CN101904856A - Application of 1,6-diphosphofructose and derivative thereof in preparing animal medical health care products - Google Patents
Application of 1,6-diphosphofructose and derivative thereof in preparing animal medical health care products Download PDFInfo
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Abstract
The invention relates to an application of 1,6-diphosphofructose and a derivative thereof in preparing animal medical health care products, belonging to the field of health care products for animals. The 1,6-diphosphofructose and the derivative thereof are applied to preparing medicines for preventing or curing myocardial ischemia, angiocardiopathy, shock and various untoward effects caused by energy shortage and enhancing the immunity of the animals. Every kilogram of the animals need 250-1,000 mg of the 1,6-diphosphofructose or the derivative thereof per 1kg of weight every day, and the 1,6-diphosphofructose or the derivant thereof is used once a day for 3-5 consecutive days. The invention provides a new application range for energy reinforcers of the 1,6-diphosphofructose and the derivative thereof which are widely used for national clinic on human, provides new resources for the research field of veterinary medicines and also provides excellent animal medical health care medicines for livestock breeding.
Description
One, technical field
The present invention relates to 1, the application in preparation animal medicine and animal health product of 6-fructose diphosphate and derivant thereof is new practical application, belongs to medicine for animals and animal health product field.
Two, background technology
1, (fructose 1, and 6-diphosphate FDP) is naturally occurring a kind of chemical compound in the cell for the 6-fructose diphosphate, be the important intermediate that cell produces in glycolytic pathway, in cell, produce pharmacological action by the activity of regulating some enzymes in the carbohydrate metabolism.
At first; FDP can permeate through cell membranes enter in the cell; participate in regulating multiple metabolic process in the cell from cellular and molecular level; thereby improve the energy metabolism of cell; increase the energy utilization; suppress the generation of free radical; and protecting myocardial cell, vascular endothelial cell, hepatocyte, kidney brain, lung and small intestinal etc. are avoided anoxybiotic infringement; can also prevent the poisoning and the toxic and side effects of some chemical substance and drug-induced cardiac muscle and other histoorgans effectively; acceleration of tissue repair is safeguarded organ dysfunction.FDP clinically can be separately or auxiliary making be used for treating tissue ischemia, anoxia and the organ injury that a variety of causes causes, cure the ancillary drug that generally is used in clinical as multiple metabolic diseases such as coronary heart disease, acute myocardial infarction, renal failure, acute cerebral infarction, chronic hepatitis gravis, pneumonia the people.
Simultaneously, 1, the 6-fructose diphosphate is the important intermediate in the glucose metabolism process, can reduce the dependency of body to aerobic metabolism, quickening phosphoric acid ketenes formula acetone acid transforms to acetone acid, increase human body energy, and directly enter in the cell as energy substrate energize, from energy, a part glucose produces 2 ATP merely, and a part FDP produces 4 ATP, be that a part FDP can increase by 2 ATP, provide lot of energy so 1,6 fructose diphosphate is can be rapider stable, keep biological organs and function of organization.
In treating epidemic disease of domestic animals control in recent years, because immunosuppressant causes or the relevant disease of secondary is more and more, refractory more and more, poultry are after the infection that suffers antibacterial and virus, the at first under attack and damage of each histoorgan, slow down and disorder along with body is metabolic, human body energy is supplied with serious the hysteresis or deficiency, thereby easier histoorgan depletion and the afunction of causing, sb.'s illness took a turn for the worse thereby make, various immunosuppressant class diseases have been destroyed animal immune system simultaneously, passivation the immunne response of body, thereby make being exposed in all unfavorable factors and the disease that body has no to protect, cause tremendous loss to aquaculture, energy hardening agent for animals thus and immunostimulant for animals become the focus that use in market gradually, and 1, the 6-fructose diphosphate can be stablized rapidly after use and offers the big energy of histoorgan (particularly cardiac muscle), make histoorgan can the opposing bacteriovirus infection in damaged tissue repair, can improve simultaneously the immunocompetence of animal body again, eliminate immunosuppressant, therefore all effects will make 1, and the 6-fructose diphosphate is in veterinary's field of veterinary performance enormous function.
