CN104666307B - Natural drug monomer compound preparation for animals and preparation and application thereof - Google Patents

Natural drug monomer compound preparation for animals and preparation and application thereof Download PDF

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CN104666307B
CN104666307B CN201510067966.1A CN201510067966A CN104666307B CN 104666307 B CN104666307 B CN 104666307B CN 201510067966 A CN201510067966 A CN 201510067966A CN 104666307 B CN104666307 B CN 104666307B
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natural drug
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王荣迁
冯展波
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Qingdao Shi Weiya Biology Pharmacy Co Ltd
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Abstract

The present invention relates to a kind of natural drug monomer compound preparation for animals, belong to the active field of particular treatment of compound or pharmaceutical preparation; Each constituent mass percentage ratio is: caffeic acid: 1-10%, taraxasterol: 1-5%, aesculetin: 1-10%, adjuvant: 10-40% and water for injection: 35-85%.The present invention provides preparation method and the using method of described monomer compound preparation simultaneously; Beneficial effect is: overcome that Chinese medicine compound preparation effective ingredient is indefinite, content is unstable, the inapparent problem of curative effect, in domestic animal heating, ketoacidosis, shortens female animal and produces stages of labor aspect and have therapeutic effect; The ejection preparation that preparation method of the present invention obtains, ingredient is stable, separate out without crystal, and is convenient to suitability for industrialized production and preservation steady in a long-term.

Description

Natural drug monomer compound preparation for animals and preparation and application thereof
Technical field
The present invention relates to a kind of animal-used compound preparation, particularly relate to a kind of natural drug monomer compound preparation for animals, belong to the active field of particular treatment of compound or pharmaceutical preparation.
Background technology
In Animal diseases treatment, along with the abuse of antibiotic, chemicals and hormone medicine, its cause that the drug resistance of animal strengthens, drug residue, animal teratogenesis and the harm etc. to ecological environment becomes clear day by day.Due to the life-time service such as synthetic antibacterial agents, antibiotic, hormone bring the day by day serious of problem, add the reasons such as Western medicine compound research cost rises, developing thought is exhausted, the formula find in natural drug efficiently, have no side effect, had no drug resistance and preparation have become the new ideological trend of world's new drug development.
Natural drug refers to the natural product having pharmacologically active that the occurring in natures such as animal, plant and mineral exist.Natural drug is not equal to Chinese medicine or Chinese herbal medicine, there are the experience and prescription that utilize natural drug disease therapy in a lot of country in the world, and these experiences and prescription go through clinical experiment in 1,100, the effectiveness of its medicine of sufficient proof and safety.At present, developed country utilizes advanced pharmaceutical technology and technique, has had a large amount of natural medicinal formulations to be exploited, has been used for the treatment of mankind's relevant disease, achieves immense success.As common salicin (natural aspirin), extract exactly the earliest and obtain from bark of willow, the aspirin of its effect in antiinflammatory, analgesia etc. and synthetic is similar, but side effect is less.
Natural medicinal formulations, particularly medicine monomer formulation, its natural sex is good, purity is high, side effect is little, not easily produce the advantages such as drug resistance, is that chemical synthetic drug is incomparable.Along with the development of science and technology, increasing natural drug is exploited, and particularly active drug composition is more and clearer and more definite, extract and purifying technique more and more complete, provide condition for preparing natural drug monomer formulation.
Veterinary drug is as a branch of pharmaceutical field, and abroad, its research and development, producing and selling and application, be all subject to strict supervision and control; But China's veterinary drug is still in the frontier area of pharmacy, is not taken seriously always; Its result caused is exactly that various medicine spreads unchecked, drug dependence, excessive use, forbidden drug use etc. phenomenon of common occurrence, as clenbuterol hydrochloride, antibiotic abuse, cause huge food safety hidden danger.Along with China's economic development, living standards of the people improve, and legal system is more sound, will be more and more stricter to the supervision of field of veterinary, also can be more and more higher to the instructions for use of medicine, and specialized and high quality will become the general orientation of field of veterinary development.
