CN104306389A - Lincomycin-spectinomycin compound nano-emulsion - Google Patents
Lincomycin-spectinomycin compound nano-emulsion Download PDFInfo
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- CN104306389A CN104306389A CN201410555616.5A CN201410555616A CN104306389A CN 104306389 A CN104306389 A CN 104306389A CN 201410555616 A CN201410555616 A CN 201410555616A CN 104306389 A CN104306389 A CN 104306389A
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- spectinomycin
- lincomycin
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
Abstract
The invention provides lincomycin-spectinomycin compound nano-emulsion, and belongs to the technical field of pharmacy. The compound nano-emulsion is prepared from the following components in parts by weight: 1-20 parts of lincomycin hydrochloride, 1-25 parts of spectinomycin, 15-40 parts of surfactant, 1-25 parts of co-surfactant, 1-16 parts of oil and 18-75 parts of water. The compound nano-emulsion is a novel preparation which is combined with characteristics of lincomycin hydrochloride and lincomycin hydrochloride, and has the advantages of uniform grain diameter distribution, good fluidity, high stability, good permeability and good bioavailability; the compound nano-emulsion can be quickly phagocytosed by reticuloendothelial cells after being taken orally, drugs can quickly take effects, and constant plasma concentration and pharmacological effect can be maintained, the bioavailability can be improved, drug effect can be enhanced, and using amount and taking times of the medicine can be reduced.
Description
Technical field
The invention belongs to pharmaceutical technology sectors, be specifically related to a kind of lincomycin-spectinomycin compound nanometer emulsion.
Background technology
Lincomycin hydrochloride (Lincomycin Hydrochloride) is white crystalline powder, and soluble in water or methanol, is slightly soluble in ethanol.Lincomycin hydrochloride is narrow-spectrum antibiotic, and its effect is similar to erythromycin, has better effect, have efficiently especially to anaerobic bacteria, S. aureus L-forms and streptococcus pneumoniae gram positive coccus.Lincomycin hydrochloride can the synthesis of anti-bacteria cell protein, is clinically mainly used in responsive microbial various infection, as pneumonia, meningitis, endocarditis, cellulitis, tonsillitis, erysipelas, furuncle and urinary system infection etc.Because this product can enter in osseous tissue, there is special affinity with bone, therefore be specially adapted to lonely microbial infection and S. aureus L-forms osteomyelitis.
Spectinomycin is a kind of aminocyclitol antibiotic be combined into by neutral sugar and aminocyclitol one glycosidic bond, mainly has height antibacterial activity to Diplococcus gonorrhoeae, also has good antibacterial activity to the Diplococcus gonorrhoeae producing beta lactamase; To many enterobacteriaceae lactobacteriaceae tool moderate antibacterial activities.Pu Luofeideng bacterium and Pseudomonas aeruginosa are usually to this product drug resistance; Often still responsive to streptomycin, gentamycin, tobramycin etc. to the bacterial strain of this product drug resistance.These product have good action to ureaplasma urealyticum, to chlamydia trachomatis and treponema pallidum non-activity.The mechanism of action of these product is combined with bacterial ribosome 30S subunit, the synthesis of anti-bacteria protein.Veterinary pharmacologically, spectinomycin is used for preventing and treating colibacillosis, fowl cholera, fowl salmonellosis.Combine with lincomycin, can be used for preventing the acute and chronic respiratory tract disease etc. that piglet diarrhea, the mycoplasmal pneumonia of pig and Frustrate blood and mycoplasma cause.
At present, on market, more existing lincomycins and spectinomycin combined dosage form, as soluble powder, water type injection, oil suspension injection etc., be injecting drug use.This is because existing dosage form is normally used is the hydrochloride form of spectinomycin, and spectinomycin hydrochloride is soluble in water, exists under the pH environment of small intestinal with the high valence ion form of high polarity, fat-soluble minimum, orally not easily to absorb.Further, spectinomycin aqueous solution is unstable, easily hydrolysis occurs thus loses biological activity.But in practice, the treatment of a lot of disease needs medication 5-7 day more than, and injecting drug use is very inconvenient.
Summary of the invention
Object of the present invention aims to provide a kind of new compound preparation---lincomycin-spectinomycin compound nanometer emulsion.
