CN1895662A - Use of kerato cell growth factor-2 in treatment of chronic cervicitis medicine - Google Patents
Use of kerato cell growth factor-2 in treatment of chronic cervicitis medicine Download PDFInfo
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Abstract
An application of the horny cell growing factor-2 in preparing the medicine in the form of vaginal suppository, effervescent tablet, gel, etc for treating chronic cervcitis is disclosed.
Description
Technical field
The present invention relates to the purposes in pharmaceutical field, (Keratinocyte growth factor-2 is KGF-2) as the purposes for preparing the treatment chronic cervicitis medicine more specifically to relate to a kind of body keratinized cell growth factor-2.
Background technology
(Keratinocyte growth factor-2 KGF-2) claims that again (fibroblast growth factor-10 FGF-10), is one of FGF family member to fibroblast growth factor-10 to body keratinized cell growth factor-2.It is by fibroblast and the secretion of other Interstitial cell, specificity target cell is various epithelial cells, specific receptor is tyrosine kinase receptor FGFR2 IIIb (KGFR) and FGFR1 IIIb, mainly bearing the signal transmission between Interstitial cell-epithelial cell, is the interactional cytokine of matter-epithelium between adjusting.The KGF-2 specificity promotes epithelial proliferation and differentiation and migration, is multifunctional signal molecule important during the embryonic organ grows.Can stimulate the epithelial regeneration of wound circumference, differentiation and migration, but fibroblast and endotheliocyte are not then had direct effect.KGF-2 can be used for the treatment of multiple epidermis injury relevant disease clinically, to multiple tissue, organ, the prevention and the reparation that comprise the epithelium/substrate damage of skin, cornea, lung, respiratory tract, gastrointestinal tract, hair follicle, bladder etc. play an important role, reparation, other somatomedin of reproduction ratio to burn, ulcer, incision have more significant effect, and can reduce the formation of cicatrix, safety research also shows its single-minded people's of acting on normal epithelial, in vivo and in vitro people KGFR (+) is gone up all non-stimulated multiplication effect of dermoid tumor.The KGF-2 injection repifermin of U.S. human genome company exploitation has entered the II clinical trial phase, and the project of carrying out has venous ulcer, because of mucositis and ulcerative colitis that treatment of cancer is brought out, and part of test results has been showed good prospects for application.At present, KGF-2 more and more is subjected to people's attention with its outstanding advantage, but KGF-2 does not see relevant research report as yet to the therapeutical effect of chronic cervicitis.
Chronic cervicitis (cervical erosion) is Cervical chronic inflammatory injury disease.Its paathogenic factor is more, and infection, chemical substance stimulation and the mechanical injuries etc. of virus and antibacterial are arranged.Cervical erosion can be true erosion, pseudoerosion.In chronic cervicitis, cervical erosion and cervix uteri process more again carry out repeatedly, make chronic cervicitis become a kind of healing property of difficulty inflammation, and its mechanism it be unclear that.Often adopt various naturopathy at present clinically, as freezing, electricity is pressed, laser, infrared ray etc., it is the columnar epithelium that destroys the cervical erosion face, its necrosis is come off, squamous epithelial cancer by new life covers, but there are postoperative hemorrhage, infection, healing time is long, the narrow formation of neck tube is sterile possibility, and have the problems such as untoward reaction is many that influence, and patient's daily life has also been brought inconvenience in the majority vaginal delivery.
Summary of the invention
The object of the present invention is to provide a kind of new purposes of body keratinized cell growth factor-2, i.e. new application in pharmacy.
In fact, the present invention relates to the application of a kind of body keratinized cell growth factor-2 in the medicine of preparation treatment chronic cervicitis, nontoxic to human body, nonirritant, safe in utilization, respond well.
Technical scheme provided by the invention is that KGF-2 is used for preparation treatment chronic cervicitis medicine.
KGF-2 of the present invention comprises recombinant human keratinized cell growth factor-2 or human body keratinized cell growth factor-2.