Caffeic acid belongs to styrene acid compounds, extensively distributes in plant, as Herba Taraxaci, Flos Chrysanthemi Indici, coffee & tea leaf etc.Caffeic acid has multiple pharmacological effect, mainly comprise that cardiovascular protection, antimutagenic are anticancer, antibacterial, antiviral, blood fat reducing, blood sugar lowering, leukemia, immunomodulating, function of gallbladder promoting hemostasis and antioxidation etc.Existing people's medication caffeic acid sheet at present, for preventing hemorrhage or hemostasis during surgical operation, and the hemostasis of the hemorrhage such as internal medicine, department of obstetrics and gynecology; Also for leukopenia, thrombocytopenia that a variety of causes causes.
Taraxasterol is a kind of important drugs composition in plant dandelion, has hepatic cholagogic, antitumor, protection stomach avoid damage and treatment gynaecopathia aspect, Be very effective.Taraxasterol is one of quality detecting index important in Herba Taraxaci pharmaceutical preparation.
Aesculetin belongs to coumarin kind compound, and it has antibacterial, antiinflammatory, antitussive, eliminates the phlegm, eases pain, promotes the aspect effects such as uric acid discharge, in the product of preparation people medication, applies more and more extensive.
The domestic veterinary drug almost not having a kind of natural drug monomer component to make at present, only with the preparation that simple extract is made, as astragalin injection.The maximum problem of this type of medicine is the mixture that astragalus polysaccharides is made up of plurality of active ingredients, and the component content of any one sugar is wherein also inconsistent, and lacks effective examination criteria and method; Secondly, medicine is easily subject to the impact of the place of production, treatment process, is difficult to the effective ingredient stable content ensureing every batch.The instability of active constituent content, causes difficulty to actual medication, cannot ensure the stability of each dosage: too much, easily cause damage, very few, then curative effect is not obvious.
Summary of the invention
The object of this invention is to provide a kind of natural drug monomer compound preparation for animals, overcome the problems such as Chinese medicine compound preparation effective ingredient is indefinite, content is unstable, curative effect is not remarkable; The present invention provides the preparation method of described monomer compound preparation simultaneously, is convenient to suitability for industrialized production and preservation veterinary formulations steady in a long-term; The present invention also provides the using method of monomer compound preparation.
Natural drug monomer compound preparation for animals of the present invention, the mass percent of each component is:
Caffeic acid: 1-10%, taraxasterol: 1-5%, aesculetin: 1-10%, adjuvant: 10-40% and water for injection: 35-85%.
Wherein, the mass percent of preferred each component is: caffeic acid: 5-10%, taraxasterol: 1-3%, aesculetin: 3-7%, adjuvant: 15-35% and water for injection: 50-70%.
Wherein, most preferably the mass percent of each component is: caffeic acid: 7.5%, taraxasterol: 2.5%, aesculetin: 5%, adjuvant: 25% and water for injection: 60%.
Described adjuvant adopts propylene glycol, PEG-200 and Sulfobutyl ether β _ cyclodextrin.
Further, propylene glycol in adjuvant, the mass ratio of PEG-200 and Sulfobutyl ether β _ cyclodextrin is preferred: 3:3:4.
In the present invention, the Main Function of adjuvant is dissolved by five kinds of materials of the present invention, increases its stability in aqueous, and promote medicine absorption in vivo and utilization; The Main Function of described water for injection is dissolved substance and adjuvant.
The preparation method of natural drug monomer compound preparation for animals of the present invention is:
(1) in water for injection, add adjuvant, fully stirring, mix homogeneously obtain mixed liquor;
(2) repeatedly add caffeic acid on a small quantity in the mixed liquor obtained to step (1), be stirred to it and all dissolve; Then solution is divided into 3 parts, the mass ratio of first part, second part and the 3rd part is: 3:1:2;
(3) in second part of solution, add taraxasterol, add aesculetin, repeatedly add on a small quantity respectively in the 3rd part of solution, limit edged is stirred to it and dissolves;
(4) by second part of solution and the 3rd part of solution mixing, and stir; Again first part of solution is added, obtain mixed liquor;
(5) after step (4) gained mixed liquor is stablized, adjust ph; After pH value is stable, adds water for injection, obtain the product determining final volume and weight; Product, through post processing, obtains natural drug monomer compound preparation product for animals of the present invention.
