Suspending aid composition for dosing of automatic water drinking line and method for dosing of automatic water drinking line

Abstract

The invention discloses a suspending agent composition for automatic water drinking line dosing and a method for automatic water drinking line dosing, the suspending agent composition comprises xanthan gum, a thickening inhibitor and an optional thickening inhibition reinforcing agent, the thickening inhibitor is selected from alcohol compounds, ketone compounds and polyether, and the thickening inhibitor is selected from the group consisting of alcohol compounds, ketone compounds and polyether. The thickening inhibition enhancer is selected from salts such as sulfate, hydrochloride and / or sylvite, sodium salt, ammonium salt or a composition of the sulfate, the hydrochloride and / or the sylvite, the sodium salt and the ammonium salt. The viscosity of the material liquid containing the high-concentration suspending agent prepared from the suspending agent composition is not greatly different from the viscosity of the diluted material liquid, and the material liquid can be added into a waterline through a dosing pump to obtain a water medium with suspension property, so that solid drug particles can be uniformly suspended in the waterline.

Description

Technical Field

[0001] The invention belongs to the field of suspending agent compositions, and in particular relates to a suspending agent composition for adding medicine to an automatic drinking water line and a method for adding medicine to the automatic drinking water line. Background Art

[0002] With the current trend of large-scale farming, the scale of breeding is getting larger and larger, so group drug administration has become a problem that modern farming must face. Drug administration methods are mainly divided into active methods (for animals, such as mixed feeding, drinking water, etc.) and passive methods (such as injection, eye drops, oral administration, etc.). Among the above methods, drinking water administration is the most advantageous, because this method has the advantages of low labor intensity, high uniformity of mixing of soluble drug solutions, and low animal stress, making it the first choice for group drug administration in farms.

[0003] People have also developed a variety of automatic dosing equipment for drinking water medication, such as fermentation dosing integrated machine, dosing pump (proportional dosing pump), etc. The fermentation dosing integrated machine can add the liquid medicine to the water line at a set flow rate for direct use or dilution to a specific proportion concentration; using a proportional dosing pump, no additional power is required, the high-concentration liquid medicine is sucked into the water line through the flow of water, and diluted to the required set concentration according to the preset dilution multiple, generally between 50 and 200; when using high-concentration liquid medicine for dilution and addition, only 1 / 50 to 1 / 200 (according to the set dilution multiple) of the expected liquid medicine needs to be prepared manually, which greatly reduces the workload of liquid medicine preparation. However, the use of proportional pump dosing equipment generally requires that the drug has good water solubility, and it is necessary to meet the requirements that the drug remains dissolved in the high-concentration liquid medicine before dilution and the low-concentration liquid medicine in the water line after dilution (more importantly), so that the uniform addition and use of the drug can be smoothly achieved. If there are solid particles in the high-concentration drug solution before dilution and / or solid particles in the diluted drug solution, the use is restricted. The main reason is that the sedimentation of solid particles causes uneven dosing or blocks the water spout of the drinking water line. The solubility of some drugs in water can meet the preparation of drug solutions with clinical concentrations, but its solubility is not enough to prepare high-concentration drug solutions with a concentration of 50 to 200 times the clinical concentration. In fact, many drugs used in clinical practice will have insoluble solid particles in such high-concentration drug solutions, which limits the scope of use of waterline drugs. Another situation is that the drug solution itself is a high-concentration solution prepared using its non-aqueous good solvent (organic solvent), but after the drug solution (the solvent is an organic solvent) is diluted with water, there is drug precipitation. The reason is still that the drug has low solubility in water, and even if it is prepared with water at a concentration for clinical use, it is still impossible to obtain a solution form. Such solid drug particles precipitated in the water line will form sedimentation, resulting in the risk of blocking the water spout. There is also a situation where the drug itself is a particle, and it always exists in the form of solid particles, whether in a high-concentration drug solution or in a diluted clinical concentration drug solution. For example, in the process of giving animals coccidia oocyst vaccine drinking water immunization, the coccidia vaccine oocysts are always in the form of particles (depending on the specific species, the particle size is between a dozen and several dozen microns). This coccidia oocyst vaccine drug is kept in a suspended state during use, which is a prerequisite for obtaining its good immune effect.

[0004] There are various types of drugs used in aquaculture. According to the solubility and / or properties of the drugs themselves under different conditions, suspension is required for solid particles to obtain uniform drug intake. Naturally, this suspension requirement is also related to the size of the particles. For example, although it is not a homogeneous system of solution, it is a microemulsion system. Although the dispersed phase exists in the form of small droplets, the droplets are very small, generally less than 100 nanometers, and in fact, there will be no phase separation and sedimentation, so there is no need to use a suspending agent. For drugs with suspension requirements, the requirements for suspension of the drug solution are different in different usage scenarios. For example, if there is only a suspension requirement for high-concentration drug solution, a suspending agent can be added only to the high-concentration drug solution. In general, the drug solution is stored outside the waterline at this time, and stirring can eliminate the influence of sedimentation to a certain extent. This situation where only the suspension requirements of the drug in the high-concentration drug solution before dilution need to be paid attention to is easier to achieve. The more difficult situation is the situation where the drug has a suspension requirement in the waterline (that is, the drug cannot be well dissolved in the waterline at its clinical concentration, or it is completely insoluble). Although it is easy to prepare a liquid medicine that can meet the drug suspension requirements in the water line, for example, by adjusting the amount of suspending agent, suitable suspension can be obtained, which only requires a certain number of attempts to obtain satisfactory results, but the actual clinical use concentration of many drugs is very low, so the actual prepared liquid medicine needs to be quantified according to the actual overall drinking water volume of the group of animals. For farms with thousands to tens of thousands of breeding animals, it is necessary to prepare dozens of liters or even hundreds of liters of liquid medicine, which is a very large workload, time-consuming and labor-intensive. In this case, if a small amount of high-concentration suspension can be prepared, and then diluted to a predetermined volume by a dosing device, and the diluted water medium meets the drug suspension requirements and meets the concentration used in clinical practice, it will be an ideal way. However, this ideal method is difficult to achieve. The main reason is that after most common suspending agents are prepared into suspensions, the concentration of the suspending agent is positively correlated with the viscosity of the suspension, but it is not a linear relationship. Generally, the degree of viscosity increase is much greater than the degree of concentration increase. Similarly, when the suspension is diluted, the degree of viscosity reduction is much greater than the degree of concentration reduction. This makes the viscosity of the suspension increase rapidly when the concentration of the suspending agent increases, so that it loses fluidity and cannot be added through the dosing equipment, that is, it does not have good addition operability. For example, if it is necessary to use a dosing pump to add a vaccine suspension and make it meet the suspension requirements after dilution, it is necessary to prepare a 50-200 times concentrated suspension, which means that the concentration of the suspending agent in the prepared high-concentration suspension (feed liquid) is 50-200 times the concentration of the suspending agent in the suspension (feed liquid) that meets the suspension requirements in the waterline.For general suspending agents, such as xanthan gum, the clinical concentration that meets the suspension requirements of coccidia vaccine is about 0.08% (viscosity is about 40-90mPa.s, which can meet the suspension requirements of coccidia oocysts for no less than 6 hours). If a 50-200 times concentrate (suspension containing a high concentration of suspending agent) is prepared with water, the concentration of xanthan gum in the concentrate needs to reach 4.16%-16.7%, and its viscosity will be at least greater than 7Pa.s (based on the liquid product with a xanthan gum content of 8%-15%, its viscosity can reach 15000-30000cp (i.e. mPa.s) Li Jingwei. Production and Application of Microbial Polysaccharide-Xanthan Gum. Beijing: China Agricultural Science and Technology Press, 1995.87). The fluidity of this viscosity of liquid is very poor, and it is difficult to add it to the water line through the dosing equipment, and it has lost the actual addition operability. Moreover, it is difficult to quickly mix and dilute such a high viscosity liquid with water after adding it to water to obtain the required viscosity of the liquid. If the addition operability of high-concentration suspension is to be maintained, the content or concentration of the suspending agent needs to be reduced. However, when the suspension is diluted to the predetermined volume, the 50-200 times dilution cannot meet the suspension requirements of the drug. This makes it difficult to achieve high-multiple dilution and automatic dosing of drugs that need to be suspended using dosing equipment.

[0005] At present, when drugs in the form of solid particles (such as coccidia vaccine oocysts) are administered through drinking water, they are usually prepared into a suspension with a clinical concentration that meets the suspension requirements and is directly injected into the water line without dilution. Although this process saves labor compared to the operation of packaging the prepared suspension into drinking bottles, the process still requires the preparation of a large volume of suspension, and the labor intensity is still relatively high.

