CN105726552A - Application of paromomycin to preparation of medicine for treating trichomonas vaginitis - Google Patents
Application of paromomycin to preparation of medicine for treating trichomonas vaginitis Download PDFInfo
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- CN105726552A CN105726552A CN201610081869.2A CN201610081869A CN105726552A CN 105726552 A CN105726552 A CN 105726552A CN 201610081869 A CN201610081869 A CN 201610081869A CN 105726552 A CN105726552 A CN 105726552A
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- Prior art keywords
- paromomycin
- medicine
- trichomonal vaginitis
- infusorian
- application
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
Abstract
The invention provides novel application of paromomycin to preparation of medicine for treating trichomonas vaginitis.The application of paromomycin to preparation of medicine for treating trichomonas vaginitis is implemented by inhibiting trichomonas vaginalis.Compared with the prior art, the application of paromomycin to preparation of medicine for treating trichomonas vaginitis has the advantages that paromomycin of low concentration has a good killing action on trichomonas vaginitis, has an obvious effect on inhibition of trichomonas vaginitis and can be used for preparing medicine for treating trichomonas vaginitis so as to solve the problems of drug resistance and high side effect existing in an existing drug.
Description
Technical field
The invention belongs to medicinal chemistry art, be specifically related to paromomycin application in preparation treatment trichomonal vaginitis medicine.
Background technology
Trichomonal vaginitis (trichomonalvaginitis, TV) is per vaginam trichomonal inflammatory diseases of female genital tract, is one of modal sexually transmitted disease (STD).According to WHO, the whole world has 1.8 hundred million people to infect TV every year.TV infects in women except mainly causing vaginitis, also can cause cervicitis, urethritis, sterile etc..TV is also relevant to complication in many terms, causes premature rupture of fetal membrane, premature labor, low birthweight infant etc..TV infects can cause male's trichomonal vaginitis illness (including nongonococcal urethritis, prostatitis etc.).TV infection is also the risk factor of other sexually transmitted disease (STD).Recent study finds, TV infects the propagation increasing HIV (human immunodeficiency virus) (HIV), and trichomonal vaginitis has become very important sexually transmitted disease (STD).
Healthy women vagina is because of Effect of Lactobacillus, and pH value maintains between 3.8～4.4, can suppress other bacterial growths, is unfavorable for that infusorian grows, and is called the self purification of vagina.But infusorian consumes glycogen in vagina, hinder the zymohydrolysis of lactobacillus, affect lactic acid concn, so that vagina pH transfers neutrality or alkalescence to.Vagina physiological period after gestation and menstruation makes pH close to neutral, and these are all conducive to infusorian to breed, thus infect higher with relapse rate.The active drug treating now trichomonal vaginitis is metronidazole, and research finds, although metronidazole has the effect suppressing and killing infusorian, but also can produce drug resistance simultaneously, in addition fetus has the report of teratogenesis, and pregnancy women disables.It is therefore desirable to the medicine of the treatment trichomonal vaginitis of development of new.
Paromomycin is aminoglycoside antibiotics, and Grain-positive and negative bacteria, Shigella and S. aureus L-forms and ameba are all had relatively high inhibition effect, and leishmania, Cryptosporidium, filaricide etc. are also had good action.It is mainly used in treatment intestinal amebiasis, bacillary dysentery and bacillary intestinal infection, taeniasis etc. clinically.Paromomycin is oral not to be absorbed.Not yet there is bibliographical information paromomycin that trichomonal vaginitis is had inhibitory action at present.
Present invention firstly discovers that trichomonal vaginitis is had good inhibiting effect by paromomycin, it may be used for the medicine of preparation treatment trichomonal vaginitis.
Summary of the invention
In view of this, the invention is directed to the purposes of a kind of paromomycin, specifically for preparing the application in treatment trichomonal vaginitis medicine, to solve the drug resistance of existing medicine existence and the problem that side effect is big..
For reaching above-mentioned purpose, the technical scheme of the invention is achieved in that
The purposes of a kind of paromomycin, is that the structural formula of wherein said paromomycin is for preparing the application in treatment trichomonal vaginitis medicine:
Further, described paromomycin is realized by suppression trichomonal vaginitis for preparing the application in treatment trichomonal vaginitis medicine.
