CN104324363A - Drug for treating cervical erosion and cervical cancer - Google Patents
Drug for treating cervical erosion and cervical cancer Download PDFInfo
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- CN104324363A CN104324363A CN201410514777.XA CN201410514777A CN104324363A CN 104324363 A CN104324363 A CN 104324363A CN 201410514777 A CN201410514777 A CN 201410514777A CN 104324363 A CN104324363 A CN 104324363A
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Abstract
A drug for treating cervical erosion and cervical cancer is characterized by being prepared from taxus chinensis extract and mannatide, wherein a weight percentage ratio of the taxus chinensis extract to the mannatide is 10:90-95:5. Effective components of the drug are composed of the taxus chinensis extract and the mannatide. The drug is a composition and can be prepared into following externally-use dosage forms: a suppository, a lotion, a gel and the like. The drug has effects of treating the cervical erosion and the cervical cancer and preventing precancerous lesions.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of cervical erosion and cervical cancer, prevention precancerous lesion.
Background technology
Cervical cancer is one of modal malignant tumor of gynecological, walks abreast with breast carcinoma.In world wide, annual cervical cancer new cases about 46.6 ten thousand example, wherein about has more than 20 ten thousand examples dead, is only second to breast carcinoma.In developing country, cervical cancer then belongs to common multiple gynecological tumor, the seniority among brothers and sisters umber one.For the treatment of cervical cancer, mainly operation and radiotherapy.The fast development of anti-cancer chemical medicine in recent years, thinks in the past and the chemotherapy invalid to cervical cancer has now become the common method of auxiliary treatment, especially late or recidivist.Now, commercially available main anti-cancer chemical medicine has: a class: cisplatin, carboplatin, paclitaxel; Two classes: 5-fluorouracil, ifosfamide, hycamtin, gemcitabine etc.
Cervical erosion is gynaecopathia common clinically, is more common in married woman, and active treatment cervical erosion is significant to prevention cervical cancer.The method for the treatment of cervical erosion common clinically mainly contains (1) topical medications: silver nitrate, compound recipe dichromic acid first solution, trichloroacetic acid, disinfection class medicine, interferon etc.; (2) physiotherapy: laser therapy, high-frequency electrical rubbing hot medicated compress, cold therapy; (3) operative therapy etc.Lack evident in efficacy, that patient adaptability is good medicine clinically.
Taxus taxaceae (Taxaceae) Taxus (Taxus.L) plant, comprises Taxus mairei [T.mairei var.mairei (Lemcc et Level) cheng et L.K.Fu] and Xizang Taxus chinensis (T.wallichiana Zucc), T. yunnanensis (T.yunnanensis Cheng et.L.K.Fu), Chinese Ramulus et folium taxi cuspidatae [T.chinensis(Pilger) Rehd.], Ramulus et folium taxi cuspidatae (T.cuspidata .Sieb.et.Zucc.) and Taxus media (T.media).Ramulus et folium taxi cuspidatae contains the characteristic of paclitaxel, has anticancer, stomach invigorating, blood sugar lowering, blood pressure lowering, antiinflammatory, the building body effect such as refrigerant.And the paclitaxel extracted in Chinese yew, be used to Therapeutic cancer.Taxus leaf be used as medicine can antiinflammatory, pain relieving, treatment scabies; Seed is used for the treatment of food stagnation, dyspepsia and ascariasis; Bark is used as medicine and treats diabetes etc.Inducing diuresis to remove edema, treatment nephropathy, diabetes, nephritis edema, dysuria, gonorrhea, the kidney warming is also had to stimulate the menstrual flow, treat the effects such as menoxenia, postnatal blood stasis, dysmenorrhea.
Summary of the invention
Object of the present invention, be to provide a kind of medicine with treatment cervical erosion and cervical cancer, this medicine is that effective ingredient forms by Ramulus et folium taxi cuspidatae Extract and mannatide, this pharmaceutical composition is prepared into the exterior-applied formulations such as suppository, lotion, gel, have treatment cervical erosion and cervical cancer, prevention precancerous lesion effect.
