CN108619232A - A kind of mattress Huang oral solution and preparation method thereof for treating chicken Drug acute liver damage - Google Patents

A kind of mattress Huang oral solution and preparation method thereof for treating chicken Drug acute liver damage Download PDF

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CN108619232A
CN108619232A CN201810491053.6A CN201810491053A CN108619232A CN 108619232 A CN108619232 A CN 108619232A CN 201810491053 A CN201810491053 A CN 201810491053A CN 108619232 A CN108619232 A CN 108619232A
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oral solution
huang
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何永明
李紫元
肖洁怡
龙小铃
伦健炽
邱文才
梁伟燊
唐陆平
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Foshan University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539Scutellaria (skullcap)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/28Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282Artemisia, e.g. wormwood or sagebrush
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0087Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps

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  • Natural Medicines & Medicinal Plants (AREA)
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Abstract

The present invention provides a kind of mattress Huang oral solutions and preparation method thereof for treating chicken Drug acute liver damage.The preparation method includes step:1) 1 part of 2 parts of oriental wormwood and scutellaria are taken by weight, are impregnated 0.8~2 hour after cleaning;2) by medicinal material and water by weight 1:10 input containers are decocted, and are decocted 1~3 hour.Compared with prior art, the beneficial effects of the invention are as follows:The side's of tearing open experiment is carried out to mattress Cape jasmine detoxification particles, filter out can effective medicine acute liver damage prescription mattress Huang oral solution.Mattress Huang oral solution has no significant effect cardiovascular system, respiratory system and nervous system.Acute toxicity test shows that the LD50 of mattress Huang oral solution is more than 5000mg/kg, practical nontoxic.The drug is used for a long time to have no adverse reaction to animal body.

Description

A kind of mattress Huang oral solution and preparation method thereof for treating chicken Drug acute liver damage
Technical field
The present invention relates to medical preparation technical field, more particularly to a kind of mattress for treating chicken Drug acute liver damage is yellow The preparation method of oral solution and the compound Chinese patent medicine.
Background technology
Liver is internal maximum body of gland, and major function is secretion of bile, while having removing toxic substances, defence, substance generation It thanks, hematopoiesis and the storage functions such as blood.Liver is internal main removing toxic substances organ, and noxious material is acted on through liver cell mostly, makes its poison Property disappear, weaken or combine be converted into solable matter, excreted with bile or urine.Bacterium, disease in daily life Poison, drug abuse, various liver diseases can all be caused by being exposed to toxic environment etc. for a long time.Due in stimulation liver function, repairing Multiple wounded hepatocytes damage etc. lacks effective therapy and drug, and it is dead that liver diseases have become global height One of rate disease.In recent years due to hepatic injury (drug-induced liver injury, DILI) incidence of drug initiation Rising year by year.It is reported that having about 30000 kinds of drugs and compound has potential hepatotoxicity wind agitation, wherein the medicine listed Object has more than 1000 to plant.The drug of hepatic injury is caused to have analgesic-antipyretic (such as paracetamol, APAP), antibiotic, non-steroid Body anti-inflammatory drugs, antitumor drug and anti-tubercular drug etc..It is worth watchful, Chinese herbal medicine causes the ratio of hepatic injury gradually Increase;In addition, part beauty, weight-reducing and health products can also cause to damage to liver.In livestock and poultry intensive culture, it is limited by Breeding environment and cultivation density, there is multiple types to be used in combination, over much dosage for the use (especially antibacterials) of drug The problem of abuse, increases year by year so as to cause the drug induced hepatic injury incidence of livestock and poultry.
Mattress Cape jasmine detoxification particles are made of oriental wormwood, cape jasmine, radix scutellariae, giant knotweed, uncaria gomi herbs, cure mainly the virus of duckling Property hepatitis.Virus hepatitis has certain approximation with DILI in symptom, but due to the difference of pathogenesis, mattress Cape jasmine Detoxification particles can not directly apply to treatment DILI.
