CN104274532A - Compound griseofulvin antibacterial medicine - Google Patents
Compound griseofulvin antibacterial medicine Download PDFInfo
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- CN104274532A CN104274532A CN201410561152.9A CN201410561152A CN104274532A CN 104274532 A CN104274532 A CN 104274532A CN 201410561152 A CN201410561152 A CN 201410561152A CN 104274532 A CN104274532 A CN 104274532A
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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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/57—Magnoliaceae (Magnolia family)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
Abstract
The invention provides a compound griseofulvin antibacterial medicine, and belongs to the technical field of medicines. The medicine is nano-emulsion prepared from anise aqueous extract and griseofulvin serving as effective ingredients. The nano-emulsion is mainly prepared from the following components in parts by weight: 1-18 parts of anise aqueous extract, 15-40 parts of a surfactant, 1-18 parts of a co-surfactant, 1-20 parts of griseofulvin, 1-20 parts of oil and 20-70 parts of distilled water; griseofulvin and anise aqueous extract are compounded, the antibacterial capabilities of the griseofulvin and anise aqueous extract can be mutually promoted and improved, and the antibacterial effect is more stable; the nano-emulsion preparation is capable of improving the solubility and permeability of griseofulvin, can be absorbed by lymph system when taken orally, so that the first-pass effect and barrier of molecules passing through gastrointestinal tracts can be overcome, and the bioavailability of the medicine can be improved.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of oil-in-water type nano-emulsion---the compound antibacterial nano-emulsion being effective ingredient with anistree water extract and griseofulvin.
Background technology
Griseofulvin is the attritive powder of white or off-white color; Odorless, mildly bitter flavor.Griseofulvin energy Antifungi mitosis, makes mitotic fusellal fabric rupture, and stops metaphase.Be deposited in the keratic precursor of skin, hair, keratin can be impelled to support antifungal and invade; After infection keratin comes off, replace health tissues.The cutaneous fungal infection caused Epidermophyton, Microsporon and trichophyton is effective, comprises Candida and antibacterial is invalid to other fungal infection.
Griseofulvin can be deposited on the horny layer of skin, hair, first after absorbing, and combine with its keratin, prevent the continuation of sensitive skin tinea bacterium etc. from invading, be present in the cuticular pathomycete of shallow table coming off and leave human body then with skin or hair, only seldom amount is distributed to other body fluid and tissue.It is in intrahepatic metabolism deactivation, and main metabolite is 6-methyl griseofulvin and glucal acylate thereof, and blood eliminates half-life (T
1/2) be 14 ~ 24 hours.From urine in medicine original shape discharge person less than 1 part, discharge from feces with original shape for about 16 parts ~ 36 parts.
Fructus Anisi Stellati, nature and flavor acrid, sweet, warm, Gui Jing: enter spleen, kidney channel.Latin: Fructus Anisi Stellati, another name: Fructus Anisi Stellati, oceangoing ship Fructus Foeniculi, Octagonal bead, Radix Cacaliae Ainsliaeflorae, anistree Fructus Anisi Stellati, anise, Fructus Anisi Stellati, spiced anise, extract part: mature fruit, meridian distribution of property and flavor: temperature; Pungent; Return liver,kidney,spleen, stomach warp, function cures mainly: warming YANG to expel cold, regulating QI to relieve pain.For colic of cold type stomachache, lumbago due to renal deficiency, gastrofrigid vomiting, coldness and pain in the epigastrium.Usage and dosage: for oral administration: to decoct soup, 3 ~ 6g; Or enter ball, loose.External: appropriate, grinds into powder and dresses.Taboo: hyperactivity of fire caused by deficiency of YIN person prohibits clothes.Star anise extract has fungistatic effect, and its water decoction has inhibitory action to tubercule bacillus and bacillus subtilis; Its ethanol extraction all has stronger inhibitory action to staphylococcus aureus, streptococcus pneumoniae, diphtheria corynebacterium, bacillus subtilis, vibrio cholera, Bacillus typhi, Salmonella paratyphi, dysentery bacterium, escherichia coli and common pathogen.Its alcohol extract is in vitro to gram-positive bacterium (staphylococcus aureus.Streptococcus pneumoniae, diphtheria corynebacterium etc.) bacteriostasis similar to potassium salt of penicillin 20 units/ml; Similar to streptomycin sulfate 50 units/ml to the bacteriostasis of gram negative bacteria (bacillus subtilis, escherichia coli, vibrio cholera and typhoid fever, paratyphoid fever, dysentery bacterium etc.); The bacteriostasis of fungus is greater than to benzoic acid and the salicylic acid of 1 part.Anistree water extract is soluble in water, and the dissolubility in water is 18g/100ml.Be insoluble in chloroform, benzene and petroleum ether etc.
