CN104367989A - Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine - Google Patents
Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine Download PDFInfo
- Publication number
- CN104367989A CN104367989A CN201410561205.7A CN201410561205A CN104367989A CN 104367989 A CN104367989 A CN 104367989A CN 201410561205 A CN201410561205 A CN 201410561205A CN 104367989 A CN104367989 A CN 104367989A
- Authority
- CN
- China
- Prior art keywords
- nosiheptide
- polygynax
- oil
- nano
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention relates to an oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine which is a nanoemulsion preparation taking neomycin sulfate and nosiheptide as effective components. The antimicrobial medicine comprises the following components in parts by weight: 1 to 20 parts of neomycin sulfate, 15 to 35 parts of surfactant, 0 to 20 parts of cosurfactant, 1 to 25 parts of nosiheptide, 1 to 25 parts of oil and 20 to 70 parts of distilled water. The antimicrobial medicine has a good pharmacological function and an excellent antimicrobial effect via combination of neomycin sulfate and nosiheptide, and is very simple in preparation method and easy to popularize.
Description
Technical field
The invention belongs to field of medicaments, particularly relate to a kind of antibacterials, be specially a kind of oil-in-water type polygynax and nosiheptide nano-emulsion antibacterial drug.
Background technology
Polygynax, English name Neomycin Sulphate, mycifradin sulfate, CAS:1405-10-3, EINECS:215-773-1, molecular formula: C
23h
48n
6o
17s, molecular weight: 712.7222.Polygynax is a kind of aminoglycoside antibiotics, containing 2-deoxystreptamine structure, can the biosynthesis of Profilin matter, thus reach and press down Bactericidal effect, in alkaline solution, antibacterial action is stronger.There is potent bactericidal action to gram negative bacteria and part gram positive bacteria, have inhibitory action to actinomycetes, leptospira, ameba.Be usually used in treating and control to polygynax sensitive organism (escherichia coli, dysentery bacterium, staphylococcus aureus, Salmonella, Arizona bacterium, Bacillus proteus, charcoal maggot bacillus, streptococcus, Brucella, term bacillus etc.) infect the disease such as enteritis, dysentery, infective rhinitis, respiratory tract infection caused, also have certain curative effect to streptococcus pneumoniae, bacillus pyocyaneus, pasteurellosis bacillus and tubercule bacillus.
Polygynax is white or off-white powder, and odorless, very easily draws wet, soluble in water, almost insoluble in the organic solvents such as ethanol, ether, acetone or chloroform.Medicine mostly is polygynax oral tablet, but oral little absorption, need Long-term Oral escalated dose, be easy to cause inappetence, feel sick, the untoward reaction of the digestive tract reaction such as diarrhoea, based on the problems referred to above, the present invention is intended to improve the peanut ability of body to this medicine by changing dosage form, reduces untoward reaction rate, improves its therapeutic effect.
Summary of the invention
The object of the present invention is to provide a kind of oil-in-water type polygynax, nosiheptide nano-emulsion.
For achieving the above object, the technical scheme that the present invention proposes is:
Oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug, its effective ingredient is polygynax and nosiheptide.
The parts by weight of the effective ingredient of described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug consist of: polygynax 1-20 part, nosiheptide 1-25 part.
The parts by weight of described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug consist of: polygynax 1-20 part, surfactant 15-35 part, cosurfactant 0-20 part, nosiheptide 1-25 part, oily 1-25 part, distilled water 20-70 part.
Preferably, the parts by weight of described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug consist of: polygynax 1-10 part, surfactant 20-30 part, cosurfactant 1-15 part, nosiheptide 1-10 part, oily 5-20 part, distilled water 25-65 part.
Preferably, the parts by weight of described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug consist of: polygynax 7.6 parts, 28 parts, surfactant, cosurfactant 4 parts, nosiheptide 6.1 parts, oil 12 parts, distilled water 42.3 parts.
In the present invention, described surfactant is polyoxyl 40 hydrogenated castor oil (RH-40), castor oil polyoxyethylene ether 40(EL-40), in Tween 80 or PLURONICS F87 any one or with the mixture of span80.
