, different letter representatives have significant difference, and same letter represents there was no significant difference, and significance is α=0.05.
(3) impact on fish body oxidation resistance and MDA
Fish belong to the alternating temperature vertebrate of lower grade, and its specific immune response ability is relatively low, and therefore, nospecific immunity is significant in its immune defense.TAC, superoxide dismutase and glutathione peroxidase reflection body antioxidant capacity and immune defense ability.Lysozyme is a kind of non-specific humoral immunity factor, extensively be present in fish skin mucus, enteron aisle mucus, serum and macrophage, its activity change can reflect the variation of fish non-specific immunity, and lysozyme activity raises, and the non-specific immune function of fish strengthens.MDA is the oxidation end-product of Free Radical after lipid generation peroxidization in organism, has cytotoxicity.
TAC, superoxide dismutase and glutathione peroxidase are measured, be the results are shown in Table three.Each group of silymarin aspect TAC, activity of glutathione peroxidase all and between blank group C, there is significant difference (P<0.05).
S10, S25, S40, S50 group has significant difference (P<0.05) with the superoxide dismutase activity of blank group C, and S0.1 group and blank group C superoxide dismutase activity there was no significant difference (P>0.05), but S0.1 superoxide dismutase activity is higher than blank group C.
Lysozyme activity result shows, each group of silymarin, positive controls D1 and positive controls D2 lysozyme activity be all higher than blank group C, but between each group, there are no significant difference (P>0.05).Silymarin can improve fish body lysozyme activity, strengthens the immune defense function of fish body.
The demonstration of lipid peroxidation product MDA result, each group of silymarin has significant otherness (P<0.05) with blank group C mda content, and silymarin is respectively organized mda content significantly lower than blank group C.S0.1, S10, S50 organize mda content lower than positive controls D1, and have significant difference (P<0.05).S25 and S40 group mda content is approaching with positive controls D1, but respectively with positive controls D1 there was no significant difference (P>0.05).Each group of silymarin is compared with positive controls D2, and silymarin is respectively organized mda content all lower than positive controls D2, and the two has significant difference (P<0.05).Show that silymarin can significantly reduce mda content in serum, reduce the damaging action of lipid peroxidation product to body.
The silymarin group of Different adding amount is active at superoxide dismutase, glutathione peroxidase, TAC and lysozyme activity are higher than blank group C, higher than or approach positive controls D1 and positive controls D2.For Serum MDA content, the silymarin group of Different adding amount is lower than blank group C, simultaneously lower than or approach positive controls D1 and positive controls D2.
Show to add silymarin and can improve the oxidation resistance of body and reduce MDA, improve the immune defense ability of body, strengthen premunition.Each group of addition of different silymarins is compared with positive controls D2 with positive controls D1, and comparing, the action effect of bringing into play within the scope of few additive is more obvious.
Table three: the impact on fish body anti-oxidation function
Indicate: in subscript, different letter representatives have significant difference, and same letter represents there was no significant difference, and significance is α=0.05.
(4) impact on fish bodily form body and meat quality
The coefficient of condition of fish body, the body (in Table four) of body length/height ratio and internal organ index reflection fish body.Coefficient of condition represents the ratio of long cube of the body weight of fish body and body.Result shows the coefficient of condition there was no significant difference (P>0.05) between each group of silymarin and blank group C, but coefficient of condition of each group of silymarin higher than blank to organizing C.S0.1, S10, S25, S40 group fish body internal organ exponential sum body length/height compare respectively and between blank group C, positive controls D1 and positive controls D2 all without significant difference (P>0.05), the internal organ index of S50 is lower than blank group C, and S50 body length/height ratio is higher than blank group C.Internal organ index reduces, and the edible ratio of fish body improves, and for consumers, increases edible part and is highly profitable.
Nutritional labeling impact (in Table five) on fish body.Each group of result demonstration silymarin is compared with blank group C, and along with the increase of silymarin addition, the moisture of muscle is reducing, and crude protein composition is the trend of increase, and crude fat presents the trend of reduction.There is significant difference (P<0.05) with blank group C in silymarin group S0.1 group muscle moisture, and crude protein and crude fat difference not remarkable (P>0.05).Between the crude protein of silymarin group S50 group muscle and blank group C, there is significant difference (P<0.05).Moisture, crude protein and the crude fat there was no significant difference (P>0.05) between each group of full fish.
