CN114425056A - Stem cell exosome composition for improving asthma - Google Patents

Stem cell exosome composition for improving asthma Download PDF

Info

Publication number
CN114425056A
CN114425056A CN202011098420.XA CN202011098420A CN114425056A CN 114425056 A CN114425056 A CN 114425056A CN 202011098420 A CN202011098420 A CN 202011098420A CN 114425056 A CN114425056 A CN 114425056A
Authority
CN
China
Prior art keywords
stem cell
asthma
cell exosome
group
composition according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202011098420.XA
Other languages
Chinese (zh)
Inventor
陈俊峰
李检平
林洁
梅寒
许璐云
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ningbo Sinosat Biotechnology Co ltd
Original Assignee
Ningbo Sinosat Biotechnology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ningbo Sinosat Biotechnology Co ltd filed Critical Ningbo Sinosat Biotechnology Co ltd
Priority to CN202011098420.XA priority Critical patent/CN114425056A/en
Publication of CN114425056A publication Critical patent/CN114425056A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2066—IL-10
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0662—Stem cells
    • C12N5/0665—Blood-borne mesenchymal stem cells, e.g. from umbilical cord blood
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y113/00—Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13)
    • C12Y113/11—Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13) with incorporation of two atoms of oxygen (1.13.11)
    • C12Y113/11017—Indole 2,3-dioxygenase (1.13.11.17)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/02—Atmosphere, e.g. low oxygen conditions
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Biomedical Technology (AREA)
  • Pulmonology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Hematology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Rheumatology (AREA)
  • Microbiology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Otolaryngology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention relates to a stem cell exosome composition for improving asthma, which is characterized by comprising stem cell exosomes as active ingredients and 1-3% of ectoin, and compared with the prior art, the stem cell exosome composition has the following advantages: the composition of the stem cell exosome and the ectoin can reduce or block the release of TNF-alpha and IL-1 beta, and can improve the synthesis of IL-10, and is expected to become an effective method for treating asthma in the future.