Further, the pharmaceutical pack of described treatment trichomonal vaginitis is containing paromomycin or paromomycin pharmaceutically acceptable salt, hydrate or their combination and adjuvant.
Further, described medicine is selected from suppository, gel, aerosol, tablet, capsule, pill, oral liquid, granule, powder, injection, syrup, medicated wine, tincture, distillate medicinal water, membrane or their combination.
Further, the administering mode of described treatment trichomonal vaginitis medicine includes external, spraying, suction, oral, injection, implantation or their combination.
Relative to prior art, the paromomycin described in the invention has the advantage that for preparing the application in treatment trichomonal vaginitis medicine
Namely trichomonal vaginitis is just had good killing action by paromomycin under low concentration, there is the effect significantly suppressing trichomonal vaginitis, may be used for the medicine of preparation treatment trichomonal vaginitis, to solve the drug resistance of existing medicine existence and the problem that side effect is big.
Accompanying drawing explanation
The accompanying drawing constituting the part of the invention is used for providing being further appreciated by the invention, and the schematic description and description of the invention is used for explaining the invention, is not intended that the improper restriction to the invention.In the accompanying drawings:
Fig. 1 illustrates the paromomycin inhibitory action dose-response curve (mtt assay detection) to trichomonal vaginitis；
Fig. 2 illustrates different time points paromomycin inhibitory action dosage-response curve (detection of trypan blue counting method) to trichomonal vaginitis.
Detailed description of the invention
Unless otherwise indicated, term used herein is respectively provided with the implication that those skilled in the art's routine is understood, and for the ease of understanding the present invention, terms more used herein has been carried out following definitions.
Using in the specification and in the claims, odd number type " " and " this " include plural reference, clearly state unless the context otherwise.Such as, term " (one) cell " includes the cell of plural number, including its mixture.
All of Digital ID, for instance pH, temperature, time, concentration, including scope, is all approximation.It is to be understood that, although all add term " about " before all of Digital ID of always not clear and definite narration.Simultaneously it will also be understood that, although always not clear and definite narration, reagent described herein is only example, and its equivalent is known in the art.
The invention is described in detail below in conjunction with embodiment and accompanying drawing.
Wherein, in embodiment, main experimental material used and source thereof include:
1. infusorian worm strain
Separation and Culture in the trichomonal vaginitis patient's secretions provided by General Hospital of Tianjin Medical Univ.'s OPD of Obs & Gyn.
2. experimental drug and reagent
Paromomycin: Powdered, effluent Nan Fu core pharmaceutcal corporation, Ltd provides.
Tetramethyl azo azoles salt (MTT): Shanghai Sheng Gong biological engineering company limited, article No.: TB0799-1g, lot number: XP1008B3012J, rank: analytical pure, specification 1g.
Dimethyl sulfoxide (DMSO): Shanghai Sheng Gong biological engineering company limited, article No.: DN3039A, lot number: SJ0731S4013J, rank: analytical pure, specification 500mL, dissolves purple crystal for mtt assay.
NaCl: Yong Ye bio tech ltd, Shanghai, article No.: 100376
Peptone: OXOID, article No.: LP0042, lot number: 1462108
Cysteine hydrochloride: Amresco company, article No.: E305, lot number: 1484C287
Maltose: Amresco company, article No.: 1B1184, lot number: 6423C208
3. key instrument
Biohazard Safety Equipment: Thailand of Spain thing reaches (Telstar), model: BioIIA.
CO2Incubator: Shi Doukai instrument and equipment (Shanghai) Co., Ltd., model: STIKIL-161HI.
Inverted phase contrast microscope: producer: Olympus, model: CKX41.
Electronic balance: Shanghai Ao Haosi Instrument Ltd., model: AR2202CN；
4 DEG C of refrigerators: Qingdao HaiEr Co., Ltd, model: BCD-192KJ；
4. the compound method of agents useful for same includes:
Hepar-peptone-glucose medium: Hepar Sus domestica 15g is cut into small pieces, is put in the mid-4 DEG C of refrigerator overnight of distilled water, next day heated and boiled 1h, cross leaching filtrate, during less than 100ml, supply with distilled water, every 100ml filtrate is separately added into NaCl0.5g, peptone 2g, cysteine hydrochloride 0.2g, maltose 1g, heating for dissolving, adjust pH value to 5.6, autoclaving, it is put in 4 DEG C of Refrigerator stores standby.Add aseptic inactivated serum 20%, antibiotic 500U/ml before use.
