CN109512999A - The application of synergetic effect additive of the fatty alcohol of oxygen-containing hydrocarbon derivative as polymyxins - Google Patents
The application of synergetic effect additive of the fatty alcohol of oxygen-containing hydrocarbon derivative as polymyxins Download PDFInfo
- Publication number
- CN109512999A CN109512999A CN201811326331.9A CN201811326331A CN109512999A CN 109512999 A CN109512999 A CN 109512999A CN 201811326331 A CN201811326331 A CN 201811326331A CN 109512999 A CN109512999 A CN 109512999A
- Authority
- CN
- China
- Prior art keywords
- polymyxins
- drug
- alcohol
- oxygen
- animal
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/142—Amino acids; Derivatives thereof
- A23K20/147—Polymeric derivatives, e.g. peptides or proteins
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The present invention discloses the application of synergetic effect additive of the fatty alcohol of oxygen-containing hydrocarbon derivative as polymyxins.Oxygen-containing hydrocarbon derivative containing 4-18 carbon atom includes fatty alcohol, fatty acid and fatty glyceride can be used as polymyxins synergist, inhibit the synergetic effect additive of sensitive strain and the reversal of drug resistance agent of polymyxins especially as polymyxins, and disclose the Pharmaceutical composition of the polymyxins synergist, the Pharmaceutical composition is also applied in the drug and additive for animal feed of preparation treatment polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases by the further present invention, more efficiently application space is provided for the application of polymyxins, there is highly important application value in pharmaceutical field and animal-breeding field.
Description
The present invention is March 4 2016 patent application day, application number 201610124829.1, and denomination of invention is oxygen-containing hydrocarbon
Divisional application of the derivative as the application of the synergetic effect additive of polymyxins.
Technical field
The invention belongs to biological medicine and feed additive fields, and in particular to oxygen-containing hydrocarbon derivative is as polymyxins
Synergetic effect additive application.
Background technique
Polymyxins is a kind of polypeptide antibiotics extracted from poly-viscosity bacillus fermentation liquid, mainly include aerosporin,
B, five kinds of different components such as C, D and E.Wherein polymyxin B is then applied to physianthropy clinic, it is considered to be the mankind tackle carbon
The absolute weapon of penems drug resistance enterobacteriaceae lactobacteriaceae, and polymyxin e is most widely used antibiotics of animal class growth
One of promotor.With the extensive use of antibiotic, the drug resistance of bacterium has become global difficult medical problem, and especially leather is blue
The multidrug resistance (MDR) of family name's negative bacteria is particularly problematic.The related new drug resistant gene MCR-1 of polymyxins is mediated recently
The report of a possibility that Drug Resistance of E. coli and its horizontal transmission causes panic discussion of the whole world to bacterial drug resistance, load
Heart polymyxins is broken as the last line of defense of bacterial diseases in humans chemotherapy.Come over the past several decades, Ren Menyi
Directly in the drug resistance for attempting to delay or eliminate bacterium, but rarely has major progress.Therefore, exploitation can eliminate the drug resistance of polymyxins
Property composition, for improve polymyxins effect, prolong its service life and be of great significance.Further, since more Acarasiales
The system toxicity of element is very big, is unable to high dose use, if there is synergistic component exploitation compound medicinal formulation (especially to infuse
Penetrate agent) then have realistic meaning for the toxic side effect, raising drug safety and the curative effect that reduce polymyxins.
Summary of the invention
The object of the present invention is to provide a kind of oxygen-containing hydrocarbon derivatives for containing 4~18 carbon atoms as polymyxins
Drug or animal feed addition of the synergetic effect additive in preparation treatment polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases
It is applied in agent.
Polymyxins synergetic effect additive of the present invention is that a kind of novel non-antibiotic class polymyxins is synergistic
Agent, for the oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms.
The oxygen-containing hydrocarbon derivative for containing 4~18 carbon atoms of the invention is being made as the synergetic effect additive of polymyxins
It is applied in the drug or additive for animal feed of standby treatment polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases.
In a synergistic technical solution, the oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms is to contain
There are the saturation or unsaturated fatty alcohol of the linear chain or branched chain of 4~18 carbon atoms, structure is as shown in formula I:
Wherein, R1Selected from C3-17Saturated alkyl, the C of linear chain or branched chain3-17The unsaturated alkyl of linear chain or branched chain.
In a synergistic technical solution, the R1It preferably is selected from C9-11Saturated alkyl, the C of linear chain or branched chain9-11Directly
The unsaturated alkyl of chain or branch.
In the technical solution of another synergy, the oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms is
The saturation or unsaturated aliphatic aldehyde of linear chain or branched chain containing 4~18 carbon atoms have the structure as shown in formula II:
Wherein, R2Selected from C3-17Saturated alkyl, the C of linear chain or branched chain3-17The unsaturated alkyl of linear chain or branched chain.
In the technical solution of another synergy, the fatty aldehyde is preferably the straight chain containing 10-12 carbon atom
Or the saturated or unsaturated fatty aldehyde of branch.
In the technical solution of another synergy, the oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms is
The saturation or unsaturated fatty acid of linear chain or branched chain containing 4~18 carbon atoms have the structure as shown in formula III:
Wherein, R3For C3-17The saturated alkyl or C of linear chain or branched chain3-17The unsaturated alkyl of linear chain or branched chain.
In the technical solution of another synergy, the R3Preferably C9-11The saturated alkyl of linear chain or branched chain or
C9-11The unsaturated alkyl of linear chain or branched chain.
In the technical solution of another synergy, the oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms is
The saturation of linear chain or branched chain of the structure containing 4~18 carbon atoms as shown in formula IV or the esterification of unsaturated fatty acid are derivative
Object:
Wherein, R4Selected from C3-17Saturated alkyl, the C of linear chain or branched chain3-17The unsaturated alkyl of linear chain or branched chain；R5It is selected from
C1-18Saturated alkyl, the C of linear chain or branched chain1-18Unsaturated alkyl, the C of linear chain or branched chain1-18The hydroxyl of linear chain or branched chain replaces alkane
Base.
Further, the ester of the saturation of the linear chain or branched chain containing 4~18 carbon atoms or unsaturated fatty acid
Change derivative is its glyceride.
In the technical solution of another synergy, the saturation of the linear chain or branched chain containing 4-18 carbon atom or
The glyceride of unsaturated fatty acid is preferably the monoglyceride of the fatty acid.
