CN101861973A - Method for uniformly dispersing and effectively dissolving low-dose and indissoluble active ingredients in preparation out - Google Patents
Method for uniformly dispersing and effectively dissolving low-dose and indissoluble active ingredients in preparation out Download PDFInfo
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Abstract
The invention relates to a method uniformly dispersing and effectively dissolving low-dose and indissoluble active ingredients in a preparation out. The method protects the low-dose and indissoluble active ingredients in the preparation to the utmost by a simple approach of the preparation and/or a pre-treating approach, under the condition of basically not increasing the cost, on the premise of enabling the low-dose and indissoluble active ingredients to be uniformly dispersed, and skillfully by a physical isolation method and/or a physical-chemical isolation method. The physical isolation methods or the physical-chemical isolation methods which are finished by using a menstruum or excipients comprises the following methods such as a menstruum pelletizing isolation method for ensuring that sensitive components do not generate viscosity, a separate pelletizing isolation method, and a broken grain wrapping method, a menstruum-transferring crystallization wrapping method, a spray drying wrapping method, a spray drying crystallization wrapping method and the like for wrapping the active ingredients, which are used for solving the problem of uniformly dispersing the low-dose and indissoluble active ingredients, and solving the problem of low content of the active ingredients after the low-dose and indissoluble active ingredients are uniformly dispersed. A measured result of the content can reach over 90 percent of a labeled amount.
Description
Technical field
The present invention relates to a kind of food, medicine, feed formulations and preparation method thereof,
Background technology
As everyone knows, even dispersion low dose of in food, medicine, the feed formulations, the slightly solubility composition is an existing preparation difficult problem, particularly low dose of, slightly solubility western medicine composition needs and when plant extracts and/or animal extracts mix preparation, result low dose of, slightly solubility western medicine composition assay is often on the low side.For reach preparation quality standard require preparation producer often the upper limit feed intake, even transfinite and feed intake.
The result of low dose, the slightly solubility western medicine composition assay of this moment is on the low side, often because the low dose, slightly solubility composition and the composition that add extremely chemical reaction or physical crosslinking have taken place in the plant extracts of complexity and/or a certain or multiple composition in the animal extracts, huge legendary turtle is closed, is catching, wraps up.Though it is not detected when assay, enter gastrointestinal reaction thing, cross-linking agent, huge legendary turtle compound, catching thing, after wrappage digested, the content that is hidden by preparation tends to discharging in full, brings into play its due effect.Why dosage is little for low dose of active ingredient, is because its effective dose and dosis toxica are more approaching.Therefore, the upper limit feeds intake, even transfinites and feed intake, and can stay very large potential danger to preparation.
Water extraction and alcohol precipitation method is awkward in the traditional Chinese medicine extraction separation process: water extraction and alcohol precipitation method is a kind of process for purification that is most widely used at present, its principle is that middle pharmaceutically active ingredient was not only water-soluble but also be dissolved in alcohol, and often contain mucilaginous substance, polysaccharide, gelatinized starch, pectin, natural gum, protein, resin, pigment etc. in the aqueous extract, can precipitate effectively with the ethanol of debita spissitudo and remove.Reach 60% and can remove desizing as containing alcohol amount in the soup, contain alcohol and measure and reach at 75% o'clock, except that minority invalid components such as tannin, water colo(u)r, most of impurity is all precipitable to be removed, and greatly reduces the rate of extract.Because this method is simple to operate, technology and equipment are less demanding, so use till today from early seventies always, become the process for purification of " legal " at present.But, alcohol deposition method is in refining, whether kept active ingredient, what remove all is invalid components, more and more report this is held the suspicious attitude, think that this method has many irrationalities: (1) particularly loss of effective components is serious along with the raising Chinese medicine total solid of concentration of alcohol, is difficult to guarantee the validity of this preparation.(2) because of alcohol deposition method needs a large amount of alcohol, waste makes cost up more than 30% during recovered alcohol, and the production cycle is long.