Based on above-mentioned purpose, this invention takes following technical scheme: lincomycin-spectinomycin compound nanometer emulsion, its weight consists of: lincomycin hydrochloride 1 ~ 20 part, spectinomycin 1 ~ 25 part, 15 ~ 40 parts, surfactant, cosurfactant 1 ~ 25 part, oil 1 ~ 16 part, 18 ~ 75 parts, water.
The weight of described compound nanometer emulsion consists of: lincomycin hydrochloride 1 ~ 14 part, spectinomycin 5 ~ 15 parts, 20 ~ 35 parts, surfactant, cosurfactant 1 ~ 10 part, oil 1 ~ 12 part, 20 ~ 50 parts, water.
The weight of described compound nanometer emulsion consists of: lincomycin hydrochloride 7 parts, spectinomycin 5 ~ 15 parts, 28 parts, surfactant, cosurfactant 4 parts, oil 12 parts, 39 parts, water.
Described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene (40) ether, Tween 80 or PLURONICS F87 any one or with the mixture of span80.
Described cosurfactant is selected from ethanol, 1,2-PD, PEG400 and glycerol.
Described grease separation is from soybean oil, cinnamic aldehyde, Ethyl formate, ethyl oleate, fatty glyceride, Oleum Ricini, Oleum Brassicae campestris, linoleic acid, ethyl n-butyrate., isopropyl myristate, ethyl acetate and oleic acid.
Described oil is isopropyl myristate.
Nano-emulsion (nanoemulsion), also known as microemulsion (microemulsion), is by spontaneous transparent or semitransparent homodisperse systems formed such as water, oil, surfactant and cosurfactants.In general, nano-emulsion is divided into three types, i.e. oil-in-water type nano-emulsion (O/W), water-in-oil type nanoemulsion (W/O) and bicontinuous nano-emulsion (B.C).Nano-emulsion has the unrivaled advantage of other preparations many: 1. for isotropic transparency liquid, belongs to thermodynamically metastable fixed system, through pressure sterilizing or centrifugally can not make it layering; 2. technique is simple, and preparation process does not need special installation, can spontaneously be formed, and nano-emulsion particle diameter is generally 1 ~ 100nm; 3. viscosity is low, can reduce pain during injection; 4. there is slow release and targeting; 5. improve the dissolubility of medicine, reduce medicine enzymolysis in vivo, can be formed the protective effect of medicine and improve the absorption of gastrointestinal tract to medicine, improving the bioavailability of medicine.
Material rate is obtained according to the present invention, what prepare is oil-in-water type nano-emulsion, its preparation method can be: take spectinomycin, surfactant and cosurfactant stirred at ambient temperature in proportion even, and then instillation is dissolved with the distilled water (lincomycin hydrochloride aqueous solution) of lincomycin hydrochloride; The initial stage system dripping lincomycin hydrochloride aqueous solution can become sticky thick, and along with the increase gradually of lincomycin hydrochloride aqueous solution, system stickiness increases gradually; When the amount of aqueous solution increases to a certain degree, system becomes oil-in-water type from Water-In-Oil, and its viscosity can turn suddenly rare, namely obtains water white oil-in-water type nano-emulsion; Continue to add remaining aqueous solution, obtain lincomycin-spectinomycin compound nanometer emulsion cost.Lincomycin hydrochloride dissolves by the water that also can first take a morsel, and adds remaining water again after being added system.
Its emulsion particle diameter of the nano-emulsion that the present invention obtains is 30.1 ~ 71.8nm, and mean diameter is 53.3nm.It is directly oral that this nano-emulsion can be used as oral liquid, also can be encapsulated in capsule further or make lyophilized powder.
The present invention adds bland cosurfactant as ethanol, 1 in medicine, 2-propylene glycol, glycerol, Macrogol 200, Liquid Macrogol or PEG400, except hydrotropy effect, cosurfactant is mainly in order to the hydrophile-lipophile balance value (HLB) of adjustment form surface-active agent, oil water interfacial tension is reduced further, increases profit and the rigidity of limitans.Cosurfactant penetrates in interfacial film, promotes to form the very little film of radius of curvature, expands the newborn district area of nano-emulsion.
The present invention provides in conjunction with the characteristic of lincomycin hydrochloride and spectinomycin and is a kind ofly suitable for oral novel form, its product cut size is evenly distributed, good fluidity, stability is high, there is good permeability and bioavailability: can be engulfed by reticuloendothelial cell rapidly after oral administration, make medicine rapid-onset and maintain constant blood drug level and pharmacodynamics effect, bioavailability improves, strengthen drug effect, thus reduces consumption and the access times of medicine.