Cure in the clinical drug therapy the modern, 1, the 6-fructose diphosphate often (for example: 1 is employed with the form of various salts, 6-fructose diphosphate sodium, magnesium, calcium etc.), so both but enhancing body was to 1, the absorbability of 6-fructose diphosphate, additional metal ion has been introduced new effect for this medicine again simultaneously, same mechanism also is employed and confirms in animal medicine, for example 1,6-fructose diphosphate calcium is keeping 1, outside the effect of 6-fructose diphosphate, and the rehabilitation after can preventing the osteoporosis of animal again and be beneficial to fracture simultaneously; 1,6-fructose diphosphate magnesium is more outstanding aspect stabilizing blood pressure, adjusting cardiomotility, enhancing lymphocytic emiocytosis ability.So 1,6-fructose diphosphate derivant has expanded 1, and the medicinal efficacy of 6-fructose diphosphate has improved 1, and the medical value of 6-fructose diphosphate is 1, and the application of 6-fructose diphosphate in animal medicine made something perfect even more perfect.
Three, summary of the invention
Technical problem:
The invention provides a kind of 1, the new application in animal medicine and animal health product of 6-fructose diphosphate and derivant thereof.Provide a kind of new, have no side effect and have prevention or treatment animal cardiac muscle ischemia, cardiovascular disease, shock and because energy shortage or the caused various untoward reaction of metabolism disorder and the medicine that strengthens animal immunizing power.
Technical scheme:
1,6-fructose diphosphate and derivant thereof are as preparation prevention or treatment animal cardiac muscle ischemia, cardiovascular disease, shock, hepar damnification and hepatopathy, kidney injury and nephropathy, pneumonia and various subclinical pulmonary heart disease are because the application in the medicine of energy shortage or multiple organ failure, MOF that metabolism disorder causes and shock, described 1,6-fructose diphosphate and derivant thereof specifically are meant: 1, and 6-fructose diphosphate and 1,6-fructose diphosphate sodium, magnesium, calcium salt compounds.Every day, every kg body weight was used 250mg-1000mg1,6-fructose diphosphate or derivatives thereof, every day 1 time, logotype 3-5 days, pharmaceutical formulation comprises: liquid drugs injection, powder needle injection type, powder loose, oral liquid and paste are licked the agent peroral dosage form, also comprise the FDP combination drug that contains medical additive, excipient.In described preparation 1,6-fructose diphosphate and derivant thereof account for 0.1%～100% of mixture weight.
1,6-fructose diphosphate and derivant thereof are as the application in the medicine of preparation enhancing animal immunizing power, comprise humoral immunization and cellular immunization, pressed continuous application 20 days, use once a day, with 1,6-fructose diphosphate and derivant thereof are with the application of 30-90mg/kg as interpolation medicine in the drinking-water of preparation chicken, or medicinal application to add in the feedstuff of 60-120mg/kg as the preparation pig, described 1,6-fructose diphosphate and derivant thereof specifically are meant: 1, and 6-fructose diphosphate and 1,6-fructose diphosphate sodium, magnesium, calcium salt compounds.
Beneficial effect:
The present invention is first with 1, and 6-fructose diphosphate and derivant thereof are applied in animal medicine (animal health product) field.Relate generally to conduct preparation prevention or treatment animal cardiac muscle ischemia, cardiovascular disease, shock and because the application in the medicine of caused various untoward reaction of energy shortage and enhancing animal immunizing power.With 1,6-fructose diphosphate magnesium merges the heart failure dog to bronchopneumonia and treats experiment; Studied 1 simultaneously, 6-fructose diphosphate magnesium (FDP-Mg) is to the protective effect mechanism of myocardial damage due to the isoproterenol (Iso); And with 1,6-fructose diphosphate (FDP-Na, FDP-Ca) is fed to laboratory animal (pig, chicken) respectively, and growth performance, immunologic function to laboratory animal after experiment finishes detect comparison, and the result who draws is as follows:
1. adopt 1,6-fructose diphosphate magnesium merges the heart failure dog to bronchopneumonia and carries out injection for curing, using dosage for by every day every kg body weight 250mg vein splash into, every day 1 time, logotype 5 days, the result proves 1,6-fructose diphosphate magnesium use group recovers normal gradually than the matched group heart rate, peripheral circulation depletion is clearly better, and therapeutic effect is obvious.
2. give FDP-Mg (250-1000mg/kg when give Iso every day; 3d) can obviously reduce serum CK, LDH level, suppress CK, LDH release in the cardiac muscular tissue, improve serum and SOD of heart tissue activity; reduce the MDA level, rat myocardium from injury due to the Iso is had good protective action.