In addition, the nanometer technology that slightly solubility and/or insoluble active ingredient is ground into nanometer or inferior nanometer powder is widely used in preparation, but owing in the process that raw material is ground into nanoparticle, need wasteful energy, so the consumption of nanometer powder in preparation also belongs to dosage on the low side, also exist above-mentioned low dose, hardly soluble active ingredient to be difficult for a homodisperse difficult problem.Add reunion characteristic and porosity characteristic that nanometer powder is connected with, in the preparation process, if be mixed together, because the reunion characteristic of nanometer powder is not accomplished nano-dispersed at all, to such an extent as to curative effect and ordinary preparation do not have too big-difference with other powder; If nano material is placed after required water of preparation process or the ultrasonic depolymerization of ethanol as adhesive and other composition mix preparations, can reach aim of even dispersion, but if in the preparation when containing plant extracts and/or animal extracts, because plant extracts that composition is extremely complicated and/or a certain or multiple composition physics to porous nanometer material in the heating process of drying in the animal extracts are being caught, parcel, crosslinked, nano material is reunited once again, and lose nano material even freedom of suspendible in liquid, to such an extent as to curative effect and ordinary preparation do not have too big-difference, if wrappage can not be by the curative effect of digestion nanometer formulation even as ordinary preparation in intestines and stomach.
Summary of the invention:
In order to address the above problem, researcher of the present invention proposes the method low dose of in a kind of preparation, that hardly soluble active ingredient evenly disperses efficient stripping.
First contribution of the present invention is that researcher of the present invention surprisingly finds, content or dissolution rate are on the low side behind low dose, the hardly soluble active ingredient preparation, it is inhomogeneous not to be that active ingredient is mixed, but described active ingredient and composition are due to extremely the plant extracts of complexity and/or a certain or multiple sensitive composition generation chemical reaction in the animal extracts or physical crosslinking, huge legendary turtle are closed, are catching, wrap up.
Described sensitive composition is meant, in plant extracts and/or the animal extracts can with the alkaloids of low dose of, hardly soluble active ingredient physical and chemical reaction, organic acid, polysaccharide, protein-based, mucilaginous substance class, tannin class, resinae, pigment etc.
Impurity such as polysaccharide, protein-based, mucilaginous substance class, tannin class, resinae, pigment particularly.
Second contribution of the present invention is, after putting above-mentioned viewpoint in order, the breach of dealing with problems no longer is the mixing inequality that the standard preparation operation may cause, but how to avoid low dose, hardly soluble active ingredient to be subjected to injury above-mentioned sensitive composition chemistry, physics.
The method that makes active ingredient in the preparation evenly disperse efficient stripping of the present invention is meant that physics that low dose of in the preparation, hardly soluble active ingredient or nanometer powder are finished by solvent or auxiliary material or physical chemistry isolates the method for avoiding in the process of granulation heat drying closing, catching, wrapping up with sensitive composition generation chemical reaction or physical crosslinking, huge legendary turtle the efficient stripping of even dispersion that is protected.
Described physics or physical chemistry partition method be meant for fear of low dose of, hardly soluble active ingredient and above-mentioned sensitive ingredients in granulation process behind the wetting material of usefulness adhesive solvent (water and/or ethanol), and chemical reaction or physical crosslinking take place in the process of particle drying (be heated promote reaction), huge legendary turtle is closed, is catching, wrap up, physics or the physical chemistry isolation finished by solvent or auxiliary material.
Described preparation mainly comprises: food, medicine, feed formulations.
Described low dose, hardly soluble active ingredient comprise; Low dose of solvable active ingredient and/or hardly soluble active ingredient (Nano/micron powder) and/or insoluble active ingredient (Nano/micron powder) and/or far infrared nano/micron powder.
Describedly be used for solvent that physics or physical chemistry isolates and can select the granulation process of corresponding preparations such as food, medicine, feed can wetting material not make sensitiveness compositions such as polysaccharide, protein-based, mucilaginous substance class, tannin class, resinae, pigment produce the solvent of viscosity again, as: concentration is higher than the ethanol more than 80%, and more preferably concentration is higher than the ethanol more than 85%.
The enough big physically-isolated hydrophilic solid that can be used for of using dosage in preparation that the described auxiliary material that is used for physics or physical chemistry isolation can select corresponding preparations such as food, medicine, feed can not influence active constituent content measuring is used auxiliary material always.
The described preferred enough big physically-isolated water miscible crystal type that can be used for of using dosage in preparation that is meant that corresponding preparations such as food, medicine, feed can not influence active constituent content measuring of auxiliary material that physics or physical chemistry isolates that is used for is used auxiliary material always.
