CN103638052A - Polyrhachis dives extractive, and preparation and medical purpose thereof - Google Patents
Polyrhachis dives extractive, and preparation and medical purpose thereof Download PDFInfo
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Abstract
The invention relates to a Polyrhachis dives extractive, and preparation and medical purpose thereof. Specifically, the invention relates to a traditional Chinese medicine Polyrhachis dives extractive with function of controlling fungal infection diseases, and a preparation method and medical purpose thereof in preparation of antifungal drugs. The Polyrhachis dives extractive provided by the invention is prepared by organic solvent immersion and extraction on dried bodies of Polyrhachis dives. The extractive has significant activity on inhibiting the growth of Candida albicans, and can be prepared into tablets, granules, capsules, pills, an oral liquid, dripping pills, a coating agent, an external liniment, a film agent, an ointment, a spraying agent, an injection, a transdermal patch and an aerosol, and used in the preparation of medicines, daily chemical products or medical devices for prevention and treatment of fungal infections.
Description
Technical field
The present invention relates to medical technical field, particularly, the present invention relates to a kind of bitooth multi-ant extract with antifungal activity and preparation method thereof, the pharmaceutical composition that contains this extract and the purposes in preparation control fungal infection medicine thereof.
Background technology
Along with medical science applied development, various novel drugs and new technique are widely used as the medical procedure such as broad ectrum antibiotic, hormone, various intubation catheter technology, chemotherapy, transplanting, and HIV infects and tumor, the case increasing year by year that causes human immunity system to be destroyed gradually, thus the mycotic sickness rate that causes deep fungal infection to cause is more and more high; And on the other hand, along with being widely used of mankind's abuse of antibiotics and clinical antifungal drug, causing traditional antibiotic can not effectively resist some serious fungal infection and antibacterial infection, the drug resistance phenomenon of fungus is day by day serious.The antibiotic effect of tradition has met with remarkable bottleneck, and most of antibacterials, fungus have produced significant Drug resistance to common antibiotic; The concurrent fungal infections such as HIV sufferers, patient with severe symptoms, fire victim more make sufferer hang by a hair.Therefore, searching wide spectrum, antifungal new drug efficient, low toxicity have become the focus of drug research.
Research to fastbacteria/intractable fungus is extremely urgent.The disease that fungal infection causes can be divided into following four classes substantially: studies of invasive fungal infections and systemic mycosis (as aspergillosis and candidiasis etc.), mucosal pattern mycosis (as " thrush " etc.), shallow phenotype dermatomycosis (as " tinea pedis " or " tinea capitis ", " tinea unguium " etc.) and anaphylactic type mycosis (as asthma and chronic inflammatory disease etc.).In above four class mycosises, with the first kind, the mankind are endangered to maximum, then three class mycosises are relatively light.According to the clinical statistics data from external, in dying from the crowd of infectious disease, have 4% to be to die from general aspergillosis mushroom fungal infection, about 2% people dies from general monilial infection.Clinical statistics data shows, once patient suffers from general aspergillosis, its mortality rate is up to 85%, as suffer from blood candidiasis its mortality rate reached 40%.Utilize existing antifungal drug treatment systemic mycosis or the mycotic effect of blood infection type so far still cannot be satisfactory.Therefore, pharmacy circle is being found the newtype drug that can suppress systemic fungal infection.
At present, the antifungal drug of having developed listing both at home and abroad mainly contains four large classes, i.e. echinocandin (echinocandins) class (as Caspofungin and meter Ka Min etc.) of polyenoid class (as amphotericin B), triazole type (as fluconazol, miconazole, econazole, Itraconazole and ketoconazole etc.), alkyl amine (as terbinafine) and listing newly developed.Front three major types antifungal agent is the old medicine of 20th century exploitation listing, and echinocandin class is the new drug of exploitation listing at the beginning of 21 century.The health azole of old kind is as the onset by lanosterol 14 demethylases in Antifungi ergosterol biosynthesis such as fluconazol, itraconazole, voriconazole, posaconazole, and this type of old brand health triazole antifungal agent thing antimicrobial spectrum is compared with narrow and resistance to pressure grows with each passing day.Though new varieties antifungal drug antimicrobial spectrum expands, metabolisming property and physicochemical property are not good, and water solublity is low, bioavailability is poor; Needs of patients high fat diet is in order to drug absorption, or take the extraordinary dosage form of high price can onset; For increasing cyclodextrin that water solublity adds etc., also to renal insufficiency person, bring larger threat.