The technical scheme adopted is:
Treat a medicine for cervical erosion and cervical cancer, it is characterized in that by the percentage by weight of Ramulus et folium taxi cuspidatae Extract and mannatide be that 10%:90%-95%:5% makes.
Treat a medicine for cervical erosion and cervical cancer, it is characterized in that being made up of the percentage by weight 70%:30%-95%:5% of Ramulus et folium taxi cuspidatae Extract and mannatide.
Ramulus et folium taxi cuspidatae Extract of the present invention, is characterized in that the composition containing following percentage by weight: paclitaxel 0.5-10, Ramulus et folium taxi cuspidatae element IV 5-40, total lignans are 2-30, polysaccharide 20-30, total flavones 10-30.
Ramulus et folium taxi cuspidatae Extract of the present invention, it is characterized in that from the leaf, stem, branch, fruit, root etc. of Ramulus et folium taxi cuspidatae being that raw material extracts.
Wherein Ramulus et folium taxi cuspidatae Extract has antiinflammatory, anti-tumor function.
Mannatide is as the sensitizer of immunostimulant and Ramulus et folium taxi cuspidatae Extract.
A kind of medicine for the treatment of cervical erosion and cervical cancer of the present invention, is characterized in that being prepared into the exterior-applied formulations such as suppository, lotion, gel.
Medicine can be used for the treatment of cervical erosion and cervical cancer, and achieves extraordinary effect, and the clinical treatment for such disease provides a kind of new method.
accompanying drawing explanation
Fig. 1 is each hole medicine final concentration (for fluconazol) situation schematic diagram in micro-drug sensitive plate.
detailed description of the invention
Treat a medicine for cervical erosion and cervical cancer, it is characterized in that:
Take 5g extract, sweet polysaccharide peptide 0.5 dissolves and is scattered in 50mL gelatin distilled water (1:1), add glycerol heating evaporation in water-bath, fill with mould, cool the demoulding, to obtain final product;
The weight proportion of gelatin and distilled water is 1:1.
Ramulus et folium taxi cuspidatae Extract is: paclitaxel 5%, Ramulus et folium taxi cuspidatae element IV 22.3%, total lignans are 11.4%, polysaccharide 26%, total flavones 17%.
Observe the clinical efficacy that embodiment 1 treats cervical erosion: vaginal suppository is placed in cervical erosion, indwelling 4 ~ 6 hours, 2 ~ 3 times/week totally three weeks was 1 course for the treatment of.
Result
The therapeutic outcome of the routine cervical erosion of table 1. 282
Conclusion: after treatment, cure rate is high, rotten to the corn and have the erosive inflammation of cAMP content all to have therapeutical effect to intractable palace, and treat within latter 1 year, follow up a case by regular visits to without 1 example recurrence, show multi-resistance and there is good raising immunity of organisms, promote the reparation of wound tissue, the effect of the many-side such as the Growth and reproduction of inhibition tumor cell.
embodiment 2:
Ramulus et folium taxi cuspidatae Extract II: paclitaxel 6.5%, Ramulus et folium taxi cuspidatae element IV 21.7%, total lignans are 15.6%, polysaccharide 22.9%, total flavones 19.2%.Take 5g extract, sweet polysaccharide peptide 0.3g dissolves and is scattered in 30mL distilled water.
embodiment 3:
Ramulus et folium taxi cuspidatae Extract II: paclitaxel 6.5%, Ramulus et folium taxi cuspidatae element IV 21.7%, total lignans are 15.6%, polysaccharide 22.9%, total flavones 19.2%.Take 5g extract, sweet polysaccharide peptide 1g dissolves and is scattered in 30mL distilled water.
embodiment 4:
Ramulus et folium taxi cuspidatae Extract II: paclitaxel 6.5%, Ramulus et folium taxi cuspidatae element IV 21.7%, total lignans are 15.6%, polysaccharide 22.9%, total flavones 19.2%.Take 5g extract, sweet polysaccharide peptide 0.5g dissolves and is scattered in 30mL distilled water.
