CN107412241A - A kind of Syringin pharmaceutical composition and its application in cervicitis is treated - Google Patents
A kind of Syringin pharmaceutical composition and its application in cervicitis is treated Download PDFInfo
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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
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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
- A61K31/11—Aldehydes
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Abstract
The present invention relates to a kind of Syringin pharmaceutical composition and its application in cervicitis is treated.Syringin pharmaceutical composition of the present invention, it is characterised in that in parts by weight, the pharmaceutical composition contains 13 parts of Syringin, 0.5 1.5 parts of cinnaldehydrum.Pharmaceutical composition of the present invention is better than the therapeutic effect of one-component Syringin or cinnaldehydrum to cervicitis to the therapeutic effect of rat cervicitis.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of Syringin pharmaceutical composition and its in cervicitis is treated
Using.
Background technology
Syringin (Syringin) belongs to phenylpropanoids, and there is hemostasis, anti-inflammatory, analgesia, enhancing to be immunized, protect
The pharmacological action such as liver, antidepression, antitumor, it is usually used in hemostasis and anti-liver poison.Cinnaldehydrum is Chinese tradition Chinese medicine material cassia twig
Or the main component of Cortex Cinnamomi volatile oil, be olefine aldehydr class organic compound, have anti-inflammatory, antipyretic-antalgic, antitumor, antibacterial, hypoglycemic,
The multiple pharmacological effects such as anti-fat and neuroprotection.However, at present national Bureau of Drugs Supervision do not ratify it is any based on Syringin
Want the new drug of raw material.
Cervicitis is one of gynaecology's common disease, and its lesion includes cervix, colpitis and canal of uterine cervix mucosal inflammation.
The present invention provides a kind of Syringin pharmaceutical composition for being used to treat cervicitis.
The content of the invention
The present invention provides a kind of pharmaceutical composition, it is characterised in that in parts by weight, the pharmaceutical composition contains purple fourth
Fragrant glycosides 1-3 parts, cinnaldehydrum 0.5-1.5 parts.The pharmaceutical composition also optionally includes pharmaceutically acceptable auxiliary material (such as injection
Water, pharmaceutical carrier, surfactant, diluent, excipient, antioxidant, stabilizer, solubilizer etc.).
Another optimal technical scheme of the present invention provides aforementioned pharmaceutical compositions, it is characterised in that Syringin and cinnaldehydrum
Mass ratio be 2:1-4:1.
Another technical scheme of the present invention provides aforementioned pharmaceutical compositions, it is characterised in that the formulation of described pharmaceutical composition
For solid pharmaceutical preparation, liquid preparation or semisolid preparation.
Another technical scheme of the present invention provides aforementioned pharmaceutical compositions, it is characterised in that the formulation of described pharmaceutical composition
For slow-release controlled-release and enteric capsulation, tablet, supensoid agent, microemulsion, sub-micellar emulsion or injection.
Another technical scheme of the present invention provides aforementioned pharmaceutical compositions and is treating and/or preventing gynaecological imflammation, especially
Application in cervicitis, vaginitis.
Another technical scheme of the present invention provides aforementioned pharmaceutical compositions and is preparing treatment and/or prevention gynaecological imflammation medicine
In application, especially preparing treatment and/or prevention cervicitis, the application in colpitis medicine.
Syringin in aforementioned pharmaceutical compositions of the present invention includes Syringin and pharmaceutically acceptable lilac
Glycosides salt;Cinnaldehydrum includes cinnaldehydrum and pharmaceutically acceptable cinnaldehydrum salt.
The various formulations that pharmaceutical composition of the present invention is related to can according to pharmaceutical field technical specification and require (such as pharmacopeia,
Textbook or other methods of the prior art, also can be according to number of patent application:Similar side described in 201710594462.4
Method) be prepared into respectively the preparation for meeting clinical treatment and anti-treating cervicitis demand and its suitable all size and formulation (including
Solid pharmaceutical preparation, liquid preparation and semisolid preparation) such as slow-release controlled-release and enteric capsulation, tablet, supensoid agent, microemulsion, sub-micro
Emulsion contains the same single and various injections of multicomponent associativity.