In the present invention, described cosurfactant is one in dehydrated alcohol, 1,2-PD, PEG400 or glycerol or combination in any.
In the present invention, 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.
Preferably, described oil is cinnamic aldehyde.
Based on oil-in-water type polygynax, the nosiheptide nano-emulsion antibacterial drug of above-mentioned formula, its preparation method is: accurately take nosiheptide, surfactant, cosurfactant and oil, stir under room temperature (25 DEG C) condition, then slowly instillation is dissolved with the distilled water of polygynax wherein; 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, and namely what now produce is water white polygynax, nosiheptide nano-emulsion product.
In the said goods, the diameter of aspirin particle of polygynax, nosiheptide nano-emulsion between 37.5 ~ 71.4nm, mean diameter is 56.2nm, can directly take, also can through encapsulated or through process such as lyophilized powder technology.
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.
Nosiheptide is the Thiopeptide antibiotics produced by S.actuosus fermentation, very strong inhibitory action is had to gram positive bacteria, by the growth suppressing the elongation factor Tu in translation process and G to suppress gram positive bacteria, also suppress the synthesis of guanosine three, four phosphatase simultaneously.Nosiheptide is a kind of yellow or yellow green crystallization, and be insoluble in water, fusing point 310-320 DEG C, molecular formula is C
51h
43n
13o
12s
6, elementary composition is C:49.6%, H:4.0%, N:14.4%, O:16.7%, S:15.8%, its molecular structure is made up of five thiazole rings or reduction thiazole ring, pyridine ring, indole ring, a threonine and a glutamic acid, and side chain is a dehydroalanine.
Nosiheptide not easily absorbs in intestinal, excretes and can decompose rapidly, therefore have noresidue, not easily produce drug resistance, and with other antibiotic also without cross resistance, little to environmental effect, Chang Zuowei animal specific, is added in feedstuff.
In the present invention, human body is to the transhipment of polygynax and nosiheptide and absorb extremely difficult, nano-emulsion substrate provides good dissolving environment for nosiheptide, can through Lymphatic time oral, overcome first pass effect and molecule by barrier during gastrointestinal tract, greatly improve the dissolubility of nosiheptide, reduce medicine first pass effect in vivo, promote nosiheptide gastrointestinal absorption; In addition, the combination of polygynax and nosiheptide, while maintaining nosiheptide drug effect, also improves the antibacterial ability of polygynax, makes antibacterial more stable, better effects if.
The present invention adds bland cosurfactant as ethanol, 1 in medicine, 2-propylene glycol, glycerol or PEG400, except hydrotropy effect, more can 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 is incorporated in interfacial film, promotes the formation of radius of curvature very membranelle, expands the newborn district area of nano-emulsion, improves the activity of nano-emulsion further, improves the effect that water soluble drug is combined with fat-soluble medicine.
Compared with prior art, the invention has the advantages that:
(1) nano-emulsion emulsion particle diameter narrow distribution of the present invention, system is transparent, good stability; There is lower surface tension, there is good mobility, taking convenience;
(2) polygynax and nosiheptide compound, fungistatic effect is better;
(3) first pass effect can be overcome after oral administration, promote the gastrointestinal absorption of medicine, nosiheptide and polygynax nano-particle can be engulfed by reticuloendothelial cell rapidly, medicine rapid-onset can be made, and maintain constant blood drug level and pharmacodynamics effect, improve the bioavailability of medicine, strengthen drug effect, the consumption reducing medicine and access times, curative effect is better, drug effect is more stable;
(4) preparation method of nano-emulsion is very simple, consumes energy low, impels medicine to be easier to promote;
(5) preparation has good mobility, and can directly use as oral liquid, also can utilize encapsulated or be lyophilized into powder through lyophilized powder technology, application mode is enriched flexibly.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope photo of oil-in-water type polygynax in embodiment 1, nosiheptide nano-emulsion antibacterial drug;
Fig. 2 is the grain size distribution of oil-in-water type polygynax in embodiment 1, nosiheptide nano-emulsion antibacterial drug.
Detailed description of the invention
Below in conjunction with concrete preferred embodiment, the invention will be further described, but protection domain not thereby limiting the invention.
