CN107802598A - A kind of nano medicament carrying system of equisetin and its derivative and preparation method thereof and the application in skin soft-tissue infection - Google Patents

A kind of nano medicament carrying system of equisetin and its derivative and preparation method thereof and the application in skin soft-tissue infection Download PDF

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CN107802598A
CN107802598A CN201711226336.XA CN201711226336A CN107802598A CN 107802598 A CN107802598 A CN 107802598A CN 201711226336 A CN201711226336 A CN 201711226336A CN 107802598 A CN107802598 A CN 107802598A
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equisetin
nano
mrsa
derivative
electrostatic spinning
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陈剑鸿
石三军
罗明和
明月
李园园
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Third Affiliated Hospital of PLA Army Medical University
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • DTEXTILES; PAPER
    • D04BRAIDING; LACE-MAKING; KNITTING; TRIMMINGS; NON-WOVEN FABRICS
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    • D04H1/00Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres
    • D04H1/70Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres
    • D04H1/72Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged
    • D04H1/728Non-woven fabrics formed wholly or mainly of staple fibres or like relatively short fibres characterised by the method of forming fleeces or layers, e.g. reorientation of fibres the fibres being randomly arranged by electro-spinning

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Abstract

Application the present invention relates to novel multifunctional nano drug-loading system of a kind of anti-MRSA equisetins (equisetin) and its derivative and preparation method thereof and in skin soft-tissue infection MRSA, and combine nanometer and electrostatic spinning technique, specific surface area is big, porosity is high, breathable moisture permeability the is good nano electrostatic spinning of having the advantages that applied to skin soft-tissue infection is prepared into, new clinical treatment is provided for skin soft-tissue infection MRSA.The present invention not only solves the drug delivery system problem of anti-MRSA equisetins (equisetin) and its derivative skin soft tissue MRSA infection, the bioavilability of medicine is improved simultaneously, dual-sustained-release is realized, can be applied in the treatment of skin soft-tissue infection.

Description

A kind of nano medicament carrying system of equisetin and its derivative and preparation method thereof and Application in skin soft-tissue infection
Technical field
The invention belongs to the field of pharmaceutical preparations of medical science, is related to a kind of equisetin (equisetin) and its derives Novel multifunctional nano drug-loading system of thing and preparation method thereof and the application in skin soft-tissue infection MRSA.
Background technology
Staphylococcus aureus is a kind of important pathogen, it can cause complexity skin soft-tissue infection, bacteremia, The illnesss such as endocarditis.And the appearance of methicillin-resistant staphylococcus aureus (MRSA) and its constantly strengthening into one for drug resistance Step is degrading this situation, and it makes the extended hospital stay 66% of patient, treats holistic cost and the death rate is respectively increased 54% With 64%.MRSA already turns into one of most refractory three big infection diseases in the world side by side with hepatitis B and AIDS.MRSA's is quick Diffusion further limit the service life of some antibiotic, us is needed constantly to introduce new anti-MRSA antibiotic and new Treatment means.
Skin and soft tissue infection is that suppurative pathogenic bacteria invade epidermis, corium and inflammatory disease caused by hypodermis Disease, including epifolliculitis, furuncle, carbuncle, Burn Infection and postoperative infection etc..Staphylococcus aureus be cause skin and The main pathogenic fungi of soft tissue purulent infection, its caused disease of skin can cause the lasting repeated infection of skin, it is difficult to fully recover from an illness More, and long-term existence is not easy to eradicate in environment.The appearance of methicillin-resistant staphylococcus aureus (MRSA) and drug resistance Constantly enhancing is further degrading this situation, and skin and soft tissue as caused by Methicillin-resistant Staphylococcus aureus (MRSA) infection Infect accounting up to (20-40%).Therefore, the skin preparation of new high-efficiency is developed clinically with particularly significant for MRSA Meaning.
The content of the invention
The present invention relates to the novel multifunctional nano drug-loading system of a kind of equisetin (equisetin) and its derivative and Its preparation method and the application in skin soft-tissue infection MRSA.