Meanwhile, the preparation method of nano-emulsion is easy, energy consumption is low, has wide marketing prospect.Gained nano-emulsion product can directly orally use, or is processed into other dosage forms further through encapsulated and lyophilized powder technology.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope photo of lincomycin in embodiment 1-spectinomycin compound nanometer emulsion;
Fig. 2 is the grain size distribution of lincomycin in embodiment 1-spectinomycin compound nanometer emulsion.
Detailed description of the invention
Below in conjunction with specific embodiment and dependence test experiment the present invention will be further described.
one) embodiment
For making description concise and to the point, provide each specific embodiment in the form of a list below.
The list of table 1 each embodiment component
The preparation method of embodiment 1-10 is: take lincomycin hydrochloride and be dissolved in distilled water and be mixed with lincomycin hydrochloride aqueous solution; Take spectinomycin, surfactant, cosurfactant, stirred at ambient temperature mix homogeneously, then slowly instill lincomycin hydrochloride aqueous solution.Along with the increase of the distillation water yield, system viscosity increases; When the amount adding distilled water makes system become oil-in-water type nano-emulsion from Water-In-Oil, system viscosity is thinning from the state of most thickness, forms water white nano-emulsion system; Add remaining lincomycin hydrochloride aqueous solution, get product.
two) test experiments
(1) granularmetric analysis
Observe the nano-emulsion product of embodiment 1-10 under transmission electron microscope, find that drop is that class is spherical, good dispersion, without adhesion.Fig. 1 is the transmission electron microscope photo of lincomycin in embodiment 1-spectinomycin compound nanometer emulsion.Utilize the nano-emulsion of Malvern Particle Size Analyzer to embodiment 1 to detect, testing result as shown in Figure 2.As can be seen from Figure 2, emulsion particle diameter is distributed between 30.1 ~ 71.8nm, and mean diameter is 53.3nm.
(2) stability analysis
The nano-emulsion product of Example 1-10 carries out high speed centrifugation test, photo-stability testing, temperature stability test etc. respectively, observe the stability of lincomycin of the present invention-spectinomycin compound nanometer emulsion, be confirmed whether that the wild effects such as layering, muddiness or crystal precipitation occur.
high speed centrifugation is tested
Sample thief loads in centrifuge tube, with centrifugal 10 min of the rotating speed of 15000 r/min.Centrifugally rear sample to be observed, find each embodiment sample still can keep after centrifugation centrifugal before clear state, there is not the phenomenons such as layering, muddiness or crystal precipitation.
photo-stability testing
Getting each embodiment sample loads in water white vial, sealing, is positioned over 10d under normal lighting conditions, observes respectively at 1d, 2d, 4d, 6d, 8d, 10d sampling.Result shows, within the 10d observation period, each embodiment sample all keeps clear state, has no the wild effects such as layering, muddiness or crystal precipitation.
temperature stability test
Get each embodiment sample, every each embodiment divides three parts, loads in water white vial, sealing.Each point of sample is positioned over respectively 4 DEG C, keeps sample in room temperature (25 DEG C) and 40 DEG C of environment and investigate 30d, observe every 5d sampling.Result shows, within the 30d observation period, lincomycin, the spectinomycin nano-emulsion of embodiment 1-10 all keep clear under three kinds of temperature conditions, have no the wild effects such as layering, muddiness or crystal precipitation.
long-term stable experiment
3 batches of nano-emulsions are sealed in Brown Glass Brown glass bottles and jars only, be placed in (25 ± 2) DEG C, relative humidity (60 ± 5) % condition lower 12 months, sample respectively at when 0,3,6,9 and 12 months, investigate character and the changes of contents of nano-emulsion, and list of references statistical analysis technique, calculate the effect duration of lincomycin-spectinomycin compound nanometer emulsion.Result of the test shows under long term test condition, and the outward appearance of lincomycin-spectinomycin compound nanometer emulsion keeps clear and bright, homogeneous always, has no the phenomenons such as layering, complexion changed, flocculation and breakdown of emulsion; Lincomycin in system and spectinomycin content extend in time and reduce gradually, and the equation of linear regression provided according to content-time changing curve, the effect duration calculating lincomycin-spectinomycin is 35.12 months (with time short person for standard).