Antifungal drug in triazole class is the first generation or the second filial generation is all to there being the fungus-caused systemic infection unsatisfactory curative effect of silk no matter; Although and echinocandin class antifungal new drug has certain curative effect to this class disease, yet its greatest problem facing is: there is no peroral dosage form, be only limited to injection (and only limiting to hospital's use), therefore patient uses rather inconvenience.Secondly, although echinocandin is pretty good to the sick fungal infection curative effect that waits of Candida spp, it is expensive, so limited the sales volume in they markets beyond developed country.It is reported, in China market, the retail price of every Caspofungin injection (dosage is 50 milligrams) is 3,148 yuan, and the meter Ka Min price that Japan produces is slightly lower, but every (dosage is 50 milligrams) also wants 650 yuan.Therefore, the current the most frequently used general antifungal drug of China's hospital clinical is still Fluconazole and terbinafine.
In sum, finding as early as possible novel antifungal drug and active substance source, is that many decades medicine workers need the promptly task of top priority of development from now on.Chinese medicine and natural drug are because of advantages such as the low difficult generation drug resistance of its untoward reaction in treatment, in widespread attention; The various folk prescriptions of being made by Chinese medicine or natural product or compound preparation and Chinese medicine and western medicine compatibility agent, be applied to clinically more and more, shows good effect.Because Chinese medicine and natural drug have the features such as aboundresources, toxic and side effects be low, domestic expert is just aiming at sight this field, excavate Chinese medicine treasure-house, try hard to find the medicine of the various diseases that effectively Antifungi infection causes, and our early-stage Study has been seen hope.
The insecticide of having recorded and having named on the earth, its kind surpasses 1,000,000 kinds, accounts for the more than 80% of whole regnum animale kind, and wherein China approximately has 150,000 kinds.In very long evolutionary process, insecticide has become the animal species of advantage on the earth.It is estimated, the total biomass of insecticide surpasses all animal total biomasses on the earth, is one of untapped biological group in the world today.And pharmaceutical insects is the ingredient in Chinese pools of traditional Chinese medicine, according to records, there is the insecticide of medical value approximately to have more than 800 to plant, 14 orders 35 that are under the jurisdiction of Insecta are above section level.Many insects Chinese medicine is because of determined curative effect extensive use clinically.In recent years, the excavation of insecticide source medicinal ingredient and pharmaceutical insects, in the original effect aspect some difficult miscellaneous diseases for the treatment of, have been caused to vast medical worker and bughunter's very big interest, the research of pharmaceutical insects has had considerable progress.Inventor team is engaged in the exploitation research of pharmaceutical insects for a long time, and successfully developed and take the medicines such as " Kangfuxin Liquid ", " Ganglong capsule " that Blatta seu periplaneta is raw material, " Xinmailong injection ", cure mainly: the ischemic cardiovascular and cerebral vascular diseases such as traumatic surface, hepatitis B, acute and chronic heart failure and ventricular premature contraction such as burn and scald etc.