The preparation method for the formulation that pharmaceutical composition of the present invention is related to, belong to the conventional preparation method of art of pharmacy,
It is that those skilled in the art are real according to prior art (such as other technologies specification of pharmacopeia, textbook and pharmaceutical field) can
Now prepare, the present invention repeats no more to the customary preparation methods of above-mentioned formulation.
Compared with prior art, the advantage of the invention is that:(1) pharmaceutical composition provided by the invention is to rat cervicitis
Therapeutic effect of the therapeutic effect better than one-component Syringin or cinnaldehydrum to cervicitis, while the present invention provides specific ratio
Therapeutic effect of the pharmaceutical composition of Syringin (1-3 parts) and cinnaldehydrum (0.5-1.5 parts) composition of example to rat cervicitis
Better than composition (such as the Syringin of other ratios:Cinnaldehydrum=1:2 pharmaceutical composition);(2) present invention is by purple
Appropriate cinnaldehydrum is added in syringin, significantly enhances treatment effect of the Syringin pharmaceutical composition to cervicitis, vaginitis
Fruit.
Embodiment
For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But
It is that these embodiments only are not used for limiting the scope of the present invention or implementation principle, reality of the invention for being better understood from inventing
The mode of applying is not limited to herein below.
Embodiment 1
Bulk drug:1 part of Syringin, 0.5 part of cinnaldehydrum
By above-mentioned parts by weight, Syringin 10g, cinnaldehydrum 5g are taken, (preferably carboxymethyl is fine with appropriate conventional pharmaceutical adjuvants
Tie up plain sodium, magnesium stearate), mix, tablet is made according to common process.
Embodiment 2
Bulk drug:1 part of Syringin, 1.5 parts of cinnaldehydrum
By above-mentioned parts by weight, Syringin 10g, cinnaldehydrum 15g are taken, (preferably 1% tells with appropriate conventional pharmaceutical adjuvants
Temperature -80, polyethylene glycol 400), mix, after adding suitable quantity of water to make fully dissolving, filtration is degerming, dispenses, and freeze-drying, produces injection
Use aseptic powdery.
Embodiment 3
Bulk drug:3 parts of Syringin, 0.5 part of cinnaldehydrum
By above-mentioned parts by weight, Syringin 30g is taken, cinnaldehydrum 5g, is added together with appropriate emulsifying agent in oil, stirring makes
It dissolves, as oil phase;Stabilizer, osmotic pressure regulator and antioxidant are added to the water, stirring makes its dissolving, as water
Phase;Oil phase is added in aqueous phase, high speed shear is disperseed, and forms colostrum;Colostrum adjusts pH to 6.0-7.5, high-pressure homogenising, obtains smart breast,
Produce sub-micellar emulsion.
Embodiment 4
Bulk drug:2 parts of Syringin, 0.5 part of cinnaldehydrum
By above-mentioned parts by weight, Syringin 20g, cinnaldehydrum 5g are taken, allows addition with the industry regulation in major auxiliary burden
After solubilizer (such as Tween-80) mixing measured below plus suitable quantity of water make fully dissolving, emulsifying agent and positive silicic acid second are sequentially added
Ester, it is thoroughly mixed and is formed uniformly mixed solution A, solution A is then added into reaction unit (equipped with magnetic stirrer, temperature
Meter, condensation reflux unit and dropping funel), (500 revs/min) stirrings at a high speed are sheared 10 minutes, and the colostrum for forming clear oil exists
Under room temperature condition (25 DEG C), gelatin solution is progressively added dropwise into reaction unit, main effect component and forms O/W types under stirring
Droplet, it is wrapped in inside emulsifying agent micella, reacts 2h, calcium chloride solution is added dropwise after tetraethyl orthosilicate is fully hydrolyzed, through breast
Active ingredient Nano capsule is formed after agent micellar surface reaction precipitation, parcel, solidification, obtaining active ingredient after reaction completely is
Capsule-core, the Nano capsule that calcium silicates is cyst wall, the amount of tetraethyl orthosilicate and calcium chloride is added by adjusting, prepares different core wall ratios
Active ingredient Nano capsule sustained release preparation, produce.
