CN108210928A - It is applied in composition and its tissue repair comprising mescenchymal stem cell and vitamin - Google Patents

It is applied in composition and its tissue repair comprising mescenchymal stem cell and vitamin Download PDF

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Publication number
CN108210928A
CN108210928A CN201810328580.5A CN201810328580A CN108210928A CN 108210928 A CN108210928 A CN 108210928A CN 201810328580 A CN201810328580 A CN 201810328580A CN 108210928 A CN108210928 A CN 108210928A
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vitamin
composition
stem cell
mescenchymal stem
natriuretic peptide
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CN108210928B (en
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曲晓峰
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Jiangxi Han's joint stem cell technology Co., Ltd.
Tianjin AmCellGene Engineering Co., Ltd.
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Changchun Bobon Enterprise Management Consulting Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41781,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Abstract

The present invention relates to the applications in a kind of composition and tissue repair comprising mescenchymal stem cell and vitamin, belong to medical domain.In the composition, a concentration of (1 7) × 10 of the mescenchymal stem cell5A/ml;A concentration of 0.1 10mg/ml of the vitamin.In addition, the natriuretic peptide of 10 100ng/ml and the angiotensin II receptor antagonist (AngII receptor antagonists) of 0.1 0.5mg/ml can also be included in the composition.

Description

It is applied in composition and its tissue repair comprising mescenchymal stem cell and vitamin
Technical field
The present invention relates to the applications in a kind of composition and tissue repair comprising mescenchymal stem cell and vitamin, belong to Medical domain.
Background technology
Mescenchymal stem cell (mesenchymal stem cells, MSCs) is the non-Hematopoietic Stem with a variety of differentiation potentials Cell, because it is easy to detach from the tissues such as marrow, adipose tissue, synovial membrane, periosteum, tooth, placenta, umbilical cord, and with height Effect differentiation potential, nutritional activities, immunomodulatory properties and huge donor pond, MSCs have caused stem-cell therapy domain expert Great interest, and be considered as cytothesis treatment potential tool.However, the source of MSCs and decontamination procedure are to it Treatment potential is still most important, and the standardization of best MSCs separable programmings certainly helps its best clinical practice.MSCs exists Various kinds of cell pedigree can be not only divided under its specific environment, but also having makes it successfully carry out the immune of allograft Inhibit efficiency.Actively tend to inflammatory or tumor tissues in addition, MSCs has in vivo, promote the characteristics such as vascularization, in vitro Have many advantages, such as to be easily isolated culture amplification, be easy to be transfected and stablized by foreign gene expression.
Although stem cell always illustrates rosy prospect in the treatment of many diseases, researches show that in target tissue at present It is relatively low to be implanted into MSCs recall rate ratios, has seriously affected repairs of the MSCs to target organ tissue.This may be with MSCs in target Field planting in tissue is related, but it is prior that it is low, which to migrate the ratio for reaching target tissue and being colonized and (going back to the nest), for MSCs intravasculars Factor.Therefore it is the key that MSCs treatment diseases to improve MSCs and go back to the nest to target organ.In general, in MSCs clinical practices, Injection fashion has vein transplantation, artery transplantation and local transplantation.Vein transplantation rate of going back to the nest is relatively low, but method security is high.Artery The rate of going back to the nest of transplanting will be apparently higher than vein transplantation, but artery transplantation increases the possibility of arteriole occlusion.And local transplantation Although can directly note MSCs in target organ, risk is larger in clinical practice, and local MSCs is usually due to ischemic Nutrition is lacked before therapeutic effect is generated with regard to dead.
Hepatic sclerosis is the performance of whole latter stage of various chronic liver disease development, and with liver proliferation of fibrous tissue, pseudolobuli is formed as allusion quotation Type feature, normal liver cell is largely impaired at this time destroys, and hepatic parenchymal cells quantity is reduced, when the damage that liver is subject to is more than it During compensation, the wretched insufficiency of the various functions such as liver its synthesis, deposit, removing toxic substances, immune will be led to, generate therewith it is a series of with Corresponding clinical symptoms and performance, serious threat people's health still lack effective remedy measures for hepatic sclerosis at present, Liver transfer operation hinders it in clinical extensive development due to the limitation of various conditions.The research and probe of stem cell field makes to have Derive from a wealth of sources, the MSCs for the advantages such as immunogenicity is weak, Proliferation, Differentiation ability is strong is in terms of End-stage liver disease is treated, show tempting Clinical value, be expected to break through for the treatment zone of related End-stage liver disease.