embodiment 5:
Ramulus et folium taxi cuspidatae Extract II: paclitaxel 6.5%, Ramulus et folium taxi cuspidatae element IV 21.7%, total lignans are 15.6%, polysaccharide 22.9%, total flavones 19.2%.Take 5g extract, sweet polysaccharide peptide 0.7g dissolves and is scattered in 30mL distilled water.
embodiment 2-5 antibacterial effect verification experimental verification
1. micro-dilution method detects embodiment 2-5 to the antibacterial effect of strain subject
According to American National clinical laboratory standardization committee (CLSI, former NCCL
s) micro-dilution method promulgated carries out medicament sensitivity test to candida mycoderma (M27-A scheme), filamentous fungi (M38-A2 scheme).
The preparation of trace drug sensitive plate:
Make diluent with RPMI1640 liquid and medicinal liquid to be measured is made 10 grades of doubling dilutions.According to trial test result, the final concentration all the time of medicine to be measured and control solvent (40% ethanol) is decided to be 4 times of diluted concentrations of stock solution, stops 2048 times of diluted concentrations that final concentration is stock solution, from the 1st hole to the 10th hole concentration sesquialter dilution from high to low; The initial final concentration of control drug fluconazol is 64 μ g/mL, and stopping final concentration is 0.125 μ g/mL; The initial final concentration of control drug itraconazole, ketoconazole is 16 μ g/mL, and stopping final concentration is 0.03125 μ g/mL; The initial final concentration of control drug cephamycin, streptomycin is 500 μ g/mL, and stopping final concentration is 0.98 μ g/mL.1 ~ 11 hole, every hole adds 100 μ l bacteria suspensions respectively, and every pore fungi suspension concentration is 3 × 10
4cFU/ml, the 12nd hole does not add.11st hole is as growth control hole, and the 12nd hole is as blank control wells.
The judgement of minimum inhibitory concentration (MIC)
Postvaccinal micro-drug sensitive plate is placed in 5min that micro oscillator vibrates, and after Homogeneous phase mixing, candida mycoderma and antibacterial culturing 24h, after filamentous fungi cultivates 72h, observe strain subject growing state, and read result.When not stirring compared with control wells, carry out result interpretation by following standard comparing: 0 is that naked eyes are clear; 1 is slightly fuzzy; 2 significantly lower (50% is suppressed) for turbidity; 3 slightly lower for turbidity; 4 do not lower for turbidity.Medicine to be measured gets 2 (turbidity significantly lowers) for MIC judgement terminal.All tests repeat through 3 times.
Quality-control strains monilia krusei repeats 3 times and carries out drug sensitive experiment, and the fluctuation range of result display MIC is no more than 1 drug concentration gradient, all in the Quality-control strains MIC critical field that the M27-A of CLSI announces (table 2).
The MIC(μ g/ml of table 2. Quality-control strains)
Micro-dilution method testing result shows, solvent has no significant effect antibacterial effect.4 kinds of medicines to be measured all have certain inhibit activities to various clinical common bacteria, fungal bacterial strain, and wherein the antibacterial activity of the antibacterial activity Medications Example more to be measured 2 of embodiment 3, embodiment 5, embodiment 4 is high.And medicine to be measured to the antibacterial effect of staphylococcus aureus, Candida glabrata, monilia krusei, trichophyton, alpha fungus and Sporothrix schenckii better (table 3).