Increase along with silymarin addition, internal organ index reduces, edible ratio increases, and the crude protein composition of muscle increases, can improve the deposition of nutriment, nutritional quality tool for fish body has some improvement, and can reach the requirement of marketing fish aspect fish body build and body weight.This,, to changing meat, the build of intensive culture fish, significantly reduces internal organ index, and the edible ratio that improves fish has good effect.Show to add silymarin and can improve flesh of fish meat quality and local flavor.
Table four: the impact on fish bodily form body index
Group Coefficient of condition % Internal organ index (%) Body length/height ratio
Blank group C 1.67±0.33 9.03±1.62 ab 4.82±0.33 ab
Positive controls D1 1.82±0.09 10.10±0.99 a 4.72±0.15 ab
Positive controls D2 1.83±0.07 9.19±0.75 ab 4.66±0.13 a
S0.1 1.73±0.21 10.12±0.95 a 4.75±0.20 a
S10 1.81±0.09 10.14±0.97 a 4.73±0.12 a
S25 1.83±0.14 9.70±1.16 ab 4.72±0.23 a
S40 1.79±0.08 9.83±1.22 ab 4.82±0.16 ab
S50 1.77±0.09 8.64±0.75 b 4.96±0.31 b
Indicate: in subscript, different letter representatives have significant difference, and same letter represents there was no significant difference, and significance is α=0.05.
Table five: on the impact of fish body composition (% dry)
Indicate: in subscript, different letter representatives have significant difference, and same letter represents there was no significant difference, and significance is α=0.05.
Embodiment 8
Prepare containing silymarin composition or containing silymarin derivative composition:
(1) by silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine), white carbon, zeolite powder, maize cob meal are pulverized, and cross 80 mesh standard sieves, standby;
(2) take respectively silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) 10g, white carbon 100g, zeolite powder 150g, maize cob meal 740g, standby.
(3) above-mentioned raw materials is added in the small-sized mixer of stainless steel (Central-South pharmaceutical machine production) and mixes, be prepared in per kilogram composition containing effective silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) 10g.Composition in feed adds according to 0.1%.
Carp basal feed formula proportion of composing be take air dry matter percentage by weight and is calculated as wheat 18%, rice bran 20%, dregs of beans 15%, the dish dregs of rice 15%, digested tankage 5%, fish meal 5%, soya-bean oil 2%, calcium dihydrogen phosphate 2%, bentonite 2%, B B-complex 0.1%, composite mineral matter 0.8%, all the other are cotton dregs 15%.During preparation, each raw material all needs to pulverize after 40 orders standby.
The carp feed that contains silymarin derivative (legalon monomester succinate) for adding the composition of above-mentioned containing silymarin derivative (legalon monomester succinate) in above-mentioned carp basal feed formula, making the effective content of silymarin derivative in carp feed per ton (legalon monomester succinate) is 10g, then makes feed by this area common method.
Utilize the carp feed of above-mentioned carp basal feed and above-mentioned containing silymarin derivative (legalon monomester succinate) in area, Tangshan, to carry out respectively carp culture test.The carp of above-mentioned basal feed of throwing something and feeding is called for short " J group ", and the carp of above-mentioned containing silymarin derivative (legalon monomester succinate) feed of throwing something and feeding is called for short SH group.Throw in carp seed size average out to 100g left and right for two groups, culturing time is 6 months, and pond area is respectively 10 mu.
In breeding process, regularly dissect fish body and check, found that, SH group is compared with J group, the former dissects fish body internal organ and observes substantially without illness outbreak the whole culture-cycle, and enteron aisle is normal, liver pancreas color is normal, scarlet, elastic force is good, fat-free liver and liver fibrosis phenomenon, and epidermal mucus is abundant.