Invention content
Existing mattress Cape jasmine detoxification particles cannot be used directly for treatment DILI, and the purpose of the present invention is to provide one kind to be applicable in In the oral drugs of Drug acute liver damage, and especially suitable for using chicken as treatment object.
A kind of preparation method of mattress Huang oral solution that treating chicken Drug acute liver damage, includes the following steps:
1) 1 part of 2 parts of oriental wormwood and scutellaria are taken by weight, are impregnated 0.8~2 hour after cleaning;
2) by medicinal material and water by weight 1:10 input containers are decocted, and are decocted 1~3 hour.
Further, the step 2 in triplicate, merges liquid.
Wherein, the soaking time of step 1 is 1 hour;The decocting time of step 2 is 2 hours.
The mattress Huang oral solution of chicken Drug acute liver damage is treated made from above-mentioned preparation method, dosage is 15~20g/kg.
Compared with prior art, the beneficial effects of the invention are as follows:The side's of tearing open experiment is carried out to mattress Cape jasmine detoxification particles, is filtered out Can effective medicine acute liver damage prescription mattress Huang oral solution.Mattress Huang oral solution is to cardiovascular system, respiratory system It is had no significant effect with nervous system.Acute toxicity test shows that the LD50 of mattress Huang oral solution is more than 5000mg/kg, practical nontoxic. The drug is used for a long time to have no adverse reaction to animal body.
Specific implementation mode
In the examples where no specific technique or condition is specified, according to technology or condition described in document in the art Or it is carried out according to product description.Reagents or instruments used without specified manufacturer, being can be by acquisition purchased in market Conventional products.
Embodiment 1, the structure of rat APAP liver injury models.
Be injected intraperitoneally male mouse with 800mg/kg paracetamol (APAP), when 28h after can obtain best big raticide Physical property liver injury model confirms whether model construction succeeds by taking a blood sample to detect.
Embodiment 2, the prescription of orthogonal test preferred therapeutic Drug acute liver damage.
2-1. animals and feeding environment
SD male rats 200, (200 ± 20) g;It is provided by Guangdong Province's Experimental Animal Center, quality certification number:SCXK (Guangdong) 2013-0002.All animal feedings are in Foshan Science &. Technology College's animal house, and indoor temperature control is at 20-25 DEG C, phase To humid control in 50%-70%.Natural lighting.Normal diet is fed, and rat is freely eaten and drinks water during experiment, greatly Mouse bedding and padding are disinfection corncob.
2-2. preferred agents orthogonal tests
It is tested using orthogonal Table Design mattress Cape jasmine detoxicating liquid compatibility of drugs, the Drug Acute Hepatic that rat APAP is made Damage is treated.Using the biochemical indicator of liver as evaluation criterion, with oriental wormwood, cape jasmine, oriental wormwood × cape jasmine, radix scutellariae, giant knotweed, hook Rattan is 6 factors, and two levels of each factor, design orthogonal test table is as follows (being shown in Table 1).
1 orthogonal optimization compatibility of drugs of table is tested
Orthogonalization compatibility of drugs experimental design is following (being shown in Table 2).
2 L of table8(27) orthogonalization compatibility of drugs experimental design
According to the above orthogonal table, nine groups of experiments are designed.First group is oriental wormwood 360g, cape jasmine 180g, giant knotweed 200g, Huang A kind of reed mentioned in ancient books 180g, uncaria 200g full presciption medicines, second group is oriental wormwood 360g, cape jasmine 180g, and third group is oriental wormwood 360g, radix scutellariae 180g, the Four groups for oriental wormwood 360g, giant knotweed 200g, uncaria 200g, the 5th group for cape jasmine 180g, radix scutellariae 180g, giant knotweed 200g, the 6th group For cape jasmine 180g, uncaria 200g, the 7th group is radix scutellariae 180g, uncaria 200g, and the 8th group is giant knotweed 200g, the 9th group of blank pair According to.By above per group of formula, with liquid than 1:15,30min is impregnated before decocting, boils by intense fire, liquid is poured out after being cooked by slow fire 1h, Same dose boiling boiling same time is added, merges liquid, it is spare to be concentrated into 1g/mL for filtered through gauze.
