CN108771703A - Application of the pharmaceutical composition in the drug for preparing prevention laying hen Salmonella infection disease - Google Patents
Application of the pharmaceutical composition in the drug for preparing prevention laying hen Salmonella infection disease Download PDFInfo
- Publication number
- CN108771703A CN108771703A CN201810475926.4A CN201810475926A CN108771703A CN 108771703 A CN108771703 A CN 108771703A CN 201810475926 A CN201810475926 A CN 201810475926A CN 108771703 A CN108771703 A CN 108771703A
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- China
- Prior art keywords
- egg
- skullcapflavone
- salmonella
- pharmaceutical composition
- laying hen
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Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 52
- 206010039438 Salmonella Infections Diseases 0.000 title claims abstract description 35
- 206010039447 salmonellosis Diseases 0.000 title claims abstract description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 29
- 230000002265 prevention Effects 0.000 title claims abstract description 23
- 229940079593 drug Drugs 0.000 title claims abstract description 17
- 229930192484 Skullcapflavone Natural products 0.000 claims abstract description 59
- CZRGNFVQUYWGKP-UHFFFAOYSA-N Skullcapflavone I Natural products COC=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1O CZRGNFVQUYWGKP-UHFFFAOYSA-N 0.000 claims abstract description 59
- 241000607142 Salmonella Species 0.000 claims abstract description 33
- 238000001514 detection method Methods 0.000 claims abstract description 33
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims abstract description 22
- 229930064664 L-arginine Natural products 0.000 claims abstract description 22
- 235000014852 L-arginine Nutrition 0.000 claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims abstract description 10
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- 239000002994 raw material Substances 0.000 claims abstract description 4
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 24
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- XDQITMCFPPPMBC-TUANDBMESA-N scutelloside Natural products OC[C@H]1O[C@@H](O[C@@H]2O[C@@H]3C[C@H]4[C@H](O)[C@@H](O)[C@@](O)(CO3)[C@@H]24)[C@H](O)[C@@H](O)[C@@H]1O XDQITMCFPPPMBC-TUANDBMESA-N 0.000 description 6
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
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- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- FXNFHKRTJBSTCS-UHFFFAOYSA-N Baicalein Natural products C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 description 1
- 206010009192 Circulatory collapse Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 208000006731 Salmonella Food Poisoning Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- HIMJIPRMECETLJ-UHFFFAOYSA-N Wogonin Natural products COc1cc(O)c(O)c2C(=O)C=C(Oc12)c3ccccc3 HIMJIPRMECETLJ-UHFFFAOYSA-N 0.000 description 1
- LNOHXHDWGCMVCO-UHFFFAOYSA-N Wogonoside Natural products C1=C(O)C(C(C=C(O2)C=3C=CC=CC=3)=O)=C2C(OC)=C1OC1OC(C(O)=O)C(O)C(O)C1O LNOHXHDWGCMVCO-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
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- UDFLTIRFTXWNJO-UHFFFAOYSA-N baicalein Chemical compound O1C2=CC(=O)C(O)=C(O)C2=C(O)C=C1C1=CC=CC=C1 UDFLTIRFTXWNJO-UHFFFAOYSA-N 0.000 description 1
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- 230000003203 everyday effect Effects 0.000 description 1
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- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
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- 229960003760 florfenicol Drugs 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000021393 food security Nutrition 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
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- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical class O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
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- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
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- 230000000644 propagated effect Effects 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
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- 230000003612 virological effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLTFNNCXVBYBSX-UHFFFAOYSA-N wogonin Chemical compound COC1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=CC=C1 XLTFNNCXVBYBSX-UHFFFAOYSA-N 0.000 description 1
- LNOHXHDWGCMVCO-NTKSAMNMSA-N wogonin 7-O-beta-D-glucuronide Chemical compound C1=C(O)C(C(C=C(O2)C=3C=CC=CC=3)=O)=C2C(OC)=C1O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LNOHXHDWGCMVCO-NTKSAMNMSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Neurosurgery (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention provides application of the pharmaceutical composition in drug, raising Layer Production Performance, reduction eggshell and the egg content for preparing prevention laying hen Salmonella infection disease carry detection of Salmonella quantity and improve laying hen Egg Quality, and each raw material medicaments in part by weight is calculated as in described pharmaceutical composition：30-50 parts of skullcapflavone, 20-40 parts of L-lysine, 30-50 parts of L-arginine.The pharmaceutical composition that the present invention is prevented with the laying hen Salmonella infection disease that " origin conditioning " is core, have the characteristics that green safe, not tolerific, substitute antibiotics, it not only can effectively press down and kill detection of Salmonella, adjustable laying hen immunity of organism phylactic power defensive power simultaneously, egg source contact scar caused by the horizontal transmission and potential endogenous displacement of reduction chicken group's detection of Salmonella, improves egg laying performance egg quality, effectively avoids food-safety problem caused by the property detection of Salmonella of egg source.