In order to explore, develop novel antifungal natural drug, the present invention be take pharmaceutical insects Formica fusca as object of study.Formica fusca claims again " Formica fusca ", " ant ", " elder brother Fu ", " ant ", " horse ant ", " ZHUANGYUANZI ", be a kind of social insect, Formica fusca is subordinate to Insecta (Class Insecta), Hymenoptera (Hymenoptera), apocrita (Apocrita), Formicoidea (Formicoidea), Formicidae (Formicidae).Ant species is various, and the whole world has 260 genus, approximately has kind more than 16,000, and that has named at present has a kind more than 8,800.China estimates to reach more than 2,000 kinds, wherein named nearly 600 kinds.The CHEN Zang-Qi Tang Dynasty that is recited as the earliest that Formica fusca is used as medicine is shown < < Bencao Shiyi > >, wherein just has the description of " unipods ant cures mainly the swollen deep carbuncle of furuncle, smash painting "; The Li Shizhen (1518-1593 A.D.) < < of Ming Dynasty Compendium of Materia Medica > >, the ZHAO Xue-Min < < of Qing Dynasty A Supplement to the Compendium of Materia Medica > > etc. also include Formica fusca as Chinese medicine, think that ant larva has effects such as " lactogenic juice, damp colors ", can close " strong medicine (being tonic) ".The Formica fusca of at present China's clinical practice is less than 20 kinds, wherein named and conventional what be used as medicine is to comprise the brown woods ant of mercerising, intend all of 10 kinds of nontoxic Formica fuscas of Formicidae animal such as black many wings ant, bitooth multi-ant.Cure mainly the dizzy tinnitus of suffering from a deficiency of the kidney, insomnia and dreamful sleep, impotence and seminal emission, rheumatic arthralgia, apoplectic hemiplegia, numb hand and foot, lupus erythematosus, scleroderma, dermatomyositis, carbuncle furuncle, venom.Recent researches finds, Formica fusca has antiinflammatory, analgesia, raising immunity, reduces gastric acid secretion, pre-ulcer generation, epilepsy, the anti-frightened effect such as stick up; Medical ant has the pharmacological action that regulates human body hormonal system aspect, particularly rheumatoid, diabetes, cancer etc. are all had to good therapeutic effect (" the development and utilization overview of China's medical ant ", Institutes Of Chifeng's journal (natural science edition), 2011,27 (7): 22-24).
Formica fusca, except being used as medicine, is gone back edible, 70 multiple nutritional components that it contains needed by human; Wherein rich in protein, accounts for 42%～67%, and the adult of Formica fusca reaches 55% containing protein, and ovum can reach 67%; Crude protein content reaches more than 42%; Contain 26 kinds of free amino acids, the aminoacid that adds proteolysis is totally 27 seed amino acids, and the total amount of free amino acid can reach 1,868 milligram/100 grams, and hydrolysis amino acid reaches 3,994 milligrams/100 grams, wherein has 8 kinds to be the aminoacid of needed by human; Meanwhile, also contain 28 kinds of free fatties in Formica fusca body, wherein oleic acid 62.44%, Palmic acid 21.14%, palmitoleic acid 11.03%.In Formica fusca body, also contain multiple hormone, (Formica fusca body includes 19 kinds of enzymes and coenzyme to organized enzyme, as FAD, SOD etc., these materials are to the renewal of the energy metabolism of body, brain cell and improve cerebral anoxia situation and play an important role), high-energy phosphate compound and formaldehyde (be mainly cursive script formaldehyde C
10h
16o
2, be terpenes derivant, have the function of good relaxing muscles and tendons to promote blood circulation, its nourishing ability can compare favourably with wild ginseng), formic acid (formic acid, some content is up to 20% of body weight, concentration reaches 70%).In addition, also contain abundant vitamin in Formica fusca body, comparatively outstanding have vitamin A, C, D, E, B1, B2, a B12, for human health provides abundant nutrient substance; In addition, according to surveying and determination, Formica fusca body includes 28 kinds of trace element, as: manganese, zinc, selenium, magnesium, calcium, phosphorus, chromium, ferrum, iodine, molybdenum, fluorine etc., wherein the content of zinc is the highest, therefore wind resistance damp disease (" progress of medical ant ", food and pharmaceutical evident in efficacy, 2006,8 (01A): 26-28).
As above-mentioned, because the health of Formica fusca is exactly a nutrition library and pharmaceutical factory, so it is medicinal high with edibility.Leaf cutting ant (the Attini family in America is originated in scientist's research of the U.S., Apterostigma dentigerum), the actinomycetes Pseudonocardia spp. that finds the symbiosis of this kind of Formica fusca health body surface can produce can Antifungi Escovopsi ssp. and a kind of cyclic peptide antibiotic Dentigerumycin(" Dentigerumycin:a bacterial mediator of an ant-fungus symbiosis " of part candidiasis bacterial strain, Nat Chem Biol.2009,5 (6): 391-393).Yet, leaf cutting ant Apterostigma dentigerum is only distributed in the some areas such as America Costa Rica, and also do not find in other place with the actinomycetes Pseudonocardia spp. of its symbiosis, so Dentigerumycin cannot prepare further to develop in a large number.The scientist of Australia finds in the secretions of metapleura gland (metapleural gland) that originates in Australian Bulldog ant (Bulldog ant) Myrmecia nigriscapa can anti-bacteria, the metapleura parathyrine (metapleurins) (" Ants and antibiotics " of conk, ECOS, 1989,61:27-28).Yet Bulldog ant (Myrmecia nigriscapa and sibling species) is Australian extraordinary insecticide, other countries and area do not distribute; And metapleurins is collected as stimulating living Bulldog ant, makes its metapleura glandular secretion go out the antibiotic active substance of class, therefore, be difficult to meet the further required a large amount of samples of research and development.
Bitooth multi-ant (Polyrhachis dives Smith), claim again two prominent thorniness ants, two red thorniness ant, refer to Formicidae (Formicidae) Polyrhachis (Polyrhachis spp.) insecticide, be distributed in Burma, Vietnam, Cambodia, Sri Lanka, Thailand, the Malay Peninsula, Philippine country in Southeast Asia and Japan, Australia, Ba Buya New Guinea; Within Chinese territory, be distributed in the ground such as Hebei, Shandong, Zhejiang, Anhui, Shanghai, Fujian, Guangdong, Guangxi, Guizhou, Hunan, Hainan, Taiwan, Hong Kong, Macao, Gansu, Yunnan.Bitooth multi-ant is a kind of in nearly 20 kinds " Formica fuscas " of applying on China's tcm clinical, the long 5.3-6.3 millimeter of worker ant body, and body black, sometimes with brown, alitrunk, rear abdomen drape over one's shoulders golden yellow pubescence, and head pubescence is more sparse, and rear abdomen is silver gray.Feeler attachment region is away from clypeus.Pronotary antero-lateral horn, 2 straight lunges of each tool of median segment backboard.Outside pronotary thorn reaches out, slightly lower curved.Median segment backboard thorn is upright, is separated from each other, and bends towards outside.Peduncle knot top each tool one of two side angles bends towards the lunge of postabdomen, has 2-3 little tooth between thorn; Postabdomen is short.
The inventor finds the be used as medicine large quantity research of Formica fusca of China, and bitooth multi-ant has antifungal activity, and the inventor, again according to lot of documents investigation and related experiment, has designed the preparation technology of the bitooth multi-ant extract with Antifungi growth effect.Through the inventor, look into new discovery, relevant report or the patent of the pharmaceutical preparation of in the past all preparing as principal agent without the bitooth multi-ant extract identical with the present invention, more without using above-mentioned preparation for preventing and treating the bibliographical information of fungal infection disease.The discovery of antifungal result of the test, bitooth multi-ant extract has significant antifungal activity, completes thus the present invention.
Summary of the invention
The object of this invention is to provide a kind of bitooth multi-ant extract with antifungal activity.
The present invention also provides the preparation method of bitooth multi-ant extract: by weight ratio, be that the organic solvent soaking at room temperature that 30-300 doubly measures is extracted bitooth multi-ant polypide, soak and extract three times, each time is 2-24 hour, concentrating under reduced pressure reclaims solvent, dry, pulverize, obtain product.Wherein, organic solvent refers to the aqueous solution that is less than 5 lower alcohol with carbon atom, preferably ethanol or the methanol solution of 50%-98%; The preferred vacuum decompression of drying means is dried or lyophilization.