[0006] To achieve the automatic dosing of drugs in the form of solid particles (such as coccidia vaccine oocysts) through automatic dosing equipment, a suspending agent composition is required, the viscosity of the prepared liquid containing high-concentration suspending agents is not much different from the viscosity of the liquid containing low-concentration suspending agents obtained after dilution (for example, the dilution ratio is 20 to 200 times), preferably close, for example, the viscosity of the two is 1:20 to 50:1; further 1:3: to 20:1, further 1:3 to 3:1; even 1:2 to 2:1, so that both can meet the requirements of fluidity and suspension before and after dilution, and can quickly complete hydration in a short time during the high-fold dilution process. There is no suspending agent composition that meets this requirement in the prior art, nor is there such a dosing method. Therefore, it is of great practical significance to develop such a suspending agent composition. Developing a dosing method that can be highly diluted with the suspending agent with the suspension requirement will change the existing waterline dosing pattern. Summary of the invention

[0007] An object of one aspect of the present invention is to provide a suspending agent composition for dosing in an automatic drinking water line, the suspending agent composition comprising xanthan gum and a thickening inhibitor, and optionally, a thickening inhibitor enhancer,

[0008] The thickening inhibitor is selected from alcohol, ketone or polyether or a combination thereof,

[0009] The thickening inhibition enhancer is selected from salts, and the salts are selected from sulfates, hydrochlorides and / or potassium salts, sodium salts, ammonium salts or combinations thereof.

[0010] In another preferred embodiment, the alcohol is selected from ethanol, propanol, ethylene glycol, propylene glycol, glycerol, butanetriol, tert-butyl alcohol or a combination thereof.

[0011] In another preferred embodiment, the ketone is selected from acetone.

[0012] In another preferred embodiment, the polyether is selected from polymers formed by one or more of ethylene glycol, propylene glycol, butylene glycol, pentanediol, hexanediol, glycerol, or a combination thereof.

[0013] In another preferred embodiment, the salt is selected from sodium sulfate, potassium sulfate, lithium sulfate, ammonium sulfate, sodium chloride, potassium chloride, lithium chloride, ammonium chloride or a combination thereof.

[0014] In another preferred embodiment, the weight ratio of the xanthan gum to the thickening inhibitor is 1:1.5-19, more preferably 1:2-10, and most preferably 1:2.5-4.0.

[0015] In another preferred example, the weight ratio of the salt to xanthan gum is 0.1:1 to 2:1.

[0016] In another preferred embodiment, the thickening inhibitor is selected from polyether, and the polyether is selected from polyethylene glycol and / or polyethylene glycol polypropylene glycol block copolymer. In another preferred embodiment, the number average molecular weight of polyethylene glycol and / or polyethylene glycol polypropylene glycol block copolymer is 1000-8000, more preferably 2000-6000, and most preferably 3000-5000.

[0017] In another preferred embodiment, the suspending agent composition is in the form of particles. In another preferred embodiment, the particles are spherical and / or quasi-spherical. In another preferred embodiment, the particle size of the spherical and / or quasi-spherical particles is less than 3 mm, more preferably 0.2 to 2.0 mm.

[0018] In another preferred embodiment, the preparation method of the suspending agent composition comprises the following steps:

[0019] The polyether is heated until it is completely melted, and then xanthan gum and an optional thickening inhibitor enhancer are added to the molten polyether, stirred evenly, and granulated to obtain the suspending agent composition.

[0020] In another preferred embodiment, the aqueous suspension composition for dosing in automatic drinking water lines provided by the present invention comprises xanthan gum, a thickening inhibitor and water, and optionally a thickening inhibitor enhancer, wherein the mass concentration of the xanthan gum is 5 to 9%.

[0021] The present invention also provides a method for adding medicine to an automatic drinking water line, comprising the following steps:

[0022] (1) mixing the above suspending agent composition with water to prepare a liquid containing high concentration xanthan gum, wherein the mass concentration of the xanthan gum is 5 to 9%; or providing the above aqueous suspending agent composition;

[0023] (2) preparing the drug into a uniformly dispersed liquid;

[0024] (3) adding the high-concentration xanthan gum liquid prepared in step (1) to the automatic drinking water line through a first dosing pump, so that the viscosity of the water medium in the water line is 10 to 500 mPa.s at 6 rpm, and adding the drug-containing liquid prepared in step (2) to the automatic drinking water line at a downstream position of the high-concentration xanthan gum liquid added to the automatic drinking water line through a second dosing pump, so that the drug is uniformly dispersed in the water medium in the automatic drinking water line,

[0025] The liquid containing high concentration of xanthan gum and the liquid containing medicine are diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times.

[0026] In another preferred embodiment, in the above-mentioned method of adding medicine to the automatic drinking water line, in step (3), the slurry is added to the automatic drinking water line so that the viscosity of the water medium in the water line is 20 to 400 mPa.s at 6 rpm, and more preferably 40 to 300 mPa.s.

[0027] In another preferred embodiment, in the above-mentioned method of adding medicine to the automatic drinking water line, the dilution ratios of the liquid containing high concentration of xanthan gum and the liquid containing medicine can be the same or different.

[0028] In another preferred embodiment, in step (1) of the method for adding medicine to the automatic drinking water line, the viscosity of the above-mentioned suspending agent composition is mixed with water to prepare a liquid containing a high concentration of xanthan gum, or the viscosity of the above-mentioned aqueous suspending agent composition after being diluted 50 to 200 times is 1:20 to 50:1, more preferably 1:5 to 20:1, further 1:3 to 20:1, and further 1:3 to 3:1.

[0029] In another preferred embodiment, the method for adding medicine to an automatic drinking water line provided by the present invention comprises the following steps:

[0030] (1) mixing the above suspending agent composition with water to prepare a liquid containing high concentration of xanthan gum, wherein the weight content of xanthan gum is 5-9%, or providing the above aqueous suspending agent composition,

[0031] (2) adding the drug to the high-concentration xanthan gum solution of step (1) or the aqueous suspending agent composition,

[0032] (3) adding the drug-containing liquid prepared in step (2) to the automatic drinking water line through a drug dosing pump, so that the viscosity of the water medium in the water line is 10 to 500 mPa.s at 6 rpm, and the drug is evenly dispersed therein,

[0033] The drug-containing liquid is diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times.

[0034] In another preferred embodiment, in the above-mentioned method of adding medicine to the automatic drinking water line, in step (3), the slurry is added to the automatic drinking water line so that the viscosity of the water medium in the water line is 20 to 400 mPa.s at 6 rpm, and more preferably 40 to 300 mPa.s.

[0035] In another preferred embodiment, in step (1) of the method for adding medicine to the automatic drinking water line, the viscosity of the suspending agent composition is mixed with water to prepare a liquid containing a high concentration of xanthan gum, or the viscosity of the aqueous suspending agent composition after being diluted 50 to 200 times is 1:20 to 50:1, more preferably 1:5 to 20:1, further 1:3 to 20:1, and further 1:3 to 3:1.

[0036] In another preferred embodiment, in the method for adding medicine to an automatic drinking water line of the present invention, the medicine is selected from a medicine whose liquid material of clinical use concentration contains insoluble particles (that is, the medicine in the liquid material of clinical use concentration is not soluble in water or cannot be completely soluble in water to obtain a solution), and the insoluble particles are less than 100 μm and greater than 1 μm;

[0037] In another preferred embodiment, in the method for adding medicine to an automatic drinking water line of the present invention, the medicine is preferably selected from the group consisting of coccidia oocyst vaccines, chemical suspensions or feed additives.

[0038] In another preferred embodiment, the coccidia oocyst vaccine is selected from chicken coccidia oocyst vaccine, rabbit coccidia oocyst vaccine, pigeon coccidia oocyst vaccine, duck coccidia oocyst vaccine, goose coccidia oocyst vaccine, pig coccidia oocyst vaccine, cattle coccidia oocyst vaccine, sheep coccidia oocyst vaccine, dog coccidia oocyst vaccine, cat coccidia oocyst vaccine, and guinea pig coccidia oocyst vaccine.

[0039] In another preferred embodiment, the chemical drug suspension is selected from albendazole suspension and toltrazuril suspension.

[0040] In another preferred embodiment, the feed additive is selected from vitamin additives, trace element additives, and probiotic additives.

[0041] In another preferred example, the probiotic additive is selected from the probiotic additive containing Clostridium butyricum, Bacillus subtilis, Bacillus licheniformis, yeast, Enterococcus faecalis, Enterococcus faecium, Bacillus coagulans, lactic acid bacteria or a combination thereof.

[0042] In another preferred embodiment, the method for administering a coccidia oocyst vaccine to an automatic drinking water line provided by the present invention comprises the following steps:

[0043] (1) mixing a spherical particle suspending agent composition comprising xanthan gum, polyether and optionally a viscosity suppressing enhancer with water to prepare a liquid containing high concentration of xanthan gum, wherein the weight content of the xanthan gum is 5 to 9%;

[0044] (2) preparing the coccidia oocyst vaccine into a uniformly dispersed liquid;

[0045] (3) adding the high-concentration xanthan gum liquid prepared in step (1) to the automatic drinking water line through a first dosing pump, so that the viscosity of the water medium in the water line is 10-500 mPa.s at 6 rpm, and adding the liquid containing the coccidia oocyst vaccine to the automatic drinking water line at a position downstream of the addition of the high-concentration xanthan gum liquid to the automatic drinking water line through a second dosing pump, so that the drug is uniformly dispersed in the water medium in the automatic drinking water line.

[0046] The suspension is diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times.

