CN110269880A - A kind of clear particle of wormwood artemisia indigo plant epidemic disease, preparation method and application - Google Patents
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, preparation method and application Download PDFInfo
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- 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)
- A61K36/19—Acanthaceae (Acanthus family)
- A61K36/195—Strobilanthes
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- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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- 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)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
- A61K36/315—Isatis, e.g. Dyer's woad
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- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
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- 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)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
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- 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)
- A61K36/85—Verbenaceae (Verbena family)
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation 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
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
The invention belongs to veterinary Chinese medicine technical field more particularly to a kind of clear particles of wormwood artemisia indigo plant epidemic disease, preparation method and application.The present invention is in the preparation process of the clear particle of wormwood artemisia indigo plant epidemic disease, alpine yallow herb and other raw materials are extracted using ethanol reflux extraction combination water boiling and extraction method, alcohol-soluble and water-soluble effective active composition are sufficiently obtained, principle active component is preferably saved in the final clear particle of wormwood artemisia indigo plant epidemic disease.The preparations such as Chinese traditional herbs pulvis in compared with the existing technology crude fiber content is high, effective component is difficult to the deficiency dissolved out, since the active constituent content in the clear particle of wormwood artemisia indigo plant epidemic disease of the invention is higher, it is easy to absorb, bioavilability is high, lung channel, Liver Channel, kidney channel can be invaded resisting heat symptoms caused by an exopathgen outside Muscovy duck parvovirus, liver protection protects kidney etc. and more preferably plays clinical effectiveness.In addition, the clear particle of wormwood artemisia indigo plant epidemic disease of the invention quick and complete can be dissolved in livestock and poultry drinking water, cultivation drinking-water system is not blocked, and scale poultry-farm is facilitated to use.
Description
Technical field
The invention belongs to veterinary Chinese medicine technical field more particularly to a kind of clear particles of wormwood artemisia indigo plant epidemic disease, preparation method and application.
Background technique
Muscovy duck parvovirus disease (Muscovy Duck Parvovirosis, MP) is commonly called as " three weeks diseases ", is thin by kind duck
One kind caused by small virus (Muscovy Duck Parvovirus, MPV) is acute, septic, viral infectious.Mainly invade
Muscovy duckling within 3 week old of evil, has high degree in contact infectiousness, and morbidity and mortality are all very high, it is characterized in that asthma, abdomen
It rushes down, internal organs bleeding, ataxia and nervous symptoms, seriously affects the growth of kind duck.This disease can all occur throughout the year, be harm
One of the principal disease of duck industry.
The domestic prevention and treatment to MP at present, clinically substantially there is vaccine, antiviral chemical drug and the several aspects of Chinese herb prevention.Although
The use of vaccine plays certain prevention and control action to the prevalence of MP, but due to the highly infectious and MPV serum of MP
The complexity of type has lesser intersecting protective even without intersecting protective between different serotypes strain, makes immunoprophylaxis
It complicates and prevention cost increases.Therefore, MP makes at present still in immune duck group and nonimmune duck mass-sending life and propagation to aviculture
At serious economic loss.Treatment in terms of chemical drug for this disease is based on treating the symptoms, because the chemistry such as Ribavirin is anti-
In the disabling of food animal, clinic mostly uses the antimicrobial antiphlogistics such as quinolones, cephalo-type, prevents secondary infection virus drugs, with
For the purpose of reducing the death rate, but it is exceeded to often result in antibiotic residue, threatens human health and life security.Paid examination in terms of Chinese medicine
Dissipated etc. with Antiphlogistic Powder of Schizonepetae and Ledebouriellae, Chinese ephedra ramulus cinnamomi, with improve immunity, it is clearing heat and detoxicating based on, and spice medication is inconvenient, at high cost,
Cure rate is low.
Therefore, a kind of Chinese materia medica preparation that can effectively treat Muscovy duck parvovirus disease how is obtained, is the technology of this field
Personnel's technical problem urgently to be resolved.
Summary of the invention
The present invention in view of the deficiency of the prior art, provides that a kind of clinical use is convenient and the preferable wormwood artemisia of curative effect is blue
The clear particle of epidemic disease, preparation method and application.
The technical scheme to solve the above technical problems is that a kind of clear particle of wormwood artemisia indigo plant epidemic disease, component is according to weight
Number meter includes 20-35 parts of alpine yallow herb, 10-20 parts of Radix Isatidis, 10-25 parts of folium isatidis and 5-15 parts of Radix Glycyrrhizae.
Preferably, the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, component include 25 parts of alpine yallow herb, Radix Isatidis 15 in parts by weight
Part, 20 parts of folium isatidis and 10 parts of Radix Glycyrrhizae.
Preferably, the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, further includes pharmaceutical diluents and binder.