(control drug MIC is μ g/ml to the minimum inhibitory concentration of table 3. 4 kinds of medicines to be measured; Medicine MIC to be measured is the extension rate of stock solution)
MIC | Fluconazol | Itraconazole | Ketoconazole | Cephamycin | Streptomycin | 40% ethanol | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
Staphylococcus aureus | - | - | - | <0.98 | 7.8 | >4 | 16 | 256 | 64 | 128 |
Escherichia coli | - | - | - | <0.98 | 15.6 | >4 | 8 | 8 | 8 | 8 |
Pseudomonas aeruginosa | - | - | - | 500 | 31.3 | >4 | 8 | 16 | 16 | 16 |
Salmonella typhi | - | - | - | <0.98 | 7.8 | >4 | 8 | 8 | 8 | 6 |
Shigella dysenteriae | - | - | - | <0.98 | 15.6 | >4 | 8 | 8 | 16 | 32 |
Candida albicans | 0.25 | <0.03125 | <0.03125 | - | - | >4 | 4 | 4 | 16 | 64 |
Candida tropicalis | 1 | <0.03125 | <0.03125 | - | - | >4 | >4 | 16 | 8 | 64 |
Candida glabrata | 16 | 2 | 1 | - | - | >4 | 64 | 128 | 32 | 256 |
Monilia krusei | 32 | 0.5 | 0.5 | - | - | >4 | 16 | 16 | 16 | 256 |
Candida parapsilosis | <0.125 | <0.03125 | <0.03125 | - | - | >4 | 4 | 4 | 16 | 128 |
Monilia guilliermondii | 2 | 0.25 | <0.03125 | - | - | >4 | 8 | 32 | 32 | 32 |
Aspergillus fumigatus | >64 | 0.125 | 4 | - | - | >4 | 4 | 8 | 8 | 32 |
Aspergillus flavus | >64 | 0.03125 | 1 | - | - | >4 | 4 | 8 | 4 | 16 |
Fusarium oxysporum | >64 | >16 | >16 | - | - | >4 | 8 | 8 | 8 | 8 |
Trichophyton | 1 | 0.03125 | <0.03125 | - | - | >4 | 64 | 128 | 128 | 128 |
Alpha fungus | 64 | 0.125 | 0.5 | - | - | >4 | 32 | 32 | 128 | 128 |
Sabouraudites lanosus | 64 | 0.125 | 0.5 | - | - | >4 | 32 | 64 | 64 | 64 |
Sporothrix schenckii | 64 | 0.125 | 0.125 | - | - | >4 | 128 | 64 | 64 | 128 |
2. agar diffusion method detects the fungistatic effect of medicine to be measured
collecting cells
Bacteria suspension is prepared with 0.9 % physiological saline solution (containing 0.5% Tween-80).With blood cell counting plate, bacteria suspension concentration is adjusted to 0.5 ~ 5 × 10
6cFU/ml.
the mensuration of medicine bacterial restrain to be measured
Dip bacteria suspension with sterile cotton swab, on tube wall, unnecessary bacterium liquid is removed in extruding.Be coated with whole PDA or LA slat chain conveyor primary surface with cotton swab, flat board rotated 60 degree, be coated with 3 times, most tailing edge flat board periphery is coated with one week.
By the sterilizing Oxford cup of good for labelling medicine name, be placed in culture medium, press gently, make it contact tight with culture medium, each flat board can put 3 ~ 4 Oxford cups.After several minutes, respectively to dripping quantitative medicinal liquid to be measured (50 μ L) in each cup, with the solvent of equivalent for negative control, with control drug (10 μ L) for positive control.Antibacterial and yeast are placed in 37 DEG C of incubators and cultivate 24 h, filamentous fungi is placed in 28 DEG C of incubators and cultivates 48 h, observed result.Test in triplicate.
Judge the antibacterial effect of medicine according to the size of bacterial restrain, bacterial restrain has no strain growth with naked eyes and is limited.Use vernier caliper measurement inhibition zone diameter, be accurate to millimeter.Inhibition zone diameter is larger, illustrates that medicine to be measured is better for the inhibition detecting bacterium, otherwise less.
evaluate regulation
(1) judgement of bacteriostatic activity:
Inhibition zone diameter is greater than 11mm person (medicine feeding hole diameter 10mm), has been judged to bacteriostatic activity.