In described step (4), it is mass ratio that second part of solution and the 3rd part of solution add velocity ratio.
In described step (5), pH value regulates reagent to adopt concentration to be the HCL solution of 1mol/L and the NaOH solution of 1mol/L;
In described step (5), pH value range of accommodation is 5.0-8.0.
In described preparation method, each step temperature controls at 20-80 DEG C, and mixing speed controls at 10-100r/min.
In described step (5), last handling process comprises: by product filtration, fill, then carry out sterilization treatment; After product cooling subject to sterilization, obtain product.
In last handling process, the pore size filter that filter process adopts is 0.22 ~ 10 micron, and flow rate of liquid is 0.1-10L/min, and temperature is 10-50 DEG C, air pressure 0.1-1MPa;
In last handling process, fill condition is: air purity rank is 100 grades, and room temperature is 15-30 DEG C;
In last handling process, sterilising temp is 102-140 DEG C, and sterilization time is 1-60 minute.
Because caffeic acid is difficult to dissolve in cold water, and easy degeneration after high temperature sterilize, having crystal to separate out, is prepare one of injection and the maximum difficulty of oral administration solution.The present invention, in conjunction with caffeic acid pharmaceutical properties and structural formula feature, finds through great many of experiments, by the sequencing of conservative control temperature, auxiliary material proportion, raw material adding rate and interpolation, effectively can overcome above-mentioned difficulties.
The using method of described preparation is intramuscular injection, intravenous injection or oral, and effective using dosage is 0.01-1mL/kg body weight, every day.
Compared with prior art, beneficial effect of the present invention is:
(1) instant invention overcomes Chinese medicine compound preparation effective ingredient indefinite, the problem of content instability; Overcome conventional medicament preparation simple combination, the inapparent problem of curative effect.
(2) the present invention is in domestic animal heating, ketoacidosis, and shortening female animal production stages of labor aspect has therapeutic effect; Meanwhile, it is too low also can to treat livestock temperature, realizes the two-ways regulation to body temperature.
(3) ejection preparation that obtains of preparation method of the present invention, ingredient is stable, separate out without crystal; Overcome the problem that natural drug monomer formulation dissolubility is low, medicine is unstable.
(4) the invention provides the preparation method of described monomer compound preparation, be convenient to suitability for industrialized production, gained veterinary formulations is convenient to steady in a long-term preservation.
Accompanying drawing explanation
Fig. 1 is the process chart of preparation method of the present invention.
Detailed description of the invention
Below in conjunction with accompanying drawing 1, adopt preparation embodiment and pharmacological examples to be explained in detail the present invention, wherein preparing embodiment 1 is optimal case of the present invention.
Preparation embodiment 1
Described natural drug monomer compound preparation for animals, each constituent mass is:
2.5kg) and water for injection: 6kg (adjuvant amounts to caffeic acid: 0.75kg, taraxasterol: 0.25kg, aesculetin: 0.5kg, propylene glycol: 0.75kg, PEG-200:0.75kg, Sulfobutyl ether β _ cyclodextrin: 1kg:.