The present invention is used to prepare the medicine for the treatment of chronic cervicitis with KGF-2.In order to realize that the present invention by the following technical solutions: KGF-2 is prepared vaginal suppository, vagina effervescence, vagina gel and other available vagina administration dosage form as active ingredient.For clearer elaboration the present invention, specifically introduce implementation: with weight portion in vaginal suppository, vagina effervescence, three kinds of dosage forms of vagina gel, can adopt KGF-2 0.01-3, glycerol 100-140, gelatin 30-50, mannitol 3-5, phosphate 7-14, human albumin 0.5-2.5, pure water 15-35, preparation vaginal suppository; Adopt KGF-2 0.01-3, glycerol 0.5-1, citric acid 6-14, sodium bicarbonate 6-10, lactose 18-25, PEG-6000 1.5-3, preparation vagina effervescence; KGF-2 0.01-3, Acritamer 940 8-14, glycerol 30-60, propyl p-hydroxybenzoate 0.5-1.5, triethanolamine 1-3, pure water 950-1050, preparation vagina gel.
Advantage of the present invention:
1. the KGF-2 that adopts of the present invention can effectively promote the propagation of cervix uteri squamous epithelial cancer, and the cervix uteri face that makes the chronic cervicitis erosion is squamous epithelization again, quickens the healing of cervical erosion.
2.KGF-2 make the minimizing of cervical tissue inflammatory cell, IL-8 and PGE
2Content descends, and can significantly improve histopathology morphological change degree in the cervix uteri inflammatory process.
3.KGF-2 can significantly reduce the cervical squamous cells IL-8 and the PGE of the beta induced inflammatory conditions of IL-1
2Secretion, reduce the generation of inflammatory mediator, bring into play effective antiinflammatory action.
4.KGF-2 human body there is not toxic and side effects, nonirritant, safe in utilization, respond well.
5. the present invention adopts conventional vagina administration dosage form, technology maturation, and production technology is simple.
6. the present invention adopts the vagina administration mode, convenient drug administration, and no pain does not have sequela.
The specific embodiment
Various details embodiment, but content of the present invention is not limited thereto fully.
Embodiment 1: recombinant human keratinized cell growth factor-2 or human body keratinized cell growth factor-2 (KGF-2) are used to prepare the vaginal suppository for the treatment of chronic cervicitis.Prescription: KGF-2 0.4g, glycerol 120g, gelatin 40g, mannitol 4g, phosphate 10g, human albumin 2g.Method for making: take by weighing prescription gelatin 40g, add the pure water of equivalent, flood and put heating for dissolving in the water-bath in 1 hour, add glycerol 120g again, stir, boil off the redundant moisture loss of weight to 180g, add mannitol 4g, human albumin 2g, phosphate 10g, stir evenly, temperature remains on 37 ℃-40 ℃, add KGF-2 0.4g, stir evenly moulding, natural cooling, the die orifice of pruning overflows part, the demoulding, sealing.
Embodiment 2:KGF-2 is used to prepare the vagina effervescence for the treatment of chronic cervicitis.Prescription: KGF-20.4g, glycerol 0.6g, citric acid 10g, sodium bicarbonate 8g, lactose 20g, PEG-6000 2g.Method for making: lactose is divided into two parts, portion and KGF-2, glycerol, citric acid mixing, another part and sodium bicarbonate mixing are made adhesive with the 5%PVP dehydrated alcohol respectively and are granulated, after 40 ℃ of dryings, granulate, adding PEG-6000 mixing, tabletting.
Embodiment 3:KGF-2 is used to prepare the vagina gel for the treatment of chronic cervicitis.Prescription: KGF-2 2g Acritamer 940 12g, glycerol 50g, propyl p-hydroxybenzoate 1g, triethanolamine 1.5g, pure water adds to 1000g.Method for making: get carbomer and be sprinkled in an amount of pure water, fully stir, make swelling, be uniformly dispersed, add KGF-2, glycerol and propyl p-hydroxybenzoate respectively,, add triethanolamine and transfer pH to transparent thick with carbomer solution mixing and stirring, add pure water at last to capacity, packing.
Embodiment 4:KGF-2 dialogue interleukin 1 beta (IL-1 β) is induced the influence of rat cervical squamous cells inflammation.