Description

Stem cell exosome composition for improving asthma
Technical Field
The invention relates to the technical field of pharmaceutical compositions for improving asthma, in particular to a specific stem cell exosome composition for improving asthma.
Background
Asthma is a chronic respiratory disease affecting approximately 3 million people worldwide, causing 25 million deaths each year. Current asthma therapies, including corticosteroids and beta-agonists, subjects treated with beta-agonist based therapies may relieve their asthmatic symptoms, but their underlying airway inflammation remains. Thus, subjects requiring long-term use of beta-agonists are at greater risk of severe exacerbation of asthma, resulting in hospitalization and death. Severe asthma patients are reported to often require treatment with high doses of corticosteroid hormones, which may be associated with systemic side effects and do not necessarily improve lung function or quality of life. In addition, asthma sufferers continue to develop sporadic asthma attacks, which are often associated with provocative factors, including viral or bacterial infections, air pollution in the environment, and the inability to prevent asthma attacks in most patients. After long-term use, the blood sugar and blood pressure in the body can be increased, the resistance of the human body is reduced, the gastric mucosa can be stimulated to induce gastrointestinal bleeding, and the elderly are easy to suffer from osteoporosis. This therefore highlights an urgent need for effective treatment of asthma.
For example, chinese patent application No. CN201880059290.3 (application publication No. CN 111093680A), entitled "method for treating Allergic Airway Disease (AAD)/asthma", discloses a method for treating allergic airway disease/asthma using mesenchymal stem cells, which has been demonstrated by an allergic airway disease mouse model simulating several features of human asthma that exhibit immunomodulatory and anti-inflammatory properties through direct cell contact and paracrine factor secretion. Administration of exogenous mesenchymal stem cells was shown to reduce Th2 proliferation and to reduce Th2 preference, which contributed to AAD, and inhibition of dendritic cell activation, migration, and antigen presentation had been observed. A reduction in eosinophil-associated proinflammatory cytokines was observed in bronchoalveolar lavage fluid, and mesenchymal stem cells were shown to actively reduce the presence and activity of inflammation-causing cells in these models compared to AI-inhibiting corticosteroids. However, since the exact cause of asthma is not clear, the therapeutic effect of a single component (e.g., mesenchymal stem cells) may be temporary and may occur only in certain patients, and thus, continuous research and clinical trials are required. To overcome these limitations, it is necessary to develop a new therapeutic agent for treating asthma.
Disclosure of Invention
The first technical problem to be solved by the present invention is to provide a novel pharmaceutical composition for improving asthma in view of the current state of the art.
The second technical problem to be solved by the present invention is to provide a use of a stem cell exosome isolated from umbilical cord-derived mesenchymal stem cells in the preparation of a medicament for preventing or treating asthma, aiming at the current situation of the prior art.
The technical scheme adopted by the invention for solving the first technical problem is as follows: the pharmaceutical composition for improving asthma is characterized in that: comprises a stem cell exosome as an active ingredient.
Further, the stem cell exosomes are isolated from the inter-umbilical stem cells cultured under hypoxic conditions.
Further, the hypoxic conditions are induced by 2% to 9% oxygen or by a hypoxic cell sensitizer.
Further, the stem cell exosomes comprise bioactive factors indoleamine 2,3 dioxygenase (IDO) and interleukin-10.
Further, the pharmaceutical composition comprises a stem cell exosome and ectoin.
Further, the concentration of the ectoin is 1% to 3%.
Further, the pharmaceutical composition comprises the stem cell exosomes at a concentration of 150-200 ug/ml.
Further, the pharmaceutical composition is for intratracheal administration or inhalation.
Further, the pharmaceutical composition is an aerosolized medicament.
In order to solve the second technical problem, the present invention also provides a use of a stem cell exosome isolated from umbilical cord-derived mesenchymal stem cells in the preparation of a medicament for preventing or treating asthma.
Compared with the prior art, the invention has the following advantages: the composition of the stem cell exosome and the ectoin can reduce or block the release of TNF-alpha and IL-1 beta, and can improve the synthesis of IL-10, and is expected to become an effective method for treating asthma in the future.
Drawings
FIG. 1 is a flowchart for the preparation of a pharmaceutical composition for ameliorating asthma according to example 1 of the present invention;
FIG. 2 is a reference chart showing the steps of the nebulization treatment of asthma rats of different groups with the pharmaceutical composition according to example 3 of the present invention;
FIG. 3 is a bar graph showing the relative expression levels of TNF- α in lung tissue in normal rats and in asthmatic rats of different groups according to example 3 of the present invention;
FIG. 4 is a bar graph showing the relative expression levels of serum TNF- α in normal rats and in asthmatic rats of different groups according to example 3 of the present invention;
FIG. 5 is a bar graph showing the relative expression levels of IL-1. beta. in lung tissue in normal rats and in asthmatic rats of different groups in example 3 of the present invention;