Described natural drug monomer compound preparation for animals, its preparation method is:
(1) at 50 DEG C, 2.5kg water for injection is joined in reactor A; Add propylene glycol, PEG-200 and Sulfobutyl ether β _ cyclodextrin respectively successively, fully stir, maintenance rotating speed is 30r/min, until mix homogeneously obtains mixed liquor;
(2) at 50 DEG C, caffeic acid is divided 25 times, each 30g, join in the mixture in reactor A, be stirred to it and all dissolve, maintenance rotating speed is 30r/min; Then solution is divided into 3 parts, be transferred in reactor B, reactor C and reactor D respectively according to the ratio of 3:1:2, temperature is all constant in 50 DEG C;
(3) in reactor C, add taraxasterol, divide 25 times, each 10g adds; In reactor D, add aesculetin, divide 25 times, each 20g adds; Abundant stirring, until the complete drug dissolution in reactor; Maintenance rotating speed is 30r/min, and temperature is 50 DEG C;
(4) solution in reactor C and reactor D is added in standardize solution tank E by the speed that velocity ratio is 1:2, mix and stir; Added by solution in reactor B, limit edged stirs to obtain mixed liquor again;
(5), after mixed liquor is stablized, regulate temperature to be 37 DEG C, add the HCL solution of 1mol/L and the NaOH solution adjust ph of 1mol/L, abundant stirring and evenly mixing; After pH value stabilizes to 6.5, add water for injection, obtain the diluent 10kg determining final volume and weight, now, water for injection quality accounts for 60% of gross mass;
(6) by the diluent via hole diameter in standardize solution tank E be the filter element of 0.45 micron, transfer in sub-packing pot F with the flow velocity of 1L/min, it is 20 DEG C that temperature controls, and air pressure is 0.2MPa; Be 100 grades in air purity rank, room temperature is under the condition of 20 DEG C, the solution in sub-packing pot F is dispensed into volume and is 125mL and in the aseptic cillin bottle without thermal source amber transparent, dispensed loading amount is 100mL, then gland, sealing; Cillin bottle is placed in sterilizing cabinet, and at 120 DEG C, sterilizing 10 minutes, takes out after natural cooling, obtains product of the present invention (being designated as A).
Preparation embodiment 2
Described natural drug monomer compound preparation for animals, each constituent mass is:
2.8kg) and water for injection: 6kg (adjuvant amounts to caffeic acid: 0.5kg, taraxasterol: 0.1kg, aesculetin: 0.6kg, propylene glycol: 0.84kg, PEG-200:0.84kg, Sulfobutyl ether β _ cyclodextrin: 1.12kg:.
Described natural drug monomer compound preparation for animals, its preparation method is:
(1) at 40 DEG C, 2kg water for injection is joined in reactor A; Add propylene glycol, PEG-200 and Sulfobutyl ether β _ cyclodextrin respectively successively, fully stir, maintenance rotating speed is 50r/min, until mix homogeneously obtains mixed liquor;
(2) at 60 DEG C, caffeic acid is divided 20 times, each 25g, join in the mixture in reactor A, be stirred to it and all dissolve, maintenance rotating speed is 50r/min; Then solution is divided into 3 parts, be transferred in reactor B, reactor C and reactor D respectively according to the ratio of 3:1:2, temperature is all constant in 60 DEG C;
(3) in reactor C, add taraxasterol, divide 20 times, each 5g adds; In reactor D, add aesculetin, divide 30 times, each 20g adds; Abundant stirring, until the complete drug dissolution in reactor; Maintenance rotating speed is 40r/min, and temperature is 60 DEG C;
(4) solution in reactor C and reactor D is added in standardize solution tank E by the speed that velocity ratio is 1:2, mix and stir; Added by solution in reactor B, limit edged stirs to obtain mixed liquor again;
(5), after mixed liquor is stablized, regulate temperature to be 45 DEG C, add the HCL solution of 1mol/L and the NaOH solution adjust ph of 1mol/L, abundant stirring and evenly mixing; After pH value stabilizes to 6.8, add water for injection, obtain the diluent 10kg determining final volume and weight, now, water for injection quality accounts for 60% of gross mass;
(6) by the diluent via hole diameter in standardize solution tank E be the filter element of 0.7 micron, transfer in sub-packing pot F with the flow velocity of 5L/min, it is 30 DEG C that temperature controls, and air pressure is 0.3MPa; Be 100 grades in air purity rank, room temperature is under the condition of 15 DEG C, the solution in sub-packing pot F is dispensed into volume and is 125mL and in the aseptic cillin bottle without thermal source amber transparent, dispensed loading amount is 100mL, then gland, sealing; Cillin bottle is placed in sterilizing cabinet, and at 135 DEG C, sterilizing 8 minutes, takes out after natural cooling, obtains product of the present invention (being designated as B).
