CN102441171A - Local temperature-sensitive antibacterial drug sustained-release agent and preparation method thereof - Google Patents
Local temperature-sensitive antibacterial drug sustained-release agent and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the technical field of medical biological materials. In recent years, the local antibacterial drug sustained-release agent arouses the enormous attention of people, but the preparation materials do not have temperature-sensitive characteristics, have the problems of biocompatibility, biodegradability and the like and have complicated sustained-release preparation methods. The invention provides a local temperature-sensitive antibacterial drug sustained-release agent and a preparation method thereof. The sustained-release agent takes a temperature-sensitive polymer material (hydroxybutyl chitosan) as a sustained-release carrier, and the special temperature-sensitive characteristics of the sustained-release carrier are utilized to embed antibacterial drugs, thereby preparing a local temperature-sensitive drug sustained-release agent capable of being injected or implanted. The sustained-release agent provided by the invention can be injected or implanted into a focus or operation part to realize local sustained-release administration, thereby preventing or treating bacterial infection. The sustained-release agent provided by the invention has the advantages of injectability, temperature sensitivity, good biocompatibility and biodegradability and the like, maintains local effective drug concentration, and does not influence wound healing.
Description
Technical field
The present invention relates to the biomaterial for medical purpose technical field, be specifically related to temperature sensitive type antimicrobial drug slow releasing agent of a kind of topical application and preparation method thereof.
Background technology
The bacterial infection treatment mainly is whole body administering modes such as administered through oral, vein, intramuscular injection antibacterials, and medicine is through absorbing the effect that blood circulation plays treatment that gets into.But its shortcoming is for a lot of chronic lesions, particularly local lesion, because blood is not smooth; Blood drug level is low etc.; Can not obtain the drug level of continuous and effective in lesions position, be not enough to thorough killing bacteria, and increase the restriction that drug dose can receive poisonous side effect of medicine.Simultaneously, administration number of times is frequent, also brings misery and inconvenience to the patient.
Therefore in recent years, the part has caused people's very big concern with the antimicrobial drug slow release formulation.Like one Chinese patent application CN200810301576.6, denomination of invention: a kind of antibiotic slow releasing injection, publication number: CN101283981 of containing; One Chinese patent application CN200810301569.6, denomination of invention: a kind of antibiotic slow releasing agent and application thereof, publication number: CN101301270 of containing; One Chinese patent application CN200610200474.6; Denomination of invention: a kind of sustained-release antibiotic preparation of topical application, publication number: CN1883706 etc. are through the local antimicrobial drug slow releasing preparation of using of preparation injectable; Keep local effectively drug level, play the effect of treatment.But these formulation materials all do not possess temperature-sensing property, have problem and this type of slow release method for preparing complicacies such as biocompatibility and biological degradability simultaneously.
Temperature sensitive property hydroxyl butyl chitosan is through the natural macromolecule amylose chitosan is carried out chemical modification; The hydroxyl butyl group is grafted on the molecular backbone of chitosan; The introducing of hydrophilic radical has changed the hydrogen bond action equilibrium system in the aqueous phase system, thereby has caused temperature sensitive property.Hydroxyl butyl chitosan has good water-solubility and temperature sensitive property; Its phase transition temperature is lower; Gelation speed is fast, in the time of 37 ℃, can form the gel of certain intensity in 60 seconds, and its temperature sensitive property is reversible (referring to the Chinese patent CN200910052695.7 of the applicant in application on June 9th, 2009; Denomination of invention: temperature sensitive chitosan preparation and preparation thereof and application, publication number: CN101579353).
The preparation of temperature sensitive property hydroxyl butyl chitosan, the research of biological function are at the early-stage in the world, and the applied research in the slow release drug-loading system does not appear in the newspapers as yet.
Summary of the invention
The object of the present invention is to provide a kind of temperature sensitive type antimicrobial drug slow releasing agent of topical application.Another object of the present invention provides the method for preparing of this temperature sensitive type antimicrobial drug slow releasing agent.