Inhibition zone diameter is less than or equal to 11mm person (medicine feeding hole diameter 10mm), is judged to without bacteriostatic activity.
(2) negative control group should produce without bacterial restrain.Otherwise invalidate the test.
(3) size by comparing bacterial restrain evaluates various antibacterial effect
(4) 3 repeated trials, all have bacteriostatic activity by person, are judged to effectively.
result
Agar diffusion method testing result shows, solvent has no significant effect antibacterial effect.4 kinds of medicines to be measured all have certain inhibit activities to various clinical common bacteria, fungal bacterial strain.And medicine to be measured is to staphylococcus aureus, Shigella dysenteriae, Candida glabrata, monilia krusei, trichophyton, alpha fungus, Sabouraudites lanosus and Sporothrix schenckii effect better (table 4).
The antibacterial circle diameter (mm) of table 4. 4 kinds of medicines to be measured
Antibacterial circle diameter (mm) | Fluconazol | Itraconazole | Ketoconazole | Cephamycin | Streptomycin | 40% ethanol | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
Staphylococcus aureus | - | - | - | 19 | 34 | 0 | 8 | 19 | 9 | 11 |
Escherichia coli | - | - | - | 18 | 26 | 0 | 10 | 10 | 11 | 9 |
Pseudomonas aeruginosa | - | - | - | 27 | 20 | 0 | 8 | 11 | 9 | 8 |
Salmonella typhi | - | - | - | 30 | 23 | 0 | 10 | 9 | 11 | 10 |
Shigella dysenteriae | - | - | - | 18 | 36 | 0 | 20 | 10 | 9 | 14 |
Candida albicans | 15 | 10 | 19 | - | - | 0 | 11 | 13 | 14 | 0 |
Candida tropicalis | 0 | 0 | 20 | - | - | 0 | 10 | 11 | 15 | 0 |
Candida glabrata | 18 | 17 | 25 | - | - | 0 | 15 | 16 | 14 | 0 |
Monilia krusei | 17 | 11 | 23 | - | - | 0 | 11 | 16 | 11 | 11 |
Candida parapsilosis | 11 | 11 | 15 | - | - | 0 | 10 | 11 | 12 | 0 |
Monilia guilliermondii | 18 | 11 | 22 | - | - | 0 | 12 | 11 | 13 | 0 |
Aspergillus fumigatus | 0 | 11 | 18 | - | - | 0 | 8 | 9 | 13 | 8 |
Aspergillus flavus | 12 | 14 | 19 | - | - | 0 | 9 | 10 | 12 | 7 |
Fusarium oxysporum | 10 | 11 | 12 | - | - | 0 | 10 | 11 | 12 | 10 |
Trichophyton | 0 | 20 | 27 | - | - | 0 | 14 | 23 | 20 | 17 |
Alpha fungus | 0 | 16 | 29 | - | - | 0 | 6 | 18 | 6 | 7 |
Sabouraudites lanosus | 0 | 15 | 26 | - | - | 0 | 12 | 19 | 19 | 15 |
Sporothrix schenckii | 0 | 7 | 11 | - | - | 0 | 19 | 24 | 0 | 14 |
embodiment 6:
Ramulus et folium taxi cuspidatae Extract III: paclitaxel 6.5%, Ramulus et folium taxi cuspidatae element IV 21.7%, total lignans are 15.6%, polysaccharide 22.9%, total flavones 19.2%.Take 5g extract, sweet polysaccharide peptide 2.0g dissolves and is scattered in 30mL distilled water.