Wherein, the pharmaceutical diluents are one or more of starch, sucrose, dextrin, lactose or inorganic salts;
The binder is one or more of distilled water, ethyl alcohol, sucrose, polyethylene glycol or cellulose derivative.
Beneficial effect using the above scheme is, the ratio of briquetting of granule can be improved in pharmaceutical diluents and binder, changes
Kind melting, reduces its hygroscopicity, so that the stationary phase of particle storage is longer, it is ensured that clinical efficacy.The preferably above-mentioned medicine of the present invention
Object diluent and binder, however, it is not limited to this, can improve drug quality, ensure curative effect and to the medicine of animal nonhazardous
Object diluent and binder.
Preferably, 0.4-0.7mg sesquiterpenoids ingredient and 0.15-0.20mg ucleosides are contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Ingredient.
It is highly preferred that containing 0.5-0.7mg sesquiterpenoids ingredient and 0.18-0.20mg nucleosides in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Constituents.
Second object of the present invention is to provide the preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, and steps are as follows:
(1) 20-35 parts of alpine yallow herb, 10-20 parts of Radix Isatidis, 10-25 parts of folium isatidis and 5-15 parts of Radix Glycyrrhizae are taken, are crushed to respectively
Coarse powder;
(2) the alpine yallow herb coarse powder for taking step (1), is extracted using alcohol reflux, obtains alcohol extract and the alcohol extracting dregs of a decoction;By gained
Alcohol extract concentration, obtains alcohol extracting cream;
(3) the alcohol extracting dregs of a decoction for taking step (2), Radix Isatidis coarse powder, smalt leaf coarse powder and the Radix Glycyrrhizae for adding step (1) are thick
Powder is soaked in water, and is decocted and is extracted, obtains Aqueous extracts;Aqueous extracts are concentrated, alcohol precipitation, be concentrated again after, obtain water and mention cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, obtains mixing dried cream powder;After
It is continuous that pharmaceutical diluents and binder is added, it mixes, through wet granulation, drying, whole grain, obtains the clear particle of wormwood artemisia indigo plant epidemic disease.
Further, it in step (1), by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, crushes, obtains respectively
To the coarse powder of 24-80 mesh.
Beneficial effect using above-mentioned further scheme is to increase medicinal material specific surface area, be conducive to effective ingredient
Dissolution improves the recovery rate of medicinal material effective component, and then guarantees curative effect of medication.
Further, in step (2), the alpine yallow herb coarse powder of step (1) is placed in the first multi-function extractor, second is added
Alcohol repeats refluxing extraction 2-5 times, each 1-3h, and filtering obtains alcohol extract and the alcohol extracting dregs of a decoction;Again by alcohol extract 50-60 DEG C,
It is concentrated under the conditions of 0.05-0.15MPa, obtains the alcohol extracting cream that relative density is 1.05-1.15.
Further, in step (2), the concentration of ethyl alcohol is 60-90wt%, the dosage weight of the ethyl alcohol and alpine yallow herb coarse powder
Amount is than being (6-12): 1.
Beneficial effect using above-mentioned further scheme is operated by alcohol extracting, and the alcohol-soluble extracted in alpine yallow herb is main
Effective active composition -- sesquiterpenoids.
Further, in step (3), by the alcohol extracting dregs of a decoction of step (2) and the Radix Isatidis coarse powder of step (1), smalt leaf coarse powder
It is placed in the second multi-function extractor with Radix Glycyrrhizae coarse powder, is uniformly mixed to obtain mixture, the water of 8-20 times of mixture weight, leaching is added
0.5-2h is steeped, repeats to decoct and extract 2-3 times, each 1-2.5h, filtering obtains Aqueous extracts;Aqueous extracts are concentrated into relative density
The clear cream of 1.05-1.15 (50 DEG C) is added ethyl alcohol to its concentration into clear cream and reaches 50-70wt%, carry out alcohol precipitation, stands 12-
48h takes supernatant to be concentrated under the conditions of 60-65 DEG C, 0.05-0.15MPa, obtains the water that relative density is 1.05-1.15 and mentions cream.
Beneficial effect using above-mentioned further scheme is to propose operation by water, extract in Radix Isatidis, folium isatidis and Radix Glycyrrhizae
The main effective active composition-ucleosides of water solubility.
Further, in step (4), the atomizing pressure of spray drying is 0.3-0.6MPa, charging rate 200-600mL
h-1, inlet air temperature is 155-175 DEG C, and leaving air temp is 50-75 DEG C.
Third object of the present invention is to provide the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease in treatment Muscovy duck parvovirus disease field
Using.
The usage and dosage of the clear particle of wormwood artemisia indigo plant epidemic disease of the present invention is daily 0.5-3g/kg weight, is added in birds drinking-water
It is freely drunk for fowl.
