CN106074603A - A kind of stem cell combined preparation for treating Erectile Dysfunction - Google Patents
A kind of stem cell combined preparation for treating Erectile Dysfunction Download PDFInfo
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Abstract
The invention discloses the application in preparation treatment Erectile Dysfunction medicine of the fat stem cell associating endothelial progenitor cells, and a kind of stem cell combined preparation for treating Erectile Dysfunction, it is the fat stem cell (ADSCs) originated by people and people's endothelial progenitor cells (EPCs) mixed preparing forms, give full play to the advantage of two kinds of stem cell of ADSCs and EPCs, the paracrine action utilizing ADSCs promotes propagation and the differentiation of EPCs, thus the blood vessel endothelium of repairing damage, significantly improve rat diabetes erectile dysfunction symptom；And overcome that ADSCs cannot to be implanted into internal rear survival rate the highest to blood vessel endothelium differentiation and EPCs, the shortcoming that after transplanting, its propagation, differentiation capability decline.The technical operation of ADSCs of the present invention associating EPCs treatment Erectile Dysfunction is simple, and preparation simplicity has very important clinical meaning and wide application prospect.
Description
Technical field
The invention belongs to biomedicine technical field.It is used for treating diabetic erection function more particularly, to one
The stem cell combined preparation of obstacle.
Background technology
Erectile Dysfunction (diabetic erectile dysfunction, DED) patient increases year by year,
Existing therapy is to its unsatisfactory curative effect.The most clinical gamma therapy 5 type phosphodiesterase inhibitor
The effective percentage only 50%～60% of (phosphodiesterase type 5 inhibitor, PDE-5I) treatment DED.
Existing research think DED originate and core pathogenesis is cavernous body of penis vascular endothelium dysfunction, at this
On the basis of secondary erect relevant nerve, infringement and a series of pathophysiological change such as smooth muscle.We are by research DED rat
Model validation its spongy body endotheliocyte eNOS, VEGF and expression of receptor thereof all decline, and Jesmin etc. finds DED rat spongy body
Apoptosis of vascular endothelial cell increases, and causes nitric oxide (NO) release to reduce, causes Dysfunction of vascular endothlial cells；Afterwards may be used
Cause spongy body vessel wall thickening to cause narrow, the thrombosis of small artery and blood capillary tube chamber, cause cavernosal tissue to lack
Anoxemia, and then cause penile erectile function to go down, and penis Microangiopathy further results in nerve, smooth muscle ischemia lacks
Oxygen, increases the weight of erection disturbance.
In recent years, the research of stem cell transplantation therapy brings hope to the treatment of DED.Fat stem cell (ADSCs) moves
Plant treatment DED, it is possible to improve erection function to a certain extent, can by secretion of VEGF, HGF, FGF2, CXCL5 etc. growth because of
Son improves local microenvironment, promotes the propagation of local function cell (such as vascular endothelial cell), improves vascular endothelial function；But
It is that ADSCs can not directly be divided into vascular endothelial cell in vivo, limits its curative effect.First Application EPCs such as Gou in 2011
Transplantation treatment DED, it is intended to rely on the propagation of EPCs, differentiation to repair impaired spongy body endothelial function and supplementary peripheral blood
EPCs；Found that EPCs really can be incorporated into the angiosomes of spongy body and breed, is divided into endotheliocyte, after transplanting
The erection function of DED rat obtains part and improves, but curative effect is not good enough.Our research also demonstrate that the above results, finds simultaneously
It is the highest that EPCs is implanted into internal rear survival rate, and after transplanting, its propagation, differentiation capability decline, and limit its curative effect and application prospect.
Summary of the invention
The technical problem to be solved in the present invention is to overcome being not enough to of existing treatment Erectile Dysfunction medicine
And the defect that stem cell is applied in this field, it is provided that one is reasonable, convenient, therapeutic effect preferably combines stem cell medicine, relates to
And the application that two kinds of stem cell are in disease treatment, specifically fat stem cell (ADSCs) and endothelial progenitor cells (EPCs) associating
Application in preparation treatment Erectile Dysfunction medicine.