antitumor activity in vitro (MIT method):
Take the logarithm trophophase Hela cell with after 0.25% trypsin and 0.02%EDTA digestion, dilutes with culture fluid.In 96 well culture plates, every hole adds the DEME culture fluid of 200 μ L (containing 5 000/mL tumor cell) containing 10%FBS, and cell puts 37 DEG C, 10%CO
2after cultivating 24 h, experimental group 1 adds the degerming sample of dilute sample of embodiment 6 respectively, and concentration is 10,20,40,80, the culture fluid of 160 μ g/mL (by contained extract gauge), experimental group 2 adds Ramulus et folium taxi cuspidatae Extract III (not adding sweet polysaccharide peptide), and concentration is the same.Matched group then adds the culture fluid of equal-volume solvent, often organizes 4 holes, repeats 4 times.Put 37 DEG C, 10%CO
2after cultivating 5d, abandoning supernatant, adds the serum-free medium containing 0.2mg/mL M'IT of the 200 fresh configurations in μ l/ hole, and 37 DEG C are continued to cultivate 4h, abandon supernatant, add 200 μ l DMSO, after vibration mixing, microplate reader is 570 nm with wavelength, and reference wavelength is 450 am, measures OD value.
Growth of tumour cell suppression ratio=(1-experimental group three hole absorbance average/negative control group absorbance average) × 100%
With the variable concentrations of same sample to the mapping of growth of tumour cell suppression ratio, obtain half-inhibition concentration (IC with regression equation
50).
The external inhibiting tumor assay result of table 5 embodiment 6 sample
Have result in table known, embodiment 6 has the ability of obvious In Vitro Anti Hela Growth of Cells, has significant anti-tumor activity, and sweet polysaccharide peptide add the external tumor suppression ability significantly improving Ramulus et folium taxi cuspidatae Extract III.
Claims (7)
1. treat a medicine for cervical erosion and cervical cancer, it is characterized in that being prepared into by Ramulus et folium taxi cuspidatae Extract and mannatide, the percentage by weight of Ramulus et folium taxi cuspidatae Extract and mannatide is 10:90-95:5.
2. a kind of medicine for the treatment of cervical erosion and cervical cancer according to claim 1, is characterized in that the composition containing following percentage by weight: paclitaxel 0.5-10, Ramulus et folium taxi cuspidatae element IV 5-40, total lignans are 2-30, polysaccharide 20-30, total flavones 10-30.
3. a kind of medicine for the treatment of cervical erosion and cervical cancer according to claim 1, is characterized in that described Ramulus et folium taxi cuspidatae Extract, be from the leaf of Ramulus et folium taxi cuspidatae, stem, branch, fruit, root be that raw material extracts.
4. a kind of medicine for the treatment of cervical erosion and cervical cancer according to claim 1, is characterized in that being prepared into suppository, lotion, gel external type.
5. treat a medicine for cervical erosion and cervical cancer, it is characterized in that having the effect for the treatment of cervical erosion and cervical cancer, prevention precancerous lesion.
6. treat a medicine for cervical erosion and cervical cancer, it is characterized in that Ramulus et folium taxi cuspidatae Extract is as antiinflammatory, antitumor finite element.
7. treat a medicine for cervical erosion and cervical cancer, it is characterized in that the sensitizer of mannosazone as immunostimulant and Ramulus et folium taxi cuspidatae Extract.
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2011087343A2 (en) * | 2010-01-18 | 2011-07-21 | (주)이젠바이오텍 | Composition for treating cancer related to an hpv infection |
CN102178704A (en) * | 2011-04-15 | 2011-09-14 | 杨骅力 | Anti-inflammatory drug prepared from taxus chinensis essential oil and taxus chinensis extract |
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2014
- 2014-09-30 CN CN201410514777.XA patent/CN104324363A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011087343A2 (en) * | 2010-01-18 | 2011-07-21 | (주)이젠바이오텍 | Composition for treating cancer related to an hpv infection |
CN102178704A (en) * | 2011-04-15 | 2011-09-14 | 杨骅力 | Anti-inflammatory drug prepared from taxus chinensis essential oil and taxus chinensis extract |
Non-Patent Citations (2)
Title |
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程梅英: "甘露聚糖肽治疗宫颈糜烂260例临床观察", 《四川医学》 * |
黄少江等: "放疗结合瘤体局部注射甘露聚糖肽治疗宫颈癌的临床观察", 《中国医药导刊》 * |
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