Case study on implementation
Table 1 case study on implementation formula
| Embodiment | Nosiheptide/g | Polygynax/g | Surfactant/g | Cosurfactant/g | Oil/g | Water/g |
| 1 | 6.1 | 7.6 | 28（EL-40） | 4(ethanol) | 12(cinnamic aldehyde) | 42.3 |
| 2 | 6.5 | 7.9 | 25（EL-40） | 3(1,2-propylene glycol) | 14(linoleic acid) | 43.6 |
| 3 | 5.5 | 6.5 | 28（RH-40） | 7(glycerol) | 11(Oleum Ricini) | 42 |
| 4 | 4.2 | 2.2 | 35（RH-40） | 5(ethanol) | 12(ethyl oleate) | 41.6 |
| 5 | 4.5 | 2.5 | 25(Tween 80) | 15(glycerol) | 13(cinnamic aldehyde) | 40 |
| 6 | 4.5 | 9.8 | 20(Tween 80) | 4(PEG400) | 16(soybean oil) | 45.7 |
Preparation method: accurately take nosiheptide, surfactant and cosurfactant, stirs under room temperature (25 DEG C) condition, and then slowly the distilled water of polygynax has been dissolved in instillation wherein; Along with the increase of the distillation water yield, system stickiness 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, and namely what now produce is water white polygynax, nosiheptide nano-emulsion product.
Analysis of cases
(1) particle diameter is observed
Observe the nano-emulsion product of embodiment 1 ~ 6 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 embodiment 1 product.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, product nano-emulsion diameter Distribution is between 37.5 ~ 71.4nm, and mean diameter is 56.2nm.
(2) stability test
The nano-emulsion product of Example 1 ~ 6 carries out high speed centrifugation test, photo-stability testing, temperature stability test etc. respectively, observes the stability of product nano-emulsion of the present invention, has been confirmed whether that the wild effects such as layering, muddiness or crystal precipitation occur.
1. high speed centrifugation test: get the outturn sample for preparing in right amount in centrifuge tube, with centrifugal 10 min of the rotating speed of 15 000r/min, after centrifugal test, sample still keep centrifugal before clear, have no the wild effects such as layering, muddiness or crystal precipitation.
2. photo-stability testing: the outturn sample for preparing in right amount loaded in transparent good colourless, transparent vial, sealing, is positioned over 10d under normal lighting conditions, observes respectively at 1d, 2d, 4d, 6d, 8d, 10d sampling.Result shows that the every increment product of sample all keep clear, has no the wild effects such as layering, muddiness or crystal precipitation.
3. temperature stability test: the outturn sample for preparing in right amount loaded in the good flint glass bottle of transparency, sealing, is positioned over 4 DEG C, keeps sample in room temperature (25 DEG C) and 40 DEG C three and investigate each 30d, every 5d sampling observation under temperature conditions.Result shows, sample all keeps clear under these three kinds of temperature conditions, has no the wild effects such as layering, muddiness or crystal precipitation.
4. 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, the effect duration of calculation sample.Result of the test shows under long term test condition, and the outward appearance of sample keeps clear and bright, homogeneous always, has no the phenomenons such as layering, complexion changed, flocculation and breakdown of emulsion; Folium Nelumbinis extract in system and ceftriaxone content extend in time and reduce gradually, the equation of linear regression that its content-time changing curve provides, and the effect duration calculating sample is 37.15 months (with time short person for standard).
(3) toxicity test
With commercial sulfuric acid neomycin (polygynax sheet) for contrast agents, carry out acute toxicity test according to new drug nonphosphorylated neurofilament H method: repeated dose toxicity test, genetic toxicity test (comprising Ames 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:
To Mouse Acute Toxicity experiment conclusion: contrast with commercial sulfuric acid neomycin tablet, nano-emulsion does not occur measuring interior untoward reaction and death.
The result of the genetic toxicity tests such as Salmonella reversion test, mouse inbred strain and testis chromosomal aberration test is feminine gender.
The result that rat 30d feeds product of the present invention shows: contrast with commercial sulfuric acid neomycin tablet, within experimental period, in nano-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.
Long term toxicity test conclusion: contrast with commercial sulfuric acid neomycin tablet, within experimental period, in nano-emulsion metering, this medicine has no rat untoward reaction for three months at continuous gastric infusion, 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.