In the technical solution of another synergy, the saturation of the linear chain or branched chain containing 4-18 carbon atom or
The glyceride of unsaturated fatty acid is preferably the diglyceride of the fatty acid.
In the technical solution of another synergy, the saturation of the linear chain or branched chain containing 4-18 carbon atom or
The glyceride of unsaturated fatty acid is the triglycerides of the fatty acid.
In the technical solution of another synergy, the saturation of the linear chain or branched chain containing 4-18 carbon atom or
The carbonyl end of the esterification derivative of unsaturated fatty acid is preferably the carbonyl containing 10-12 carbon atom.
Oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms and polymyxins can be used in combination and to form medicine by the present invention
Use composition.
The present invention provides Pharmaceutical composition, includes the more of the above-mentioned oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms
Colistin synergetic effect additive and polymyxins.
In a technical solution, the Pharmaceutical composition further comprise pharmaceutically acceptable excipient, carrier,
Adjuvant, solvent or their any combination.
In a technical solution, the Pharmaceutical composition also includes polymyxins.
In another technical solution, the polymyxins is selected from aerosporin, polymyxin B, Polymyxin C, glues more
Rhzomorph D, polymyxin e etc..
In another technical solution, the polymyxins is preferably polymyxin B.
In another technical solution, the polymyxins is preferably polymyxin e.
The present invention also provides contain synergy of the oxygen-containing hydrocarbon derivative of 4~18 carbon atoms as polymyxins
Application of the agent in the drug of preparation treatment polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases.
In a technical solution, the drug of the described Pharmaceutical composition preparation comprising polymyxins synergetic effect additive at
Dividing is polymyxins synergetic effect additive, pharmaceutically acceptable carrier, excipient, solvent and adjuvant.
In another technical solution, the drug of the Pharmaceutical composition preparation comprising polymyxins synergetic effect additive
Ingredient is one of polymyxins, polymyxins synergetic effect additive, pharmaceutically acceptable carrier, excipient, solvent and assistant
Agent.
In another technical solution, the drug of the Pharmaceutical composition preparation comprising polymyxins synergetic effect additive exists
It can be given by way of oral, injection or local application for treating by polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases
Medicine.
In a technical solution, the drug of disease caused by the treatment polymyxins sensitive bacteria or drug-fast bacteria is for controlling
The mankind are treated because the disease caused by polymyxins sensitive bacteria or drug-fast bacteria infection includes that the surface of a wound, urinary tract, eye, ear, tracheae, skin are glutinous
Film, enteric infection, septicemia, peritonitis, meningitis etc..
In another technical solution, the drug of disease caused by the treatment polymyxins sensitive bacteria or drug-fast bacteria is used for
Cultivated animals are treated because of the disease caused by polymyxins sensitive bacteria or drug-fast bacteria infection.
The present invention also provides contain synergetic effect additive of the oxygen-containing hydrocarbon derivative of 4~18 carbon atoms as polymyxins
Preparing the application in additive for animal feed.
In a technical solution, the production performance that the additive for animal feed is used to improve animal promotes animal raw
It is long.
In another technical solution, the additive for animal feed further also includes that other nutritional feeds add
Add agent and non-nutritional feed additive.
The additive for animal feed is suitable for the livestock and poultry of each growth phase.
The domestic animal includes the food such as pig, ox, sheep, horse, rabbit, donkey, deer, cat, dog, fox, ermine or racoon dog of each growth phase
The cultivation of grass or non-a vegetarian animal.
The domestic animal includes the cultivation of the poultries such as chicken, guinea fowl, duck, goose, dove or the quail of each growth phase.
The bioassay results of in vitro and in vivo show the 4-18 carbon contained in Pharmaceutical composition provided by the invention original
The oxygen-containing hydrocarbon derivative of son is very weak to polymyxins sensitive bacteria or the equal inhibitory activity of drug-fast bacteria, and while sharing with polymyxins is more
Colistin has the function of synergy to the inhibitory activity of polymyxins sensitive bacteria or drug-fast bacteria.
Animal-breeding experiment the result shows that, the 4-8 carbon atom contained in Pharmaceutical composition provided by the invention contains
The effect for not having to the bacterium infection of animal and preventing and controlling is used alone simultaneously to the productivity of animal in the hydrocarbon derivative of oxygen
Can there is no improvement, when the cultivation for being united and applied in animal with polymyxins is very significant to the control effect of Animal diseases, also
The production performance of animal can be improved significantly.
Any embodiment in either present invention face can be combined with other embodiments, as long as they are not
It will appear contradiction.In addition, any technical characteristic can be adapted for other realities in any embodiment of either side of the present invention
The technical characteristic in scheme is applied, as long as they are not in contradiction.Mentioned-above content only outlines of the invention certain
Aspect, but it is not limited to these aspects.These aspects and otherwise content will make more specific complete description below.
Term "comprising" of the present invention is open language mode, and expression can also contain other than the ingredient referred to
The certain ingredients that do not point out.
Term " alkyl " of the present invention is the alkyl for removing a hydrogen atom less in alkane molecule and becoming；"C3-17Directly
The saturated alkyl of chain or branch " indicates that alkyl is the straight-chain alkyl containing 3~17 carbon atoms without unsaturated bond or has
The alkyl of branch；"C3-17The unsaturated alkyl of linear chain or branched chain " indicates that alkyl is to contain 3~17 carbon originals containing double bond
Sub straight-chain alkyl or the alkyl with branch；"C1-18The hydroxyl substituted alkyl group of linear chain or branched chain " is indicated by one or more hydroxyls
The straight-chain alkyl containing 1-18 carbon atom that base replaces or with the alkyl of branch.
Polymyxins is the antibiotic property polypeptide being found in poly-viscosity bacillus culture solution, has five kinds of A, B, C, D, E etc., antimicrobial spectrum
It is mutually similar and have a wide reach, to most of Gram-negative bacterias such as Pseudomonas aeruginosa, Escherichia coli, bacillus canalis capsulatus, thermophilic
Blood bacillus, Enterobacter, detection of Salmonella, shigella dysenteriae, Bordetella pertussis, Pasteurella and vibrios etc. have very strong antibacterial action,
Common antibody-resistant bacterium has the part bacterial strain of Escherichia coli, Pseudomonas aeruginosa, salmonella, Shigella, Klebsiella etc..