FIG. 6 is a bar graph showing the relative expression levels of serum IL-1. beta. in normal rats and in asthmatic rats of different groups in example 3 of the present invention;
FIG. 7 is a bar graph showing the relative expression amounts of IL-10 in lung tissue in normal rats and asthmatic rats of different groups in example 3 of the present invention;
FIG. 8 is a bar graph showing the relative expression levels of serum IL-10 in normal rats and in asthmatic rats of different groups in example 3 of the present invention.
Detailed Description
The invention is further described by the following embodiments in conjunction with the drawings.
Example 1 preparation of Stem cell exosome composition for ameliorating asthma
The stem cell Exosome (Exosome) is a lipid inclusion structure, and substances such as cell factors, mRNA and the like are wrapped inside the stem cell Exosome, so that the immunity of a human body can be adjusted through immune cells, inflammatory reaction can be inhibited through the cell factors, and the lung function is improved and protected. Ectoin (Ectoin) is an amino acid derivative and belongs to an extremophilic enzyme component. Extreme electrolytes are protective molecules with little stress that can protect extreme microorganisms and plants from the harmful environmental effects of habitats such as salt lakes, spas, ice cubes, deep sea or desert survivors (Ectoin). The anti-pollution efficacy of Ectoin (Ectoin) has been demonstrated in a number of studies (in vitro and in vivo clinical). To date, it is also the only antipollution active ingredient approved for use in medical products and medical applications, including the prevention of pollution-induced pulmonary diseases such as asthma. Exosomes are tiny vesicles secreted by umbilical cord stem cells, with a diameter of about 30-200nm, and 5um sized particles can reach the bronchioles and alveoli, thus the volume of exosomes is very suitable for aerosolization.
The method comprises the following specific steps:
[ primary bronchial epithelial cells/tracheal epithelial cells derived from asthma patients were purchased from LONZA under the accession number (LONZA CC2932s), cultured with 500mL of LONZA's medium CC-3171(BEBM bronchial epithelial cell growth basal medium), and CC-4175(BEGM SingleQuots supplement and growth factor) until day 22, and differentiated into transepithelial resistance, mucin production, and cilia production. When the cell fusion degree reaches 70-80%, washing the cells with normal saline for 2 times, and performing starvation culture with compound electrolyte injection; after starvation culture for 12-24 hours, the fusion degree of the first batch of cells reaches 90% -95%, cell supernatant is collected, centrifuged for 5-8min under the condition of 3000-4500g, sediment is removed, and centrifuged to obtain supernatant for later use (A);
② culturing umbilical cord mesenchymal stem cells: selecting 3 tubes of P3 generation mesenchymal stem cells from the stem cell bank for resuscitation, and recovering 1 × 10e in total7Cells, the inoculation density of which is 30% -60% of the maximum fusion degree respectively; complete culture medium of T4 for culturing cells plus 10% human blood platelet lysate; after the inoculation of the cells is finished, the cells are placed in a culture box with the temperature of 37 ℃, the hypoxia concentration of 2-9 percent and the volume concentration of 5 percent of carbon dioxide for hypoxia culture, and the stem cells are activated under the condition of simulating the lack of oxygen of human asthmaRelease of hypoxia inducible factor, HIF, and related factors; when the cell fusion degree reaches 70-80%, washing the cells with normal saline for 2 times, adding the supernatant (A) obtained in the first step with compound electrolyte injection, and performing starvation culture; after starvation culture is carried out for 12-24 hours, the cell fusion degree reaches 90% -95%, 2-3 × 10e7 stem cell culture supernatant is collected, centrifugation is carried out for 5-8min under the condition of 3000-4500g to remove precipitates, the centrifuged supernatant is filtered by an ultracel-10 ultrafiltration membrane, and finally 200ul volume of concentrated supernatant containing various cell factors and exosomes (B) is obtained;
③ the composition of the specific stem cell exosome and ectoin: the concentrated supernatant exosomes (B) are added into 10ml of normal saline containing 1-3% of ectoin to be re-suspended to prepare an atomizing agent, so that the specific stimulation umbilical cord stem cell exosomes and 1-3% of ectoin are combined according to a formula to improve asthma in an atomizing mode, and the specific preparation process refers to the figure 1.
Example 2 establishment of asthma rat animal model
(1) Method and material
Selecting female SD rats with the weight of 120-180g, and raising the SD rats in a controlled environment at a 12-hour illumination/12-hour dark illumination cycle to freely obtain water and laboratory food; before any experiment was performed, all mice were provided with an adaptation period of 4-5 days, divided into normal (group a), asthmatic (group B), asthmatic (group C), asthmatic (group D) groups of 13 rats each.
(2) Experimental reagent and instrument
Physiological saline; 25 g/bottle of egg white albumin; 2 ml/count of inactivated bordetella pertussis vaccine; 500g of aluminum hydroxide per bottle; an ultrasonic atomizer.
(3) Molding method
Firstly, adaptively feeding rats for one week before the rats are modeled.
