CN102526082B - Compound glycyrrhizin soluble powder for livestock and preparation method thereof - Google Patents
Compound glycyrrhizin soluble powder for livestock and preparation method thereof Download PDFInfo
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- CN102526082B CN102526082B CN 201110425509 CN201110425509A CN102526082B CN 102526082 B CN102526082 B CN 102526082B CN 201110425509 CN201110425509 CN 201110425509 CN 201110425509 A CN201110425509 A CN 201110425509A CN 102526082 B CN102526082 B CN 102526082B
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Abstract
The invention belongs to the field of veterinary drugs and discloses compound glycyrrhizin soluble powder for livestock and a preparation method thereof. The compound glycyrrhizin soluble powder for livestock is processed into soluble powder with glycyrrhizin acid ammonium, glycine, methionine, taurine and glutamine as active components and other acceptable auxiliary materials in pharmacy. The process comprises the steps of performing ultramicro grinding treatment on medicine of glycyrrhizin acid ammonium and the like, and drying all medical components and auxiliary materials; and evenly mixing treated glycyrrhizin acid ammonium, other medicine, selected fillers, cosolvent and an adhesion resistant agent according to equivalent progressively-increasing method, splitting, packing and obtaining. The soluble powder has the functions of protecting livers, enhancing immunity, nourishing intestinal mucosa cells and the like and can be applied to prevention and cure of infectious and drug-induced liver injury of livestock. When the compound glycyrrhizin soluble powder for livestock is used, the soluble powder is dissolved in set water, and live stock can drink freely.
Description
Technical field
The invention belongs to field of veterinary, relate to a kind of poultry compound glycyrrbizic acid monoamine soluble powder and preparation method thereof.
Background technology
In recent years, in the animal husbandry cultivation practice, even bacterial infection, viral infection, parasitic infection disease medicine source liver damage class disease are trend occurred frequently.The generation of these diseases and evolution, add a large amount of all kinds of antibacterials, anti-parasite medicine and antiviral drugs of using in the process of control, more or less all can affect the liver function of animal, cause liver all kinds of inflammation, liver enzyme amount and active not normal to occur, Biochemical Indices In Serum is unusual, even new " diseases " such as hepatic fibrosis and hepatic necrosis occur.These liver function injury seriously restrict prognosis of disease, then affect the growth promoter of animal, even cause animal dead.
Alleviate the medicine of repairing poultry liver function aspect, still rare.The present invention is fully investigating on the basis, from veterinary clinic medication actual demand, take widely used SNMC pharmaceutical formulation medically as square foundation, repair the medicine of intestinal mucosa cells in conjunction with other liver nutrients and enhancing human body immunity power, nutrition, common prescription, filter out and have hepatoprotective and increase the new veterinary drug preparation of exempting from and repairing Function of intestinal mucosa, be complementary the dosage form selection soluble powder with poultry intensive culture administration convenience.
Radix Glycyrrhizae is widely used Chinese medicine material; modern pharmacology research confirms; it has antiinflammatory, antioxidation, anti-hepatic fibrosis; resist hepatotoxicity, flow, prevent the multiple efficacies such as apoptosis and the generation of promotion endogenous steroid in Cell protection film, adjusting immunologic function, the inhibition Ca2+.Series glycyrrhizin class Department of Pharmacy is from the conjugate of the glucuronic acid enoxolone of licorice stem extraction; comprise monomer or the compound medicines such as monoammonium glycyrrhizinate, compound glycyrrbizic acid monoamine, glycyrrhizic acid diamidogen, Isoglycyrrhiza acid, all have with the similar antiinflammatory of natural Radix Glycyrrhizae, protect liver plasma membrane, antibiooxidation and improve liver function, antiallergic, adjusting immunologic function and strengthen the effects such as phagocyte vigor detoxifies.At present, glycyrrhizin class medicine related preparations is the most frequently used medicine that protects the liver on the clinical medicine, accounts for liver-gallbladder disease medication share the first, considerably beyond other drug, wherein more uses at most with compound glycyrrbizic acid monoamine tablet and injection.
Compound glycyrrbizic acid monoamine tablet or injection are produced (trade name: U.S. energy), went on the market for treating skin disease the hepatopathy that begins to be used for the treatment of in 1958 in 1948 by Minophagen Pharmaceutical Co L.Late nineteen seventies has been seen formal report as clinical prevention chronic hepatitis medicine.After this, this medicine is as preventing and treating the standard drug of chronic hepatitis, by for a long time, use widely.1985, China began with compound glycyrrbizic acid glycoside preparation for treating chronic viral hepatitis.The medical practice of decades confirms that it can significantly improve the impaired liver function of chronic hepatitis patient, falls enzyme and reduces bilirubinic effective percentage about 80%, improves the Biochemical Indices In Serum of liver cirrhosis patient.