Every group of 10 rats make SD rat Drug acute hepatic injury models, after modeling using upper chapter optimization method 12h starts to treat rat, respectively in 12h, for 24 hours, every group of 36h gavage is carried out with 20g/kg active compounds, to rat after 48h Abdominal cavity blood sampling detection serological index.Acquisition liver is weighed, and liver coefficient is calculated;Liver is fixed with 10% formalin solution It is dirty, block sections are made, is dyed using HE, pathologic finding is carried out under microscope.
It can be obtained from hepatic tissue pathology result, the 1st, 2,3,4,5 group of liver cell has different degrees of vacuolar degeneration, 3rd group more serious, and the 4th, 5 group of denaturation degrees are lighter, and is all deposited with slight bile;6th group of hepatic tissue has more serious Bile deposits and large stretch of necrosis of liver cells, drug do not play therapeutic effect and deepened the damage of hepatic tissue;7th group has gently Micro- steatosis, the 8th group of hepatic tissue is all more normal, and drug plays good therapeutic effect;Blank group has moderate Cell vacuolar degeneration and bile deposition.
According to blood biochemical result and pathology section examination, oriental wormwood, radix scutellariae, three herbal medicine of giant knotweed is selected to carry out dose increasing The orthogonal test subtracted.
2-3. optimizes dose orthogonal test
The dose that drug has been screened using orthogonal Table Design increases and decreases experiment, and the Drug made to rat APAP is acute Hepatic injury is treated.Using the biochemical indicator of liver as evaluation criterion, with oriental wormwood, radix scutellariae, giant knotweed is three factors, Mei Geyin Plain two levels, design orthogonal test gauge outfit such as table 3.
3 orthogonal optimization dose of table increase and decrease experiment gauge outfit
Four groups of experiments are designed according to orthogonal arrage 3.First group of oriental wormwood 360g, radix scutellariae 180g, giant knotweed 200g;Second group of oriental wormwood 360g, radix scutellariae 90g, giant knotweed 100g;Third group oriental wormwood 180 g, radix scutellariae 180g, giant knotweed 100g;4th group of oriental wormwood 180g, radix scutellariae 90g, 100 g of giant knotweed;It is another that blank control is added, as shown in table 4.By above per group of formula, with liquid than 1:15, leaching before decocting 30min is steeped, boils by intense fire, liquid is poured out after being cooked by slow fire 1h, same dose boiling boiling same time is added, merges liquid, yarn Cloth filters, and it is spare to be concentrated into 1g/mL decoctions.
4 L of table4(23) orthogonal optimization dose increase and decrease experimental design
Every group of 10 rats make SD rat Drug acute hepatic injury models using the best approach that a upper chapter screens, 12h starts to treat rat after modeling, respectively in 12h, for 24 hours, every group of 36h gavage is carried out with 20g/kg active compounds, after 48h It takes a blood sample to rat abdominal cavity and detects serological index.Acquisition liver is weighed, and liver coefficient is calculated;With 10% formalin solution Fixed liver, is made block sections, is dyed using HE, pathologic finding is carried out under microscope.
3rd group of hepatic tissue has steatosis, the 1st group and the 4th group of sinus hepaticus atrophy, the 2nd group of liver cell to have vacuole change Property.
The increase and decrease of three herbal medicine compatibility dosage does not have therapeutic effect to DILI, but by the result of drug screening it is found that three Herbal medicine is the drug effect for having treatment DILI, is thus inferred, there is the drug for having antagonism to treatment DILI in three herbal medicines Combination needs to carry out next step screening.
2-4. drug ratios are tested
Oriental wormwood, radix scutellariae, giant knotweed are matched two-by-two, and comparative example carries out parallel test, design experiment, (table 5).
Compatibility mechanism designs two-by-two for 5 oriental wormwood of table, radix scutellariae, giant knotweed
1g/mL active compounds will be concentrated to after drug decocting using decocting method identical with step 2-3.Every group of 5 rats, Use method modeling as described above, administration, detection identical items.