With commercially available Nosiheptide premixed agent for contrast agents, carry out acute toxicity test according to new drug nonphosphorylated neurofilament H method: repeated dose toxicity test, genetic toxicity test (comprising Ames 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:
To Mouse Acute Toxicity experiment conclusion: contrast with commercially available Nosiheptide premixed agent, nano-emulsion does not occur measuring interior untoward reaction and death.
The result of the genetic toxicity tests such as Salmonella reversion test, mouse inbred strain and testis chromosomal aberration test is feminine gender.
The result that rat 30d feeds product of the present invention shows: contrast with commercially available Nosiheptide premixed agent, within experimental period, in nano-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.
Long term toxicity test conclusion: contrast with commercially available Nosiheptide premixed agent, within experimental period, in nano-emulsion metering, this medicine has no rat untoward reaction for three months at continuous gastric infusion, 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) test of pesticide effectiveness
In this test, get the escherichia coli (be labeled as respectively and mix sense bacterium source A, B, C, D) of separate sources respectively, be inoculated in ordinary nutritional meat soup and carry out cellar culture, get broth culture and carry out bacteriostatic test with test group medicinal liquid respectively, observe antibacterial situation and measure the size of inhibition zone.Result shows, composite nano-emulsion of the present invention has better fungistatic effect than polygynax, nosiheptide and their simple mixtures.
Because nosiheptide is used for feed additive, effectively can play the effect that sterilization strengthens immunity, effect of the present invention is significantly good, as shown in table 2, when compound nanometer emulsion of the present invention is as feed additive, there is more significantly gaining effect than common nosiheptide.
Other pharmacodynamic analysis of table 2 is tested
Claims (9)
1. oil-in-water type polygynax, a nosiheptide nano-emulsion antibacterial drug, is characterized in that, effective ingredient is polygynax and nosiheptide.
2. oil-in-water type polygynax according to claim 1, nosiheptide nano-emulsion antibacterial drug, is characterized in that, the parts by weight of described effective ingredient consist of: polygynax 1-20 part, nosiheptide 1-25 part.
3. oil-in-water type polygynax according to claim 2, nosiheptide nano-emulsion antibacterial drug, it is characterized in that, the parts by weight of described nano-emulsion antibacterial drug consist of: polygynax 1-20 part, surfactant 15-35 part, cosurfactant 0-20 part, nosiheptide 1-25 part, oily 1-25 part, distilled water 20-70 part.
4. oil-in-water type polygynax according to claim 3, nosiheptide nano-emulsion antibacterial drug, it is characterized in that, the parts by weight of described nano-emulsion antibacterial drug consist of: the parts by weight of described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug consist of: polygynax 1-10 part, surfactant 20-30 part, cosurfactant 1-15 part, nosiheptide 1-10 part, oily 5-20 part, distilled water 25-65 part.
5. oil-in-water type polygynax according to claim 4, nosiheptide nano-emulsion antibacterial drug, it is characterized in that, the parts by weight of described nano-emulsion antibacterial drug consist of: polygynax 7.6 parts, 28 parts, surfactant, cosurfactant 4 parts, nosiheptide 6.1 parts, oil 12 parts, distilled water 42.3 parts.
6. according to claim 3 ~ 5 arbitrary described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug, it is characterized in that, described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or PLURONICS F87 any one or with the mixture of span80.
7. according to claim 3 ~ 5 arbitrary described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug, it is characterized in that, described cosurfactant is one in dehydrated alcohol, 1,2-PD, PEG400 or glycerol or combination in any.
8. according to claim 3 ~ 5 arbitrary described oil-in-water type polygynax, nosiheptide nano-emulsion antibacterial drug, 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.