It is an object of the invention to provide fat stem cell associating endothelial progenitor cells at preparation treatment diabetic erection function
Application in disorder remedies.
Another object of the present invention is to provide a kind of stem cell combined preparation for treating Erectile Dysfunction.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Fat stem cell (ADSCs) associating endothelial progenitor cells (EPCs) is in preparation treatment Erectile Dysfunction medicine
Application.
Wherein it is preferred to, described endothelial progenitor cells behaviour endothelial progenitor cells.
Preferably, the ratio of described fat stem cell and endothelial progenitor cells is 1～2:1～2.
It is highly preferred that the ratio of described fat stem cell and endothelial progenitor cells is 1:1.
Preferably, the concentration of described fat stem cell is 1.0～10.0 × 106/ml。
It is highly preferred that the concentration of described fat stem cell is 3.0～6.0 × 106/ml。
Most preferably, the concentration of described fat stem cell is 5.0 × 106/ml。
Preferably, the concentration of described endothelial progenitor cells is 1.0～10.0 × 106/ml。
It is highly preferred that the concentration of described endothelial progenitor cells is 3.0～6.0 × 106/ml。
Most preferably, the concentration of described endothelial progenitor cells is 5.0 × 106/ml。
A kind of stem cell combined preparation for treating Erectile Dysfunction, the fat comprising effective dose is dry thin
Born of the same parents (ADSCs) associating endothelial progenitor cells (EPCs).
Preferably, in described stem cell combined preparation, the ratio of fat stem cell and endothelial progenitor cells is 1～2:1
～2.
It is highly preferred that in described stem cell combined preparation, the ratio of fat stem cell and endothelial progenitor cells is 1:1.
It addition, it is highly preferred that described stem cell combined preparation is to be mixed system by fat stem cell, endothelial progenitor cells and PBS
For forming.
Preferably, the concentration of described fat stem cell is 1.0～10.0 × 106/ml。
It is highly preferred that the concentration of described fat stem cell is 3.0～6.0 × 106/ml。
Most preferably, the concentration of described fat stem cell is 5.0 × 106/ml。
Preferably, the concentration of described endothelial progenitor cells is 1.0～10.0 × 106/ml。
It is highly preferred that the concentration of described endothelial progenitor cells is 3.0～6.0 × 106/ml。
Most preferably, the concentration of described endothelial progenitor cells is 5.0 × 106/ml。
Preferably, described PBS is 1 × PBS.
Particularly preferably, the preparation method of described stem cell combined preparation is as follows:
After centrifugal to fat stem cell and endothelial progenitor cells, wash 1～3 time (preferably 1 time) with 1 × PBS respectively, and use cytometer
Number plate counting, being prepared as cell concentration respectively in addition 1 × PBS is 1.0～10.0 × 1061 × PBS preparation of/ml, by two kinds
Preparation is according to 1～2:1～2(preferred 1:1) ratio mixing, obtain fat stem cell and endothelial progenitor cells joint injection liquid.
Wherein it is preferred to, it is that to be prepared as cell concentration in addition 1 × PBS respectively be 3.0～6.0 × 106The 1 of/ml ×
PBS preparation.
It is highly preferred that be that to be prepared as cell concentration in addition 1 × PBS respectively be 5.0 × 1061 × PBS preparation of/ml.
It addition, the application that above-mentioned stem cell combined preparation is in preparation prevents and treats the medicine of Erectile Dysfunction,
And the medicine preventing and treating Erectile Dysfunction thus prepared, the most all within protection scope of the present invention.