However, in the application of MSCs treatment hepatic sclerosis, other than the problem of rate of going back to the nest after transplanting mentioned above is low, return There is also some problems for the induction differentiation of stem cell after nest.Some researches show that MSCs can be divided into flesh after individual is transplanted to Fibroblast leads to collagen deposition, so as to aggravate liver fibrosis, leads to individual aggravation.Therefore, how target is provided Organ go back to the nest rate and induce its be divided into purpose histocyte be this field be badly in need of solve the technical issues of.
Invention content
The first aspect of the present invention is to provide a kind of composition, including mescenchymal stem cell and vitamin.
In one embodiment, in the composition, a concentration of (1-7) × 10 of the mescenchymal stem cell5A/ ml;A concentration of 0.1-10mg/ml of the vitamin.
In another embodiment, the vitamin is selected from:Vitamin A, vitamin B3, vitamin B5, vitamin B6, One or more of vitamin D, vitamin E, vitamine M (folic acid) and Co-Q10.
In scheme is further carried out, the vitamin is made of vitamin B3 and vitamine M;Weight between the two Than being 1:0.1-0.5.
In yet another embodiment, the natriuretic peptide and 0.1-0.5mg/ of 10-100ng/ml is also included in the composition The angiotensin II receptor antagonist (AngII receptor antagonists) of ml.
In specifically embodiment, the natriuretic peptide is atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) or c-type natriuretic peptide;It is excellent It is selected as c-type natriuretic peptide.
In yet another embodiment, the angiotensin II receptor antagonist is selected from Eprosartan (eprosartan) and Telmisartan (telmisartan).
In another embodiment, the mescenchymal stem cell can be marrow, adipose tissue, synovial membrane, periosteum, tooth Tooth, placenta or umbilical cord mesenchymal stem cells.
In one more specifically embodiment, the composition, including (1-7) × 105The mesenchyma of a/ml is done carefully Born of the same parents, the vitamin B3 of 1-3mg/ml, the vitamine M of 0.1-1.5mg/ml, the natriuretic peptide and 0.2-0.4mg/ml of 30-50ng/ml Angiotensin II receptor antagonist.
The second aspect of the present invention is to provide a kind of pharmaceutical preparation for including above-mentioned composition, by composition and pharmaceutically Acceptable auxiliary material composition.Further, the pharmaceutical preparation is injection.
The third aspect of the present invention is to provide application of the above-mentioned composition in tissue repair drug is prepared.The tissue is repaiied It is again the tissue repair after liver fibrosis.
In above-mentioned composition purposes, aforementioned pharmaceutical compositions can be prepared into according to the animal state of an illness and agents area Suitable pharmaceutical preparation is to facilitate medication, and for the present invention, the administration time and administration number of times of composition are needed according to disease Depending on the specific diagnostic result of feelings, within this technical scope grasped in those skilled in the art.For example, by the treatment to mouse Scheme is applied on the person, and all drugs can change the effective dose of mouse by the drug effective dose of people It calculates, this is obvious for those of ordinary skill in the art.
The fourth aspect of the present invention is to provide a kind of preparation method of above-mentioned composition, including
1) mescenchymal stem cell is prepared;
2) mescenchymal stem cell of harvest is diluted to treatment concentration with buffer solution, then according to respective concentration by vitamin B3, vitamine M, natriuretic peptide and angiotensin II receptor antagonist are added in cell suspension, are placed in incubator and are incubated after 1h i.e. .
It is a discovery of the invention that vitamin B3 can improve stem cell to the rate of going back to the nest of liver organization, and inhibit it to fiber finer Born of the same parents break up;Natriuretic peptide and angiotensin II receptor antagonist have the function of expansion blood vessel in itself, this is conducive to mesenchyma and does Cell going back to the nest to target organ tissue by blood vessel, and can prevent from causing blood in infusion process due to high-concentration dry cell Pipe embolization;Further it has also been found that natriuretic peptide and angiotensin II receptor antagonist are filled between can also inducing Matter stem cell into hepatocyte breaks up;Itself own antioxidation of vitamine M (folic acid) can improve liver fibrosis damage, and And further it has to the synergistic functions of above-mentioned three kinds of substances.