When oriental wormwood and radix scutellariae proportioning are 2:When 1, compared with the control group, CHE, AST, DBIL, ALP, 5-NU and TP have aobvious The reduction of work, compared with other test groups, AST, ALT, 5-NU, TBIL, TBA, TP, CHE are also substantially reduced, so from Result above can obtain oriental wormwood and radix scutellariae 2:1 ratio can play drug induced hepatic injury better therapeutic effect.
Control group, the 6th group of liver cell enlargement it can be seen from pathological section, there is a vacuolar degeneration, sinus hepaticus atrophy, and the 3rd Group and the 4th group of slight enlargement of liver cell, the 5th group and the 7th group has slight steatosis, the 1st group, the 2nd group of lesion unobvious.
2-5. conclusion
Oriental wormwood is that main component is volatile oil and chlorogenic acid compound, and chlorogenic acid is the main component of hepatic cholagogic, from From the point of view of experimental result, oriental wormwood is the main active drug for treating hepatic injury, and in orthogonal test, oriental wormwood is in treatment rat DILI Several main liver biochemical indicators on effect it is not notable, but in comprehensive score, the presence of oriental wormwood can be lowered obviously Score, it was demonstrated that effect of the oriental wormwood in treating DILI.In the orthogonal experiment of dose increase and decrease, because each compatibility is mitigating DILI Critical biochemical index in effect it is not notable, suspect oriental wormwood, radix scutellariae, have antagonism work to the treatment of DILI between three herbal medicine of giant knotweed With.Therefore pair thirdly herbal medicine has carried out compatibility two-by-two, and dose proportioning is also studied, it is found that oriental wormwood is combined with radix scutellariae After medication, hepatic injury therapeutic effect can be played caused by APAP.
Radix scutellariae is mainly made of chemical compositions such as flavonoids, glycoside, terpenoid and volatile oil, wherein flavonoids Ingredient scutelloside is liver protecting main function substance, in orthogonal test, it can be deduced that radix scutellariae is in the rat blood serum of DILI ALT have certain reduction effect, comprehensive score that can obtain, the validity that radix scutellariae treats rat DILI.In radix scutellariae and tiger It is obtained in the compatibility of drugs treatment DILI results of cane, radix scutellariae is the specific original there is antagonism in treatment DILI with giant knotweed Because needing more deep exploration, oriental wormwood and radix scutellariae in ratio 2:1 when, it is significant in efficacy to DILI.
Cape jasmine main component is iridoid glycoside, organic acid and pigment, predominantly crocin etc., and Gardenoside has anti- Scorching, cholagogic, antipyretic effect, Gardenia Yellow can effectively inhibit mouse AST, ALT, LDH and liver caused by carbon tetrachloride The raising of MDA contents and liver index reduces the content of GSH, alleviates focal necrosis in lobuli hepatis.But it can from experimental result To find out, in the treatment of rat Drug acute liver damage caused by APAP, cape jasmine does not play a protective role, and The effect of hepatic injury is promoted, ALT, AST, TBIL, DBIL, TBA etc. mainly in the index of liver biochemistry, have significant increase, make The damage of liver increases.Gardenoside has potential hepatotoxicity wind agitation, and has dose dependent.But in the side for the treatment of hepatic injury Face has not been reported, and needs further studied.To obtain better effect in medicine physical property hepatic injury, therefore cast out Cape jasmine Son.
Giant knotweed main component is anthraquinones, diphenylethylene compounds, tannin and polysaccharide etc..With extensive medicine Reason activity.Hong Zhaoyou etc. is studies have shown that Huzhang can promote the microcirculation of hepatic injury tissue, inhibition leucocyte, blood platelet Adherency to hepatic endothelial cells promotes the regeneration of stem cell.Related report polygonin can significantly reduce carbon tetrachloride to big AST caused by mouse, the raising of ALT, main mechanism is the expression for inhibiting TNF-α, and it is related to improve Bcl-2/Bax ratios. In this experimental result, for giant knotweed in orthogonal test independent medication, the APAP that can significantly improve causes the medicine of rat Physical property hepatic injury reduces the content of ALT, TBA in rat blood serum.But with oriental wormwood, when radix scutellariae drug combination, effect is unknown It is aobvious, respectively with oriental wormwood, radix scutellariae compatibility, it can show that giant knotweed and radix scutellariae have antagonism work when treating drug hepatic injury caused by APAP With reason requires study;With the drug combination of oriental wormwood, although drug effect and oriental wormwood and radix scutellariae (2:1) effect is weaker, but deposits Acted in potential drug therapy, need from compatibility of drugs, dose proportioning, indication etc. do deeper into research.