Preparation embodiment 3
Described natural drug monomer compound preparation for animals, each constituent mass is:
2.4kg) and water for injection: 6.2kg (adjuvant amounts to caffeic acid: 0.6kg, taraxasterol: 0.3kg, aesculetin: 0.7kg, propylene glycol: 0.72kg, PEG-200:0.72kg, Sulfobutyl ether β _ cyclodextrin: 0.96kg:.
Described natural drug monomer compound preparation for animals, its preparation method is:
(1) at 50 DEG C, 3kg water for injection is joined in reactor A; Add propylene glycol, PEG-200 and Sulfobutyl ether β _ cyclodextrin respectively successively, fully stir, maintenance rotating speed is 40r/min, until mix homogeneously obtains mixed liquor;
(2) at 50 DEG C, caffeic acid is divided 20 times, each 30g, join in the mixture in reactor A, be stirred to it and all dissolve, maintenance rotating speed is 40r/min; Then solution is divided into 3 parts, be transferred in reactor B, reactor C and reactor D respectively according to the ratio of 3:1:2, temperature is all constant in 50 DEG C;
(3) in reactor C, add taraxasterol, divide 20 times, each 15g adds; In reactor D, add aesculetin, divide 35 times, each 20g adds; Abundant stirring, until the complete drug dissolution in reactor; Maintenance rotating speed is 40r/min, and temperature is 50 DEG C;
(4) solution in reactor C and reactor D is added in standardize solution tank E by the speed that velocity ratio is 1:2, mix and stir; Added by solution in reactor B, limit edged stirs to obtain mixed liquor again;
(5), after mixed liquor is stablized, regulate temperature to be 30 DEG C, add the HCL solution of 1mol/L and the NaOH solution adjust ph of 1mol/L, abundant stirring and evenly mixing; After pH value stabilizes to 6.0, add water for injection, obtain the diluent 10kg determining final volume and weight, now, water for injection quality accounts for 62% of gross mass;
(6) by the diluent via hole diameter in standardize solution tank E be the filter element of 0.1 micron, transfer in sub-packing pot F with the flow velocity of 0.5L/min, it is 25 DEG C that temperature controls, and air pressure is 0.25MPa; Be 100 grades in air purity rank, room temperature is under the condition of 35 DEG C, the solution in sub-packing pot F is dispensed into volume and is 125mL and in the aseptic cillin bottle without thermal source amber transparent, dispensed loading amount is 100mL, then gland, sealing; Cillin bottle is placed in sterilizing cabinet, and at 105 DEG C, sterilizing 45 minutes, takes out after natural cooling, obtains product of the present invention (being designated as C).
Pharmacological examples 1
Product of the present invention is adopted to treat milch cow ketoacidosis in puerperal
1.1 medicine preparations: for preparing according to method described in preparation embodiment 1-3 obtains product A, B, C, and D, E and F product adopting similar approach to prepare, and concrete each constituent mass ratio is in table 1:
The each constituent mass ratio of table 1 A-F medicine
Medicine Caffeic acid Taraxasterol Aesculetin Adjuvant Water for injection
A group 7.5% 2.5% 5% 25% 60%
B group 5% 1% 6% 28% 60%
C group 6% 3% 7% 24% 62%
D group 7.5% / 5% 25% 62.5%
E group 7.5% 2.5% / 25% 65%
F group / 2.5% 5% 25% 67.5%
1.2 laboratory animals: choose scale pasture mature cow, puerperal 1-10 days, Blood ketone body content more than the severe ketonemia cattle of 3mmol/L, as experimental subject.