At present, on market, the existing antifungal drug as griseofulvin tablet, does not see the report by anistree water extract and griseofulvin coupling, griseofulvin tablet exist oral after can absorb incomplete from gastrointestinal absorption, the dissolution rate of medicine is slow, the shortcoming of bioavailability difference; Anistree water extract has well antibacterial and bactericidal effect, but it belongs to Chinese medicine, it is antibacterial and bactericidal action slow, and the present invention is by a large amount of experiments, by anistree water extract and griseofulvin coupling, obtain the composite antibacterial drugs containing anistree water extract and griseofulvin.
Summary of the invention
The object of the invention is to provide a kind of compound recipe griseofulvin antibacterials.
Based on above-mentioned purpose, this invention takes following technical scheme: compound recipe griseofulvin antibacterials, its effective ingredient is griseofulvin and anistree water extract.
The weight of described effective ingredient consists of: griseofulvin 1 ~ 20 part, anistree water extract 1 ~ 18 part.
Described pharmaceutical dosage form is nano-emulsion.
The weight of described nano-emulsion consists of: anistree water extract 1 ~ 18 part, 15 ~ 40 parts, surfactant, cosurfactant 1 ~ 18 part, griseofulvin 1 ~ 20 part, oil 1 ~ 20 part, distilled water 20 ~ 70 parts.
The weight of described nano-emulsion consists of: anistree water extract 1 ~ 12 part, 15 ~ 35 parts, surfactant, cosurfactant 1 ~ 12 part, griseofulvin 5 ~ 15 parts, oil 1 ~ 15 part, distilled water 25 ~ 65 parts.
The weight of described nano-emulsion consists of: anistree water extract 6.9 parts, 30 parts, surfactant, cosurfactant 5 parts, griseofulvin 6.2 parts, oil 13 parts, distilled water 35.1 parts.
Described surfactant is Cremophor RH 40 (RH-40), castor oil polyoxyethylene ether 40(EL-40), in Tween 80 and PLURONICS F87 any one or with the mixture of span80.
Described cosurfactant is selected from ethanol, 1,2-PD, Macrogol 200, Liquid Macrogol, PEG400 and glycerol.Cosurfactant is except hydrotropy effect, and cosurfactant mainly in order to the hydrophile-lipophile balance value (HLB) of adjustment form surface-active agent, makes oil water interfacial tension reduce further, increases profit and the rigidity of limitans.Cosurfactant is incorporated in interfacial film, and the film that radius of curvature can be promoted very little is formed, and expands the newborn district area of nano-emulsion.
Described grease separation is from soybean oil, cinnamic aldehyde, Ethyl formate, ethyl oleate, fatty glyceride, Oleum Ricini, Oleum Brassicae campestris, linoleic acid, ethyl n-butyrate., isopropyl myristate, ethyl acetate and oleic acid.
Described oil is linoleic acid.