Embodiment 5
Bulk drug:1 part of Syringin, 2 parts of cinnaldehydrum
By above-mentioned parts by weight, Syringin 10g, cinnaldehydrum 20g are taken, tablet is made according to the method for embodiment 1.
Embodiment 6
Bulk drug:Syringin
Syringin 10g is taken, tablet is made according to the method for embodiment 1.
Embodiment 7
Bulk drug:Cinnaldehydrum
Cinnaldehydrum 5g is taken, tablet is made according to the method for embodiment 1.
Embodiment 8
Experiment material
1st, animal and bacterium strain, cell line:SD rats, SPF levels, female, body weight 180-220g, purchased from The Fourth Military Medical University
Experimental Animal Center, quality certification number are SYXK (Shan) 2012-001.HPV16 transfection cell strains, ARPE-19/HPV-16 cells are beautiful
ATCC poison DSMZ of state presents, lot number CRL-2502;African green monkey kidney cell (Vero) draws strain from Beijing consonance medical science
Basis institute of institute cell centre;Virus, herpes simplex virus type 2 (HSV-2) draw strain from Chinese Academy of Medical Sciences's biology and technology
Research institute, tissue culture infective dose (TCID50) it is 1 × 10-5.5, -80 DEG C of refrigerators preservations.Bacterial strain, golden yellow grape
Coccus 26003,331,360,361 plants;26101 plants of staphylococcus albus;MRSE type strain, 104,108 plants;Large intestine
Angstrom uncommon bacterium 44113,23,117,178 plants;Pseudomonas aeruginosa 10102,209,210,211 plants;10,12 plants of beta streptococcus;Deformed rod
Bacterium type strain;Gonococcus type strain;Candida albicans type strain is purchased from National Institute for Food and Drugs Control's strain room.
2nd, medicine and reagent:Syringin, 500 grams, lot number 20171227-2, HLPC purity 98.3%, cinnaldehydrum 500
Gram, HLPC purity>98%;Prepared by Medicine Research Academy of medicine holding group of Shaanxi Province.Policresulen bolt (cucurbit island country Supreme Being's medicine
Industry Co., Ltd, lot number 160901.40), acyclovir slice (Ou Yi Shi Pharmaceutical Group Pharmaceutical Co, lot number
270130812) 10g/L mother liquors, are made into high purity water before in vitro test, it is standby after filtration sterilization;Ezup pillars viral DNA extracts
Kit (Sheng Gong bioengineering limited company, lot number 17043471Y), SYBR Premix Ex Taq kits (Japan
TaKaRa companies, lot number AK3101), HPV16 enzyme linked immunological kits (Bioisystech Co., Ltd of upper ingression section, lot number
201606), DMEM/F12 culture mediums (Gibco companies of the U.S., lot number 1720768), nutrient broth (NB, the extensive and profound in meaning biological skill in Beijing
Art Co., Ltd, lot number 20170905).
3rd, laboratory apparatus:Piko Real96 types quantitative real time PCR Instrument (Thermo companies of the U.S.), Enspire types are multi-functional
ELIASA (PerkinElmer), IX71 types inverted phase contrast microscope (Japanese Olympus companies), 731 type CO2Incubator and
MSC1.8 types Biohazard Safety Equipment (is purchased from Thermo companies of the U.S.).
4th, primer sequence:HPV16 E6 gene primers, upstream 5'-TCAAAAGCCACTGTGTCC-3', downstream 5'-
TTACAGCTGGGTTTCTCT-3', the primer of people's GAPDH genes, upstream 5'-CTCCTCCACCTTTGCGACTG-3', downstream
5'-TCCTCTTGTGCTCTTGCTGG-3', the prosperous bio tech ltd's synthesis of Beijing AudioCodes.