1.3 experimental technique
1) choose cattle in puerperal, measure its blood acetone number;
2) qualified 180 experiment Niu Suiji are divided into 6 groups, each 30 of A-F group;
3) often organize cattle, administered intramuscular, dosage 30mL/ head, 9 administrations in morning, once-a-day, are used in conjunction three;
4) the 4th day, blood sampling, measured blood ketone content.
1.4 experimental results are as table 2:
Before and after table 2 is treated, milk Sanguis Bovis seu Bubali acetone number changes
Group Blood acetone number (mmol/L) before experiment Blood acetone number (mmol/L) after experiment
A group 3.21±0.12 0.87±0.07
B group 3.11±0.10 1.12±0.10
C group 3.12±0.12 1.23±0.10
D group 3.12±0.11 1.89±0.09
E group 3.14±0.10 2.17±0.11
F group 3.09±0.10 2.08±0.10
Result shows: after the treatment of A, B, C group, blood acetone number is starkly lower than D-F group, illustrate and effectively can treat milch cow ketoacidosis in puerperal according to the composing prescription preparation prepared by the present invention, successful is better than the combination of two kinds of medicines, and adopts the therapeutic effect of component A to be better than the therapeutic effect of B, component C.
Pharmacological examples 2
Product of the present invention is adopted to treat milch cow puerperal high fever
2.1 Experimental agents preparation methoies, control drug preparation method are with pharmacological examples 1;
2.2 laboratory animals: choose scale pasture mature cow, puerperal 1-7 days, rectal temperature is experimental subject more than 39.5 DEG C of cattle.
2.3 experimental technique
1) choose qualified experiment cattle, measure its rectal temperature;
2) qualified 90 experiment Niu Suiji are divided into 6 groups, each 15 of A-F group;
3) often organize cattle, administered intramuscular, dosage 30mL/ head, morning, 9 administrations, were administered once;
4) after administration, within first 12 hours, measured body temperature once every 2 hours, within latter 12 hours, measured body temperature once every 4 hours, continuously monitoring 24 hours.
2.4 experimental results are as table 3.
In table 3 therapeutic process, milch cow body temperature situation of change
Group 0h 2h 4h 6h 8h 10h 12h 16h 20h 24h
A group 40.1℃ 39.8℃ 39.6℃ 39.3℃ 39.0℃ 38.9℃ 38.8℃ 38.5℃ 38.6℃ 38.4℃
B group 40.3℃ 39.9℃ 39.6℃ 39.3℃ 39.3℃ 39.5℃ 39.0℃ 38.9℃ 38.9℃ 38.8℃
C group 40.2℃ 39.8℃ 39.7℃ 39.5℃ 39.3℃ 38.2℃ 38.9℃ 38.8℃ 38.7℃ 38.7℃
D group 39.9℃ 39.8℃ 39.9℃ 39.7℃ 39.9℃ 39.9℃ 39.7℃ 40.1℃ 39.9℃ 39.9℃
E group 40.0℃ 40.0℃ 40.9℃ 39.8℃ 40.1℃ 39.9℃ 39.9℃ 39.7℃ 39.8℃ 39.6℃
F group 40.1℃ 39.9℃ 40.9℃ 39.7℃ 39.9℃ 40.1℃ 39.8℃ 39.9℃ 39.9℃ 39.5℃
Result shows: after the treatment of A, B, C group, milch cow body temperature is starkly lower than D-F group, illustrate and effectively can treat milch cow high temperature in puerperal according to the composing prescription preparation prepared by the present invention, successful is better than the combination of two kinds of medicines, and adopts the therapeutic effect of component A to be better than the therapeutic effect of B, component C.
Pharmacological examples 3
Adopt product of the present invention on the impact of sow stages of labor
3.1 Experimental agents preparation methoies, control drug preparation method are with embodiment 1.
3.2 laboratory animals: choose scale pasture and wait to produce sow (2-3 parity), antenatal 1-3 days.