Experimental technique: 1. cell separation and cultivation
Rat cervical squamous cells (RCEC) cell separation and cultivation: put to death rat, the tissue of getting uterus neck is cut into 1～2mm
3Fritter, use aseptic Hank ' s balance liquid (to contain 15mmolL
-1HEPES, penicillin 100kUL
-1, streptomycin 100mgL
-1, amphotericin 0.25mgL
-1, pH 7.4) and wash 0.1% collagenase (189kUL 3 times
-1) 37 ℃ of digestion 50 minutes, with 37 ℃ of digestion of 0.2% trypsin 20 minutes, Hank ' s balance liquid washed twice suspended with growth medium then, will be inoculated in from the tissue of two animal cervix uteri in the 60mm culture dish, at 34 ℃, 5%CO
2Cultivate in the incubator.Growth medium is that A and B (1: 1) two parts are formed, and A and B composition are as follows:
(A) 24 hours conditioned mediums: DMEM culture medium (containing 10%FBS) is cultivated the culture medium of Swiss 3T3 cell after 24 hours; (B) the cervical epithelial cells culture medium (cervical epithelial growthmedium, CEGM): form by HamF12 and RPMI-1640 (1: 1), add 7.5% porcine blood serum, insulin (10 μ gL again
-1), transferrins (10mgL
-1), hydrocortisone (6.5mgL
-1), cholera toxin (0.1nmolL
-1), Medulla Bovis seu Bubali extract (150mgL
-1).
After 3 days, discard culture medium, with D-Hanks gently rinsing remove fragment of tissue.Add CEGM then and cultivate, after cell reaches fusion, with D-Hanks rinsing 1 hour, add 0.025% trypsin and 0.5mmolL then earlier
-1EDTA (1: 1) digestion suspends again with CEGM, is inoculated into then on the 100mm culture dish that is covered with collagen gel in advance.This secondary culture can go down to posterity, and interpolation 0.1% collagenase 0.005L is hatched up to collagen at 34 ℃ and liquefied fully (about 1 hour) earlier, with D-Hanks washed cell suspension, reuse 0.025% trypsin and 0.5mmolL
-1EDTA (1: 1) 37 ℃ digestion 10 minutes, cell suspension through the washing after be suspended in again among the CEGM, be inoculated in the culture plate that is covered with collagen gel in advance, the experiment with the 2nd～3 generation cell.Trypan blue detects the cell motility rate greater than 95%, cell purity is identified the SABC SABC method that adopts, there is the coverslip of cell from culture plate, to take out growth, acetone fixed, with mouse anti rat cell keratin multi-resistance is one anti-, diaminobenzidine (DAB) colour developing, it is positive that endochylema is dyed pale brown color person, and negative control is set up in experiment simultaneously.Microscopically is observed the colour developing result, and the cell positive rate reaches more than 95%.
2. cell grouping and processing
Cell suspension is transferred to 1 * 10
9L
-1, being inoculated in 24 well culture plates, culture fluid does not contain calf serum.With each cell culture hole is a sample individuality, is divided into normal control group, inflammation matched group at random, KGF-20.1,1.0,10 and 100ngm1
-1Group, 3 multiple holes are established in every kind of processing.KGF-2 group adds KGF-2 respectively to final concentration 0.1,1.0, and 10 and 100ngml
-1, normal control group and inflammation matched group add culture fluid, put 34 ℃, 5%CO
2Cultivate in the incubator after 24 hours, it is 5ngml that inflammation matched group and KGF-2 group add final concentration
-1IL-1 β, put 34 ℃, 5%CO
2Cultivated 6 hours in the incubator.Collect every group of supernatant respectively and measure IL-8 and PGE respectively with radio immunoassay
2Content.This test repeats 2 times.
Experimental result:
With the inflammation matched group relatively, KGF-2 0.1,1.0,10 and 100ngml
-1Group IL-8 and PGE
2Content obviously reduces, with 100ngml
-1The group effect is the strongest.The results are shown in Table 1.
Table 1.KGF-2 is to rat cervical squamous cells secretion IL-8 and PGE
2Effect (x ± s, pg/ml)
| Grouping | IL-8/pg·ml -1 | PGE 2/pg·ml -1 |
| Normal control group inflammation matched group KGF-2 organizes 0.1ngml -1 1.0ng·ml -1 10ng·ml -1 100ng·ml -1 | 212.16±48.19 11320.12±1103.12 ** 7917.38+696.36 # 5014.17±735.20 ## 3648.12±238.80 ## 1520.67±188.18 ## | 20.36±2.32 60.75±4.03 ** 45.12±3.51 # 33±3.12 ## 29±2.91 ## 16±2.10 ## |
Compare with the normal control group:
*P＜0.01; Compare with the inflammation matched group,
#P＜0.05,
##P＜0.01.x±s，n＝6
The result shows, compares with the inflammation matched group, and each group of KGF-2 can both significantly reduce rat cervical squamous cells secretion IL-8 and PGE
2, illustrate that KGF-2 can suppress, alleviate rat cervix cells inflammation, and its effect is concentration dependent, with 100ngml
-1The group effect is the strongest.