(3) toxicity test
With commercially available sharp proceomycin for contrast agents, carry out acute toxicity test according to new drug nonphosphorylated neurofilament H method: repeated dose toxicity test, genetic toxicity test (comprising Salmonella reversion test, Micronuclei In The Mouse Bone Marrow test, the test of In vitro culture mammalian cell chromosome mutation), reproductive toxicity test (General Reproductiv e Toxicity Assessment, sensitive period to teratogenic agent toxicity test, perinatal toxicity are tested), carcinogenic test, immunotoxicity test and Local irritation study, result of the test is as follows:
This product is to Mouse Acute Toxicity experiment conclusion: contrast with commercially available sharp proceomycin, and lincomycin-spectinomycin compound nanometer emulsion does not occur measuring interior untoward reaction and death.
The Salmonella reversion test of product of the present invention, the result of the genetic toxicity test such as mouse inbred strain and testis chromosomal aberration test are feminine gender.
The result that rat 30d feeds product of the present invention shows: contrast with commercially available sharp proceomycin, within experimental period, in lincomycin of the present invention-spectinomycin compound nanometer emulsion metering, each test group of animals growth promoter is good, the indexs such as body weight, food ration, routine blood test, blood biochemistry, organ coefficient are all within normal range, and histopathologic examination is no abnormality seen also.
This product long term toxicity test conclusion: contrast with commercially available sharp proceomycin, within experimental period, in lincomycin-spectinomycin compound nanometer emulsion dosage, gastric infusion has no rat untoward reaction for three months continuously, every Index for examination is all within normal range, and its main organs of pathologic finding and target organ are showed no the toxic pathological change that this guiding drug rises.
(4) pharmacokinetics
Result of the test shows, lincomycin of the present invention-spectinomycin compound nanometer emulsion oral absorption rapidly, completely.Blood eliminates half-life (t
1/2b) be 1 ~ 2 hour, renal hypofunction person (creatinine clearance rate < 20ml/ minute) can extend to 20 ~ 35 hours.These product are mainly discharged through kidney with prototype, discharge about 100% after single administration in 48 hours in urine with prototype.
Claims (7)
1. lincomycin-spectinomycin compound nanometer emulsion, it is characterized in that, the weight of described compound nanometer emulsion consists of: lincomycin hydrochloride 1 ~ 20 part, spectinomycin 1 ~ 25 part, 15 ~ 40 parts, surfactant, cosurfactant 1 ~ 25 part, oil 1 ~ 16 part, 18 ~ 75 parts, water.
2. lincomycin-spectinomycin compound nanometer emulsion as claimed in claim 1, it is characterized in that, the weight of described compound nanometer emulsion consists of: lincomycin hydrochloride 1 ~ 14 part, spectinomycin 5 ~ 15 parts, 20 ~ 35 parts, surfactant, cosurfactant 1 ~ 10 part, oil 1 ~ 12 part, 20 ~ 50 parts, water.
3. lincomycin-spectinomycin compound nanometer emulsion as claimed in claim 2, it is characterized in that, the weight of described compound nanometer emulsion consists of: lincomycin hydrochloride 7 parts, spectinomycin 10 parts, 28 parts, surfactant, cosurfactant 4 parts, oil 12 parts, 39 parts, water.
4. lincomycin-spectinomycin the compound nanometer emulsion as described in as arbitrary in claim 1-3, it is characterized in that, described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene (40) ether, Tween 80 or PLURONICS F87 any one or with the mixture of span80.
5. lincomycin-spectinomycin the compound nanometer emulsion as described in as arbitrary in claim 1-3, it is characterized in that, described cosurfactant is selected from ethanol, 1,2-PD, PEG400 and glycerol.
6. lincomycin-spectinomycin the compound nanometer emulsion as described in as arbitrary in claim 1-3, it is characterized in that, described grease separation is from soybean oil, cinnamic aldehyde, Ethyl formate, ethyl oleate, fatty glyceride, Oleum Ricini, Oleum Brassicae campestris, linoleic acid, ethyl n-butyrate., isopropyl myristate, ethyl acetate and oleic acid.