The present invention about for treating in the stem cell combined preparation of Erectile Dysfunction, fat stem cell
(ADSCs) being derived from the mescenchymal stem cell of fatty tissue, this cell amplification ability is strong, and secrete cytokines kind is many, tool
Having multi-lineage potential, immunogenicity is low, and acquisition methods is simple.ADSCs treatment erection disturbance typically uses penis sponge
The mode of internal injection, improves, by paracrine action, the key that endothelial function is treatment.And EPCs is a class energy directional proliferation
It is divided into the precursor of mature blood endothelial cell, is originating primarily from bone marrow, can directional migration and the blood adhering to damaged
Inside pipe wall, is on the one hand divided into mature blood endothelial cell, directly forms newborn endothelium and repairs injured blood vessel；On the other hand release
A large amount of angiogenic growth factors (such as VEGF etc.), stimulate endothelial cell proliferation, migration around damage field, accelerate damaged blood vessels
Endothelialization again, thus quickly repair vascular endothelial function.EPCs really can be incorporated into the angiosomes of spongy body and breed, divides
Turning to endotheliocyte, after transplanting, the erection function of DED rat obtains part and improves, but curative effect is not good enough, EPCs be implanted into internal after
Survival rate is the highest, and after transplanting, its propagation, differentiation capability decline, and limit its curative effect and application prospect.The present invention gives full play to
The advantage of two kinds of stem cell of ADSCs and EPCs, utilizes the paracrine action of ADSCs to promote propagation and the differentiation of EPCs, thus repaiies
The blood vessel endothelium of multiple damaged, significantly improves rat diabetes erectile dysfunction symptom；And overcome ADSCs cannot be to
It is the highest that blood vessel endothelium differentiation and EPCs are implanted into internal rear survival rate, the shortcoming that after transplanting, its propagation, differentiation capability decline.Thus
Reach the purpose learnt from other's strong points to offset one's weaknesses.
It addition, in the solution of the present invention, for fat stem cell (ADSCs) and the source of endothelial progenitor cells (EPCs) and system
Preparation Method does not do strict restriction, can be the most known preparation method or acquisition methods.As special in the most authorized invention
A kind of method obtaining endothelial progenitor cells disclosed in profit 200910196288.3, hatches the most available by commercial medullary cell
Suspension cell is endothelial progenitor cells.The separation and Culture side of a kind of fat stem cell disclosed in patent of invention 201010568873.4
Method, and the acquisition methods etc. of a kind of fat stem cell disclosed in patent of invention 201210018269.3.
Embodiment of the present invention part provides a kind of enforceable selection scheme:
(1) separation and Culture of fat stem cell
Obtaining human hypodermic fat (such as patient's abdominal subcutaneous fat) by liposuction under local anaesthesia, type i collagen enzyme digestion obtains former
Fat subsitutes stem cell, centrifugal that cell precipitates, after addition basal medium is resuspended, at saturated humidity, 5%CO2, 37 DEG C of standard rings
Under border, utilize cell culture fluid to be inoculated in culture bottle after cultivating, cultivate and pass in good time.During cell dissociation, use EDTA-pancreas
Enzymic digestion, PBS washed cell, ADSCs is re-seeded into the culture bottle of the heart, within every three days, passes on once, until cell reaches required
The cell concentration wanted, i.e. terminates Secondary Culture.Use osteogenic induction and Von Kossa dyeing, adipogenic induction and oil red O stain mirror
Its Multidirectional Differentiation ability fixed.
(2) separation and Culture of endothelial progenitor cells: the peripheric venous blood (such as extraction detection in peripheral blood of patients underwent) collected is through PBS
After equimultiple dilution, diluent is added as Ficoll lymphocyte separation medium enterprising line density gradient centrifugation in 2:1 ratio, takes outstanding
The mononuclearcell in liquid intermediate layer, with EGM-2MV culture medium resuspended after, be inoculated in the culture dish of pre-coated fibronectin splicing variants
In, at saturated humidity, 5%CO2, cultivate under 37 DEG C of standard environments.Change liquid after 72h, remove non-adherent cell, within later every 3 days, change
Liquid.During cell dissociation, using EDTA-trypsinization, PBS washed cell, EPCs is re-seeded into new culture bottle, every three days
Pass on once, until cell reaches required cell concentration, i.e. terminate Secondary Culture.Flow cytometry detection CD31,
The EPCs cell surface markers such as CD34, CD73, CD105, CD117, CD133；Immunofluorescence analysis detection CD31, vWF, VEGFR1
Deng EPCs cell surface marker；It is divided into vascular endothelial cell and forms blood vessel to utilize lumen of vessels spline structure to form testing inspection
Ability.Make to identify in aforementioned manners EPCs.