② the rats in groups B to D are sensitized by injecting 1ml of antigen liquid (each ml of antigen liquid contains 100mg of ovalbumin, 100mg of aluminum hydroxide dry powder and 5 × 10e9 inactivated Bordetella pertussis vaccines) into the abdominal cavity. When asthma is stimulated after 2 weeks, each group of rats is respectively placed in a semi-closed mouse cage, 5% egg white albumin physiological saline is atomized and inhaled for 40min, and the stimulation is carried out for 1 time every day for 8 days continuously. The mice in group A are injected with normal saline instead of antigen solution, the injection site and the injection dosage are the same as those in group B, group C and group D, wherein the injection is atomized and inhaled into the normal saline of ovalbumin, and the concentration of the ovalbumin is 0.05 mg/mL.
(4) Asthma rat model Observation
Asthmatic rats develop several main features: asthmatic rats (group B), asthmatic rats (group) and asthmatic rats (group D) exhibited tachypnea, slowed breathing or dysrhythmia in the critically ill, mild cyanosis, flaccid limbs, sluggishness of movement, unresponsiveness and were accepted in the art as a clinical model of asthma.
EXAMPLE 3 nebulization treatment of asthma rat animals Using pharmaceutical compositions
After the asthma rat animal model is established, the pharmaceutical composition is used for carrying out atomization treatment on the asthma rat animal, and the specific steps are as follows:
the normal group (group A) of rats uses physiological saline to replace antigen liquid;
② asthma rats (group B) receive the composition of the specific exosome (containing stem cell factor) and ectoin in the ultrasonic atomizer for 7 days in the box, and the composition is sprayed 30 minutes per day;
③ asthma rats (group C) received 7 days in the box by the ultrasonic atomizer, and sprayed with physiological saline 30 minutes a day;
(iv) asthma rats (group D) receive the treatment for 7 days in the chamber with the ultrasonic nebulizer, and spray physiological saline + 1-3% ectoin 30 minutes per day, and the specific nebulization treatment step chart can refer to fig. 2;
anaesthetizing normal group (A group) and asthma rat (B), asthma rat (C) and asthma rat (D) on day 8, collecting 20 ml blood, centrifuging to obtain serum, dissecting to obtain 50mg lung tissue, homogenizing in frozen lysis buffer, centrifuging at 4 deg.C for 5 min at 12000rpm to obtain 50ul supernatant;
sixthly, performing enzyme-linked immunosorbent assay (ELISA) on the serum and the supernatant to analyze the IL-1 beta, TNF-alpha and IL-10 levels, and referring to the results of FIGS. 3 to 8;
wherein, as can be seen from FIGS. 3-6, the effect of the pharmaceutical composition on TNF- α and IL-1 β in lung tissue is semi-quantitatively determined from HE stained lung sections, and both play a key role in asthma and are the activators of inflammatory cytokine networks, accelerating and strengthening factors and tissue injury factors, TNF- α and IL-1 β in lung tissue and in serum are the same as in normal group (group A) rats after asthma rats (group B) received 7 consecutive days of specific stem cell exosomes and the atomization of the ectoine composition, but TNF- α and IL-1 β levels in lung tissue and serum are significantly higher in asthma rats (group C) after receiving 7 consecutive days of physiological saline than in control SD rats (group A) and asthma rats (group B), TNF- α and IL-1 β in lung tissue and serum after asthma rats (group D) received 7 consecutive days of 1-3% ectoine The level of blood has been slightly increased.
Effect of specific pharmaceutical compositions on TNF- α and IL-1 β in pulmonary tissue:
Figure BDA0002724522860000051
note: group C in TNF- α of lung tissue, P < 0.01 compared to group a; p < 0.01 compared to group B; p < 0.05 compared to group D;
lung tissue IL-1 β in group C, P < 0.001 compared to group a; p < 0.01 compared to group B.
Effect of specific pharmaceutical compositions on serum TNF- α and IL-1 β:
Figure BDA0002724522860000052
note: group C in TNF- α of serum, P < 0.01 compared to group a; p < 0.01 compared to group B; p < 0.05 compared to group D;
serum IL-1 β in group C, P < 0.001 compared to group a; p < 0.001 compared to group B.
The effect of specific pharmaceutical compositions on pulmonary IL-10 and serum IL-10:
Figure BDA0002724522860000061
note: lung IL-10 in group C, P < 0.01 compared to group a; p < 0.01 compared to group B; p < 0.05 compared to group D;
serum IL-1 β in group C, P < 0.01 compared to group a; p < 0.01 compared to group B.
The results of fig. 7 and 8 show that IL-10 is a cytokine discovered in recent years, is produced by mononuclear macrophages, T cells, B cells and the like, is a strong immunosuppressive factor with multi-directional biological activity, has an anti-inflammatory effect, and has potential application prospects in treating bronchial asthma by IL-10. The level of IL-10 in lung tissue and serum after 7 consecutive days of physiological saline in asthmatic rats (group C) was significantly lower than in control SD rats (group A) and asthmatic rats (group B). After 7 consecutive days of nebulization of the specific stem cell exosomes and ectoin composition with asthma rats (group B), the IL-10 levels in lung tissue and serum were identical to those of the control SD rats (group a), and after 7 consecutive days of 1-3% ectoin asthma rats (group D), the IL-10 levels in lung tissue and serum were slightly reduced. Therefore, the composition of the stem cell exosome and 1-3% of ectoin can trigger the generation of IL-10 to inhibit inflammation promoting factors including TNF-a and IL-1b beta, and is expected to become an effective method for treating asthma in the future. While one advantage of the present invention is that stem cell exosomes in combination with ectoin can be used alone to treat asthma, it is to be understood that stem cell exosomes in combination with ectoin can be combined with another asthma therapy, e.g., when an asthma subject has an existing asthma treatment regimen comprising, for example, corticosteroid or beta-agonist therapy, and is subsequently treated in combination with ectoin, a physician can still treat the asthma subject with the other asthma therapy.