Specific embodiment
Can also the present invention further be understood by embodiment, wherein the embodiment illustrates some preparations or user Method.It is to be appreciated, however, that these embodiments do not limit the present invention.The change of the present invention of currently known or further exploitation Change is considered within the scope of the invention described herein and claimed below.
In the present invention, according to the common sense of those skilled in the art, the concentration of mescenchymal stem cell in the present composition, Vitamin B3, vitamine M, natriuretic peptide and angiotensin II receptor antagonist concentration be only that stem cell medicine is just configured Concentration when good, since mescenchymal stem cell is active, it is thus impossible to the concentration after being interpreted as matching placement location for a period of time.
In addition, source for mesenchymal stem cells used in the present invention is extensive, however it is not limited to which the mesenchyma of particular source is done carefully Born of the same parents, the mescenchymal stem cell can be prepared by methods known in the art or be obtained by commercial channel.
For the present composition, in addition to mescenchymal stem cell, other compositions can be lured separately as stem cell Agent is led to apply or the vitamin B3 of 1-3mg/ml, the vitamine M of 0.1-1.5mg/ml, the natriuretic peptide of 30-50ng/ml and The angiotensin II receptor antagonist of 0.2-0.4mg/ml
It is prepared by 1 adipose tissue mescenchymal stem cell (ADMSCs) of embodiment
(1) human fat tissue is taken, D-Hank ' the s balanced salt solutions for being 7.2-7.4 with pH value are centrifuged repeatedly flushing, and centrifugation is gone Except extra blood;
(2) adipose tissue is rubbed as 1-2mm3Fritter adds in the digestive juice isometric with taken adipose tissue and disappears Change, be put into shaking table 37 DEG C, 190rpm digestion 30min;It adds in isometric BME culture mediums containing 15%FBS and terminates digestion; The digestive juice be concentration be respectively 0.1% pancreas enzyme -EDTA, 0.3% type i collagen enzyme D-Hank ' s balance salt it is molten Liquid;
(3) stratification blows and beats D-Hank ' the s balanced salt solutions that bottom cell is 7.2-7.4 with pH value repeatedly, cleaning Totally;The liquid washed down is filtered through 100 mesh screens, and removal does not digest tissue, and centrifugation discards supernatant liquid, by fat stem cell Suspension and erythrocyte cracked liquid are with 1:1 mixing is incubated 2 minutes, 4 DEG C, centrifuge 5min under the conditions of centrifugal force 450g, is trained using BME Foster base weight hangs fat stem cell;
(4) by the stem cell of acquisition according to 2-3 × 104/cm2Density be inoculated in culture bottle, add in culture solution and (contain L- Glutamine 1mmol/L, basic fibroblast growth factor 2 0ng/ml, epidermal growth factor 5ng/ml, leukaemia inhibit because The BME culture mediums of sub- 5ng/ml), it is placed in 37 DEG C, CO2Concentration 5%, humidity 95% incubator in cultivated, will be former after 1 day Culture solution suction is abandoned, and is replaced fresh culture solution, is discarded non-adherent cell, and replacement culture solution is primary within every 24 hours later, treats cell Growth reaches 80% fusion, and in culture bottle plus 0.25% pancreas enzyme -EDTA is digested, by 1:3 passages, after obtaining secondary culture Human fat tissue mescenchymal stem cell stem cell.
The adipose tissue mescenchymal stem cell obtained is detected through antigen, between the adipose tissue with CD34, CD31 and CD45 Mesenchymal stem cells account for total stem cell ratio less than 1%;It is filled between adipose tissue with CD29, CD73, CD90, CD105 and CD49d Matter stem cell is higher than 95% in the ratio of total stem cell.
It is prepared by 2 composition of embodiment
The ADMSCs that embodiment 1 obtains is diluted to 3 × 10 with PBS buffer solution5A/ml, then will according to respective concentration 2mg/ml vitamin B3s, 0.8mg/ml vitamine Ms, 40ng/ml c-types natriuretic peptide and 0.3mg/ml Eprosartans are added to carefully In born of the same parents' suspension, be placed in incubator and be incubated after 1h to obtain the final product.