Description
Technical field
The invention belongs to veterinary drug technical fields, and in particular to pharmaceutical composition is preparing prevention laying hen Salmonella infection disease
Application in drug, systems which pharmaceutical composition is in drug, the raising egg for preparing prevention laying hen Salmonella infection disease
Chicken egg laying performance reduces eggshell and egg content carrying detection of Salmonella quantity and improves the application in laying hen Egg Quality.
Background technology
The food-safety problem caused by food-borne causal agent increasingly obtains the attention of people, wherein detection of Salmonella
(Salmonella) food safety question caused by is the major reason that long-standing problem poultry industry develops in a healthy way.In U.S.
State, large-scale egg recall event become food security focus of attention again by the Salmonella infection of egg.Detection of Salmonella can
To infect egg by two kinds of approach of vertical transmission and horizontal transmission.The Salmonella infection caused by egg is considered as mankind's sense
One of the main reason for contaminating detection of Salmonella.Under normal conditions, old man, child and some to have the patient of immune deficiency to be easy infection husky
Door bacterium, shows as nausea,vomiting,diarrhea after infection, serious circulatory failure to occur and dead.There are about 3,700,000 every year in the U.S.
People infects detection of Salmonella, and the economic loss thereby resulted in is up to more than 6,400 ten thousand to 1 hundred million dollars.The infection of China's detection of Salmonella is also relatively tighter
Weight, is analyzed, between 20 years of 1983-2002, Shandong Province occurs Salmonella food poisoning 286 and rises altogether, in 11228 people according to investigations
Poison, 15 people are dead, and case fatality rate is up to 0.13%.
Currently, the control measure of salmonella gallinarum infectious disease mainly takes vaccine inoculation, monitoring to eliminate positive chicken and periodically throw
Large dosage of antibacterials are fed with temporary prevention effect.Vaccine inoculation is a kind of promising approach of control Salmonella infection, but by
Numerous in detection of Salmonella serotype, existing inactivated vaccine and Attenuate vaccine for particular serotype, Vaccine effectiveness is extremely limited, novel
Broad-spectrum high efficacy vaccine is still among research.Positive chicken is eliminated in monitoring, and purification chicken group's detection of Salmonella, economic cost is high, mostly in breeding public affairs
Department implements, and the latter is widely used in breeder breeding field and breeding layer chicken field, and the unreasonable use of antibiotic also results in detection of Salmonella
Drug tolerance of strain enhances, and Antibiotic Resistance is broadening.Studies have shown that from the sixties in last century begin, salmonella gallinarum to penicillin, streptomysin,
The drug resistance presentation of sulfa drugs, tetracycline, kanamycins and gentamicin etc. significantly increases variation tendency.Meanwhile state
Clear stipulaties laying cycle of laying hens antibiotic disabled list, a variety of common antibiotic must not be used for the chicken of laying period for family.
In July, 2017, because Doxycycline and Florfenicol are exceeded in egg, two breeding layer chicken field of Nanyang is main to be sentenced in accordance with the law.Therefore,
It is the Strategic Demand for ensureing laying hen industry health sane development to develop green safe, high-efficiency environment friendly substitute antibiotics new product.