Experimental method
1st, inhibitory action of the Syringin to HSV-2:Take the culture plate inoculation 100TCID for growing up to cell monolayer50Virus
Liquid, 100 μ l/ holes, puts 37 DEG C of -5%CO2After being adsorbed 1 hour in incubator, the Syringin of gradient dilution is separately added into, it is conventional
If normal cell group, viral group and positive drug group;It is continuous to cultivate, cytopathy situation is observed under daily inverted microscope, works as virus
Log when group cytopathy is 4 grades (IV).Cytopathy is judged by 6 grades of standards:"-", cell growth is normal, disease-free
Become and occur;" ± ", cytopathy are less than the 10% of whole individual layer;" I ", cytopathy account for the 25% of whole cell monolayer with
Under;" II ", cytopathy account for less than the 50% of whole cell monolayer;" III ", cytopathy account for whole cell monolayer
Less than 75%;" IV ", cytopathy account for more than the 75% of whole cell monolayer.50%, which is calculated, by Reed-Muench suppresses dense
Spend (IC50) and therapeutic index (TI) be TI=TC50/IC50。
2nd, inhibitory action of the Syringin to HPV16 E6 gene expressions:ARPE-19/HPV-16 cells are inoculated in culture
In bottle, cell length is treated to 80%, adds the Syringin of gradient dilution, 37 DEG C of -5%CO2Culture 48 hours, is extracted using DNA
Kit extracts DNA.PCR reacts:95 DEG C -30 seconds;95 DEG C -5 seconds, 59 DEG C -30 seconds, totally 55 circulation;Solubility curve is analyzed.Make
The C of sample is respectively detected with sequence detection system software analysis PCR processestValue.Using Δ Δ CtMethod calculates
The relative expression quantity of HPV16 viruses.
3rd, the vitro antibacterial activity of Syringin:Nutrient broth will be added in 96 well culture plates, medicine hole adds isometric
Decoction, set 7 dilution factors altogether, separately set bacterium group.By the bacterium solution of 37 DEG C of cultures 18 hours, every milliliter is diluted to nutrient broth
Containing 1 × 105Individual bacterium, each μ L of bacterium solution 10 are added in every hole, culture plate is put into 37 DEG C of incubators and cultivated 24 hours, with turbidity
Bacterial growth is whether there is for each hole of index checking, not show turbidity, the decoction dilution factor in that hole of the bacterium without growth is as most
Low Mlc (MIC).
4th, effect of the pharmaceutical composition (embodiment 1-7 bulk drugs) of the present invention to rat cervicitis:Experiment is divided into HPV16 senses
Dye, bacteria mixed infection (EHEC, gonococcus and staphylococcus aureus), chemical substance infect 3 batches of experiments.Every batch of examination
Test and take female rats 100, be randomly divided into normal group, model group, Policresulen bolt group and embodiment 1-7 bulk drug groups, often
Group 10.In addition to normal group, density 1 × 10 is used in 3 batches of experiments respectively6Individual/mL HPV16 cell liquid, density 6 × 106Individual/mL's
Mixed bacteria liquid or 25% Hydroxybenzene mucilage, inject at rat uterine neck, 0.2ml/ is only.First scraped 3 times with syringe needle before injection, cause son
Palace surface damage.Injected 1 time every 2 days, totally 3 times, cause infection model;Normal group under equal conditions injects distilled water.Make
Mould starts Policresulen bolt intravaginal administration after 24 hours (capacity is 50 μ l/kg);Embodiment 1-7 bulk drugs gavage (ig, is held
Product is 5ml/kg), one time a day, continuous 12 days, normal group and model group under equal conditions gave matrix.The 2nd day after last dose
Animal is dissected, wins uterine neck and vagina.HPV infection model takes a part of uterine neck measure HPV16 expression (absorbance A expression).Palace
Neck visually observes criterion:"-", rat vagina, uterine neck are normal without swelling, no hyperemia, color;"+", rat vagina, uterine neck
There is a mild hyperaemia, swelling unobvious, color is normal;" II ", rat vagina, uterine neck have hemostasis, uterine neck swelling;" III ", rat are cloudy
Road lesion is light, but uterine neck has an obvious hemostasis, color mulberry, and uterine neck has an obvious tumefaction, and outward appearance uterine neck is thicker.Vagina visually observes
Judge mark:"-", rat vagina epithelium angling is normal, has no hyperplasia, has no retrogression, and structure is normal;"+", on rat vagina
Cornu cutaneum hyperplasia unobvious, it is upper subcutaneously to have no inflammation;" II ", rat vagina epithelium have slight hyperplasia, subcutaneously there is mild inflammation;
" III ", rat vagina epithelial proliferation is obvious, and has cell division, there is retrogression.Observation is outer daily for chemical substance infection model
Yin disease becomes, and the 13rd day anatomic observation vagina, the cervical lesionses situation after administration.Vulvar disease grade criterion:"-", it is cloudy
Road, cervical mucosal are in pink colour, without congested swelling, secretion without exception;"+", the slight congested, swelling of vagina, cervical mucosal are failed to understand
Aobvious, secretion without exception;" II ", vagina, cervical mucosal hyperemia swelling is obvious, has certain secretion;" III ", vagina, uterine neck
Mucous membrane hyperemia swelling is obvious, abnormal secretion, is dispersed in blutpunkte or small point-like is rotten to the corn." IV ", vagina, cervical mucosal hyperemia are bright
Show, fester or have purulent secretion, ponding.