It is prepared by 3 composition of embodiment
The ADMSCs that embodiment 1 obtains is diluted to 6 × 10 with PBS buffer solution5Then a/ml adds in the dimension of 3mg/ml Raw element B3, the vitamine M of 1.5mg/ml, the natriuretic peptide of 50ng/ml and the Eprosartan of 0.2mg/ml are placed in incubator and are incubated 1h Afterwards to obtain the final product.
4 ADMSCs vitro conversion researchs of embodiment
RPMI1640 culture mediums of the ADMSCs that embodiment 1 obtains containing 10%FBS is resuspended, is adjusted to 3 × 105A/ Ml is placed in 5ml/ wares in culture dish, and different component is added in different culture dishes, and observation ADMSCs is starlike to hepatic lineage or liver Transformation efficiency.
Specific each group addO-on therapy is following (final concentration):
Group 1:Any component is not added
Group 2:4mg/ml vitamin B3s and 1.6mg/ml vitamine Ms
Group 3:80ng/ml c-types natriuretic peptide and 0.6mg/ml Eprosartans
Group 4:2mg/ml vitamin B3s, 0.8mg/ml vitamine Ms, 40ng/ml c-types natriuretic peptide and 0.3mg/ml Yi Puluo Sha Tan
Group 5:5 μ g/ml M-CSF, 2 μ g/ml HGF and 10 μ g/ml FGF-4
Each group culture dish is cultivated 14 days in incubator, draws culture medium in culture dish, is added in 4% paraformaldehyde and is consolidated in room temperature It is 1 hour fixed, the positive rate of each group cell expression ALB, AFP and GFAP, parallel repetition 3 are then measured using immunofluorescence method It is secondary, it is averaged.
Concrete outcome is as follows:
ALB (%) AFP (%) GFAP (%)
Group 1 8.3±4.6 2.1±0.4 10.8±2.1
Group 2 45.4±5.9** 25.2±3.8** 5.6±1.4**
Group 3 21.7±5.1** 6.8±2.6* 9.3±2.6
Group 4 76.5±6.3**## 49.4±4.9**# 1.7±0.5**##
Group 5 49.8±4.7** 36.7±3.2** 19.6±2.9**
It is examined through Oneway-ANOVA, * and * * are represented compared with group 1, p<0.05 or 0.01;## represents the P compared with other groups< 0.01
It is known in the art that ALB and AFP are the protein labelings that mescenchymal stem cell is converted to hepatic lineage, GFAP is to liver The label of sternzellen conversion;Sternzellen forms myofibroblast by transdifferentiation in vivo, and then causes liver fine Dimensionization.Therefore it is converted in induction stem cell to hepatic lineage, and it is inhibited to be converted to sternzellen.The above results show combination The addO-on therapy of object inhibits it to be converted to sternzellen so that stem cell preferably to be induced to be converted to hepatic lineage;This field is conventional Although derivant can induce hepatic lineage to convert, also there is a certain proportion of cell transformation for sternzellen, this is also likely to be Convenient stem cells composition can not play a major reason of therapeutic effect in vivo.
5 composition of embodiment leads to CCl4 the influence of Rat Liver Fibrosis Model
Adult SD male rat, weight 200g or so is selected, is randomly divided into control group, liver cirrhosis group and administration group.Control Group is subcutaneously injected physiological saline, liver cirrhosis group and administration group on every Mondays, three, five be subcutaneously injected 60% carbon tetrachloride-soybean oil, Dosage is 0.3ml/100g, starts to be administered after 8 weeks;Control group and liver cirrhosis group tail vein infusion 2ml physiological saline, administration group tail 2ml composition solutions are injected intravenously, administration group concrete scheme is as follows:
Group 1:3×105The PBS buffer solution of the ADMSCs of a/ml
Group 2:3×105ADMSCs, 4mg/ml vitamin B3 of a/ml and the PBS buffer solution of 1.6mg/ml vitamine Ms
Group 3:3×105ADMSCs, 80ng/ml c-type natriuretic peptide of a/ml and the PBS of 0.6mg/ml Eprosartans delay Fliud flushing
Group 4:3×105ADMSCs, 2mg/ml vitamin B3,0.8mg/ml vitamine Ms, the 40ng/ml c-type sodium of a/ml Urinate the PBS buffer solution of peptide and 0.3mg/ml Eprosartans
Weekly administration is primary, and successive administration puts to death rat, blood is taken to centrifuge after 4 weeks, measures Human Serum Albumin (ALB), alkali Acid phosphatase (ALP) and glutamic-pyruvic transaminase (ALT).In addition, each group rat liver tissue is taken to cook frozen section, and in fluorescence microscopy The cell number that DAPI is marked in random 5 visual field observation liver organizations of picking under mirror.