The features of the present invention and beneficial effect are:
1, in traditional Chinese medicine ingredients of the invention, alpine yallow herb is clearing heat and detoxicating, food digesting stomach fortifying, wind-dispelling cholagogue;Radix Isatidis heat-clearing solution
Poison, cool blood relieving sore-throat;Folium isatidis is clearing heat and detoxicating, blood cooling and ecchymoses removing;Radix Glycyrrhizae is invigorated the spleen and benefited qi, expelling phlegm and arresting coughing and middle emergency, removing toxic substances reconcile
All medicines alleviate drug toxicity, strong, and solve alpine yallow herb toxicity and all medicines.Above-mentioned each taste medicine shares, and kidney, detumescence are protected in removing toxic substances liver protection
It relieves pain, a surname's drop is harmonious, and clear respectful collaboration, benefit is evident, resists heat symptoms caused by an exopathgen intrusion lung channel, liver outside infectiousness Muscovy duck parvovirus to reach
Combined therapy effect through, kidney channel, can be substantially reduced or effectively removes lassitude, appetite stimulator, production performance decline, especially
Be breathe, cough, diarrhea, the pneumonia even clinical symptoms such as ephritis, play the therapeutic effect for the treatment of both manifestation and root cause of disease.
2, the present invention utilizes suitable composition of raw materials ratio, and the excellent clear particle of wormwood artemisia indigo plant epidemic disease of therapeutic effect is made;Meanwhile this hair
Bright pure Chinese medicine resourceful using the Northwest, excellent quality is made, from a wealth of sources, low in cost, noresidue, nontoxic secondary work
With high financial profit is suitable for large-scale production and application.
3, the effective component in alpine yallow herb generally in the prior art, is extracted using the method that water decocts, but water decocted
Journey is only capable of extracting the water soluble ingredients such as polysaccharide, organic acid and glycoside in alpine yallow herb, can not will be in alpine yallow herb
The alcohol-solubles main pharmacodynamics constituents extraction such as sesquiterpenoids come out, cannot substantially effectively play it so as to cause medicinal raw material
The drug effect come.The present invention is in the preparation process of the clear particle of wormwood artemisia indigo plant epidemic disease, using ethanol reflux extraction combination water boiling and extraction method
Alpine yallow herb and other raw materials are extracted, alcohol-soluble and water-soluble effective active composition are sufficiently obtained so that it is main effectively at
Dividing can preferably be saved in the final clear particle of wormwood artemisia indigo plant epidemic disease.The system such as Chinese traditional herbs pulvis in compared with the existing technology
Agent crude fiber content is high, effective component is difficult to the deficiency dissolved out, since the effective component in the clear particle of wormwood artemisia indigo plant epidemic disease of the invention contains
Amount is higher, is easy to absorb, and bioavilability is high, can more preferably play clinical effectiveness.In addition, the clear particle of wormwood artemisia indigo plant epidemic disease of the invention
It quick and complete can be dissolved in livestock and poultry drinking water, not block cultivation drinking-water system, scale poultry-farm is facilitated to use.
Specific embodiment
Principles and features of the present invention are described below in conjunction with example, the given examples are served only to explain the present invention, and
It is non-to be used to limit the scope of the invention.
Embodiment 1
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, component include 25 parts of alpine yallow herb, 15 parts of Radix Isatidis, smalt in parts by weight
20 parts and 10 parts of Radix Glycyrrhizae of leaf.
The preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, steps are as follows:
(1) by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, high speed is crushed respectively, respectively obtains 65 mesh
Coarse powder;
(2) the alpine yallow herb coarse powder of step (1) is placed in the first multi-function extractor, addition 8 times of weight of alpine yallow herb coarse powder,
The ethyl alcohol of concentration 70wt% repeats refluxing extraction 2 times, each 1.5h, and filtering, merging filtrate obtains alcohol extract and the alcohol extracting dregs of a decoction;
Alcohol extract is concentrated under the conditions of 50 DEG C, 0.05MPa again, obtains the alcohol extracting cream that relative density is 1.1;
(3) the alcohol extracting dregs of a decoction of step (2) and the Radix Isatidis coarse powder of step (1), smalt leaf coarse powder and Radix Glycyrrhizae coarse powder are placed in
In second multi-function extractor, it is uniformly mixed to obtain mixture, 12 times of mixture weight of water is added, impregnates 1.0h, repeats to decoct
It extracts 2 times, each 2h, filtering obtains Aqueous extracts;Aqueous extracts are concentrated into the clear cream that relative density is 1.1 (50 DEG C), into clear cream
Ethyl alcohol to its concentration is added and reaches 50wt%, carries out alcohol precipitation, stands for 24 hours, supernatant is taken to be concentrated under the conditions of 65 DEG C, 0.05MPa,
It obtains the water that relative density is 1.1 and mentions cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, atomizing pressure 0.4MPa,
Charging rate is 400mLh-1, inlet air temperature is 170 DEG C, and leaving air temp is 60 DEG C, obtains mixing dried cream powder;Continuously add sugarcane
Sugar and dextrin mix, through wet granulation, drying, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
High performance liquid chromatography (annex 0512) is detected, and 0.5mg sesquiterpenoids is contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Ingredient and 0.18mg gradient elution.The clear particle of wormwood artemisia indigo plant epidemic disease is distributed into bag, every bag of 500g.