Cultivation finishes, and discovery SH group is compared with J group, and the former fish body coefficient of condition is high, physique good, and muscle tight ness rating is high, and fat content is low, without the hemorrhage phenomena of mortality of irritability, and resistance to long-distance transport, the average specification of carp reaches 1.0kg left and right; SH group feed coefficient is 1.5, compared with J group feed coefficient, has reduced by 0.2.SH group is compared with J group, and the former cultivates per kilogram carp can save 0.8 yuan of feed cost, has reduced aquaculture cost, has improved raiser's economic benefit; Reduce feedstuff feeding amount and waste simultaneously, reduce water body elimination of nitrogen and environmental pollution; Fish body premunition improves, and drug dose reduces greatly, has improved social benefit and ecological benefits.
Embodiment 9:
Prepare containing silymarin composition or containing silymarin derivative composition:
(1) by silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine), white carbon, zeolite powder, maize cob meal are pulverized, and cross 80 mesh standard sieves, standby;
(2) take respectively silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) 25g, white carbon 100g, zeolite powder 200g, maize cob meal 675g, standby.
(3) above-mentioned raw materials is added in the small-sized mixer of stainless steel (Central-South pharmaceutical machine production) and mixes, mixture homogeneity reaches more than 95%, the coefficient of variation≤5%.Be prepared in per kilogram composition containing effective silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) 25g.Composition in feed adds according to 0.1%.
Grass carp basal feed formula proportion of composing is counted with air dry matter percentage by weight: corn 8%, wheat bran 20%, rice bran 10%, malt root 6%, dregs of beans 15%, cotton dregs 15%, the dish dregs of rice 15%, digested tankage 2%, fish meal 2%, soya-bean oil 2%, calcium dihydrogen phosphate 2%, bentonite 2%, B B-complex 0.1%, composite mineral matter 0.8%, wherein raw materials used need were pulverized after 40 orders, through modified, granulation, cooling, the air-dry grass carp basal feed of making.
The feed of grass carp that contains silymarin derivative (silibinin meglumine) for adding the composition of above-mentioned containing silymarin derivative (silibinin meglumine) in above-mentioned grass carp basal feed formula, the effective content that makes silymarin derivative (silibinin meglumine) in feed of grass carp per ton is 25g, wherein raw materials used need were pulverized after 40 orders, through modified, granulation, cooling, the air-dry feed of grass carp that contains silymarin derivative (silibinin meglumine) of making.
Employing contains the feed of grass carp that this example contains silymarin derivative (silibinin meglumine), in Soils in Yingkou District, Liaoning, carry out culture experiment, 5 mu of pond cultures 170 days, stocking size 100g left and right, in breeding process, fish body is checked, found that fish body anti-stress ability is strong, epidermal mucus secretion is normal, dissects internal organ and finds that liver pancreas color is scarlet, flexible, enteron aisle intestines wall thickness, without enteritis symptom, ingests normal.After cultivation finishes then, the average specification of grass carp reaches 1.6kg/ tail, fish body coefficient of condition reaches 2.1, fish body premunition improves, and cultivation survival rate reaches more than 88%, forms motility rate improved 18% than the cultivation of the present embodiment grass carp basal feed, feed coefficient has reduced by 0.2, save 0.32 yuan/jin of feed cost, cultivation dosage reduces, and has ensured the security of aquatic products.
Embodiment 10:
Prepare containing silymarin composition or containing silymarin derivative composition:
(1) by silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine), taurine, white carbon, zeolite powder, maize cob meal are pulverized, and cross 80 mesh standard sieves, standby;
(2) take respectively silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) 25g, taurine 5g, white carbon 100g, zeolite powder 200g, maize cob meal 670g, standby.
(3) above-mentioned raw materials is added in the small-sized mixer of stainless steel (Central-South pharmaceutical machine production) and mixes, mixture homogeneity reaches more than 95%, and the coefficient of variation≤5% is prepared composition.Be prepared in per kilogram composition containing effective silymarin or silymarin derivative (being legalon monomester succinate or silibinin meglumine) 25g.Composition in feed adds according to 0.1%.
Penaeus Vannmei is prepared with basal feed: fish meal 23%, globulin powder 3%, flour 20%, peanut meal 22%, fish oil 1%, phosphatide oil 1.5%, cuttlefish cream 4%, shrimp shell meal 4%, calcium dihydrogen phosphate 2.2%, B B-complex 0.1%, composite mineral matter 0.8%, adhesive 0.5%, surplus is dregs of beans, each raw material through modified, slaking, granulation, after air-dry, cooling, make prawn with basal feed for cultivation, with the prawn of this basal feed cultivation, be made as blank group.
The shrimp that comprises the composition that contains silymarin or silymarin derivative is prepared with feed: above-mentioned shrimp with adding the above-mentioned composition 0.1% that contains silymarin derivative (silibinin meglumine) on basal feed formula basis, each raw material through modified, slaking, granulation, after cooling, air-dry, make shrimp with feed for cultivation, with the prawn of this feed cultivation, be made as test group.
Adopt above-mentioned two kinds of feeds to carry out high density culture of Penaeus vannamei in area, Hangu, Tianjin, in breeding process, test group is compared with blank group, and the death rate of prawn obviously reduces, and survival rate has improved 20% compared with blank group cultivation group.Test group prawn ingests in process, and Feeding Velocity improves, and prawn can all ingest to the bait of throwing something and feeding in 30min left and right, and feed waste amount reduces by 5%, and raiser's culture benefit improves.Go out shrimp September, average specification per jin is in 25 tail left and right, and listing specification is larger, and build is good.
Embodiment 11
The preparation method of the composition of containing silymarin or silymarin derivative is with embodiment 4.
Described composite formula is white carbon 150g, zeolite powder 300g, maize cob meal 500g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 50g.
Embodiment 12
The preparation method of the composition of containing silymarin or silymarin derivative is with embodiment 4.
Described composite formula is white carbon 100g, zeolite powder 100g, maize cob meal 760g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 40g.
Embodiment 13
The preparation method of the composition of containing silymarin or silymarin derivative is with embodiment 4.
Described composite formula is white carbon 50g, zeolite powder 200g, maize cob meal 725g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 25g.
Embodiment 14
The preparation method of the composition of containing silymarin or silymarin derivative is with embodiment 5.
Described composite formula is white carbon 150g, zeolite powder 300g, maize cob meal 490g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 50g, taurine 10g.
Embodiment 15
The preparation method of the composition of containing silymarin or silymarin derivative is with embodiment 5.
Described composite formula is white carbon 100g, zeolite powder 100g, maize cob meal 752g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 40g, taurine 8g.
Embodiment 16
The preparation method of the composition of containing silymarin or silymarin derivative is with embodiment 5.
Described composite formula is white carbon 50g, zeolite powder 200g, maize cob meal 720g, silymarin or described silymarin derivative (being legalon monomester succinate or silibinin meglumine) 25g, taurine 5g.

Claims (3)

1. the watch for animals animal feed of liver, is characterized in that, wherein comprises the composition of containing silymarin or the composition of containing silymarin derivative;
The silymarin that described composition comprises percentage by weight 0.01%~5% or silymarin derivative;
The white carbon of percentage by weight 5%~15%, 10%~30% zeolite powder;
The taurine of percentage by weight 0.5~1%;
Described feed, wherein the weight ratio of silymarin or silymarin derivative is 0.0001 ‰~0.05 ‰.
2. animal feed according to claim 1, is characterized in that, described silymarin derivative is legalon monomester succinate or silibinin meglumine.
3. animal feed according to claim 1, it is characterized in that, described animal feed comprises wheat, corn, soybean, dregs of beans, wheat bran, fine rice bran, cotton dregs, the dish dregs of rice, digested tankage, meat meal tankage, fish meal, yeast, salt, calcium dihydrogen phosphate, mineral matter, vitamin, amino acid, zeolite powder, bentonite, soya-bean oil.
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RU2663994C1 (en) * 2017-10-24 2018-08-14 Федеральное государственное бюджетное научное учреждение "Краснодарский научный центр по зоотехнии и ветеренарии" ФГБНУ КНЦЗВ Feed additives for poultry with hepatoprotective and antitoxic action
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