Antibacterials of the present invention are prepared by following steps: 1) take griseofulvin, oil, surfactant and cosurfactant, anistree water extract and water by described weight ratio; 2) under room temperature condition, griseofulvin, oil, surfactant and cosurfactant are stirred and obtain oil-phase solution; 3) anistree water extract is dissolved in water, obtains aqueous phase solution; 4) aqueous phase solution is joined in oil-phase solution, stir and obtain described nano-emulsion.Its detailed process is: when the initial stage drips aqueous phase solution, system can become sticky thick, and along with the increase gradually of aqueous phase solution, system stickiness increases; When the amount of aqueous phase solution increases to a certain degree, system becomes oil-in-water type from Water-In-Oil, and its viscosity can turn suddenly rare, now for adding the critical point of aqueous phase solution during this nano-emulsion of preparation, now can continue to add aqueous phase solution, to obtain rarer nano-emulsion.When preparing aqueous phase solution, Rhizoma Coptidis extract dissolves by the water that also can first take a morsel, and adds remaining water again after being added system.
The nano-emulsion particle diameter that the present invention obtains is between 38.9 ~ 80.1nm, and mean diameter is 56.8nm, can be made into oral liquid directly oral, also can be encapsulated in capsule further or make lyophilized powder.
Nano-emulsion (nanoemulsion), also known as microemulsion (microemulsion), is by spontaneous transparent or semitransparent homodisperse systems formed such as water, oil, surfactant and cosurfactants.In general, nano-emulsion is divided into three types, i.e. oil-in-water type nano-emulsion (O/W), water-in-oil type nanoemulsion (W/O) and bicontinuous nano-emulsion (B.C).Nano-emulsion has the unrivaled advantage of other preparations many: 1. for isotropic transparency liquid, belongs to thermodynamically metastable fixed system, through pressure sterilizing or centrifugally can not make it layering; 2. technique is simple, and preparation process does not need special installation, can spontaneously be formed, and nano-emulsion particle diameter is generally 1 ~ 100nm; 3. viscosity is low, can reduce pain during injection; 4. there is slow release and targeting; 5. improve the dissolubility of medicine, reduce medicine enzymolysis in vivo, can be formed the protective effect of medicine and improve the absorption of gastrointestinal tract to medicine, improving the bioavailability of medicine.
Anistree water extract adopts steam distillation, comprise the following steps: get the fresh anistree branch and leaf of 100g or dry fruit (Fructus Anisi Stellati dried fruit adding distil water soaked overnight) in flask, extract with vapor distillation, till distillate is about 500mL, saltout with NaCl after placing cooling, separate grease, then use anhydrous Na
2sO
4be drying to obtain.
Anistree water extract and griseofulvin compound, both antibacterial abilities can be mutually promoted and be promoted, and make nano-emulsion and the bioavailability of medicine is improved.Specifically, technical scheme of the present invention has following advantage:
(1) preparation obtained is by oral administration: griseofulvin is insoluble in water, and human body is to the transhipment of this medicine and absorb extremely difficult.Be made into nano-emulsion preparation, drastically increase dissolubility and the permeability of griseofulvin, can through Lymphatic time oral, overcome first pass effect and molecule by barrier during gastrointestinal tract.
(2) griseofulvin and anistree water extract are organically combined, improve the antibacterial effect of medicine, improve the treatment ability of medicine, the antibacterial effect of preparation entirety is more stable, and effect is more direct.
(3) onset is rapid: engulfed by reticuloendothelial cell rapidly after administration, makes medicine rapid-onset, and maintains constant blood drug level and pharmacodynamics effect, improves the bioavailability of medicine, and drug effect is enhanced simultaneously, and the consumption of medicine and access times reduce.
(4) obtained nano-emulsion particle size distribution is narrower, and system is transparent, good stability, has lower surface tension, has good mobility, taking convenience.
(5) obtained nano-emulsion also can thin up further, thus obtains the nano-emulsion of variable concentrations medicament contg.