The described most preferred corresponding preparations such as food, medicine, feed that are meant of auxiliary material that are used for physics or physical chemistry isolation can not influence the enough big alcohol insoluble matter that the can be used for physically-isolated water miscible crystal type auxiliary material commonly used of using dosage in preparation of active constituent content measuring.
The alcohol insoluble matter of described water miscible crystal type auxiliary material commonly used including, but not limited to:
Monose:
Wood sugar, glucose,
Disaccharides:
Sucrose, lactose, maltose
Amino acid:
Aspartic acid, glycine, glutamic acid, methionine, lysine, arginine,
Peptide:
Glutathione
Ester:
Glucolactone,
Alcohol:
Xylitol, inositol, maltitol, lactitol
Salt:
Neopelex, sodium carbonate, potash, sodium acid carbonate, saleratus, sodium isoascorbate, sodium ascorbate, sodium sulfite, sodium hydrogensulfite, sodium glutamate, calcium pantothenate, sodium citrate, potassium citrate, sodium alginate, potassium alginate, potassium hydrogen tartrate, sodium chloride, sodium thiosulfate, sodium sulphate, aluminum sulfate, ammonium sulfate, sodium succinate, borax, acid polyethylene sodium, arginine monohydrochloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, diammonium hydrogen phosphate, phosphocholine.
Physics or the physical chemistry partition method of finishing by solvent or auxiliary material of the present invention comprises: do not make the sensitiveness composition produce the solvent granulation isolation method of viscosity, the isolation method of granulating respectively, with broken pack after the granulation that effective ingredient is wrapped up, change physical isolation such as solvent crystal pack, spray-drying pack, spray-drying crystallization pack, be used for solving low dose of, hardly soluble active ingredient and evenly disperse a difficult problem; Solution is low dose of, hardly soluble active ingredient evenly disperses the back active constituent content to reduce a difficult problem.Wherein,
Low dose of solvable active ingredient is fit to solvent granulation isolation method, difference granulation.
Hardly soluble active ingredient (Nano/micron powder) and/or insoluble active ingredient (Nano/micron powder) and/or far infrared nano/micron powder, crush method, the pack of commentaries on classics solvent crystal, spray-drying pack, spray-drying crystallization pack after the granulation that is fit to effective ingredient is wrapped up.
Described solvent granulation isolation method, be meant with the solvable active ingredient of low dose be dissolved in heavy dose of do not make the sensitiveness composition produce the wetting agent solvent of viscosity after, add the partition method of granulating in other solid supplementary materials that mix again equably to.Or after hardly soluble active ingredient and other solid supplementary materials mix, add the partition method that heavy dose of wetting agent solvent that does not make the sensitiveness composition produce viscosity is granulated again equably.
Described heavy dose of wetting agent is meant that the consumption of used wetting agent solvent in the granulation process is 1.5～10 times of normal adhesive solvent consumption.
Described respectively granulation, the extract that is meant low dose, hardly soluble active ingredient and contains sensitive composition is granulated respectively, after the drying, mixes, a kind of formulation method of packing or preparation again.
This method relatively is fit to supplementary product consumption and/or does not contain the preparation of other active ingredient dosage of sensitive composition greater than total formulation weight amount 30%.And this method has certain active ingredient to mix the sorrow of inequality.
Described granulation back crush method, be meant low dose, slightly solubility effectively become to be dissolved in the solvent with auxiliary material and/or other active ingredient of not containing sensitive composition mix, granulate, dry, pulverize after, mix with other composition again, granulate, a kind of formulation method of dry, packing or preparation.
This method relatively be fit to supplementary product consumption and/or do not contain other active ingredient dosage of sensitive composition less preparation.And last adhesive of granulating is preferably selected the higher ethanol of concentration, with the influence of further reduction sensitive composition.
The pack of described commentaries on classics solvent crystal is meant and utilizes raw material insoluble characteristic in A and B solvent; And auxiliary material easily dissolving in the A solvent, insoluble characteristic in the B solvent, the supersaturated solution that forms auxiliary material with a spot of A solvent under heated state is standby, and the B solvent by will containing insoluble active ingredient powder or A solvent solutions add the mode in the another kind of solvent under ultrasonic, condition of stirring, the insoluble active ingredient powder of ultrasound suspending in B solvent or A solvent carried out the crystallinity parcel of auxiliary material in the A solvent, and through centrifugal, dry, pulverize after, mix with other composition again, granulate, a kind of formulation method of drying, packing or preparation.