Concrete outcome is as follows:
1st, composition influences ALB, ALP and ALT content in serum
ALB(g/L) ALP(U/L) ALT(U/L)
Control group 38.9±3.4 107±12 28±7
Liver cirrhosis group 20.1±2.8## 259±26## 157±16##
Group 1 26.7±4.3** 193±17** 118±21**
Group 2 32.4±3.1** 176±22** 96±15**
Group 3 33.8±2.9** 162±19** 74±16**
Group 4 39.5±3.7** 131±14** 42±11**
2nd, composition is to stem cell homing effects
The content of present invention merely illustrates some claimed specific embodiments, one of them or more skill Recorded technical characteristic can be combined with arbitrary one or more technical solutions in art scheme, these are combined and obtain Technical solution also in the application protection domain, technical solution is disclosed in the present invention just as obtained from these are combined It is specifically recorded in content the same.

Claims (10)

1. a kind of composition, including mescenchymal stem cell and vitamin.
2. composition according to claim 1, which is characterized in that a concentration of (1-7) × 10 of the mescenchymal stem cell5 A/ml;A concentration of 0.1-10mg/ml of the vitamin.
3. composition according to claim 1, which is characterized in that the vitamin is selected from:Vitamin A, vitamin B3, dimension One or more of raw element B5, vitamin B6, vitamin D, vitamin E, vitamine M (folic acid) and Co-Q10.
4. composition according to claim 3, which is characterized in that the vitamin is made of vitamin B3 and vitamine M; Weight ratio between the two is 1:0.1-0.5.
5. according to claim 1-3 any one of them compositions, which is characterized in that also include 10- in the composition The natriuretic peptide of 100ng/ml and the angiotensin II receptor antagonist (AngII receptor antagonists) of 0.1-0.5mg/ml.
6. according to claim 5 any one of them composition, which is characterized in that the natriuretic peptide is atrial natriuretic peptide (ANP), brain sodium Peptide (BNP) or c-type natriuretic peptide;Preferably c-type natriuretic peptide.
7. according to claim 5 any one of them composition, which is characterized in that the angiotensin II receptor antagonist choosing From Eprosartan (eprosartan) and Telmisartan (telmisartan).
8. according to claim 5 any one of them composition, which is characterized in that the composition, including (1-7) × 105 The mescenchymal stem cell of a/ml, the vitamin B3 of 1-3mg/ml, the vitamine M of 0.1-1.5mg/ml, the natriuresis of 30-50ng/ml The angiotensin II receptor antagonist of peptide and 0.2-0.4mg/ml.
9. a kind of pharmaceutical preparation for including any one of the claim 1-8 composition, by composition and pharmaceutically acceptable Auxiliary material composition.
10. application of any one of the claim 1-8 compositions in tissue repair drug is prepared;The tissue repair is liver Tissue repair after fibrosis.
CN201810328580.5A 2018-04-12 2018-04-12 Composition containing mesenchymal stem cells and vitamins and application thereof in tissue repair Active CN108210928B (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106038596A (en) * 2016-05-26 2016-10-26 深圳爱生再生医学科技有限公司 Stem cell preparation capable of resisting hepatic fibrosis and preparation method of stem cell preparation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106038596A (en) * 2016-05-26 2016-10-26 深圳爱生再生医学科技有限公司 Stem cell preparation capable of resisting hepatic fibrosis and preparation method of stem cell preparation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
赵鸽等: "血管钠肽抑制肝纤维化的实验研究", 《中国普通外科杂志》 *
郭津生: "重视肝纤维化的诊治", 《临床肝胆病杂志》 *

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