Embodiment 2
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, component include 35 parts of alpine yallow herb, 10 parts of Radix Isatidis, smalt in parts by weight
25 parts and 15 parts of Radix Glycyrrhizae of leaf.
The preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, steps are as follows:
(1) by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, high speed is crushed respectively, respectively obtains 24 mesh
Coarse powder;
(2) the alpine yallow herb coarse powder of step (1) is placed in the first multi-function extractor, addition 6 times of weight of alpine yallow herb coarse powder,
The ethyl alcohol of concentration 90wt% repeats refluxing extraction 5 times, each 1.0h, and filtering, merging filtrate obtains alcohol extract and the alcohol extracting dregs of a decoction;
Alcohol extract is concentrated under the conditions of 60 DEG C, 0.1MPa again, obtains the alcohol extracting cream that relative density is 1.15;
(3) the alcohol extracting dregs of a decoction of step (2) and the Radix Isatidis coarse powder of step (1), smalt leaf coarse powder and Radix Glycyrrhizae coarse powder are placed in
In second multi-function extractor, it is uniformly mixed to obtain mixture, 20 times of mixture weight of water is added, impregnates 0.5h, repeats to decoct
It extracts 2 times, each 2.5h, filtering obtains Aqueous extracts;Aqueous extracts are concentrated into the clear cream that relative density is 1.05 (50 DEG C), Xiang Qing
Ethyl alcohol to its concentration is added in cream and reaches 60wt%, carries out alcohol precipitation, stands 12h, take supernatant under the conditions of 60 DEG C, 0.15MPa
Concentration obtains the water that relative density is 1.05 and mentions cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, atomizing pressure 0.6MPa,
Charging rate is 200mLh-1, inlet air temperature is 155 DEG C, and leaving air temp is 75 DEG C, obtains mixing dried cream powder;Continuously add sugarcane
Sugar and dextrin mix, through wet granulation, drying, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
High performance liquid chromatography (annex 0512) is detected, and 0.7mg sesquiterpenoids is contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Ingredient and 0.15mg gradient elution.The clear particle of wormwood artemisia indigo plant epidemic disease is distributed into bag, every bag of 500g.
Embodiment 3
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, component include 20 parts of alpine yallow herb, 20 parts of Radix Isatidis, smalt in parts by weight
10 parts and 5 parts of Radix Glycyrrhizae of leaf.
The preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, steps are as follows:
(1) by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, high speed is crushed respectively, respectively obtains 80 mesh
Coarse powder;
(2) the alpine yallow herb coarse powder of step (1) is placed in the first multi-function extractor, 12 times of weights of alpine yallow herb coarse powder is added
The ethyl alcohol of amount, concentration 60wt% repeats refluxing extraction 2 times, each 3.0h, and filtering, merging filtrate obtains alcohol extract and alcohol extracting medicine
Slag;Alcohol extract is concentrated under the conditions of 50 DEG C, 0.15MPa again, obtains the alcohol extracting cream that relative density is 1.05;
(3) the alcohol extracting dregs of a decoction of step (2) and the Radix Isatidis coarse powder of step (1), smalt leaf coarse powder and Radix Glycyrrhizae coarse powder are placed in
In second multi-function extractor, it is uniformly mixed to obtain mixture, 8 times of mixture weight of water is added, impregnates 2h, repeats to decoct and extract
3 times, each 1.0h, filtering obtains Aqueous extracts;Aqueous extracts are concentrated into the clear cream that relative density is 1.15 (50 DEG C), into clear cream
Ethyl alcohol to its concentration is added and reaches 70wt%, carries out alcohol precipitation, stands 48h, supernatant is taken to be concentrated under the conditions of 65 DEG C, 0.15MPa,
It obtains the water that relative density is 1.15 and mentions cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, atomizing pressure 0.3MPa,
Charging rate is 600mLh-1, inlet air temperature is 175 DEG C, and leaving air temp is 50 DEG C, obtains mixing dried cream powder;Continuously add sugarcane
Sugar and dextrin mix, through wet granulation, drying, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
High performance liquid chromatography (annex 0512) is detected, and 0.4mg sesquiterpenoids is contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Ingredient and 0.2mg gradient elution.The clear particle of wormwood artemisia indigo plant epidemic disease is distributed into bag, every bag of 500g.