Claims (10)

1. A stem cell exosome composition for ameliorating asthma, characterized by: comprises a stem cell exosome as an active ingredient.
2. The stem cell exosome composition according to claim 1, characterized in that: the stem cell exosomes are isolated from inter-umbilical stem cells cultured under hypoxic conditions.
3. The stem cell exosome composition according to claim 2, characterized in that: the hypoxic conditions are induced by 2% to 9% oxygen or by hypoxic cell sensitizers.
4. The stem cell exosome composition according to claim 1, characterized in that: the stem cell exosomes comprise the bioactive factors indoleamine 2,3 dioxygenase (IDO) and interleukin-10.
5. A stem cell exosome composition according to any one of claims 1 to 4, characterised in that: the stem cell exosome preparation composition comprises stem cell exosomes and ectoin.
6. The stem cell exosome composition according to claim 5, characterized in that: the concentration of the ectoin is 1% -3%.
7. The stem cell exosome composition according to claim 6, characterized in that: the pharmaceutical composition contains stem cell exosomes at a concentration of 150-200 ug/ml.
8. A stem cell exosome composition according to claim 5 or 6, characterised in that: the pharmaceutical composition is for intratracheal administration or inhalation.
9. The stem cell exosome composition according to claim 8, characterized in that: the pharmaceutical composition is an aerosolized medicament.
10. Use of a stem cell exosome isolated from umbilical cord-derived mesenchymal stem cells in the preparation of a medicament for the prevention or treatment of asthma.
CN202011098420.XA 2020-10-14 2020-10-14 Stem cell exosome composition for improving asthma Pending CN114425056A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011098420.XA CN114425056A (en) 2020-10-14 2020-10-14 Stem cell exosome composition for improving asthma

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011098420.XA CN114425056A (en) 2020-10-14 2020-10-14 Stem cell exosome composition for improving asthma

Publications (1)

Publication Number Publication Date
CN114425056A true CN114425056A (en) 2022-05-03

Family

ID=81309690

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011098420.XA Pending CN114425056A (en) 2020-10-14 2020-10-14 Stem cell exosome composition for improving asthma

Country Status (1)

Country Link
CN (1) CN114425056A (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103857394A (en) * 2011-09-09 2014-06-11 比托普股份公司 Therapeutic uses of ectoin

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103857394A (en) * 2011-09-09 2014-06-11 比托普股份公司 Therapeutic uses of ectoin