Embodiment 5:KGF-2 treats the applied research of the vaginal suppository of chronic cervicitis in preparation:
1. vaginal irritation test:
Experimental technique:
1. grouping: get 8 of health, the harmless rabbit of vagina, be divided into 2 groups at random, 4 every group, be respectively KGF-2 vaginal suppository group and substrate matched group by body weight.
2. administration
2.1 usage and dosage: vagina administration, every day 1 time, each one.
2.2 administration: get each 1 of KGF-2 vaginal suppository and substrate during test, olive oil is lubricated, inserts respectively in test group and the matrix group rabbit vagina.Continue after the administration to observe 4 hours, find that medicine comes off, in time send back to.
2.3 administration frequency: every day 1 time, 12 days successive administrations.
3. observation index
3.1 overview: carry out general situation every day and observe, observe local red and swollen, the congestive symptom of rabbit medication before each administration, continued to observe in 4 hours after the administration.
3.2 pathological examination: after the last medication 48 hours, the air tap inserting method was put to death rabbit, and ovary, uterus are taken out in the lump together with vagina.Perusal medication contrafluxion, redness, ooze out, phenomenon such as degeneration, 4% neutral formalin is fixed, histopathologic examination is carried out in the conventional organization section.
The result:
1. overview: duration of test is not seen the medicine obscission.After the last administration 48 hours, draw materials and organize naked eyes not see the obvious stimulation reaction symptom.
2. microscope inspection
2.1 the vagina tissue structure is normal, epithelium of cervix uteri is formed by the monolayer cilia epithelium, no cell infiltration, and each group of test does not see that with matrix group obvious pathomorphism changes.
2.2 endometrium is complete smooth, blood vessel does not have hyperemia, expansion under the inner membrance, does not also have obvious cell infiltration, and each group of test compares no significant difference with matrix group.
2.3 ovarian cortex, medullary substance are clear, middle matter prosperity is distributed in the substrate more, and each group of test and matrix group be no significant difference relatively.
The result shows under this experimental condition that the KGF-2 vaginal suppository does not have the obvious stimulation effect to the rabbit vagina mucosa.
2.KGF-2 vaginal suppository is to the therapeutical effect of experimental rat cervicitis:
Experimental technique:
1. the foundation of the scorching model of rat uterus neck
The scorching model of preparation rat uterus neck: with Radix Acaciae senegalis the phenol suspendible is prepared 25% phenol rubber cement, inject 0.4ml to modeling rat vagina deep, three days once, totally three times.
2. grouping and processing
Rat is divided into 6 groups at random: 15 of normal control groups, 15 of negative control group, 15 of positive controls and three dosage groups of KGF-2 (each 15).After the modeling the 3rd day, beginning vagina topical, 1/day, continuous 12 days.KGF-2 treatment group is given KGF-2 40,80 and 160 μ gkg respectively
-1D
-1Positive controls is given policresulen 5000 μ gkg
-1D
-1, negative control group is given blank substrate suppository.
3. the general situation of rat is observed
Whether dry, vagina has or not flow liquid (blood) etc. if observing the rat vagina mouth.
4. cervical tissue PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM
Put to death animal in 24 days after the last administration, dissect the vagina of drawing materials, use 10% formalin fixed, paraffin embedding, section, HE dyeing to cornua uteri place tissue.Each sample is chosen same paraffin section of same area, examine under a microscope the mucosa at cervix uteri position and mucosa thereof down between the morphological changes of various tissue components of matter.Computer image analysis systematic analysis inflammatory cell quantity etc. is adopted in 3 visuals field that picked at random is non-overlapped.