The method have the advantages that
The present invention studies discovery, and two kinds of stem cell combined uses of ADSCs and EPCs are used for treating Erectile Dysfunction,
The effect of Synergistic can be reached, ADSCs and EPCs stem cell mix preparation is transplanted to Erectile Dysfunction
Rat body in, the erection function situation of rat can be significantly improved, improve the cavernous body of penis endothelial function that diabetes are caused
Obstacle.
Two kinds of stem cell combined uses of ADSCs and EPCs, it is possible to the advantage making full use of two kinds of stem cell, play ADSCs
With the advantage of two kinds of stem cell of EPCs, utilize the paracrine action of ADSCs to promote propagation and the differentiation of EPCs, thus repair impaired
The blood vessel endothelium of wound, significantly improves rat diabetes erectile dysfunction symptom；And overcome ADSCs cannot be to Ink vessel transfusing
It is the highest that skin differentiation and EPCs are implanted into internal rear survival rate, the shortcoming that after transplanting, its propagation, differentiation capability decline, thus reaches to take
The purpose that long benefit is short.
It addition, two kinds of stem cell of ADSCs and EPCs have the advantages such as amplification ability is strong, preparation is simple, immunogenicity is low, and
And, the preparation method of the stem cell combined preparation of ADSCs and EPCs is simple, utilizes the stem cell combined preparation for treating of ADSCs and EPCs
Erectile Dysfunction, the stem cell mix preparation that can be used for clinical treatment as thinking exploitation has extremely important
Clinical meaning and wide application prospect.
Accompanying drawing explanation
Fig. 1 is morphology (A) and multiplication capacity (B) analysis result after ADSCs and cEPC co-cultures 14 days.
Fig. 2 be ADSCs and EPCs combined transplantation treatment DED rat intracavernous pressure (ICP) and intracavernous pressure after 28 days/
Mean arterial pressure (ICP/MAP) measurement result.
Fig. 3 is ADSCs and EPCs combined transplantation treatment DED rat Endothelium Cell of Penial Corpus Cavernosum mark CD31 after 28 days
Immunofluorescence results with eNOS.
Detailed description of the invention
Further illustrate the present invention below in conjunction with Figure of description and specific embodiment, but embodiment is not to the present invention
Limit in any form.Unless stated otherwise, the present invention uses reagent, method and apparatus are the examination of the art routine
Agent, method and apparatus.
Unless stated otherwise, following example agents useful for same and material are commercial.
Embodiment 1 fat stem cell and the preparation of endothelial progenitor cells combination formulations
1, the separation and Culture of fat stem cell
Obtaining human hypodermic fat (such as patient's abdominal subcutaneous fat) by liposuction under local anaesthesia, type i collagen enzyme digestion obtains former
Fat subsitutes stem cell, centrifugal that cell precipitates, after addition basal medium is resuspended, at saturated humidity, 5%CO2, 37 DEG C of standard rings
Under border, utilize cell culture fluid to be inoculated in culture bottle after cultivating, cultivate and pass in good time.During cell dissociation, use EDTA-pancreas
Enzymic digestion, PBS washed cell, ADSCs is re-seeded into the culture bottle of the heart, within every three days, passes on once, until cell reaches required
The cell concentration wanted, i.e. terminates Secondary Culture.
Osteogenic induction and Von Kossa dyeing, adipogenic induction and oil red O stain is used to identify its Multidirectional Differentiation ability.