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BIN XU等: "Stem cell derived exosomes-based therapy for acute lung injury and acute respiratory distress syndrome: A novel therapeutic strategy", LIFE SCIENCES, vol. 254, 1 August 2020 (2020-08-01), pages 3 *
FATEMEH MIRERSHADI等: "Unraveling the therapeutic effects of mesenchymal stem cells in asthma", STEM CELL RESEARCH & THERAPY, vol. 11, no. 400, 15 September 2020 (2020-09-15), pages 6 *
ULRICH SYDLIK等: "The Compatible Solute Ectoine Protects against Nanoparticle-induced Neutrophilic Lung Inflammation", AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 180, no. 1, 25 March 2009 (2009-03-25) *
叶锦豪等: "低氧预处理脐带间充质干细胞来源的外泌体对内皮细胞功能的影响", 中国病理生理杂志, vol. 36, no. 8, 25 August 2020 (2020-08-25) *
张蘋等: "低氧预处理人脐带间充质干细胞促进其源性外泌体对心肌梗死后心肌损伤的修复", 中国组织工程研究, 25 March 2019 (2019-03-25) *
高小月等: "人脐带间充质干细胞在组织损伤修复中的研究进展", 生物医学工程与临床, vol. 22, no. 2, 13 March 2018 (2018-03-13), pages 2 *

Similar Documents

Publication Publication Date Title
US20230330164A1 (en) Composition comprising lactoferrin and probiotic bacterial strains for oral use with antiviral action
CN111265500B (en) Pharmaceutical composition for preventing and treating COVID-19 and preparation method thereof
US20110020279A1 (en) Rabies cure
JP5970465B2 (en) Composition comprising peptide and viral neuraminidase inhibitor
WO2018188124A1 (en) Colonizing probiotic preparation, applications thereof, and medicament
WO2019011286A1 (en) Antiviral use of mussel adhesive proteins
CN111394304A (en) Stem cell conditioned culture supernatant for repairing respiratory system injury and preparation thereof
CN111956667A (en) Application of multifunctional stem cell exosome and mesenchymal stem cell lysate in preparation of medicine for treating allergic rhinitis
KR102186420B1 (en) Composition for preventing, improving or treating of allergic diseases comprising Staphylococcus succinus 14BME20 as an active ingredient
CN114425056A (en) Stem cell exosome composition for improving asthma
US20230414730A1 (en) A composition comprising extra-cellular vesicles from mesenchymal stem cells and alpha-1 antitrypsin for the treatment of viral infections
EP3995130A1 (en) A composition comprising extra-cellular vesicles from mesenchymal stem cells and alpha-1 antitrypsin for the treatment of viral infections
CN111358813B (en) Salt fog mixture for protecting respiratory tract
CN117224518B (en) Application of sofalcone in preparation of medicine for preventing/treating allergic asthma
CN111419883B (en) Preparation method of nasal spray for treating allergic rhinitis
KR102568093B1 (en) Composition for preventing or treating allergic diseases comprising Bifidobacterium longum as an active ingredient
RU2800051C2 (en) Method of treatment and/or prevention of asthma, asthma aggression, allergic asthmatic disorders and/or respiratory disorders associated with microbiota
CN111214495B (en) Application of mycobacterium vaccae for injection in preparation of medicine for preventing and treating respiratory system RSV infection
EP4248986A1 (en) Use of polypeptide having superoxide dismutase activity and extracellular vesicles for treatment or prevention of respiratory viral infection
WO2008064552A1 (en) Use of cholinesterase for manufacturing an anti-tachykinins medicament
US20220143111A1 (en) Method of treating and/or preventing asthma, asthma exacerbations, allergic asthma and/or associated conditions with microbiota related to respiratory disorders
CN117281832A (en) Product for treating respiratory diseases and application thereof
KR20230008844A (en) Peptides for the prevention or treatment of COVID-19
CN116999541A (en) Antioxidant nano-enzyme with gelatinase inhibition effect, and preparation method and application thereof
CN117137971A (en) Oviductus Ranae composition and Chinese medicinal composition for relieving cough and asthma, and preparation method and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination