CN104888222A - Medicinal composition for treating complex infection and preparation method of medicinal composition - Google Patents
Medicinal composition for treating complex infection and preparation method of medicinal composition Download PDFInfo
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- CN104888222A CN104888222A CN201510312876.4A CN201510312876A CN104888222A CN 104888222 A CN104888222 A CN 104888222A CN 201510312876 A CN201510312876 A CN 201510312876A CN 104888222 A CN104888222 A CN 104888222A
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- 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
- A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
Abstract
The invention relates to a medicinal composition for treating complex infection and a preparation method thereof. The medicinal composition is characterized by comprising an active ingredient selected from one of glycopeptides antibacterial drugs of telavancin, dalbavancin, oritavancin, vancomycin, teicoplanin or a pharmaceutically acceptable salt thereof, and also comprising polyene and echinocandin type antifungal agents, and being prepared into a freeze-dried powder injection by adopting a conventional process. The medicinal composition provided by the invention realizes combined application of the antibacterial drugs and the antifungal agents, can simultaneously give play to an antibacterial infection effect and an antifungal infection effect, and is convenient for clinical use.
Description
Technical field:
The invention belongs to field of medicine preparing technology, be specifically related to comprise glycopeptide class antibacterials and antifungal medicine composition and preparation method thereof.
Background technology:
Along with the extensive use of antibiotic, antitumor drug, immunosuppressant and traumatic Clinics and the increase of immunodeficiency syndrome sickness rate, the patient of concurrent bacterial fungus MOI is increasing.As patient's many concurrent bacterial fungal infection such as hematological system tumor, diabetes, acquired immune deficiency syndrome (AIDS).Pathogen is often Candida albicans, staphylococcus aureus, staphylococcus epidermidis, intestinal streptococcus etc., and mostly is multi-drug resistant bacteria.Treat very thorny, cause aggravation, case fatality rate increases.
Though having there is drug resistance situation in glycopeptide class antibacterials vancomycin and teicoplanin, but still is widely used in clinical.In the process of reply drug resistance, there is a collection of novel glycopeptide antibiotics, current novel glycopeptide class antibacterials are as Te Lawan star, dalbavancin and oritavancin, more large effect is shown than vancomycin or Linezolid in the various bacterial isolates of antagonism, all there is preparation to obtain FDA approval listing, be used for the treatment of bacteriological infection caused by the sensitive organism such as MRSA, micrococcus scarlatinae.Immunocompromised patient, as used broad ectrum antibiotic, glucocorticoid, immunosuppressant etc. in a large number, is easy to concurrent deep fungal infection, and pathogenic bacterium mostly are deep candidiasis, aspergillosis and cryptococcus etc.Three class medicines are had to can be used for the antifungal therapy of system at present: polyenoid class, as amphotericin B; Echinocandin class, as caspofungin acetate, FK463, anidulafungin, Basifungin.Said medicine mostly is intravenously administrable, and need once a day or twice, the course for the treatment of is longer, ten days to some months not etc., AIDS patient even needs lifelong medication.
Preparation is not also had to be used for the treatment of MOI clinically at present, bacterial-infection resisting and anti-fungal infection scheme are separately administrations, repeatedly being used alternatingly of two class medicines, administration is loaded down with trivial details, and treatment time is long, make troubles to Clinical practice, also bring the misery of administration to patient simultaneously, therefore, the eager effect needing a kind of pharmaceutical composition simultaneously can play bacterial-infection resisting and anti-fungal infection, facilitate Clinical practice, improve patient adaptability.
Summary of the invention:
Based on this, the invention provides containing glycopeptide class antibacterials and antifungal medicine composition lyophilized injectable powder and preparation method thereof, said preparation can play the effect of bacterial-infection resisting and anti-fungal infection simultaneously, simplifies dosage regimen, shorten treatment time, facilitate Clinical practice and patient to accept.
The pharmaceutical composition for the treatment of MOI provided by the invention, is characterized in that its active constituents of medicine is glycopeptide class antibacterials and antifungal drug.Wherein, described glycopeptide class antibacterials can be selected from the one in Te Lawan star, dalbavancin, oritavancin, vancomycin, teicoplanin or its pharmaceutically acceptable salt, described antifungal drug polyenoid class can be selected from amphotericin B, echinocandin class can be selected from caspofungin acetate, FK463, anidulafungin, Basifungin one wherein, and the ratio of glycopeptide class antibacterials and antifungal drug is 1:1-15:1.