Polymyxins synergetic effect additive of the present invention is that the oxygen-containing hydrocarbon derivative containing 4~18 carbon atoms is selected from
The saturated or unsaturated fatty alcohol of linear chain or branched chain containing 4-18 carbon atom, straight chain or branch containing 4-18 carbon atom
The saturated or undersaturated aliphatic acid of the saturated or unsaturated fatty aldehyde of chain, linear chain or branched chain containing 4-18 carbon atom,
Its structure is respectively as shown in Formulas I, Formula II and formula III:
Wherein, R1、R2And R3For C3-17The saturated alkyl or C of linear chain or branched chain3-17The unsaturated alkyl of linear chain or branched chain；Also
It can be selected from the esterification derivative of the saturated or undersaturated aliphatic acid of the linear chain or branched chain containing 4-18 carbon atom.
The saturated or unsaturated fatty alcohol of the linear chain or branched chain containing 4-18 carbon atom is selected from propyl alcohol, fourth
Alcohol, n-amyl alcohol, hexanol, enanthol, octanol, nonyl alcohol, decyl alcohol, tip-nip, laruyl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol or this
Corresponding isomerism alcohol of a little alcohol etc. and these alcohol correspond to the insatiable hunger containing the double bond in an end of the chain or chain of carbon atom number
And fatty alcohol.
The saturated or undersaturated aliphatic acid of the linear chain or branched chain containing 4-18 carbon atom is selected from propionic acid, fourth
Acid, valeric acid, caproic acid, enanthic acid, octanoic acid, n-nonanoic acid, capric acid, hendecoic acid, lauric acid, myristic acid, palmitinic acid, stearic acid or these
The unsaturation containing the double bond in an end of the chain or chain of corresponding isomerism acid of acid etc. and the corresponding carbon atom number of these acid
Fatty acid.
The saturated or unsaturated fatty aldehyde of the linear chain or branched chain containing 4-18 carbon atom is selected from butyraldehyde, penta
Aldehyde, hexanal, enanthaldehyde, octanal, aldehyde C-9, the hendecanal, lauryl aldehyde, myristic aldehyde, palmital, stearaldehyde or these aldehyde are same point corresponding
Iso-aldehyde etc. and these aldehyde correspond to unsaturated aliphatic aldehyde of the carbon atom number containing double bond in an end of the chain or chain.
The esterification derivative of the saturated or undersaturated aliphatic acid of the linear chain or branched chain containing 4-18 carbon atom
Selected from propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, octanoic acid, n-nonanoic acid, capric acid, hendecoic acid, lauric acid, myristic acid, palmitinic acid,
Isomerisms of stearic acid or these acid acid or these corresponding carbon atom numbers of acid containing the double bond in an end of the chain or chain not
The esterification products of saturated fatty acid and the monohydric alcohol containing 1-18 carbon atom or polyalcohol, such as methanol ester, the ethyl alcohol of above-mentioned acid
Ester, propyl alcohol ester, butyl alcohol ester, amylalcohol ester, hexanol ester, enanthol ester, octanol ester, nonyl alcohol ester, decyl ester, undecyl alcohol ester, laurel alcohol ester,
Nutmeg alcohol ester, palm alcohol ester, stearic alcohol ester, monoglyceride, diglyceride, triglycerides etc..
Oxygen-containing hydrocarbon derivative of the present invention containing 4-18 carbon atom is petrochemical industry fine chemical product, is contained
Have the linear chain or branched chain of 4-18 carbon atom saturated or undersaturated aliphatic acid can from the straight chain containing 4-18 carbon atom or
The saturated or unsaturated fatty alcohol or fatty aldehyde of branch are prepared through peroxidating, and esterification further occurs with alcohol and generates
Esterification derivative.The selection control of esterification condition such as feed ratio, reaction temperature, catalyst etc. in a certain range will be described
The reaction controlling that fatty acid and polyalcohol occur is in mono-esterification, double esterification etc., such as fatty mono glyceride, fatty acid glycerine dibasic acid esters
With the preparation of fatty acid triglycercide etc..
Oxygen-containing hydrocarbon derivative of the present invention containing 4-18 carbon atom includes straight containing 4-18 carbon atom
The saturated or unsaturated rouge of the saturated or unsaturated fatty alcohol of chain or branch, linear chain or branched chain containing 4-18 carbon atom
Fat aldehyde, the saturated or undersaturated aliphatic acid of linear chain or branched chain containing 4-18 carbon atom and straight containing 4-18 carbon atom
The research of the Bioexperiment in vitro such as esterification derivative of the saturated or undersaturated aliphatic acid of chain or branch passes through Microdilution
Method measures each compound to the minimal inhibitory concentration (MIC) of polymyxins sensitive bacteria and drug-fast bacteria and containing in same concentrations
There is under the condition of culture of the hydrocarbon derivative of 4-18 carbon atom polymyxins to the minimum of polymyxins sensitive bacteria and drug-fast bacteria
Mlc.The experimental results showed that the saturation of all linear chain or branched chains containing 4-18 carbon atom of the present invention or not
The fatty alcohol of saturation, linear chain or branched chain containing 4-18 carbon atom saturated or unsaturated fatty aldehyde, contain 4-18 carbon
The saturation of the saturated or undersaturated aliphatic acid of the linear chain or branched chain of atom and the linear chain or branched chain containing 4-18 carbon atom or
The esterification derivative of unsaturated fatty acid is to polymyxins sensitive bacteria (MIC<4.0ppm) and drug-fast bacteria (MIC>4.0ppm)
Inhibitory activity is very weak, MIC >=800ppm；The saturation of all linear chain or branched chains containing 4-18 carbon atom of the present invention or
The saturated or undersaturated aliphatic acid of unsaturated fatty alcohol and the linear chain or branched chain containing 4-18 carbon atom is biological in vitro
When experimental study under same concentrations with polymyxins collective effect in test strain, function and effect of the polymyxins to sensitive bacteria
Present 10-20 times of enhancing, and, enhancing about 50 times more significant to the function and effect of antibody-resistant bacterium, it shows obviously to more
The effect of the synergistic function of colistin sensitive bacteria and the drug resistance inversion to polymyxins drug-fast bacteria；But contain 4-18 carbon
The esterification derivative of the saturated or undersaturated aliphatic acid of the linear chain or branched chain of atom in vitro with polymyxins collective effect in
Test strain, be used alone test of the polymyxins to the function and effect major part of sensitive bacteria or drug-fast bacteria and polymyxins
Effect is consistent or similar, surprisingly when there is free hydroxyl group in esterification derivative such as the monoglyceride of fatty acid and fatty acid
Diglyceride has external synergistic function to polymyxins.