For example: auxiliary material is chosen in easily dissolving in the water (A), the auxiliary material of insoluble characteristic in ethanol (B).
Described spray-drying pack or spray-drying crystallization pack, be meant and utilize auxiliary material in water, to dissolve, the characteristic of in spray-drying process, separating out rapidly, to low dose of, hardly soluble active ingredient powder wraps up or the crystallinity parcel after, mix with other composition again, granulate, a kind of formulation method of dry, packing or preparation.
Comparable advantage:
The method low dose of in the preparation of the present invention, that hardly soluble active ingredient evenly disperses efficient stripping; by simple preparation means and/or preprocessing means; substantially do not increasing under the condition of cost; low dose of active ingredient or nanometer powder obtain under the homodisperse prerequisite in making preparation; pass through physical isolation method dexterously; make low dose, hardly soluble active ingredient in the preparation be subjected to protecting to greatest extent, can make the assay result reach more than 90% of labelled amount.
The specific embodiment:
Further specify the present invention with embodiment below, but the present invention is not limited.
Concentrated type maijunan sheet that embodiment 1, a kind of taking dose are little or capsule formula and preparation method thereof former prescription:
Hydrochioro 8g
Pueraria Flavonid (content 80%) 260g
An ancient unit of weight rattan total alkali (content 50%) 120g
Assistant, excipient 112g
1000 of compressing tablet or can capsules.(gross weight 500g)
Preliminary treatment, getting Hydrochioro nanometer powder 8g is suspended in the 30ml water under ultrasonic state, add that sucrose 50g heating for dissolving cools below 60 ℃ standby in the assistant, other gets ethanol 70ml, under ultrasonic, stirring condition, add fast in the standby nanometer Hydrochioro sucrose solution, mix, centrifugal, ethanolic solution is standby; Hydrochioro sucrose precipitation is dry, pulverizing is standby.
Preparation,
Get standby Hydrochioro sucrose powder 58g, Pueraria Flavonid (content 80%) 260g, an ancient unit of weight rattan total alkali (content 50%) 120g, assistant, excipient 62g mixes, granulate with above-mentioned standby ethanolic solution, drying, the adding lubricant is an amount of, 1000 of compressing tablet or can capsules, promptly.
Note:
The dosage sucrose that utilizes is sealed the possibility problem of the even mixed distribution of Hydrochioro when finishing preparation to the commentaries on classics solvent of Hydrochioro sucrose powder.
Utilize sucrose undissolved characteristic in ethanol, it is finished in the alcohol granulation process the tight crystallinity of Hydrochioro is protected.
Facing a difficult choice of embodiment 2, nanometer powder
After most of nanometer powder is put into water or ethanol, in any case jolting all exists with the graininess of reuniting.Can fully be suspended in the water or in the ethanol by ultrasonic processing, be difficult for sinking for a long time after the placement.But it should be noted that in user's hand and do not have Ultrasound Instrument.
Most of nanometer powder is put into ethanol and is mixed by the prescription that ultrasonic processing back adding has sensitive composition, and it is dry to granulate, and dissolves in once more in the water, can get suspension after the jolting, precipitates immediately after the placement.
As seen the nanometer powder in preparation is no longer free, the purpose that the high dispersive when having lost them and being made into nanometer easily absorbs.
The preliminary treatment of embodiment 3, nanometer powder
With sucrose that adds pure crystallization pack or spray-drying crystallization pack preparation or lactose crystn parcel property nanoparticle;
After sucrose or lactose crystn parcel property nanoparticle directly place water and jolting, can be dispersed into nanoparticle suspension solution rapidly with the same effect of ultrasonic processing.
Sucrose or lactose crystn parcel property nanoparticle adds in the prescription with sensitive composition and mixes, after the alcohol granulation drying, dissolve in the water once more and jolting after, can be dispersed into nanometer powder suspension solution rapidly with the same effect of ultrasonic processing.
