JPH05503432A - Animal feed additives and methods for inactivating mycotoxins present in animal feed - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] name of invention Animal feed additives and methods for inactivating mycotoxins present in animal feed Background of the invention The present invention provides phyllosilicates/metal ions that function as mycotoxin inactivators. as a contaminant in animal feed by adding sequestrant compositions to animal feed. It relates to a method of inactivating mycotoxins that may be present.

Mycotoxins are chemicals produced by ubiquitous bacteria and fungi. can make the difference between profits and losses in poultry and livestock farming. be. Animals are affected by agricultural products containing mycotoxins being converted into animal feed. This common reality makes them extremely susceptible to harm from mycotoxins. did Therefore, mycotoxicosis or mycotoxin-induced diseases often occur in animals. do.

The best-studied and most widespread of these chemicals is Aspergillus fungi Flavis species and Para A closely related compound biosynthesized by Parasiticus sp. A general review of the scientific literature indicates that aflatoxins are a group of coumarin derivatives that You can easily find it by looking. Aflatoxin is 1) a powerful carcinogen. 2) stable in food and feed and capable of various processing Relatively unaffected by the process: 3) as residues in animal and human tissues; 4) following discoveries linked to animal and human diseases; , is listed as a toxic food and food-derived chemical in many contexts.

The vast majority of poultry and livestock exposures to aflatoxins are of a long-term nature. However, low levels of these chemicals can also increase mortality, e.g. ``Marginal contamination'' that occurs through the consumption of food that does not produce clear signs of disease . Rather, long-term exposure to aflatoxins may have economically important effects on animals, e.g. Growth rate, feed conversion, and increased susceptibility to infection and stress This produces a suppression of immune capacity that can lead to a decrease in resistance capacity.

Numerous approaches are available to reduce aflatoxin levels in agricultural products. It has been evaluated experimentally. This includes within the limits of regulatory guidelines, i.e. 20 pp. by mixing with aflatoxin-free grains to obtain levels of b or below. dilution: physical methods of separation, e.g. washing, density separation and selective fractionation, solvent extraction ; biological inactivation; thermal inactivation; as well as various acids, aldehydes, oxidizing agents and and chemical inactivation using alkaline substances. These approaches are , lack of efficiency, economic limitations of the original proposal, unacceptable changes in feed rates, or potential It has been relatively unsuccessful on a commercial scale due to the introduction of disadvantageous substances. However, This provides an easy, cost-effective, and practical way to decontaminate or detoxify animal feed. There is a great need for a practical and safe method.

The applicant recognizes the wide range of adverse effects of aflatoxins in animal feed. may bind efficiently to aflatoxins during ingestion by animals or otherwise We have developed an additive that inactivates aflatoxin using a formula. combined or unbound Activated aflatoxin is then excreted into the animal, causing harm to the animal. Beneficial effects are little or completely eliminated.

Clays such as montmorillonite are described in U.S. Pat. No. 3,687,680. As shown in Figure 1, poultry feed has traditionally been used at a low level of 1% of animal food. It has been incorporated in. The effects associated with the addition of montmorillonite include These included increases in longitudinal velocity and body weight, as well as reductions in mortality. Zeolite ( Smith, Journal of Animal Science (J, 80imal 5science) , 1980, Vol. 1, 50(2), pp. 278-285), bentonite ( Carson, Master's thesis, University of Guelph, Canada.

(1982) and used bleaching clay from canola oil refining (Smith). .

Canadian Journal of Animal Science (Can, J^nimal 5science), 1 984, Vol. 1, pp. 64, 725-732) is added to regular feed for rats and abolished the adverse effects of T-2 toxin and zearalenone in mature and immature pigs. Which indicates that. Various liquids from various clay minerals including montmorillonite Adsorption of aflatoxin B1 from the medium has also been reported (Mashimako and therefore The goal of the present invention is to not promote undesirable side effects such as weight loss in animals. It eliminates the adverse effects of mycotoxins present in feed, especially aflatoxin. To provide an animal feed additive that can Minimal amounts of these additives and normal Mycotoxins in animals, especially poultry and pigs, through co-administration with food feed Another aspect of the present invention is to provide a method for preventing the effects of ingestion of That's the goal.

Surprisingly, the inventors have discovered that sequestrants commonly used in food processing a second component selected from the group of agents capable of inactivating mycotoxins; The simultaneous incorporation of phyllosilicates, preferably montmorillonite clays, is highly effective. Furthermore, it is possible to produce a substance that exhibits aflatoxin adsorption capacity in vitro. , this type of substance significantly reduces the effects of aflatoxin exposure, enhancing They also discovered that they exhibit the ability to act in vivo.

Additionally, this type of formulation can be used as feed additives to eliminate mycotoxins, e.g. Ability to efficiently bind aflatoxin and ingest it together with animal feed was also found. Bound mycotoxin-additive complexes are not significantly adsorbed during digestion. excreted in animal feces.

Additives used in the present invention as feed additives and auxiliaries, i.e. Acid salt/sequestrant complexes help maintain normal weight gain in animals, e.g. poultry. It is thought that it acts as a promoting biometal ion sequestrant. These additives are Reduces maternal mycotoxin levels, especially aflatoxin, but this The quality can be utilized for its assimilation in the gastrointestinal tract during feed intake. these The additive efficiently binds to mycotoxins and eliminates them in the middle. Ru. These additives may be used in animal feed contaminated with mycotoxins, especially aflatoxins. Feed additions to provide protection against mycotoxins during feed intake and digestion It is also effective when used in the minimum amount as an agent. The additives according to the invention may be used in small quantities. , for example from 0.05 to 1.5% by weight of the food, preferably from 0.1 to 0. 5% by weight, most preferably in an amount ranging from 0.2 to 0.6% by weight of the feed food. Combined with virtually complete animal food.

One embodiment of the present invention increases the mycotoxin inactivation ability of phyllosilicate minerals. A suitable phyllo coated with a small amount of water-soluble sequestering agent, sufficient to strengthen Dry granular animal feed additive 1 containing particles of silicate minerals.

Another aspect of the invention is that the biodegradable feed is contaminated with mycotoxins. phyllosilicate minerals that can inactivate mycotoxins. coated with a sufficient amount of sequestering agent to increase cotoxin inactivation capacity. mixed with a small amount of mycotoxin inactivator consisting of particles of phyllosilicate minerals. Includes dry solid animal feed additives.

In a preferred embodiment of the invention, said phyllosilicate is a green clay, most Preferably, divalent exchangeable cations plus trivalent exchangeable cations/- It is a montmorillonite clay with an exchangeable cation ratio of more than 7.

Preferred phyllosilicates for use in the practice of this invention have two types of binding sites: 1) clay 2) those located at the basal plane of the particle, and 2) those located at the edge of the clay particle. It is a montmorillonite clay known to contain Connection with aflatoxin The nature of the sites involved in this process is unknown, but three possibilities exist. vinegar That is: 1) Binding occurs only at basal sites; 2) Binding occurs only at marginal sites: or 3) binding occurs at both the basal site and the peripheral site.

