CN102091269B - Medicament for treating lead poisoning of ruminant - Google Patents
Medicament for treating lead poisoning of ruminant Download PDFInfo
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- CN102091269B CN102091269B CN2011100602074A CN201110060207A CN102091269B CN 102091269 B CN102091269 B CN 102091269B CN 2011100602074 A CN2011100602074 A CN 2011100602074A CN 201110060207 A CN201110060207 A CN 201110060207A CN 102091269 B CN102091269 B CN 102091269B
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Abstract
The invention discloses a medicament for treating lead poisoning of ruminant, composed by compounding vegetable medicines. The medicament disclosed by the invention comprises the following medicines in parts by weight: 3-30 of glabrous greenbrier rhizome, 3-35 of radix isatidis, 4-28 of liquorice, 3-20 of dangshen, 2-15 of coptis and 2-15 of tangle. Shown by tests, the medicament disclosed by the invention has a better lead removing effect, has higher cure rate, high effect taking speed and low toxic side effects on preventing and treating lead poisoning of ruminants, and has stable quality when stored under a prescribed condition.
Description
Technical field
The present invention relates to a kind of veterinary drug, particularly a kind ofly form, be used to treat the saturnine medicine of ruminant by compound plant medicine.
Background technology
Human make a large amount of pollutant get into environment in nature remodeling, when utilizing nature, produced many environmental problems, heavy metal is exactly one of common polluter.The environmental pollution of plumbous (Pb) increases the weight of along with the fast development of mankind's activity and industry day by day.Lead has very strong toxicity, has become one of " five poisonous creatures: scorpion, viper, centipede, house lizard, toad " (hydrargyrum, chromium, cadmium, lead, arsenic) in the heavy metal.Mining, metal smelting, vehicle exhaust are main sources plumbous in the environment.Mining mineral resource is that human so far maximum-norm changes earth surface view and the organized mankind's activity that destroys face of land ecosystem.Lead can pass through runoff and leaching polluted surface water and subsoil water, worsens hydrological environment, also can be through approach such as directly contact, food chain harm poultry and human health.The research of the sick integrated control technique of poultry lead poisoning; Improvement for ecological environment; The safety of animal products, the development of economic trade and human health is all with significant, also with the present stage conservation culture advocated of China; Low-carbon economy is closely related, therefore is the emphasis and the focus of research at present.Till settled the present, Chinese scholars has been studied lead poisoning from different perspectives, and is especially comparatively extensive to children ' s lead poisoning research, and a series of medicines are targetedly arranged simultaneously, but less to the research of animal lead poisoning, especially the lead poisoning of ruminant treatment rarely has report.
Summary of the invention
The present invention is a kind of saturnine medicine of ruminant of treating.
Medicine of the present invention is formed and each drug weight part is: Rhizoma Smilacis Glabrae 3~30, Radix Isatidis 3~35, Radix Glycyrrhizae 4~28, Radix Codonopsis 3~20, Rhizoma Coptidis 2~15, Thallus Laminariae (Thallus Eckloniae) 2~15.
Process for preparing medicine of the present invention is: each medicine water is soaked into post-heating fully decoct, get the water extract.Its use is to supply to use animal oral.
It is each medical material to be put into water soak into post-heating to 90 ℃ extraction 3 times fully that the present invention selects method for preparing, each 2 hours, merges medicinal liquid; (4000 change/min) 15min with centrifuge is centrifugal after solution to be concentrated cold to the room temperature; Remove deposition, ethanol is slowly added in the concentrated solution, make pure content reach 70%; After leaving standstill, carry out concentration, recovered alcohol does not get final product to there being the alcohol flavor.