Invention content
In order to solve the problems in the existing technology, the present invention provides it is a kind of safe and reliable, without hormone, without side-effects
And the application of the pharmaceutical composition of the prevention laying hen Salmonella infection disease of medicament residue, it can be used for purifying laying hen detection of Salmonella, drop
Egg source contact scar caused by the horizontal transmission and potential endogenous displacement of low chicken group detection of Salmonella, improves egg quality, effectively avoids
Food-safety problem caused by the property Salmonella of egg source.
The present invention provides pharmaceutical composition in drug, the raising Egg Production of Laying Hens for preparing prevention laying hen Salmonella infection disease
It can, reduce eggshell and egg content carry detection of Salmonella quantity and improves the application in laying hen Egg Quality, described pharmaceutical composition
In each raw material medicaments in part by weight be calculated as：30-50 parts of skullcapflavone, 20-40 parts of L-lysine, 30-50 parts of L-arginine.
Preferably, each raw material medicaments in part by weight is calculated as in described pharmaceutical composition：35 parts of skullcapflavone, L-lysine 30
Part, 35 parts of L-arginine.
Preferably, the preparation method of the skullcapflavone is：It is carried with dimethyl sulphoxide solution after baikal skullcap root decoction pieces are crushed
It takes, filtrate is collected by filtration, filtrate is subjected to UF membrane, skullcapflavone concentrate is obtained, is then spray-dried.
Preferably, the preparation method of the skullcapflavone is：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, 5-10 is added
Times 50% dimethyl sulphoxide solution of medicinal material weight, 40-60 DEG C extracts 1-3 time, 30-90 minute each, filters, merging filtrate, selects
With the inorganic ceramic membrane of 10nm, 25-40 DEG C of flow 1.2-1.8L/min, pressure 0.12MPa and feed temperature carry out film point
From obtaining skullcapflavone concentrate, with 100-150 DEG C of inlet air temperature, the condition of feed volume flow 6-12mL/min is sprayed
It is dry.
Preferably, the preparation method of the skullcapflavone is：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, 5 times of medicines are added
50% dimethyl sulphoxide solution of material weight, 40 DEG C extract 2 times, 60 minutes every time, filtration, merging filtrate, select that 10nm's is inorganic
Ceramic membrane, flow 1.5L/min, pressure 0.12MPa and 30 DEG C of feed temperature carry out UF membrane, obtain skullcapflavone concentrate,
With 120 DEG C of inlet air temperature, the condition of feed volume flow 9mL/min is spray-dried.
Preferably, described pharmaceutical composition is to weigh skullcapflavone, L-lysine and L-arginine according to recipe quantity, mix
It is even to obtain the final product.
Preferably, the Layer Production Performance is laying rate and average egg weight.
Preferably, the raising laying hen Egg Quality is to improve shell thickness and reduction egg breakage rate.
The present invention is according to traditional veterinary drug theory and modern nutritional pharmacological principle, by effective component of chinese medicine and nutrient
It combines, forms the pharmaceutical composition prevented with the laying hen Salmonella infection disease that " origin conditioning " is core, have
Green safe, not tolerific feature.Wherein radix scutellariae is common traditional Chinese medicine, has the work(such as clearing heat and detoxicating, arresting bleeding and miscarriage prevention
Effect.Radix scutellariae drug activity ingredient is mainly flavonoids, such as scutelloside, wogonoside and its aglucon baicalein, wogonin, tool
There are the multiple pharmacological effects such as viral antibacterium, anti-inflammatory, protect liver and anticancer.L-lysine and L-arginine are the required amino of body
Acid other than general trophic function, while also having multiple-effect biological activity.Wherein, L-lysine has anti-inflammatory and antalgic, protection liver
Cell, diuresis, immunological enhancement and antivirus action.L-arginine is the nitric oxide production precursor substance of body, can be one
Nitric oxide synthase (NOS) catalysis generates biologically active NO, so as to improve mucosal structure, enhances immunity of organisms.Together
When, the use of L-lysine and L-arginine also has the work for increasing skullcapflavone dissolving and improving skullcapflavone bioavilability
With the medication demand of suitable large-scale cultivation waterline administration route.Pharmaceutical composition of the present invention, which not only can effectively press down, kills sramana
Bacterium, while can be horizontal by adjusting laying hen immunological defense and intestinal health, therefore can effectively reduce the level of laying hen detection of Salmonella
Egg source contact scar caused by with potential endogenous displacement is propagated, laying hen detection of Salmonella is purified, reduces the horizontal transmission of chicken group's detection of Salmonella
With egg source contact scar caused by potential endogenous displacement, egg laying performance egg quality is improved, effectively avoids egg source property detection of Salmonella dirty
Food-safety problem caused by dye.
Specific implementation mode
Embodiment below facilitates a better understanding of the present invention, but does not limit the present invention.Experiment in following embodiments
Method is unless otherwise specified conventional method.Test material as used in the following examples is unless otherwise specified city
It sells.
The pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention includes each component of following mass fraction：
30-50 parts of skullcapflavone, 20-40 parts of L-lysine, 30-50 parts of L-arginine.
Skullcapflavone in above-mentioned composition is prepared according to following extracting method, obtain the content of skullcapflavone with
Scutelloside meter is up to 90-96%.
(1) skullcapflavone extracts：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, 5-10 times of 50% diformazan of medicinal material weight is added
Base sulfoxide solution, 40-60 DEG C extracts 1-3 times, 30-90 minutes each, filtration, and merging filtrate is spare.
(2) UF membrane：The filtrate that step (1) is obtained carries out UF membrane, and UF membrane condition is：Select the inorganic pottery of 10nm
Porcelain film, 25-40 DEG C of flow 1.2-1.8L/min, pressure 0.12MPa and feed temperature, obtains skullcapflavone concentrate.
(3) it is spray-dried：The skullcapflavone concentrate that step (2) obtains is spray-dried, spray drying condition is：
100-150 DEG C of inlet air temperature, feed volume flow 6-12mL/min.
When being extracted with following optimal conditions, the content of skullcapflavone is obtained in terms of scutelloside, reaches highest, it is reachable
95.0% or more.
(1) skullcapflavone extracts：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, it is sub- that 5 times of 50% dimethyl of medicinal material weight are added
Sulfolane solution, 40 DEG C extract 2 times, 60 minutes every time, filter, merging filtrate is spare.
(2) UF membrane：The filtrate that step (1) is obtained carries out UF membrane, and UF membrane condition is：Select the inorganic pottery of 10nm
Porcelain film, flow 1.5L/min, pressure 0.12MPa and 30 DEG C of feed temperature, obtain skullcapflavone concentrate.
(3) it is spray-dried：The skullcapflavone concentrate that step (2) obtains is spray-dried, spray drying condition is：
120 DEG C of inlet air temperature, feed volume flow 9mL/min.
The preparation method of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：In prescription ratio, weigh
Skullcapflavone, L-lysine and L-arginine, mixing, packing to get.
Embodiment 1
The formula of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：
30 parts by weight of skullcapflavone, 20 parts by weight of L-lysine, 30 parts by weight of L-arginine.
Wherein, the preparation method of skullcapflavone is：
(1) skullcapflavone extracts：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, it is sub- that 5 times of 50% dimethyl of medicinal material weight are added
Sulfolane solution, 40 DEG C extract 2 times, 60 minutes every time, filter, merging filtrate is spare.
(2) UF membrane：The filtrate that step (1) is obtained carries out UF membrane, and UF membrane condition is：Select the inorganic pottery of 10nm
Porcelain film, flow 1.5L/min, pressure 0.12MPa and 30 DEG C of feed temperature, obtain skullcapflavone concentrate.
(3) it is spray-dried：The skullcapflavone concentrate that step (2) obtains is spray-dried, spray drying condition is：
120 DEG C of inlet air temperature, feed volume flow 9mL/min.The content of obtained skullcapflavone reaches highest in terms of scutelloside, can
Up to 95.0%.