[0047] The polyether is selected from polyethylene glycol and / or polyethylene glycol polypropylene glycol block copolymer, and

[0048] The viscosity inhibition enhancer is selected from potassium chloride, sodium chloride, sodium sulfate, and potassium sulfate.

[0049] In another preferred embodiment, in the method for administering coccidian oocyst vaccine through the automatic drinking water line, the weight ratio of xanthan gum to polyether in the suspending agent composition is 1:4-5, and the number average molecular weight of the polyether is 3000-5000.

[0050] In another preferred embodiment, in the method of administering coccidia oocyst vaccine through the above-mentioned automatic drinking water line, the high-concentration xanthan gum liquid prepared in step (1) has a polyether content of 15 to 30% and a water weight content of 50 to 70%; and the viscosity of the aqueous medium obtained after the liquid is diluted is 20 to 200 mPa.s.

[0051] In another preferred embodiment, in the method for administering coccidia oocyst vaccine through the automatic drinking water line, the weight content of water in the coccidia oocyst vaccine suspension obtained in step (1) is 55-65%.

[0052] In another preferred embodiment, in the method for administering coccidia oocyst vaccine through the automatic drinking water line, the number average molecular weight of the polyethylene glycol is 3000-5000.

[0053] In another preferred embodiment, in the method of administering coccidian oocyst vaccine through the automatic drinking water line, the viscosity of the high-concentration xanthan gum solution obtained in step (1) and its viscosity after being diluted 50 to 200 times are in the ratio of 1:20 to 50:1, more preferably 1:3 to 20:1, and further 1:3 to 3:1.

[0054] In another preferred embodiment, the method for administering a coccidia oocyst vaccine to an automatic drinking water line provided by the present invention comprises the following steps:

[0055] (1) mixing a particle suspension composition comprising xanthan gum, a polyether and optionally a viscosity suppressant enhancer with water to prepare a liquid containing high concentration xanthan gum, wherein the weight content of the xanthan gum is 5-9%, and adding a coccidia oocyst vaccine to the liquid;

[0056] (2) adding the coccidia oocyst vaccine-containing solution prepared in step (1) to the drinking water line through a dosing pump, so that the water medium in the automatic drinking water line has a suspension property and the drug is evenly dispersed therein,

[0057] The liquid is diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times.

[0058] In another preferred embodiment, in the method of administering coccidia oocyst vaccine through the automatic drinking water line, a liquid containing high concentration of xanthan gum is added to the automatic drinking water line so that the viscosity of the water medium in the water line is 20 to 400 mPa.s at 6 rpm, preferably 40 to 300 mPa.s.

[0059] In another preferred embodiment, in the method for administering coccidian oocyst vaccine through the automatic drinking water line, the weight ratio of xanthan gum to polyether in the suspending agent composition is 1:4-5, and the number average molecular weight of the polyether is 3000-5000.

[0060] In another preferred embodiment, in the method of administering coccidia oocyst vaccine through the above-mentioned automatic drinking water line, the high-concentration xanthan gum liquid prepared in step (1) has a polyether content of 15 to 30% and a water weight content of 50 to 70%; and the viscosity of the aqueous medium obtained after the liquid is diluted is 20 to 200 mPa.s.

[0061] In another preferred embodiment, in the method for administering coccidia oocyst vaccine through the automatic drinking water line, the weight content of water in the coccidia oocyst vaccine suspension obtained in step (1) is 55-65%.

[0062] In another preferred embodiment, in the method for administering coccidia oocyst vaccine through the automatic drinking water line, the number average molecular weight of the polyethylene glycol is 3000-5000.

[0063] In another preferred embodiment, in the method of administering coccidian oocyst vaccine through the automatic drinking water line, the viscosity of the high-concentration xanthan gum solution obtained in step (1) and its viscosity after being diluted 50 to 200 times are in the ratio of 1:20 to 50:1, more preferably 1:3 to 20:1, and further 1:3 to 3:1. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] Figure 1 The viscosity values ​​corresponding to the suspension composition formed by xanthan gum and polyethylene glycol prepared in Example 1 of the present application are prepared with water into liquids (suspensions) containing different xanthan gum concentrations.

[0065] Figure 2 The spherical particle suspending agent composition formed by xanthan gum and polyethylene glycol prepared in Example 1 of the present application is in a state of uniform dispersion prepared with water (suspending agent: water=1:2).

[0066] Figure 3 The invention relates to a suspension agent composition formed by xanthan gum and polyethylene glycol in a state of a liquid prepared with water (suspending agent: water = 1:2 (weight ratio)) which is hydrated and precipitated into a mass. The preparation method of the suspension agent composition formed by xanthan gum and polyethylene glycol is as follows: polyethylene glycol 4000 (solidification point measured to be 54-56° C.) is heated to 80° C. to become a transparent liquid, xanthan gum is added in batches under stirring, and then dispersed for 10 minutes under high-speed stirring at 1000 rpm to obtain a uniformly dispersed liquid, cooled, and then crushed to obtain a large-block suspension agent composition with an irregular shape. For example, these large-block suspension agent compositions are irregular shapes with a size greater than 3 mm and an average size of 5 mm to 10 mm. DETAILED DESCRIPTION

[0067] In view of the existing large-scale livestock and poultry farming, it is usually necessary to prepare a large volume of clinical concentration of drug solution during the drug addition process through the automatic drinking water line, which is time-consuming and laborious. The inventor of the present application unexpectedly found through in-depth research that a composition of alcohol compounds, ketone compounds or polyether substances and xanthan gum is mixed with water to obtain a suspension containing high concentration of xanthan gum with good fluidity (the suspension with good fluidity can be added to the water line through an automatic drug addition device), and the suspension still has ideal suspension after being diluted 20 to 200 times. On this basis, the present invention was completed.

[0068] According to the preparation method of xanthan gum, organic solvents, such as isopropanol, ethanol, and acetone, can promote its precipitation from water (Li Jingwei. Production and Application of Microbial Polysaccharide-Xanthan Gum. Beijing: China Agricultural Science and Technology Press, 1995. p7, p88), and the optimal amount of solvent is about 45-60%. The inventors of the present application further verified that the amount of isopropanol used can inhibit the hydration of xanthan gum. In the presence of isopropanol, ethanol or acetone, even if the suspension contains a high concentration of xanthan gum, the viscosity of the suspension is still very low and the fluidity is still good. However, the flash point of isopropanol, ethanol or acetone is low, and there are safety risks during storage and use. Alcohol substances with high flash points have reduced water solubility and gradually increased freezing points, and cannot be conveniently used in water lines. On this basis, the inventors of the present application found through further research that solid polyethers with larger molecular weights can have similar effects to isopropanol, and can also be used as viscosity inhibitors (thickening inhibitors) for aqueous suspensions containing high concentrations of xanthan gum.

[0069] Therefore, the thickening inhibitor used for the suspending agent composition of the present invention is a water-soluble alcohol compound, a ketone compound, a polyether or a combination thereof. The alcohol compound can be ethanol, propanol, propylene glycol, glycerol, butylene glycol, butanetriol, tert-butyl alcohol or a combination thereof. The ketone compound can be acetone. The polyether can be a polymer formed by one or more of ethylene glycol, propylene glycol, butylene glycol, pentanediol, hexanediol, glycerol, or a combination of the polyethers.

[0070] In actual use, the suspending agent added to the water line by an automatic dosing device (such as a proportional dosing pump or a fermentation dosing machine) includes xanthan gum, a thickening inhibitor and water. Considering flash point, safety, etc., the thickening inhibitor is preferably a polyether, more preferably a polyether formed by ethylene glycol, and more preferably polyethylene glycol; more preferably, polyethylene glycol having a freezing point higher than 40°C and lower than 80°C, and a number average molecular weight lower than 10,000. It is further preferred that the polyethylene glycol has a number average molecular weight of more than 200, and it is further preferred that the number average molecular weight of the polyethylene glycol is 1,000 to 10,000, and it is further preferred that the number average molecular weight of the polyethylene glycol is 1,000 to 8,000, for example, 2,000 to 6,000, 3,000 to 5,000.

[0071] The xanthan gum and thickening inhibitor used in the suspending agent composition of the present invention are preferably present in solid form for easy storage and transportation. It is further preferred that the solid is in the form of particles. The particle shape is selected from spherical and / or spherical particles.

[0072] The suspending agent composition of the present invention may further comprise a thickening inhibition enhancer, wherein the thickening inhibition enhancer is selected from salts, and the salts are preferably selected from sulfates, hydrochlorides and / or potassium salts, sodium salts, ammonium salts or combinations thereof; the ratio of the salts to the xanthan gum is 0.1:1 to 2:1.

[0073] The sulfate is selected from sodium sulfate, potassium sulfate, lithium sulfate and ammonium sulfate.

[0074] The hydrochloride is selected from sodium chloride, potassium chloride, lithium chloride and ammonium chloride.

[0075] The potassium salt is selected from potassium sulfate and potassium chloride.

[0076] The sodium salt is selected from sodium sulfate and sodium chloride.

[0077] The ammonium salt is selected from ammonium sulfate and ammonium chloride.