Comparative example 1
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, component include 25 parts of alpine yallow herb, 15 parts of Radix Isatidis, smalt in parts by weight
20 parts and 10 parts of Radix Glycyrrhizae of leaf.
The preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, steps are as follows:
(1) by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, high speed is crushed respectively, respectively obtains 65 mesh
Coarse powder;
(2) the alpine yallow herb coarse powder of step (1), Radix Isatidis coarse powder, smalt leaf coarse powder and Radix Glycyrrhizae coarse powder are placed in multi-functional mention
It takes in tank, it is uniformly mixed to obtain mixture, 12 times of mixture weight of water is added, impregnates 1.0h, repeats to decoct extraction 2 times, every time
2h, filtering, obtains Aqueous extracts;Aqueous extracts be concentrated into relative density be 1.1 (50 DEG C) clear cream, into clear cream be added ethyl alcohol to its
Concentration reaches 50wt%, carries out alcohol precipitation, stands for 24 hours, takes supernatant to be concentrated under the conditions of 65 DEG C, 0.05MPa, obtain relative density
Cream is mentioned for 1.1 water;
(3) water of step (2) is mentioned into cream spray drying, atomizing pressure 0.4MPa, charging rate 400mLh-1, into
Air temperature is 170 DEG C, and leaving air temp is 60 DEG C, obtains mixing dried cream powder;Sucrose and dextrin are continuously added, is mixed, through wet process system
Grain, dry, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
High performance liquid chromatography (annex 0512) is detected, and 0.06mg sesquiterpenoids is contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Ingredient and 0.17mg gradient elution.The clear particle of wormwood artemisia indigo plant epidemic disease is distributed into bag, every bag of 500g.
Comparative example 2
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, component include 15 parts of alpine yallow herb, 25 parts of Radix Isatidis, smalt in parts by weight
5 parts and 20 parts of Radix Glycyrrhizae of leaf.
The preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, steps are as follows:
(1) by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, high speed is crushed respectively, respectively obtains 65 mesh
Coarse powder;
(2) the alpine yallow herb coarse powder of step (1) is placed in the first multi-function extractor, addition 8 times of weight of alpine yallow herb coarse powder,
The ethyl alcohol of concentration 70wt% repeats refluxing extraction 2 times, each 1.5h, and filtering, merging filtrate obtains alcohol extract and the alcohol extracting dregs of a decoction;
Alcohol extract is concentrated under the conditions of 50 DEG C, 0.05MPa again, obtains the alcohol extracting cream that relative density is 1.1;
(3) the alcohol extracting dregs of a decoction of step (2) and the Radix Isatidis coarse powder of step (1), smalt leaf coarse powder and Radix Glycyrrhizae coarse powder are placed in
In second multi-function extractor, it is uniformly mixed to obtain mixture, 12 times of mixture weight of water is added, impregnates 1.0h, repeats to decoct
It extracts 2 times, each 2h, filtering obtains Aqueous extracts;Aqueous extracts are concentrated into the clear cream that relative density is 1.1 (50 DEG C), into clear cream
Ethyl alcohol to its concentration is added and reaches 50wt%, carries out alcohol precipitation, stands for 24 hours, supernatant is taken to be concentrated under the conditions of 65 DEG C, 0.05MPa,
It obtains the water that relative density is 1.1 and mentions cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, atomizing pressure 0.4MPa,
Charging rate is 400mLh-1, inlet air temperature is 170 DEG C, and leaving air temp is 60 DEG C, obtains mixing dried cream powder;Continuously add sugarcane
Sugar and dextrin mix, through wet granulation, drying, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
High performance liquid chromatography (annex 0512) is detected, and 0.23mg sesquiterpenoids is contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Ingredient and 0.19mg gradient elution.The clear particle of wormwood artemisia indigo plant epidemic disease is distributed into bag, every bag of 500g.
Comparative example 3
A kind of clear particle of wormwood artemisia indigo plant epidemic disease, component include 40 parts of alpine yallow herb, 5 parts of Radix Isatidis, folium isatidis in parts by weight
30 parts and 10 parts of Radix Glycyrrhizae.