2, the separation and Culture of endothelial progenitor cells
Diluent, after PBS equimultiple dilutes, is pressed 2:1 ratio by the peripheric venous blood (such as extraction detection in peripheral blood of patients underwent) collected
Example adds as Ficoll lymphocyte separation medium enterprising line density gradient centrifugation, takes the mononuclearcell in suspension intermediate layer, uses
After EGM-2MV culture medium is resuspended, it is inoculated in the culture dish of pre-coated fibronectin splicing variants, at saturated humidity, 5%CO2、37℃
Cultivate under standard environment.Change liquid after 72h, remove non-adherent cell, within later every 3 days, change liquid.During cell dissociation, use EDTA-
Trypsinization, PBS washed cell, EPCs is re-seeded into new culture bottle, within every three days, passes on once, until cell reaches institute
The cell concentration needed, i.e. terminates Secondary Culture.
Flow cytometry detection CD31, the EPCs cell surface marker such as CD34, CD73, CD105, CD117, CD133；Exempt from
Epidemic disease fluorescence analysis detection CD31, the EPCs cell surface marker such as vWF, VEGFR1；Lumen of vessels spline structure is utilized to form testing inspection
It is divided into vascular endothelial cell and forms the ability of blood vessel.
Make to identify in aforementioned manners EPCs.
3, the preparation of stem cell combined preparation
Wash 1 time with 1 × PBS after centrifugal for ADSCs and EPCs collected, count with cell counting count board, add in 1 × PBS
Being prepared as cell concentration respectively is 5.0 × 106Two kinds of preparations are mixed into fat according to 1:1 ratio by 1 × PBS preparation of/ml
Stem cell and endothelial progenitor cells joint injection liquid.
Embodiment 2 fat stem cell and endothelial progenitor cells co culture system in vitro and ADSCs are in vitro for EPCs propagation and differentiation
Impact
1, method
EPCs is placed in transwell with ADSCs or SMC co-culture, takes EPCs after certain time and carry out following detection: the 1st,
The multiplication capacity being measured EPCs by MTS method analysis in 7,14 days；Use H2O2-injured and CCK-8 method, detect anti-apoptotic energy
Power (is survived)；In Vitro Angiogenesis Assay Kit test kit, detection EPCs is used to be divided into vascular endothelial cell
Ability and vascularization ability；Observe ADSCs for EPCs propagation and the impact of differentiation.Use ELISA, Western
The methods such as blot, PCR, detection ADSCs secrete cytokines situation (VEGF, HGF, FGF2, CXCL5), EPCs Proliferation and apoptosis divide
The related gene expressions (Ki-67, Cas-3, TUNEL) such as change.
2, result is as shown in Figure 1.
After ADSCs and EPCs co-cultures 14 days, morphology as figure A shown in, multiplication capacity as shown in panelb, by ADSCs with
After EPCs co-cultures 14 days, more independent EPCs or SMC of multiplication capacity and EPCs of EPCs co-culture higher (* p < 0.05), and
EPCs showed increased (figure A) is also shown in morphology.
Embodiment 3 fat stem cell and the application test of endothelial progenitor cells combination formulations
1, the structure of Erectile Dysfunction (DED) rat model
(1), after rat adaptability raises 1 week, 40mg/kg body weight left lower quadrant intracavitary administration is pressed with streptozotocin (STZ).STZ is molten
The compound method of liquid: use 0.1mol/L sodium citrate citrate buffer solution (PH4.0), prepares 10mg/ in ice bath
MlSTZ, notes lucifuge, i.e. joins and i.e. uses；Matched group sodium citrate citrate buffer solution row lower-left lumbar injection.Observe injection
Rat symptom after STZ, detects blood glucose, random time blood glucose value after one week > 16.7mmol/L is diabetes (DM) rat model.