The present invention specifically adopts temperature sensitive type degradable biomaterial hydroxyl butyl chitosan as slow-released carrier; Even embedding antibacterials under cryogenic conditions are processed antimicrobial drug sustained-release gel preparation, and it is injected into or implants the local infection focus; Or operative site, be used for treatment or prevention local infection.It is a solution state when low temperature, and is gel state under the Human Physiology temperature.Utilize this temperature-sensing property, hydrogel dissolves the water solublity antibacterials when the cryogenic fluid state; And when being injected in the tissue such as subcutaneous, muscle; The solution that contains antibacterials can change gel rapidly in position; This moment, antibacterials were evenly distributed in the gel; Medicine discharges from gel under the dual promotion of diffusion and gel self Degradation stably in vivo, thereby reaches the medicament slow release purpose.
The present invention provides a kind of temperature sensitive type antimicrobial drug slow releasing agent of local usefulness; This slow releasing agent makes through following method: at first (greater than 0 ℃ and less than 20 ℃) prepares homogenizing hydroxyl butyl chitosan solution under low temperature or room temperature state; Then wherein with the embedding of antibacterials homodisperse; Stir, promptly be able to the antimicrobial drug slow releasing agent of hydroxyl butyl chitosan as slow-released carrier.
Above-mentioned temperature sensitive type antimicrobial drug slow releasing agent can be slow releasing injection or sustained-release implant.
The present invention also provides a kind of method for preparing of temperature sensitive type antimicrobial drug slow releasing agent of local usefulness; This method is specially: (greater than 0 ℃ and less than 20 ℃) uses solvent to prepare 1-10% (W/V) hydroxyl butyl chitosan solution down under low temperature or room temperature state; Speed with 50-200 rev/min in container stirred 2-6 hour, made solution be homogeneous state; Add 0.1%-50% (W/V) the antibacterials solution of a certain amount of same solvent preparation then, drug level is 0.1%-20% (W/V) eventually; 50-200 rev/min was stirred 1-3 hour, made solution be homogeneous state, promptly got.
Described solvent can be distilled water, normal saline, water for injection, pH6.8-pH7.5 buffer etc.
Described antibacterials should be the water solublity antibacterials; These medicines do; But be not limited to: beta-lactam class antibacterials; Cephalosporins antibacterials particularly are like cefazolin sodium, cefalotin, cefacetrile, cefapirin, cefathiamidine, cefazedone, cefradine, cefuroxime, cefotiam, cefamandole, cefonicid, ceforanide, cefotaxime, ceftriaxone, ceftazidime, cefoperazone, ceftizoxime, cefodizime, cefpiramide, cefmenoxime, cefsulodin, cefpirome, cefepime etc.; Or the cephamycin-type antibacterials, like cefoxitin, cefmetazole, cefotetan, cefbuperazone, cefminox etc.; Or the lincomycin class, clindamycin, lincomycin etc.; Or polypeptide class antibacterials, like vancomycin, norvancomycin, teicoplanin etc.; Or carbostyril family antibacterial drugs, replace husky star, Gemifloxacin etc. like norfloxacin, ciprofloxacin, ofloxacin, enoxacin, pefloxacin, lomefloxacin, fleroxacin, Sparfloxacin, Pazufloxacin, clinafloxacin, Grepafloxacin, amifloxacin, Tuo Shusha star, Pu Ruisha star, Orbax, olamufloxacin., the husky star of car coat, levofloxacin, Gatifloxacin, promise; And the salt of said medicine or ester.
Described antibacterials can be the combination of above-mentioned any one or two or more medicines.
The temperature sensitive type antimicrobial drug slow releasing agent of a kind of local usefulness of the present invention promptly can form the gel of certain intensity 37 ℃ the time in 60 seconds under physiological temp.