The preparation method of the above-mentioned clear particle of wormwood artemisia indigo plant epidemic disease, steps are as follows:
(1) by alpine yallow herb, Radix Isatidis, folium isatidis and Radix Glycyrrhizae after 60 DEG C of drying, high speed is crushed respectively, respectively obtains 65 mesh
Coarse powder;
(2) the alpine yallow herb coarse powder of step (1) is placed in the first multi-function extractor, addition 8 times of weight of alpine yallow herb coarse powder,
The ethyl alcohol of concentration 70wt% repeats refluxing extraction 2 times, each 1.5h, and filtering, merging filtrate obtains alcohol extract and the alcohol extracting dregs of a decoction;
Alcohol extract is concentrated under the conditions of 50 DEG C, 0.05MPa again, obtains the alcohol extracting cream that relative density is 1.1;
(3) the alcohol extracting dregs of a decoction of step (2) and the Radix Isatidis coarse powder of step (1), smalt leaf coarse powder and Radix Glycyrrhizae coarse powder are placed in
In second multi-function extractor, it is uniformly mixed to obtain mixture, 12 times of mixture weight of water is added, impregnates 1.0h, repeats to decoct
It extracts 2 times, each 2h, filtering obtains Aqueous extracts;Aqueous extracts are concentrated into the clear cream that relative density is 1.1 (50 DEG C), into clear cream
Ethyl alcohol to its concentration is added and reaches 50wt%, carries out alcohol precipitation, stands for 24 hours, supernatant is taken to be concentrated under the conditions of 65 DEG C, 0.05MPa,
It obtains the water that relative density is 1.1 and mentions cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, atomizing pressure 0.4MPa,
Charging rate is 400mLh-1, inlet air temperature is 170 DEG C, and leaving air temp is 60 DEG C, obtains mixing dried cream powder;Continuously add sugarcane
Sugar and dextrin mix, through wet granulation, drying, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
High performance liquid chromatography (annex 0512) is detected, and 0.61mg sesquiterpenoids is contained in the clear particle of every 1g wormwood artemisia indigo plant epidemic disease
Gradient elution is not detected in ingredient.The clear particle of wormwood artemisia indigo plant epidemic disease is distributed into bag, every bag of 500g.
Preclinical study of pharmacy
Below to the clinical prodrug of the clear particle of wormwood artemisia indigo plant epidemic disease obtained by the clear particle of wormwood artemisia indigo plant epidemic disease obtained by embodiment 1-3 and comparative example 1-3
Carry out test comparative studies.
1, antitussive effect is tested
Experimental method: Kunming mouse 70, weight 18-22g, half male and half female is randomly divided into 7 groups, every group 10.Test
1 group, 2 groups and 3 groups is taken the clear particle of wormwood artemisia indigo plant epidemic disease obtained by embodiment 1-3 respectively;It compares 1 group, 2 groups and 3 groups and takes comparative example respectively
The clear particle of wormwood artemisia indigo plant epidemic disease obtained by 1-3;Model group takes pure water.Each group is gastric infusion 1 time daily, and successive administration three days, dosage was shown in
Table 1.After last dose 1h, 1 every time, mouse is sequentially placed into 500mL closed beaker, at the uniform velocity constant pressure sprays into 30% ammonium hydroxide
10s causes cough, and record causes cough incubation period (to the cough number in the time s) and 2mi n for occurring coughing i.e. since by spraying, to calculate
Inhibiting rate takes the average of test group, control group and model group to be compared as the cough-relieving index of the medicine, counts credit
Analysis, concrete outcome are shown in Table 1.
The 1 clear particle of wormwood artemisia indigo plant epidemic disease of table antitussive effect (N=10)
Note: compared with model group, P < 0.01 * P < 0.05, * *.
From table 1 it follows that the cough latent period longest of 1 group of test, cough number is minimum;Test 2 groups and 3 groups of test
Cough latent period and cough number take second place;The cough latent period and cough number for compareing 1 group, 2 groups and 3 groups are only better than model
Group.Since the sesquiterpenoids ingredient in alpine yallow herb and the gradient elution in Radix Isatidis have stronger clearing heat and detoxicating, anti-inflammatory town
Bitterly, ventilating the lung and relieving cough, expectorant powder junction effect, and the present invention extracts sesquiterpenoids components matching water extract-alcohol precipitation using alcohol reflux and extracts
Effective active composition in medicinal material can fully be extracted from crude drug, and is effectively saved in by gradient elution
It in the final clear particle of wormwood artemisia indigo plant epidemic disease, acts synergistically with other medicines ingredient, so that effect of the drug in terms of eliminating phlegm and relieving asthma
It is stronger.It is compared from above data as can be seen that cough can be obviously prolonged using the clear particle of wormwood artemisia indigo plant epidemic disease prepared by method of the invention
Incubation period reduces cough number, has good therapeutic effect.
2, safety evaluatio and stability experiment
Mouse Acute Toxicity experiment fails to measure median lethal dose (LD50), therefore routinely further test medicine is carried out
Maximal tolerance dose (MTD) measurement.By maximum tolerance determination, the practical dosage of mouse is calculated, it may be assumed that 0.4mL/10g
Weight × 3 × 50% × 100 × 2.55g/mL=153g/kg weight, are equivalent to the crude drug amount of 153g/kg weight.Experiment shows
The invention belongs to clinical safety range preparations, can be considered nontoxic grade;Applied to prevention and treatment Muscovy duck parvovirus good security.