3.3 experimental techniques:
1) qualified 120 experiment sows are divided into 6 groups, each 20 of A-F group at random;
2) often sow is organized, just before giving birth time, administered intramuscular, drug dose is 20mL/ head;
3), after administration, record and give birth to from first piglet the time that afterbirth discharges completely.
3.4 experimental results are as table 4:
Table 4 sow duration of labor situation
Group A group B group C group D group E group F group
Duration of labor (hour) 2.5±0.20 2.8±0.31 2.7±0.22 3.5±0.21 3.7±0.29 3.6±0.15
Result shows: A, B, C group treatment sow duration of labor is obviously less than D-F group, illustrating can effective shortening labor time according to the composing prescription preparation prepared by the present invention, successful is better than the combination of two kinds of medicines, and adopts the therapeutic effect of component A to be better than the therapeutic effect of B, component C.Duration of labor is shorter, and piglet survival ratio is higher, otherwise survival rate reduces.
Pharmacological examples 4
Adopt the therapeutic effect that the present invention generates heat to domesticated dog
4.1 Experimental agents preparation methoies, control drug preparation method are with embodiment 1.
4.2 laboratory animals: choose large-scale domesticated dog plant and to grow up domesticated dog (30-40kg), body temperature is more than 39 DEG C.
4.3 experimental techniques:
1) domesticated dog that qualified 60 experiments grown up is divided into 6 groups, each 10 of A-F group at random;
2) often organize domesticated dog, administered intramuscular, drug dose is 5mL/, and morning, 9 administrations, were administered once;
3) after administration, body temperature was measured once every 1 hour, continuously monitoring 6 hours.
4.4 experimental results are as table 5.
In table 5 therapeutic process, domesticated dog Temperature changing situation
Group 0h 1h 2h 3h 4h 5h 6h
A group 39.5℃ 39.3℃ 39.1℃ 38.7℃ 38.5℃ 37.9℃ 37.7℃
B group 39.6℃ 39.5℃ 39.3℃ 38.9℃ 38.7℃ 38.0℃ 37.9℃
C group 39.5℃ 39.4℃ 39.3℃ 38.8℃ 38.7℃ 38.1℃ 37.8℃
D group 39.4℃ 39.3℃ 39.2℃ 39.4℃ 39.2℃ 39.4℃ 39.4℃
E group 39.3℃ 39.4℃ 39.3℃ 39.4℃ 39.3℃ 39.4℃ 39.4℃
F group 39.5℃ 39.4℃ 39.3℃ 39.5℃ 39.4℃ 39.3℃ 39.5℃
Result shows: after the treatment of A, B, C group, domesticated dog body temperature is starkly lower than D-F group, illustrate and can effectively treat domesticated dog high temperature according to the composing prescription preparation prepared by the present invention, successful is better than the combination of two kinds of medicines, and adopts the therapeutic effect of component A to be better than the therapeutic effect of B, component C.
Pharmacological examples 5
Adopt the present invention to the therapeutic effect of sow hypothermia
5.1 Experimental agents preparation methoies, control drug preparation method are with case study on implementation one.
5.2 laboratory animals: choose adult Large White 60 (130-140kg), rectal temperature is lower than 37 DEG C.
5.3 experimental techniques:
1) qualified 60 experiment pig are divided into 6 groups at random, each 10 of A-F group;
2) often organize pig, administered intramuscular, drug dose is 5mL/ head, and morning, 9 administrations, were administered once;
3) after administration, body temperature was measured once every 1 hour, continuously monitoring 6 hours.
5.4 experimental results are as table 6.