Described pharmaceutical composition is lyophilized powder form, and its excipient is selected from one or more in mannitol, lactose, sucrose, fructose; PH adjusting agent be selected from hydrochloride buffer, acetate buffer solution, tartaric acid buffer, citrate buffer, citrate buffer solution one or more, by mass percentage, the quality sum of described novel glycopeptide class antibacterials and antifungal drug accounts for the 5-90% of compositions gross mass, and the quality sum of described excipient and pH adjusting agent accounts for the 10-95% of compositions gross mass.Present invention also offers the method for pharmaceutical compositions, its technique is: precision takes the principal agent of recipe quantity, adds appropriate water for injection and dissolves; Add the excipient of recipe quantity and pH adjusting agent successively in above-mentioned solution, regulate pH; With ultrafiltration membrance filter, then use filtering with microporous membrane; Be settled to full dose, subpackage, vacuum lyophilization, tamponade, Zha Gai, after passed examination, labeling is packed and obtains drug combination injection.
Its purposes of pharmaceutical composition of the present invention is treatment or the infection of prevention bacteria mixed fungi.Said composition can play the synergism of antibacterials and antifungal drug, facilitates clinical administration.
Detailed description of the invention:
Below in conjunction with embodiment, embodiment of the present invention are described in detail, but it will be understood to those of skill in the art that the following example only for illustration of the present invention, and should not be considered as limiting scope of the present invention.
Embodiment 1
Te Lawan star hydrochlorate 250g (in Te Lawan star), anidulafungin 50g, mannitol 300g, hydrochloride buffer is appropriate.
Its preparation technology is: precision takes Te Lawan star hydrochlorate and the anidulafungin of recipe quantity, adds appropriate water for injection and dissolves; Add the mannitol of recipe quantity, hydrochloride buffer successively in above-mentioned solution, regulate pH to 5.0, afterwards with 0.1 μm of ultrafilter membrane removing thermal source, filtrate, through 0.22 μm of microporous filter membrane aseptic filtration, injects and is settled to 15L with water, is then packed as 1000 bottles, lyophilization, tamponade, rolls lid, and after passed examination, compositions powder ampoule agent for injection is packed and obtained to labeling.
Investigate pharmaceutical composition freeze-dried powder preparation prepared by embodiment 1 and successively apply Te Lawan star and anidulafungin commercial preparation to the therapeutic effect of mice MOI model
Laboratory animal: SPF level BALB/c mouse, 80,15 ~ 20g, is provided by Zhongshan University's Experimental Animal Center.
Bacterial strain: Candida albicans (Candida albicans) SC-5314, MRSA-252, provided by The 2nd Army Medical College new drug development center.
Experimental technique:
1. the cultivation of infection bacterial strain distinguishes inoculating strain SC-5314 in husky fort glucose agar medium with preparation, MRSA-252 is in MH agar culture medium in inoculation, transferred species 2 times, all at 35 DEG C, cultivate 24h, bacteria suspension is prepared into physiological saline solution, with blood cell counting plate counting, wherein SC-5314 concentration is 5 × 10
6cFU/ml, MRSA-252 concentration is 5.0 × 10
9cFU/ml.
2. mice is divided into 4 groups by the foundation of mice MOI model and treatment at random, often organizes 20, is respectively infected group, compositions treatment group, separately medication group and PBS matched group.First three groups mice is respectively through tail vein injection 0.1ml bacterium liquid, and PBS control group mice is through tail vein injection equivalent physiological saline solution.After 24h, compositions treatment group intraperitoneal injection Te Lawan star associating fluconazol freeze-dried powder preparation, separately after the complete Te Lawan star of medication group lumbar injection, inject anidulafungin injection (separately medication group dosage is by human dose conversion, and each drug dose of compositions treatment group is with separating medication group) again.PBS control group mice lumbar injection equivalent physiological saline solution.Continuous use 7 days.Record the 8th day dead mouse number.Experimental result is in table 1.