The preparation method of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：According to prescription ratio, claim
Skullcapflavone 30kg, L-lysine 20kg, L-arginine 30kg, mixing, packing is taken to obtain prevention laying hen Salmonella infection disease
Pharmaceutical composition.
Embodiment 2
The formula of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：
35 parts by weight of skullcapflavone, 30 parts by weight of L-lysine, 35 parts by weight of L-arginine.
The preparation method of skullcapflavone is same as Example 1.
According to prescription ratio, skullcapflavone 35kg, L-lysine 30kg, L-arginine 35kg, mixing are weighed, packing obtains
To the pharmaceutical composition of prevention laying hen Salmonella infection disease.
Embodiment 3
The formula of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：
30 parts by weight of skullcapflavone, 40 parts by weight of L-lysine, 30 parts by weight of L-arginine.
The preparation method of skullcapflavone is same as Example 1.
According to prescription ratio, skullcapflavone 30kg, L-lysine 40kg, L-arginine 30kg, mixing are weighed, packing obtains
To the pharmaceutical composition of prevention laying hen Salmonella infection disease.
Embodiment 4
The formula of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：
40 parts by weight of skullcapflavone, 25 parts by weight of L-lysine, 35 parts by weight of L-arginine.
The preparation method of skullcapflavone is：
(1) skullcapflavone extracts：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, it is sub- that 7 times of 50% dimethyl of medicinal material weight are added
Sulfolane solution, 55 DEG C extract 1 time, 30 minutes every time, filter, merging filtrate is spare.
(2) UF membrane：The filtrate that step (1) is obtained carries out UF membrane, and UF membrane condition is：Select the inorganic pottery of 10nm
Porcelain film, flow 1.8L/min, pressure 0.12MPa and 25 DEG C of feed temperature, obtain skullcapflavone concentrate.
(3) it is spray-dried：The skullcapflavone concentrate that step (2) obtains is spray-dried, spray drying condition is：
100 DEG C of inlet air temperature, feed volume flow 12mL/min.The content of obtained skullcapflavone is in terms of scutelloside, up to 93.0%.
According to prescription ratio, skullcapflavone 40kg, L-lysine 25kg, L-arginine 35kg, mixing are weighed, packing obtains
To the pharmaceutical composition of prevention laying hen Salmonella infection disease.
Embodiment 5
The formula of pharmaceutical composition of the prevention laying hen Salmonella infection disease of the present invention is：
45 parts by weight of skullcapflavone, 35 parts by weight of L-lysine, 45 parts by weight of L-arginine.
The preparation method of skullcapflavone is：
(1) skullcapflavone extracts：Baikal skullcap root decoction pieces are crushed, 80 mesh screens are crossed, it is molten that 10 times of 50% dimethyl sulfoxide (DMSO)s of amount are added
Liquid, 60 DEG C extract 3 times, 90 minutes every time, filter, merging filtrate is spare.
(2) UF membrane：The filtrate that step (1) is obtained carries out UF membrane, and UF membrane condition is：Select the inorganic pottery of 10nm
Porcelain film, flow 1.2L/min, pressure 0.12MPa and 40 DEG C of feed temperature, obtain skullcapflavone concentrate.
(3) it is spray-dried：The skullcapflavone concentrate that step (2) obtains is spray-dried, spray drying condition is：
150 DEG C of inlet air temperature, feed volume flow 6mL/min.The content of obtained skullcapflavone is in terms of scutelloside, up to 91.0%.
According to prescription ratio, skullcapflavone 45kg, L-lysine 35kg, L-arginine 45kg, mixing are weighed, packing obtains
To the pharmaceutical composition of prevention laying hen Salmonella infection disease.
Essence and pharmaceutical composition of the present invention in order to further illustrate the present invention prevents laying hen Salmonella infection disease
Advantageous effect, applicant have carried out Clinical Treatment Test research to pharmaceutical composition of the present invention, to illustrate pharmaceutical composition of the present invention
The excellent effect of object.
Embodiment 6
(1) the evaluation of clinical curative effect experimental study of medicine composite for curing laying hen Salmonella infection disease of the present invention
1 test drug
Pharmaceutical composition of the present invention.