9. oil-in-water type polygynax according to claim 8, nosiheptide nano-emulsion antibacterial drug, is characterized in that, described oil is cinnamic aldehyde.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410561205.7A CN104367989A (en) | 2014-10-21 | 2014-10-21 | Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410561205.7A CN104367989A (en) | 2014-10-21 | 2014-10-21 | Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104367989A true CN104367989A (en) | 2015-02-25 |
Family
ID=52547348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410561205.7A Pending CN104367989A (en) | 2014-10-21 | 2014-10-21 | Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104367989A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110575532A (en) * | 2018-06-08 | 2019-12-17 | 上海莫息生物科技有限公司 | Nosiheptide soluble powder and preparation method thereof |
| CN113769060A (en) * | 2021-09-28 | 2021-12-10 | 上海交通大学医学院附属第九人民医院 | Application of nosiheptide in preparing medicine for treating periodontitis |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101670093A (en) * | 2009-09-17 | 2010-03-17 | 天津生机集团股份有限公司 | Drug composite for promoting livestock and poultry to grow and preparation method thereof |
| CN101869188A (en) * | 2010-06-11 | 2010-10-27 | 濮阳泓天威药业有限公司 | Preparation method of nosiheptide premix |
| 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 |
-
2014
- 2014-10-21 CN CN201410561205.7A patent/CN104367989A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101670093A (en) * | 2009-09-17 | 2010-03-17 | 天津生机集团股份有限公司 | Drug composite for promoting livestock and poultry to grow and preparation method thereof |
| CN101869188A (en) * | 2010-06-11 | 2010-10-27 | 濮阳泓天威药业有限公司 | Preparation method of nosiheptide premix |
| 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 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110575532A (en) * | 2018-06-08 | 2019-12-17 | 上海莫息生物科技有限公司 | Nosiheptide soluble powder and preparation method thereof |
| CN113769060A (en) * | 2021-09-28 | 2021-12-10 | 上海交通大学医学院附属第九人民医院 | Application of nosiheptide in preparing medicine for treating periodontitis |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Łukawski et al. | New oral liposomal vitamin C formulation: Properties and bioavailability | |
| Yu et al. | Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles | |
| US6140355A (en) | Pharmaceutical compositions containing rifaximin for treatment of vaginal infections | |
| CN101744763B (en) | Enrofloxacin nano emulsion and method for preparing same | |
| CN101422432B (en) | Preparation method of tilmicosin nano-emulsion antibacterial drug | |
| CN109310626A (en) | The purposes of Gram-negative kind treatment atopic dermatitis | |
| CN104352566A (en) | Oil-in-water compound chlortetracycline nanoemulsion | |
| Shahtalebi et al. | Formulation of herbal gel of antirrhinum majus extract and evaluation of its anti-propionibacterium acne effects | |
| CN102631405A (en) | Compound apigenin nanoemulsion antihypertensive drug | |
| CN104306389A (en) | Lincomycin-spectinomycin compound nano-emulsion | |
| CN104367989A (en) | Oil-in-water type neomycin sulfate nosiheptide nanoemulsion antimicrobial medicine | |
| CN104027408B (en) | Oil-in-water type compound apramycin nano-emulsion | |
| WO2011120339A1 (en) | Microemulsion formulation containing arctigenin | |
| CN102228432A (en) | Ofloxacin nanoemulsion antibacterial medicine and preparation method thereof | |
| CN104274826B (en) | A kind of oil-in-water type compound colistin nano-emulsion | |
| EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) et al. | Safety and efficacy of Sacox® microGranulate (salinomycin sodium) for chickens for fattening and chickens reared for laying | |
| CN104274405A (en) | Oil-in-water type compound ceftiofur nanoemulsion antimicrobial medicament | |
| CN104027390A (en) | Oil-in-water type compound amphotericin B nano-emulsion | |
| Armstrong et al. | Antibacterial Effects of Quinones. | |
| CN104083324B (en) | Veterinary suspoemulsion containing rifaximin as well as preparation method and application thereof | |
| CN101032507B (en) | Bacteria resisting medicine of erythrocin nanometer-emulsion and the preparing method | |
| CN104367636A (en) | Oil-in-water type compound ceftriaxone nanoemulsion antimicrobial medicine | |
| CN104352554B (en) | A kind of compound Cefquinome antibacterials | |
| CN104352433A (en) | Oil-in-water compound antimicrobial cefazolin nanoemulsion medicine | |
| CN102274228B (en) | Compound trimethoprim and sodium succinate florfenicol nanoemulsion preparation and preparation thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150225 |