Equisetin (equisetin) has good suppression gram-positive bacteria bioactivity, but golden yellow to resistance Color staphylococcus (MRSA) is still seldom.We have found that equisetin (equisetin) has good anti-MRSA activity first (MIC is 2 μ g/mL).
Present invention firstly provides equisetin (equisetin) and its derivative to prepare anti-methicillin-resistant staphylococcus Portugal Application in grape coccus (MRSA) medicine, or preparing methicillin-resistant staphylococcus aureus resistance (MRSA) skin infection and soft Application in bone tissue medicine, wherein, the structural formula of equisetin is as follows:
The structural formula of equisetin derivative is as follows:
The present invention provides a kind of equisetin (equisetin) and its derivates nanometer drug-loading system, and it is included with serum Albumin is the nano-emulsion of equisetin (equisetin) prepared by carrier and its derivative.The nano medicament carrying system adds The solubility and stability of equisetin, improve bioavilability and anti-MRSA treatment curative effects.
In a specific embodiment, the equisetin is that purchase obtains from Shanghai Xi Yuan bio tech ltd .
In a specific embodiment, equisetin (equisetin) is wrapped using BSA (bovine serum albumin(BSA)) Wrap up in, the nano-emulsion for carrying out equisetin (equisetin) makes.
The present invention also provides a kind of equisetin nano electrostatic spinning, and it is by described equisetin nano-emulsion through Static Spinning Silk technology is prepared.
Electrostatic spinning technique is a kind of solution or melt by polymer, and injection stretching is carried out using the method for high-pressure electrostatic And obtain the technology of fiber.Fiber diameter range made from electrostatic spinning is typically at tens nanometers to several microns, than traditional spinning The silk small 1-2 order of magnitude of method diameter, it has the advantages that, and specific surface area is big, porosity is high, breathable moisture permeability is good.At present, should Technology is widely studied in the biomedical sector such as field such as drug controlled release, artificial skin, wound dressing, and Increasingly it is valued by people.Electrospun fibers cloth not only can with the structure of analog cell epimatrix, have high porosity, The characteristics such as good permeability, good biocompatibility, but also it is big with specific surface area and the advantages of drugloading rate is big, in skin soft tissue There is very big application potential in infection.
Therefore mixed improving anti-MRSA antibiotic equisetin (equisetin) water solubility using nanometer technology with biology While property, we integrate the advantages that electrostatic spinning specific surface area is big, porosity is high, breathable moisture permeability is good, prepare application It is skin in equisetin (equisetin) nano electrostatic spinning preparation with dual-sustained-release ability of skin soft-tissue infection Skin soft tissue infection MRSA provides new clinical treatment.
The present invention also provides the equisetin nano medicament carrying system or prepared by the equisetin nano electrostatic spinning Application in methicillin-resistant staphylococcus aureus resistance (MRSA) medicine, or preparing anti-methicillin-resistant staphylococcus grape ball Application in bacterium (MRSA) skin infection and cartilaginous tissue medicine.
The present invention also provides the preparation method of described equisetin nano medicament carrying system, comprises the following steps:
1) seralbumin is dissolved in the water, as aqueous phase;
2) equisetin is dissolved in organic solvent, as organic phase;
3) organic phase is slowly added into the aqueous phase of ice bath, through ultrasonication, re-evaporation removes organic solvent, obtains her Fast mycin albumin nanometer rice milk.
In a specific embodiment, the preparation method of equisetin nano medicament carrying system includes:Weigh 100mg BSA (bovine serum albumin(BSA)) is dissolved in as aqueous phase in distilled water, while weighs 21mg equisetins (equisetin) use CHCl3:CH2OH (volume ratios 1:1) dissolving is used as organic phase, then organic phase is slowly added in the aqueous phase of ice bath, with 60% Power in Ultrasonic Cell Disruptor ultrasound 12min;Finally it is concentrated under reduced pressure using Rotary Evaporators and removes organic solvent, it is fast mould obtains her Plain (equisetin) albumin nanometer rice milk.