2 experimental animals
The salmonella gallinarum antibody positive chicken group of Beijing Miyun County breeding layer chicken field, this laying rate of laying hen decline
20%, broken rate of eggshell is high, is detected as using white diarrhea, fowl typhoid multivalence Avian tubercula plain agglutination test antigen (China Veterinary Drugs Supervisory Inst.'s production)
The chicken of laying eggs of detection of Salmonella antibody positive is included in this experimental study, shares 400, is egg-laying peak chicken.
3 experimental designs
The above-mentioned salmonella gallinarum antibody positive laying hen for meeting this research is randomly divided into 4 groups by 3.1 random groupings, wherein compareing
Group (100), 3 groups of experiment 1 group (embodiment 1,100), experiment 2 groups (embodiments 2,100) and experiment (embodiments 3,100
Only).
3.2 therapeutic schemes pharmaceutical composition group of the present invention (3 groups of 1 group of experiment, 2 groups of experiment and experiment), according to 0.1g/kg
Bw dosages are used in conjunction 7 days once a day.Control group, amoxicillin soluble powder, a secondary amounts, per 1kg weight 30mg,
2 times a day, it is used in conjunction 7.
3.3 efficacy determinations and detection method
3.3.1 index of assessment of curative effect
The 14th day after effective last medication treatment, sramana's bacteria antibody is detected using blood plate agglutination test, the person of turning out cloudy sentences
It is effective.
The 14th day after invalid last medication treatment, sramana's bacteria antibody is detected using blood plate agglutination test, is positive
It is invalid to be judged to.
3.3.2 after detection method fully shakes up white diarrhea, fowl typhoid multivalence Avian tubercula plain agglutination test antigen, 20 are drawn with pipettor
Then μ l drops puncture vein under chicken wings on glass plate with syringe needle, after blood outflow, draw 20 μ l blood with pipettor immediately
It is put into antigen liquid, blood is uniformly mixed with antigen, and it is about 2cm so that it is scattered to diameter, gently shakes reaction plate, carefully
Observation, judges result in 2min.It is the positive apparent particle or blocky agglutination person occur, and it is the moon that particle or agglutination person do not occur
Property, between it is above-mentioned be between the two it is suspicious, after 7 days acquiring blood again is detected confirmation.
4 data statistics
It utilizes(Version 17.0) carries out data analysis.The healing of four groups of tested chickens is evaluated in Chi-square Test
Rate, P<0.05 thinks that the difference examined is statistically significant.
5 results
Compared with the control group, the cure rate pole of medicine composite for curing laying hen Salmonella infection disease of the present invention significantly improves (p
<0.01), three other cure rates of group are respectively 88.0%, 96.0% and 94.0%, the results are shown in Table 1.
1 medicine composite for curing laying hen Salmonella infection disease clinical effect trial result of the present invention of table
Note：Same letter person difference not significantly (P is indicated with column data shoulder>0.05) different lowercase person differences, are marked
Significantly (P<0.05)；Same group same column marks different capitalization person significant difference (P<0.01).Similarly hereinafter.
6 conclusions
Pharmaceutical composition of the present invention can effectively treat laying hen Salmonella infection disease.Since the pharmaceutical composition of embodiment 2 exists
Therapeutic effect is best in curative tests result, pretends the test medicine of the clinical test to prevent laying hen Salmonella infection disease.
(2) pharmaceutical composition of the present invention prevents the clinical effectiveness of laying hen salmonella gallinarum infectious disease
1 test drug
The pharmaceutical composition of the present invention of embodiment 2.
2 experimental animals
Beijing Miyun County breeding layer chicken field, totally 3600 laying hens, 28 week old, average weight are 3.3 ± 0.4kg/.
3 purification schemes
It is not divided into control group (1800) and purification administration group (1800) according to, starts to purify medication in 28 week old,
According to 0.1g/kgbw dosages, it is administered 7 days, it is as a treatment course, later at interval of one course for the treatment of of medication in 30 days, until
58 week old are eliminated, and are shared medicine and are intervened 28 weeks.And control group is not administered, two groups are in henhouse structure, cage tool, feed, drinking-water, illumination
With it is completely the same on immune equal feeding and management conditions.