(6) the present invention adopt formula and method simple possible, be convenient to large-scale industrial production.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope photo of compound recipe griseofulvin antibacterials in embodiment 1;
Fig. 2 is the grain size distribution of compound recipe griseofulvin antibacterials in embodiment 1.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention will be further described.
embodiment 1
?compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 6.7 parts, 30 parts, surfactant (EL-40), cosurfactant (ethanol) 5 parts, griseofulvin 10.2 parts, oil (linoleic acid) 13 parts, distilled water 35.1 parts.
Its preparation method is as follows:
1) griseofulvin 10.2g, EL40 30g, ethanol 5g, anistree water extract 6.7g, linoleic acid 13g and water 35.1g is claimed;
2) under room temperature condition, griseofulvin, EL40, linoleic acid and ethanol are stirred and obtain oil-phase solution;
3) anistree water extract is dissolved in water, obtains aqueous phase solution;
4) aqueous phase solution is joined in oil-phase solution, stir and obtain nano-emulsion.
embodiment 2
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 5.3 parts, 25 parts, surfactant (EL-40), cosurfactant (1,2-PD) 15 parts, griseofulvin 9.1 parts, oil (ethyl acetate) 8 parts, distilled water 37.6 parts.
Its preparation method is with embodiment 1.
embodiment 3
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 6.4 parts, 25 parts, surfactant (RH-40), cosurfactant (glycerol) 13 parts, griseofulvin 7.6 parts, oil (isopropyl myristate) 10 parts, distilled water 38 parts.
Its preparation method is with embodiment 1.
embodiment 4
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 6.8 parts, 32 parts, surfactant (RH-40), cosurfactant (ethanol) 4 parts, griseofulvin 5.4 parts, oil (soybean oil) 11 parts, distilled water 40.8 parts.
Its preparation method is with embodiment 1.
embodiment 5
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 8.1 parts, 28 parts, surfactant (Tween 80), cosurfactant (glycerol) 4 parts, griseofulvin 5.3 parts, oil (Oleum Ricini) 15 parts, distilled water 39.6 parts.
Its preparation method is with embodiment 1.
embodiment 6
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 5.9 parts, 36 parts, surfactant (Tween 80), cosurfactant (PEG400) 4 parts, griseofulvin 7.4 parts, oil (Ethyl formate) 12 parts, distilled water 34.7 parts.
Its preparation method is with embodiment 1.
embodiment 7
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 18 parts, 40 parts, surfactant (Tween 80 20 parts, span80 20 parts), cosurfactant (PEG300) 1 part, griseofulvin 1 part, oil (oleic acid) 1 part, distilled water 39 parts.
Its preparation method is with embodiment 1.
embodiment 8
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 1 part, 15 parts, surfactant (PLURONICS F87), cosurfactant (PEG200 9 parts, PEG400 9 parts) 18 parts, griseofulvin 20 parts, oil (cinnamic aldehyde 10 parts, fatty glyceride 10 parts) 20 parts, distilled water 26 parts.
Its preparation method is with embodiment 1.
embodiment 9
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 12 parts, 35 parts, surfactant (PLURONICS F87 20 parts, span80 15 parts), cosurfactant (PEG200 0.8 part and PEG300 0.2 part) 1 part, griseofulvin 5 parts, oil (cinnamic aldehyde) 1 part, distilled water 46 parts.
Its preparation method is with embodiment 1.
embodiment 10
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 1 part, 15 parts, surfactant (Tween 80 9 parts, span80 6 parts), cosurfactant (glycerol) 12 parts, griseofulvin 15 parts, oil (ethyl oleate 10 parts, Oleum Brassicae campestris 5 parts) 15 parts, distilled water 42 parts.
Its preparation method is with embodiment 1.
embodiment 11
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 7 parts, 26 parts, surfactant (EL-40), cosurfactant (glycerol) 12 parts, griseofulvin 15 parts, oil (ethyl oleate 10 parts, oleic acid 5 parts) 15 parts, distilled water 25 parts.
