CN104523693A - Antifungal compound preparation containing chlorogenic acid and application thereof - Google Patents
Antifungal compound preparation containing chlorogenic acid and application thereof Download PDFInfo
- Publication number
- CN104523693A CN104523693A CN201410723025.4A CN201410723025A CN104523693A CN 104523693 A CN104523693 A CN 104523693A CN 201410723025 A CN201410723025 A CN 201410723025A CN 104523693 A CN104523693 A CN 104523693A
- Authority
- CN
- China
- Prior art keywords
- chlorogenic acid
- compound preparation
- medicine
- antifungal
- preparation
- 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.)
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- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 title claims abstract description 74
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 title claims abstract description 74
- 229940074393 chlorogenic acid Drugs 0.000 title claims abstract description 74
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 title claims abstract description 74
- 235000001368 chlorogenic acid Nutrition 0.000 title claims abstract description 74
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
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- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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Abstract
The invention relates to an antifungal compound preparation containing chlorogenic acid, which comprises chlorogenic acid and antifungal medicines with proportion being at 1-100: 1-50. The drug combination of chlorogenic acid and antifungal medicines can increase the curative effect of an antifungal medicine single drug and reduce the toxic and side effect; the antifungal compound preparation contains novel antifungal medicinal preparation of chlorogenic acid, can increase antifungal treatment effect of a single component of the antifungal medicines during antifungal treatment, and can obviously reduce the toxic and side effect of single component of the antifungal medicines. The antifungal compound preparation containing chlorogenic acid has the advantages of wide clinical application scope and better curative effect, and the combination usage of the chlorogenic acid and antifungal medicines has high medical application value.
Description
Technical field
The present invention relates to a kind of the antifungal compound preparation and the application thereof that comprise chlorogenic acid, relate to the application of the conbined usage of chlorogenic acid and antifungal drug simultaneously, belong to field of pharmaceutical preparations.
Background technology
Chlorogenic acid is the depside generated by caffeic acid and quinic acid, is plant a kind of phenylpropanoids through shikimic acid pathway generation in aerobic respiration process.
Chlorogenic acid has biological activity widely, and modern science has been deep into multiple fields such as food, health care, medicine and daily-use chemical industry to the bioactive research of chlorogenic acid.Chlorogenic acid is a kind of important bioactive substance, has antibacterial, antiviral, increases the effects such as leukocyte, hepatic cholagogic, antitumor, blood pressure lowering, blood fat reducing, scavenging free radicals and stimulating central nervous system system.
The poisonous side effect of medicine of anti-fungal infection commercially available is at present larger, which greatly limits clinical use.Often dosage is larger when clinical treatment medication for the antifungal drug of clinical practice, the course for the treatment of is longer, the untoward reaction produced is more, toxicity is comparatively large, to urinary system, digestive system, nervous system, endocrine and reproductive system, blood system, blood circulation, skin and other have toxic and side effects in various degree.The modal untoward reaction of such as amphotericin B is the untoward reaction of urinary system, shows as in urine and has erythrocyte, leukocyte, albumen and cast, and blood urea nitrogen and creatinine value raise, and creatinine clearance rate reduces; Also can cause renal tubular acidosis, nephrocalcinosis, discharge potassium ion in a large number and cause hypokalemia, kidney original shape diabetes insipidus; And nausea,vomiting,diarrhea and gastrointestinal hemorrhage can be there is, hepatic necrosis and acute hepatic failure; In quiet process or after quiet, can shiver with cold, high heat, headache, Nausea and vomiting, blood pressure drops, dizzy etc., if quiet excessive velocities, also can occur that arrhythmia and blood pressure sharply rise or decline, and can thrombosis be there is, form thrombophlebitis, even cause ventricular fibrillation or sudden cardiac arrest, cardiac arrhythmia etc.
Just because of antifungal agent has the untoward reaction of above-mentioned multisystem, facilitate the Study and Development of new antifungal agent on the one hand; Need the existing medicine of Appropriate application on the other hand, as drug combination, drug combination can reduce the dosage of antimycotic medicine list medicine, thus reduces its toxic and side effects.