4 test indexes are observed and record
4.1 detection of Salmonella antibody positive rates be detected on administration before (the 28th week), the 40th week and 52 weeks, using blood tablet agglutination
Testing inspection salmonella gallinarum antibody positive rate.Method is same as above.
The influence of the production performance of 4.2 pairs of tested chickens
4.2.1 egg laying performance
Laying rate：It is the every day entry egg production of unit to repeat (cage), counts laying rate.Laying rate=100 × egg production
(piece)/chicken number (only).
Average egg weight：To repeat (cage) as unit, weigh daily by piece.
Average daily gain：It using " knock-out bottom " method, to repeat (cage) as unit, counts 1 time weekly, when off-test counts
Calculate full period average daily gain.
Feedstuff-egg ratio：To repeat (cage) as unit, feedstuff-egg ratio is calculated by experimental period total egg production and feed consumption：Feedstuff-egg ratio
Food consumption total amount (kg)/often is often repeated during=measurement repeats total yield egg size (kg).
4.2.2 egg detection of Salmonella
It is carried out with reference to 4789.4-2010 microbiological test of food hygiene detection of Salmonella of GB/T.Using preceding increasing bacterium, increase bacterium pair
Detection of Salmonella is expanded, and separation bacterium pure culture is inoculated in respectively in Bacteria Identification culture medium and micro biochemical reaction tube, is set
36 DEG C of constant temperature incubations 18~for 24 hours, observing response situation, then identified.
4.2.3 egg quality
(cage) during experiment, is often repeated weekly and randomly selects 7 pieces of egg, measures following index respectively.
Egg proportion：It is measured with saline floatation method.
Egg shape index：The major diameter and minor axis of vernier caliper measurement egg calculate egg shape index.Egg shape index=major diameter/minor axis.
Shell thickness：Take respectively blunt end, middle part, sharp end eggshell reject inner shell membrane after with miking, its thickness asks flat
Mean value.As unit of mm, it is accurate to 0.01mm.
Egg breakage rate：The ratio of damaged egg number and total egg number.
5 data processings
It utilizes(Version 17.0) carries out data analysis.All statistical checks are all made of two-sided test, p<0.05
Think that the difference examined is statistically significant.
6 pharmaceutical compositions of the present invention prevent the clinical effectiveness of laying hen Salmonella infection disease
6.1 pharmaceutical compositions of the present invention prevent the effect of laying hen Salmonella infection disease
Compared with the control group, before experiment, salmonella gallinarum antibody positive rate indifference (p > 0.05) in two groups；40th week and
52nd week, laying hen detection of Salmonella antibody positive rate pole significantly reduced (p in pharmaceutical composition of the present invention<0.01).It the results are shown in Table 2.
2 pharmaceutical composition of the present invention of table prevents the clinical effect trial result of laying hen Salmonella infection disease
Influence of 6.2 pharmaceutical compositions of the present invention to the egg laying performance of tested chicken group
Compared with the control group, the average daily gain indifference (p > 0.05) of tested chicken group, and laying rate, average egg weight
It is improved with feedstuff-egg ratio, significant difference (p<0.05).Show to bestow method and purification scheme according to pharmaceutical composition of the present invention, can have
Effect improves the egg laying performance of tested laying hen group, the results are shown in Table 3.
Influence of 3 pharmaceutical composition of the present invention of table to the egg laying performance of tested chicken group
6.3 pharmaceutical compositions of the present invention carry the egg of tested chicken group the influence of detection of Salmonella
Compared with the control group, the egg eggshell of tested chicken group and egg content detection of Salmonella recall rate reduce, and difference is extremely notable
(p<0.01).It the results are shown in Table 4.