Another object of the present invention is to provide the application of bitooth multi-ant extract in preparation prevention and treatment antifungal medicine; The preferably application in the medicine of preparation prevention and treatment monilial infection disease.
Another object of the present invention is to provide the drug excipient or the carrier that contain bitooth multi-ant extract and preparation permission and is prepared into pharmaceutical composition, and prepared pharmaceutical composition can also contain other antibacteriums and/or antifungal drug.Described medicine can be made multiple dosage form by means known in the art, comprise tablet, granule, capsule, oral liquid, drop pill, varnish, externally-applied liniment, membrane, unguentum, spray, injection, transdermal patch, aerosol, controlled release or slow releasing agent, and nanometer formulation.
Through the detailed Literature Consult of the inventor, up to the present, there is no relevant bitooth multi-ant extract for the preparation of the report of antifungal drug.Bitooth multi-ant extract belongs to beyond thought discovery for the potent inhibition of conk, has definite originality, completes accordingly the present invention.
Usefulness of the present invention is: find that first bitooth multi-ant extract has the patent medicine potentiality that Antifungi is grown, prepared anti-fungal infection aspect, for exploitation becomes treatment fungal infection original new drug, provide new material base.There is potential huge Social benefit and economic benefit.A present invention again feature is: the present invention's Medical insect resources is abundant, and growth conditions is uncomplicated, can be by the extensive artificial cultivation of the outlying low developed area peasant of poverty, for shaking off poverty.It extracts, and preparation method is simple, raw material sources are conveniently easy to get, cost is low, it is little to pollute, and are beneficial to the large-scale production under energy-saving and emission-reduction condition, and industrialization prospect is very clear and definite.
preparation example 1: the preparation of bitooth multi-ant extract (1)
The present embodiment crude drug used, purchased from Lincang City, Yunnan Province Chinese Medicinal Materials Markets, is accredited as bitooth multi-ant dry product through national local joint project research center professor Yang Zizhong of medicinal extraordinary insecticide exploitation of Dali of Yunnan institute.
Get the dry bitooth multi-ant of 400.0 milligrams, be soaked in 70% alcoholic solution and extract three times under room temperature, each consumption is respectively 100,80,60 milliliters; 24,12,6 hours respectively extraction time; Leach soak, merge extractive liquid,, concentrating under reduced pressure, recovery solvent, lyophilization, weighs after pulverizing, obtains (1) 63.8 milligram of bitooth multi-ant extract.
preparation example 2: the preparation of bitooth multi-ant extract (2)
The present embodiment crude drug used, purchased from Lincang City, Yunnan Province Chinese Medicinal Materials Markets, is accredited as bitooth multi-ant ant dry product through national local joint project research center professor Yang Zizhong of medicinal extraordinary insecticide exploitation of Dali of Yunnan institute.
Get the dry bitooth multi-ant ant of 400.0 milligrams, be soaked in 75% methanol solution and extract three times under room temperature, the consumption of each 75% methanol solution is 50 milliliters, extracts 8 hours at every turn; Leach soak, merge extractive liquid,, concentrating under reduced pressure, recovery solvent, lyophilization, weighs after pulverizing, obtains (2) 59.0 milligrams of bitooth multi-ant extracts.
pharmacology embodiment 1: bitooth multi-ant extract Antifungi is active to be detected
The standardization antifungal sensitivity testing method proposing with reference to standard committee of American National clinical laboratory (NCCLS), the bitooth multi-ant extract (1) that test implementation example 1,2 prepares, the extracorporeal antifungal activity of bitooth multi-ant extract (2).
3.1 fungus type strains:
Candida albicans ATCC76615(CS3): the No2. University of Medical Sciences of PLA provides.
Candida albicans ATCC90029(5-FC Resistant strain): Beijing Hospital's Ministry of Public Health Clinical Laboratory center provides.