Summary of the invention
For above-mentioned technical problem, the object of the present invention is to provide a kind of new compound preparation comprising the antimycotic medicine of chlorogenic acid, said preparation can improve antimycotic medicine one-component antifungal therapy effect in antifungal therapy, and significantly reduces the toxic and side effects of antimycotic medicine one-component; And the conbined usage of chlorogenic acid and antifungal drug, after conbined usage, the curative effect of antimycotic medicine list medicine can be improved, and its toxic and side effects can be reduced.
Above-mentioned purpose of the present invention is achieved by the following technical solution: a kind of antifungal compound preparation comprising chlorogenic acid, comprising:
A) chlorogenic acid;
B) antimycotic medicine;
The ratio of wherein said chlorogenic acid and antimycotic medicine is 1-100:1-50.
In drug combination of the present invention, chlorogenic acid refers to the medicine of natural extract acquisition or the be allowed for clinical research through chemosynthesis acquisition, and the mass fraction of its chlorogenic acid in medicine is 10-100%; By give pharmacy can adjuvant be prepared into oral formulations or injection, wherein oral preparation drug administration dosage is 10-100mg/kg, and injection dosage is 2-15mg/kg.
In the present invention, described antimycotic medicine refers to and can suppress or the medicine of killing fungus, can be polyene antibiotics class medicine, also can be synthesis class medicine.Wherein polyene antibiotics class medicine can be polyene macrocyclic class antibiotic, chain polyenoid class, ucleosides or other non-alkene classes; Specifically, can be amphotericin B, globoroseomycin and methylpartricin.Described synthesis class medicine specifically, include but not limited in the middle of ketoconazole, fluconazol, itraconazole, flucytosine, Caspofungin, FK463, voriconazole medicine any one.
In the present invention, preferred 1:10-50 or 1-10:1 of the ratio of described chlorogenic acid and antimycotic medicine.In a concrete example, the ratio of described chlorogenic acid and antimycotic medicine can be 5:1,5:2,2:1,1:1,1:2,1:15,3:10,3:20 etc.
In the present invention, described compound preparation can be oral agents, also can be injection; Specifically, its dosage form includes but not limited to tablet, granule, pill, electuary, capsule, injection or injectable powder.
In the present invention, the compound preparation be made up of chlorogenic acid and ketoconazole, in oral formulations, its mass ratio is 10:1 to 1:10, and in injection, its mass ratio is 10:1 to 1:10.In example of the present invention, the ratio of chlorogenic acid and ketoconazole is 1:1 or 1:2.
In the present invention, the compound preparation be made up of chlorogenic acid and fluconazol, its oral formulations mass ratio is 1:1 to 1:10, and its injection mass ratio is 1:5 to 1:50.In example of the present invention, the ratio of chlorogenic acid and fluconazol is 1:1,1:2 or 3:20.
In the present invention, the compound preparation be made up of chlorogenic acid and itraconazole, its oral formulations mass ratio is 10:1 to 1:10, and its injection mass ratio is 1:5 to 1:10.In example of the present invention, the ratio of chlorogenic acid and itraconazole is 3:10 or 5:1.
In the present invention, the compound preparation be made up of chlorogenic acid and flucytosine, its oral formulations mass ratio is 5:1 to 1:20, and its injection mass ratio is 5:1 to 1:50.In example of the present invention, the ratio of chlorogenic acid and flucytosine is 2:1 or 1:15.
In the present invention, the compound preparation that it is made up of chlorogenic acid and Caspofungin, its oral formulations mass ratio is 10:1 to 1:10, and its injection mass ratio is 5:1 to 1:5.In example of the present invention, the ratio of chlorogenic acid and Caspofungin is 1:2.
In the present invention, the compound preparation be made up of chlorogenic acid and FK463, its oral formulations mass ratio is 1:1 to 1:10, and its injection mass ratio is 1:1 to 1:10.In example of the present invention, the ratio of chlorogenic acid and FK463 is 1:2.