[0078] The reason why adding an appropriate amount of salts such as potassium chloride and sodium chloride to the system can act as thickening inhibitors is similar to the effect of adding potassium chloride and the like in the process of treating xanthan gum fermentation broth (fermentation to prepare xanthan gum) to precipitate xanthan gum. Adding an appropriate amount of potassium chloride and other salts to the fermentation broth can reduce the amount of isopropanol used. The main reason is that monovalent cations (such as Na + , K +etc.) can combine with anions in polysaccharide molecules, eliminate the charge on the surface of polysaccharide molecules, and promote their precipitation in alcohol solution (Li Jingwei. Production and Application of Microbial Polysaccharide-Xanthan Gum. Beijing: China Agricultural Science and Technology Press, 1995.88), because the addition of salts in the above process can promote hydrolysis and reduce the amount of isopropanol. The inventors of the present application creatively apply the effect of reducing the amount of alcohol by the above salts to the slurry containing high concentration xanthan gum of the present invention. The addition of salts can achieve the effect of viscosity inhibition under the condition of relatively small amount of thickening inhibitor (i.e. more water), and can better adjust the viscosity of the slurry containing high concentration xanthan gum, so that it has a wider operating space. Further, the content of xanthan gum in the obtained xanthan gum composition can also be higher, otherwise a very high water content is required to disperse the entire system. If the xanthan gum content is high and the polyether content is low, the polyether solution that may be formed at a high content of water cannot inhibit the hydration of xanthan gum, and the inclusion of a viscosity inhibition enhancer can still play the effect of preparing a high concentration flowing slurry at a higher water content. In addition, unlike the method of precipitating xanthan gum by adding an alcohol solution of salts to an aqueous medium containing hydrated xanthan gum, in a system containing salts, the presence of the salts themselves inhibits the hydration of xanthan gum, which can maintain the state of the xanthan gum itself to a certain extent, and is conducive to obtaining a subsequent dispersed state; while the precipitation of xanthan gum during production (from the fermentation broth) does not directly obtain a dispersed product, but forms a flocculent mass, which requires subsequent pulverization. This is also the difference between the role of salts as hydration inhibitors in the present invention and the role and effect of similar salts used in the production of xanthan gum.

[0079] The preferred preparation method of the suspending agent composition composed of water-soluble polyether, polyethylene glycol and xanthan gum of the present invention comprises the steps of: heating polyethylene glycol to be completely melted, then adding xanthan gum to the molten polyether, stirring evenly, granulating, and cooling to obtain the suspending agent composition. The diameter of the particles obtained by the granulation method is preferably less than 3 mm, more preferably 0.2 to 2.0 mm, and further preferably 0.5 to 1.0 mm. The granulation can preferably be centrifugal cooling granulation, spray cooling granulation, etc.

[0080] The particle shape, especially spherical and / or quasi-spherical particles, is an important factor in the preparation of a high-concentration liquid of the suspending agent composition of the present invention. When the suspending agent composition of particles (especially spherical and / or quasi-spherical particles) with a particle size of about 0.5 to 1.0 mm is prepared into a high-concentration xanthan gum liquid, water is added while stirring. The polyethylene glycol in the particle-shaped composition dissolves rapidly after contacting with water to form a concentrated solution of polyethylene glycol. On the one hand, the concentrated solution has a certain viscosity (the viscosity produced by the same amount of polyethylene glycol is much smaller than that of xanthan gum, but it is still considerable at high concentrations. Although the molecular weight of the polyethylene glycol selected in this application is limited to within 10,000 and will not produce very high viscosity, the viscosity can meet certain suspension requirements when preparing high-concentration liquid), which further limits the hydration of xanthan gum after contacting with water; on the other hand, it is mainly the concentrated solution of polyethylene glycol itself that limits the hydration of xanthan gum (for example: first preparing a concentrated solution of polyethylene glycol and adding xanthan gum can significantly inhibit the hydration of xanthan gum). However, in the process of preparing the liquid containing high concentration of xanthan gum, at the beginning, the amount of water added is small, and stirring is performed while adding water, so the granular state of the suspending agent composition is still partially retained. When further water is added and stirred, the polyethylene glycol is further dissolved, and a high concentration of polyethylene glycol aqueous solution is further formed, which inhibits the hydration of the xanthan gum. At this time, the suspending agent composition continues to retain part of the granular state, while the external xanthan gum is separated from the surface of the xanthan gum composition particles due to the dissolution of the polyethylene glycol, and is dispersed in the formed polyethylene glycol solution, in a basically unhydrated state. When the weight (mass) of the further added water is approximately the same as the weight (mass) of the suspending agent composition, the polyethylene glycol is completely dissolved, and there is no granular suspending agent composition (see Figure 2), and at this time, the high concentration of polyethylene glycol aqueous solution limits the hydration of xanthan gum, so that the xanthan gum basically maintains the original state of unhydration (this state is similar to the feed liquid obtained by mixing with isopropanol, etc., but the use of polyethylene glycol makes the whole system free of low-flash-point substances, and has good safety). At this time, the viscosity of the feed liquid is partially produced by the solution of polyethylene glycol, and gradually decreases as the amount of water increases, and can be regulated and controlled to maintain suspension at the required viscosity, and the viscosity characteristics produced by this polyethylene glycol are similar to the ethanol and other materials that cannot be obtained. The viscosity on the other hand is related to the amount of xanthan gum. When the amount of water is less, xanthan gum cannot be hydrated, and more xanthan gum will also produce relatively larger viscosity. The feed liquid of viscosity described in the present invention has good fluidity due to low viscosity, and is easily pumped into the water line by the dosing pump, and because the xanthan gum is in a dispersed state, adding the water line can be quickly hydrated so that the water in the water line obtains the expected viscosity, meeting the requirement of drug suspension. If the amount of water is increased to a certain extent, the xanthan gum can be hydrated in a limited amount, and a certain viscosity can also be generated, so that the viscosity of the feed liquid can be adjusted. In actual use, when the (spherical and / or quasi-spherical) granular suspending agent is added with water on site to prepare a feed liquid (suspension) containing high-concentration xanthan gum, the xanthan gum in the feed liquid of high-concentration xanthan gum is basically not hydrated or only a small amount of hydration (xanthan gum) is evenly dispersed in the feed liquid, and the xanthan gum is in a dispersed state in the high-concentration feed liquid. When it is diluted by a high multiple, it is quickly contacted, mixed, and diluted with a large amount of water, and the area of ​​high viscosity formed during the hydration process (because hydration requires a certain time) can be avoided and directly enter the concentration range of clinical use in the water line. The drug that needs to be suspended (the amount calculated by the dilution multiple) can be added to the feed liquid of relatively low viscosity and high-concentration xanthan gum, and pumped into the water line together for dilution. It is also possible to prepare a separate solution containing high concentration of drugs and add it to the water line separately with the above-mentioned high concentration xanthan gum solution. At this time, the prepared solution only needs to meet the suspension requirements of the high concentration of drugs therein. After being added to the water line, the required suspension of the aqueous medium is provided by diluting the added high concentration xanthan gum solution.

[0081] In order to obtain the effect of rapid hydration after high dilution in water, the original particle size of the xanthan gum composition with appropriate particle size is beneficial to the entire hydration process, and generally 80 mesh or higher mesh is preferred, so that the composition particles obtained after granulation are basically dispersed in the prepared high-concentration xanthan gum liquid with the original particle size, and when highly diluted, they can be hydrated faster when in contact with water, and the required viscosity can be obtained faster in the water line, but from the perspective of use, too small xanthan gum composition particles are prone to dust, and generally the particle size of the xanthan gum composition particles is further preferred to be 300 mesh or lower mesh. Relatively large xanthan gum composition particles, such as those below 80 mesh, will be slightly slower in hydration when highly diluted, but when used in the water line, there is usually a distance from the position where the high-concentration xanthan gum liquid is added to the water line to the actual drinking position, and the water flow rate in the water line of this distance is faster, the turbulence degree is relatively large, and it is mostly in a turbulent state, which can generally meet the needs of hydration. If necessary, a static mixer or a dynamic stirring and mixing device is arranged downstream of the water adding position of the high concentration xanthan gum liquid to strengthen the hydration process and ensure the implementation and use of the hydration process.

[0082] If the composition is not a particle of the above-mentioned particle size (especially spherical particles), but a non-spherical bulk shape with a larger particle size, such as adding xanthan gum after melting polyethylene glycol and dispersing it evenly, and then cooling it, breaking it into irregular large blocks, such as large blocks larger than 2 mm, such as large blocks of 3mm-5mm, the above function (preparing a relatively uniform liquid containing a high concentration of suspending agent) cannot be achieved. The specific reasons are analyzed as follows: in the process of adding water to the bulk suspending agent composition, because the contact area between water and the bulk composition is small, even if a small amount of water is added, the water is only in partial contact with the bulk suspending agent composition, and the water cannot be uniformly contacted with the surface of the bulk suspending agent composition, so it is difficult to form a local high-concentration polyethylene glycol solution in the water-containing part, but it is easier to form a low-concentration polyethylene glycol solution. When the low-concentration polyethylene glycol solution is not enough to inhibit the hydrolysis of xanthan gum, it causes the hydration of part of the xanthan gum, and the hydrated xanthan gum further forms large micelles or fish eyes, and the non-hydrated state in which the xanthan gum is dispersed cannot be obtained. The hydrated large micelles finally formed further precipitate in the finally formed polyethylene glycol solution (such as the water amount added above, which can theoretically inhibit the concentration of xanthan gum hydration) and become a lump, and no longer form the aforementioned dispersed state, resulting in that it cannot be added to the water line by the dosing equipment and further hydrated quickly (see Figure 3 )(Similar to the precipitation of xanthan gum in xanthan gum (preparation), it needs to be processed and dried before being crushed, rather than directly obtaining powder).

[0083] The feed liquid (suspension) containing high content of xanthan gum prepared by the suspending agent composition of the present invention has a viscosity that is not much different before and after its dilution, and can be appropriately adjusted as needed, so that the feed liquid (with better fluidity) containing high concentration of xanthan gum can be added to the water line through a dosing pump, and the viscosity of the feed liquid obtained after dilution meets the suspension requirements of (granule) drugs. During the dilution process of the feed liquid containing high concentration of xanthan gum, the hydration speed of the xanthan gum in a dispersed state is fast, and the local concentration will not be too large. On the other hand, the time required for the hydration of xanthan gum makes the addition process dispersed (no fish eyes will be formed), and then quickly hydrated. Finally, the fluidity and suspension performance that can meet the dilution before and after are obtained. The above-mentioned "viscosity that is not much different" means that the suspension can meet the suspension under the corresponding state before and after dilution, and has suitable fluidity at the same time. The specific viscosity ratio before and after dilution, especially when diluted 50-200 times, is 1:20-50:1, more preferably 1:3-20:1, further 1:3-5:1, further 1:3-3:1, further 1:2-2:1. It is difficult and unnecessary to make the viscosity of the liquid before and after dilution completely consistent. A certain range can satisfy the actual use effect.

[0084] One of the main purposes of using dilution and dosing is to reduce the workload, so it is generally hoped that the dilution multiple is as large as possible, but an excessively large dilution multiple means that the amount of the initial liquid material (suspension) is too small, and the amount of liquid material sucked by the dosing pump (e.g., proportional dosing pump) each time during the actual dilution process is too small, and accurate dosing is not utilized; on the contrary, a too low dilution multiple means that the amount of the initial liquid material is large, and the magnitude of the labor reduction is not obvious. Therefore, it is ideal that the dilution multiple of the artificially prepared high-concentration suspension is 10-500 times, more preferably 50-200 times, which is also the adjustable range of the general proportional dosing pump; more preferably 75-125 times. For example, if you need to use 100L of liquid medicine in the end, it is enough to prepare about 1L of high-concentration suspension, which greatly reduces the workload of preparing the suspension and is also conducive to uniform mixing of the liquid.

[0085] In order to meet the suspension requirements of general granular drugs, the viscosity of the liquid required to meet the suspension requirements can be determined experimentally. However, according to the particle size and density of the drugs generally expected to be used in the waterline, the viscosity of the diluted liquid is 10-1000mPa.s to meet the application requirements, for example, 20-500mPa.s, 20-200mPa.s. According to the actual situation of waterline drugs, the above viscosity is usually the data measured by a rotary viscometer at 6rpm.

[0086] For drugs with too large particles and too high density, if 1000mPa.s still cannot meet the suspension requirements, it is generally not suitable to use water line dosing, and other dosing methods need to be considered; for particles with very small particle size and density, the medium viscosity is less than 10mPa.s, which can also meet the suspension requirements. Generally, it is not necessary to use suspending agents to meet the suspension requirements, so there is no need to add suspending agents.

[0087] The solid particle medicine mentioned in the present invention is generally present in the form of solid particles before and after dilution (before dilution, it is a high concentration of medicine prepared before adding to the water line, and after dilution, it is a medicine with a clinical use concentration formed after adding to the water line). For solid particle medicines that need to be suspended (for example, coccidia oocyst vaccine), it can be added to the feed liquid containing high concentration xanthan gum, and then added to the water line through a dosing pump together with xanthan gum to dilute, so that the dosing process operation is simpler and more convenient. The solid particle medicine can also be added to the water line through other approaches. For example, first the feed liquid (suspension) containing high concentration xanthan gum (the feed liquid does not contain solid particle medicine separately) is added to the water line through a dosing pump, so that the water in the water line has a certain suspension, and then the medicine liquid containing solid particle medicine is added to the water line (the medicine liquid is added to the automatic drinking water line at the downstream position of the feed liquid containing high concentration xanthan gum), but this generally requires at least two sets of dosing equipment to complete the addition of the feed liquid containing high concentration xanthan gum and the addition of the medicine liquid respectively. The liquid medium used for the liquid containing solid particle medicine generally also needs to have certain suspension, so that solid particle medicine can be evenly dispersed therein, but this liquid only needs to meet the suspension requirement of high-concentration solid particle medicine, and can be easily realized by common methods. High concentration medicine does not affect each other like this, and the application range of medicine addition is also wider. If high concentration medicine liquid obtains the uniformity during dosing as stirring by other means, it is also possible not to consider the requirement of suspension especially, as keeping the uniformity of high concentration granular medicine by stirring, it is possible not to add suspended matter in addition.

[0088] The coccidia oocyst vaccine commonly used in the breeding industry is a medicine containing solid particle oocysts. The coccidia oocysts themselves are solid particles. Therefore, no matter which method is used to add them, they are all in the form of solid particles before and after adding to the water line. When such solid particle medicine utilizes the suspending agent composition of the present invention to prepare a liquid medicine of clinical use concentration in the water line, as mentioned above, the vaccine of the coccidia oocysts can be mixed with a feed liquid (suspension) containing a high content (concentration) of xanthan gum, and pumped into the water line by a proportional dosing pump to be diluted to a clinical application concentration. Alternatively, the feed liquid containing a high content (concentration) of xanthan gum can be first pumped into the water line by a dosing pump so that the water in the water line has sufficient viscosity and suspension, and then the liquid medicine containing the vaccine of the coccidia oocysts is added to the water line at a downstream position where the feed liquid containing the high concentration of xanthan gum is added to the automatic drinking water line (this can generally be added by another dosing pump). The solution of the vaccine for coccidia oocysts herein is preferably a pre-prepared suspension of the vaccine containing a high concentration of coccidia oocysts, which only needs to meet the suspension requirements of the high concentration oocyst suspension during the dosing period.

[0089] The viscosity of the feed liquid (water suspension) prepared with a general suspending agent (e.g., xanthan gum) will increase with the increase of the concentration of the suspending agent, but if the viscosity is too high, the feed liquid will lose fluidity and cannot be added to the waterline through a conventional dosing device (e.g., a proportional dosing pump). Therefore, in order to allow the suspension to be pumped into the waterline through a proportional dosing pump, and to allow the water in the waterline to have a predetermined suspendability after being diluted in the waterline, the prepared feed liquid containing the suspending agent needs to have a relatively low viscosity (corresponding to better fluidity) and contain a high concentration of the suspending agent. This requires that the viscosity of the suspension containing a high concentration of the suspending agent is not much different from the viscosity of the low concentration suspension formed after it is diluted in the waterline (generally, the fluidity of the low-solubility feed liquid after dilution is easily satisfied). The suspending agent composition of the present invention can achieve a viscosity difference between a feed liquid (suspension) containing high-concentration xanthan gum and a low-concentration feed liquid (suspension) formed after being diluted in a water line, and can be pumped into the water line by a dosing pump, and can be diluted so that the water in the water line has a predetermined suspension property. The principle that the suspending agent composition of the present invention can achieve this effect is that the composition contains a thickening inhibitor, and the thickening inhibitor can significantly inhibit the hydration of xanthan gum in the suspension containing high-concentration xanthan gum, thereby obtaining low viscosity, and the low-concentration thickening inhibitor cannot inhibit the hydration of xanthan gum in the feed liquid containing low-concentration xanthan gum formed in the water line after the suspension containing high-concentration xanthan gum is rapidly diluted by a high multiple, thereby making the xanthan gum and water fully hydrated, and obtaining a suspension with ideal suspension property.

[0090] In the suspending agent composition of the present invention, it is generally beneficial to add a thickening inhibition enhancer, the thickening inhibition enhancer is selected from salts, the salts are preferably selected from sulfates, hydrochlorides and / or potassium salts, sodium salts, ammonium salts or combinations thereof; the ratio of the salts to the xanthan gum is 0.1:1 to 2:1. The thickening inhibition enhancer is used to obtain a thickening inhibition effect under conditions of a lower thickening inhibitor concentration, so that a higher concentration of suspending agent (relatively less thickening viscosity inhibitor) can be contained in the granular suspending agent composition, so that when water is added, a lower thickening inhibitor concentration can achieve a thickening inhibition effect.