The present invention also provides the preparation method of described equisetin nano electrostatic spinning, in the equisetin of above-mentioned preparation On the basis of albumin nanometer rice milk, in addition to step:4) polyvinylpyrrolidone (PVP) is dissolved in organic solvent, then The equisetin albumin nanometer rice milk is added, stirs and removes bubble, then nano electrostatic spinning is carried out with electrostatic spinning machine Silk.
In a more particular embodiment, the preparation method of equisetin nano electrostatic spinning includes:Weigh first 45% PVP is dissolved in 3ml ethanol, then adds equisetin (equisetin) albumin that 2mL has been successful Nano-emulsion;It is put into a stirrer and stirs 14 hours to substantially uniformity mixing, is then removed from stirring instrument, and take out stirring Son, static placement 30min to bubble-free;Electrostatic spinning is carried out with electrostatic spinning machine again, voltage 19-24KV, distance is 15cm, Flow velocity is 0.5ml/h;Equisetin (equisetin) the albumin nano electrostatic spinning finally obtained.
The present invention is mainly based on anti-MRSA antibiotic equisetin (equisetin) and its derivative, with reference to nanometer And electrostatic spinning technique, it is prepared into that specific surface area is big, porosity is high, saturating applied to skin soft-tissue infection, to have The nano electrostatic spinning dual-sustained-release preparation for the advantages that gas penetrability is good, provides new clinic for skin soft-tissue infection MRSA and controls Treatment scheme.
Brief description of the drawings
(the figure acceptance of the bid of the screening active ingredients figure of Fig. 1 equisetins (equisetin) and table equisetin (epi-equisetin) Know 1 equisetin (equisetin), identify 2 corresponding table equisetins (epi-equisetin)).
Wave spectrogram (wherein, Fig. 2-1 of Fig. 2 equisetins (equisetin) and table equisetin (epi-equisetin) For the H spectrograms of equisetin, Fig. 2-2 is the C spectrograms of equisetin, and Fig. 2-3 is the H spectrograms of table equisetin, Fig. 2-4 be table she The C spectrograms of fast mycin).
The particle diameter of Fig. 3 equisetins (equisetin) nano-emulsion, PDI (Polymer dispersity index) transmissions Electronic Speculum (TEM) figure (wherein, Fig. 3-1 is transmission electron microscope picture, and Fig. 3-2 schemes for PDI).
Fig. 4 equisetins (equisetin) nano electrostatic spinning cloth audio-visual picture and ESEM (SEM) figure (wherein, Fig. 4- 1 is nano electrostatic spinning audio-visual picture and scanning electron microscope (SEM) photograph, and Fig. 4-2 is nano electrostatic spinning grain size distribution).
Differential scanning calorimetry (DSC) figure of Fig. 5 equisetins (equisetin).
Fig. 6 equisetins (equisetin) external release profile.
The external anti-MRSA activity figures of Fig. 7 equisetins (equisetin).
Anti-MRSA activity (Fig. 8-1) and MRSA infected wound healing figures inside Fig. 8 equisetins (equisetin) (Fig. 8-2).
Embodiment
Following examples are only being expanded on further and illustrate to the present invention, without limiting the scope of the present invention.Under Face is further elaborated on the present invention with reference to embodiment, it should be appreciated to those skilled in the art that the present invention is not limited to this A little embodiments and the preparation method used.Moreover, those skilled in the art can enter according to description of the invention to the present invention Row equivalent substitution, combination, improvement or modification, but these are intended to be included in the scope of the present invention.
The anti-MRSA of the equisetin of embodiment -1 (equisetin) and table equisetin (epi-equisetin) activity Screening
Anti-MRSA screening active ingredients are carried out using K-B disk diffusion methods.Concretely comprise the following steps:A) MRSA is activated;B) culture is arrived Logarithmic phase;C) sterilized MHA culture mediums are melted, let cool about 50 DEG C, the non-scald on hand back of the body is preferred;D) appropriate logarithmic phase is added MRSA bacterium solutions are into the MHA culture mediums of sterilizing melted, to final concentration about 106/mL;E) plate is down flat while hot;F) 10 are added, 18,25ug drug containing filter papers, 30 DEG C of culture 16h observation inhibition zones.It is very strong antibacterial that the selection result shows that 1 (equisetin) has Activity, 2 (table equisetin) antibacterial activities of display take second place.Concrete outcome is shown in Fig. 1.