In the present invention, the compound preparation be made up of chlorogenic acid and voriconazole, its oral formulations mass ratio is 5:1 to 1:10, and its injection mass ratio is 1:1 to 1:10.In example of the present invention, the ratio of chlorogenic acid and voriconazole is 5:2 or 3:20.
In the present invention, as preferably, join in compound preparation give pharmacy can adjuvant, comprise filler, adhesive, the lubricant of preparing oral formulations, comprise diluent, caffolding agent, the antioxidant of preparing injection.
Further, described filler comprises lactose, starch, mannitol, hyprolose, dextrin; Described adhesive comprises polyvidone, pre-paying starch, hypromellose; Described lubricant comprises magnesium stearate, Pulvis Talci, micropowder silica gel, Polyethylene Glycol; Described diluent comprises water for injection, normal saline, glucose injection, glycerol, tween, vegetable oil; Described caffolding agent comprises mannitol, lactose, glycine; Described antioxidant comprises vitamin C, L-cysteine hydrochloride, sodium pyrosulfite, sodium sulfite.
In the present invention, the oral formulations of described compound preparation, is prepared into per unit formulation content containing chlorogenic acid 10mg-500mg; The injection of compound preparation, is prepared into per unit formulation content containing chlorogenic acid 10mg-50mg.
Another object of the present invention is to provide the application of a kind of above-mentioned compound preparation in the medicine of preparation treatment fungal infection.The fungal infection that wherein fungal infection comprises Candida, aspergillosis, dimorphic fungus cause.
Present invention also offers the conbined usage of chlorogenic acid and antimycotic medicine, significantly can reduce antimycotic medicine once daily or the caused toxic and side effects that continues medication for a long time, significantly reduce antimycotic medicine especially to the damage of internal organs.
Beneficial effect of the present invention is the drug combination of chlorogenic acid and antimycotic medicine, improves the curative effect of antimycotic medicine list medicine, and reduces its toxic and side effects; Next includes the new pharmaceutical preparation of the antifungal of chlorogenic acid, can improve antimycotic medicine one-component antifungal therapy effect in antifungal therapy, and significantly reduces the toxic and side effects of antimycotic medicine one-component.Make its clinical application range wider, better efficacy, therefore include the antifungal compound preparation of chlorogenic acid and chlorogenic acid and antimycotic Drug combination clinically and there is higher medical application be worth.
Specific embodiment
Embodiment 1 prescription one
After chlorogenic acid and ketoconazole are added appropriate filler and after adhesive, mixing of sieving, granulate, granulate, adds appropriate lubricant, tabletting.
Embodiment 2 prescription two
After chlorogenic acid and ketoconazole are added appropriate filler and after adhesive, mixing of sieving, loads capsule.
Embodiment 3 prescription three
After chlorogenic acid and fluconazol are added appropriate antioxidant, be dissolved in appropriate diluent, ultrafiltration membrance filter, sterile filling.
Embodiment 4 prescription four
After chlorogenic acid and fluconazol are added appropriate filler and after adhesive, mixing of sieving, granulate, granulate, adds appropriate lubricant, tabletting.
Embodiment 5 prescription five
After chlorogenic acid and itraconazole are added appropriate antioxidant, be dissolved in appropriate diluent, ultrafiltration membrance filter, sterile filling.
Embodiment 6 prescription six
After chlorogenic acid and itraconazole are added appropriate filler and after adhesive, mixing of sieving, loads capsule.
Embodiment 7 prescription four
After chlorogenic acid and flucytosine are added appropriate filler, mixing, loads capsule.
Embodiment 8 prescription eight
After chlorogenic acid and flucytosine are added appropriate caffolding agent and antioxidant, be dissolved in appropriate diluent, ultrafiltration membrance filter, sterile filling, lyophilization, roll lid.
Embodiment 9 prescription nine
After chlorogenic acid and Caspofungin are added appropriate antioxidant, be dissolved in appropriate diluent, ultrafiltration membrance filter, sterile filling.
Embodiment 10 prescription ten
After chlorogenic acid and FK463 are added appropriate antioxidant, be dissolved in appropriate diluent, ultrafiltration membrance filter, sterile filling.