(2) DM rat model set up 10 weeks after, select a quiet room, rat is placed in glass box, adaptation ring
Border 10min, indoor keep quite, and light dims, and is only sufficient to observe, and then inject apomorphine at neck relaxes skin
(APO) 100ug/kg, APO are dissolved in VitC and the normal saline of 0.5mg/kg, and adjustment volume is 5ml/kg, every rat
After injection, observe 30min at once, and record penis with or without erection, erection number of times.Glans penis is congested and end body of penis goes out
Now for erection 1 time.Have no that erector is DED rat.
2, fat stem cell and endothelial progenitor cells combination formulations transplantation experiments
(1) penis cavernosa injection
Pentobarbital 30mg/kg lumbar injection, after anaesthetizing successfully, cuts off foreskin, exposes penile tissue, only add at radix penis part
Blood band, 1ml syringe extraction fat stem cell and endothelial progenitor cells combination formulations 0.2ml, squeeze into cavernous body of penis；After 1 minute
Unclamp tourniquet, sew up foreskin.
(2) evaluation of rat erection situation
Mainly by measuring mean arterial pressure (MAP), intracavernous pressure (ICP) detects, and concrete grammar is as follows: pentobarbital
30mg/kg lumbar injection, after anaesthetizing successfully, carries out free under Olympus microscope and exposes the right side total tremulous pulse of strength, annular
Cut foreskin, expose crus of penis, simultaneously expose pelvic ganglia, after the heparin saline PE-50 conduit containing 250IU/ml inserted with
Monitoring MAP；Spongy body is built into the stainless pin (being full of the heparin saline of 250IU/ml) of a 23G, and the other end is connected to PE-
On 50 conduits, above-mentioned two conduits are connected with pressure transducer, and by Power Lab channel polygraph record.Bipolar
Stainless steel electrode pelvic ganglia sends and catches on cavernosal nerve, total time 1min at about 3～4mm.Stimulator parameter: single-phase rectangle
Impulse stimulation 5ms, voltage 3～5V, frequency 15Hz, ripple width 1ms, it is repeated once after the 10min of interval.
(3) cavernous body of penis morphological indexes
Measure and put to death rat after ICP, completely cut corpus cavernosum tissue, cut off foreskin and cartilage, crosscutting a bit of put immediately
Liquid nitrogen preserves, utilizes the method such as HE dyeing, immunohistochemical staining, Western blot and PCR to detect spongy body: blood vessel
Density index (CD31), propagation and apoptosis index (Ki-67, Cas-3, TUNEL), vascular endothelial function index (eNOS, vWF)
Deng expression.
3, result of the test
Result such as accompanying drawing 2, ADSCs and EPCs combined transplantation treatment DED rat after 28 days, intracavernous pressure (ICP) and spongy body
Intrinsic pressure/mean arterial pressure (ICP/MAP) measures display, individually transplants ADSCs or ECPs, or combined transplantation ADSCs and ECPs,
ICP and ICP/MAP(p < 0.05 of DED rat can be obviously improved), wherein compared with individually transplanting ADSCs or ECPs group, connection
Close transplantation group improvement result to be substantially improved, the most substantially, significantly, show the effect (p < 0.05) of Synergistic.
Such as accompanying drawing 3, ADSCs and EPCs combined transplantation treatment DED rat is after 28 days, Endothelium Cell of Penial Corpus Cavernosum mark
The immunofluorescence results of CD31 and eNOS shows, it is thin that ADSCs and EPCs combined transplantation can dramatically increase DED rat cavernous sinus endothelium
The expression of born of the same parents' mark.
Claims (10)
1. fat stem cell associating endothelial progenitor cells application in preparation treatment Erectile Dysfunction medicine.
Application the most according to claim 1, it is characterised in that described endothelial progenitor cells behaviour endothelial progenitor cells.
Application the most according to claim 1, it is characterised in that the ratio of described fat stem cell and endothelial progenitor cells is 1
～2:1～2.
Application the most according to claim 3, it is characterised in that the concentration of described fat stem cell is 1.0～10.0 × 106/
Ml, the concentration of described endothelial progenitor cells is 1.0～10.0 × 106/ml。
5. the stem cell combined preparation being used for treating Erectile Dysfunction, it is characterised in that comprise effective dose
Fat stem cell and endothelial progenitor cells.