Chinese medicine used is that " Chinese veterinary pharmacopoeia " version in 2015 records kind in inventive formulation, different is produced to several
The formulation samples of batch carry out study on the stability by method as defined in veterinary drug allusion quotation.The result shows that the preparation within 2 years has no mould
The variation of change, agglomeration and color etc., HPLC method can still detect identification ingredient, clinical treatment Muscovy duck parvovirus effect
Well.Experiments have shown that invention formulation is with good stability, therefore, the closed storage of room temperature, validity period can temporarily be determined as 2
Year.
Clinical application example 1
There is death rate raising, spiritual tired, feather in March, 2019,14000, Tai'an duck culturing factory, 16 age in days kind duck
Fluffy, two wings are sagging, and tail end is bent downwardly, and bipod is powerless, rapid drawdown of searching for food, to some extent diarrhea, ash discharge white or light green
Loose stool, and it is adhered to anus surrounding.Later period often squats, mouth breathing.Dissect symptom: liver, kidney, spleen slightly, intrapulmonary blood vessel
Hyperemia, pancreas bubble necrosis, cloaca product have a large amount of white excrement.Comprehensive diagnos is Muscovy duck parvovirus disease.
14000 ducks are divided into 4 groups at random, 3 experimental groups and 1 control group, every group 3500.During experiment, respectively
Group duck group uses identical feeding management measure.Experimental group 1,2,3 be respectively adopted the clear particle of wormwood artemisia indigo plant epidemic disease in embodiment 1,2,3 into
Row treatment, specific usage and dosage are as follows: mixed drink, the clear particle of every 500g wormwood artemisia indigo plant epidemic disease are watered 500L, freely drink, 5d is used in conjunction.Control
Group: it is treated using commercially available Antiphlogistic Powder of Schizonepetae and Ledebouriellae and Wymox, continuous use 5d, detailed directions dosage are as follows: every 500kg
Complete feed adds Antiphlogistic Powder of Schizonepetae and Ledebouriellae 1000g, is freely eaten;Every 500g amoxicillin soluble powder is watered 500L, freely drinks.
Efficacy assessment standard: effective: the state of mind and breathing are normal, and drinking-water and feed intake are normal, and pellet morphology is normal.Have
Effect: respiratory symptom mitigates, and feed intake is gradually increasing, and excrement is slightly positive often.Invalid: respiratory symptom does not mitigate, and loss of appetite is very
To abolish, excrement is water sample, and fragmentary death even increases.
Treatment results statistical data is shown in Table 2.
The 2 clear particle clinical trial results of wormwood artemisia indigo plant epidemic disease of table
Note: total significant figure=effective+effectively
As shown in Table 2: after receiving treatment, clinical symptoms are improved and are controlled duck group, and experimental group is treated total effective
Rate average out to 96.9%, the total effective rate of control group treatment are 80.5%, the significant difference (P < 0.05) between two groups.Illustrate this
The clear particle of wormwood artemisia indigo plant epidemic disease of invention has obvious effects on the treatment of Muscovy duck parvovirus disease, and better than clinical common product group.
Clinical application example 2
Weifang duckery, natural occurrence Muscovy duck parvovirus disease, randomly selects wherein 900, is divided into wormwood artemisia by totally 6190
The blue clear particle group of epidemic disease (the clear particle 500g of wormwood artemisia indigo plant epidemic disease of embodiment 1 is watered 500L, freely drinks), drug control group (Florfenicol
30.0mg/ days/kg body weight of powder, compatibility vitamin C are watered and freely drink) and blank control group, experimental period 5 days.As a result: wormwood artemisia
The blue clear particle group average mortality of epidemic disease is 0.61%, drug control group average mortality is 3.84%, blank control group is average dead
Dying rate is 7.25%.
Application examples 3
Linyi duck 3100 16 age in days kind ducks of raising have part to occur loss of appetite even abolish successively, are intended to increase yearningly
Add, apathetic, row's yellow-white, green loose stool, anus stick dirt, and part is thin, and foot is soft, often squat, and then have difficulty in breathing
Or dehisce to stretch neck breathing, some rostral cyanosis, eye nose has secretion, and death increases.Dissect is shown in that tracheae has mucus, and liver is swollen
Greatly, matter is hard, and gall-bladder, kidney enlargement are congested, there is necrosis region.The diagnosis of Binding experiment room is determined as Muscovy duck parvovirus disease.It is complete in time
Group's administration, using the clear particle of wormwood artemisia indigo plant epidemic disease of embodiment 1, dosage is watered 500L according to 500g, freely drinks, and continuous use 7 days.With
After medicine 2 days, sick duck appetite is restored, and spirit is clearly better, and row's loose stool is reduced, and sick duck is substantially without the phenomena of mortality, medication after 3 days
It fully recovers after 5 days.It pays a return visit after 3 weeks, does not recur.