As seen no matter the nanoparticle of handling by the present invention is used separately or the high dispersive can both reach them be made into nanometer in preparation time the and/or the easy purpose of absorption.
Claims (10)
1. the method low dose of in the preparation, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that, the described method that makes active ingredient in the preparation evenly disperse efficient stripping is meant that physics that low dose of in the preparation, hardly soluble active ingredient or nanometer powder are finished by solvent or auxiliary material or physical chemistry isolates the method for avoiding in the process of granulation heat drying closing, catching, wrapping up with sensitive composition generation chemical reaction or physical crosslinking, huge legendary turtle the efficient stripping of even dispersion that is protected;
Described preparation mainly comprises: food, medicine, feed formulations.
2. the method low dose of in the preparation as claimed in claim 1, that hardly soluble active ingredient evenly disperses efficient stripping is characterized in that described low dose, hardly soluble active ingredient comprise; Low dose of solvable active ingredient and/or hardly soluble active ingredient (Nano/micron powder) and/or insoluble active ingredient (Nano/micron powder) and/or far infrared nano/micron powder.
3. the method low dose of in the preparation as claimed in claim 1, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that, describedly be used for solvent that physics or physical chemistry isolates and can select the granulation process of corresponding preparations such as food, medicine, feed can wetting material not make sensitiveness compositions such as polysaccharide, protein-based, mucilaginous substance class, tannin class, resinae, pigment produce the solvent of viscosity again, as: concentration is higher than the ethanol more than 80%, and more preferably concentration is higher than the ethanol more than 85%.
4. the method low dose of in the preparation as claimed in claim 1, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that the enough big physically-isolated hydrophilic solid that can be used for of using dosage in preparation that the described auxiliary material that is used for physics or physical chemistry isolation can select corresponding preparations such as food, medicine, feed can not influence active constituent content measuring is used auxiliary material always;
The described preferred enough big physically-isolated water miscible crystal type that can be used for of using dosage in preparation that is meant that corresponding preparations such as food, medicine, feed can not influence active constituent content measuring of auxiliary material that physics or physical chemistry isolates that is used for is used auxiliary material always;
The described most preferred corresponding preparations such as food, medicine, feed that are meant of auxiliary material that are used for physics or physical chemistry isolation can not influence the enough big alcohol insoluble matter that the can be used for physically-isolated water miscible crystal type auxiliary material commonly used of using dosage in preparation of active constituent content measuring.
The alcohol insoluble matter of described water miscible crystal type auxiliary material commonly used including, but not limited to:
Monose:
Wood sugar, glucose,
Disaccharides:
Sucrose, lactose, maltose
Amino acid:
Aspartic acid, glycine, glutamic acid, methionine, lysine, arginine,
Peptide:
Glutathione
Ester:
Glucolactone,
Alcohol:
Xylitol, inositol, maltitol, lactitol
Salt:
Neopelex, sodium carbonate, potash, sodium acid carbonate, saleratus, sodium isoascorbate, sodium ascorbate, sodium sulfite, sodium hydrogensulfite, sodium glutamate, calcium pantothenate, sodium citrate, potassium citrate, sodium alginate, potassium alginate, potassium hydrogen tartrate, sodium chloride, sodium thiosulfate, sodium sulphate, aluminum sulfate, ammonium sulfate, sodium succinate, borax, acid polyethylene sodium, arginine monohydrochloride, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydrogen phosphate, dipotassium hydrogen phosphate, diammonium hydrogen phosphate, phosphocholine.
5. low dose of in the preparation as claimed in claim 1, hardly soluble active ingredient evenly disperses the method for efficient stripping, it is characterized in that, described physics or the physical chemistry partition method of finishing by solvent or auxiliary material comprises: do not make the sensitiveness composition produce the solvent granulation isolation method of viscosity, the isolation method of granulating respectively, with broken pack after the granulation that effective ingredient is wrapped up, change the solvent crystal pack, the spray-drying pack, physical isolation methods such as spray-drying crystallization pack, wherein
Low dose of solvable active ingredient is fit to solvent granulation isolation method, difference granulation;
Hardly soluble active ingredient (Nano/micron powder) and/or insoluble active ingredient (Nano/micron powder) and/or far infrared nano/micron powder, crush method, the pack of commentaries on classics solvent crystal, spray-drying pack, spray-drying crystallization pack after the granulation that is fit to effective ingredient is wrapped up.