Oxygen-containing hydrocarbon derivative of the present invention containing 4-18 carbon atom includes straight containing 4-18 carbon atom
The saturated or unsaturated rouge of the saturated or unsaturated fatty alcohol of chain or branch, linear chain or branched chain containing 4-18 carbon atom
Fat aldehyde, the saturated or undersaturated aliphatic acid of linear chain or branched chain containing 4-18 carbon atom and straight containing 4-18 carbon atom
Test mice flesh is given in the research of the Bioexperiment in vivo such as esterification derivative of the saturated or undersaturated aliphatic acid of chain or branch
All oxygen-containing hydrocarbon derivatives and polymyxins joint containing 4-18 carbon atom that invention is related to are given after note test strain
Treatment, the survival rate of statistical test process mouse.The experimental results showed that test group is not administered compared to blank attacks poison group and more Acarasiales
Element administration positive controls are combined the fat to polymyxins without the effect of synergistic or drug resistance inversion with polymyxins in vitro
Monoglyceride shows synergistic effect in Experiment on therapy in vivo.
Further, the oxygen-containing hydrocarbon derivative of the present invention containing 4-18 carbon atom includes containing 4-18 carbon
The saturated or unsaturated fatty alcohol of the linear chain or branched chain of atom, the saturation of linear chain or branched chain containing 4-18 carbon atom or not
The fatty aldehyde of saturation, linear chain or branched chain containing 4-18 carbon atom saturated or undersaturated aliphatic acid and contain 4-18 carbon
Esterification derivative of the saturated or undersaturated aliphatic acid of the linear chain or branched chain of atom etc. is controlled mammal such as weanling pig
It treats with polymyxins use in conjunction in experiment, intramuscular injection gives experimental animal edema disease of piglets type Escherichia coli fresh cultured bacterium solution, sees
Examine and statistical test during test group the death rate.It is embodied in experimental result of the present invention all former containing 4-18 carbon
The hydrocarbon derivative of son has the function of synergy to polymyxins in vivo.
Further, the oxygen-containing hydrocarbon derivative of the present invention containing 4-18 carbon atom includes containing 4-18 carbon
The saturated or unsaturated fatty alcohol of the linear chain or branched chain of atom, the saturation of linear chain or branched chain containing 4-18 carbon atom or not
The fatty aldehyde of saturation, linear chain or branched chain containing 4-18 carbon atom saturated or undersaturated aliphatic acid and contain 4-18 carbon
Esterification derivative of the saturated or undersaturated aliphatic acid of the linear chain or branched chain of atom etc. is applied to livestock and poultry etc. with polymyxins and moves
The average daily gain (ADFI) of animal, average daily gain in the breeding process are investigated in production performance research of the object in cultivation
(ADG) and return on feed such as meat feed ratio (FCR).In the breeding process of livestock and poultry, invent be related to containing 4-18 carbon atom
Compared with the use in conjunction of polymyxins hydrocarbon derivative or polymyxins positive controls and blank is not administered in hydrocarbon derivative
The production performance of the animal of group animal is significantly improved.
Of the present invention includes the polymyxins synergy of the oxygen-containing hydrocarbon derivative containing 4-18 carbon atom
Application of the Pharmaceutical composition of agent in the drug of preparation treatment polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases.
The drug of the treatment polymyxins sensitive bacteria or drug-fast bacteria infection associated diseases is for treating mankind or animal
Disease caused by polymyxins sensitive bacteria or drug-fast bacteria infection.Local application is applied to control with solution or emulsion or injection
Treat skin, ear, the infection of eye or oral disinfecting caused by sensitive bacteria, it may also be used for caused by polymyxins sensitive bacteria or drug-fast bacteria
Enteric infection, septicemia, urinary tract infections, burn or outer trauma surface infestation, meningitis, peritonitis, endocarditis, child's severe one hundred days
Cough and skin and mucosa infection.In addition, Pharmaceutical composition of the present invention can also include the other treatment in addition to polymyxins
Ingredient for example antibiotic, anti-tubercular drug, antifungal, antiviral agent, antiparasitic agent, antineoplastic, cardio-cerebrovascular drug,
Drugs for nervous, medicine for respiratory system, medicine for digestive system, immune system agents etc. are used for the treatment of other complex diseases.
Pharmaceutical composition disclosed by the invention is prepared using technology and methods well known by persons skilled in the art.By the present invention
The drug of disclosed composition preparation is prepared using technology and methods well known by persons skilled in the art, such as can be each by what is be related to
Component mixes under environment temperature and atmospheric pressure with pharmaceutically acceptable excipient, carrier, adjuvant, solvent or their combination
To prepare.
The treatment polymyxins sensitive bacteria prepared by Pharmaceutical composition of the present invention or drug-fast bacteria infection associated diseases
Drug be generally suitable for being suitble to the agent of following administration route including those in the dosage form administered to a patient by required approach
Type is such as administered orally: tablet, caplet agent, pill, contains tablet, pulvis, syrup, suspension, solution, emulsion at capsule
Deng；Parenteral administration: sterile solution agent, suspension, redissolution pulvis etc.；Cutaneous penetration: transdermal patch tablet etc.；Rectum or cavity
Administration: suppository, lotion；Inhalant dosage form: aerosol, solution, dry powder doses etc. and local administration: cream, ointment, lotion,
Solution, paste, spray, foaming agent, gelling agent etc..In a technical solution, the Pharmaceutical composition or drug can be with
It is peroral dosage form.In another technical solution, the Pharmaceutical composition or drug can be inhalant dosage form.In another technical side
In case, Pharmaceutical composition or drug of the present invention can be Topical dosage forms.In another technical solution, the medicine
It can be with nose administration with composition or drug.
Of the present invention includes the polymyxins synergy of the oxygen-containing hydrocarbon derivative containing 4-18 carbon atom
The Pharmaceutical composition of agent is preparing the application in feed addictive.
In some embodiments, provided by the invention by including the oxygen-containing hydrocarbon derivative containing 4-18 carbon atom
Polymyxins synergetic effect additive Pharmaceutical composition preparation feed addictive as animal growth promoting agent use improve feeding
Expect that there is significant effect in terms of utilization rate, the production performance for improving animal, stimulation growth of animal.Furthermore it is also possible to for moving
The prevention of the disease of object in the breeding process such as diarrhea etc..
The feed addictive is in preparation process and acceptable excipient, carrier, antioxidant, diluent, resistive connection
Block agent, solvent or their combination are prepared according to existing industrial technology method.In one embodiment, the feed addictive
Substance containing supplement and balanced nutrients.In another embodiment, the feed addictive also contains health care substance.?
In another embodiment, the feed addictive also contains Physiological effect metabolism substance.In another embodiment, described
Feed addictive also contain increase the aid digestion substance of appetite.In another embodiment, the feed addictive also contains
Processing and preservative agent substance.
The feed addictive can be liquid, solid, semisolid or gel.
On the one hand, the invention further relates to the method for promoting growth of animal, the method includes giving animal effective dose
Pharmaceutical composition of the present invention or feed addictive prepared therefrom.In one embodiment, the present invention provided by the invention
The Pharmaceutical composition or feed addictive prepared therefrom, which are added in every daily sustenance of animal in the form of independent, to be used.Another
In one embodiment, Pharmaceutical composition of the present invention or feed addictive prepared therefrom and feedstuff, feed addictive,
Carrier or diluent etc. are prepared into additive premix, concentrated feed, mixed feed, fine fodder supplement according to a certain percentage and raise
The Feed forms such as material are for animal edible.
Feedstuff of the present invention refers to from animal, plant, microorganism or minerals, raises for processing and fabricating
Expect but be not belonging to the feeding substance of feed addictive.
Feed addictive of the present invention refer to feed processing, production, use process addition it is a small amount of or micro
Substance, including nutritional feed additive and non-nutritional feed additive.Nutritional feed additive refers to for supplement feed
Nutritional ingredient and mix a small amount of or micro substance in feed, including the micro member of feed grade amino acid, vitamin, minerals
Element, enzyme preparation, nonprotein nitrogen etc..Non-nutritional feed additive refers to guarantee or improve feed quality, improve feed conversion
The effects of rate and mix a small amount of or micro substance in feed.
Carrier of the present invention is to refer to carrying active constituent, improves its dispersibility, and have good chemical stabilization
Property and adsorptivity can feeding substance.
Diluent of the present invention, which refers to, is uniformly distributed in additive raw material in material, and the additive of high concentration is former
Material is diluted to the pre-mixing agent of low concentration or the substance of premix, and micro constitutent can be separated from each other, and reduces between active constituent
It reacts to each other, to increase the stability of active constituent but not influence the physico-chemical property in relation to substance.
Additive premix of the present invention refers to by two kinds (classes) or two kinds (class) or more of nutritional feed
Based on additive, the feed prepared according to a certain percentage with carrier or diluent, including compound premixed feed, microelement
Premixed feed, vitamin premixed feed.
Concentrated feed of the present invention, which refers to mainly, has protein, minerals and feed addictive to match according to a certain percentage
The feed of system.
Mixed feed of the present invention refers to according to cultivated animals nutritional need, by a variety of feedstuffs and feed addition
The feed that agent is prepared according to a certain percentage.
Concentrate supplement of the present invention refers to supplement the nutrition of plant-eating animal, and a variety of feedstuffs and feed are added
Add the feed that agent is prepared according to a certain percentage.
In another embodiment, Pharmaceutical composition of the present invention or feed addictive prepared therefrom etc. for chicken,
The raising of the poultry such as guinea fowl, duck, goose, pigeon and quail.
In another embodiment, Pharmaceutical composition of the present invention or feed addictive prepared therefrom etc. for pig,
The raising of the domestic animals such as ox, sheep, horse, donkey, rabbit, deer, cat, dog, fox, ermine or racoon dog.
In another embodiment, Pharmaceutical composition of the present invention or feed addictive prepared therefrom etc. are used for pet
Raising.
Present invention firstly discovers that the oxygen-containing hydrocarbon derivative containing 4-18 carbon atom includes fatty alcohol, fatty acid and fat
Acid glyceride can be used as polymyxins synergist, especially as polymyxins inhibit sensitive strain synergetic effect additive and glue
The reversal of drug resistance agent of rhzomorph provides more efficiently application space for the application of polymyxins, in pharmaceutical field and animal
Cultivation field has highly important application value.
Specific embodiment:
The following examples are further illustrations of the invention, rather than limiting the invention.
Embodiment 1: oxygen-containing hydrocarbon derivative studies the extracorporeal biology of polymyxins synergistic function.
Laboratory sample: polymyxin e (19000IU/mg), polymyxin B (6000IU/mg), butyric acid, caproic acid, octanoic acid, nonyl
Acid, capric acid, undecanoic acid, lauric acid, stearic acid, undecenoic acid, neodecanoic acid, decyl alcohol, laruyl alcohol, capraldehyde, lauryl aldehyde, the glycerol list last of the ten Heavenly stems
Ester, glycerol monolaurate and decyl decylate.
Experimental strain: Escherichia coli 3Y-9 (sensitive to polymyxin e), Escherichia coli 3D-5 and salmonella CU0208
(to polymyxin e drug resistance), Pseudomonas aeruginosa B545 and Shigella 4082 (to polymyxin B drug resistance).
Experimental method: testing each laboratory sample to the external minimum inhibitory concentration (MIC) of experimental strain with micro-dilution method,
As shown in table 1.Polymyxin e or more Acarasiales when the oxygen-containing hydrocarbon derivative of 100ppm is added in test respectively in culture simultaneously
Plain B sentences the minimal inhibitory concentration of different strains when with without related oxygen-containing hydrocarbon derivative compared with the MIC value of polymyxins
Break its synergy degree.Test result is shown in Table 1 and 2.
Experimental result: oxygen-containing hydrocarbon derivative is to Escherichia coli, Pseudomonas aeruginosa, salmonella and Shigella inhibiting effect
Weak (table 1)；The oxygen-containing hydrocarbon derivative Escherichia coli sensitive to polymyxins can reduce polymyxins to the body of corresponding bacterial strain
2-4 times of outer minimal inhibitory concentration, the derivative different to antibody-resistant bacterium can reduce polymyxins to the external of different strains
64 times of minimal inhibitory concentration highest (table 2).