The foregoing is merely presently preferred embodiments of the present invention, is not intended to limit the invention, it is all in spirit of the invention and
Within principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (10)
1. a kind of clear particle of wormwood artemisia indigo plant epidemic disease, which is characterized in that its component includes that 20-35 parts of alpine yallow herb, plate are blue in parts by weight
10-20 parts of root, 10-25 parts of folium isatidis and 5-15 parts of Radix Glycyrrhizae.
2. the clear particle of wormwood artemisia indigo plant epidemic disease according to claim 1, which is characterized in that its component includes one in parts by weight
25 parts of wormwood artemisia of branch, 15 parts of Radix Isatidis, 20 parts of folium isatidis and 10 parts of Radix Glycyrrhizae.
3. the clear particle of wormwood artemisia indigo plant epidemic disease according to claim 1, which is characterized in that further include pharmaceutical diluents and binder.
4. the clear particle of wormwood artemisia indigo plant epidemic disease according to claim 3, which is characterized in that the pharmaceutical diluents are starch, sucrose, paste
One or more of essence, lactose or inorganic salts;The binder is distilled water, ethyl alcohol, sucrose, polyethylene glycol or fibre
Tie up one or more of plain derivative.
5. a kind of preparation method of any one of claim 1-4 clear particle of wormwood artemisia indigo plant epidemic disease, which is characterized in that steps are as follows:
(1) 20-35 parts of alpine yallow herb, 10-20 parts of Radix Isatidis, 10-25 parts of folium isatidis and 5-15 parts of Radix Glycyrrhizae are taken, are crushed to respectively thick
Powder;
(2) the alpine yallow herb coarse powder for taking step (1), is extracted using alcohol reflux, obtains alcohol extract and the alcohol extracting dregs of a decoction;By gained alcohol extracting
Liquid concentration, obtains alcohol extracting cream;
(3) the alcohol extracting dregs of a decoction for taking step (2) add Radix Isatidis coarse powder, smalt leaf coarse powder and the Radix Glycyrrhizae coarse powder of step (1), add
Water impregnates, and decocts and extracts, obtains Aqueous extracts;Aqueous extracts are concentrated, alcohol precipitation, be concentrated again after, obtain water and mention cream;
(4) water of the alcohol extracting cream of step (2) and step (3) is mentioned cream to mix, spray drying, obtains mixing dried cream powder;Continue to add
Enter pharmaceutical diluents and binder, mixes, through wet granulation, drying, whole grain, obtain the clear particle of wormwood artemisia indigo plant epidemic disease.
6. preparation method according to claim 5, which is characterized in that in step (1), by alpine yallow herb, Radix Isatidis, folium isatidis
With Radix Glycyrrhizae after 60 DEG C of drying, crushes respectively, obtain the coarse powder of 24-80 mesh.
7. preparation method according to claim 5, which is characterized in that in step (2), by the alpine yallow herb coarse powder of step (1)
Be placed in the first multi-function extractor, be added ethyl alcohol, repeat refluxing extraction 2-5 time, each 1-3h, filtering, obtain alcohol extract with
The alcohol extracting dregs of a decoction;Alcohol extract is concentrated under the conditions of 50-60 DEG C, 0.05-0.15MPa again, obtaining relative density is 1.05-1.15's
Alcohol extracting cream.
8. the preparation method according to claim 5 or 7, which is characterized in that in step (2), the concentration of ethyl alcohol is 60-
The dosage weight ratio of 90wt%, the ethyl alcohol and alpine yallow herb coarse powder is (6-12): 1.
9. preparation method according to claim 5, which is characterized in that in step (3), by the alcohol extracting dregs of a decoction of step (2) and
Radix Isatidis coarse powder, smalt leaf coarse powder and the Radix Glycyrrhizae coarse powder of step (1) are placed in the second multi-function extractor, are uniformly mixed to obtain mixing
The water of 8-20 times of mixture weight is added in material, impregnates 0.5-2h, repeats to decoct and extract 2-3 times, each 1-2.5h, filtering obtains
Aqueous extracts;Aqueous extracts are concentrated into the clear cream that relative density is 1.05-1.15, and ethyl alcohol to its concentration is added into clear cream and reaches 50-
70wt% carries out alcohol precipitation, stands 12-48h, supernatant is taken to be concentrated under the conditions of 60-65 DEG C, 0.05-0.15MPa, obtains opposite
Density is that the water of 1.05-1.15 mentions cream.
10. the clear particle of wormwood artemisia indigo plant epidemic disease described in a kind of claim 1 is in the application in treatment Muscovy duck parvovirus disease field.
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