The pathomorphology standards of grading are as follows:
Mucosa: only local slightly the thickening above layer 2-3 of squamous epithelial cancer level is "+", obviously thicken and be " ++ ", thicken extensively and make that mucosa is uneven is " +++": as seen some place's columnar epithelium has hypertrophy squama trend to occur to be "+", obviously squama turns to " ++ ", squamaization zone is extensively even reach uterine cavity and be " +++": rarely seen few regional squamous epithelial cancer erosion occurs and is replaced by "+" by adjacent posts columnar epithelium hypertrophy, it is " ++ " that the columnar epithelium hypertrophy obviously substitutes squamous epithelial cancer, and the squamous epithelial cancer sheet comes off and is replaced by " +++" by columnar epithelium; Rarely seen few zone is rotten to the corn, and to break through basement membrane be "+", and visible obviously mucous epithelium degeneration necrosis be " ++ ", and mucosal ulcer is " +++" with infection.
Cell infiltration: shallow-layer has a small amount of cell infiltration for "+" under rarely seen mucosa and the mucosa, and mucosa and mucosa all have the moderate cell infiltration to be " ++ " in the matter between down, mucosa down and between in the matter deep layer see that all a large amount of extensively cell infiltration are " +++".
Between the matter fibroblast proliferation: the slightly normal matched group of rarely seen fibroblast increases and is "+" in the matter, fibroblast proliferation obviously and have a small amount of collagenous fiber bundle to be " ++ ", fibroblast proliferation forms " +++" with a large amount of collagenous fiber bundles.
The comprehensive overall pathological change degree of cervix uteri is divided into following 4 grades: normal: a small amount of cell infiltration of rarely seen shallow-layer in six; Slightly: in six more than two "+"; Moderate: more than two "+", two have " ++ " in six; Severe: one has " +++" in six, and two have " ++ ", and three have "+"; Or three have " +++".
5. cervical tissue IL-8 and PGE
2Assay
From liquid nitrogen, take out tissue, take by weighing 3-5mg and put in the miniature homogenizer, add dehydrated alcohol 0.4ml, the light grinding, add normal saline 1.6ml again, grind and make homogenate, centrifugal, get supernatant, put-30 ℃ of preservations, unification adopts radio immunoassay to measure IL-8 and PGE respectively by the test kit description then
2Content.
Experimental result:
1. the rat uterus neck organizes general situation to observe
After the animal modeling, all visible movable the minimizing, the vagina collar extension has the yellow secretions of dense thick summary.After the last administration 24 hours, the most of animals of negative control group (about 12) vagina collar extension had the yellow secretions of dense thick summary, KGF-2160 μ gkg
-1Treatment only organizes that individual animal vagina collar extension has a small amount of secretions, and all the other all dry, cleanings are movable normal.
2. cervical tissue PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM
Modeling rat uterus neck is organized massive inflammatory cells infiltrated, visible epithelial erosion and mucosal ulcer, and have rotten to the corn position columnar epithelium to substitute the trend of squamous epithelial cancer.Tela submucosa telangiectasis hyperemia, interstitial edema, from mucosa between all visible massive inflammatory cells infiltrated of matter, and visible interstitial fibers hamartoplasia.KGF-2 40,80 and 160 μ gkg
-1Treatment group and negative control group corresponding site compare, and inflammatory cell infiltration obviously alleviates under the mucosa, wherein 160 μ gkg
-1The cellular morphology of treatment group and organizational structure are more near the normal control group.The results are shown in Table 2,3.
Table 2.The KGF-2 vaginal suppository is to the influence of experimental cervicitis rat cervix uteri morphological changes of various tissue components
| Grouping | Dosage/μ gkg -1 | n | Morphological changes of various tissue components | The Ridit value | 95% credibility interval | |||
| Normally | Slightly | Moderate | Severe | |||||
| Normal group model group policresulen KGF-2 | --- --- 5000 40 80 160 | 15 15 15 15 15 15 | 13 0 4 1 3 6 | 2 1 10 9 10 9 | 0 5 1 4 2 0 | 0 9 0 1 0 0 | 0.200 0.876 ** 0.447 # 0.609 # 0.491 # 0.377 ## | 0.063-0.337 0.739-1.013 0.310-0.584 0.402-0.746 0.354-0.628 0.240-0.514 |
Compare with normal group:
*P＜0.01; Compare with model group:
#P＜0.05,
##P＜0.01
Table 3.The KGF-2 vaginal suppository is to the influence of experimental cervicitis rat cervical tissue inflammatory cell number (x ± s)
| Grouping | Dosage/μ gkg -1 | n | The inflammatory cell number |
| Normal group model group policresulen KGF-2 | --- --- 5000 40 80 160 | 15 15 15 15 15 15 | 100±28 301±75 ** 150±55 ## 175±38 # 147±41 ## 128±35 ## |
Compare with normal group:
*P＜0.01; Compare with model group:
#P＜0.05,
##P＜0.01
3. to rat cervical tissue IL-8 and PGE
2The influence of content
Compare KGF-2 40,80 and 160 μ gkg with negative control group
-1Administration group rat uterus neck is organized IL-8 and PGE
2Content obviously reduces, with 160 μ gkg
-1The effect of administration group is the strongest.The results are shown in Table 4.