[0091] In a specific embodiment of the present invention, the viscosity of the suspension prepared by the xanthan gum suspending agent composition is as follows: Figure 1 As shown, the first low viscosity point is the viscosity of the liquid (suspension) containing high concentration of xanthan gum before dilution (that is, the suspension before being pumped into the water line by the dosing pump), and the second low viscosity point is the viscosity of the liquid (suspension) obtained after the suspension is added into the water line by the dosing pump and quickly diluted. It can be seen that the xanthan gum suspending agent composition realizes two liquids of different concentrations, which have similar viscosities and span the middle high viscosity area. Figure 1 The interrupted area of ​​the curve is where the viscosity exceeds the range that can be measured by the laboratory rotational viscometer. The above data is the viscosity tested at 6rpm.

[0092] from Figure 1 It can also be seen that the suspension prepared by the xanthan gum suspending agent composition of the present invention cannot be diluted step by step, because this will cause the water content to be in a state where the xanthan gum is basically not affected by the thickening inhibitor and is in a completely hydrated state. At this time, the viscosity of the suspension will be very high, thereby causing the inoperability of the hydration process.

[0093] Therefore, the use of high-dilutable dosing equipment can just meet the operating requirements of the suspending agent, which also greatly expands the application scope of high-dilutable dosing equipment.

[0094] From the perspective of practical operation, the liquid material without low flash point substances can also be obtained by first dissolving polyethylene glycol in water completely and then adding xanthan gum. However, in the process of preparing the suspension, polyethylene glycol needs to be dissolved first, and polyethylene glycol cannot be added to water together with xanthan gum, otherwise part of the xanthan gum will quickly combine with water to form fish eyes, and the xanthan gum cannot be evenly dispersed in the water medium, similar to Figure 3 The display utilizes the state in which a large block composition with irregular shapes is added with water, hydrated and precipitated.

[0095] The powdery mixture formed by simple mixing of polyethers such as polyethylene glycol 4000 and xanthan gum cannot achieve the purpose of the present application. When the mixture is added to the water, because xanthan gum does not have the protection of polyethylene glycol when in contact with water, there is no pre-formed polyether solution that suppresses the hydration of xanthan gum, and xanthan gum contacts hydration with water quickly, and wraps up xanthan gum powder to form fish eyes, and then after polyethers such as polyethylene glycol 4000 further dissolve to form a solution of sufficient concentration, it is further separated into a large mass, and further feeding operation can not be achieved, and its state is similar to the effect of the aforementioned bulk composition preparation feed liquid. It can be seen that the composition of the present invention, preparation method, spherical and / or spherical particle shape, hydration method are all important conditions for realizing the present application. Therefore, in order to realize that xanthan gum is uniformly dispersed in an aqueous medium, the present invention mixes polyethylene glycol with xanthan gum in a molten state, and then by granulation, obtains particles (spherical or spherical) with a diameter of less than 2mm. The granulation process can generally be spray granulation or centrifugal granulation, and preferably spherical or quasi-spherical particles are obtained by droplet cooling. When the particle-shaped suspending agent composition of the present invention is used to prepare a high-concentration xanthan gum liquid, water is added to the suspending agent composition while stirring. This reduces the chance of forming a low-concentration polyether solution and reduces the hydration and secondary precipitation of xanthan gum.

[0096] In the suspending agent composition of the present invention, the xanthan gum content is preferably 2-50%. A relatively higher xanthan gum content can obtain a higher dilution multiple during dilution; a relatively higher polyethylene glycol content can obtain a higher amount of water added when preparing a suspension containing a high concentration of xanthan gum; and the thickening inhibition enhancer can further adjust the operable range, so that a relatively lower thickening inhibitor concentration can obtain a hydration inhibition effect.

[0097] When the particle-shaped suspending agent composition of the present invention is used to prepare a high-concentration xanthan gum liquid, the amount of water used is 0.5 to 5 times, preferably 0.6 to 3 times, the weight of the suspending agent composition. The weight content of xanthan gum in the high-concentration xanthan gum liquid is 7.6-12%, and the weight content of water is 40-75%, preferably 50-70%.

[0098] In the description of the present invention, "multiple" means two or more than two. The numbers of the content, composition, etc. are allowed to contain errors.

[0099] In the description of the present invention, "water line" may also be referred to as "drinking water line", which are interchangeable.

[0100] In the description of the present invention, "liquid material" and "feed liquid" both refer to liquid materials and can be interchangeable.

[0101] In the description of the present invention, when "optionally" is used to describe a composition, it means that the composition may or may not contain a certain component.

[0102] The suspension (liquid) and liquid medicine mentioned in the present invention generally use water as the medium.

[0103] In the description of the present invention, the liquid or liquid material prepared using the suspending agent composition may also be referred to as a suspension.

[0104] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods for which specific conditions are not specified in the following examples are usually based on normal conditions. Unless otherwise stated, percentages and parts are weight percentages / mass concentrations. The molecular weights of the polymers mentioned below are number average molecular weights.

[0105] The chicken coccidiosis oocyst vaccine used in the following examples was produced by Foshan Zhengdian Biotechnology Co., Ltd., and the model is a quadrivalent live vaccine for chicken coccidiosis.

[0106] Example 1

[0107] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 1.

[0108] Table 1

[0109] Components Xanthan gum Polyethylene glycol 4000 Weight content 25.0％ 75.0％

[0110] The preparation process of the suspending agent particles is as follows: first, polyethylene glycol 4000 (the solidification point is measured to be 54-56°C) is heated to 80°C to become a transparent liquid, and xanthan gum is added in batches for premixing under stirring, and then dispersed for 10 minutes under high-speed stirring at 1000 rpm to obtain a uniformly dispersed liquid, and then centrifugal dispersion and cooling granulation are performed to obtain suspending agent particles composed of xanthan gum and polyethylene glycol, which are spherical as a whole, and the spherical particles or quasi-spherical particles of the suspending agent composition with a particle size of 0.3-1 mm are obtained.

[0111] Example 2

[0112] The viscosity of the spherical or quasi-spherical particles of the suspending agent composition prepared in Example 1 under different water addition conditions was measured.

[0113] Take 40g of the above suspending agent particles, add water while stirring, and test its viscosity under certain water addition conditions. The results are shown in Table 2.

[0114] Table 2

[0115]

[0116]

[0117] The curve diagram of water addition and viscosity of feed liquid was obtained by using the above data. Figure 1 From the data in Table 2 and Figure 1 It can be seen that in the process of mixing the suspending agent composition particles composed of xanthan gum and polyethylene glycol with water, the viscosity of the obtained liquid material first decreases, then rises rapidly, and then decreases again, wherein the first low point of viscosity and the second low point of viscosity are the two operating points used in the present invention. By preparing suspensions of concentrations corresponding to these two low viscosity points, the viscosity of the feed liquid containing high concentration xanthan gum can be close to the viscosity of the feed liquid containing low concentration xanthan gum, which is the basis for the suspending agent composition of the present invention to realize automatic dosing using a dosing device (e.g., a proportional dosing pump).

[0118] Example 3

[0119] With reference to the ratio of implementation 2, 40g suspending agent composition particles prepared in Example 1 were taken, water was added to 80mL, and a feed solution containing a xanthan gum mass concentration of 8.3% was obtained, and the test viscosity was 125mPa.s (6rpm). The data shown in Table 2 are different, probably because of the weighing error. The feed solution has good fluidity. The ratio dosing pump was pumped into the water line (setting 100 times of dilution multiple), and the viscosity was measured at 50 meters downstream of the feed solution, which was 90mPa.s, close to the viscosity data measured in Example 2.

[0120] Example 4

[0121] According to the previous experimental research of the inventor of the present application, a suspension (feed liquid) prepared with water and having a viscosity of 80 mPa.s can meet the suspension requirements of the chicken coccidia oocyst vaccine (the chicken coccidia oocyst vaccine is added to the suspension with this viscosity, stirred evenly, and basically does not settle for 12 hours).

[0122] With reference to the ratio of implementation 2, take the suspending agent composition particles of 40g xanthan gum and polyethylene glycol, gradually add water 70mL and be mixed with feed liquid, then add 2 bottles of * 5mL / bottles of chicken coccidiosis oocyst vaccine, 1000 feathers per bottle (preservative solution is mainly water, ZL2006100348674), obtain the suspension containing chicken coccidiosis oocyst vaccine, wherein the content of xanthan gum is 8.3%, and it is 128mPa.s (6rpm) to test its viscosity. Slightly different from the viscosity shown in the above table 2, it may be because of the slight influence of weighing error and coccidiosis oocyst vaccine. The suspension containing high-concentration chicken coccidiosis oocyst vaccine has good fluidity. By proportional pump dosing equipment, set 100 times of dilution multiple setting, take water sample at 50 meters downstream of dosing pump for measurement, viscosity is 83mPa.s, close to the viscosity data of embodiment 2 within the error tolerance range. And the quantity of chicken coccidiosis oocyst vaccine measured is also in line with expectation.