The spectral data of the equisetin of embodiment 2 (equisetin) and table equisetin (epi-equisetin) arrange and Identify collection of illustrative plates (see Fig. 2)
Compound 1 equisetin equisetin (+)-HR-ESI-MS m/z:374.2328([M+H]+,calcd for C22H32NO4,374.2326);1H NMR(CDCl3 500MHz)δ:3.28(1H,brd,H-3),5.34(1H,brs,H-4), 5.34(1H,brs,H-5),1.90(1H,brs,H-6),0.83,1.76(2H,m,H-7),1.48(1H,m,H-8),1.08, 1.69(2H,H-9),0.95,1.80(2H,m,H-10),1.62(1H,m,H-11),1.38(3H,brs,H-12),5.13(1H, m,H-13),5.18(1H,m,H-14);1.47 (3H, brs, H-15), 0.85 (3H, d, J=7Hz, H-16), 3.56 (1H, brs, H-5 '), 3.87,3.91 (2H, d, J=14Hz, H-6 '), 3.0 (3H, brs, H-7 '), 13C NMR (CDCl3,125MHz) δ: 190.3(C-1),48.7(C-2),45.0(C-3),126.9(C-4),130.8(C-5),38.5(C-6),42.1(C-7),33.2 (C-8),35.6(C-9),28.2(C-10),39.8(C-11),14.0(C-12),129.9(C-13),126.5(C-14),17.7 (C-15),22.3(C-16),177.0(C-2’),100.1(C-3),198.7(C-4’),67.3(C-5’),60.1(C-6’), 27.2(C-7’);
Compound 2 table equisetin epi-equisetin (+)-HR-ESI-MS m/z:374.2331([M+H]+,calcd for C22H32NO4,374.2326);1H NMR(CDCl3 500MHz)δ:3.26(1H,brd,H-3),5.33(1H,brs,H- 4),5.33(1H,brs,H-5),1.89(1H,brs,H-6),0.80,1.76(2H,m,H-7),1.43(1H,m,H-8),1.07, 1.68(2H,H-9),0.94,1.79(2H,m,H-10),1.60(1H,m,H-11),1.39(3H,brs,H-12),5.08(1H, m,H-13),5.18(1H,m,H-14);1.42 (3H, brs, H-15), 0.84 (3H, d, J=7Hz, H-16), 3.58 (1H, brs, H-5 '), 3.84,3.92 (2H, d, J=14Hz, H-6 '), 3.0 (3H, brs, H-7 '), 13C NMR (CDCl3,125MHz) δ: 190.3(C-1),48.7(C-2),44.9(C-3),127.0 (C-4),130.7(C-5),38.4(C-6),42.2(C-7), 33.4(C-8),35.6(C-9),28.2(C-10),39.8(C-11),14.0(C-12),129.8(C-13),126.5(C-14), 17.6(C-15),22.5(C-16),176.9(C-2’),100.4(C-3),198.6(C-4’),66.8(C-5’),59.9(C- 6’),27.1(C-7’).
It is prepared by the nano-emulsion of the equisetin of embodiment 3 (equisetin)
Equisetin (equisetin) is wrapped up using BSA (bovine serum albumin(BSA)), carries out the making of nanoparticle.Specifically Method is dissolved in as aqueous phase in distilled water to weigh 100mg BSA (bovine serum albumin(BSA)), while weighs 21mg equisetins (equisetin) CHCl3 is used:CH2OH(1:1) dissolving is used as organic phase.Then organic phase is slowly added to the aqueous phase of ice bath In, with 60% power in Ultrasonic Cell Disruptor ultrasonic 12min.Finally being concentrated under reduced pressure using Rotary Evaporators, it is organic molten to remove Agent, equisetin (equisetin) albumin nano is obtained, finally carry out the test of the particle diameter, PDI, Zeta potential of nano-emulsion And transmission electron microscope observing, as seen from the figure, equisetin (equisetin) albumin nano milk particle footpath is in 230nm or so, nanoparticle Footpath is evenly distributed, and is successful, and is specifically shown in Fig. 3.