6. as the method low dose of in claim 1, the 5 described preparations, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that, described solvent granulation isolation method, be meant with the solvable active ingredient of low dose be dissolved in heavy dose of do not make the sensitiveness composition produce the wetting agent solvent of viscosity after, add the partition method of granulating in other solid supplementary materials that mix again equably to; Or after hardly soluble active ingredient and other solid supplementary materials mix, add the partition method that heavy dose of wetting agent solvent that does not make the sensitiveness composition produce viscosity is granulated again equably;
Described heavy dose of wetting agent is meant that the consumption of used wetting agent solvent in the granulation process is 1.5～10 times of normal adhesive solvent consumption.
7. as the method low dose of in claim 1, the 5 described preparations, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that, described granulation respectively, the extract that is meant low dose, hardly soluble active ingredient and contains sensitive composition is granulated respectively, after the drying, mix, a kind of formulation method of packing or preparation again;
This method relatively is fit to supplementary product consumption and/or does not contain the preparation of other active ingredient dosage of sensitive composition greater than total formulation weight amount 30%.
8. as the method low dose of in claim 1, the 5 described preparations, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that, described granulation back crush method, be meant low dose, slightly solubility effectively become to be dissolved in the solvent with auxiliary material and/or other active ingredient of not containing sensitive composition mix, granulate, dry, pulverize after, mix with other composition again, granulate, a kind of formulation method of dry, packing or preparation;
This method relatively be fit to supplementary product consumption and/or do not contain other active ingredient dosage of sensitive composition less preparation.And last adhesive of granulating is preferably selected the higher ethanol of concentration.
9. as the method low dose of in claim 1, the 5 described preparations, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that the pack of described commentaries on classics solvent crystal is meant and utilizes raw material insoluble characteristic in A and B solvent; And auxiliary material easily dissolving in the A solvent, insoluble characteristic in the B solvent, the supersaturated solution that forms auxiliary material with a spot of A solvent under heated state is standby, and the B solvent by will containing insoluble active ingredient powder or A solvent solutions add the mode in the another kind of solvent under ultrasonic, condition of stirring, the insoluble active ingredient powder of ultrasound suspending in B solvent or A solvent carried out the crystallinity parcel of auxiliary material in the A solvent, and through centrifugal, dry, pulverize after, mix with other composition again, granulate, a kind of formulation method of drying, packing or preparation.
10. as the method low dose of in claim 1, the 5 described preparations, that hardly soluble active ingredient evenly disperses efficient stripping, it is characterized in that, described spray-drying pack or spray-drying crystallization pack, be meant and utilize auxiliary material in water, to dissolve, the characteristic of in spray-drying process, separating out rapidly, to low dose of, hardly soluble active ingredient powder wraps up or the crystallinity parcel after, mix with other composition again, granulate, a kind of formulation method of dry, packing or preparation.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104431363A (en) * | 2014-12-10 | 2015-03-25 | 张家界恒兴生物科技有限公司 | Special vegetable feed additive for poultry breeding and production method thereof |
| CN104587457A (en) * | 2015-01-13 | 2015-05-06 | 广东海大畜牧兽医研究院有限公司 | Method for preparing nanoparticle vaccine by utilizing slightly soluble or insoluble protein/polypeptide antigens |
| CN109568274A (en) * | 2017-03-24 | 2019-04-05 | 北京长峰金鼎科技有限公司 | A kind of method of granulating suitable for viscous material |
-
2009
- 2009-04-14 CN CN200910071770A patent/CN101861973A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104431363A (en) * | 2014-12-10 | 2015-03-25 | 张家界恒兴生物科技有限公司 | Special vegetable feed additive for poultry breeding and production method thereof |
| CN104587457A (en) * | 2015-01-13 | 2015-05-06 | 广东海大畜牧兽医研究院有限公司 | Method for preparing nanoparticle vaccine by utilizing slightly soluble or insoluble protein/polypeptide antigens |
| CN109568274A (en) * | 2017-03-24 | 2019-04-05 | 北京长峰金鼎科技有限公司 | A kind of method of granulating suitable for viscous material |
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Application publication date: 20101020 |