Candida albicans 98001: Wuhan DSMZ provides.
Candida albicans Y0119: Shanghai City Long March hospital provides.
3.2 reagent:
3.2.1 sabouraud's agar (sabouraud dextrose agar): Guangdong triumphant microorganism Science and Technology Ltd. product.
3.2.2 yeast extract (yeast extract): Hai Shenggong biotechnology Services Co., Ltd subpackage.
3.2.3 three morpholino nitrogen quinoline propane sulfonic acid (3-N-morpholinopropanesulfonicacid, MOPS)
3.2.4 standard antifungal injection: fluconazol (Fluconazole, FCZ), company of Yangzijiang Pharmaceutical Group.Be configured to the doubling dilution liquid of variable concentrations gradient.
3.2.5 dimethyl sulfoxide (dimethylsulfoxide, DMSO) and dimethyl formamide (dimethylformamide, DMF): Shanghai Sangon Biological Engineering Technology And Service Co., Ltd's subpackage product.
3.3 instruments:
3.3.1 electronic balance JA1203N(AB204-5, METTLER TOLEDO): Shanghai exact science instrument company product.
3.3.2SW-CJ-2FD the double one side clean work station of type: Purifying Equipment Co., Ltd., Suzhou's product.
3.3.3 water isolation type constant incubator (GSP-9160MBE): Shanghai Yiheng Scientific Instruments Co., Ltd's product.
3.3.4 electro-heating standing-temperature cultivator (HZQ-F160A): Shanghai Yiheng Scientific Instruments Co., Ltd's product.
3.3.5 U.S. Pedicellus et Pericarpium Trapae electric refrigerator (BCD-221CHC): Hefei Meiling Co. Ltd.'s product.
3.3.6 micropipettor (Proline Pipette, DragonMed Pipette): Finland Lei Bo company product.
3.3.7 cell counting count board (96well cell culture cluster): Shanghai refinement instrument company product.
3.3.8 ordinary optical microscope (Olympus): Japanese Olympus optical instrument Co., Ltd. product.
3.3.9 hot air oven (101A-2): Shanghai Chongming experimental apparatus company product.
3.3.10 vertical autoclave sterilizer (YXQ-LS-50S II): Shanghai Bo Xun Industrial Co., Ltd. product.
3.3.11 magnetic force heating stirrer (ARE): Italian VELP company product.
3.3.12 filter membrane, filter (0.22 μ m, SARTORIUS): Sartorius AG's product.
3.3.13 acidometer (PHSJ-4A): upper Nereid Ke Lei magnetic company product.
3.3.14 test tube oscillator (MS2): Guangzhou Yi Ke laboratory technique company product.
3.3.15 constant-temperature shaking incubator (THZ-18AB): Shanghai Yi Heng scientific instrument company product.
3.3.16 cryogenic refrigerator (20 ℃, section dragon BCD-219WAK): Guangdong Ke Long electrical equipment Co., Ltd product.
3.3.1796 the flat microtest plate in hole: U.S. Corning Incorporated product.
3.4 experimental techniques:
3.4.1 experimental procedure:
3.4.1.1RPMI-1640 the preparation of liquid: get 10.4 grams of RPMI-1640 powder (containing L glutamine, not containing sodium bicarbonate, GIBCO) be dissolved in 900 ml sterile waters, adding 34.53 gram of three morpholino nitrogen quinoline propane sulfonic acid (MOPS) to its endpoint concentration is 0.165 mol/L, under room temperature, with magnetic stirring apparatus, mixes 2-3 hour, and it is fully dissolved, with sodium hydroxide (1 mol/L), regulate pH value to 7.0(25 ℃), with aquesterilisa, be settled to 1 liter, Entkeimung, after subpackage ,-20 ℃ save backup.