It is prepared by equisetin (equisetin) derivative of embodiment 4 trichosetin nano-emulsion
Equisetin derivative N- demethyls equisetin (trichosetin) is wrapped using BSA (bovine serum albumin(BSA)) Wrap up in, carry out the making of nanoparticle.Specific method is dissolved in distilled water as water to weigh 100mg BSA (bovine serum albumin(BSA)) Phase, while weigh 21mg trichosetin and use CHCl3:CH2OH(1:1) dissolving is used as organic phase.Then organic phase is delayed It is slow to add in the aqueous phase of ice bath, with 60% power in Ultrasonic Cell Disruptor ultrasonic 12min.Finally depressurized using Rotary Evaporators Concentration removes organic solvent, obtains trichosetin albumin nanometer rice milks, finally carries out particle diameter, PDI, Zeta electricity of nano-emulsion The test of position, trichosetin albumin nano milk particle footpaths are evenly distributed in 210nm or so, nanometer particle size, are successful.
Equisetin derivative trichosetin structural formula is as follows,
It is prepared by the electrostatic spinning of the nano-emulsion of embodiment 5
The electrostatic spinning carrier of albumin nanometer rice milk is used as using high polymer material PVP.45% PVP dissolvings are weighed first In 3ml ethanol, equisetin (equisetin) albumin nanometer rice milk that 2mL has been successful then is added, mixing is equal It is even.It is put into a stirrer stirring to mix to substantially uniformity for 14 hours, is then removed from stirring instrument, and takes out stirrer, it is quiet 30min is only placed to bubble-free.Electrostatic spinning finally is carried out with electrostatic spinning machine, voltage 19-24KV, distance is 15cm, stream Speed is 0.5ml/h.Equisetin (equisetin) the albumin nano electrostatic spinning finally obtained.As seen from the figure, spinning is equal Even, average grain diameter spins the smooth exquisiteness of cloth, is specifically shown in Fig. 4 in 370nm.
The differential calorimetric scan of the nano electrostatic spinning of embodiment 6 characterizes
To equisetin (equisetin) active compound, nanometer and nano electrostatic spinning and PVP electrostatic spinnings carry out differential calorimetric Scanning analysis.Wherein negative absorption peak represents endothermic peak, and positive absworption peak represents exothermic peak.Equisetin (equisetin) active compound exists Occur an exothermic peak at about 267 DEG C, and do not occur in other groups;Equisetin (equisetin) nanoparticle is quiet simultaneously Electrospun does not occur new heat absorption and exothermic peak with PVP electrostatic spinnings, illustrates equisetin (equisetin) nanoparticle quilt Successfully it is spun into electrostatic spinning.See Fig. 5.