One of the surprising aspects of the present invention is that certain of the sequestering agents used in the present invention selectively binds to edge sites (this makes edge sites unavailable for binding to other molecules). Phosphates and polyphosphates (senda (Th eng), “The Chemistry of Clay-Organic Reactions (The Chemistry of C1 ay-Organic Reaction)'', Shicon Wiley & Son (John Wiley and 5ons, NY), 1974.26 (pages 4-268), the incorporation of various sequestering agents is not practical. is to increase flatoxin binding. Under these circumstances, if ■) If you work in case 2), there can be no effect of the added phosphate. Complete inhibition of aflatoxin binding is not possible, and if working in case 3) It is expected that there should be some degree of inhibition. On the contrary, any of these There may also be an increase in aflatoxin binding, even if it is actually observed. It was not expected that there would be.

Brief description of the drawing Figure 1 shows the aflatoxin binding capacity versus the loading amount of the sequestering agent “AP” on clay A. It is a diagram.

Figure 2 shows aflatoxin binding capacity versus sequestering agent type and loading amount on clay B. This is a diagram.

Figure 3 shows aflatoxin binding capacity versus sequestering agents on clays B, C, D and E. It is a diagram of “AP” load amount.

Figure 4 shows aflatoxin binding capacity versus sequestering agent type and loading amount on clay A. This is a diagram.

Figure 5 shows the aflatoxin binding capacity versus clay metal ion binding capacity at low sequestrant loading. FIG. 3 is a diagram of a sequestrant/clay combination.

Figures 6A and B show 20 ppb and 80 ppb aflatoxin induction assays, respectively. Aflatoxins versus clay in the serum of chickens fed sequestrants/clay in experiments This is a diagram of what is given only.

Figure 7ASB is the same as above except that liver tissue was used.

Figure 8-11 shows deoxynivalenol, zearalenone, ochratoxon A and FIG. 3 is a diagram of trinin binding capacity versus sequestering agent type and loading onto clay B.

Figure 12 shows the structural formulas of some common mycotoxins.

Description of preferred embodiments The additive according to the invention is used in the form of small granules or powder and must be prepared at any time before administration to the feed. It should be thoroughly mixed with animal feed by any suitable method. Used in the present invention “ The term "animal feed" or "feed food" refers to food that is susceptible to biotransformation and that is or all natural substances or processed or pond forms that can be consumed by birds. This refers to organic substances that have been modified with An example of this type of organic material is This will range from grains to pelleted feed. Use in the invention Preferred animal feeds are poultry feed and livestock feed.

In the present invention, as an inactivator for mycotoxins (e.g. aflatoxin) Additives that may be used include the phyllosilicate portion of the formulation, preferably a green clay type viscosity. Includes various sequestrant/phyllosilicate formulations that are earthy. structurally The phyllosilicate is basically a sheet of 5t(0,0H)4 tetrahedron bound together. and a bonded M2 in which M is a divalent or trivalent cation or a combination thereof It consists of a layer formed by condensation with 3(OH)s regular octahedron. . In addition to having the properties listed above, green clay also has the following properties when added to water: It also has small amounts of mobile (exchangeable) cations that can be easily solubilized. Fi Rosilicate minerals include pyrophyllite, talc, vermiculite, mica, and chao. Includes linite and serpentinite, as well as green clay. Closely related to phyllosilicates Related are fibrous clay minerals including attapulgite and sepiolite.

Examples of preferred green clays are: montmorillonite, Na-montmorillonite, Ca-montmorillonite. nmorillonite, Na-bentonite, Ca-bentonite, vaporite, no They are tronite, saponite and hectorite. The most preferred one is Relatively high (+2. +3/+1) exchangeable cation ratio (i.e. >7 ) is montmorillonite.

The sequestering agent part of this metal ion sequestering agent/clay compound is used for food processing. Contains food grade sequestering agent salts.

A partial list of substances of this type includes: sodium acetate, calcium acetate and vinegar Potassium acids: sodium citrate, calcium citrate and potassium citrate , and the free acid, and its monoisopropyl, monoglyceride stearyl and triethyl derivatives: ethylenediaminetetraacetic acid (EDTA) dihydrogen dinato Calcium salt and disodium calcium salt Calcium nigerconate and gluco Sodium phosphate; oxystearin; orthophosphate (-hydrogen-calcium salt, Dihydrogen-potassium salt, sodium aluminum salt, dihydrogen-sodium salt, -water (disodium salt, sodium trihydrogen salt); metaphosphate (hexametaphosphate salt); Lucium, sodium hexametaphosphate): pyrophosphate (tetrasodium salt, water sodium salt); sodium tripolyphosphate, calcium phytate; tartaric acid Sodium and Sodium Potassium Tartrate and Free Acids: and 1000 Sulfuric Acid Sodium may be included, as well as mixtures thereof.

Many of these sequestering agents include, for example, citrate and condensed phosphate ( For example, polyphosphates and pyrophosphates) are clay dispersants. condensed phosphate and citrate are dispersants (which pull fine particles in water into suspension, usually by reducing their viscosity). (substances that cause substances), but the levels used in these preferred embodiments are It is worth noting that it primarily acts as a flocculant. therefore , almost all of the sequestering agent/clay slurries produced in the following examples were It exhibits a much higher viscosity than the corresponding pure clay slurry. This is af The mechanism to achieve enhanced latoxin adsorption may be due to simple dispersion of clay particles. would appear to be excluded (and the available surface area is also increased).

A typical preparation of the preferred sequestering agent/phyllosilicate combination is as follows. It is: ■) Dissolve sodium tripolyphosphate (STP) in water (10:90 parts/weight) quantity ratio).

2) Dry and ground in a mixer (loss on ignition ~25% by weight) (60-100 Metsuyu) STP and clay are added to montmorillonite clay at a weight ratio of 4:96 to 7. Add the STP solution as present (on a dry basis).

3) Knead the clay/STP/water mixture for 15-30 minutes to ensure intimate mixing of each component. Execute the matching.

4) Extrude the clay/STP/water mixture (5/16" or 578" Gui).

5) Dry the resulting pellets in a dish or rotary dryer (loss on ignition 15- 25% by weight).

6) Grind the pellets to make granules (16-60 mesh) or powder (100-2 00 mesh) is formed.

Other examples of preferred methods for producing combinations are as follows: l) Quaternary birophosphate Dissolve thorium (TSPP) in water.

2) TSPP:clay ratio becomes 4:96 and obtained in montmorillonite clay Clay/TSPP/water slurry contains 15% by weight solids (clay + TSPP) Add TSPP solution as follows.

3) Mix each component for 30 minutes using a Talboy mixer.

4) The above mixture can be obtained using any suitable type of spray dryer. Microspheres have most of their diameter in the range of 60-80 microns, with 3-5% Spray dry to have free moisture.

The following examples are intended to explain the present invention, and are not included in the examples in this specification. should not be considered limiting to the invention described herein.