3. use 1,6-fructose diphosphate (FDP-Na, FDP-Ca) respectively to laboratory animal (pig, chicken) feeds, experiment finishes the growth performance (weightening finish of back to laboratory animal, feed conversion rate, feedstuff-meat ratio), immunologic function (blood parameters, lymhocyte transformation rate, the immune organ index, antibody titer) detects, the result proves: with 60mg/kg dosage is that experimental chicken was drunk water absorption FDP-Ca after 20 days, the experimental chicken weightening finish increases by 8.4%, feedstuff-meat ratio descends 12.5%, cell and humoral immunization have obtained tangible reinforcement simultaneously, and be that experiment pig is carried out spice and taken in FDP-Na after 20 days with 90mg/kg dosage, the experiment pig weightening finish increases by 7.2%, feedstuff-meat ratio descends 15.2%, diarrhea rate has descended 20%, cell and humoral immunization have obtained tangible reinforcement simultaneously, and use is without any side effects.
Above evidence: 1,6 fructose diphosphate and derivant thereof can be stablized rapidly after use and offer the big energy of histoorgan (particularly cardiac muscle), make histoorgan can be in the opposing bacteriovirus infection damaged tissue repair, can be used for prevention or treatment animal cardiac muscle ischemia, cardiovascular disease, shock and because the caused various untoward reaction of energy shortage.
Simultaneously, 1,6-fructose diphosphate and derivant thereof can obviously be improved the growth of animal performance after as feed additive animal being fed, improve food conversion ratio, and the cellular immunization and the humoral immunization of reinforcement body, remove immunosuppressant, and use is without any side effects.
The present invention for Chinese people doctor clinical in widely used energy hardening agent---1,6-fructose diphosphate and derivant thereof provide new range of application, for veterinary drug research and development field provides new resources, more aquaculture provides good animal health medicine.
Four, the specific embodiment
Following examples will the invention will be further described, but to the present invention without limits.
Date processing: data are represented with mean+SD.SPSS11.0 for Windows software is used in the t check.P≤0.05 thinks to have the significance of difference.
Implemented one: 1,6-fructose diphosphate magnesium (FDP-Mg) merges the treatment experiment of heart failure dog to 51 routine bronchopneumonia
1 materials and methods
1.1 physical data
The case of getting is the trouble dog that year January in January, 2006 to 2010, southern agricultural pets hospital was gone to a doctor, and the diagnostic criteria of bronchopneumonia merging heart failure is examined the standard revision draft with reference to the people doctor about the concurrent heart failure of infantile pneumonia and carried out.51 routine sick dogs are divided into 2 groups at random, and 30 examples are organized in treatment, male dogs 18 examples, female dog 12 examples, age＜6 month 17 example, 6 months～1 years old 9 example, 1～3 years old 4 example.Matched group 21 examples, male dogs 13 examples, female dog 8 examples, age＜6 month 11 example, 6 months～1 years old 7 example, 1～3 years old 3 example.Two groups of ages, sex, morbidity season, the course of treatment and state of an illness weights similar substantially (P＞0.05) have comparability.
1.2 Therapeutic Method
Two groups of cases all adopt ceftiofur sodium infection, deslanoside heart tonifying, FRUSEMIDE diuresis, promethazine hydrochloride calmness, oxygen uptake and Energy mixture amount (ATP 40mg+CoA 200U+ vitamin C 5.0g) etc. to carry out conventional therapy.The treatment group adds on the basis of conventional therapy with FDP-Mg (250mg/kg), is made into 10% solution vein with water for injection and splashes into every day 1 time, logotype 5 days.
1.3 observation index
From treatment beginning every 4 hours recording respiration, heart rate number of times, liver size and visual mucosa cyanosis situation respectively, until breathe, heart rate is steady, the liver size is normal.Untoward reaction in the heart failure control time of concrete observation morbidity animal, cough with asthma improvement time, hello sound extinction time and the FDP-Mg application process etc.
2 results
See that from therapeutic effect FDP-Mg treatment group can control heart failure and cough with asthma quickly, hello sound extinction time, heart failure are corrected time, breathing stationary time etc. and are all shortened, learn by statistics and handle, the treatment group is compared with matched group, has significant difference (P＜0.01), average oxygen time also shortens significant difference (P＜0.05).And the obvious adverse reaction of not seeing FDP-Mg in the treatment.Two groups of clinical efficacies relatively see Table 1.