The envelop rate of equisetin (equisetin) compound of embodiment 7 active compound, nano-emulsion and nano electrostatic spinning preparation And insoluble drug release
To the nano-emulsion of the equisetin (equisetin) of acquisition, the envelop rate that medicine is carried out using supercentrifugal process is surveyed Examination, specific method is to take 1ml nano-emulsion+1ml pancreatin (2mg/ml), 37 degree of digestion 2h+2ml methanol, after vortex 2min 25000rpm/min centrifuges 15min, takes supernatant to obtain total medicine;And free medicine measure is then to take 1ml nano-emulsions 25000rpm/ Min centrifuges 2h, takes supernatant to dissociate medicine.Simultaneously free medicine also according to the total medicine of pre-treatment method:Add 1ml and remove distilled water, 2ml methanol is added, 25000rpm/min centrifugations 15min obtains the medicine that finally dissociates after vortex 2min.To total medicine for finally obtaining and Free medicine enters HPLC analyses, calculates corresponding AUC (integral area), calculates respective concentration according still further to standard curve, finally wrap Envelope rate=1- dissociates medicine/total medicine.Last result of calculation shows that the nano-emulsion envelop rate of equisetin (equisetin) is 91.25%, equisetin (equisetin) nano-emulsion envelop rate is high.Active compound, nano-emulsion and electrostatic spinning preparation are carried out simultaneously Insoluble drug release is tested, and dissolution medium is the PBS solution containing 10% ethanol, respectively in 0,30min, 45min, 1h, 2h, 4h, 6h, 8h, 10h, 11h, 24h, 48h, sample and analyzed into HPLC.Corresponding drug concentration is calculated to the AUC after sample introduction, finally calculated Go out drug release rate, carrying out control slow fruit with the nano electrostatic spinning preparation of the nano-emulsion to equisetin and equisetin examines Examine.As a result show that equisetin (equisetin) active compound has to dash forward in 0.5h and release effect, and equisetin nano electrostatic is spun Silk preparation, which can control to dash forward, releases effect, has slow-release function.It is specifically shown in Fig. 6.
The In Vitro Bacteriostatic of embodiment 8 (MIC and antibacterial dynamics) is investigated
Respectively to equisetin (equisetin) active compound prepared, nano-emulsion, nano electrostatic spinning, negative control, Positive controls, using K-B disk diffusion methods, doubling dilution minimal inhibitory concentration (MIC) method carries out external activity investigation, enters one Step evaluates the difference of its medical value and different dosage forms.By bacterium solution culture to 0.5 Maxwell than turbid standard, with culture medium 1:100 is dilute Bacterium solution is released into experiment bacterium solution.The experiment μ l of bacterium solution 192 are respectively added to No. 1 hole, take 8 μ l sample solutions to be placed in No. 1 hole to mix and (make most Drug concentration reaches 128 μ g/ml afterwards), the experiment μ L of bacterium solution 100 are respectively added to 2-11 holes, take 100 μ l to add No. 2 from No. 1 hole Hole, the like be diluted to No. 11 holes, discard 100 μ L after mixing, No. 12 hole adds as the blank control wells for being not added with decoction The μ L of bacterium solution 200 are tested, 96 orifice plates is put in after cultivating 16-20h in 30 DEG C of constant incubators and observes result.According to the dense of each sample Degree, determine that its MIC value will test bacterium solution culture to 0.5 Maxwell than turbid standard from asepsis growth hole, with culture medium 1:100 dilutions Bacterium solution, as a result show that nanometer, nano electrostatic spinning have more preferable bacteriostatic activity.See Fig. 7-1.
Antibacterial kinetic test method is, by bacterium solution culture to 0.5 Maxwell than turbid standard, with culture medium 1:100 dilution bacterium Liquid into experiment bacterium solution.Take 10mL experiments bacterium solution to be put into each sterilizing test tubes, then be separately added into equisetin (equisetin) original Medicine, nano-emulsion, nano electrostatic spinning, negative control, positive control (after the medicine of each medicine group adds, reach drug concentration After 1/2MIC), it is put into 30 DEG C of constant incubators and cultivates, and 200 μ L tests OD600 suction is taken respectively at 4h, 8h, 12h and 16h Luminosity.As a result nano electrostatic spinning has best bacteriostatic activity, sees Fig. 7-2
SD rats anti-MRSA activity is investigated in the body of embodiment 9
1) MRSA wound infections model
It is some to choose 260g SD female rats, first by sterile scissors shaving, is then lost hair or feathers using depilatory cream, 75% Ethanol after skin surface sterilizes and dries, about 1cm2 wound is cut off using sterile scissors.35 μ L are cultivated to 0.5 Maxwell is applied to wound than the MRSA bacterium solutions of turbid standard, and wound adds after drying contains the μ of equisetin (equisetin) active compound 30 G each administration group and the positive shines group (Cefoxitin).It is taken twice daily, is administered within continuous two days, wound was cut simultaneously in the 3rd day Bacterium solution is washed with sterilized water, then dilutes 105,106,107 times with MHB culture mediums respectively, finally takes the bacterium solution after dilution The μ L of body 100 are placed in 30 DEG C of constant incubators after being coated with MHA flat boards and cultivate 24h.Finally carry out count of bacteria.As a result show Nano electrostatic spinning group can significantly reduce MRSA clump counts, see Fig. 8-1.