Uncaria mainly contains the chemical compositions such as rhynchophyllin, isorhynchophylline, Hyperoside and catechin, and main function is drop The protection of pressure, calm, anticonvulsion, anti-epileptic and Central nervous.In mattress Cape jasmine detoxification particles, mainly to duck viral liver Nervous symptoms caused by inflammation are treated.It can be obtained in this test result, uncaria makees the treatment of DILI without apparent With, therefore cast out, optimize prescription.
Embodiment 3, the safety pharmacology experiment of mattress Huang oral solution.
The influence of 3-1. cardiovascular systems, respiratory system
KM mouse are randomly divided into four groups, every group 20, half male and half female, mattress Huang oral solution by high dose group (20g/kg), in Dosage group (10g/kg), low dose group (5g/kg) gavage, and gavage volume 0.2mL/10g, blank control group gavages isometric Solvent.Use MC4000 non-invasive blood pressures analyzer and the noninvasive pulmonary function analyzer records of EMKA that preceding 1 h is administered respectively, after administration The blood pressure of 0h, 1h, 2h and 4h, pulse and breath system index of correlation.
After mattress Huang oral solution high dose and low dosage gavage 4h, blood pressure has significant decrease, middle dosage and blank control filling Each period blood pressure unobvious after stomach.It is reported that scutelloside has expansion blood vessel, and the effect to reduce blood pressure, main machine System is by blocking the voltage dependent form calcium channel on smooth muscle cell membrane and being made by actuated type calcium channel intracellular Calcium ion concentration increases.In addition it research shows that scutelloside plays the role of natriuretic diuretic, reduces periphery blood volume and cardiac blood is defeated Output so that blood pressure declines.Baicalein also has certain antihypertensive effect, but baicalein does not interfere with the blood pressure of normal rat, There is reduction effect to Hypertensive Rats.So inferring, high dose and the decline of low dose group blood pressure have with scutelloside antihypertensive effect It closes.
The respiratory rate of senior middle school's low dose group of mattress Huang oral solution, tidal volume are in each period compared with blank control group It has no significant effect, can be obtained from data, the respiratory rhythm of mouse is stablized, and the f values of each group are between 700-800 (bbm).In the past Also see the effect for not reporting oriental wormwood and radix scutellariae to respiratory system, it may be said that bright mattress Huang oral solution is given in 20g/ (kg.bw) range Medicine has no significant effect conscious mouse respiratory system.
Influence of the 3-2. mattress Huang oral solutions to nervous system
It is past according to this research shows that scutelloside 500mg/kg-1000mg/kg carry out mouse peritoneal injection, have calmness Effect, and to sleeping and awakening has dual regulation.Some researches show that scutelloside can inhibit the work of IL-1 in illumination period Property reduce slow wave sleep (SWS), GABA (A) receptor actives can be enhanced in dark cycle to increase SWS and rapid-eye-movement sleep (REMS).In the yellow Jackets sub-threshold dose hypnosis result of mouse, high, medium and low dosage has a mice sleep, and blank Dosage group is without mice sleep;In yellow Jackets threshold dose hypnosis result, time for falling asleep and the control group phase of high dose mouse It is substantially reduced than time, sleep time compared with the control group of holding time significantly increases, and mattress Huang oral solution can be reflected to sleeping The adjustment effect of dormancy.To mouse free action result analysis it is found that although each dosage group of same period mattress Huang oral solution with Control group is compared to relatively without significantly otherness (P > 0.05), but compared with before administration, each group number of activities all significantly under It drops (P < 0.05), thus it is speculated that gavage has mouse and certain stress influence so that mouse number of activities after gavage are reduced.Small The transfer rod of each group mouse known to the result of mouse coordination of function campaign rate of falling compares with 3min in 1min and is not significantly different.