Table 1 is group dead mouse situation respectively
Experimental result shows, in embodiment 1, composition freeze-drying powder preparation administration prepared by Te Lawan star and anidulafungin conbined usage, the effect of bacterial-infection resisting and anti-fungal infection can be played simultaneously, and separate compared with administration group, death toll does not have significant difference, but compositions administration group is given and is wanted simple, can treatment time be shortened, be beneficial to Clinical practice and patient's acceptance, there is practical significance.
Embodiment 2
Vancomycin hydrochloride 100g (in Te Lawan star), amphotericin B 125g, mannitol 300g, hydrochloride buffer is appropriate.
Its preparation technology is: precision takes vancomycin hydrochloride and the amphotericin B of recipe quantity, adds appropriate water for injection and dissolves; Add the mannitol of recipe quantity, hydrochloride buffer successively in above-mentioned solution, regulate pH to 5.0, afterwards with 0.1 μm of ultrafilter membrane removing thermal source, filtrate, through 0.22 μm of microporous filter membrane aseptic filtration, injects and is settled to 25L with water, is then packed as 1000 bottles, lyophilization, tamponade, rolls lid, and after passed examination, compositions powder ampoule agent for injection is packed and obtained to labeling.
Investigate pharmaceutical composition freeze-dried powder preparation prepared by embodiment 2 and successively apply vancomycin and amphotericin B commercial preparation to the therapeutic effect of mice MOI model
Laboratory animal: SPF level BALB/c mouse, 80,15 ~ 20g, is provided by Zhongshan University's Experimental Animal Center.
Bacterial strain: Candida albicans (Candida albicans) SC-5314, MRSA-252, provided by The 2nd Army Medical College new drug development center.
Experimental technique:
1. the cultivation of infection bacterial strain distinguishes inoculating strain SC-5314 in husky fort glucose agar medium with preparation, MRSA-252 is in MH agar culture medium in inoculation, transferred species 2 times, all at 35 DEG C, cultivate 24h, bacteria suspension is prepared into physiological saline solution, with blood cell counting plate counting, wherein SC-5314 concentration is 5 × 10
6cFU/ml, MRSA-252 concentration is 5.0 × 10
9cFU/ml.
2. mice is divided into 4 groups by the foundation of mice MOI model and treatment at random, often organizes 20, is respectively infected group, compositions treatment group, separately medication group and PBS matched group.First three groups mice is respectively through tail vein injection 0.1ml bacterium liquid, and PBS control group mice is through tail vein injection equivalent physiological saline solution.After 24h, compositions treatment group intraperitoneal injection Te Lawan star associating amphotericin B freeze-dried powder preparation, separately medication group lumbar injection complete vancomycin afterflush pipeline, inject amphotericin B injection (separately medication group dosage is by human dose conversion, and each drug dose of compositions treatment group is with separating medication group) again.PBS control group mice lumbar injection equivalent physiological saline solution.Continuous use 7 days.Record the 8th day dead mouse number.Experimental result is in table 2.
Table 2 is group dead mouse situation respectively
Experimental result shows, in embodiment 2, composition freeze-drying powder preparation administration prepared by vancomycin and amphotericin B conbined usage, the effect of bacterial-infection resisting and anti-fungal infection can be played simultaneously, and separate compared with administration group, death toll does not have significant difference, but compositions administration group is given and is wanted simple, can treatment time be shortened, be beneficial to Clinical practice and patient's acceptance, there is practical significance.
Embodiment 3
Dalbavancin hydrochlorate 500g (in dalbavancin), caspofungin acetate 250mg (in Caspofungin), lactose 150g, mannitol 150g, tartaric acid buffer is appropriate.
Its preparation technology is: precision takes dalbavancin hydrochlorate and the caspofungin acetate of recipe quantity, adds appropriate water for injection and dissolves; Add the mannitol of recipe quantity, lactose, tartaric acid buffer successively in above-mentioned solution, regulate pH to 5.2, afterwards with 0.1 μm of ultrafilter membrane removing thermal source, filtrate, through 0.22 μm of microporous filter membrane aseptic filtration, injects and is settled to 25L with water, is then packed as 1000 bottles, lyophilization, tamponade, rolls lid, and after passed examination, compositions powder ampoule agent for injection is packed and obtained to labeling.