In table 6 therapeutic process, temperature of pig body situation of change
Group 0h 1h 2h 3h 4h 5h 6h
A group 36.1℃ 36.5℃ 36.9℃ 37.1℃ 37.5℃ 37.4℃ 37.5℃
B group 36.1℃ 36.5℃ 36.6℃ 36.7℃ 36.9℃ 37.0℃ 37.2℃
C group 36.0℃ 36.1℃ 36.3℃ 36.4℃ 36.7℃ 36.9℃ 37.3℃
D group 36.2℃ 36.3℃ 36.5℃ 36.6℃ 36.7℃ 36.9℃ 37.2℃
E group 36.3℃ 36.5℃ 36.6℃ 36.7℃ 36.8℃ 37.0℃ 37.1℃
F group 36.1℃ 36.4℃ 36.3℃ 36.5℃ 36.8℃ 36.9℃ 37.0℃
Result shows: after the treatment of A, B, C group, temperature of pig body is a little more than D-F group, illustrate that effectively can to treat temperature of pig body according to the composing prescription preparation prepared by the present invention too low, effect is better than the combination of two kinds of medicines, and adopts the therapeutic effect of component A to be better than the therapeutic effect of B, component C.

Claims (9)

1. a natural drug monomer compound preparation for animals, is characterized in that, the mass percent of each component is: caffeic acid: 1-10%, taraxasterol: 1-5%, aesculetin: 1-10%, adjuvant: 10-40% and water for injection: 35-85%.
2. natural drug monomer compound preparation for animals according to claim 1, it is characterized in that, the mass percent of each component is: caffeic acid: 5-10%, taraxasterol: 1-3%, aesculetin: 3-7%, adjuvant: 15-35% and water for injection: 50-70%.
3. natural drug monomer compound preparation for animals according to claim 1, it is characterized in that, the mass percent of each component is: caffeic acid: 7.5%, taraxasterol: 2.5%, aesculetin: 5%, adjuvant: 25% and water for injection: 60%.
4. natural drug monomer compound preparation for animals according to claim 1, is characterized in that, described adjuvant adopts propylene glycol, and PEG-200 and Sulfobutyl ether β _ cyclodextrin, three's mass ratio is: 3:3:4.
5. a preparation method for the arbitrary described natural drug monomer compound preparation for animals of claim 1-4, is characterized in that, comprise the following steps:
(1) in water for injection, add adjuvant, fully stirring, mix homogeneously obtain mixed liquor;
(2) repeatedly add caffeic acid on a small quantity in the mixed liquor obtained to step (1), be stirred to it and all dissolve; Then solution is divided into 3 parts, the mass ratio of first part, second part and the 3rd part is: 3:1:2;
(3) in second part of solution, add taraxasterol, add aesculetin, repeatedly add on a small quantity respectively in the 3rd part of solution, limit edged is stirred to it and dissolves;
(4) by second part of solution and the 3rd part of solution mixing, and stir; Again first part of solution is added, obtain mixed liquor;
(5), after step (4) gained mixed liquor is stablized, adjust ph is to 5.0-8.0; After pH value is stable, adds water for injection, obtain the product determining final volume and weight; Product, through post processing, obtains natural drug monomer compound preparation product for animals of the present invention.
6. the preparation method of natural drug monomer compound preparation for animals according to claim 5, is characterized in that, in described step (5), pH value regulates reagent to adopt concentration to be the HCl solution of 1mol/L and the NaOH solution of 1mol/L.
7. the preparation method of natural drug monomer compound preparation for animals according to claim 5, it is characterized in that, each step temperature controls at 20-80 DEG C, and mixing speed controls at 10-100r/min.
8. the preparation method of natural drug monomer compound preparation for animals according to claim 5, it is characterized in that, in described step (5), last handling process comprises: filtered by product, fill, then carries out sterilization treatment; After product cooling subject to sterilization, obtain product.
9. the preparation method of natural drug monomer compound preparation for animals according to claim 8, is characterized in that, in last handling process, the pore size filter that filter process adopts is 0.22 ~ 10 micron, flow rate of liquid is 0.1-10L/min, and temperature is 10-50 DEG C, air pressure 0.1-1MPa; Fill condition is: air purity rank is 100 grades, and room temperature is 15-30 DEG C; Sterilising temp is 102-140 DEG C, and sterilization time is 1-60 minute.
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