Utilized to the invention property hydroxyl butyl chitosan as slow-released carrier; The temperature-sensing property of this slow-released carrier, even embedding antibacterials under low temperature or normal temperature condition are through injecting or be implanted to internal lesions position; Fast setting under physiological temp, slow releasing pharmaceutical.This dosage form can be used for bacterial infection focus position or operative site, keeps local effectively drug level, reaches the purpose that treatment or prevention of bacterial infect.
Technique effect of the present invention is following: with temperature sensitive type bioabsorbable polymer material hydroxyl butyl chitosan is slow-released carrier, has realized the syringeability of pharmaceutical carrier, has made things convenient for operation, has also reduced patient's misery simultaneously; Preparation condition is gentle, does not need the participation of materials such as cross-linking agent, initiator, and phenomenon such as no heat release in the process, has guaranteed that the slow releasing pharmaceutical activity is unaffected; The antimicrobial drug thermo-responsive hydro gel is injected to infection focus position or operative site, drug slow is discharged, keep local effectively drug level, reduce the toxic and side effects that the medicine whole body is used simultaneously; Can be according to clinical needs preparation, one or more antibiotic medicines of slow release; In addition, the most nothing of injectable temperature-sensitive hydrogel system is confirmed shape, after injection, can fully be filled in interstice, and original position undergoes phase transition in vivo subsequently, is particularly suitable for local implantation in the body.Because slow-released carrier hydroxyl butyl chitosan excellent biological compatibility and biodegradability have increased biological safety, have avoided the second operation taking-up.Because this dosage form is disposable topical application antimicrobial drug slow releasing agent, brought facility for clinical use, also significantly reduced the use amount of operation back antibacterials, meet and strictly regulate the requirement that antibacterials are used clinically.
Description of drawings
Fig. 1 is 1#, and 2#, 3#, the hydroxyl butyl chitosan gel rubber of 4# embedding cefotiam hydrochloride and blank gel, variations in temperature is to its storage modulus G ' and loss modulus G " influence.
Fig. 2 is 1#, and 2#, 3#, the hydroxyl butyl chitosan gel rubber of 4# embedding cefotiam hydrochloride and blank gel, show as sample storage modulus G ' and loss modulus G at the hardening time under 37 ℃ of conditions " along with the variation of time lengthening.
Fig. 3 is the stereoscan photograph of blank hydroxyl butyl chitosan gel rubber.
Fig. 4 is the stereoscan photograph of the hydroxyl butyl chitosan gel rubber of embedding cefotiam hydrochloride, and drug level is 2.5% (W/V).
Fig. 5 is 1#, 2#, and the medicament slow release curve of hydroxyl butyl chitosan gel rubber in the pH7.2 phosphate buffer of 3# embedding cefotiam hydrochloride, 1#, 2#, 3# gel Chinese medicine content is respectively 2.5%, 1.25%, 0.5% (W/V).
Fig. 6 is 1#, 2#, and 3#, the hydroxyl butyl chitosan gel rubber of 4# embedding cefotiam hydrochloride shows as antibacterial circle diameter to aureus with inhibition, 1#, 2#, 3# gel Chinese medicine content is respectively 2.5%, 1.25%, 0.5% (W/V).
Fig. 7 uses sample local drug concentration testing result in the body.
Fig. 8 uses sample blood drug level testing result in the body.
The specific embodiment
Below in conjunction with embodiments of the invention and accompanying drawing enforcement of the present invention is elaborated; Following examples are to be to implement under the prerequisite with technical scheme of the present invention; Provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Embodiment 1
Use 100 milliliters of distilled water preparation 2.5% (W/V) hydroxyl butyl chitosan solutions down at 4 ℃, the speed with 100 rev/mins in beaker stirred 5 hours, made solution be homogeneous state.Add 12.5% (W/V) antibacterials cefotiam hydrochloride solution of 25 milliliters of distilled water preparations then, drug level is 2.5% (W/V) eventually.100 rev/mins were stirred 2 hours, medicine are uniformly dispersed in hydroxyl butyl chitosan solution.Promptly prepare the hydroxyl butyl chitosan solution of 125 milliliters of embedding cefotiam hydrochlorides, wherein the slow-released carrier final concentration is 2%, and slow releasing pharmaceutical concentration is 2.5% (W/V).