Example I Ca-montmorillonite clay (clay A) obtained in Mississippi was treated with various levels of beer. Aflatoxin B1 binding capacity obtained when coated with sodium hydrogen lophosphate The following in vitro test was conducted to demonstrate the increase in . In this example, clay The slurry was dried (J separation water 8-12%) and ground (93-97% T-1 , 00 mesh) was mixed with water (solids content 20% by weight), and then this stirring was carried out. Various amounts of sodium birophosphate are added to the slurry containing the desired metal ions. The chaining agent level (dry weight basis) was added to obtain the desired chain agent level (dry weight basis). 3 each ingredient Stir for 0 minutes, then pour into an evaporating dish and place in an oven at 90-110°C overnight. dry After drying, the sample was pulverized in a hammer mill and subsequently sieved for subsequent testing. Fractions of i, m ~ 325 meshes were obtained. The water content, surface area and and pore volume are listed in Table 1.

Table 1 0 59 0.093 0 49.0 99.20 57 0.085 2 5 8.3 98.50 50 0.089 4 59.2 99.20 42 0 ．． 082 6 61.8 98.90 36 0.077”13 56.7 9g, 50 27 0.067 10 52.7 9g, 30 17 0.05 7 15 51.7 99.20 15 0.044 20 46.7 99. 4(1)' LOD = Weight % loss upon drying at 110°C for 4 hours.

(2) Value measured by BET method.

(3) Value measured by BHJ method.

Level 1 - Solvent 11g/toxin 40μg0 Level 2 - Solvent 100mg/t Using these substances, in vitro experiments were conducted as follows. . Weighed additive samples were placed in a 16 x 12511 I11 clean disposable glass test tube. I put it in a tube. To this was added 5.00 ml of distilled water. Shake the test tube for 15 seconds. The corn was then placed in a 37°C water bath and allowed to equilibrate for 1 hour. 1 hour later, 4 0 μg of aflatoxin Bl was introduced (in a 1 gg/μl solution).

The test tube was shaken for 15 seconds, then returned to the water bath and left at 37°C for 15 minutes. . The supernatant was carefully decanted into a clean test tube. Then, extract the supernatant and The remaining mycotoxins were collected.

This supernatant was extracted three times with 2n+1 portions of dichloromethane. This dichloromethane The solution was collected and evaporated to dryness under a stream of nitrogen prior to analysis. above The dried residue from the aflatoxin binding experiment was redissolved in a known amount of chloroform. , 2jl of this solution was placed on an HPTLC plate (Analtech). and developed using a 9/1 (volume/volume) chloroform/acetone solvent system. Ta. Quantification is performed by visually comparing with a known amount of aflatoxin B1 placed on the same plate. It was. Analysis of aflatoxin control example was by GC/MS and HPTLC. Met. All samples were run in triplicate. using sodium metal Tetrahydrofuran (THF) immediately after distillation was used as a sample for aflatoxin B1. It was used as a starting solvent. The percentage recovery of aflatoxin B1 from the supernatant was determined for each plant. The test was determined from a control sample trial. The percentage recovery of aflatoxin B1 is Found to be consistently 100% for each sample, GC/MS, TLC and confirmed by HPLC quantification.

As shown by the data in Table 1 and the attached drawing (Figure 1), clay is When containing sodium hydrogen phosphate sequestering agents, bound aflatoxy There is a significant increase in the amount of According to the graph shown in Figure 1, the maximum increase is This is achieved when the clay contains about 6% by weight of phosphate. higher in phosphate The binding efficiency clearly decreases when the clay contains 20% salt by weight. In extreme cases, the binding capacity is actually slightly lower than that of untreated clay. this, The reason for the decrease in binding efficiency at high salt loads is unknown, but as salt levels increase It is worth noting that both surface area and microporosity decrease with increasing addition (Table 1). . This is due to the increased binding caused by the addition of sequestrants and the addition of sequestrants. that there is a trade-off between surface area and microporosity reduction caused by Suggests. As expected, higher levels of additives produce more toxic (Please compare Level 1 and Level 2), 1100 III adsorbent. When used with standard aflatoxin solutions, essentially all mycotoxins Shin joins.

Example II Ca-montmorillonite clay (clay B) obtained from Minshisobi was mixed with different levels. Aflatoxin B1 binding obtained when treated with a metal ion sequestrant (salt) The following in vitro studies were conducted to demonstrate the increased capacity and stability. Example I Prepare oven-dried samples as described and spray-dried samples as described above. (see above).

Using these substances, in vitro binding experiments were conducted as follows.

A weighed sample of the additive was placed in a clean disposable glass sample measuring 16 x 125 m+a. I put it in a test tube. Add to this 5.00 ml of type III water (equivalent to double distilled deionized water). etc.) were added. The test tube was agitated for 15 seconds and then placed in a 37°C water bath. and allowed to equilibrate for 1 hour. After 1 hour, 40 μg of aflatoxin B1 was added. (in a 1 gg/μl solution). Pour this test tube at 15 minute intervals (15, 30 and 15:45) and shaken for 15 seconds. After 1 hour, the test tube was heated to 120O Centrifuge for 5 minutes at rpm to get a pellet at the bottom of the tube and a clear supernatant at the top. . The supernatant was then carefully decanted into a clean test tube. Next, this Kamisumi The remaining mycotoxin was recovered by extracting the liquid, and the binding (capacity) was measured. Residue The strength and stability of the bond was measured by extracting the clay.

Test tube capacity test/ The supernatant was extracted three times with 2 ml portions of dichloromethane. This dichloromethane The solution was collected and evaporated to dryness under a stream of nitrogen prior to analysis. Above a The dried residue from the flatoxin binding experiment was redissolved in a known amount of chloroform; Place 2uL of this solution on a HPTLC board (Analtech) and 9/1 (volume/volume) ) was developed using a chloroform/acetone solvent system. Known quantities placed on the same board It was quantified by visual comparison with aflatoxin B1. In addition, the above chloroform A portion of the sample solution was transferred to a water HPLC system (normal phase radial compression column, fluid phase and (using Bonn's solution). HPLC detection at 365 r+m Due to UV absorption at Quantification was made with a known amount of pure aflatoxin Bl. This was done by direct comparison with a standard curve.

In vitro stability test: The residual clay obtained from the above 60 minute binding experiment was extracted as follows.

First, this clay was suspended in 3 ml of methanol. Leave this at room temperature for 5 minutes Then, this suspension was centrifuged at 120 rpm for 5 minutes.

The methanol was decanted into a clean test tube. Next, the pellets were processed into five different companies' Resuspended in lomethane and left at room temperature for an additional 5 minutes. Now pour this suspension into Descend to the first (methanol) extract.

The organic phase was evaporated to dryness under a stream of nitrogen and treated with the same was analyzed using the method. Tightly bound (stable) toxin is added first Difference between the amount of toxin and the amount recovered from both the aqueous phase and the residual clay extract. It was evaluated as being.

Regarding the stability of the bonds, Table 2 shows that these Contains data on the percentage of aflatoxin tightly bound to the formulation . Apparently, these formulations form very stable complexes with aflatoxin. The majority of aflatoxin retains more than 95% of the adsorbed aflatoxin.