Investigate pharmaceutical composition freeze-dried powder preparation prepared by embodiment 3 and successively apply dalbavancin and caspofungin acetate commercial preparation to the therapeutic effect of mice MOI model
Laboratory animal: SPF level BALB/c mouse, 80,15 ~ 20g, is provided by Zhongshan University's Experimental Animal Center.
Bacterial strain: Candida albicans (Candida albicans) SC-5314, MRSA-252, provided by The 2nd Army Medical College new drug development center.
Experimental technique:
1. the cultivation of infection bacterial strain distinguishes inoculating strain SC-5314 in husky fort glucose agar medium with preparation, MRSA-252 is in MH agar culture medium in inoculation, transferred species 2 times, all at 35 DEG C, cultivate 24h, bacteria suspension is prepared into physiological saline solution, with blood cell counting plate counting, wherein SC-5314 concentration is 5 × 10
6cFU/ml, MRSA-252 concentration is 5.0 × 10
9cFU/ml.
2. mice is divided into 4 groups by the foundation of mice MOI model and treatment at random, often organizes 20, is respectively infected group, compositions treatment group, separately medication group and PBS matched group.First three groups mice is respectively through tail vein injection 0.1ml bacterium liquid, and PBS control group mice is through tail vein injection equivalent physiological saline solution.After 24h, compositions treatment group intraperitoneal injection dalbavancin associating caspofungin acetate freeze-dried powder preparation, separately medication group lumbar injection complete dalbavancin afterflush pipeline, inject caspofungin acetate injection (separately medication group dosage is by human dose conversion, and each drug dose of compositions treatment group is with separating medication group) again.PBS control group mice lumbar injection equivalent physiological saline solution.Continuous use 7 days.Record the 8th day dead mouse number.Experimental result is in table 1.
Table 3 is group dead mouse situation respectively
Experimental result shows, in embodiment 3, composition freeze-drying powder preparation administration prepared by dalbavancin and caspofungin acetate conbined usage, the effect of bacterial-infection resisting and anti-fungal infection can be played simultaneously, and separate compared with administration group, death toll does not have significant difference, but compositions administration group is given and is wanted simple, can treatment time be shortened, be beneficial to Clinical practice and patient's acceptance, there is practical significance.
Embodiment 4
Teicoplanin 1000g, FK463 150g, lactose 300g, citrate buffer solution is appropriate.
Its preparation technology is: precision takes teicoplanin and the FK463 of recipe quantity, adds appropriate water for injection and dissolves; Add the lactose of recipe quantity, citrate buffer solution successively in above-mentioned solution, regulate pH to 5.0, afterwards with 0.1 μm of ultrafilter membrane removing thermal source, filtrate, through 0.22 μm of microporous filter membrane aseptic filtration, injects and is settled to 15L with water, is then packed as 1000 bottles, lyophilization, tamponade, rolls lid, and after passed examination, compositions powder ampoule agent for injection is packed and obtained to labeling.
Investigate pharmaceutical composition freeze-dried powder preparation prepared by embodiment 4 and successively apply dalbavancin and FK463 commercial preparation to the therapeutic effect of mice MOI model
Laboratory animal: SPF level BALB/c mouse, 80,15 ~ 20g, is provided by Zhongshan University's Experimental Animal Center.
Bacterial strain: Candida albicans (Candida albicans) SC-5314, MRSA-252, provided by The 2nd Army Medical College new drug development center.
Experimental technique:
1. the cultivation of infection bacterial strain distinguishes inoculating strain SC-5314 in husky fort glucose agar medium with preparation, MRSA-252 is in MH agar culture medium in inoculation, transferred species 2 times, all at 35 DEG C, cultivate 24h, bacteria suspension is prepared into physiological saline solution, with blood cell counting plate counting, wherein SC-5314 concentration is 5 × 10
6cFU/ml, MRSA-252 concentration is 5.0 × 10
9cFU/ml.