Tetramethyl azo azoles salt (MTT) liquid storage: take MTT powder 1.0g, is dissolved in 200ml phosphate buffer (PBS), final concentration of 5mg/ml, and with 0.22 μm of membrane filtration to remove the antibacterial in solution, subpackage ,-20 DEG C keep in Dark Place.Wherein, solution preparation and use all should operate in sterile biological safety cabinet.
Describe the present invention below with reference to the accompanying drawings and in conjunction with the embodiments in detail.
Experimental example 1 utilizes mtt assay to measure the paromomycin inhibitory action to trichomonal vaginitis
1. experimental technique:
(1) cultivation of trichomonal vaginitis
Being rinsed in the culture dish added with culture medium several times by cotton swab with infusorian, added with antibiotic makes antibiotic final concentration of 1000U/ml, is placed on CO2Incubator is cultivated.Once, 800rpm/min is centrifuged 5 minutes two days transferred speciess；Abandon supernatant, add 1-2mL culture medium suspension infusorian, infusorian is passed in 2 culture dishs equipped with appropriate culture medium, continue to cultivate antibiotic amount and gradually decrease, until final not added with antibiotic.
(2) inhibitory action that infusorian is grown by paromomycin is measured
Infusorian is inoculated on 96 well culture plates, every hole 100 μ L infusorian cell suspension, 5000/hole of infusorian.Above-mentioned 96 well culture plates are placed in 37 DEG C, and in carbon dioxide (5%) incubator, incubated overnight is after 24 hours, and test group is separately added into the culture fluid of the paromomycin containing variable concentrations, and arranges the control wells being not added with medicine.Often group sets 3 parallel holes, then 96 orifice plates is placed in 37 DEG C, cultivates 48 hours in carbon dioxide (5%) incubator.
After 48 hours, every hole adds 50 μ LMTT (tetrazolium bromide) (concentration is 5mg/mL), continues to hatch 4h.Then the culture fluid in hole is transferred in 1.5mLEP pipe together with polypide, 1000r, centrifugal 5min, supernatant discarded, each EP pipe adds 150 μ LDMSO, mixing, measure the absorbance in each hole under 570nm by microplate reader.
(3) data analysis
Calculate survival rate and the suppression ratio of cell, and calculate the medicine half-inhibition concentration (IC50) to cell.Survival rate %=experimental group OD value/feminine gender model group OD value × 100%；Suppression ratio %=(1-survival rate) × 100%.
2. experimental result:
As it is shown in figure 1, be the paromomycin inhibitory action curve to trichomonal vaginitis, can draw from figure, paromomycin presents the effect suppressing infusorian when low concentration, increase along with paromomycin concentration, it is suppressed that effect strengthens, it is suppressed that effect and drug level are proportionate.Carry out the calculating of IC50 value with GraphpadPrism5 software, measurement result is IC50=22.34 μ g/ml (R2=91.38), it was shown that under low concentration, trichomonal vaginitis is just had good killing action by paromomycin.
Experimental example 2 Trypan Blue counting method measures the different time points paromomycin inhibitory action to infusorian
1. experimental technique:
(1) cultivation of trichomonal vaginitis
Being rinsed in the culture dish added with culture medium several times by cotton swab with infusorian, added with antibiotic makes antibiotic final concentration of 1000U/ml.It is placed on CO2Incubator is cultivated.Once, 800rpm/min is centrifuged 5 minutes two days transferred speciess；Abandon supernatant, add 1-2mL culture medium suspension infusorian, infusorian is passed in 2 culture dishs equipped with appropriate culture medium, continue to cultivate antibiotic amount and gradually decrease, until final not added with antibiotic.
(2) Trypan Blue counting
Spread 24 orifice plates.Infusorian is inoculated on 24 well culture plates, every hole 500 μ L cell suspension, 100000/hole.Test group is separately added into the culture medium of the paromomycin containing variable concentrations, and blank group adds the culture medium of equal volume.Respectively at 0h, 2h, 4h, 8h, 16h, during 24h, Trypan Blue counts, and by the number of blood counting chamber counting infusorian alive with dead infusorian, dyes the infusorian for death of blueness, do not dye the transparent for the infusorian that lives of blueness, be calculated as motility rate %=and live infusorian number/(infusorian number+death infusorian number of living) × 100%.