Table 2 Sodium thiosulfate ST 88.387,895,094.298.398.599 ．． 498.4 Sodium citrate S C88,395,095,092,59g, 3 97.497.095.5 Ca gluconate C08g, 390.081.780 ．． 09&399,296,395.5 Sorbitol S B 88.387.5 95,092.598,389.096.095.0 Sodium tartrate TT 88. 392.595.097.598.396.091.598.8EDTA　ED 88.395.097.598.09g, 397.099.099.8 phosphoric acid 2Na DP 88.397.097.597,098.398. (199,3 96,3 Sodium hydrogen pyrophosphate AP 88.392.590.087.398. 399.799.298.5 TetraNa Pyrophosphate 74 P 88,397,09 7.595,098.398,595,597.0 tripo! J’) Sodium phosphate 73 P 88,392,595.097.098.398.595.098 ゜3 Sodium propionate SP 88.392.587,582.598,397 , 497.094.3 Ca phytate CP88.385.077.587.0 98.392.097.198.9 Binding conditions: 1 mg adsorbent/50 mg adsorbent Adhesive/40μg toxin 40μg toxin Dichloromethane MeOH/acetone 60 minutes/37℃ 60 minutes/37℃ As shown in Figure 2, the fruit used in the clay/sequestrant formulation Qualitatively all sequestrant salts were found to be more aflate than basic clay (0% loading). Increased binding capacity for xins. The only exception is that improving the coupling capacity is unthinkable calcium phytate.

The percentage of salt loading required to achieve the maximum increase in aflatoxin binding capacity is However, most believe that the maximum is reached before adding 10% by weight of salt. It will be done. As mentioned above, the surface area and pore volume of these formulations are generally salt negative. It decreases as the load increases (see Table 3).

Table 3 Sorbitol SB 88 45 28 22 0.14---EDTA ED 88 41 24 1g 0.140,110,070.06 pyrophosphoric acid Hydrogen Na AP 8g 79 75 66 0.14--Hexametaphosphoric acid Na HP 88 74 71 72 0.140.130.120.12 pio ') TetraNa phosphate T4P 88 74 77 64 0.140.130.13 0.11 Na tripolyphosphate TaP 88 75 85 74 0.140, 120. I30.11 Various montmorillonite clays with different levels of salt ) Increased aflatoxin B1 binding capacity obtained when treated with sequestering agents The complex interaction between the particular clay/sequestering agent mixture used and To show that it varies depending on the level of sequestering agent used, the following An in vitro test was conducted. Samples were prepared as described in Example I and Example II A test tube volume test was conducted in the same manner as described in .

The data in Table 4 (please also refer to Figure 3) only applies to one of the four raw material clays (clay B). but treated with sodium birophosphate (AP) at levels in the region of 7.21% by weight. It was clearly shown that the cells exhibited increased capacity for aflatoxin B1 when are doing. This means that for some clays, the maximum increase in binding capacity is 7% by weight. It has been shown that this can be achieved even before the addition of a sequestering agent. This result is Basically consistent with the data presented in Example I. Figure 4 shows other raw material clay (clay Show what happens when A) is similarly treated with various other sequestrant salts. are doing.

Table 4 A 69.5 73.7 66.4 65. OEDTA2Na EDA 69, 5 74,6 62.4 60.1 Sodium citrate SCA 69.5 60, 1 69.3 61.7 NaHPA hexametaphosphate 69.5 57.0 53.0 41.4 Sodium phosphate DPB 89.3 95.8 92.2 93.8 Sodium hydrogen pyrophosphate APC82,982,9gl, 1 82.2 Same as above APD 77.8 62.8 63.9 46.2 Same as above APE 92 ．． 6 91.2 77.1 75.9 Same as above AP table 4 (continued) % of bound AFBI (10 mg adsorbent/40 μg toxin) A 94,9 95, 0 92.591.7 EDTA2Na EDA 94,9 93,4 87, 8 88.2 Na citrate SCA 94.9 93.4 93.7 90. 4 NaHPA hexametaphosphate 94.9 81.8 80.4 85.0 Di-Sodium Phosphate DPC95,297,296,695,1 Sodium Hydrogen Birophosphate APD 97.7 95.2 94.7 92.1 Same as above APE 96.3 93,9 95.9 94.6 Same as above AP Therefore, this example The optimum salt level to achieve flatoxin binding is determined for all adsorbent and salt combinations. This explains the fact that they are not identical with respect to For example, EDTA disodium salt and sodium citrate using a salt level of 7% by weight. shows an increase in binding when the two other salts, namely hexametaphosphate and phosphate Disodium already clearly reaches its optimum value when using a level of 7% by weight. Over. This result will help determine the optimal clay/sequestering agent mixture individually. It suggests that there must be.

Example IV The following in vitro tests were performed on montmorillonite clay coated with various sequestering agents. In this case, the desired increase in aflatoxin B1 binding capacity was achieved at a salt loading of around 4%. Show that it is optimal. In addition, the data given in this example is of some type montmorillonite, especially divalent and trivalent exchangeable cations/-valent exchange The present invention described in the present specification is characterized by a high ratio of possible cations. It has also been shown that the method of the invention is suitable for producing toxin adsorbents with increased capacity. are doing.

Each sample was generally higher in hardness with the exception of Clay C which used only 9% solid needles. Made as in Example I except that needle content (24-38%) was used. did. The test tube volume test was conducted as described in Example n.

Table 5 lists the chemical properties and properties of the montmorillonite clay used in this series of experiments. It lists the physical properties. As shown by the data in Table 6 (see also Figure 5) Clays with relatively high (+2.+3/+1) exchangeable cation ratios, such as (Clay ASB, D) also has a slurry with pH on the acidic side or base Regardless of whether you have a slurry with a neutral pH, relatively low levels of various metal ions It also indicates increased aflatoxin binding capacity after treatment with on-blocking agents. Ru. In contrast, viscosity exhibiting a relatively low (+2.+3/+1) exchangeable cation ratio Soil (Clay C, E) was treated with either of two different sequestering agent salts. shows little or no improvement in toxin binding capacity. The latter two types of viscosity Soils also generally exhibit increased toxin binding capacity upon treatment with sequestering agents. It has a smaller surface area and micropore volume than other clays.

Table 5 Chemical and physical properties of raw clay A 67 0.11 104-112 7.95 Solid needle 36% 357B 62 0.089 84-100 8.7 5 Solid needle 38% 375C300,0641119,68 Solid needle 9% 142 0D 52 0.10 80 5.51 Solid needle 38% 354E 39 0. 078 - 5.10 Solid needle 24% 3231) Surface area (SA) (BET method ) and micropore volume (PV) (BJH method) ritics) 2400.

2) Cation exchange capacity.

3) Measured using a Brookfield viscometer ( using a #3 spindle except that in sample C a #6 spindle was used).

Table 5 (continued) Chemical analysis value (weight%) Si01 ＾1203 FezOI MgOCaONa2OK, o Clay mold A 67.6 20.7 2,82 5.44 3.32 0,37 0.19 Ca--E-Morillonite B 67.1 19.4 5.87 3,85 3. 10 0.30 0.44 Ca-montmorillonite C63,521,15,0 83,414,102,120,70Na-Montmorillonite D 67.2 2 2.1 3.80 4.16 1.27 0.32 1.16 Ca/Al-Mo nmorillonite A 137.9 15.8 4,25 0.38 - 33.2B 115.4 19.2 5,18 0.94 - 22.0C58,010,041,72 ,01-1,56D 25.7 10.2 5.74 32 45.4 13. 4E 57.1 20゜2 11.2 41 - 6.67 Table 6 Physical properties/Aflatoxin B1 binding clay/salt complex: Effect of clay/salt type DP 1 7.3 3.8 712 84.02 7.7 4.3 1428 87 ．． 34 2 Paste 87.7 TP I 8.1 4.2 638 80.52 g, 1 3.5 4 86, 7 4 4.5 Paste 87.6 HP 1 7.2 3 258 g2.12 6.8 4.8 265 82. 4TP 1 8.8 4.7 5 88.12 9.0 4.7 76 93. 9 49゜0 3.3 4480 94.7rSl 9.6s, 126 88.6 2 9.7 4.2 2220 91.54 6.4 Paste 95.7 HP　1　8.6　4.5　12　85.02　8.4　7゜8　12　93. 8 4 8.1 3.7 148 94. O3CI 9.1 5.2 880 82 ．． 02 9.2 5.7 90g 87,94 9.3 6.7 1316 9 3. O5T l 8.7 4.6 300 86.42 8.6 4.7 40 8 90.04 8.6 3.4 378 94.5 Table 6 (continued) Physical properties/Aflatoxin Bl binding clay/salt complex: Effect of clay/salt type TP 1 3.6 5 29g 85, 22 3.7 4.4 230 90. 24 4.6 5.2 60 89.6 AP I 2.7 5.4 244 86.9AP L 4.7 2.3 Thin Gi 91.82 6.8 4 1590 92.8 Sodium citrate: SC = Sodium citrate: ST = Sodium thiosulfate: D P = Disodium phosphate.

Example V Occurs when a combination of clay B and 4% sodium birophosphate is used in daily life. of aflatoxins compared to when untreated base clay (Clay B) was used. To illustrate the improved binding, the following in vivo study was performed. The smell of these experiments Arbor Ackles x Peter Ran (1 week old) sX Peterson) Attach label bands to the wings of broiler chickens and Petersime's battery cage contained only 10 birds. With the exception of group 1, 25 birds were randomly placed in each room, with 2 rooms per group. these Cages were provided with a stemming heater at 95°F ± 5°F, water and food ad libitum. there was. On day 7, the fencing heater was lowered to 906F ± 5°F. irregular schedule The 100-day-old chickens were transferred to a beatershim growth battery according to the protocol. each Birds were housed 10 per room and maintained on a reasonable diet. Each group of 10 birds The sample collection period was representative of the sample collection period. Then, set the environmental temperature to 85'F ± 56F. Maintained. A thorn-shaped feeder and waterer were used.

Administration: During days 133 and 144 (24 hour period), per room of the chickens Sample consumption was measured. Based on this sample consumption value, give +4 to chickens. 0 Aflatoxin Bl (“CAFBI)” and Aflatoxin Bl (AFBI) The total amount of Calculated amount of “CAFBI and AFBI and approx. 0.015g of feed (Basic clay or basic clay/4% sodium birophosphate depending on the group) (treated (4%) or untreated) is a small enzyme that can be dissolved in grains. It was placed in a Latin capsule and passed through the level of the esophagus of each chicken. After administration, chicken Birds were returned to their chambers and fed their appropriate regular diet.

Sample collection: Sample collection times for each group of chickens are 1/2 hour, 1 hour, and 2 hours. , 4 hours and 6 hours. Liver samples and blood samples were collected at these sample collection times. got the fee. Liver samples were immediately frozen at -20°C.

Blood was aspirated into a lo-1 heparinized vacuum vessel tube and immediately frozen (up to 6 hours). After centrifugation, the serum was removed and frozen at -20°C.

Assay: Take a small sample (1.0 g) of each individual liver from the above sample and evaporate 3 times the volume. Mix distilled water and 5 ml of chloroform-methanol (2:1) using a high-speed mixer. Homogenized and assayed for levels of CAFBl using chloroform-meth Take out the nol layer and use 15111 Aqualyte Plus. Plus) (manufactured by Baker (J, T, Baker)) scintillation car The tube was placed in a clear glass scintillation tube containing the protein.

1 ml of serum was added to the 1911 scintillation cocktail. The sample count is Performed with Beckman LS 7000 scintillation counter It was. Each tube was counted over a 5 minute period using an external standard suppression correction. total The number efficiency was measured using the CAFBI standard.The total number of counts before dividing by the sample size The counting efficiency was corrected by subtracting the background counts.

, Feed Mixture Standard Comsoy (coIIl-say) initial diet was used. this The feed was mixed in a horizontal paddle mixer with a capacity of 100 kg. 0.1% or more in feed or 0.65% (dry basis) of the additive to obtain a mixed feed containing the additive. The additive was mixed with the feed. The feed was mixed for 10 minutes. Unprocessed feed is basic food It was more than that.

14 CAFBI combination drug・”CAFBI is manufactured by Morave Tsuku Biochemical Co., Ltd. k Bioch+eica1. Obtained from Brea C^). This “CAFBI” The specific radioactivity was 100-200 uci/mmol. AFBI is sigmaized Obtained from Sigma Chemicals.

Data analysis, the amount of 14CAFBI in liver and serum was determined at 0.1% additive level. Chickens treated with CAFBI 20 and 80 ppb and 05% treated with additive levels (CAFBI 20 and 80 ppb) and untreated. Treatments of chicken C4CAFBI 20 and 80 ppb) were compared.

Curve fitting program 'ESTRIP (Brown & Manno) and Manno), Pharmaceutical Science Journal (J, of Pharmaceut ical Sci, ), 1978.67 volume, 1687-1691) The pharmacokinetic variables of adsorption rate, elimination rate, and area under the curve were determined in the liver and serum. calculated regarding.

Regarding the content of “CAFBI” in liver and serum, each time point and ESTRIP Differences were analyzed for each pharmacokinetic variable determined in . The differences between treatment methods are Measured by Tukey's LSD test. We set the probability of type 1 error at a nominal level of 5%. I set it to bell.

Results Figures 6A, 6B and 7A, 7B derived from the data in Table 7 are, respectively, Two different levels of base clay or base clay plus sequestrant Chickens were fed two levels of radiolabeled aflatoxin in their regular diet. Temporal changes in the amount of +4c AFBI detected in serum and liver tissue in cases of Explain what happened using a diagram.

For both serum and liver tissue, aflatoxin levels were found in the first hour after exposure. It reaches a peak within a short period of time, and then gradually decreases over time. Control group (Suna That is, feed plus aflatoxin is present, but additives are not present: Table 7 significantly higher levels in serum and liver tissue compared to levels detected in As evidenced by the fact that low levels of aflatoxin are detected in , conventional feed containing basic clay or basic clay plus sequestering agent. Clearly provides protection against aflatoxin exposure.

Also, it is clear that the regular feed treated with basic clay plus sequestering agent is The decrease in aflatoxin detected in serum at peak times between 1 and 2 (2 to 4 (2x), and in liver tissue (20x8x), containing only basal clay. significantly better than conventional feeds containing sequestrants (not containing sequestrants). Ru. Therefore, this experiment was conducted on sensitive montmorillonite clay used in food processing aflate, which is given by treatment with typical sequestering agent salts. Provides in vivo evidence of increased syn-binding capacity.

Table 7 In vivo binding of CI4 radiolabeled aflatoxin versus time in broiler arbor a. Cress X beater run liver data: Clay B 20 0.1 40 32 30 33 2580 0.1. 23 18 1 7 20 1620 0.5 22 21 18 15 1280 0.5 1 6 13 13 20 8.5 Table 7 (continued) Blood data: Clay B 20 0.1 g, 5 23 10 5.580 0.1 4.0 18 12 420 0.5 2.5 10 5.8 1.780 0.5 1.5 9. 7 2.1 0.6 Liver data Clay B + 4% AP* 20 0.1 4.7 7.0 6.4 3.0 1.180 0.1 6.1 g, 7 6.7 3.0 1.220 0.5 0.9 2.3 L, 3 0 ．． 8 0.880 0.5 3.0 2.8 1.6 1.0 0.6 blood day Ta: Clay B + 4% AP* 20 0.1 2.4 13 3.1 2.9 1.380 0.1 4.5 11 3.2 2.3 1.320 0.5 0. ,! ! 3.1 2.3 1 ．． 6 1.480 0.5 0.6 5.4 2.1 1.4 0.9* Pyro sodium hydrogen phosphate Example VI Other mycotoxins other than aflatoxin can also be used in clay/sequestrant combinations. The following in vitro tests were conducted to demonstrate that increased binding occurs when exposed to Ta. In this set of experiments, five other commercially important mycotoxins: Xinivalenol, zearalenone, ochratoquinone A1 thrinin and T-2 I experimented with toxins. The clay/sequestrant samples used in these experiments were It was the same as that used in Example II.

Extraction and separation of these toxins were included in the in vitro volume test described in Example II. The following changes were made in the analysis.

Extraction method ■) For cearalenone, the extraction method was the same as for aflatoxin B1.

2) For ochratoquine A and citrinin, the aqueous phase was diluted with 54 aqueous HCI to acidify, then 3! Extracted twice with 1 aliquots of dichloromethane. This organic extract The output was collected and evaporated to dryness under nitrogen prior to analysis.

3) For T-2 and deoxynivalenol, dilute the aqueous phase with sodium chloride. Saturation, then 3! The mixture was extracted three times with 1 aliquots of ethyl acetate.

The organic phases were combined and evaporated to dryness under nitrogen prior to analysis.

Analysis method 1) For ochratoxin A and citrinin, the analysis method is aflatoxin. It was the same as that for B1.

2) For T-2, deoxynivalenol and zearalenone, extract the aqueous phase. The residue was dissolved in 40111 ethyl acetate. Transfer 1 μl of this solution onto the column. 12II cross-linked methyl silicone capillary column (0.2 am i.d., membrane (thickness: 33 microns). The initial temperature was maintained at 40°C for 1 minute, then 4 The temperature was increased at 0°C/min to a final temperature of 270°C. Peaks represent all of an individual sample run. The integral values for the ion chromatograms are applied under the same chromatographic conditions. Quantification was performed by comparing with a known standard using a calculator. Standards are routinely analyzed and GC/MS We confirmed that the sensitivity did not change significantly during the experiment. GC/MS takes longer time TLC analysis may be advantageous for zearalenone due to the required length. Found. Binding experiments were performed at two different adsorbent levels: 100 mg and It was performed with 10 mg adsorbent/40 μg toxin. Figures 8-11 are each 10 40 μg of deoxyniva using 0 nag of various clays/sequestering agents. When combined with lenol, zearalenone, ochratoxin A and torinin This is a bar graph showing the results obtained. With the exception of zearalenone, 10 mg Binding of other toxins using only sorbents is low (i.e. <10 %), only the results obtained at the 100 mg level were graphed. T- The result of the combination of two compounds is diol and triol derivatives (these are The subsequent conversion to (desorbed) is at least partially due to its (apparent) reduction due to binding. It was concluded that this was due to a small number of people, so I did not make a graph.

However, as is clear from the figure, each of the other toxins They show increased binding in the presence of combinations of genus sequestrants. Not everything However, there is evidence that the same clay/sequestering agent combination is effective in this context. What is the most suitable clay/metal ion for a particular toxin and sequestering agent? This may be a result of the sequestering agent ratio not being determined (e.g., Example I). II). Also, the chemical structure (and therefore reaction) of these toxins is It must also be borne in mind that the characteristics (see FIG. 12) are completely different.

On this basis, it is possible to promote increased binding of certain mycotoxins. The optimum clay/sequestering agent ratio is necessarily also optimum for the others. What I can't say is not surprising.

Example VII Sequestering agents bind mycotoxins in adsorbent materials other than montmorillonite The following in vitro tests were conducted to demonstrate the increased efficiency of This fruit In experiments, phosphoric acid treated (and untreated) pseudobomite alumina (high surface area of alumina, partially crystalline oxyhydroxide) and pyrophyllite ( 2, 1 phase has the same structure as montmorillonite, but lacks interphase cations. Aflatoxin, which binds to irosilicate), is Compared to Rironite. The phosphate used in these experiments was dihydrogen pyrophosphate. Add 1 g of Lium 50 II salt to water and adjust to 250 ml in a measuring flask. A solution of sodium hydrogen pyrophosphate was prepared. ll1g of aflatoxin B1 was added to 1lIl of methanol (reagent standard) to prepare an aflatoxin solution. . Next, 1 ml of the above phosphate solution was added to 100 mg of the above adsorbent in a test tube. The material was added and warmed at 37° C. for 1 hour in a water bath. Then add 20 μm B1 solution. It was added to the material in the test tube and heated at 37°C for 2 hours.

The same method was used for the control example (no phosphoric acid), but the phosphate solution was replaced with using pure water.

After extraction according to Example II, the residue was 1001! Dissolved in 1 chloroform I made you understand. Add 2μI of this solution to 10×I (l Cm Analtech HPTL It was placed on a C-HLF silica gel plate (lot #20888). Chloro this board A known sample was developed with a form/acetone solution (9:1 volume/volume) and placed on the same plate. Visual ratio of fluorescence (365 runs) with standard aflatoxins B1, B2 and GI It was determined by comparison.

The results reported in Table 8 indicate that the addition of phosphate was It has been shown that the adsorption of flatoxin B1 is increased.

Even when phosphates are present, e.g. alumina and pyrophyllite are adsorbents. As in the case where B of the relevant aflatoxin species (i.e. B2, Gl) Production from 1 is significantly inhibited.

These results support the use of various sequestering agents such as sodium hydrogen pyrophosphate. A common practice is to increase aflatoxin binding when used with adsorbent materials. minerals, and not limited to a narrow class of clay minerals (i.e. montmorillonites). It shows that

Table 8 Effect of adding sodium birophosphate: Binding of aflatoxins to other adsorbents Montmorillonite -23000 θ Mi Maa Akira Akira Mi FIG.3 Clay/sorbent symbol Clay/sorbent symbol EG, 6A 072J4567 time (hour) time (hour) FIG. 7A time (hour) time (hour) summary Biodegradable feed is contaminated with mycotoxins and inactivation of mycotoxins sufficient to enhance the mycotoxin inactivation ability of phyllosilicates. Myco containing particles of phyllosilicate minerals coated with a quantity of sequestering agent A dry solid feed composition that is mixed with a toxin inactivator.

Copy and translation of amended sound) Submission (Article 184-8 of the Patent Law) September 1, 1992 3. Patent applicant Name: Engelhard Corporation 4, Agent: 107 Phone: 3585-2256 5. Date of submission of corrected sound April 24, 1992 6. List of attached documents (1) Translated copy of corrected sound) 1 copy The scope of the claims 1. The phyllosilicate mineral that can inactivate mycotoxins Sufficient amount of water-soluble gold to enhance the mycotoxin deactivator power of the acid salt mineral particles For use with dry biodegradable animal feed containing particles coated with sequestrants. Dry solid granular feed additive for use.

2. The above metal ion sequestering agent can disperse the above phyllosilicate particles and in excess of the amount necessary to disperse the above phyllosilicate particles in the water. The feed additive according to claim 1, characterized in that it is present in the feed additive.

3. The above phyllosilicates have high calcium/low sodium montmorillonite viscosity. clay, and the sequestering agent is about 2 to 10% by weight based on the weight of the clay. Feed additive according to claim 1, characterized in that it is present in an amount in the range of 10%.

4. The above metal ion sequestering agents include sodium acetate, calcium acetate, and calcium acetate. Lium; for sodium citrate, calcium citrate and potassium citrate and its free acids and monoisopropyl, monoglycerides stearyl and triglycerides. Liethyl derivatives: ethylenediaminetetraacetic acid dihydrogen disodium salt and disodium salt calcium salt calcium nigerconate and sodium gluconate Nostearin: calcium hydrogen orthophosphate, potassium dihydrogen orthophosphate, Sodium aluminum orthophosphate, sodium dihydrogen orthophosphate, ortho Sodium hydrogen phosphate, sodium trihydrogen orthophosphate: potassium hexametaphosphate and sodium hexametaphosphate, tetrasodium pyrophosphate and pyrophosphate. Sodium rophosphate, sodium nitripolyphosphate, calcium phytate: tartar Sodium and potassium tartrate and their free acids: thiosulfate selected from the group consisting of sodium; and mixtures of the above. A feed additive as claimed in the claims, characterized in that:

5. The above metal ion sequestering agent is a phosphate or a citrate. The feed additive according to claim 2.

6 The above montmorillonite has divalent cations plus trivalent cations/−valent cations. characterized by having exchangeable cations with a cation ratio of more than 7 The feed additive according to claim 3.

7. The above montmorillonite has a surface area in the range of about 40 to 80 a2/g. characterized by having a total pore volume in the range of about OI to 0.3 cc/g. The feed additive according to claim 3.

8. The above phyllosilicate is an aqueous solution of phyllosilicate and sequestering agent. A claim characterized in that it is coated by spray drying the slurry. A feed additive according to Scope 1.

9. The above phyllosilicic acid uses the aqueous slurry of phyllosilicic acid as a sequestering agent. It is coated by mixing, then drying and powdering this mixture. A feed additive as claimed in the claims.

10. Biodegradable feed is contaminated with mycotoxins. Mycotoxins of the above-mentioned phyllosilicate minerals of phyllosilicates that can be inactivated Contains particles coated with a sequestering agent in an amount sufficient to enhance deactivation capacity. a dry solid liquid characterized in that it is mixed with a mycotoxin inactivator having material feed composition.

11. The above metal ion deactivator further binds the phyllosilicate particles to the above phyllosilicate particles. When coated in sufficient quantities to enhance the mycotoxin inactivation ability of rosilicate, Claims characterized in that it is possible to inactivate mycotoxins in some cases. The feed composition described in Box IO.

12. The above phyllosilicate is calcium montmorillonite. The composition according to claim 10.

13. The above calcium montmorillonite has its divalent cation plus trivalent cation. Must have exchangeable cations with an on/-valent cation ratio of more than 7 The composition according to claim 10, characterized in that:

14. The above montmorillonite has a surface area in the range of about 40 to 80 m2/g. a total pore volume in the range of about 0.1 to 0.3 cc/g. 14. The composition according to claim 13.

15. The above sequestering agents include sodium acetate, calcium acetate and calcium acetate. Lium, sodium citrate, calcium citrate and potassium citrate and its free acids and monoisopropyl, monoglycerides stearyl and triglycerides. Liethyl derivatives: ethylenediaminetetraacetic acid dihydrogen disodium salt and disodium salt Liumium calcium salt; calcium gluconate and sodium gluconate, Cystearin; calcium hydrogen orthophosphate, potassium dihydrogen orthophosphate, Sodium aluminum orthophosphate, sodium dihydrogen orthophosphate, ortho Sodium hydrogen phosphate, sodium trihydrogen orthophosphate: potassium hexametaphosphate Lucium and sodium hexametaphosphate: tetrasodium pyrophosphate and Sodium rophosphate, sodium tripolyphosphate, calcium phytate: tartar sodium and potassium tartrate and their free acids; thiosulfate selected from the group consisting of sodium: as well as mixtures of the above. 11. A composition according to claim 10, characterized in that:

16. The above-mentioned coated phyllosilicate contains about 0.025 to 1.0% of the animal feed. Composition according to claim 10, characterized in that it is present in an amount in the range of 5% by weight.

17. The above animal feed is poultry feed, pig feed or dairy feed. The composition according to claim 10.

18. Claims characterized in that the above mycotoxin is aflatoxin The composition according to Box 10.

19. The above mycotoxin is aflatoxin, and the above phyllosilicate is It is a high-calcium/low-sodium somorillonite clay and contains the metal ions listed above. The chaining agent is about 2 to 10% based on the weight of the above calcium montmorillonite. Claim 10 characterized in that the phosphate or citrate is present in an amount of Written composition.

20. Claim 10, wherein the phosphoric acid is a condensed phosphate. Composition of.

21, characterized in that the above condensed phosphate is sodium hydrogen pyrophosphate The composition according to claim 20.

22, characterized in that the above condensed phosphate is sodium hydrogen hexametaphosphate 21. The composition according to claim 20.

23. A claim characterized in that the above condensed phosphate is tetrasodium birophosphate. The composition according to claim 20.

24. A claim characterized in that the metal ion sequestering agent is sodium citrate. The composition according to claim 10.

25. Feed contains aflatoquinone BL deoxy 7 nivalenol, zearalenone, okra A matrix selected from the group consisting of toxin A1 citrinone or T-2 toxin. Contaminated with icotoxin and coated with approximately 2 to 10% by weight sequestering agent. About 0.025 to 1.5% by weight high calcium/low sodium base Dry solid animal feed composition, characterized in that it is mixed with tonite.

26, characterized in that the above feed is dry poultry feed, pig feed or dairy feed; The composition according to claim 25.

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Claims (1)

[Claims] 1. The matrix of mineral particles of phyllosilicate minerals that can inactivate mycotoxins with a sufficient amount of water-soluble sequestering agent to enhance icotoxin inactivation ability. Dry solid granular feed additive containing coated particles. 2. The above metal ion sequestering agent may further disperse the above phyllosilicate. possible and in excess of the amount necessary to disperse the above phyllosilicate particles in water. Feed additive according to claim 1, characterized in that it is present in an amount of. 3. The above phyllosilicates are high calcium/low sodium montmorillonite clays. and the sequestering agent is about 2 to 1, based on the weight of the clay. Feed additive according to claim 1, characterized in that it is present in an amount in the range 0%. 4. The sequestering agents listed above are sodium acetate, calcium acetate and potassium acetate. Um: Sodium citrate, calcium citrate and potassium citrate and its free acid and monoisopropyl, monoglycerides stearyl and triglycerides. Ethyl derivatives; dihydrogen disodium salt and disodium salt of ethylenediaminetetraacetic acid calcium salt; calcium gluconate and sodium gluconate: oxy Stearin; hydrogen orthophosphate-calcium, potassium dihydrogen orthophosphate, Sodium Aluminum Orthophosphate, Sodium Dihydrogen Orthophosphate, Orthophosphate Sodium monohydrogen phosphate, sodium trihydrogen orthophosphate; Calcium hexametaphosphate Si and Sodium Hexametaphosphate: Tetrasodium Pyrophosphate and Pyro Sodium phosphate: sodium tripolyphosphate; calcium phytate; tartaric acid Sodium and Sodium Potassium Tartrate and its Free Acid: Sodium Thiosulfate selected from the group consisting of thorium: as well as mixtures of the above. The feed additive according to claim 1, characterized in that: 5. characterized in that the above metal ion sequestering agent is a phosphate or a citrate; The feed additive according to claim 2. 6. The above montmorillonite has divalent cations plus trivalent cations/monovalent cations. characterized by having exchangeable cations with a cation ratio of more than 7 The feed additive according to claim 3. 7. The above montmorillonite has a surface area in the range of about 40 to 80 m2/g and about 0. ．． total pore volume in the range 1 to 0.3 cc/g. The feed additive according to scope 3. 8. If the above phyllosilicate is an aqueous slurry of phyllosilicate and sequestering agent, Claim characterized in that the coating is coated by spray drying The feed additive according to scope 1. 9. When the above phyllosilicic acid is used, an aqueous slurry of phyllosilicic acid is mixed with a sequestering agent. The mixture is then dried and powdered to form a coating. The feed additive according to claim 1, characterized in that: 10. Biodegradable feed is contaminated with mycotoxins; Mycotoxins of the above-mentioned phyllosilicate minerals of phyllosilicates that can be inactivated Contains particles coated with a sequestering agent in an amount sufficient to enhance deactivation capacity. a dry solid liquid characterized in that it is mixed with a mycotoxin inactivator having material feed composition. 11. The above metal ion deactivator further deactivates the phyllosilicate particles. When coated in sufficient quantities to enhance the mycotoxin inactivation ability of rosilicate, The claimed invention is also characterized in that it is possible to inactivate mycotoxins in some cases. Feed composition according to range 10. 12. The above phyllosilicate is calcium montmorillonite. The composition according to claim 10. 13. Calcium montmorillonite mentioned above has divalent cations plus trivalent cations. Must have exchangeable cations with an on/monovalent cation ratio of more than 7 The composition according to claim 10, characterized in that: 14. The above montmorillonite has a surface area in the range of about 40 to 80 m2/g and about a total pore volume in the range of 0.1 to 0.3 cc/g. The composition according to claim 13. 15. The sequestering agents listed above are sodium acetate, calcium acetate and calcium acetate. Lium; for sodium citrate, calcium citrate and potassium citrate and its free acids and monoisopropyl, monoglycerides stearyl and triglycerides. Liethyl derivative; dihydrogen disodium salt and disodium salt of ethylenediaminetetraacetic acid calcium salt; calcium gluconate and sodium gluconate; Cystearin: monocalcium hydrogen orthophosphate, potassium dihydrogen orthophosphate, Sodium aluminum orthophosphate, sodium dihydrogen orthophosphate, ortho Sodium monohydrogen phosphate, sodium trihydrogen orthophosphate; potassium hexametaphosphate Lucium and sodium hexametaphosphate; tetrasodium pyrophosphate and Sodium rophosphate; Sodium tripolyphosphate; Calcium phytate: Tartar sodium and potassium tartrate and their free acids; thiosulfate selected from the group consisting of sodium; and mixtures of the above. 11. A composition according to claim 10, characterized in that: 16. The coated phyllosilicate is about 0.025 to 1.5 of the animal feed. 11. A composition according to claim 10, characterized in that it is present in an amount in the range of % by weight. 17. characterized in that the above animal feed is poultry feed, pig feed or dairy feed; The composition according to claim 10. 18. Claims characterized in that the above mycotoxin is aflatoxin. The composition according to Box 10. 19. The above mycotoxin is aflatoxin, and the above phyllosilicate is It is a high-calcium/low-sodium montmorillonite clay and contains the metal ions listed above. The chaining agent is about 2 to 10% based on the weight of the above calcium montmorillonite. Claim 10 characterized in that the phosphate or citrate is present in an amount of Compositions as described. 20. Claim 10, wherein the phosphoric acid is a condensed phosphate. Composition of. 21. The above condensed phosphate is sodium hydrogen pyrophosphate. The composition according to claim 20. 22. Characteristic that the above condensed phosphate is sodium hydrogen hexametaphosphate 21. The composition according to claim 20. 23. A claim characterized in that the above condensed phosphate is tetrasodium pyrophosphate. The composition according to claim 20. 24. The above metal ion sequestering agent is sodium citrate. The composition according to claim 10. 25. The feed contains aflatoxin B1, deoxynivalenol, zearalenone, and octopus. selected from the group consisting of latoxin A, citrinone or T-2 toxin Contaminated with mycotoxins and approximately 2 to 10% by weight of sequestering agents. Approximately 0.025 to 1.5% high calcium/low sodium coated Dry solid animal feed composition, characterized in that it is mixed with bentonite. 26. characterized in that the above feed is dry poultry feed, pig feed or dairy feed; The composition according to claim 25.