Embodiment 2
Use 100 milliliters of distilled water preparation 2.5% (W/V) hydroxyl butyl chitosan solutions down at 4 ℃, the speed with 100 rev/mins in beaker stirred 5 hours, made solution be homogeneous state.Add 6.25% (W/V) antibacterials cefotiam hydrochloride solution of 25 milliliters of distilled water preparations then, drug level is 1.25% (W/V) eventually.100 rev/mins were stirred 2 hours, medicine are uniformly dispersed in hydroxyl butyl chitosan solution.Promptly prepare the hydroxyl butyl chitosan solution of 125 milliliters of embedding cefotiam hydrochlorides, wherein the slow-released carrier final concentration is 2%, and drug level is 1.25% (W/V).
Embodiment 3
Use 100 milliliters of distilled water preparation 2.5% (W/V) hydroxyl butyl chitosan solutions down at 4 ℃, the speed with 100 rev/mins in beaker stirred 5 hours, made solution be homogeneous state.Add 2.5% (W/V) antibacterials cefotiam hydrochloride solution of 25 milliliters of distilled water preparations then, drug level is 0.5% (W/V) eventually.100 rev/mins were stirred 2 hours, medicine are uniformly dispersed in hydroxyl butyl chitosan solution.Promptly prepare the hydroxyl butyl chitosan solution of 125 milliliters of embedding cefotiam hydrochlorides, wherein the slow-released carrier final concentration is 2%, and drug level is 0.5% (W/V).
Embodiment 4
Use 125 milliliters of distilled water preparation 2% (W/V) hydroxyl butyl chitosan solutions down at 4 ℃, the speed with 100 rev/mins in beaker stirred 5 hours, made solution be homogeneous state.Promptly prepare 125 milliliters of hydroxyl butyl chitosan solutions, be the blank of drug not, wherein the slow-released carrier final concentration is 2% (W/V).
Embodiment 5
Use 100 milliliters of normal saline preparation 1.5% (W/V) hydroxyl butyl chitosan solutions down at 15 ℃, the speed with 50 rev/mins in beaker stirred 3 hours, made solution be homogeneous state.Add the antibacterials clindamycin hydrochloride solution of 1.5% (W/V) of 50 ml physiological salines preparation then, drug level is 0.5% (W/V) eventually.50 rev/mins were stirred 1 hour, medicine are uniformly dispersed in hydroxyl butyl chitosan solution.Promptly prepare 150 milliliters of the hydroxyl butyl chitosan solutions of embedding clindamycin, wherein the slow-released carrier final concentration is 1%, and drug level is 0.5% (W/V).
Embodiment 6
Use 100 milliliters of water for injection preparation 6% (W/V) hydroxyl butyl chitosan solutions down at 10 ℃, the speed with 200 rev/mins in beaker stirred 6 hours, made solution be homogeneous state.Add 15% (W/V) antibacterials Ofloxacin solution of 50mL normal saline preparation then, drug level is 0.5% (W/V) eventually.200 rev/mins were stirred 3 hours, medicine are uniformly dispersed in hydroxyl butyl chitosan solution.Promptly prepare 150 milliliters of the hydroxyl butyl chitosan solutions of embedding ofloxacin, wherein the slow-released carrier final concentration is 4%, and drug level is 5% (W/V).
Embodiment 7: external rheological property detects
The first step according to embodiment 1, embodiment 2, embodiment 3, embodiment 4, prepares the hydroxyl butyl chitosan solution and the blank solution of embedding antibacterials cefotiam hydrochloride respectively; Drug level 1# is 2.5%; 2# is 1.25%, and 3# is 0.5% (W/V), and 4# is the blank of drug not.