Table 1 liang group therapeutic outcome relatively
Annotate: two groups of different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
3 discuss and conclusion
Pneumonia and heart failure are the critical illness of toy in clinical, belong to congestive heart failure, the also corresponding minimizing of coronary blood supply during heart failure, myocardial cell is in the hypoxic-ischemic state, causes the phosphofructokinase inactivation, and endogenous FDP reduces, ATP produces not enough, oxygen-derived free radicals increases, and causes amyocardia, and cardiac output reduces.It is the major reason of young animal death.
FDP is the important intermediate in the glucose metabolism process, can pass through feedback mechanism activating phosphatase fructokinase, make FDP rising in the cell, promote glycolysis and bypass metabolism, ATP generates, increase cell membrane stability, improve myocardium shrinkage function, cardiac output is increased, FDP also can suppress oxygen-derived free radicals release simultaneously, alleviate cardiac damage, blood circulation promoting.Thereby the cardiac muscular tissue of Hypoxia and ischemia is protected, improves cardiac function.Its mechanism of action can reduce: 1. improve the energy metabolism of hypoxic cell; 2. membrane stabilizing action, 3. Hangzhoupro peroxidating, the microcirculation when 4. improving anoxia; 5. arrhythmia; 6. strengthen myocardial contraction, improve cardiac function.
This result shows that the treatment group that is added with FDP has significant difference with the matched group comparison at aspects such as hello sound extinction time, heart failure correction time, breathing stationary times aspect clinical efficacy, prompting merges the heart failure curative effect certainly with FDP treatment bronchopneumonia, is worthy of popularization.
Implemented two: 1, the 6-fructose diphosphate causes the protective effect research of rat myocardium from injury to isoproterenol
1 material and method
1.1 material and main agents
Chengdu Instruement Factory produces LMS-2B type two and leads physiograph, Japanese photoelectricity medical electronic apparatus company limited is produced ECG-0851K type electrocardiograph, day island proper Tianjin CL-7200 type automatic clinical chemistry analyzer, Switzerland AUL company produces AVL-988-3 type electrolyte analyser; Creatine kinase (creatine kinase, CK), lactic acid dehydrogenase (lactate dehydrogenase, LDH), (phosphorus P) measures test kit and builds up Bioisystech Co., Ltd's production by Nanjing Phos; FDP-Na is that Shanghai Xinya Pharmaceutical Industry Co. Ltd. produces, and every gram contains FDP0.75g, and the molecular weight of FDP is 340, and FDP content conversion administration is pressed in experiment; FDP-Mg is provided by Nanjing University of Technology, and molecular weight is 364, and wherein the molecular proportion of FDP: Mg is 1: 1, and content of magnesium is 6.59%, and product purity is more than 95%; Magnesium sulfate is analytical pure, is produced by Shanghai chemical reagent factory, and Iso is produced by Tian Feng pharmaceutical factory, Shanghai.
1.2 experiment grouping and animal model
70 of Wistar rats, male and female half and half, body weight 200-250g, Nanjing Military Command's hospital general's Experimental Animal Center provides, and divides 7 groups at random, 10 every group.The myocardial damage group: subcutaneous multi-point injection isoproterenol (Iso) 8mg/kg, inject same dose again behind 24h, the 48h.FDP-Mg protection group: the tail vein gives FDP-Mg 250,500 and 1000mg/kg respectively in per injection Iso, wherein 50,100 and 200mg/kg finish in 10min angular vein injection, residual drug is constant infusion in 1h.FDP-Na, the magnesium sulfate matched group: the tail vein gives FDP-Na 530mg/kg and magnesium sulfate 150mg/kg respectively in per injection Iso, wherein FDP-Na 100mg/kg and magnesium sulfate 30mg/kg finish in the injection of 10min angular vein, and residual drug is constant infusion in 1h.According to molecular weight conversion, FDP-Mg500mg respectively with 530mg FDP-Na in contained Mg in contained FDP and the 150mg magnesium sulfate
2+Quite.The normal control group: multiple spot is subcutaneous to be given and the isopyknic normal saline of administration group with the tail vein.Respectively organize rat in the experimental implementation process and all remain on waking state.