2. mice is divided into 4 groups by the foundation of mice MOI model and treatment at random, often organizes 20, is respectively infected group, compositions treatment group, separately medication group and PBS matched group.First three groups mice is respectively through tail vein injection 0.1ml bacterium liquid, and PBS control group mice is through tail vein injection equivalent physiological saline solution.After 24h, compositions treatment group intraperitoneal injection teicoplanin associating FK463 freeze-dried powder preparation, separately medication group lumbar injection complete teicoplanin afterflush pipeline, inject MFG sodium injection (separately medication group dosage is by human dose conversion, and each drug dose of compositions treatment group is with separating medication group) again.PBS control group mice lumbar injection equivalent physiological saline solution.Continuous use 7 days.Record the 8th day dead mouse number.Experimental result is in table 4.
Table 4 is group dead mouse situation respectively
Experimental result shows, in embodiment 1, composition freeze-drying powder preparation administration prepared by teicoplanin and FK463 conbined usage, the effect of bacterial-infection resisting and anti-fungal infection can be played simultaneously, and separate compared with administration group, death toll does not have significant difference, but compositions administration group is given and is wanted simple, can treatment time be shortened, be beneficial to Clinical practice and patient's acceptance, there is practical significance.
Embodiment 5
Oritavancin diphosphate 405g (in oritavancin), caspofungin acetate 50g (in Caspofungin), sucrose 300g, mannitol 200g, acetate buffer solution is appropriate.
Its preparation technology is: precision takes oritavancin diphosphate and the caspofungin acetate of recipe quantity, adds appropriate water for injection and dissolves; Add the mannitol of recipe quantity, sucrose, acetate buffer solution successively in above-mentioned solution, regulate pH to 4.5, afterwards with 0.1 μm of ultrafilter membrane removing thermal source, filtrate, through 0.22 μm of microporous filter membrane aseptic filtration, injects and is settled to 25L with water, is then packed as 1000 bottles, lyophilization, tamponade, rolls lid, and after passed examination, compositions powder ampoule agent for injection is packed and obtained to labeling.
Investigate pharmaceutical composition freeze-dried powder preparation prepared by embodiment 5 and successively apply oritavancin and caspofungin acetate commercial preparation to the therapeutic effect of mice MOI model
Laboratory animal: SPF level BALB/c mouse, 80,15 ~ 20g, is provided by Zhongshan University's Experimental Animal Center.
Bacterial strain: Candida albicans (Candida albicans) SC-5314, MRSA-252, provided by The 2nd Army Medical College new drug development center.
Experimental technique:
1. the cultivation of infection bacterial strain distinguishes inoculating strain SC-5314 in husky fort glucose agar medium with preparation, MRSA-252 is in MH agar culture medium in inoculation, transferred species 2 times, all at 35 DEG C, cultivate 24h, bacteria suspension is prepared into physiological saline solution, with blood cell counting plate counting, wherein SC-5314 concentration is 5 × 10
6cFU/ml, MRSA-252 concentration is 5.0 × 10
9cFU/ml.
2. mice is divided into 4 groups by the foundation of mice MOI model and treatment at random, often organizes 20, is respectively infected group, compositions treatment group, separately medication group and PBS matched group.First three groups mice is respectively through tail vein injection 0.1ml bacterium liquid, and PBS control group mice is through tail vein injection equivalent physiological saline solution.After 24h, compositions treatment group intraperitoneal injection oritavancin associating caspofungin acetate freeze-dried powder preparation, separately medication group lumbar injection complete oritavancin afterflush pipeline, inject caspofungin acetate preparation (separately medication group dosage is by human dose conversion, and each drug dose of compositions treatment group is with separating medication group) again.PBS control group mice lumbar injection equivalent physiological saline solution.Continuous use 7 days.Record the 8th day dead mouse number.Experimental result is in table 5.
Table 5 is group dead mouse situation respectively
Experimental result shows, in embodiment 1, composition freeze-drying powder preparation administration prepared by oritavancin and caspofungin acetate conbined usage, the effect of bacterial-infection resisting and anti-fungal infection can be played simultaneously, and separate compared with administration group, death toll does not have significant difference, but compositions administration group is given and is wanted simple, can treatment time be shortened, be beneficial to Clinical practice and patient's acceptance, there is practical significance.