Second step; 1#, 2#, 3#; The hydroxyl butyl chitosan solution of the hydrochloric cefotiam of 4# and blank solution; Use flow graph to detect its temperature sensitive rheological characteristic, show as variations in temperature sample storage modulus G ' and loss modulus G " influence (temperature range 5-50 ℃), and under 37 ℃ of isothermys hardening time of sample.
The result is as shown in Figure 1, and 4 sample critical solidification temperatures are 20 ℃.When being lower than 20 ℃, G ' is lower than G ", sample shows as the liquid solution with viscosity under this state; When being higher than 20 ℃, G ' is greater than G ", sample shows as the rubber-like solid gel under this state, and temperature is high more, and gel strength is big more.Fig. 2 shows that under 37 ℃ of isothermys, in 60 seconds, 4 samples are cured as stable elastic gel by solution state.The result also shows the solidification temperature of medicine carrying gel and blank gel and does not have obvious difference hardening time.
Embodiment 8: morphological analysis
The first step according to embodiment 1, embodiment 4, prepares the hydroxyl butyl chitosan solution and the blank solution of embedding antibacterials cefotiam hydrochloride respectively, and the 1# drug level is 2.5%, and 4# is the blank of drug not.
In second step, the hydroxyl butyl chitosan solution of 1#, the hydrochloric cefotiam of 4# and blank solution are respectively got 5 milliliters, place mould, and 37 ℃ are solidified into gel in following 10 minutes.Use the freezer dryer freeze drying example then.
The 3rd step, with 1#, the dried sample of 4#, cutting metal spraying, the microcosmic internal structure of use sem observation sample.
Result such as Fig. 3, shown in Figure 4, dried medicine carrying and barren hydroxyl butyl chitosan gel rubber are porous RF.From microphotograph, it can also be seen that, on the hole wall of the hydroxyl butyl chitosan sample of medicine carrying thin one deck particulate material is arranged, and the hole wall of the blank sample of medicine carrying is smoothless.Show that medicine is evenly dispersed in the hydroxyl butyl chitosan gel rubber.
Embodiment 9: in-vitro simulated slow release check
The first step according to embodiment 1, embodiment 2, embodiment 3, embodiment 4, prepares the hydroxyl butyl chitosan solution and the blank solution of embedding antibacterials cefotiam hydrochloride respectively; Drug level 1# is 2.5%; 2# is 1.25%, and 3# is 0.5% (W/V), and 4# is the blank of drug not.
In second step, the hydroxyl butyl chitosan solution of 1#, 2#, 3#, the hydrochloric cefotiam of 4# and blank solution are respectively got 1 milliliter, place sample cell, are gel state under 37 ℃, add 5 milliliters of pH7.2 phosphate buffers then.Place 37 ℃, under 80 rev/mins of oscillating conditions, 1～7 day, get 5 milliliters of sustained-release liquids of collection respectively at special time, detection of drugs content is replaced 5 milliliters of fresh pH7.2 phosphate buffers in addition.
The 3rd step, use ultraviolet spectrophotometer, detect the content of cefotiam hydrochloride down in the 256nm wavelength.
The result is as shown in Figure 5, and about 80% CFH is released out in 12 hours, follows by the lasting release slowly of medicine.The lixiviating solution of 4# blank gel is under the 256nm wavelength, and no ultraviolet absorption peak shows that slow-released carrier hydroxyl butyl chitosan does not have influence to the detection of medicament contg.
Embodiment 10: external antibacterial check
The first step, according to embodiment 1, embodiment 2, embodiment 3, embodiment 4, preparation contains the hydroxyl butyl chitosan solution of antibacterials cefotiam hydrochloride respectively; Drug level 1# is 2.5%; 2# is 1.25%, and 3# is 0.5% (W/V), and 4# is the blank of drug not.