Embodiment 11 prescription 11
After chlorogenic acid and voriconazole are added appropriate caffolding agent and antioxidant, be dissolved in appropriate diluent, ultrafiltration membrance filter, sterile filling, lyophilization, roll lid.
Embodiment 12 prescription 12
After chlorogenic acid and voriconazole are added appropriate filler and after adhesive, mixing of sieving, granulate, granulate, adds appropriate lubricant, tabletting.
Embodiment 13 toxicity contrast test
1, animal SD rat, male and female half and half, body weight 120 ~ 140g.
2, medicine-feeding test gets healthy SD rat, male and female half and half.By body weight random packet, be respectively compound preparation group, one-component positive controls, negative group matched group, often organize 10.Disposable oral or intravenous administration, Continuous Observation 14 days after administration, observes animal toxicity symptom and death condition.7th, within 14 days, surviving animals body weight is claimed.
Result
Administration same day, one-component positive controls rat sign occurs significantly abnormal, and symptom slows down to some extent two days later, but does not eliminate completely, and the abnormal sign Symptoms last of part is to off-test, and process of the test has the phenomena of mortality; There is slight exception in compound preparation group small part rat sign, after second day, symptom is eliminated substantially completely, but diet recovers slowly, and process of the test is without Lethal cases; Negative group matched group non-evident sympton and Lethal cases.
During to off-test, one-component positive controls rat, body weight increases not obvious; Compound preparation group, body weight increases to some extent, but too late in negative control group.Concrete test data is in table one and table two.
Embodiment 14 comparative efficacy test
1, the large ear rabbit of animal Japan, female, body weight 200-240g.
2, strain Aspergillus fumigatus, becomes 1 × 10 with normal saline
7the aspergillus fumigatus spores suspension of cfu/ml.
3, medicine-feeding test is by large for Japan ear rabbit by body weight random packet, often organizes 10, is respectively compound formulation group, one-component positive controls, negative control group; Every intramuscular injection dexamethasone 0.375mg/kg, gives 3 days continuously; Auricular vein injection 1 × 10 in 4th day
7the aspergillus fumigatus spores suspension 1ml of cfu/ml, gives commensurability dexamethasone every other day after giving spore.
24h starts auricular vein administration or oral administration after inoculation, and every day is administered once, successive administration 5 days.At duration of test, intramuscular injection every day penicillin (150,000 U/kg) and celebrating mycin (5.6 ten thousand/only) to prevent bacteriological infection, until off-test.
72h puts to death animal after treatment is finished, asepticly wins part liver,spleen,kidney, lung tissue, weighs, add the aseptic PBS solution of 1ml, Potter-Elvehjem Tissue Grinders homogenate, is laid in husky fort chloramphenicol agar sugar plating medium after homogenate dilution, cultivate 4 days counting bacterium colonies for 26 DEG C.To convert to obtain the CFU/g of every organ according to counted clump count.
4, result of the test
By administration after 5 days, each test group all has obvious antibacterial effect, especially compound preparation group, has the significance difference opposite sex.Concrete test data is in table three-Biao eight.
The embodiment 15 drug combination test of pesticide effectiveness
1, the large ear rabbit of animal Japan, female, body weight 200-240g.
2, strain Aspergillus fumigatus, becomes 1 × 10 with normal saline
7the aspergillus fumigatus spores suspension of cfu/ml.
3, material chlorogenic acid, commercial, and purity is respectively 42.38% and 99.86% two sample; Amphotericin B, commercial, New Drug Research company limited of North China pharmacy group of manufacturer.
4, medicine-feeding test is by large for Japan ear rabbit by body weight random packet, often organizes 10, is respectively drug combination group, positive controls, negative control group; Every intramuscular injection dexamethasone 0.375mg/kg, gives 3 days continuously; Auricular vein injection 1 × 10 in 4th day
7the aspergillus fumigatus spores suspension 1ml of cfu/ml, gives commensurability dexamethasone every other day after giving spore.