The external minimal inhibitory concentration of 1 polymyxins of table and oxygen-containing hydrocarbon derivative to Gram-negative bacterias such as Escherichia coli
(MIC,ug/ml)
External minimal inhibitory concentration of the polymyxins to different strains under the conditions of the oxygen-containing hydrocarbon derivative 100ppm of table 2
(MIC,ug/ml)
Note: under the conditions of 100ppm different oxygen-containing hydrocarbon derivatives, polymyxin e is tested to Escherichia coli and salmonella
Minimal inhibitory concentration, test polymyxin B is to the external minimal inhibitory concentration of Pseudomonas aeruginosa and Shigella.
Dose study of 2 capric acid of embodiment to polymyxins collaboration bacteriostasis
Laboratory sample: polymyxin e, polymyxin B, capric acid；
Experimental strain: Escherichia coli 3Y-9 (sensitive to polymyxin e), Escherichia coli 3D-5 and salmonella CU0208
(to polymyxin e drug resistance), Pseudomonas aeruginosa B545 and Shigella 4082 (to polymyxin B drug resistance).
Experimental method: polymyxin e when containing various concentration capric acid respectively in culture with the test of micro checkerboard method
Or polymyxin B is to the external minimum inhibitory concentration of corresponding bacterial strain.
Experimental result: capric acid is to correlation test bacterial strain inhibitory activity weak (table 1)；And in the capric acid use in conjunction of various concentration
Under, as the polymyxins of improving of capric acid concentration reduces the minimal inhibitory concentration of corresponding bacterial strain, in apparent now dosage effect
Relationship (table 3).
External minimum inhibitory concentration (MIC, ug/ml) of the polymyxins to different bacterium under the conditions of 3 various concentration capric acid of table
Note: under different capric acid concentration conditions, test polymyxin e is antibacterial dense to the minimum of Escherichia coli and salmonella
Degree, external minimal inhibitory concentration of the test polymyxin B to Pseudomonas aeruginosa and Shigella.
3 animal experiment of embodiment: capric acid and glycerol list last of the ten Heavenly stems ester grind polymyxin B synergistic function in Mice Body
Study carefully
Laboratory sample: capric acid, glycerol list last of the ten Heavenly stems ester；
Experimental animal: mouse, half male and half female, 140, weight 18-22g；
Experimental method: mouse similar in 140 weight is randomly divided into 7 groups, and every group 20, half male and half female, each test group is small
By table 4,1 hour drug different with intramuscular injection for every eight hours is attacked after poison, drug before attacking poison are used in conjunction 3 days mouse.At first administration 1 hour
Challenge infection Pseudomonas aeruginosa B545 strain 2 × 10 is injected intraperitoneally afterwards7CFU/ mouse, observe challenge infection after in 1 week each test group it is dead
Die rate.
Experimental result: mouse challenge test is the results show that capric acid and glycerol list last of the ten Heavenly stems ester can cooperate with enhancing polymyxin B anti-
The effect of Pseudomonas aeruginosa reduces the death rate of test mice.(table 4).
4 capric acid of table and glycerol list last of the ten Heavenly stems ester are in Mice Body to the test result of polymyxin B synergistic function
Note: 5 be that polymyxin B (by the amount of 2mg/kg weight) and capric acid (by the amount of 300mg/kg weight) mixing is laggard
Row intramuscular injection, 7 groups be by polymyxin B (by the amount of 2mg/kg weight) and glycerol list last of the ten Heavenly stems ester (by the amount of 300mg/kg weight)
Intramuscular injection is carried out after mixing.
4 animal experiment of embodiment: the research of glycerol list last of the ten Heavenly stems ester and polymyxin e Collaborative Control hydropsy for baby pigs
Laboratory sample: 3D-5 plants of polymyxin e (colistine sulfate), glycerol list last of the ten Heavenly stems ester, Escherichia coli (edema disease of piglets types
Escherichia coli)；
Experimental animal: the miscellaneous weanling pig of Ternary Pig ternary, 180,24 ages in days, weight is close；
Experimental method: 180 24 age in days Ternary Pig ternary weanling pigs are randomly divided into 7 groups, every group 30.Feed is customization
The child care powder of any drug is not added.Each test group piglet 1 hour and attacks after poison intramuscular injection for every eight hours not before attacking poison by table 5
Same drug, drug are used in conjunction 3 days.After first administration 1 hour intramuscular injection challenge infection Escherichia coli 3D-5 strain 5 ×
108CFU/ mouse, observe challenge infection after in 1 week each test group son the death rate.
Experimental result: than glycerol list last of the ten Heavenly stems ester or sulfuric acid is used alone when glycerol list last of the ten Heavenly stems ester and colistine sulfate use in conjunction
More significant to the therapeutic effect of hydropsy for baby pigs when colistin, the two shows significantly to act synergistically.(table 5)
The test result of table 5 glycerol list last of the ten Heavenly stems ester and polymyxin e Collaborative Control hydropsy for baby pigs
Note: 6 be by colistine sulfate (by the amount of 2mg/kg weight) and glycerol list last of the ten Heavenly stems ester (by 200mg/kg weight
Amount) mixing after carry out intramuscular injection.
5 animal experiment of embodiment: the effect disquisition of decyl decylate and the polymyxin e use in conjunction in broiler fodder
By 1200 plumage, 1 age in days, big yellow-feather broiler is randomly divided into 6 groups fastly, every group of 4 repetitions, each 50 plumage of repetition.Divide by table 6
Group simultaneously adds colistine sulfate (polymyxin e) or/and decyl decylate respectively in feed.Experimental period cage is freely eaten
And drinking-water, the survival rate of each test group, weight gain and feedstuff-meat ratio in 21 days statistical test phases.Test result shows, decyl decylate with
Production performance when colistine sulfate combination group is than being applied alone significantly improves, and is in dosage correlation (table 6).
The use in conjunction effect of 6 capric acid of table and polymyxin e in broiler chicken material
Claims (9)
1. the oxygen-containing hydrocarbon derivative for containing 4~18 carbon atoms is mostly viscous in preparation treatment as the synergetic effect additive of polymyxins
It is applied in the drug or additive for animal feed of rhzomorph sensitive bacteria or drug-fast bacteria infection associated diseases；
The oxygen-containing hydrocarbon derivative is fatty alcohol of the structure containing 4~18 carbon atoms as shown in formula I:
Wherein, R1Selected from C3-17The saturated alkyl of linear chain or branched chain.