Its preparation method is with embodiment 1.
embodiment 12
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 1 part, 15 parts, surfactant (EL-40), cosurfactant (glycerol) 1 part, griseofulvin 5 parts, oil (ethyl oleate 10 parts, soybean oil 3 parts) 13 parts, distilled water 65 parts.
Its preparation method is with embodiment 1.
embodiment 13
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 6 parts, 30 parts, surfactant (RH-40 24 parts, span80 6 parts), cosurfactant (glycerol) 12 parts, griseofulvin 6 parts, oil (linoleic acid) 25 parts, distilled water 20 parts.
Its preparation method is with embodiment 1.
embodiment 14
Compound recipe griseofulvin antibacterials, its weight consists of: anistree water extract 1 part, 15 parts, surfactant (Tween 80 9 parts, span80 6 parts), cosurfactant (ethanol) 1 part, griseofulvin 5 parts, oil (linoleic acid) 8 parts, distilled water 70 parts.
Its preparation method is with embodiment 1.
embodiment 15: test
15.1 granularmetric analyses
Observe the compound recipe griseofulvin antibacterials product of embodiment 1-14 under transmission electron microscope, find that drop is that class is spherical, good dispersion, without adhesion.Fig. 1 is the transmission electron microscope photo of embodiment 1 compound recipe griseofulvin antibacterials.Utilize Malvern Particle Size Analyzer to detect to the nano-emulsion of embodiment 1, as shown in Figure 2, as can be seen from the figure, emulsion particle diameter is distributed between 38.9 ~ 80.1nm testing result, and mean diameter is 56.8nm.
stability analysis
The compound recipe griseofulvin antibacterials product of Example 1-14 carries out high speed centrifugation test, photo-stability testing, temperature stability test etc. respectively, observe the stability of compound recipe griseofulvin antimicrobial nano breast of the present invention, be confirmed whether that the wild effects such as layering, muddiness or crystal precipitation occur.
high speed centrifugation is tested
Sample thief loads in centrifuge tube, with centrifugal 10 min of the rotating speed of 15000 r/min.Centrifugally rear sample to be observed, find each embodiment sample still can keep after centrifugation centrifugal before clear state, there is not the phenomenons such as layering, muddiness or crystal precipitation.
photo-stability testing
Getting each embodiment sample loads in water white vial, sealing, is positioned over 10d under normal lighting conditions, observes respectively at 1d, 2d, 4d, 6d, 8d, 10d sampling.Result shows, within the 10d observation period, each embodiment sample all keeps clear state, has no the wild effects such as layering, muddiness or crystal precipitation.
temperature stability test
Get each embodiment sample, each embodiment divides three parts, loads in water white vial, sealing.Each point of sample is positioned over respectively 4 DEG C, keeps sample in room temperature (25 DEG C) and 40 DEG C of environment and investigate 30d, observe every 5d sampling.Result shows, within the 30d observation period, the compound recipe griseofulvin antibacterials of embodiment 1-14 all keep clear under three kinds of temperature conditions, have no the wild effects such as layering, muddiness or crystal precipitation.
long-term stable experiment
Get each embodiment sample, each embodiment divides three parts, load sealing in Brown Glass Brown glass bottles and jars only, be placed in (25 ± 2) DEG C, relative humidity (60 ± 5) % condition lower 12 months, sample respectively at when 0,3,6,9 and 12 months, investigate character and the changes of contents of nano-emulsion, based on the expiration date of drug measuring method of regression analysis, calculate the effect duration of compound recipe griseofulvin antibacterials.Result of the test shows under long term test condition, and the outward appearance of compound recipe griseofulvin antibacterials keeps clear and bright, homogeneous always, has no the phenomenons such as layering, complexion changed, flocculation and breakdown of emulsion; Griseofulvin in system and anistree water extract content extend in time and reduce gradually, the equation of linear regression provided by its content-time changing curve, the effect duration calculating compound recipe griseofulvin antibacterials is 37.15 months (with time short person for standard).