In second step, compound concentration is 1.5 * 10
8The staphylococcus aureus bacteria suspension of individual/milliliter is uniformly coated on the MH flat board, and the Oxford cup is placed on it,, adds in the cup of Oxford 0.2 milliliter/pipe with 1#, 2#, 3# medicine carrying solution.Observe its antibacterial circle diameter through cultivating the back.Cultivated 72 hours, gel replacement to new being coated with continued on the bacterium MH flat board to cultivate, observe its antibacterial circle diameter and change.
The result was as shown in Figure 6, and tangible inhibition zone all appearred in 1#, 2#, 3# medicine carrying gel at 1-9 days, all can effectively suppress the growth of staphylococcus aureus.And along with the increase of gel medicine concentration, antibacterial circle diameter also obviously increases.The blank hydroxyl butyl of 4# chitosan only had certain contact inhibition to staphylococcus aureus in 1-3 days, and obviously than a little less than the antibacterial medicines effect.
Embodiment 11: use sample blood and local drug concentration detection in the body
The first step, according to embodiment 1, the hydroxyl butyl chitosan solution of preparation embedding antibacterials cefotiam hydrochloride, wherein drug level 1# is 2.5%.Other uses distilled water to prepare the aqueous solution that concentration is 2.5% cefotiam hydrochloride, as contrast.
Second step was an experimental subject with the rat, and it is divided into two groups: group 1 is the hydroxyl butyl chitosan solution of 2.5% embedding cefotiam hydrochloride with drug level, is expelled in the leg muscle of rat every injection 0.4ml; Group 2 is 2.5% cefotiam hydrochloride aqueous solution with the matched group drug level, is expelled in the leg muscle of rat every injection 0.4ml.
The 3rd step, injection back 1,2,6,24,48 hour, sampling respectively detects rat topical place's drug level and blood Chinese medicine concentration.
Result such as Fig. 7, shown in Figure 8 compare with the aqueous solution of local injection antibacterials, the thermo-responsive hydro gel of embedding medicinal can be in the injection site fugitive slow releasing pharmaceutical, in 48 hours and keep part drug level effectively.And can prolong blood Chinese medicine concentration to 48 hour.
Claims (10)
1. the temperature sensitive type antimicrobial drug slow releasing agent of a local usefulness; It is characterized in that this slow releasing agent makes through following method: greater than 0 ℃ and less than 20 ℃ temperature under preparation homogenizing hydroxyl butyl chitosan solution; Then wherein, promptly obtain with the antimicrobial drug slow releasing agent of hydroxyl butyl chitosan as slow-released carrier with the embedding of antibacterials homodisperse.
2. the temperature sensitive type antimicrobial drug slow releasing agent of a kind of local usefulness according to claim 1; The concrete method for preparing that it is characterized in that this slow releasing agent is following: greater than 0 ℃ and less than 20 ℃ temperature under use solvent to prepare 1-10% (W/V) hydroxyl butyl chitosan solution; Speed with 50-200 rev/min in container stirred 2-6 hour, made solution be homogeneous state; 0.1%-50% (W/V) the antibacterials solution that adds the same solvent preparation then makes drug level be 0.1%-20% (W/V) eventually; 50-200 rev/min was stirred 1-3 hour, made solution be homogeneous state, promptly got.
3. the temperature sensitive type antimicrobial drug slow releasing agent of a kind of local usefulness according to claim 2 is characterized in that wherein said solvent is distilled water, normal saline, water for injection or pH6.8-pH7.5 buffer.
4. according to the temperature sensitive type antimicrobial drug slow releasing agent of claim 1,2 or 3 described a kind of local usefulness, it is characterized in that wherein said antibacterials are water solublity antibacterials.