3.4.1.2 the preparation of storing solution: storing solution concentration should be 10 times of application liquid, 5-FC(5-fluorouracil) and FCZ(fluconazol) be 1,280 mcg/ml, Amb(amphotericin B) and KETO(ketoconazole) be 320 mcg/ml, with electronic balance, take respectively each 10 milligrams of 5-FC, FCZ, KETO and Amb, 5-FC dissolves with 1 milliliter of distilled water, FCZ dissolves with 1 milliliter of dimethyl formamide (DMF), Amb and KETO use respectively dimethyl sulfoxine (DMSO) to dissolve, with RPMI-1640, be diluted to storage liquid concentration afterwards, after subpackage ,-70 ℃ save backup.
3.4.1.3 apply the preparation of liquid: with RPMI-1640 liquid, storing solution is done to after 1:10 dilutes, remake multiple proportions rare, FCZ, 5-FC and Amb are that 128 mcg/ml-0.25 mcg/ml are made 10 serial concentration, KETO is 10 series concentration of 32 mcg/ml-0.06 mcg/ml, is 2 times of final concentrations.
3.4.1.4 the preparation of micro-susceptibility culture plate: use disposable 96 orifice plates, 1-10 row add respectively the application liquid of the testing drug of 10 Concentraton gradient, from high concentration to low concentration.The 11st row add RPMI-1640, every hole 100 microlitres, and the 12nd row, as blank, are put into-20 ℃ of refrigerators standby, and during use ,-4 ℃, 4 ℃, warp and room temperature are each 1 hour.
3.4.1.5 the activation of candidiasis and dilution: by bacterial strain to be measured at YPD Agar culture medium (1% yeast extract, 1% peptone, 2% glucose) upper activation after twice, cut-off footpath be greater than 1 millimeter bacterium colony a little in 3 milliliters of physiological saline solution, mix and make bacteria suspension, get a little, with the bacterial cell number in four large grids of hemocyte technology plate counting, the X that averages, now bacterial cell number is X * 10
4cFU/ milliliter, with RPMI-1640 liquid, adjusting concentration is 3 * 10
4cFU/ milliliter (twice final concentration).
3.4.1.6 application of sample: add candidiasis suspension on the above-mentioned culture plate that contains testing drug preparing, every hole 100 microlitre blanks do not add, and concussion is put into 35 ℃, wet box (prevent evaporating of micro plate and affect the concentration of medicine) after mixing and hatched observed result after 24-48 hour.
3.4.1.7 naked eyes judged result: take growth control blank as foundation, (is MIC with 80% inhibition
80) for observing terminal, growth obviously reduces, liquid is slightly muddy; Well-grown in positive growth simultaneously, blank is limpid, without bacterial growth.In the scope of Quality Control bacterial strain ZhiMICZhi U.S. Clinical microorganism laboratory standard CLSI M27-A2 scheme regulation, show that experimental result is effective.
3.5 experimental results:
3.5.1 the sensitivity of Quality Control strain to antifungal drug: four kinds of positive drugs meet CLSIM27-A2 scheme for the requirement of Quality Control strain type strain to Quality Control strains A TCC90029 and 98001 type strain drug sensitivity tests.That is: the MIC value variation that repeats to carry out above for 3 times AmB, 5-FC, FCZ and KETO is no more than 2 Concentraton gradient.
3.5.2 the antifungal activity of testing sample (bitooth multi-ant extract (1), bitooth multi-ant extract (2), positive control) the results are shown in Table 1.
The inhibitory action of each bacterial strain of table 1 test sample dialogue color candidiasis
3.6 conclusions:
By adopting the vitro inhibition conk of " Herbs By Broth Microdilution " research bitooth multi-ant extract active, experimental study shows: thorniness belongs to bitooth multi-ant extract has clear and definite anti-candida albicans active.Illustrate that it is potential Antifungi growth activity material, there is further exploitation and be worth.