Embodiment 4, the acute toxicity and long term toxicity test of mattress Huang oral solution.
Acute toxicity test refers to that animal once receives single dose or receives multidose tested material interior for 24 hours, short-term Inside there is the experiment of toxic reaction.Purpose is in the case where tested material is without other references, is long term toxicity test, spy Different toxicity test and clinical research dose design provide reference, and provide the target organ that further may deeply observe.Long-term poison Property experiment be on the basis of acute toxicity, further look at and evaluate tested material in the case that repeat administration toxic reaction, There is provided may to the damaging of body, accumulation and target organ etc. in vivo for information about, derive reactionless dosage, be the non-of drug The core content of clinical safety evaluation.The acute toxicity test of mattress Huang oral solution and long term toxicity test according to《Veterinary drug is acute Toxicity test (LD50 measurement) guideline》With《Veterinary drug 30 days and feeding test for 90 days guideline》It carries out.
The influence of 4-1. mattress Huang Oral Liquid On Mice acute toxicities
Given low is up to 6000mg/kg in this test result, and administration has no any death, dissect observation after 7 days Internal organ no abnormality seen.According to《Veterinary drug acute toxicity test (LD50 measurement) guideline》, drug LD50 is more than 5000mg/kg It is it is believed that reality is nontoxic, so mattress Huang oral solution is actually nontoxic.
Influence of the 4-2. mattress Huang oral solutions to rat long term toxicity
According to《Veterinary drug 30 days and feeding test for 90 days guideline》With the acute toxicity test of mattress Huang Oral Liquid On Mice As a result known to:For can not ask the test medicine of LD50,30 days feeding trials to cover the 100 of the possible intake of animal as far as possible Multiple dose, accordingly, it is determined that the maximum dose level of the subchronic toxicity test of mattress Huang oral solution is 75g/kg.
The main component of mattress Huang oral solution is volatile oil, polysaccharide, amino acid, cumarin, flavonoids, chromogen ketone and green Ortho acid is showed no xicity related report.
It is testing 30 days and when convalescence, the male and female rat of each dosage group is with the growth of week old, weight gain, and with Blank control group is not notable (P > 0.05) compared to difference.Each group male rat feed intake first increases reduces (3 week old feed intakes again It is maximum), then tend to be steady;The feed intake of female mice decreased significantly after 3 weeks;The male rat amount of drinking water year week old of each group Increase and increases, and female mice amount of drinking water is first to increase to tend to be steady afterwards.The growth rate of rat gradually increases in first three weeks, after Three weeks be that growth rate slows down, first increase to reduce afterwards with the feed intake of rat and match.In terms of amount of drinking water, male mouse is with week old Increase, amount of drinking water increase, meet physiological law;Female mice amount of drinking water first increases to tend to be steady afterwards, meets its physiological law.By This has no adverse effects to rat body weight, feed intake and amount of drinking water it is found that taking mattress Huang oral solution for a long time.
