CN102077905B - Method for producing enteric cysteamine hydrochloride coated granules - Google Patents
Method for producing enteric cysteamine hydrochloride coated granules Download PDFInfo
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- CN102077905B CN102077905B CN2010105813664A CN201010581366A CN102077905B CN 102077905 B CN102077905 B CN 102077905B CN 2010105813664 A CN2010105813664 A CN 2010105813664A CN 201010581366 A CN201010581366 A CN 201010581366A CN 102077905 B CN102077905 B CN 102077905B
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- cysteamine hydrochloride
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- hydrochloride coated
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- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 229940097265 cysteamine hydrochloride Drugs 0.000 title claims abstract description 33
- 239000007931 coated granule Substances 0.000 title claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 239000002775 capsule Substances 0.000 claims abstract description 55
- 239000000463 material Substances 0.000 claims abstract description 23
- 239000000725 suspension Substances 0.000 claims abstract description 22
- 239000003094 microcapsule Substances 0.000 claims abstract description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000004090 dissolution Methods 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 238000004062 sedimentation Methods 0.000 claims description 10
- 108010010803 Gelatin Proteins 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000000796 flavoring agent Substances 0.000 claims description 6
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- 229920000159 gelatin Polymers 0.000 claims description 6
- 239000008273 gelatin Substances 0.000 claims description 6
- 235000019322 gelatine Nutrition 0.000 claims description 6
- 235000011852 gelatine desserts Nutrition 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 6
- 210000002784 stomach Anatomy 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 3
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 239000008098 formaldehyde solution Substances 0.000 abstract 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 10
- 229960003151 mercaptamine Drugs 0.000 description 10
- 238000012360 testing method Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
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- 102000018997 Growth Hormone Human genes 0.000 description 3
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- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000122 growth hormone Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
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- 230000002496 gastric effect Effects 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
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- 230000004060 metabolic process Effects 0.000 description 2
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- YXXURDJTDAAEPH-UHFFFAOYSA-N 2-aminopropanethioic s-acid Chemical compound CC(N)C(S)=O YXXURDJTDAAEPH-UHFFFAOYSA-N 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 229930192334 Auxin Natural products 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
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- 241000282849 Ruminantia Species 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 239000010828 animal waste Substances 0.000 description 1
- 239000002363 auxin Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
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- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 235000020997 lean meat Nutrition 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a method for producing enteric cysteamine hydrochloride coated granules, which comprises the following process steps: 1, combining cysteamine hydrochloride and a capsule material to prepare mixed suspension; 2, adding the mixed suspension into 5-percent acetic acid solution, mixing at 50 DEG C to form coacervated capsules, adding water at 30 to 40 DEG C in a volume which is 1 to 3 times that of the coacervated capsules to form suck capsules, adding 37-percent formaldehyde solution and mixing at 10 DEG C to form solidified capsules; 3, washing the solidified capsules till no formaldehyde smell is given off to form microcapsules; and 4, dying under vacuum to obtain cysteamine hydrochloride coated granule preparation. In the method, the cysteamine hydrochloride coated with an imported coating material is prevented from being oxidized in any environment and the properties of the cysteamine hydrochloride coated granules are stable, the dissolution rate of the cysteamine hydrochloride coated granules in stomach is smaller than 2 percent, and the use of the cysteamine hydrochloride coated granules in a large dose does not cause canker; the cysteamine hydrochloride is released in intestinal tract accurately and can dissolve and be absorbed completely; and thus, the bioavailability is improved greatly. The product can be added into an auxiliary material as a raw material to form the low-content cysteamine hydrochloride coated granules.
Description
Technical field
The present invention relates to feedstuff and field of feed additive technology, relate in particular to the production method of enteric cysteamine hydrochloride coated granules.