Table 4.The KGF-2 vaginal suppository is to experimental cervicitis rat cervical tissue IL-8 and PGE
2The influence of content (OD, x ± s)
| Grouping | Dosage/μ gkg -1 | n | IL-8/μg·kg -1 | PGE 2/μg·kg -1 |
| Normal group model group policresulen KGF-2 | --- --- 5000 40 80 160 | 8 8 8 8 8 8 | 2.77±0.56 87.40±7.91 ** 78.76±7.94 68.20±8.92 # 58.87±7.85 ## 38.64±6.68 ## | 0.59±0.13 1.35±0.35 ** 0.65±0.23 ## 1.09±0.19 0.87±0.16 # 0.78±0.22 ## |
Compare with normal group:
*P＜0.01; Compare with model group:
#P＜0.05,
##P＜0.01
The result shows that using exogenous KGF-2 can significantly improve cervicitis rat cervical tissue pathomorphology change degree, can make the minimizing of rat cervical tissue inflammatory cell, IL-8 and PGE
2Content descends, with KGF-2160 μ gkg
-1The effect of treatment group is the strongest.Show that KGF-2 has good therapeutical effect to the experimental rat cervicitis, its mechanism may with downward modulation IL-8 and PGE
2The inflammatory reaction of mediation is relevant.
Claims (1)
1, the application of a kind of body keratinized cell growth factor-2 in the medicine of preparation treatment chronic cervicitis.
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|---|---|---|---|
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|---|---|---|---|
| CNB2006100192736A CN100551438C (en) | 2006-06-06 | 2006-06-06 | The application of body keratinized cell growth factor-2 in the treatment chronic cervicitis medicine |
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|---|---|
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| CN100551438C CN100551438C (en) | 2009-10-21 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721682B (en) * | 2009-11-10 | 2013-01-23 | 苏州金盟生物技术有限公司 | Application of recombinant human fibroblast growth factor 7 mutant in preparing medicament for treating cervical erosion |
| CN106798915A (en) * | 2017-03-21 | 2017-06-06 | 郭燕立 | A kind of utilization rhEGF treatment cervical erosion and the gel of damage and preparation method thereof |
| CN112375803A (en) * | 2020-11-16 | 2021-02-19 | 石河子大学 | Screening method and application of anti-inflammatory active ingredient ethyl gallate in gallnut |
| CN114452375A (en) * | 2021-12-30 | 2022-05-10 | 温州医科大学慈溪生物医药研究院 | Application of rehabilitation new liquid and FGF-10 in synergistically regulating intestinal flora and improving immune system steady state |
-
2006
- 2006-06-06 CN CNB2006100192736A patent/CN100551438C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721682B (en) * | 2009-11-10 | 2013-01-23 | 苏州金盟生物技术有限公司 | Application of recombinant human fibroblast growth factor 7 mutant in preparing medicament for treating cervical erosion |
| CN106798915A (en) * | 2017-03-21 | 2017-06-06 | 郭燕立 | A kind of utilization rhEGF treatment cervical erosion and the gel of damage and preparation method thereof |
| CN112375803A (en) * | 2020-11-16 | 2021-02-19 | 石河子大学 | Screening method and application of anti-inflammatory active ingredient ethyl gallate in gallnut |
| CN112375803B (en) * | 2020-11-16 | 2024-05-07 | 石河子大学 | Screening method of anti-inflammatory active component ethyl gallate in gallnut and application thereof |
| CN114452375A (en) * | 2021-12-30 | 2022-05-10 | 温州医科大学慈溪生物医药研究院 | Application of rehabilitation new liquid and FGF-10 in synergistically regulating intestinal flora and improving immune system steady state |
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|---|---|
| CN100551438C (en) | 2009-10-21 |
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Granted publication date: 20091021 Termination date: 20100606 |