Experimental result
1st, Syringin antiviral effect in vitro
(1) external anti-HSV-2 virus functions:Syringin has obvious inhibitory action to HSV-2 in vitro, its IC50
It is 6.9 (tables 1) for 1.000 μ g/mL, TI.
The anti-HSV-2 lesions effect in vitro of the Syringin of table 1
(2) inhibitory action of the Syringin to HPV16 E6 genes:Syringin has to HPV16 E6 genes in vitro
Obvious inhibitory action, the log values of its middle dose group E6 gene expression amounts are compared with viral group with significant difference (table 2).
Inhibitory action of the Syringin of table 2 to HPV16 E6 gene expressions
Compared with viral group:*P < 0.05.
2nd, Syringin vitro antibacterial activity:Syringin to staphylococcus aureus (26003,331,360, No. 361),
Staphylococcus albus 26101, MRSE type strain (104, No. 108), beta streptococcus (10, No. 12), large intestine angstrom
Uncommon bacterium (44113,23,117, No. 178), Pseudomonas aeruginosa (10102,209,210, No. 211), proteus type strain, gonococcus
Type strain, Candida albicans type strain are respectively provided with obvious inhibitory action, its minimal inhibitory concentration is respectively 56.56,
56.56、28.28、28.28、113.12、56.56、56.56、113.12、28.28、28.28、14.14、28.28、56.56、
56.56th, 56.56,28.28,28.28,56.56,14.14,56.56,56.56 μ g/mL (table 3).
The Syringin of table 3 is in vitro to the inhibitory action of bacterium
3rd, embodiment 1-7 bulk drugs infect HPV16 the effect for causing rat cervicitis
(1) effect that causes rat chronic cervicitis is infected HPV16:Normal rats vagina, uterine neck are visually observed without swollen
Swollen, no hyperemia, color is normal;Model group partial rat vagina, uterine neck have obvious tumefaction, and outward appearance uterine neck is thicker, and color is more normal,
Lesion degree relatively becomes apparent from normal group;Embodiment 1-4 bulk drugs group to the vagina of animal, uterine neck from color to section, disease
Change has obvious therapeutic action, and therapeutic effect is better than the bulk drug group of embodiment 5 and bulk drug group (the i.e. Syringin of embodiment 6
Group);The therapeutic effect unobvious (table 4) of the bulk drug group of embodiment 7 (i.e. cinnaldehydrum group).
Each experimental group infects HPV16 the influence (n=10) for causing rat chronic cervicitis under the naked eyes of table 4
(2) effect that causes rat vagina inflammation is infected HPV16:Control rats vagina structure is normal;Model group vagina
The obvious inflammatory disorderses such as tissue thickens, oedema and bleeding;Embodiment 1-4 bulk drugs group has to the vagina lesion of animal significantly to be controlled
Treatment acts on (table 5).