7. lincomycin-spectinomycin the compound nanometer emulsion as described in as arbitrary in claim 6, it is characterized in that, described oil is isopropyl myristate.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108670951A (en) * | 2018-07-05 | 2018-10-19 | 河南牧翔动物药业有限公司 | A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals and preparation method thereof |
| CN111388498A (en) * | 2020-03-23 | 2020-07-10 | 山东迅达康兽药有限公司 | Spectinolincomycin hydrochloride soluble powder capable of being mutually dissolved with oil seedlings after being dissolved in water and preparation method thereof |
| CN112006985A (en) * | 2020-07-30 | 2020-12-01 | 瑞普（天津）生物药业有限公司 | Powder injection diluent and preparation method and application thereof |
| CN114748495A (en) * | 2022-05-18 | 2022-07-15 | 广东温氏大华农生物科技有限公司 | Oil-water-soluble veterinary linke grand scale compound preparation and preparation method and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048748A (en) * | 2010-12-27 | 2011-05-11 | 华南农业大学 | Lincomycin and spectinomycin compound oil suspension injection and preparation method and application thereof |
| CN102641282A (en) * | 2012-03-07 | 2012-08-22 | 西北农林科技大学 | Compound erythromycin ethylsuccinate nano emulsion antibacterial agent and preparation method thereof |
| CN102973582A (en) * | 2012-11-07 | 2013-03-20 | 河南牧翔动物药业有限公司 | Compound florfenicol and neomycin sulfate nanoemulsion formulation and preparation method thereof |
| WO2013105101A8 (en) * | 2012-01-13 | 2014-01-30 | Department Of Biotechnology | Solid lipid nanoparticles entrapping hydrophilic/ amphiphilic drug and a process for preparing the same |
| CN104027390A (en) * | 2014-05-14 | 2014-09-10 | 河南牧翔动物药业有限公司 | Oil-in-water type compound amphotericin B nano-emulsion |
| CN104027408A (en) * | 2014-05-14 | 2014-09-10 | 河南牧翔动物药业有限公司 | Oil-in-water type compound apramycin nano-emulsion |
-
2014
- 2014-10-20 CN CN201410555616.5A patent/CN104306389A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102048748A (en) * | 2010-12-27 | 2011-05-11 | 华南农业大学 | Lincomycin and spectinomycin compound oil suspension injection and preparation method and application thereof |
| WO2013105101A8 (en) * | 2012-01-13 | 2014-01-30 | Department Of Biotechnology | Solid lipid nanoparticles entrapping hydrophilic/ amphiphilic drug and a process for preparing the same |
| CN102641282A (en) * | 2012-03-07 | 2012-08-22 | 西北农林科技大学 | Compound erythromycin ethylsuccinate nano emulsion antibacterial agent and preparation method thereof |
| CN102973582A (en) * | 2012-11-07 | 2013-03-20 | 河南牧翔动物药业有限公司 | Compound florfenicol and neomycin sulfate nanoemulsion formulation and preparation method thereof |
| CN104027390A (en) * | 2014-05-14 | 2014-09-10 | 河南牧翔动物药业有限公司 | Oil-in-water type compound amphotericin B nano-emulsion |
| CN104027408A (en) * | 2014-05-14 | 2014-09-10 | 河南牧翔动物药业有限公司 | Oil-in-water type compound apramycin nano-emulsion |
Non-Patent Citations (1)
| Title |
|---|
| 傅超美 等: "《中药药剂学》", 31 August 2014, 中国医药科技出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108670951A (en) * | 2018-07-05 | 2018-10-19 | 河南牧翔动物药业有限公司 | A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals and preparation method thereof |
| CN111388498A (en) * | 2020-03-23 | 2020-07-10 | 山东迅达康兽药有限公司 | Spectinolincomycin hydrochloride soluble powder capable of being mutually dissolved with oil seedlings after being dissolved in water and preparation method thereof |
| CN112006985A (en) * | 2020-07-30 | 2020-12-01 | 瑞普（天津）生物药业有限公司 | Powder injection diluent and preparation method and application thereof |
| CN114748495A (en) * | 2022-05-18 | 2022-07-15 | 广东温氏大华农生物科技有限公司 | Oil-water-soluble veterinary linke grand scale compound preparation and preparation method and application thereof |
| CN114748495B (en) * | 2022-05-18 | 2023-02-03 | 广东温氏大华农生物科技有限公司 | Oil-water double-soluble veterinary linke grand compound preparation and preparation method and application thereof |
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Application publication date: 20150128 |