[0123] Example 5

[0124] Referring to the ratio of implementation 2, 40g of the suspending agent composition particles were taken, and water was added to 80mL to obtain a feed liquid containing high concentration xanthan gum, wherein the content of xanthan gum was 8.3%, and a 50-fold dilution ratio was set, and it was added to the water line through a first proportion dosing pump; in addition, albendazole suspension was prepared according to 25 times of the liquid (25% weight content, commercially available veterinary drug, water as solvent, thickener and surfactant were added, and its viscosity was 4000mPa.s at 6rpm, which could meet the suspension requirements, but after 25 times dilution, the viscosity was about 40mPa.s, which could not meet the suspension requirements), a 50-fold dilution ratio was set, and under stirring, the second proportion dosing pump was used to add the feed liquid containing high concentration xanthan gum to the automatic drinking water line at the downstream position where the automatic drinking water line was added. The viscosity of the liquid in the automatic drinking water line was measured at 50 and 200 meters downstream of the second proportional dosing pump. The results were 616mPa.s and 620mPa.s respectively. The viscosities at both locations were within the allowable error range. The sedimentation of the liquid at these two locations was observed respectively, and no obvious sedimentation was observed within three hours.

[0125] Example 6

[0126] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 3 (40 g was taken for hydration process).

[0127] Table 3

[0128] Components Xanthan gum Polyethylene glycol 4000 Weight content 12.5％ 87.5％

[0129] The suspension agent composition particles were prepared by referring to the preparation method of Example 1, and the particles were sieved to obtain suspension agent composition particles with a particle size of 0.3 to 1 mm. Then, the suspension agent composition particles were prepared into liquid containing different concentrations of xanthan gum according to Example 2, and the viscosity test was performed, and the data shown in Table 4 and similar data were obtained. Figure 1 The viscosity-water addition amount curve can achieve the dosing purpose of the present invention.

[0130] Table 4

[0131]

[0132] Example 7

[0133] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 5.

[0134] Table 5

[0135]

[0136] The suspension composition particles were prepared according to the preparation method of Example 1, and the particles were sieved to obtain particles with a particle size of 0.4 to 1.4 mm. Then, the suspension composition particles were prepared into liquids containing different concentrations of xanthan gum according to Example 2, and the viscosity was tested to obtain similar Figure 1 The viscosity-water addition amount curve can achieve the dosing purpose of the present invention.

[0137] Example 8

[0138] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 6.

[0139] Table 6

[0140]

[0141]

[0142] Referring to Example 2, 40 g of the suspending agent composition particles were prepared into liquids containing different concentrations of xanthan gum, and the viscosity test was performed to obtain similar Figure 1 The viscosity-water addition amount curve can achieve the dosing purpose of the present invention.

[0143] Table 7

[0144]

[0145] Example 9

[0146] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 8.

[0147] Table 8

[0148] Components Xanthan gum Polyethylene glycol 3000 Yuan Ming powder Weight content 35.29％ 58.82％ 5.89％

[0149] The preparation process of the suspending agent particles is as follows: first, polyethylene glycol 3000 (the solidification point is measured to be 51-53° C.) is heated to 75° C. to become a transparent liquid, and xanthan gum and sodium sulfate (anhydrous sodium sulfate) are added in batches for premixing under stirring, and then dispersed for 10 minutes under high-speed stirring at 1000 rpm to obtain a uniformly dispersed liquid, and then centrifuged and cooled to granulate to obtain suspending agent particles composed of xanthan gum, polyethylene glycol and sodium sulfate, which are spherical as a whole, and are sieved to obtain spherical particles of the suspending agent composition with a particle size of 0.3-1 mm.

[0150] Then, referring to Example 2, 42.5 g of the suspending agent composition particles were prepared into liquids containing different concentrations of xanthan gum, and viscosity tests were performed to obtain the data shown in Table 9 and similar results. Figure 1 The viscosity-water addition amount curve can achieve the dosing purpose of the present invention.

[0151] Table 9

[0152]

[0153] Example 10

[0154] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 10.

[0155] Table 10

[0156] Components Xanthan gum Polyethylene glycol 3000 Sodium sulfate Weight content 23.53％ 70.59％ 5.88％

[0157] The spherical particles of the suspending agent composition with a diameter of 0.3 to 1 mm were obtained by referring to the preparation method of Example 9.

[0158] Take 42.5g of the above suspending agent particles, add water while stirring, and test its viscosity under certain water addition conditions. The results are shown in Table 11.

[0159] Table 11

[0160]

[0161]

[0162] Compared with the results in Table 2, the first low viscosity point shifts toward the water direction and the low viscosity direction, which means that a relatively low viscosity inhibitor can achieve the effect when no viscosity inhibitor is added, and a lower viscosity operating point can be obtained, so that when the xanthan gum concentration in the xanthan gum composition is higher, a lower viscosity and better operability can be obtained. If no sodium sulfate is added, the viscosity of the feed liquid near the lowest viscosity operating point is relatively large, especially for compositions containing high content of xanthan gum, the operability is reduced.

[0163] Embodiment 11

[0164] A xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 12.

[0165] Table 12

[0166] Components Xanthan gum Polyethylene glycol 3000 Yuan Ming powder Weight content 47.06％ 47.06％ 5.88％

[0167] The spherical particles of the suspending agent composition with a diameter of 0.3 to 0.9 mm were obtained by referring to the preparation method of Example 9.

[0168] Take 42.5g of the above suspending agent particles, add water while stirring, and test its viscosity under certain water addition conditions. The results are shown in Table 13.

[0169] Table 13

[0170]

[0171]

[0172] In this embodiment, sodium sulphate is used. When 80 g of water is added (low viscosity point), the viscosity of the liquid is 1600 mPa.s, while the low viscosity point of the liquid without sodium sulphate (when 70 g of water is added) is about 4000 mPa.s (see Table 15 of Example 12 below), which is not conducive to operation. According to the addition of water to 23960 g and the addition of water to 80 g, the dilution multiple can reach about 200 times.

[0173] Example 12

[0174] A xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 14.

[0175] Table 14

[0176] Components Xanthan gum Polyethylene glycol 3000 Yuan Ming powder Weight content 50％ 50％ 0％

[0177] The spherical particles of the suspending agent composition with a diameter of 0.3 to 0.9 mm were obtained by referring to the preparation method of Example 9.

[0178] Take 40g of the above suspending agent particles, add water while stirring, and test its viscosity under certain water addition conditions. The results are shown in Table 15.

[0179] Table 15

[0180]

[0181] The first low point viscosity of this embodiment without using sodium sulfate is 4000 mp.s, which is about three times that of embodiment 11. The operability is worse than that of embodiment 11, and the dispersion and hydration speeds in water are also slower. Obviously, adding sodium sulfate can improve the operability of high xanthan gum content, maintain a lower viscosity at a relatively lower PEG content, and play the role of viscosity inhibition promoter, so that the whole operation has better operability and increases the dilutable ratio.

[0182] Embodiment 13

[0183] A xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 16.

[0184] Table 16

[0185] Components Xanthan gum Polyethylene glycol 3000 water Weight content 8.33％ 25.00％ 66.67％

[0186] The polyethylene glycol 3000 was melted, xanthan gum was added and stirred evenly, and then water was added and stirred to obtain a flowing liquid. It was directly diluted 100 times, and the viscosity after dilution was about 87 mPa.s, which was close to the result in Table 2. It was used for waterline dosing of chicken coccidiosis vaccine, and the effect similar to that of Example 4 was obtained.

[0187] Embodiment 14

[0188] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 17.

[0189] Table 17

[0190] Components Xanthan gum Polyethylene glycol 6000 water Weight content 8.33％ 25.00％ 66.67％

[0191] Add polyethylene glycol 6000 to water to dissolve, add xanthan gum after fully dissolving and stir evenly to obtain a feed liquid containing high concentration xanthan gum and low viscosity. The feed liquid is directly diluted 100 times, and the viscosity after dilution is close to the viscosity before dilution (90mPa.s / 140mPa.s). It is used for chicken coccidiosis vaccine waterline dosing, and an effect similar to Example 4 can be obtained.

[0192] Embodiment 15

[0193] A xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 18.

[0194] Table 18

[0195] Components Xanthan gum Polyethylene glycol 4000 Potassium chloride Weight content 10％ 80％ 10％

[0196] The polyethylene glycol 4000 was melted, xanthan gum and potassium chloride were added and stirred evenly, and microcapsules were prepared by spray cooling method, and the microcapsules were sieved to obtain suspension composition particles with a particle size of 0.3 to 1 mm. Then, referring to Example 2, different amounts of water were added to the suspension composition particles to prepare liquids containing different concentrations of xanthan gum, and viscosity tests with different amounts of water were performed to obtain similar Figure 1 The viscosity-water addition amount curve can achieve the dosing purpose of the present invention. However, the viscosity can be inhibited at a lower polyethylene glycol content.

[0197] Example 16

[0198] A xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 19.

[0199] Table 19

[0200] Components Xanthan gum Polyethylene glycol 6000 Potassium sulfate Weight content 35％ 50％ 15％

[0201] The polyethylene glycol 6000 was melted, xanthan gum and potassium sodium sulfate were added and stirred evenly, and microcapsules were prepared by spray cooling method, and the microcapsules were sieved to obtain suspension composition particles with a particle size of 0.3 to 1 mm. Then, referring to Example 2, different amounts of water were added to the suspension composition particles to prepare liquids containing different concentrations of xanthan gum, and viscosity tests with different amounts of water were performed to obtain similar Figure 1The viscosity-water addition amount curve can achieve the dosing purpose of the present invention. However, the viscosity suppression effect can be obtained under the condition of lower polyethylene glycol viscosity.