4 pharmaceutical composition of the present invention of table carries the egg of tested chicken group the influence of detection of Salmonella
Influence of 6.4 pharmaceutical compositions of the present invention to the Egg Quality of tested chicken group
Compared with the control group, the egg proportion and egg shape index indifference (p > 0.05) of the egg of tested chicken group, and eggshell
Thickness significantly improves (p<0.05) and egg breakage rate pole significantly reduces (p<0.01).It the results are shown in Table 5.
Influence of 5 pharmaceutical composition of the present invention of table to the Egg Quality of tested chicken group
| Group | Egg proportion | Egg shape index | Shell thickness | Egg breakage rate % |
| Control group | 1.08 | 1.26±0.01 | 0.34±0.01a | 2.5A |
| Test group | 1.08 | 1.27±0.01 | 0.37±0.02b | 0.4B |
7 conclusions bestow method according to pharmaceutical composition of the present invention and prevent intervention stratege, and it is husky can effectively to reduce tested chicken group
Door bacteria antibody positive rate, improves egg laying performance, reduces egg detection of Salmonella carrying rate, improves egg quality.
Finally it should be noted that：The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention,
Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used
With technical scheme described in the above embodiments is modified or equivalent replacement of some of the technical features.
All within the spirits and principles of the present invention, any modification, equivalent replacement, improvement and so on should be included in the present invention's
Within protection domain.
Claims (8)
1. pharmaceutical composition prepare prevention laying hen Salmonella infection disease drug, improve Layer Production Performance, reduce eggshell and
Egg content carries detection of Salmonella quantity and improves the application in laying hen Egg Quality, and each bulk pharmaceutical chemicals are by weight in described pharmaceutical composition
Amount part is calculated as：30-50 parts of skullcapflavone, 20-40 parts of L-lysine, 30-50 parts of L-arginine.
2. application according to claim 1, it is characterised in that：Each raw material medicaments in part by weight meter in described pharmaceutical composition
For：35 parts of skullcapflavone, 30 parts of L-lysine, 35 parts of L-arginine.
3. application according to claim 1 or 2, it is characterised in that：The preparation method of the skullcapflavone is：Radix scutellariae is drunk
Piece is extracted after crushing with dimethyl sulphoxide solution, and filtrate is collected by filtration, filtrate is carried out UF membrane, obtains skullcapflavone concentration
Then liquid is spray-dried.
4. application according to claim 3, it is characterised in that：The preparation method of the skullcapflavone is：By baikal skullcap root decoction pieces
It crushes, crosses 80 mesh screens, 5-10 times of 50% dimethyl sulphoxide solution of medicinal material weight is added, 40-60 DEG C extracts 1-3 times, each 30-
90 minutes, filtration, merging filtrate selected the inorganic ceramic membrane of 10nm, flow 1.2-1.8L/min, pressure 0.12MPa and material
25-40 DEG C of liquid temperature carries out UF membrane, skullcapflavone concentrate is obtained, with 100-150 DEG C of inlet air temperature, feed volume flow 6-
The condition of 12mL/min is spray-dried.
5. application according to claim 4, it is characterised in that：The preparation method of the skullcapflavone is：By baikal skullcap root decoction pieces
It crushes, crosses 80 mesh screens, 5 times of 50% dimethyl sulphoxide solutions of medicinal material weight are added, 40 DEG C extract 2 times, 60 minutes every time, filter
It crosses, merging filtrate, selects the inorganic ceramic membrane of 10nm, flow 1.5L/min, pressure 0.12MPa and 30 DEG C of feed temperature, into
Row UF membrane obtains skullcapflavone concentrate, and with 120 DEG C of inlet air temperature, the condition of feed volume flow 9mL/min carries out spraying and does
It is dry.
6. according to claim 1-4 any one of them applications, it is characterised in that：Described pharmaceutical composition is claimed according to recipe quantity
Take skullcapflavone, L-lysine and L-arginine, mixing to obtain the final product.
7. application according to claim 1, it is characterised in that：The Layer Production Performance is laying rate and average egg weight.
8. application according to claim 1, it is characterised in that：The raising laying hen Egg Quality is to improve shell thickness and drop
Low egg breakage rate.
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