Background technology
Cysteamine (Cys-teamine, CS) claims again β-mercaptoethylmaine cysteamine, and molecular formula C2H7NS is the mesostate of aminothiopropionic acid.CS is the ingredient of coenzyme A, contains sulfhydryl-group activity and hydrogen base and multiple physiological action is arranged, and the metabolism elements such as the growth hormone of animal, thyroxine, insulin are played the inhibition regulating action.Studies show that in a large number: CS can reduce the content of tumor growth chalone, indirectly improves the concentration of growth hormone GH, promotes growth of animals or poultry, and can improve the price of deed, improves carcass quality.Cysteamine can also effectively promote animal body to absorption and the utilization of calcium, phosphorus, reduces the content of phosphorus in the animal wastes, is conducive to environmental conservation.Cysteamine hydrochloride is the hydrochlorate of cysteamine, studies show that in a large number of the animals such as rat, pig, chicken, duck, goose, cattle, sheep, after the reasonable interpolation in the feedstuff, cysteamine hydrochloride is exhausted somatostatin, the growth axis of regulation and control animal, promote the secretion of growth hormone, strengthen the metabolism of energy, albumen, calcium, phosphorus etc., animal is had in various degree growth promoting function; And can improve the price of deed, lean meat percentage and improve carcass quality.But cysteamine is very easy to be oxidized to disulphide in air lost efficacy, and can stimulate coat of the stomach under one's belt, produced serious gastric ulcer, Gu it can not be applied to large-scale industrial production.And cysteamine hydrochloride also has the shortcomings such as fusing point low (70.2～70.7 ℃), easy deliquescence, chemical property active (easily oxidation, easy complexation etc.), so that it is not easy to be applied to large-scale industrial production.
Summary of the invention
Defects for existing cysteamine and cysteamine hydrochloride existence, the applicant has carried out improving research, a kind of production method of enteric cysteamine hydrochloride coated granules is provided, carry out cysteamine hydrochloride first and the capsule material is made suspension, again suspension made cohesion capsule, sedimentation capsule, solidified capsule, make at last microcapsule, make the cysteamine in any environment can oxidation, character is stable, can heavy dose of life-time service.
Originally put the technical scheme that invention adopts as follows:
A kind of production method of enteric cysteamine hydrochloride coated granules, processing step is as follows:
(1) combination of cysteamine hydrochloride and capsule material:
With 1 weight portion cysteamine hydrochloride and 0.2 ~ 0.5 weight portion capsule material mixed dissolution, form suspension; The gelatin solution that described capsule material is mass concentration 2.5 ~ 5.0% and the gumwater of mass concentration 2.5 ~ 5.0%, both weight ratios are 1:1;
(2) formation of cohesion capsule, sedimentation capsule, curing capsule:
The acetum that adds mass concentration 5% in the suspension that step (1) obtains in 50 ℃ of lower mixing, until suspension PH is adjusted into 4.0 ~ 4.5, forms the cohesion capsule; 30 ~ 40 ℃ the water that adds again 1 ~ 3 times of volume forms the sedimentation capsule; Then the formalin that adds 2.5mL mass concentration 37%, in 10 ℃ of lower mixing, with mass concentration be 20% NaOH to adjust PH be 8.0 ~ 9.0, form the curing capsule;
(3) formation of microcapsule:
The curing capsule that step (2) is obtained is washed to formaldehydeless flavor, forms microcapsule;
(4) microcapsule that step (3) is obtained carries out vacuum drying and obtains finished product.
Useful technique effect of the present invention is:
The enteric cysteamine hydrochloride dosage form that the present invention adopts the microcapsule inclusion technique to make in any environment can oxidation, and character is stable.Less than 2%, and can pass through ruminant tumor gastric at the dissolution of gastric, avoid the stimulation of cysteamine to coat of the stomach, overcome the life-time service cysteamine and caused the problems such as gastric ulcer; This product discharges rapidly at intestinal, reaches the optimal absorption effect, has avoided many untoward reaction, can heavy dose of life-time service, and effectively auxin level in the control agent greatly improves bioavailability; And safe and efficient, nontoxic, noresidue, easy to use.This product can be used as raw material adding adjuvant and makes the low content cysteamine hydrochloride coated granules.
Description of drawings
Fig. 1 is process chart of the present invention.
Fig. 2 is that the present invention is on the contrast figure of the impact of piglets daily gain.
Fig. 3 is that the present invention is on the contrast figure of the impact of piglets material anharmonic ratio.
The specific embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is described.