[0202] Embodiment 17

[0203] The xanthan gum suspending agent composition was prepared. The composition of the suspending agent composition is shown in Table 20.

[0204] Table 20

[0205] Components Xanthan gum Isopropyl alcohol water Weight content 10％ 30％ 60％

[0206] Add xanthan gum to isopropanol and stir evenly. Then add water while stirring until the system contains 60% water. The system viscosity is still low and has good fluidity. It can be used for high dilution and added to the automatic drinking water line.

[0207] Different xanthan gums may have different viscosities, but the present invention can obtain a first low point with low viscosity at a high concentration, and the viscosity after dilution can be obtained by dilution.

[0208] The above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. The above embodiment of the present invention can also be modified in various ways. That is, all simple, equivalent changes and modifications made according to the claims and the contents of the specification of the present invention fall within the scope of protection of the claims of the present invention. The contents not described in detail in the present invention are all conventional technical contents.

Claims

1. A suspending agent composition for dosing in an automatic drinking water line, characterized in that: The suspending agent composition comprises xanthan gum and a thickening inhibitor, and optionally, a thickening inhibition enhancer, The thickening inhibitor is selected from alcohol compounds, ketone compounds, polyethers, or a combination thereof. The thickening inhibition enhancer is selected from salts, and the salts are selected from sulfates, hydrochlorides and / or potassium salts, sodium salts, ammonium salts or combinations thereof.

2. The suspending agent composition according to claim 1, characterized in that The alcohol compound is selected from ethanol, propanol, ethylene glycol, propylene glycol, glycerol, butylene glycol, butanediol, tert-butyl alcohol or a combination thereof, and / or The ketone compound is selected from acetone, and / or The polyether is selected from a polymer formed by one or more of ethylene glycol, propylene glycol, butylene glycol, pentanediol, hexanediol, glycerol, or a combination of the polymers, and / or The salt is selected from sodium sulfate, potassium sulfate, lithium sulfate, ammonium sulfate, sodium chloride, potassium chloride, lithium chloride, ammonium chloride or a combination thereof, and / or The weight ratio of the xanthan gum to the thickening inhibitor is 1:1.5-19, more preferably 1:2-10, most preferably 1:2.5-4.0, and / or The weight ratio of the salt to the xanthan gum is 0.1:1 to 2:

1.

3. The suspending agent composition according to claim 2, characterized in that The thickening inhibitor is selected from polyethers, and the polyethers are selected from polyethylene glycol and / or polyethylene glycol polypropylene glycol block copolymers, More preferably, the number average molecular weight of the polyethylene glycol and / or polyethylene glycol-polypropylene glycol block copolymer is 1000-8000, more preferably 2000-6000, most preferably 3000-5000.

4. The suspending agent composition according to claim 3, characterized in that The suspending agent composition is in the form of particles, and more preferably, the particles are spherical and / or spherical-like in shape.

5. The suspending agent composition according to claim 4, characterized in that The preparation method of the suspending agent composition comprises the following steps: The polyether is heated until it is completely melted, and then xanthan gum and an optional thickening inhibitor enhancer are added to the molten polyether, stirred evenly, and granulated to obtain the suspending agent composition.

6. An aqueous suspending agent composition for dosing in an automatic drinking water line, characterized in that: The suspending agent composition comprises xanthan gum, a thickening inhibitor and water, and optionally a thickening inhibitor enhancer, The thickening inhibitor is selected from alcohol compounds, ketone compounds, polyethers, or a combination thereof. The thickening inhibition enhancer is selected from salts, and the salts are selected from sulfates, hydrochlorides and / or potassium salts, sodium salts, ammonium salts or combinations thereof, The mass concentration of xanthan gum is 5-9%.

7. A method for adding medicine to an automatic drinking water line, characterized in that: The method comprises the following steps: (1) mixing the suspending agent composition according to any one of claims 1 to 5 with water to prepare a liquid containing high concentration xanthan gum, wherein the mass concentration of the xanthan gum is 5 to 9%; or Providing the aqueous suspending agent composition of claim 6; (2) preparing the drug into a uniformly dispersed liquid; (3) adding the high-concentration xanthan gum liquid prepared in step (1) to the automatic drinking water line through a first dosing pump, so that the viscosity of the water medium in the water line is 10 to 500 mPa.s at 6 rpm, and adding the drug-containing liquid prepared in step (2) to the automatic drinking water line at a downstream position where the high-concentration xanthan gum liquid is added to the automatic drinking water line through a second dosing pump, so that the drug is uniformly dispersed in the water medium in the automatic drinking water line. The liquid containing high concentration of xanthan gum and the liquid containing medicine are diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times.

8. A method for adding medicine to an automatic drinking water line, characterized in that: The method comprises the following steps: (1) mixing the suspending agent composition according to any one of claims 1 to 5 with water to prepare a liquid containing high concentration of xanthan gum, wherein the weight content of xanthan gum is 5 to 9%, or providing the aqueous suspending agent composition according to claim 6; (2) adding the drug to the high-concentration xanthan gum-containing solution or the aqueous suspending agent composition of step (1); (3) adding the drug-containing liquid prepared in step (2) to the automatic drinking water line through a drug dosing pump, so that the viscosity of the water medium in the water line is 10 to 500 mPa.s at 6 rpm, and the drug is evenly dispersed therein, The drug-containing liquid is diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times.

9. The method for adding medicine to an automatic drinking water line according to claim 7 or 8, characterized in that: The ratio of the viscosity of the suspension agent composition according to any one of claims 1 to 5 mixed with water to prepare a liquid containing high concentration of xanthan gum or the aqueous suspension agent composition according to claim 6 to the viscosity after being diluted 50 to 200 times is 1:20 to 50:1, preferably 1:3 to 20:1, and / or The drug is selected from drugs whose liquid materials prepared at clinical use concentrations contain insoluble particles, wherein the insoluble particles are smaller than 100 μm and larger than 1 μm, Preferably, the drug is selected from coccidia oocyst vaccine, chemical drug suspension or feed additive.

10. A method for administering a coccidia oocyst vaccine in an automatic drinking water line, characterized in that: The method comprises the following steps: (1) mixing a particle suspending agent composition comprising xanthan gum, a polyether and optionally a viscosity suppressing enhancer with water to prepare a liquid containing a high concentration of xanthan gum, wherein the weight content of the xanthan gum is 5 to 9%; (2) preparing the coccidia oocyst vaccine into a uniformly dispersed liquid; (3) adding the high-concentration xanthan gum liquid prepared in step (1) to the drinking water line through a first dosing pump, so that the viscosity of the water medium in the water line is 10-500 mPa.s at 6 rpm, and adding the coccidia oocyst vaccine liquid prepared in step (2) to the automatic drinking water line at a position downstream of the high-concentration xanthan gum liquid being added to the automatic drinking water line through a second dosing pump, so that the drug is uniformly dispersed in the water medium in the automatic drinking water line, The liquid containing high concentration of xanthan gum and the liquid containing coccidia oocyst vaccine are diluted in the automatic drinking water line at a ratio of 20 to 200 times, preferably 50 to 100 times. The polyether is selected from polyethylene glycol and / or polyethylene glycol polypropylene glycol block copolymer, and The viscosity inhibition enhancer is selected from potassium chloride, sodium chloride, sodium sulfate, and potassium sulfate.

11. A method for administering a coccidia oocyst vaccine in an automatic drinking water line, characterized in that: The method comprises the following steps: (1) mixing a particle suspension composition comprising xanthan gum, a polyether and optionally a viscosity suppressant enhancer with water to prepare a liquid containing high concentration xanthan gum, wherein the weight content of the xanthan gum is 5-9%, and adding a coccidia oocyst vaccine to the liquid; (2) adding the coccidia oocyst vaccine solution prepared in step (1) to the drinking water line through a dosing pump, so that the viscosity of the water medium in the drinking water line is 10 to 500 mPa.s at 6 rpm, and the drug is evenly dispersed therein, The liquid is diluted in the automatic drinking water line by 20 to 200 times, preferably 50 to 100 times. The polyether is selected from polyethylene glycol and / or polyethylene glycol polypropylene glycol block copolymer, and The viscosity inhibition enhancer is selected from potassium chloride, sodium chloride, sodium sulfate, and potassium sulfate.

12. The method for administering coccidia oocyst vaccine to an automatic drinking water line according to claim 10 or 11, characterized in that: The weight ratio of xanthan gum to polyether in the suspending agent composition is 1:4-5, and the number average molecular weight of the polyether is 3000-5000, and / or In the high-concentration xanthan gum solution obtained in step (1), the content of polyether is 15-30%, the weight content of water is 50-70%, the viscosity of the aqueous medium obtained after the solution is diluted in the water line is 20-200 mPa.s, and / or The viscosity ratio of the high-concentration xanthan gum solution obtained in step (1) to the viscosity after being diluted 50 to 200 times is 1:20 to 50:1, preferably 1:3 to 20:1.

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