toxicity test
With commercially available griseofulvin tablet for contrast agents, carry out acute toxicity test according to new drug nonphosphorylated neurofilament H method: repeated dose toxicity test, genetic toxicity test (comprising Ames test, Micronuclei In The Mouse Bone Marrow test, the test of In vitro culture mammalian cell chromosome mutation), reproductive toxicity test (General Reproductiv e Toxicity Assessment, sensitive period to teratogenic agent toxicity test, perinatal toxicity are tested), carcinogenic test, immunotoxicity test and Local irritation study, result of the test is as follows:
This product is to Mouse Acute Toxicity experiment conclusion: contrast with commercially available griseofulvin tablet, and compound recipe griseofulvin antibacterials do not occur measuring interior untoward reaction and death.
The Salmonella reversion test of product of the present invention, the result of the genetic toxicity test such as mouse inbred strain and testis chromosomal aberration test are feminine gender.
The result that rat 30d feeds product of the present invention shows: contrast with commercially available griseofulvin tablet, within experimental period, in the metering of compound recipe griseofulvin antibacterials, each test group of animals growth promoter is good, the indexs such as body weight, food ration, routine blood test, blood biochemistry, organ coefficient are all within normal range, and histopathologic examination is no abnormality seen also.
This product long term toxicity test conclusion: contrast with commercially available griseofulvin tablet, within experimental period, in the metering of compound recipe griseofulvin antibacterials, this medicine has no rat untoward reaction for three months at continuous gastric infusion, every Index for examination is all within normal range, and its main organs of pathologic finding and target organ are showed no the toxic pathological change that this guiding drug rises.
15.4
pharmacokinetic experiment
Pharmacokinetic experiment is carried out to the nano-emulsion obtained by embodiment 1.
Compound recipe griseofulvin antibacterials absorbed following oral administration of the present invention is promoted to 97%, be deposited in the keratin of skin, hair and fingernail after absorption, just can measure in keratodermatitis after oral a few hours, only fraction is distributed in body fluid and tissue, blood drug level peaking in 24 hours, T
1/2(half-life) about 30 hours is mainly the nor-griseofulvin of 6-at intrahepatic metabolism, discharges with urine, and ampoule is discharged with original shape less than 1% from urine, and non-absorbent part is discharged from feces with original shape.
Pharmacokinetic experiment is carried out to other embodiments, all have also been obtained similar result.
drug effect contrast experiment
The compound recipe griseofulvin antibacterials that Example 1 obtains are tested pig tinea corporis, carry out contrast test with the medicine be simply mixed to get of anistree water extract and griseofulvin simultaneously.
Pig tinea corporis experimental technique: the pig suffering from tinea corporis choosing 10 about 20 kilograms, be divided into two groups, often organize 10, be labeled as experimental group and matched group respectively, the compound recipe griseofulvin antibacterials that experimental group adopts embodiment 1 to obtain carry out wiping treatment, and the antibacterials that matched group adopts anistree water extract and griseofulvin to be simply mixed to get carry out wiping treatment, and application area should be greater than tinea corporis area, every day 2 times, after being used in conjunction three days, observe curative effect.The results are shown in Table shown in 1.Wherein anistree water extract with simple mixing of griseofulvin refer to anistree water extract 6.7 parts, griseofulvin 10.2 parts, distilled water 83.1 parts mix and get final product.
Table 1 pig tinea corporis contrast test
| ? | Anistree water extract simply mixes with griseofulvin (according to two medicine content in compound nanometer emulsion embodiment 1) | This compound recipe griseofulvin antibacterials (embodiment 1) |
| Pig tinea corporis cure rate | 71% | 88.4% |
As known from Table 1, adopt compound recipe griseofulvin antibacterials of the present invention to reach 88.4% to pig tinea corporis cure rate, and the antibacterials that anistree water extract and griseofulvin are simply mixed to get only reach 71% to pig tinea corporis cure rate.