2. application according to claim 1, which is characterized in that the fatty alcohol containing 4~18 carbon atoms is selected from
It is propyl alcohol, butanol, n-amyl alcohol, hexanol, enanthol, octanol, nonyl alcohol, decyl alcohol, tip-nip, laruyl alcohol, myristyl alcohol, palmityl alcohol, hard
Lipidol or the corresponding isomerism alcohol of these alcohol.
3. application according to claim 1, which is characterized in that the fatty alcohol is the rouge containing 10-12 carbon atom
Fat alcohol, R1Selected from C9-11The saturated alkyl of linear chain or branched chain.
4. application according to claim 1, which is characterized in that the polymyxins is selected from aerosporin, polymyxins
B, Polymyxin C, polymyxin D or polymyxin e.
5. application according to claim 1, which is characterized in that the treatment polymyxins sensitive bacteria or drug-fast bacteria infection
The drug behaviour of associated diseases is used or animal treatment polymyxins sensitive bacteria or the drug of drug-fast bacteria infection associated diseases.
6. applying according to claim 1 or 5, which is characterized in that the polymyxins sensitive bacteria or drug-fast bacteria infection
Associated diseases include the surface of a wound, urinary tract, eye, ear, tracheae, skin and mucosa, the infection of enteron aisle and septicemia, peritonitis and meningitis.
7. application according to claim 1, which is characterized in that the additive for animal feed is growth of animal promotion
Agent.
8. application according to claim 7, which is characterized in that the animal includes the livestock and poultry of each growth phase.
9. application according to claim 8, which is characterized in that the livestock and poultry be chicken, guinea fowl, duck, goose, dove, quail,
Pig, ox, sheep, horse, rabbit, donkey, deer, cat, dog, fox, ermine or racoon dog.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811326331.9A CN109512999B (en) | 2016-03-04 | 2016-03-04 | Use of aliphatic alcohols containing oxygenated hydrocarbon derivatives as a synergist for polymyxins |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610124829.1A CN106377757B (en) | 2016-03-04 | 2016-03-04 | Application of oxygen-containing hydrocarbon derivative as synergist of polymyxin |
| CN201811326331.9A CN109512999B (en) | 2016-03-04 | 2016-03-04 | Use of aliphatic alcohols containing oxygenated hydrocarbon derivatives as a synergist for polymyxins |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610124829.1A Division CN106377757B (en) | 2016-03-04 | 2016-03-04 | Application of oxygen-containing hydrocarbon derivative as synergist of polymyxin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109512999A true CN109512999A (en) | 2019-03-26 |
| CN109512999B CN109512999B (en) | 2022-05-10 |
Family
ID=57916610
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610124829.1A Active CN106377757B (en) | 2016-03-04 | 2016-03-04 | Application of oxygen-containing hydrocarbon derivative as synergist of polymyxin |
| CN201811326331.9A Active CN109512999B (en) | 2016-03-04 | 2016-03-04 | Use of aliphatic alcohols containing oxygenated hydrocarbon derivatives as a synergist for polymyxins |
| CN201811326275.9A Pending CN109512998A (en) | 2016-03-04 | 2016-03-04 | The application of synergetic effect additive of the esterification derivative of oxygen-containing hydrocarbon derivative as polymyxins |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610124829.1A Active CN106377757B (en) | 2016-03-04 | 2016-03-04 | Application of oxygen-containing hydrocarbon derivative as synergist of polymyxin |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811326275.9A Pending CN109512998A (en) | 2016-03-04 | 2016-03-04 | The application of synergetic effect additive of the esterification derivative of oxygen-containing hydrocarbon derivative as polymyxins |
Country Status (2)
| Country | Link |
|---|---|
| CN (3) | CN106377757B (en) |
| WO (1) | WO2017147958A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019036770A1 (en) * | 2017-08-24 | 2019-02-28 | University Of South Australia | Antimicrobial compositions and methods of use |
| CN107753470B (en) * | 2017-10-09 | 2021-04-27 | 武汉大学 | Small molecule inhibitor of polymyxin drug-resistant protein and application thereof |
| CN109568494B (en) * | 2019-01-22 | 2021-11-19 | 浙江中医药大学 | Application of bletilla striata alcohol extract in preparation of polymyxin antibacterial synergist |
| CN112755174B (en) * | 2021-02-26 | 2022-11-18 | 沈阳药科大学 | Polymyxin derivatives, preparation method and application thereof |
| CN115813890B (en) * | 2022-11-30 | 2024-02-23 | 扬州大学 | Application of dendrobinol as polymyxin adjuvant in preparation of medicines for treating bacterial infectious diseases |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB647925A (en) * | 1948-05-19 | 1950-12-28 | Wellcome Found | Improvements relating to the extraction and purification of an antibiotic |
| US5120711A (en) * | 1988-04-01 | 1992-06-09 | Egis Gyogyszergyar | Synergistically active veterinary compositions and process for preparing same |
| US5587358A (en) * | 1994-05-09 | 1996-12-24 | Asahi Kasei Kogyo Kabushiki Kaisha | Potentiators of antimicrobial activity |
| WO1999045771A1 (en) * | 1998-03-12 | 1999-09-16 | The Procter & Gamble Company | Tissue paper having antimicrobial skin lotion |
| US20020165130A1 (en) * | 1998-06-22 | 2002-11-07 | Johnson Eric A. | Method of sensitizing microbial cells to antimicrobial compounds |
| CN101370453A (en) * | 2005-12-14 | 2009-02-18 | 扎尔斯制药公司 | Compositions and methods for dermal delivery of drugs |
| CN101970461A (en) * | 2008-02-08 | 2011-02-09 | 北方抗生素有限公司 | Short fatty acid tail polymyxin derivatives and uses thereof |
| CN102112125A (en) * | 2008-07-18 | 2011-06-29 | e-生物有限公司 | Antibacterial combination therapy for the treatment of gram positive bacterial infections |
| CN104922100A (en) * | 2013-12-31 | 2015-09-23 | 广州英赛特生物技术有限公司 | Beta-Hinokitol derivative and application thereof in preparing special antimicrobial agent for animals and fodder antimicrobial growth promoter |