Stem cell combined preparation the most according to claim 5, it is characterised in that described fat stem cell and endothelial progenitor cells
Ratio be 1～2:1～2.
Stem cell combined preparation the most according to claim 5, it is characterised in that described stem cell combined preparation is done by fat
Cell, endothelial progenitor cells and PBS are mixed with and form.
Stem cell combined preparation the most according to claim 7, it is characterised in that the concentration of described fat stem cell is 1.0
～10.0 × 106/ ml, the concentration of described endothelial progenitor cells is 1.0～10.0 × 106/ ml, described PBS are 1 × PBS.
Stem cell combined preparation the most according to claim 8, it is characterised in that the preparation side of described stem cell combined preparation
Method is as follows:
Wash with 1 × PBS after centrifugal to fat stem cell and endothelial progenitor cells respectively, and count, add in 1 × PBS and make respectively
Standby one-tenth cell concentration is 1.0～10.0 × 106Two kinds of preparations are mixed by 1 × PBS preparation of/ml according to the ratio of 1～2:1～2
Close, obtain fat stem cell and endothelial progenitor cells joint injection liquid.
10. the medicine of Erectile Dysfunction prevented and treated by the arbitrary described stem cell combined preparation of claim 5～9 in preparation
In application.
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| CN107412264A (en) * | 2017-05-10 | 2017-12-01 | 健生生物技术有限公司 | For treating the medicine and its preparation and application of male erectile disorder |
| CN109010920A (en) * | 2018-09-29 | 2018-12-18 | 四川新生命干细胞科技股份有限公司 | A kind of cosmetic formulation containing stem cell, progenitor cells and extracellular matrix |
| CN109954001A (en) * | 2018-04-04 | 2019-07-02 | 天津欣普赛尔生物医药科技有限公司 | For treating the umbilical cord mesenchymal stem cells of erectile dysfunction and its combination formulations and preparation method and medication of excretion body |
| CN111304150A (en) * | 2020-02-25 | 2020-06-19 | 昆明医科大学 | ADSCs and EPCs stem cell system capable of promoting graft microcirculation blood supply recovery |
| CN111419877A (en) * | 2020-03-13 | 2020-07-17 | 北京中瑞联合生物科技有限公司 | Medicine for treating male erectile dysfunction and preparation method thereof |
| CN113662968A (en) * | 2021-09-18 | 2021-11-19 | 哈尔滨科技实业开发有限公司 | A pharmaceutical composition for preventing or treating erectile dysfunction |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107412264A (en) * | 2017-05-10 | 2017-12-01 | 健生生物技术有限公司 | For treating the medicine and its preparation and application of male erectile disorder |
| CN109954001A (en) * | 2018-04-04 | 2019-07-02 | 天津欣普赛尔生物医药科技有限公司 | For treating the umbilical cord mesenchymal stem cells of erectile dysfunction and its combination formulations and preparation method and medication of excretion body |
| CN109010920A (en) * | 2018-09-29 | 2018-12-18 | 四川新生命干细胞科技股份有限公司 | A kind of cosmetic formulation containing stem cell, progenitor cells and extracellular matrix |
| CN111304150A (en) * | 2020-02-25 | 2020-06-19 | 昆明医科大学 | ADSCs and EPCs stem cell system capable of promoting graft microcirculation blood supply recovery |
| CN111419877A (en) * | 2020-03-13 | 2020-07-17 | 北京中瑞联合生物科技有限公司 | Medicine for treating male erectile dysfunction and preparation method thereof |
| CN113662968A (en) * | 2021-09-18 | 2021-11-19 | 哈尔滨科技实业开发有限公司 | A pharmaceutical composition for preventing or treating erectile dysfunction |
| CN113662968B (en) * | 2021-09-18 | 2023-09-19 | 哈尔滨科技实业开发有限公司 | Pharmaceutical composition for treating erectile dysfunction |
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