1.3 testing index and method
Disconnected neck is got blood behind cardiac muscle and the serum enzymatic determination rat last injection Iso 60min, and centrifugal (2400 * g) make serum for examination.Speed is cored dirty, removes trunk, and atrium and connective tissue shred, and makes 10% homogenate with phosphate buffer (pH 7.4) for medium milling, and centrifugal (it is to be measured to get supernatant after 30000 * g).The N-acetylcystein method is adopted in the CK determination of activity, and the acetone acid system is adopted in the LDH determination of activity.
Cardiac muscle, serum superoxide dismutases vigor and mda content are measured and are prepared cardiac muscular tissue's supernatant and serum as stated above, and pyrogallol autoxidation method is measured the SOD vigor, and the thiobarbituricacid method is measured MDA content.
2 results
2.1 influence to serum zymetology and lipid peroxidation product content
The myocardial damage group is compared with the normal control group, and serum CK and LDH level obviously raise, and shows that cardiac muscle impaired back CK and LDH are released into blood and increase.Give serum CK and LDH level that FDP-Mg then can dose dependent reduces due to the Iso damage and raise, the effect of 1000mg/kg FDP-Mg group is the most obvious.The myocardial damage group is compared with the normal control group, and activity of SOD in serum obviously reduces, and MDA content obviously raises.Give FDP-Na and can significantly improve activity of SOD in serum, reduce MDA content, magnesium sulfate then there are no significant effect (P＞0.05).Giving FDP-Mg can improve activity of SOD in serum by dose dependent, reduces MDA content, and the active rising of 1000mg/kg FDP-Mg group SOD is better than the FDP-Na group, reaches normal control group level substantially, and detailed results sees Table 2.
Table 2 FDP-Mg is to the influence (n=10) of serum zymetology and lipid peroxidation product content
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.2 influence to cardiac muscular tissue's zymetology and lipid peroxidation product content
Myocardial damage group CK of cardiac muscular tissue and LDH level significantly reduce, and FDP-Na and magnesium sulfate all can obviously reduce myocardium CK and the LDH release that the Iso damage causes.The release of CK and LDH obviously reduces in FDP-Mg 500 and the 1000mg/kg group cardiac muscular tissue, and effect significantly is better than FDP-Na and magnesium sulfate group.FDP-Mg 250mg/kg organizes myocardium CK level and also obviously raises than the damage group.Myocardial damage group SOD of heart tissue is active obviously to be reduced, and lipid peroxidation product MDA content obviously raises.Give FDP-Na simultaneously and can significantly improve the SOD of heart tissue activity, reduce the MDA level, magnesium sulfate does not then have effect (P＞0.05).Give FDP-Mg energy dose dependent rising SOD of heart tissue activity simultaneously, reduce the MDA level, 1000mg/kg FDP-Mg group reduces more obvious than the FDP-Na group to myocardium MDA level, reach the normal group level, and detailed results sees Table 3.
Table 3 FDP-Mg to the influence of cardiac muscular tissue's zymetology and lipid peroxidation product content (weight in wet base, n=10)
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
3 discuss and conclusion
Enzyme such as CK, LDH is released into how much being proportionate with the myocardial necrosis degree of blood in the cardiac muscle.This experiment FDP-Na, magnesium sulfate and FDP-Mg all can alleviate myocardial damage due to the Iso, show as obvious reduction serum CK and LDH level, suppress that CK and LDH discharge in the cardiac muscular tissue.Iso causes the mechanism of myocardial damage to think at present because the generation of oxygen-derived free radicals, due to the lipid peroxidation and intracellular calcium overload of cell membrane, the myocardial metabolism disorder myocardial damage take place and development in also play an important role.FDP can promote sugared anerobic glycolysis, suppresses aerobic oxidation, thereby reduces the generation of oxygen-derived free radicals; FDP also has the antioxidation to the similar effectiveness of SOD, can directly suppress the generation of granulocyte oxygen-derived free radicals.Similar to FDP, FDP-Mg can significantly improve serum and SOD of heart tissue activity, reduces lipid peroxidation product MDA content, and the anti-peroxidation effect may be one of important mechanism of its anti-myocardial damage.
Losing of magnesium is the important symbol of cell injury in the cell, and the change of human body magnesium can influence K
+, Ca
2+Metabolism, and influence resting membrane electric potential and cell multipole. Mg in the cell
2+Reduce, may be relevant with intracellular Ca2+ and/or activation glycogenolysis.Mg supplementation can promote intracellular energy to produce, and reduces phosphagen and Mg-ATP and produces.