5 each experimental group of table infects HPV16 the influence (n=10) for causing rat vagina inflammation
4th, embodiment 1-7 bulk drugs cause the effect of rat chronic cervicitis to bacteria mixed infection
(1) influence of rat chronic cervicitis is caused to bacteria mixed infection:Visually observe normal rats vagina, uterine neck without
Swelling, no hyperemia, color are normal;Model group partial rat vagina, uterine neck have obvious tumefaction, and outward appearance uterine neck is thicker, color surface
Mulberry, section uterine neck is thicker, has a small amount of pink colour mucus to ooze out in individual animal uterine cavity, lesion degree is brighter compared with normal group
It is aobvious;Embodiment 1-4 bulk drug groups vagina, uterine neck are from color to section, and lesion is significantly improved, and therapeutic effect is better than embodiment
5 bulk drug groups and the bulk drug group of embodiment 6 (i.e. Syringin group);The treatment effect of the bulk drug group of embodiment 7 (i.e. cinnaldehydrum group)
Fruit unobvious (table 6).
Each experimental group causes the effect (n=10) of rat chronic cervicitis to bacteria mixed infection under the naked eyes of table 6
(2) the scorching effect of rat vagina is caused to bacteria mixed infection:Control rats vagina structure is normal, and model group is visible
The inflammatory lesions such as vagina tissue thickens, bleeding, swelling;Embodiment 1-4 bulk drugs group has to vagina lesion significantly improves effect
(table 7).
7 each experimental group of table causes the scorching effect (n=10) of rat vagina to bacteria mixed infection
5th, the effect of rat chronic cervicitis is caused to chemical substance:Normal rat vagina, uterine neck do not have obvious lesion, mould
There are the lesions such as bleeding, swelling, secretion in type group rat, and "+" level lesion is 5, and " II " level lesion is 4, " III " level lesion
For 1, lesion degree is more serious;Embodiment 1-4 bulk drug groups significantly improve the lesion degree of rat vagina, uterine neck, with model
Group compares with marked difference (table 8).
Each experimental group Pyrogentisinic Acid rubber cement of table 8 causes the effect (n=10) of rat chronic cervicitis
Above experimental result, show the addition of appropriate cinnaldehydrum, be remarkably improved Syringin to caused by various factors
The therapeutic effect of rat cervicitis and vaginitis, the therapeutic effect of especially 1-4 of embodiment of the present invention pharmaceutical compositions are notable.It is former
Cause is probably the physicochemical property that cinnaldehydrum changes Syringin by certain effect so that it has been given play to significant anti-inflammatory and lived
Property, the pharmacological action of pharmaceutical composition of the present invention is that single-activity component can not replace, and the present invention achieves unexpected
Technique effect.
Claims (8)
1. a kind of pharmaceutical composition, it is characterised in that in parts by weight, the pharmaceutical composition contains Syringin 1-3 parts, osmanthus
Skin aldehyde 0.5-1.5 parts.
2. the pharmaceutical composition described in claim 1, it is characterised in that also optionally include pharmaceutically acceptable auxiliary material.
3. the pharmaceutical composition described in claim 2, it is characterised in that the pharmaceutically acceptable auxiliary material be selected from water for injection,
Pharmaceutical carrier, surfactant, diluent, excipient, antioxidant, stabilizer, solubilizer.
4. the pharmaceutical composition described in claim any one of 1-3, it is characterised in that the mass ratio of Syringin and cinnaldehydrum is
2:1-4:1。
5. the pharmaceutical composition described in claim any one of 1-4, it is characterised in that the formulation of described pharmaceutical composition is solid
Preparation, liquid preparation or semisolid preparation.
6. the pharmaceutical composition described in claim any one of 1-5, it is characterised in that the formulation of described pharmaceutical composition for sustained release,
Controlled release and enteric capsulation, tablet, supensoid agent, microemulsion, sub-micellar emulsion or injection.
7. the pharmaceutical composition described in claim any one of 1-6, it is characterised in that the Syringin in described pharmaceutical composition
Selected from Syringin and/or pharmaceutically acceptable Syringin salt;Cinnaldehydrum is selected from cinnaldehydrum and/or pharmaceutically acceptable
Cinnaldehydrum salt.
8. pharmaceutical composition the answering in treatment and/or prevention gynaecological imflammation medicine is prepared described in claim any one of 1-7
With the especially application in treatment and/or prevention cervicitis, colpitis medicine is prepared.
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