The thorniness preparing in the present invention belongs to insecticide bitooth multi-ant extract can be combined with pharmaceutically conventional adjuvant or carrier, prepares and has prevention and treat medicine and pharmaceutical composition or health product or the cosmetics of everyday use by fungus-caused infection such as Candida albicans.The dosage form that above-mentioned various kinds of drug compositions, health product or cosmetics of everyday use can adopt comprises tablet, granule, capsule, oral liquid, drop pill, varnish, externally-applied liniment, membrane, unguentum, spray, injection, transdermal patch, aerosol, controlled release or slow releasing agent, and nanometer formulation.
Thorniness of the present invention belongs to insecticide bitooth multi-ant extract can also infect the medicine of associated conditions and crude drug thereof as polyenoid class (as amphotericin B) with the treatment fungus bacterium that now gone on the market, triazole type is (as fluconazol, miconazole, econazole, Itraconazole and ketoconazole etc.), the kinds such as the echinocandin (echinocandins) of alkyl amine (as terbinafine) and listing newly developed are combined use, prepare compositions or the compound preparation with treatment fungal infection associated conditions effect activity, can expect and become treatment fungal infection disease medicine/health product or cosmetics of everyday use.Above-mentioned various kinds of drug compositions, medicine/health product or cosmetics of everyday use can adopt the dosage forms such as tablet, granule, capsule, oral liquid, drop pill, varnish, membrane, unguentum, liniment, injection, transdermal patch, aerosol or spray, comprise the now conventional preparation of generally acknowledged pharmaceutics general knowledge of employing and various slow release, controlled release form or nanometer formulation.
When above-mentioned description elaboration is of the present invention, the object that embodiment is provided is simultaneously to illustrate actual mechanical process of the present invention and meaning of the present invention.In the time of within the scope of entering the claims in the present invention and its equivalent, practical application of the present invention comprises all general variations, cooperation, or improves.
Claims (5)
1. a bitooth multi-ant extract, to it is characterized by this extract be that bitooth multi-ant polypide is soaked and extracts three times through organic solution, merge extractive liquid,, reclaims solvent, dry obtaining at concentrating under reduced pressure; Wherein, organic solvent refers to the aqueous solution that is less than 5 lower alcohol with carbon atom, and consumption is weight ratio: 30-300 doubly measures; Immersion extraction time is 2-24 hour.
2. according to the bitooth multi-ant extract of claim 1, it is characterized in that: the organic solvent in preparation process refers to ethanol or the methanol solution of 50%-98%; Drying means refers to that vacuum decompression is dried or lyophilization.
3. the arbitrary bitooth multi-ant extract of claim 1-2 is prevented and treated the application in fungal infection medicine in preparation.
4. a pharmaceutical composition with anti-fungal infection, is characterized in that: this pharmaceutical composition contains bitooth multi-ant extract, pharmaceutic adjuvant and the pharmaceutical carrier arbitrary according to claim 1-2 for the treatment of effective dose.
5. according to the pharmaceutical composition of claim 4, its dosage form is tablet, granule, capsule, oral liquid, drop pill, varnish, externally-applied liniment, membrane, unguentum, spray, injection, transdermal patch or aerosol.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104546923A (en) * | 2014-12-29 | 2015-04-29 | 陈乃宏 | Polyrhachis vicina roger extract as well as extraction method and application thereof |
| CN106309504A (en) * | 2016-10-25 | 2017-01-11 | 桂林淮安天然保健品开发有限公司 | Black ant extract and preparation technology thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104546923A (en) * | 2014-12-29 | 2015-04-29 | 陈乃宏 | Polyrhachis vicina roger extract as well as extraction method and application thereof |
| CN104546923B (en) * | 2014-12-29 | 2018-10-09 | 陈乃宏 | A kind of Polyhachis vicina Roger extract and its extracting method and application |
| CN106309504A (en) * | 2016-10-25 | 2017-01-11 | 桂林淮安天然保健品开发有限公司 | Black ant extract and preparation technology thereof |
| CN106511393A (en) * | 2016-10-25 | 2017-03-22 | 桂林淮安天然保健品开发有限公司 | Black ant extract and preparing method thereof |
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