As shown in Figure 1, process of the present invention is divided following steps:
(1) combination of cysteamine hydrochloride and capsule material:
With 1 weight portion cysteamine hydrochloride and 0.2 ~ 0.5 weight portion capsule material mixed dissolution, form suspension; The gelatin solution that consists of mass concentration 2.5 ~ 5.0% of described capsule material and the gumwater of mass concentration 2.5 ~ 5.0%, both weight ratios are 1:1;
(2) formation of cohesion capsule, sedimentation capsule, curing capsule:
The acetum that adds mass concentration 5% in the suspension that step (1) obtains in 50 ℃ of lower mixing, until suspension PH is adjusted into 4.0 ~ 4.5, forms the cohesion capsule; 30 ~ 40 ℃ the water that adds again 1 ~ 3 times of volume forms the sedimentation capsule; Then the formalin that adds 2.5mL mass concentration 37%, in 10 ℃ of lower mixing, with mass concentration be 20% NaOH to adjust PH be 8.0 ~ 9.0, form the curing capsule;
(3) formation of microcapsule:
The curing capsule that step (2) is obtained is washed to formaldehydeless flavor, forms microcapsule;
(4) microcapsule that step (3) is obtained carries out vacuum drying and obtains finished product.
In order better to explain the present invention, the present invention will be further described below in conjunction with the specific embodiment.
Embodiment 1
With 1 part of cysteamine hydrochloride and 0.2 part of capsule material (gumwater of the gelatin solution of mass concentration 2.5% and mass concentration 2.5%, weight ratio 1:1) mixed dissolution, form suspension.The acetum that adds an amount of mass concentration 5% in suspension in 50 ℃ of lower mixing, is adjusted to 4.0 with suspension PH, forms the cohesion capsule.The water that adds again 30 ℃ of 1 times of volumes forms the sedimentation capsule.Then the formalin that adds 2.5mL mass concentration 37%, in 10 ℃ of lower mixing, adjusting PH with the NaOH of an amount of mass concentration 20% is 8.0, forms the curing capsule.The curing capsule that obtains is washed to formaldehydeless flavor, forms microcapsule.The microcapsule that obtains is carried out vacuum drying obtain finished product.
Embodiment 2
With 1 part of cysteamine hydrochloride and 0.3 part of capsule material (gumwater of the gelatin solution of mass concentration 4.0% and mass concentration 4.0%, weight ratio 1:1) mixed dissolution, form suspension.The acetum that adds an amount of mass concentration 5% in suspension in 50 ℃ of lower mixing, is adjusted to 4.2 with suspension PH, forms the cohesion capsule.The water that adds again 35 ℃ of 2 times of volumes forms the sedimentation capsule.Then the formalin that adds 2.5mL mass concentration 37%, in 10 ℃ of lower mixing, adjusting PH with the NaOH of an amount of mass concentration 20% is 8.5, forms the curing capsule.The curing capsule that obtains is washed to formaldehydeless flavor, forms microcapsule.The microcapsule that obtains is carried out vacuum drying obtain finished product.
Embodiment 3
With 1 part of cysteamine hydrochloride and 0.5 part of capsule material (gumwater of the gelatin solution of mass concentration 5.0% and mass concentration 5.0%, weight ratio 1:1) mixed dissolution, form suspension.The acetum that adds an amount of mass concentration 5% in suspension in 50 ℃ of lower mixing, is adjusted to 4.5 with suspension PH, forms the cohesion capsule.The water that adds again 40 ℃ of 3 times of volumes forms the sedimentation capsule.Then the formalin that adds 2.5mL mass concentration 37%, in 10 ℃ of lower mixing, adjusting PH with the NaOH of an amount of mass concentration 20% is 9.0, forms the curing capsule.The curing capsule that obtains is washed to formaldehydeless flavor, forms microcapsule.The microcapsule that obtains is carried out vacuum drying obtain finished product.
Below by controlled trial effect of the present invention is described:
The cysteamine hydrochloride product (test group 1 ~ 3) of above-described embodiment 1 ~ 3 is added in the piglet feed in identical ratio respectively with existing cysteamine hydrochloride product (matched group), take under identical feeding condition, for 4 groups of swinerys, draw following data after a period of time:
(1) daily gain: as shown in Figure 1, matched group material anharmonic ratio is 280g, use test group 1 daily gain of embodiment 1 product to be 320g, use test group 2 daily gains of embodiment 2 products to be 325g, use test group 3 daily gains of embodiment 3 products to be 322g, improved 12.5%, 16.1%, 15.0% than matched group respectively.
(2) the material anharmonic ratio ratio of standard feed amount and pig weightening finish (consume): as shown in Figure 2, matched group material anharmonic ratio is 1.55%, using the test group 1 material anharmonic ratio of embodiment 1 product is 1.44%, using the test group 2 material anharmonic ratioes of embodiment 2 products is 1.41%, using the test group 3 material anharmonic ratioes of embodiment 3 products is 1.42%, has reduced by 7.09%, 9.03%, 8.39% than matched group respectively.