24h starts auricular vein administration or oral administration after inoculation, and every day is administered once, successive administration 5 days; The first auricular vein of drug combination group is to amphotericin B, and dosage is 2mg/kg, and administration to terminate in rear 24h auricular vein instillation chlorogenic acid or gavage to chlorogenic acid again.At duration of test, intramuscular injection every day penicillin (150,000 U/kg) and celebrating mycin (5.6 ten thousand/only) to prevent bacteriological infection, until off-test.
72h puts to death animal after treatment is finished, asepticly wins part liver,spleen,kidney, lung tissue, weighs, add the aseptic PBS solution of 1ml, Potter-Elvehjem Tissue Grinders homogenate, is laid in husky fort chloramphenicol agar sugar plating medium after homogenate dilution, cultivate 4 days counting bacterium colonies for 26 DEG C.To convert to obtain the CFU/g of every organ according to counted clump count.
5, result of the test
Result of the test shows, chlorogenic acid and antimycotic Drug combination can improve the curative effect of antimycotic medicine list medicine significantly, describe chlorogenic acid in drug combination, have collaborative effect; Concrete data are in table ten one.
Embodiment 16 drug combination toxicity contrast test
1, animal rabbit, male, body weight 2.0 ± 0.2kg;
2, material chlorogenic acid, commercial, purity 99.86%; Amphotericin B, commercial, New Drug Research company limited of North China pharmacy group of manufacturer.
3, test method is by rabbit by body weight random packet, often organizes 5, is respectively chlorogenic acid and amphotericin B drug combination group, amphotericin B matched group; Drug combination group elder generation is by auricular vein to amphotericin B, and dosage is 4mg/kg, and administration terminates in rear 24h again in 2mg/kg (with chlorogenic acid) dosage auricular vein instillation chlorogenic acid; Matched group is with the amphotericin B administration of drug combination group; Once a day, successive administration 7 days.At duration of test, respectively at before second time administration before administration, after first time administration and after last administration 24h from rabbit femoral vein blood, detect ALT, AST, T-BiL and BUN, Cr.
Result of the test
Result of the test shows, antimycotic drug-positive grouping machine internal organs of the body official has obvious damage, and drug combination grouping machine internal organs of the body official is without obvious damage; Drug combination group has the significance difference opposite sex compared with antimycotic drug-positive matched group, illustrates that chlorogenic acid and antimycotic Drug combination significantly can alleviate the damage of antimycotic medicine to internal body viscera organ; Concrete data are in table ten two.
Table ten one drug combination test of pesticide effectiveness result (lgcfu ± s)
Each medicine group compares * p < 0.05, * * p < 0.01 with negative group.
Table ten two drug combination medicine toxicity comparative test result
After administration with compare *: p < 0.05 before administration; *: p < 0.01; Drug combination group compares △: p < 0.05 with matched group; △ △: p < 0.01.
Claims (10)
1. comprise an antifungal compound preparation for chlorogenic acid, comprising:
A) chlorogenic acid;
B) antimycotic medicine;
The ratio of wherein said chlorogenic acid and antimycotic medicine is 1-100:1-50.
2. compound preparation as claimed in claim 1, wherein said chlorogenic acid mass fraction is in the formulation 10-100%; Described chlorogenic acid dosage in oral formulations is 10-100mg/kg, and in injection, dosage is 2-15mg/kg.
3. compound preparation as claimed in claim 1 or 2, described antimycotic medicine is polyene antibiotics class medicine or synthesis class medicine.
4. compound preparation as claimed in claim 3, described polyene antibiotics class medicine is selected from one or more in amphotericin B, globoroseomycin and methylpartricin; Described synthesis class medicine is selected from one or more in ketoconazole, fluconazol, itraconazole, flucytosine, Caspofungin, FK463, voriconazole medicine.
5. the compound preparation as described in any one of claim 1-4, the ratio of described chlorogenic acid and antimycotic medicine is 1:10-50 or 1-10:1; Be preferably 5:1,5:2,2:1,1:1,1:2,1:15,3:10 or 3:20.
6. the compound preparation as described in any one of claim 1-5, described compound preparation is oral agents or injection; Be preferably tablet, granule, pill, electuary, capsule, injection or injectable powder.