The present invention is an object of study with heavy metal lead etc., through etiology analyses such as the sick incidence of heavy metal poisoninies such as the plumbous cadmium of complete survey poultry and the chamber inspections that experimentizes, makes up the lead poisoning animal model; Radix Isatidis, Radix Glycyrrhizae have been filtered out with Rhizoma Smilacis Glabrae; Radix Codonopsis; Rhizoma Coptidis, Thallus Laminariae (Thallus Eckloniae) are the pharmaceutical composition of principal agent, and this medical instrument has the remarkable efficacy of clearing away heat-damp and promoting diuresis, detoxifcation emergency.Rhizoma Smilacis Glabrae, Rhizoma Coptidis heat-clearing and toxic substances removing, dampness among the side of the present invention; The Radix Isatidis heat-clearing and toxic substances removing; The Radix Codonopsis invigorating the spleen and replenishing QI, the spleen invigorating lung benefiting; Thallus Laminariae (Thallus Eckloniae) hard masses softening and resolving, detumescencing diuresis add chelation; Radix Glycyrrhizae emergency detoxifcation is in harmonious proportion hundred medicines.All medicines are united the effect that utilization reaches clearing away heat-damp and promoting diuresis, detoxifcation emergency, can discharge intravital lead rapidly, and ill ruminant is got well.
The results showed that the present invention has Plumbum removing effect preferably.Prevent and treat the anti-animal lead poisoning of striving and have the fast and low advantage of its toxic and side effects of higher cure rate, produce effects.And medicine of the present invention storage quality under rated condition is stable.
The specific embodiment
Adopt: Rhizoma Smilacis Glabrae 3~30, Radix Isatidis 3~35, Radix Glycyrrhizae 4~28, Radix Codonopsis 3~20, Rhizoma Coptidis 2~15, Thallus Laminariae (Thallus Eckloniae) 2~15,6 herbal medicines.Accurately take by weighing each medicine in last several ratios, medical material is put into water and is soaked into post-heating to 90 ℃ fully and extract 3 times, and each 2 hours, merge medicinal liquid, centrifugal (15min of 4000 commentaries on classics/min) removes deposition with centrifuge after solution to be concentrated cold to the room temperature.Ethanol is slowly added in the concentrated solution, and the limit edged stirs, and makes pure content reach 70%.Left standstill 12 hours, supernatant is placed concentration tank, recovered alcohol is not to there being the alcohol flavor, and concentrated solution adds distilled water again to be regulated total amount and contain crude drug 1g, relative density 1.10-1.15 (50 ℃-60 ℃) to every milliliter.
Clinical trial
The lead poisoning mouse model makes up and control drug screening research: set up the lead poisoning model with mice, mice is after dying around the lead poisoning, and the blood lead content utmost point is significantly higher than normal group mice (P<0.01), and hemoglobin (Hb) is lower than the normal group mice.During the contamination, dye plumbous group and compare body weight gain situation difference not statistically significant with matched group, the diet of each contamination group mice, active situation are compared with matched group and are not seen obviously unusually; During the Drug therapy, it is variant that administration group and matched group are compared body weight gain.The negative control group mice Hb utmost point is significantly higher than other each group (P<0.01), and the Hb that takes traditional Chinese compound medicine group of the present invention is significantly higher than nutrient group, nutrient chelating agen and positive controls (P<0.05).Explain that taking therapeutic effect of the present invention significantly is superior to nutrient and nutrient chelating agen group.After irritating clothes medicine of the present invention; Each experimental mice MDA, GSH, T-AOC level and negative control group have significant difference; And difference is not remarkable between each experimental group; Not statistically significant, it is interior owing to dying MDA, GSH and the T-AOC that lead poisoning produces to explain that the present invention can eliminate the mice body, can improve the oxidation resistance of dying the lead poisoning mice.So the present invention can be used as the optimal drug combination of Plumbum removing.
The sheep clinical trial
After 100 close cold sheep adaptabilities of little tail of body weight were raised a week, it was subsequent use to randomly draw 10 blood sample collections, begins to irritate clothes 25mg/kg.w.d concentration lead acetate afterwards; Gather blood weekly, and (instrument: Jena, Germany Zeenit700 type) detect lead content respectively, the blood sample lead concentration is 0.0035 μ g/mL before the modeling to utilize NITRATE BY FLAME ATOMIC to absorb graphite furnace method; Sheep blood sample lead content reaches 1.225 μ g/mL after 8 weeks, and the clinical manifestation sheep only drinks water and appetite descends, and happiness is crouched motionless; The thin hair of body is burnt; Shed, a part sheep gingiva has spongy lead, thinks that in conjunction with plumbous testing result and clinical symptoms sheep lead poisoning model construction is successful.
Clinical trial: 100 sheep are divided into 5 groups at random; 30 of low dose group (30mL/g/d), 30 of middle dose groups (60mL/g/d), 30 of high dose group (90mL/g/d); 10 of medicine contrast DSMA (0.2g/mL/d) groups add 10 of negative control group (healthy animal); Handle each group according to above dosage, negative control group does not process.Gather the blood testing lead content weekly, the result shows with low dose group 30mL//day Plumbum removing best results, can blood lead content be reduced to 0.0228 μ g/mL by 1.225 μ g/mL after 4 weeks.
The result shows that lead content reaches 1.225 μ g/mL in the blood, can successfully make up the lead poisoning animal model so that 25mg lead/kg.w.d concentration lead acetate solution filling stomach is after 8 weeks; The caused animal that reaches 1.763 μ g/mL when blood lead content is poisoned to death.Select for use high, medium and low three dosage of the present invention to carry out the optimal dose screening, 30mL//day group Plumbum removing effect is best as a result.With 30mL/ only/day dosage 4 weeks can reduce blood lead content 80% after irritating clothes the present invention to sheep, result of the test is seen table 1.
Table 1 pharmaceutical intervention is to the influence (the μ g/ml of unit) of sheep blood lead content
Medicine of the present invention influences lead poisoning sheep body trace element
The present invention is to the influence of copper content in the lead poisoning sheep body: the result shows; After sheep was dyed lead poisoning, intravital copper level also decreased, after the present invention's treatment; Copper content and negative control group there was no significant difference in each experimental group sheep tissue; All rise to normal level, but copper content decreases in the blood, referring to table 2.
Table 2 Drug therapy is to the influence (the μ g/ml of unit) of copper content in the sheep whole blood
The present invention is to the influence of zinc content in the lead poisoning sheep body, and the result shows, after sheep is dyed lead poisoning; Intravital zinc element level decreases; Contamination sheep is after the present invention's treatment, and intravital zinc element level raises to some extent, and zinc element content does not have significant difference in low dose group and the negative control group tissue; Explain that low dose group of the present invention is to the zinc element level effect of increasing significantly in the lead poisoning animal body, referring to table 3.
Table 3 Drug therapy is to the influence (unit: μ g/ml) of zinc content in the sheep blood
In order to estimate the influence of the present invention to lead poisoning sheep blood parameters
Detected the blood parameters of lead poisoning sheep, the result show respectively organize the lead poisoning model behind the oral administration lead acetate in the mouse blood CREA, SAT, ALT, ALP content rising is in various degree arranged, wherein the high dose group ascensional range is maximum; TP, ALB content have different decline in addition, and the high dose group fall is maximum; The above content no change of negative control group.After showing oral lead acetate, the hepatic and renal function of sheep has infringement in various degree, and high dose group infringement is obviously, the oral administration lead acetate be described after the modeling of sheep lead poisoning model successfully.After the present invention's treatment; Each item index be tending towards normal and the DMSA medication therapy groups relatively, the present invention is to the repair of the hepatorenal damage that caused by lead poisoning and DMSA effect quite; The two there was no significant difference; And with the positive controls significant difference, the hepatorenal damage that the present invention causes lead poisoning be described, repair good safety evaluation
For clear and definite toxic and side effects of the present invention, in the hope of its safety is made accurately, objective appraisal, for the clinical trial medication provides scientific basis, guarantee clinical drug safety, carried out the toxicity test of said preparation.
Through mice is carried out LD of the present invention
50Test shows, press 5g/kg body weight, 8g/kg body weight, 10g/kg body weight to the mouse peritoneal injection after, observe continuously through 7d; All ANOMALOUS VARIATIONS is not all observed in aspects such as the spirit of mice, appetite, the colour of skin, secretions, eye, breathing, muscular movement, no dead mouse in the 7d; After slaughtering in the 8th day; Each organizes the mice internal organs does not all have pathological changes, and pathological characters is not found in the liver,kidney,spleen histological examination yet.Fail to find out the dosage of 100% dead mouse at the maximum administration volume 10mL/kg of the Cmax 1g/mL of medicine and mouse peritoneal injection.Therefore the lumbar injection mode can't be measured the LD of medicine
50, medicine lumbar injection LD
50>10g/kg.According to the result evaluation standard of " veterinary drug test requirement specification compilation ", the present invention is judged to actual nontoxic.
Measured maximum dosage-feeding as requested.In maximum dosage-feeding test, 4 gastric infusions in 16 hours are at every turn with the maximum administration volume administration of mouse stomach administration; Discomfort appears having slightly in animal after removing administration; Do not like activity, outside the degradation symptom, mice in order in 10 days of normal observation under the feed intake; Abnormal phenomena do not occur, and none is only dead.According to the account form of maximum tolerance multiple, this present invention is 80 times with respect to the maximum multiple of the clinical consumption of sheep.
In order to grasp because of using continuously the present invention to produce the toxicity and the order of severity, and development after the drug withdrawal and recovery situation, for drafting data for clinical drug use dosage reference is provided.Press 40000mg/kg, 20000mg/kg, 10000mg/kg and 0 dosage and give the mouse stomach administration, 28d has carried out subacute toxicity test of the present invention on mice continuously; In experimental period, each organizes mice diet, behavior; Feces is all normal; Physically well develop, do not have any poisoning symptom, and hemogram and blood physiology biochemical indicator, CREA, ALT, ALP, AST, TP, ALB are all in normal range.No obvious tissue pathologies change such as liver,kidney,spleen and small intestinal, each group (high dose, in, low dosage) of the present invention is not remarkable with the matched group comparing difference.The result shows that the present invention is safe.
In sum, the present invention has low toxicity, few side effects, can be used for clinical practice.
Stability study
These article are according to the listing terms of packing, and high light and high temperature have no significant change to character of the present invention, discriminating, pH, content; In temperature: 40 ℃ ± 2 ℃, relative humidity: quickened 3 months under 75% ± 5% condition, medicine character, discriminating, pH value, relative density, content do not have significant change.In temperature: 25 ℃ ± 2 ℃ relative humiditys: long term test is 24 months under 60% ± 10% condition, and medicine character, pH, relative density, discriminating obviously do not become.Above-mentioned result of the test shows that these article storage quality under rated condition is stable, and therefore will fix tentatively effect duration is 2 years.
Claims (3)
1. the saturnine medicine of treatment ruminant is characterized in that the composition and the weight portion of the active component of medicine is: Rhizoma Smilacis Glabrae 3~30, Radix Isatidis 3~35, Radix Glycyrrhizae 4~28, Radix Codonopsis 3~20, Rhizoma Coptidis 2~15, Thallus Laminariae (Thallus Eckloniae) 2~15.
2. the method for preparing of the said treatment of claim 1 ruminant lead poisoning medicine is characterized in that each medicine water is soaked into post-heating fully to be decocted, and gets the water extract.
3. method for preparing according to claim 2 is characterized in that each medical material is put into water soaks into post-heating to 90 ℃ extraction 3 times, each 2 hours fully; Merge medicinal liquid, centrifugal after solution to be concentrated cold to the room temperature with centrifuge, 4000 commentaries on classics/min; 15min removes deposition, slowly adds ethanol in the concentrated solution; Make pure content reach 70%, after leaving standstill, carry out concentration, recovered alcohol does not get final product to there being the alcohol flavor.
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