Above-mentioned two groups of experiments show, product of the present invention can reach the optimal absorption effect, avoids untoward reaction, improve the feed intake of pig, increase raiser's economic benefit.
Above-described only is preferred implementation of the present invention, the invention is not restricted to above embodiment.Be appreciated that other improvement and variation that those skilled in the art directly derive or associate under the prerequisite that does not break away from spirit of the present invention and design, all should think to be included within protection scope of the present invention.
Claims (1)
1. the production method of an enteric cysteamine hydrochloride coated granules is characterized in that processing step is as follows:
(1) combination of cysteamine hydrochloride and capsule material:
With 1 weight portion cysteamine hydrochloride and 0.2 ~ 0.5 weight portion capsule material mixed dissolution, form suspension; The gelatin solution that described capsule material is mass concentration 2.5 ~ 5.0% and the gumwater of mass concentration 2.5 ~ 5.0%, both weight ratios are 1:1;
(2) formation of cohesion capsule, sedimentation capsule, curing capsule:
The acetum that adds mass concentration 5% in the suspension that step (1) obtains in 50 ℃ of lower mixing, until suspension pH is adjusted into 4.0 ~ 4.5, forms the cohesion capsule; 30 ~ 40 ℃ the water that adds again 1 ~ 3 times of volume forms the sedimentation capsule; Then the formalin that adds 2.5mL mass concentration 37%, in 10 ℃ of lower mixing, with mass concentration be 20% NaOH to adjust pH be 8.0 ~ 9.0, form the curing capsule;
(3) formation of microcapsule:
The curing capsule that step (2) is obtained is washed to formaldehydeless flavor, forms microcapsule;
(4) microcapsule that step (3) is obtained carries out vacuum drying and obtains finished product.
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| CN2010105813664A CN102077905B (en) | 2010-12-10 | 2010-12-10 | Method for producing enteric cysteamine hydrochloride coated granules |
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| CN2010105813664A CN102077905B (en) | 2010-12-10 | 2010-12-10 | Method for producing enteric cysteamine hydrochloride coated granules |
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| CN102077905B true CN102077905B (en) | 2013-01-02 |
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| TWI649100B (en) | 2013-06-17 | 2019-02-01 | 地平線罕見醫學製藥有限責任公司 | Delayed release cysteamine bead formulation, and preparation and use thereof |
| CN103652366B (en) * | 2013-09-17 | 2017-07-07 | 杭州康德权饲料有限公司 | A kind of stabilization micro-capsule coating Mercaptamine and preparation method thereof |
| US10143665B2 (en) | 2015-11-17 | 2018-12-04 | Horizon Orphan Llc | Methods for storing cysteamine formulations and related methods of treatment |
| CN108185183A (en) * | 2018-01-15 | 2018-06-22 | 环山集团股份有限公司 | Regulate and control the feed of growing-finishing pigs speed by growth axis |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1358499A (en) * | 2000-12-13 | 2002-07-17 | 华扩达生化实业有限公司 | Animal phisiologicla and biological activity regulation agent composition containing cysteamine and its salt |
| CN101288662A (en) * | 2008-05-09 | 2008-10-22 | 济南大学 | Xanthophyll micro-capsule and its preparation method |
| CN101653426A (en) * | 2009-09-16 | 2010-02-24 | 冯利萍 | Slow release pellet of high-stability type cysteamine hydrochloride and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1358499A (en) * | 2000-12-13 | 2002-07-17 | 华扩达生化实业有限公司 | Animal phisiologicla and biological activity regulation agent composition containing cysteamine and its salt |
| CN101288662A (en) * | 2008-05-09 | 2008-10-22 | 济南大学 | Xanthophyll micro-capsule and its preparation method |
| CN101653426A (en) * | 2009-09-16 | 2010-02-24 | 冯利萍 | Slow release pellet of high-stability type cysteamine hydrochloride and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 武志勇等.肠溶包被半胱胺对猪生产性能应用研究.《江西饲料》.2007,(第06期),42-43. * |
| 胥传来等.半胱胺微胶囊的研制与生产.《饲料工业》.2002,第23卷(第02期),9-11. * |
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