2) wound healing
It is some to choose 260g SD female rats, first by sterile scissors shaving, is then lost hair or feathers using depilatory cream, 75% Ethanol after skin surface sterilizes and dries, about 1cm2 wound is cut off using sterile scissors.By 35 μ L cultivate to 0.5 Maxwell is applied to wound than the MRSA bacterium solutions of turbid standard, and adds contain the μ g of equisetin (equisetin) active compound 30 immediately Each administration group and positive shine group (Cefoxitin).Respectively at 0,5,9,13 day observation wound healing situation and healing area, knot Fruit shows that nanoparticle electrostatic spinning group can remarkably promote the metainfective SD female rats wound healings of MRSA, sees Fig. 8-2.
Although embodiments of the present invention are illustrated in specification, these embodiments are intended only as prompting, It should not limit protection scope of the present invention.It is equal that various omission, substitution, and alteration are carried out without departing from the spirit and scope of the present invention It should include within the scope of the present invention.

Claims (6)

1. a kind of equisetin (equisetin) and its nano medicament carrying system of derivative, it is characterised in that it is included with serum Albumin is equisetin prepared by carrier and its derivates nanometer breast.
2. a kind of equisetin nano electrostatic spinning, it is characterised in that it is received by equisetin in claim 1 and its derivative Rice milk is prepared through electrostatic spinning technique.
3. the equisetin described in claim any one of 1-2 and its equisetin described in the nano medicament carrying system of derivative and Application of the nano electrostatic spinning of its derivative in methicillin-resistant staphylococcus aureus resistance (MRSA) medicine is prepared, or Prepare the application in methicillin-resistant staphylococcus aureus resistance (MRSA) skin infection and cartilaginous tissue medicine.
4. equisetin (equisetin) and its derivative are preparing methicillin-resistant staphylococcus aureus resistance (MRSA) medicine In application, or in methicillin-resistant staphylococcus aureus resistance (MRSA) skin infection and cartilaginous tissue medicine is prepared should With, wherein, the structural formula of equisetin is as follows:
The structural formula of equisetin derivative is as follows:
R2=H or CH3
R3=H or CH3
5. the preparation method of the nano medicament carrying system of equisetin (equisetin) and its derivative described in claim 1, its It is characterised by, comprises the following steps:
1) seralbumin is dissolved in the water, as aqueous phase;
2) equisetin is dissolved in organic solvent, as organic phase;
3) organic phase is slowly added into the aqueous phase of ice bath, through ultrasonication, re-evaporation removes organic solvent, and it is fast mould to obtain her White protein nano breast.
6. the preparation method of the nano electrostatic spinning of equisetin (equisetin) class compound described in claim 2, it is special Sign is, on the basis of the albumin nanometer rice milk of equisetin (equisetin) class compound of the preparation described in claim 5 On, in addition to step:
4) polyvinylpyrrolidone (PVP) is dissolved in organic solvent, then adds the equisetin albumin nanometer rice milk, Stir and remove bubble, then nano electrostatic spinning is carried out with electrostatic spinning machine.
CN201711226336.XA 2017-11-29 2017-11-29 A kind of nano medicament carrying system of equisetin and its derivative and preparation method thereof and the application in skin soft-tissue infection Pending CN107802598A (en)

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JUNJI INOKOSHI,ET AL.: "Epi-trichosetin,a new undecaprenyl pyrophosphate synthase inhibitor,produced by Fusarium oxysporum FKI-4553", 《THE JOURNAL OF ANTIBIOTICS》 *
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Application publication date: 20180316