In blood routine and blood biochemical detection, RBC, HCT and MCH and blank group pair of hero mouse high dose group at 30 days Than apparent relatively low (P < 0.05), the MCV and EO% of low dose group are significantly higher than high dose group (P < 0.05), and EO% is significantly high In blank group (P < 0.05).The LY% of female mice middle dose group is significantly higher than blank group (P < 0.05), and NE% is substantially less than blank Group (P < 0.05).MCH, MPV and PDW of low dose group are significantly higher than high dose group (P < 0.05).At 45 days, the male high agent of mouse The RDW of amount group and low dose group is significantly higher than blank group (P < 0.05), and the RBC of low dose group is significantly higher than blank group (P < 0.05), EO% is substantially less than blank group (P < 0.05);The RDW of female mice middle dosage is significantly high with blank group (P < 0.05), high The LY# and NE% of dosage group are substantially less than other each groups (P < 0.05).The detection numerical value of WBC male and female mouse is in normal range (NR) (2.92~11.15) × 109/L (♀), (2.08~11.78) × 109/L (♂);Male mouse WBC increases at any time to be become without apparent Change, female mice WBC period dosage group no significant differences compared with the control group in addition to 45 days low dose groups, infer female mice WBC with Time increases and increases, and drug has certain influence to RBC, HCT and MCH of male rat, on the blood routine of female mice influence compared with It is small, but the main routine blood indexes of each group each period are in normal range (NR) (RBC:(6.16~7.97) × 1012/L (♀), (6.04~8.33) × 1012/L (♂);HGB (124.23~163.19) g/L (♀), (123.81~166.04) g/L (♂)). Each group hematological indices except platelet count with it is previously reported value it is bigger than normal, blood platelet increase may with animal age, detection reagent, The factors such as detecting instrument are related.Blood parameters, the high dose group AST of hero mouse is substantially less than blank group (P at 30 days < 0.05), TBA, AS/AL, LDL and ADA are apparently higher than blank group, and ALT is significantly higher than other each groups;Middle dosage GGT is significantly high In other each groups, LDL is significantly higher than blank group, and BUN is substantially less than other each groups;Low dosage TG, LAP and TBA are significantly higher than Blank group;The ALP and 5-NU of blank group are significantly higher than other each groups.The low dosage of hero mouse and the ALB of middle dosage are notable at 45 days Higher than blank group.At 30 days, the high dose group HDL and CHO of female mice are significantly higher than blank group, and GLB is substantially less than middle dose group, UA is substantially less than low dose group;TG, UA and GLB of middle dose group are significantly higher than blank group, and A/G is substantially less than blank group;It is low LAP, TBA and CREAT of dosage are significantly higher than blank group, and UA is significantly higher than high dose group and blank group, and DBIL is significantly higher than it His each group;The TP of blank group is substantially less than other each groups.At 45 days, equal no significant difference between the indices of each group.By Above it is found that drug has certain influence to the liver function of rat, blood fat and kidney function, but in normal range (NR).
In pathological index, each group Rats Organs and Tissues index comparison among groups are without significant difference (P > 0.05).Take blank control The heart, liver, spleen, lung, kidney, stomach, small intestine, the testis of group and high dose group rat, ovary carry out histotomy observation, and mattress Huang is oral For liquid high dose group with control group Histological section without apparent lesion, institutional framework is normal.

Claims (6)

1. a kind of preparation method of mattress Huang oral solution that treating chicken Drug acute liver damage, it is characterised in that including following step Suddenly:
1) 1 part of 2 parts of oriental wormwood and scutellaria are taken by weight, are impregnated 0.8~2 hour after cleaning;
2) by medicinal material and water by weight 1:10 input containers are decocted, and are decocted 1~3 hour.
2. the preparation method of the mattress Huang oral solution for the treatment of chicken Drug acute liver damage according to claim 1, feature It is:The step 2 in triplicate, merges liquid.
3. the preparation method of the mattress Huang oral solution for the treatment of chicken Drug acute liver damage according to claim 1 or 2, special Sign is:The soaking time of step 1 is 1 hour.
4. the preparation method of the mattress Huang oral solution for the treatment of chicken Drug acute liver damage according to claim 1 or 2, special Sign is:The decocting time of step 2 is 2 hours.
5. a kind of mattress Huang oral solution for treating chicken Drug acute liver damage, which is characterized in that by any one of Claims 1 to 4 Made by the preparation method.
6. the mattress Huang oral solution for the treatment of chicken Drug acute liver damage according to claim 5, which is characterized in that the mattress The dosage of yellow oral solution is 15~20g/kg.
CN201810491053.6A 2018-05-21 2018-05-21 A kind of mattress Huang oral solution and preparation method thereof for treating chicken Drug acute liver damage Pending CN108619232A (en)

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CN101396427A (en) * 2007-09-30 2009-04-01 天津瑞普生物技术集团有限公司 Traditional Chinese medicine oral liquid for treating poultry virus hepatitis and hepatic injury
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Application publication date: 20181009