The compound tablet of glycyrrhizin agent is by monoammonium glycyrrhizinate (Ammoni Glycyrrhetate, GL), glycine (glycine, GLY), DL-methionine (DL-methionine, MET) prescription, every contains: glycyrrhizin 25mg (ammonium glycyrrhizinate 35mg), glycine 25mg, methionine 25mg.Compound Glycyrrhizin Injection Concomitant is replaced methionine with cysteine, and formula proportion is constant.Research confirms; GL has the pharmacological actions such as protection liver plasma membrane, antiinflammatory, antiviral, immunomodulating and steroid sample; also can induce gamma interferon; strengthen NKT (NK) cytoactive; alleviate the hepatocellular degeneration necrosis, reduce glutamate pyruvate transaminase; suppress liver collagen fiber hypertrophy, prevent that hepatic fibrosis from forming, and promotes the pharmacological actions such as bilirubin metabolism.GLY significantly reduces chronic hepatitis patients plasma endotoxin (endotoxin, ET), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) level.ET can increase the weight of hepatic injury and inspire various complication, and all there are intestinal endotoxemia (IETM) in various degree in various acute and chronics, hepatitis gravis, liver cirrhosis and liver cancer patient, and IETM can bring out hepatic fibrosis, liver cirrhosis and canceration of hepatic cell.Research is found: 1. GLY can block the ET receptor, suppresses ET and brings into play its biological effect, obviously alleviates the hepatic injury of the endotoxin induction liver injury animals model due to the endotoxin.2. GLY is a kind of newfound cytoprotective, can directly protect hepatocyte and its inflammation and degree of necrosis are obviously alleviated, and significantly improves liver function, has protecting the liver, falls enzyme, jaundice.3. GLY regulates renal function, prevents the pseudo-aldosterone symptom of GL.MET can improve the liver detoxification ability; reduce anaphylaxis; MET and adenosine triphosphate (ATP) catalyze and synthesize SAM (S-Adenosyl-L-Methionine through adenosyl transferase in the body; SAM); SAM is as the precursor of methyl donor and physiological sulfur-based compound (such as aminothiopropionic acid, taurine, glutathione and coenzyme A etc.); participate in important biochemical reaction in the body, be conducive to liver cell regeneration, differentiation and regulate hepatocyte function.When hepatocyte is badly damaged, SAM exhausts that exogenous additional SAM can recover flowability and the sodium pump function of hepatocyte plasma membrane, promotes that the endogenous detoxifcation material such as reduced glutathione is synthetic, improves hepatocyte dna methylation level, promotes liver cell regeneration.
Have both at home and abroad in a large number about the preparation effect of compound glycyrrbizic acid monoamines and the report used at clinical medicine thereof, relate generally to it and be used for preventing and treating various viral hepatitis, toxic hepatitis, liver cirrhosis, hepatocarcinoma, Hepatic artery chemotherapy etc.On the veterinary clinic, though Radix Glycyrrhizae is arranged as the report of Chinese medicine in clinical use, there is not yet the report that compound glycyrrbizic acid monoamines preparation is used at veterinary clinic.
Taurine is nutritious and protective effect to hepatocyte.1. be trophic factor for hepatocytes.Promote hepatic tissue cell to grow, promote the absorption of lipid, suppress hepatocellular apoptosis; 2. protect hepatocyte.The effects such as by participating in phospholipid metabolism, protecting film phospholipid is avoided degraded, and the biological effects such as anti peroxidation of lipid are stablized liver plasma membrane, and protection liver cell nuclear ribonucleoside triphosphote enzyme and minimizing extracellular matrix are synthetic; 3. anti-hepatic fibrosis.Have the activation that suppresses hepatic stellate cell, suppress the nucleus formation of the TGF-β 1 of cytokine.
Glutamine is the intestinal mucosa nutrient.Energy and metabolic precursor thereof can be provided, keep the normal form of intestinal, 26S Proteasome Structure and Function and other histoorgan normal functions.Be in particular in: 1. be the main energy source of enterocyte, in order to keep the many metabolic processes that depend on ATP; 2. its metabolite polyamines all plays an important role in the processes such as reparation of propagation, differentiation and the impaired enteric epithelium of intestinal cell; 3. the synthetic NO of its metabolite is playing the part of important role at aspects such as the secretion of regulating and control intestinal and integrity; 4. the synthetic sweet skin of paddy skin is protecting intestinal to avoid in the infringement of antibacterial and toxin positive role being arranged; 5. be the main energy source of multiple quick somatoblast (lymphocyte of activation and enterocyte etc.), also can promote lymphocyte propagation.6. not only can keep the non-specific immunity of intestinal part, can also improve its specific immune function and improve the anti-oxidation function of body.Under normal circumstances, body can be by the endogenous needs that synthesize to satisfy each histoorgan, particularly intestinal.But when the stress state such as wound, disease, because a body histoorgan has strengthened the utilization to the intestinal mucosa reparative factor, if can not in time be replenished fully from external, probably cause its exhaustion.Existing animal experiment proves: ectogenic intestinal mucosa reparative factor can promote stress rear intestinal structure, function and immunologic function and hetero-organization organ dysfunction normal thereof.
Summary of the invention
The objective of the invention is the defects for prior art, a kind of poultry compound glycyrrbizic acid monoamine soluble powder is provided.
Another object of the present invention provides the preparation method of this compound glycyrrbizic acid monoamine soluble powder.
Purpose of the present invention can be achieved through the following technical solutions:
Poultry, are equipped with other pharmaceutically acceptable adjuvants and make soluble powder take glycyrrhizic acid monoammonium, glycine, methionine, taurine and glutamine as active component with compound glycyrrbizic acid monoamine soluble powder.
Wherein, described other pharmaceutically acceptable adjuvants comprise filler, cosolvent and caking inhibiter.
Described filler be selected from anhydrous glucose, lactose, sucrose, anhydrous sodium sulfate, sodium bicarbonate, sodium carbonate, mannitol, sorbitol, soluble starch, xylitol or the microcrystalline Cellulose any one or multiple.
Described cosolvent be selected from sodium sulfite, sodium sulfite, sodium salicylate, hexamethylenamine, sodium lauryl sulphate, polyvinylpyrrolidone, poloxamer, citric acid, sodium citrate, sodium dihydrogen phosphate or the sodium hydrogen phosphate any one or multiple.
Described caking inhibiter be selected from micropowder silica gel, Kaolin, crospolyvinylpyrrolidone, sodium bicarbonate, pregelatinized Starch or the anhydrous sodium sulfate any one or multiple.
Each amounts of components is preferably in the described compound glycyrrbizic acid monoamine soluble powder:
Described poultry carry out superfine grinding with glycyrrhizic acid monoammonium first with the preparation method of compound glycyrrbizic acid monoamine soluble powder, and (pharmacopeia stipulates that No. 9 sieve sieve aperture internal diameters (meansigma methods) are: 75 ± 4.1um) to cross No. 9 sieves; Take by weighing respectively glycyrrhizic acid monoammonium raw material, glycine, methionine, taurine, glutamine and filler, cosolvent, caking inhibiter after the processing by recipe quantity, increase progressively mixing method by equivalent, mix homogeneously, packing, and get final product.
The selected dosage form of this preparation is soluble powder, and clinical indication is bacterial infection hepatitis, medicine source liver damage and hepatic fibrosis, viral hepatitis etc.
Clinical practice: this soluble powder has hepatoprotective and increases and exempt from and the effect such as nutrition intestinal mucosa cells, is used for control poultry infectivity and medicine source liver damage.During use, preparation is dissolved in the water of regulation, poultry are freely drunk and get final product.
Usage and consumption are: prevention is used.Pig, fowl: per 100 grams are watered the 250-500 kilogram, and poultry, fowl are freely drunk, and are administered once weekly.Use during disease.Pig, fowl: per 100 grams are watered the 125-250 kilogram, freely drink, and every other day once, are used in conjunction 3 times.
Beneficial effect:
The present invention is take SNMC related preparations prescription as the basis; high in conjunction with many reasons of poultry liver damage disease sickness rate; total symptom also comprise because of the heating inflammation cause intestinal mucosa to come off; the livestock and poultry Pathophysiology characteristics such as intestinal absorption function damage symptom; first with taurine and glutamine and the use of compound glycyrrbizic acid monoamine associating prescription; can be effectively for this disease symptoms group occurred frequently; strengthen hepatoprotective and repair Function of intestinal mucosa, make this product have the protection liver plasma membrane; improve liver function; antiinflammatory; regulate immunity; strengthen phagocyte vigor and nutrition intestinal mucosa cells; maintain or repair the effects such as intestinal mucosa absorption function.Soluble powder is fit to the administration of Animal Populations drinking-water.The present invention considers the convenience of veterinary drug clinical administration, selects the soluble powder that is fit to colony's administration.By principal agent is carried out superfine grinding, made into the sieve impalpable powder No. 9; The adjuvant screening increases the cosolvent of principal agent dissolving, has solved and guaranteed the dissolubility of said preparation in water; Select to prevent moisture absorption adjuvant, guarantee the vitro stability of preparation, guarantee effectiveness, the stability of preparation administration, better bring into play the effect of active component.
The specific embodiment:
Embodiment 1
Prescription:
Make altogether 100 bags, every bag 100 gram
Method for making: glycyrrhizic acid monoammonium is carried out superfine grinding, made into the impalpable powder of No. 9 sieves, with glycyrrhizic acid monoammonium and other drug components and the adjuvant dried of handling well; Take by weighing glycyrrhizic acid monoammonium after the processing and other medicines and selected filler, cosolvent, caking inhibiter, equivalent incremental method mix homogeneously by prescription; Packing; And get final product.
Embodiment 2
Prescription:
Make altogether 100 bags, every bag 100 gram
Method for making: with embodiment 1.
Embodiment 3
Prescription:
Make altogether 100 bags, every bag 100 gram
Method for making: with embodiment 1.
Embodiment 4
Prescription:
Make altogether 100 bags, every bag 100 gram
Method for making: with embodiment 1.
Embodiment 5 medicine water solublity and study on the stability:
The experiment of medicine water solublity: in above-mentioned example prescription ratio, each prepares 100 bags.Each example is got 3 bags, and every bag 100 gram all can be dissolved in (20 ℃) in 40 premium on currency fully, and the preparation dissolubility satisfies the poultry clinical administration and adopts " thirsty method " (concentrating high concentration drinking-water) needs.
Preparation stability is investigated: above-mentioned example prescription, prepare three batches, each batch all prepares 100 bags, according to accelerated test requirement in " Chinese veterinary pharmacopoeia " 2010 editions soluble powder stability experiments, press powder preparation stability high spot reviews index request, character, content, granularity, related substance, the outward appearance uniformity, moisture all meet " Chinese veterinary pharmacopoeia " (2010) version requirement.
Claims (2)
1. poultry are with compound glycyrrbizic acid monoamine soluble powder; it is characterized in that take glycyrrhizic acid monoammonium, glycine, methionine, taurine and glutamine as active component; be equipped with other pharmaceutically acceptable filleies, cosolvent and caking inhibiter and make soluble powder, each amounts of components is:
Glycyrrhizic acid monoammonium 150-450 weight portion
Glycine 150-350 weight portion
Methionine 150-350 weight portion
Taurine 1800-3100 weight portion
Glutamine 750-2250 weight portion
Cosolvent 100-400 weight portion
Caking inhibiter 100-400 weight portion
Filler adds to 10000 weight portions;
Wherein, described filler be selected from lactose, sucrose, anhydrous glucose, anhydrous sodium sulfate, sodium bicarbonate, sodium carbonate, mannitol, sorbitol, soluble starch, xylitol or the microcrystalline Cellulose any one or multiple;
Described cosolvent be selected from sodium sulfite, sodium sulfite, sodium salicylate, hexamethylenamine, sodium lauryl sulphate, polyvinylpyrrolidone, poloxamer, citric acid, sodium citrate, sodium dihydrogen phosphate or the sodium hydrogen phosphate any one or multiple;
Described caking inhibiter be selected from micropowder silica gel, Kaolin, crospolyvinylpyrrolidone, sodium bicarbonate, pregelatinized Starch or the sodium sulfate any one or multiple.
2. poultry claimed in claim 1 is characterized in that first glycyrrhizic acid monoammonium being carried out superfine grinding with the preparation method of compound glycyrrbizic acid monoamine soluble powder, cross sieve No. 9; Take by weighing glycyrrhizic acid monoammonium raw material, glycine, methionine, taurine, glutamine and filler, cosolvent, caking inhibiter after the processing by recipe quantity, increase progressively mixing method by equivalent, mix homogeneously, packing, and get final product.
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| CN1686151A (en) * | 2005-04-04 | 2005-10-26 | 张红军 | Enteric dissolving preparation of compound glycyrrbizic acid and its salt and its preparation method |
| CN100358531C (en) * | 2005-06-10 | 2008-01-02 | 北京正大绿洲医药科技有限公司 | Glycyrrhizin drop pills and preparation method thereof |
| CN1957943A (en) * | 2005-11-04 | 2007-05-09 | 何岩 | Injection of monoamine cysteine of glycyrrhizicacid and preparation |
| CN101288651A (en) * | 2008-06-20 | 2008-10-22 | 孙向阳 | Compound glycyrrhizin dispersible tablet and preparation method thereof |
| CN101317852B (en) * | 2008-06-27 | 2010-06-30 | 张勇 | Powder injection of compound glycyrrhizic acid glycosides and preparation method thereof |
| CN101766641A (en) * | 2010-01-20 | 2010-07-07 | 北京凯因科技股份有限公司 | Compound glycyrrhizin injection preparation |
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