Claims (9)
1. treat the pharmaceutical composition of MOI, it is characterized in that, its active constituents of medicine is glycopeptide class antibacterials and antifungal drug, and the ratio of glycopeptide class antibacterials and antifungal drug is 1:1-15:1.
2. pharmaceutical composition according to claim 1, it is characterized in that, glycopeptide class antibacterials are the one in Te Lawan star, dalbavancin, oritavancin, vancomycin, teicoplanin or its pharmaceutically acceptable salt.
3. pharmaceutical composition according to claim 1, it is characterized in that, antifungal drug polyenoid class is amphotericin B, and echinocandin class is the one in Caspofungin, MFG, anidulafungin or its pharmaceutically acceptable salt.
4. require described pharmaceutical composition according to right 1, it is characterized in that, described pharmaceutical composition is lyophilized powder form.
5. pharmaceutical composition according to claim 1, the excipient wherein also containing pharmaceutically acceptable amount, described excipient is one or more in mannitol, lactose, sucrose, fructose.
6. pharmaceutical composition according to claim 1, wherein also comprises pH adjusting agent, and described pH adjusting agent is hydrochloride buffer, acetate buffer solution, tartaric acid buffer, citrate buffer, citrate buffer solution.
7. pharmaceutical composition according to claim 1, is characterized in that, the quality sum of described glycopeptide class antibacterials and antifungal drug accounts for the 5-90% of gross mass, and the quality sum of described excipient and pH adjusting agent accounts for the 10-95% of gross mass.
8. pharmaceutical composition according to claim 1, its preparation method is: precision takes the principal agent of recipe quantity, adds appropriate water for injection and dissolves; Add the excipient of recipe quantity and pH adjusting agent successively in above-mentioned solution, regulate pH; With ultrafiltration membrance filter, then use filtering with microporous membrane; Be settled to full dose, subpackage, vacuum lyophilization, tamponade, Zha Gai, after passed examination, labeling is packed and obtains drug combination injection.
9. pharmaceutical composition according to claim 1, its purposes is treatment or the infection of prevention bacteria mixed fungi.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926706A (en) * | 2018-09-30 | 2018-12-04 | 温州市中心医院 | A kind of pharmaceutical composition and preparation method thereof for treating infection |
| CN110859950A (en) * | 2019-11-25 | 2020-03-06 | 武汉大学 | Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application thereof |
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| US20040142026A1 (en) * | 2002-10-29 | 2004-07-22 | Transave, Inc. | Sustained release of antiinfectives |
| CN1969874A (en) * | 2006-12-07 | 2007-05-30 | 重庆医药工业研究院有限责任公司 | Externally applied pharmaceutical composition of abafungin |
| CN101396363A (en) * | 2007-09-28 | 2009-04-01 | 重庆医药工业研究院有限责任公司 | Composite antibacterial drugs composition containing abafungin |
| CN102512379A (en) * | 2011-12-16 | 2012-06-27 | 深圳市健元医药科技有限公司 | Novel Echinocandin antifungal pharmaceutical composition and preparation method thereof |
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2015
- 2015-06-09 CN CN201510312876.4A patent/CN104888222A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040142026A1 (en) * | 2002-10-29 | 2004-07-22 | Transave, Inc. | Sustained release of antiinfectives |
| CN1969874A (en) * | 2006-12-07 | 2007-05-30 | 重庆医药工业研究院有限责任公司 | Externally applied pharmaceutical composition of abafungin |
| CN101396363A (en) * | 2007-09-28 | 2009-04-01 | 重庆医药工业研究院有限责任公司 | Composite antibacterial drugs composition containing abafungin |
| CN102512379A (en) * | 2011-12-16 | 2012-06-27 | 深圳市健元医药科技有限公司 | Novel Echinocandin antifungal pharmaceutical composition and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926706A (en) * | 2018-09-30 | 2018-12-04 | 温州市中心医院 | A kind of pharmaceutical composition and preparation method thereof for treating infection |
| CN110859950A (en) * | 2019-11-25 | 2020-03-06 | 武汉大学 | Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application thereof |
| CN110859950B (en) * | 2019-11-25 | 2021-08-10 | 武汉大学 | Pharmaceutical composition for candida albicans echinocandin drug-resistant bacteria and application thereof |
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