5. the temperature sensitive type antimicrobial drug slow releasing agent of a kind of local usefulness according to claim 4, it is characterized in that wherein said antibacterials be selected from following any one or two or more: cefazolin sodium, cefalotin, cefacetrile, cefapirin, cefathiamidine, cefazedone, cefradine, cefuroxime, cefotiam, cefamandole, cefonicid, ceforanide, cefotaxime, ceftriaxone, ceftazidime, cefoperazone, ceftizoxime, cefodizime, cefpiramide, cefmenoxime, cefsulodin, cefpirome, cefepime, cefoxitin, cefmetazole, cefotetan, cefbuperazone, cefminox, clindamycin, lincomycin, vancomycin, norvancomycin, teicoplanin, norfloxacin, ciprofloxacin, ofloxacin, enoxacin, pefloxacin, lomefloxacin, fleroxacin, Sparfloxacin, Pazufloxacin, clinafloxacin, Grepafloxacin, amifloxacin, Tuo Shusha star, Pu Ruisha star, Orbax, olamufloxacin., the husky star of car coat, levofloxacin, Gatifloxacin, promise are for husky star, Gemifloxacin.
6. according to the temperature sensitive type antimicrobial drug slow releasing agent of claim 1,2 or 3 described a kind of local usefulness, it is characterized in that this slow releasing agent is slow releasing injection or sustained-release implant.
7. the method for preparing of the temperature sensitive type antimicrobial drug slow releasing agent of a local usefulness as claimed in claim 1; Concrete steps are following: greater than 0 ℃ and less than 20 ℃ temperature under use solvent to prepare 1-10% (W/V) hydroxyl butyl chitosan solution; Speed with 50-200 rev/min in container stirred 2-6 hour, made solution be homogeneous state; 0.1%-50% (W/V) the antibacterials solution that adds the same solvent preparation then makes drug level be 0.1%-20% (W/V) eventually; 50-200 rev/min was stirred 1-3 hour, made solution be homogeneous state, promptly got.
8. the method for preparing of the temperature sensitive type antimicrobial drug slow releasing agent of local usefulness according to claim 7 is characterized in that wherein said solvent is distilled water, normal saline, water for injection or pH6.8-pH7.5 buffer.
9. according to the method for preparing of the temperature sensitive type antimicrobial drug slow releasing agent of claim 7 or 8 described local usefulness, it is characterized in that wherein said antibacterials are water solublity antibacterials.
10. the method for preparing of the temperature sensitive type antimicrobial drug slow releasing agent of local usefulness according to claim 9, it is characterized in that wherein said antibacterials be selected from following any one or two or more: cefazolin sodium, cefalotin, cefacetrile, cefapirin, cefathiamidine, cefazedone, cefradine, cefuroxime, cefotiam, cefamandole, cefonicid, ceforanide, cefotaxime, ceftriaxone, ceftazidime, cefoperazone, ceftizoxime, cefodizime, cefpiramide, cefmenoxime, cefsulodin, cefpirome, cefepime, cefoxitin, cefmetazole, cefotetan, cefbuperazone, cefminox, clindamycin, lincomycin, vancomycin, norvancomycin, teicoplanin, norfloxacin, ciprofloxacin, ofloxacin, enoxacin, pefloxacin, lomefloxacin, fleroxacin, Sparfloxacin, Pazufloxacin, clinafloxacin, Grepafloxacin, amifloxacin, Tuo Shusha star, Pu Ruisha star, Orbax, olamufloxacin., the husky star of car coat, levofloxacin, Gatifloxacin, promise are for husky star, Gemifloxacin.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105902483A (en) * | 2016-01-13 | 2016-08-31 | 上海其胜生物制剂有限公司 | Preparation method of temperature-sensitive material suitable for transdermal delivery |
| CN115337467A (en) * | 2022-08-16 | 2022-11-15 | 万瑞飞鸿(北京)医疗器材有限公司 | Drug coating, intravascular stent, and preparation method and application thereof |
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2011
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105902483A (en) * | 2016-01-13 | 2016-08-31 | 上海其胜生物制剂有限公司 | Preparation method of temperature-sensitive material suitable for transdermal delivery |
| CN115337467A (en) * | 2022-08-16 | 2022-11-15 | 万瑞飞鸿(北京)医疗器材有限公司 | Drug coating, intravascular stent, and preparation method and application thereof |
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Application publication date: 20120509 |