This experiment demonstration, during myocardial damage, serum and myocardium Mg
2+Content reduce, the ATP metabolism reduces the content that makes myocardium Phos and reduces.FDP-Mg can significantly improve cardiac muscle and serum Mg to the dual function characteristics of myocardial metabolism performance FDP and magnesium
2+Level.In a word, FDP-Mg has protective effect to the Iso myocardial damage, effect and FDP-Na, and magnesium sulfate is similar or more excellent, may with anti-peroxidation and to improve myocardial metabolism relevant.
Implement 31,6-fructose diphosphate calcium (FDP-Ca) is to fertility performance, the Immune Function test of chicken
1 materials and methods
1.1 physical data
Choose the uniform healthy chick of 21 ages in days, 160 plumage body weight, be divided into 4 groups at random, 40 every group, chicken free choice feeding and drinking-water, vaccine immunity and raising are carried out routinely, and grouping and disposition are as shown in table 4, and experiment periods is 20 days.Weigh when testing preceding and off-test, write down the weight of food consumption every day, 1,6-fructose diphosphate calcium adds in drinking-water.
The grouping of table 4 test chicken and processing
Annotate: each medicine adds for drinking-water, and continuous 20 days, once a day.
1.2 experimental technique:
1.2.1 the index of fertility performance:
After experiment finishes, to experimental chicken increase weight, the statistical computation of feedstuff-meat ratio.
1.2.2 the mensuration of blood parameters
First after the medication, get 20 chickens at random experiment 8:00 in the 20th day early morning (stopping before this to raise 12 hours) every group, the heart blood sampling, every part of blood sample is all put into the test tube of EDTA anticoagulant tube and no anticoagulant respectively, uses the check of blood biochemical automatic analyzer after the blood specimen collection, and anticoagulation is measured total white blood cells, lymphocyte number, non-anticoagulation is measured serum albumin (globulin, albumin) content in the serum.
1.2.3 immune organ index
Extract 20 chickens immediately out for every group in the 20th day blood sampling back and weigh, slaughter blood sampling back all blood-letting, carefully takes out thymus, and spleen and fabricius bursa are rejected and adhered to fatty tissue, accurately weighs after blotting blood and slime with filter paper, and record weight is calculated the immune organ index.Immune organ (thymus, spleen and fabricius bursa) index=immune organ weight (mg)/test chicken live-weight (g)
1.2.4 antibody titer influence test
Test group and matched group carried out the immunity (1 plumage part) of newcastle disease vaccine at the 0th day, experiment back the 10th day, and the 20th day, the blood sampling separation of serum was measured antibody titer with blood clotting inhibition method.
2 result of the tests
2.1FDP-Ca improvement to the experimental chicken fertility performance
Test after 20 days, FDP-Ca sees Table 5 to the influence of chicken body fertility performance, and its fertility performance to chicken all has raising effect in various degree, and there were significant differences than other groups for wherein middle and high dosage group.
Table 5 FDP-Ca is to the influence of test chicken fertility performance
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.2 FDP-Ca is to the improvement of experimental chicken blood parameters
After 20 days, FDP-Ca sees Table 6 to chicken body blood parameters in the experiment, compares chicken in the experimental group with matched group
Blood parameters in various degree raising is all arranged.
Table 6 FDP-Ca is to the influence of the 20th day blood parameters of test chicken
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.3 FDP-Ca is to the exponential influence of experimental chicken immune organ
The immune organ index of each group of experiment sees Table 7, and wherein middle high dose group has notable difference than other groups, and as seen, the FDP-Ca of middle high dose has obviously promoted the immune organ of chicken body to reach maturity.
Table 7 FDP-Ca is to the exponential influence of test chicken immune organ (unit: mg/g)
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.4 FDP-Ca is to the influence of experimental chicken newcastle epidemic disease antibody titre
Experimental chicken carries out hanging down 10 days, the 20th day after the newcastle disease vaccine immunity in the experiment, and newcastle epidemic disease antibody titre of each group of experiment sees Table 8, and wherein middle high dose group has notable difference than other groups, and as seen, the FDP-Ca of middle high dose has obviously promoted the antibody generation of chicken body.
Table 8 FDP-Ca to immunity after the 10th day, respectively organized the influence of newcastle epidemic disease antibody titre in 20 days
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
Implement 41,6-fructose diphosphate sodium (FDP-Na) is to fertility performance, the Immune Function test of pig
1 materials and methods
1.1 physical data
Choose preceding 5 days 40 of the ablactational baby pig (male and female half and half) of wean, be divided into 4 processed group at random, 10 every group, powder is fed, on a small quantity repeatedly, free choice feeding, drinking-water, the conventional raising and immunity, FDP-Na carries out spice and feeds, experimental period is 20 days, weighs before the test, and grouping and disposition are as shown in table 9:
The grouping of table 9 test pig and processing
Annotate: each medicine is that spice adds, continuous 20 days, once a day.
1.2 test method
1.2.1 the fertility performance index detects
After the off-test, respectively every group is weighed and experiment with computing phase consumption feedstuff, calculate experimental period weightening finish, diarrhea disease percentage, feedstuff-meat ratio respectively.
1.2.2 blood parameters
First after the medication, get 5 experiment pig at random experiment 8:00 in the 20th day early morning (stopping before this to raise 12 hours) every group, carry out the vena cava anterior blood sampling, every part of blood sample is all put into the test tube of EDTA anticoagulant tube and no anticoagulant respectively, uses the check of blood biochemical automatic analyzer after the blood specimen collection, and anticoagulation is measured total white blood cells, lymphocyte number, non-anticoagulation is measured serum albumin (globulin, albumin) content in the serum.
1.2.3 immune organ index
Extract 5 experiment pig immediately out for every group in the 20th day blood sampling back and weigh, slaughter blood sampling back all blood-letting, carefully takes out thymus, and spleen proposes to adhere to fatty tissue, accurately weighs after blotting blood and slime with filter paper, and record weight is calculated the immune organ index.Immune organ (thymus, spleen) index=immune organ weight (mg)/test chicken live-weight (g)
1.2.4 antibody titer influence test
Test group was carried out the swine Fever Vaccine immunity on the 0th day in test, measured the 10th day, the 20th day hog cholera antibody titre.
2 result of the tests
2.1 FDP-Na is to the improvement of experiment pig fertility performance
Test after 20 days, FDP-Na sees Table 10 to the influence of experiment pig fertility performance, and its fertility performance to experiment pig all has raising effect in various degree, and wherein middle high dose group has notable difference than other groups.
Table 10 FDP-Na is to the influence of test pig fertility performance
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.2 FDP-Na is to the improvement of experiment pig blood parameters
In the experiment the 20th day, FDP-Na saw Table 11 to the pig blood biochemical indicator, and its blood parameters to pig all has raising effect in various degree.
Table 11 FDP-Na is to the influence of the 20th day blood parameters of test pig
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.3 FDP-Na is to the exponential influence of experiment pig immune organ
The immune organ index of each group of experiment sees Table 12, and wherein middle high dose group has notable difference than other groups, and as seen, the FDP-Na of middle high dose has obviously promoted the immune organ of experiment pig to reach maturity.
Table 12 FDP-Na is to test pig immune organ index (unit; Mg/g)
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
2.4 FDP-Na is to the influence of experiment pig hog cholera antibody titre
Experiment pig was carried out after the swine Fever Vaccine immunity the 10th day, the 20th day in the experiment, and hog cholera antibody titre of each group of experiment sees Table 12, wherein in high dose group have notable difference than other groups, as seen, the FDP-Na of middle high dose has obviously promoted the antibody generation of experiment pig.
Table 12 FDP-Na is to respectively organizing swine fever ELISA antibody blocking rate to immunity after 20 days
Annotate: the different persons of same column data shoulder mark represent significant difference, and lower case is represented P＜0.05; Capitalization is represented P＜0.01.
Claims (6)
1.6-fructose diphosphate and derivant thereof the application in preparation animal healthcare products, be meant that it is as preparation prevention or treatment animal cardiac muscle ischemia, cardiovascular disease, shock, hepar damnification and hepatopathy, kidney injury and nephropathy, because energy shortage or the caused various untoward reaction of metabolism disorder, pneumonia and various subclinical pulmonary heart disease, because the application in the medicine of energy shortage or multiple organ failure, MOF that metabolism disorder causes and shock, described and derivant specifically is meant 1,6-fructose diphosphate and 1,6-fructose diphosphate sodium, magnesium, calcium salt compounds.