7. the compound preparation as described in any one of claim 1-6, described compound preparation also comprises filler, adhesive, lubricant, diluent, caffolding agent, antioxidant; Preferred described filler is selected from one or more in lactose, starch, mannitol, hyprolose, dextrin; Described adhesive is selected from one or more in polyvidone, pre-paying starch, hypromellose; Described lubricant is selected from one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, Polyethylene Glycol; Described diluent is selected from one or more in water for injection, normal saline, glucose injection, glycerol, tween, vegetable oil; Described caffolding agent is selected from one or more in mannitol, lactose, glycine; Described antioxidant is selected from one or more in vitamin C, L-cysteine hydrochloride, sodium pyrosulfite, sodium sulfite.
8. the compound preparation as described in any one of claim 1-7, in the oral formulations of described compound preparation, per unit preparation is containing chlorogenic acid 10mg-500mg; In the injection of compound preparation, per unit preparation is containing chlorogenic acid 10mg-50mg.
9. the application of compound preparation in the medicine of preparation treatment fungal infection as described in any one of claim 1-8; The fungal infection that preferred described fungal infection comprises Candida, aspergillosis, dimorphic fungus cause.
10. the application that compound preparation reduces antimycotic medicine once daily in preparation or continues medication for a long time in the medicine of caused toxic and side effects as described in any one of claim 1-9; Be preferably and reduce antimycotic medicine to the application in the medicine of the damage of internal organs in preparation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410723025.4A CN104523693A (en) | 2014-12-03 | 2014-12-03 | Antifungal compound preparation containing chlorogenic acid and application thereof |
| PCT/CN2015/095246 WO2016086776A1 (en) | 2014-12-03 | 2015-11-23 | Antifungal compound formulation containing chlorogenic acid and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410723025.4A CN104523693A (en) | 2014-12-03 | 2014-12-03 | Antifungal compound preparation containing chlorogenic acid and application thereof |
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| Publication Number | Publication Date |
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| CN104523693A true CN104523693A (en) | 2015-04-22 |
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| CN201410723025.4A Pending CN104523693A (en) | 2014-12-03 | 2014-12-03 | Antifungal compound preparation containing chlorogenic acid and application thereof |
Country Status (2)
| Country | Link |
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| CN (1) | CN104523693A (en) |
| WO (1) | WO2016086776A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016086776A1 (en) * | 2014-12-03 | 2016-06-09 | 四川九章生物科技有限公司 | Antifungal compound formulation containing chlorogenic acid and application thereof |
| CN106692990A (en) * | 2017-01-13 | 2017-05-24 | 广东省实验动物监测所 | Antifungal synergistic drug in-vivo screening method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690543A (en) * | 2013-12-24 | 2014-04-02 | 广西医科大学 | Composition and method for killing aspergillus fumigatus |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2568730T3 (en) * | 2010-10-06 | 2016-05-04 | The Board Of Trustees Of The University Of Arkansas | Anti-biofilm compositions and methods of use |
| CN104523693A (en) * | 2014-12-03 | 2015-04-22 | 四川九章生物科技有限公司 | Antifungal compound preparation containing chlorogenic acid and application thereof |
-
2014
- 2014-12-03 CN CN201410723025.4A patent/CN104523693A/en active Pending
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- 2015-11-23 WO PCT/CN2015/095246 patent/WO2016086776A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690543A (en) * | 2013-12-24 | 2014-04-02 | 广西医科大学 | Composition and method for killing aspergillus fumigatus |
Non-Patent Citations (1)
| Title |
|---|
| FRED A.ANDREWS ET AL: "Enhancement of amphotericin B activity by a series of compounds related to phenolic antioxidants", 《JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016086776A1 (en) * | 2014-12-03 | 2016-06-09 | 四川九章生物科技有限公司 | Antifungal compound formulation containing chlorogenic acid and application thereof |
| CN106692990A (en) * | 2017-01-13 | 2017-05-24 | 广东省实验动物监测所 | Antifungal synergistic drug in-vivo screening method |
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| Publication number | Publication date |
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| WO2016086776A1 (en) | 2016-06-09 |
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Application publication date: 20150422 |