Claims (10)
1. compound recipe griseofulvin antibacterials, its effective ingredient is griseofulvin and anistree water extract.
2. compound recipe griseofulvin antibacterials as claimed in claim 1, it is characterized in that, the weight of described effective ingredient consists of: griseofulvin 1 ~ 20 part, anistree water extract 1 ~ 18 part.
3. compound recipe griseofulvin antibacterials as claimed in claim 1 or 2, it is characterized in that, described pharmaceutical dosage form is oil-in-water type nano-emulsion.
4. compound recipe griseofulvin antibacterials as claimed in claim 3, it is characterized in that, the weight of described nano-emulsion consists of: anistree water extract 1 ~ 18 part, 15 ~ 40 parts, surfactant, cosurfactant 1 ~ 18 part, griseofulvin 1 ~ 20 part, oil 1 ~ 20 part, distilled water 20 ~ 70 parts.
5. compound recipe griseofulvin antibacterials as claimed in claim 4, it is characterized in that, the weight of described nano-emulsion consists of: anistree water extract 1 ~ 12 part, 15 ~ 35 parts, surfactant, cosurfactant 1 ~ 12 part, griseofulvin 5 ~ 15 parts, oil 1 ~ 15 part, distilled water 25 ~ 65 parts.
6. compound recipe griseofulvin antibacterials as claimed in claim 5, it is characterized in that, the weight of described nano-emulsion consists of: anistree water extract 6.9 parts, 30 parts, surfactant, cosurfactant 5 parts, griseofulvin 6.2 parts, oil 13 parts, distilled water 35.1 parts.
7. the compound recipe griseofulvin antibacterials as described in as arbitrary in claim 4-6, it is characterized in that, described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 and PLURONICS F87 any one or with the mixture of span80.
8. the compound recipe griseofulvin antibacterials as described in as arbitrary in claim 4-6, it is characterized in that, described cosurfactant is selected from ethanol, 1,2-PD, Macrogol 200, Liquid Macrogol, PEG400 and glycerol.
9. the compound recipe griseofulvin antibacterials as described in as arbitrary in claim 4-6, it is characterized in that, described grease separation is from soybean oil, cinnamic aldehyde, Ethyl formate, ethyl oleate, fatty glyceride, Oleum Ricini, Oleum Brassicae campestris, linoleic acid, ethyl n-butyrate., isopropyl myristate, ethyl acetate and oleic acid.
10. compound recipe griseofulvin antibacterials as claimed in claim 9, it is characterized in that, described oil is linoleic acid.
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| CN112970787A (en) * | 2021-02-25 | 2021-06-18 | 云南贝泰妮生物科技集团股份有限公司 | Anise fennel plant antiseptic and bacteriostatic composition and preparation process and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1261790A (en) * | 1997-07-29 | 2000-08-02 | 法玛西雅厄普约翰美国公司 | Self-emulsifying formulation for lipophilic compounds |
| CN103877065A (en) * | 2012-12-20 | 2014-06-25 | 中国科学院大连化学物理研究所 | Lipid carrier, indissolvable pharmaceutical composition and preparation method thereof |
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- 2014-10-21 CN CN201410561152.9A patent/CN104274532A/en active Pending
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|---|---|---|---|---|
| CN1261790A (en) * | 1997-07-29 | 2000-08-02 | 法玛西雅厄普约翰美国公司 | Self-emulsifying formulation for lipophilic compounds |
| CN103877065A (en) * | 2012-12-20 | 2014-06-25 | 中国科学院大连化学物理研究所 | Lipid carrier, indissolvable pharmaceutical composition and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112970787A (en) * | 2021-02-25 | 2021-06-18 | 云南贝泰妮生物科技集团股份有限公司 | Anise fennel plant antiseptic and bacteriostatic composition and preparation process and application thereof |
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