2. application according to claim 1 is characterized in that, by using every day 1 time, logotype 3-5 days, uses 1 in the used medicine of every kilogram of the weight of animals every day, 6-fructose diphosphate or derivatives thereof 250mg-1000mg.
3. application according to claim 1 and 2 is characterized in that, described pharmaceutical preparation comprises: liquid drugs injection, powder needle injection type, powder loose, oral liquid and paste are licked the agent peroral dosage form, also comprise the FDP combination drug that contains medical additive, excipient.
4. application according to claim 1 and 2 is characterized in that, in described pharmaceutical preparation 1,6-fructose diphosphate and derivant thereof account for 0.1%～100% of mixture weight.
5. application according to claim 3 is characterized in that, in described pharmaceutical preparation 1,6-fructose diphosphate and derivant thereof account for 0.1%～100% of mixture weight.
6.1,6-fructose diphosphate and derivant thereof are as the application in the medicine of preparation enhancing animal immunizing power, comprise humoral immunization and cellular immunization, pressed continuous application 20 days, use once a day, with 1,6-fructose diphosphate and derivant thereof are with the application of 30-90mg/kg as interpolation medicine in the drinking-water of preparation chicken, or medicinal application to add in the feedstuff of 60-120mg/kg as the preparation pig, described 1,6-fructose diphosphate and derivant thereof specifically are meant: 1, and 6-fructose diphosphate and 1,6-fructose diphosphate sodium, magnesium, calcium salt compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2010102480081A CN101904856A (en) | 2010-08-06 | 2010-08-06 | Application of 1,6-diphosphofructose and derivative thereof in preparing animal medical health care products |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010102480081A CN101904856A (en) | 2010-08-06 | 2010-08-06 | Application of 1,6-diphosphofructose and derivative thereof in preparing animal medical health care products |
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| CN2010102480081A Pending CN101904856A (en) | 2010-08-06 | 2010-08-06 | Application of 1,6-diphosphofructose and derivative thereof in preparing animal medical health care products |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104706645A (en) * | 2013-12-11 | 2015-06-17 | 武汉威立得生物医药有限公司 | Application of fructose bisphosphate in preparation of drugs for treating hepatitis C virus (HCV) |
| CN104906117A (en) * | 2015-05-29 | 2015-09-16 | 武汉威立得生物医药有限公司 | Application of 1,6-fructose diphosphate in preparation of medicine for preventing and treating enveloped virus infection and virus inactivating agents |
| CN105248936A (en) * | 2015-10-15 | 2016-01-20 | 南京同凯兆业生物技术有限责任公司 | Application of fructose-1, 6-diphosphate dicalcium salt in layer feed additive |
| CN108378243A (en) * | 2018-05-17 | 2018-08-10 | 南京同凯兆业生物技术有限责任公司 | A kind of feed for sow additive and its application |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104706645A (en) * | 2013-12-11 | 2015-06-17 | 武汉威立得生物医药有限公司 | Application of fructose bisphosphate in preparation of drugs for treating hepatitis C virus (HCV) |
| CN104706645B (en) * | 2013-12-11 | 2017-08-01 | 武汉威立得生物医药有限公司 | Application of the fructose diphosphate in preventing and treating infection with hepatitis C virus medicine is prepared |
| CN104906117A (en) * | 2015-05-29 | 2015-09-16 | 武汉威立得生物医药有限公司 | Application of 1,6-fructose diphosphate in preparation of medicine for preventing and treating enveloped virus infection and virus inactivating agents |
| CN104906117B (en) * | 2015-05-29 | 2018-06-01 | 武汉威立得生物医药有限公司 | Application of the 1,6- diphosphofructoses in the drug of prevention infection of coated virus and virus inactivator is prepared |
| CN105248936A (en) * | 2015-10-15 | 2016-01-20 | 南京同凯兆业生物技术有限责任公司 | Application of fructose-1, 6-diphosphate dicalcium salt in layer feed additive |
| CN108378243A (en) * | 2018-05-17 | 2018-08-10 | 南京同凯兆业生物技术有限责任公司 | A kind of feed for sow additive and its application |
| CN108378243B (en) * | 2018-05-17 | 2021-05-25 | 南京同凯兆业生物技术有限责任公司 | Feed additive for sows and application thereof |
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