(3) data analysis
It is calculated with GraphpadPrism5 software.
2. experimental result:
Recording the paromomycin effect to trichomonal vaginitis for counting method as shown in table 1, Fig. 2 show paromomycin concentration-Survival curves to trichomonal vaginitis.
Table 1 paromomycin extracorporeal corrosioning vagina wool trichomonad effect different action time
Experimental data shows in the identical time along with the increase of drug level, and the killing action of infusorian is strengthened by paromomycin；Same drug level, increase over time, the killing action of infusorian is strengthened (wherein by paromomycin, IC50 in table 1 is half-inhibition concentration, because during effect 2h, the more weak infusorian of inhibitory action of infusorian is not above the death of half and cannot calculate IC50 by paromomycin, therefore omits, along with the inhibitory action of infusorian is strengthened by the paromomycin that extends of action time, infusorian mortality rate increases, and IC50 value reduces).
The foregoing is only the preferred embodiment of the invention; not in order to limit the invention; within all spirit in the invention and principle, any amendment of making, equivalent replacement, improvement etc., should be included within the protection domain of the invention.
Claims (5)
1. the purposes of paromomycin, it is characterised in that be for preparing the application in treatment trichomonal vaginitis medicine.
2. the purposes of paromomycin according to claim 1, it is characterised in that: described paromomycin is realized by suppression trichomonal vaginitis for preparing the application in treatment trichomonal vaginitis medicine.
3. the purposes of paromomycin according to claim 1 and 2, it is characterised in that: the pharmaceutical pack of described treatment trichomonal vaginitis is containing paromomycin or paromomycin pharmaceutically acceptable salt, hydrate or their combination and adjuvant.
4. the purposes of paromomycin according to claim 3, it is characterized in that: described medicine is selected from suppository, gel, aerosol, tablet, capsule, pill, oral liquid, granule, powder, injection, syrup, medicated wine, tincture, distillate medicinal water, membrane or their combination.
5. the purposes of paromomycin according to claim 3, it is characterised in that: the administering mode of described treatment trichomonal vaginitis medicine includes external, spraying, suction, oral, injection, implantation or their combination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610081869.2A CN105726552A (en) | 2016-02-05 | 2016-02-05 | Application of paromomycin to preparation of medicine for treating trichomonas vaginitis |
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| CN201610081869.2A CN105726552A (en) | 2016-02-05 | 2016-02-05 | Application of paromomycin to preparation of medicine for treating trichomonas vaginitis |
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| CN201610081869.2A Pending CN105726552A (en) | 2016-02-05 | 2016-02-05 | Application of paromomycin to preparation of medicine for treating trichomonas vaginitis |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309459A (en) * | 2016-08-18 | 2017-01-11 | 天承南运(天津)科技有限公司 | Application of paromomycin sulfate in preparation of neutrophil inhibitor |
| WO2020006392A1 (en) * | 2018-06-28 | 2020-01-02 | Chemistryrx | Compositions and methods for treating trichomonas |
-
2016
- 2016-02-05 CN CN201610081869.2A patent/CN105726552A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| MARIAA.KEATING ETAL: "Trichomonas vaginalis Infection in a Tertiary Care Vaginitis Center", 《SEXUALLY TRANSMITTED DISEASES》 * |
| S C TAYAL ETAL: "Paromomycin treatment of recalcitrant Trichomonas vaginalis", 《INTERNATIONAL JOURNAL OF STD & AIDS》 * |
| 岳洋等: "4种常见阴道炎诊断及治疗的研究进展", 《包头医学院学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309459A (en) * | 2016-08-18 | 2017-01-11 | 天承南运(天津)科技有限公司 | Application of paromomycin sulfate in preparation of neutrophil inhibitor |
| WO2020006392A1 (en) * | 2018-06-28 | 2020-01-02 | Chemistryrx | Compositions and methods for treating trichomonas |
| US11471473B2 (en) * | 2018-06-28 | 2022-10-18 | Chemistry Rx | Compositions and methods for treating trichomonas |
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Application publication date: 20160706 |
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