| CN105030744A (en) * | 2015-07-09 | 2015-11-11 | 广州英赛特生物技术有限公司 | Application of substituted benzene guanidine derivative serving as polymyxins antibiotic potentiator |
| CN105263525A (en) * | 2013-04-12 | 2016-01-20 | 维奥姆生物科学有限公司 | Composition and formulation of antimicrobial agents, processes thereof and methods for treating microbial infections |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA06002719A (en) * | 2003-09-09 | 2006-09-04 | 3M Innovative Properties Co | Antimicrobial compositions and methods. |
| WO2006120494A1 (en) * | 2005-05-13 | 2006-11-16 | Advanced Scientific Developements | Pharmaceutical combination comprising an antibacterial agent and an active substance selected from carveol, thymol, eugenol, borneol and carvacrol |
| CN104274826B (en) * | 2014-10-21 | 2016-04-20 | 河南牧翔动物药业有限公司 | A kind of oil-in-water type compound colistin nano-emulsion |
-
2016
- 2016-03-04 CN CN201610124829.1A patent/CN106377757B/en active Active
- 2016-03-04 CN CN201811326331.9A patent/CN109512999B/en active Active
- 2016-03-04 CN CN201811326275.9A patent/CN109512998A/en active Pending
- 2016-03-30 WO PCT/CN2016/077921 patent/WO2017147958A1/en active Application Filing
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB647925A (en) * | 1948-05-19 | 1950-12-28 | Wellcome Found | Improvements relating to the extraction and purification of an antibiotic |
| US5120711A (en) * | 1988-04-01 | 1992-06-09 | Egis Gyogyszergyar | Synergistically active veterinary compositions and process for preparing same |
| US5587358A (en) * | 1994-05-09 | 1996-12-24 | Asahi Kasei Kogyo Kabushiki Kaisha | Potentiators of antimicrobial activity |
| WO1999045771A1 (en) * | 1998-03-12 | 1999-09-16 | The Procter & Gamble Company | Tissue paper having antimicrobial skin lotion |
| US20020165130A1 (en) * | 1998-06-22 | 2002-11-07 | Johnson Eric A. | Method of sensitizing microbial cells to antimicrobial compounds |
| CN101370453A (en) * | 2005-12-14 | 2009-02-18 | 扎尔斯制药公司 | Compositions and methods for dermal delivery of drugs |
| CN101970461A (en) * | 2008-02-08 | 2011-02-09 | 北方抗生素有限公司 | Short fatty acid tail polymyxin derivatives and uses thereof |
| CN102112125A (en) * | 2008-07-18 | 2011-06-29 | e-生物有限公司 | Antibacterial combination therapy for the treatment of gram positive bacterial infections |
| CN105263525A (en) * | 2013-04-12 | 2016-01-20 | 维奥姆生物科学有限公司 | Composition and formulation of antimicrobial agents, processes thereof and methods for treating microbial infections |
| CN104922100A (en) * | 2013-12-31 | 2015-09-23 | 广州英赛特生物技术有限公司 | Beta-Hinokitol derivative and application thereof in preparing special antimicrobial agent for animals and fodder antimicrobial growth promoter |
| CN105030744A (en) * | 2015-07-09 | 2015-11-11 | 广州英赛特生物技术有限公司 | Application of substituted benzene guanidine derivative serving as polymyxins antibiotic potentiator |
Non-Patent Citations (3)
| Title |
|---|
| KOUSHIK MUKHERJEE等: "Antibacterial activity of long-chain fatty alcohols against mycobacteria", 《FEMS MICROBIOL LETT》 * |
| PETAR KNEZEVIC 等: "Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii", 《J ETHNOPHARMACOL》 * |
| 张赛赛 等: "一种新型食品防腐剂-L-月桂酰胺精氨酸盐酸盐乙醇酯", 《食品工业科技》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017147958A1 (en) | 2017-09-08 |
| CN109512999B (en) | 2022-05-10 |
| CN109512998A (en) | 2019-03-26 |
| CN106377757A (en) | 2017-02-08 |
| CN106377757B (en) | 2020-05-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ragaa et al. | Studying the effect of formic acid and potassium diformate on performance, immunity and gut health of broiler chickens | |
| KR101228993B1 (en) | Fermentation and culture method, fermented plant extract, fermented plant extract powder and composition containing the fermented plant extract | |
| CN109512999A (en) | The application of synergetic effect additive of the fatty alcohol of oxygen-containing hydrocarbon derivative as polymyxins | |
| CN109527222A (en) | It is a kind of prevent and treat vomitoxin poisoning symptom feed addictive and its application | |
| CN108719595A (en) | A kind of alternative feeding antibiotic and the composition that can be used as phagostimulant | |
| Andronikashvili et al. | Possibility of application of natural zeolites for medicinal purposes | |
| de Lourdes Angeles et al. | Mechanisms of action of humic substances as growth promoters in animals | |
| Iqbal et al. | Effect of essential oil and organic acid on performance, gut health, bacterial count and serological parameters in broiler | |
| KR20210053637A (en) | Probiotic yeast Kluyveromyces marxianus A5 from kefir and uses thereof | |
| CN101982176B (en) | Compound sodium selenite-vitamin E oral nano-emulsion preparation for livestock and preparation method thereof | |
| CN110201142A (en) | A kind of compound preparation and preparation method thereof for preventing and treating hen salpingitis | |
| KR100218977B1 (en) | Fodder and driking water additive for improving the resistance to stress and immunity of useful animals | |
| TW201006467A (en) | Coccidiosis control agent and feed containing the same | |
| JPS6366191A (en) | Antibiotic ll-e 19020 alpha and beta | |
| WO2022012326A1 (en) | Application of e-10-hydroxy-2-decenoic acid in field of poultry breeding | |
| WO2017143667A1 (en) | Feed composition and applications thereof in preparing animal feed additive | |
| CN112913978B (en) | Piglet intestinal flora regulator | |
| Odede | Use of non-antibiotic growth promoters in chicken broiler production in Kenya | |
| JP2583382B2 (en) | Livestock and poultry feed containing purslane | |
| KR102258773B1 (en) | An animal feed form with poultry productivity improvement | |
| KR102588133B1 (en) | Ordor reducing composition | |
| RU2787022C1 (en) | Method for use of fodder additive, when growing broiler chickens | |
| Suryawanshi et al. | Effect of Sodium Butyrate, Sodium Salt of Medium Chain Fatty Acids (Dicosan) in Combatting Clostridium perfringens Induced Necrotic Enteritis in Broiler Chicken | |
| Al-Jebory et al. | Improving Chicken Growth Performance with Nano Silver Added to Drinking Water | |
| KR950009945B1 (en) | "veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |