WO2014082514A1 - 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 - Google Patents
一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 Download PDFInfo
- Publication number
- WO2014082514A1 WO2014082514A1 PCT/CN2013/086018 CN2013086018W WO2014082514A1 WO 2014082514 A1 WO2014082514 A1 WO 2014082514A1 CN 2013086018 W CN2013086018 W CN 2013086018W WO 2014082514 A1 WO2014082514 A1 WO 2014082514A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chlorine dioxide
- stem cells
- stem cell
- cells
- differentiation
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Definitions
- the present invention is in the field of regenerative medicine, and specifically relates to a method for initiating proliferation, migration and differentiation of stem cells in a mammal, and to the use of chlorine dioxide for the preparation of a medicament for initiating proliferation, migration and differentiation of stem cells. Background technique
- Regenerative medicine is now attracting attention as a new treatment for these problems.
- Regenerative medicine refers to a method of actively utilizing stem cells to perform structural regeneration and functional recovery of organs or tissues that are dysfunctional or dysfunctional due to illness or accident. According to the way of using stem cells, regenerative medicine is roughly divided into the following three types:
- the current mainstream research direction of regenerative medicine is a method involving introduction of a patient's body from the outside through cell transplantation (ie, methods of the above categories (1) and (2)), but in practice, it has not been carried out on a large scale, and 1) Medical ethics issues are involved in the class approach.
- differentiated cells are externally introduced into a patient's body for use in the fields of dermatology, ophthalmology, and orthopedics, the target tissue or organ being a tissue or organ constructed of one or a very limited variety of cells (eg, skin) , bone, cartilage, cornea and muscle tissue).
- the target tissue or organ being a tissue or organ constructed of one or a very limited variety of cells (eg, skin) , bone, cartilage, cornea and muscle tissue).
- solid organs constructed by various types of cells e.g., heart, liver, lung, kidney, and brain
- the following method is a known method of introducing undifferentiated cells from the outside of a patient's body:
- a method of treatment of angiogenesis which involves introducing stem cells from outside the body of a patient in severe ischemic diseases and cardiovascular diseases to promote angiogenesis and form new blood vessels (We i ssman IL: Translating stem and Progenitor cel l bi lology to the cl inic: Barriers and opportunities. Science. 287:1442-1446, 2000).
- in situ tissue regeneration that is, stimulation originally existed in patients (here patients defined as those who need certain medical means to achieve the desired goal, such as beauty goals, does not mean medically The person who meets the standard of disease)
- the stem cells inside the body ie, the stem cells inside the body, and/or from the patient's own blood source or bone marrow-derived stem cells
- stem cells with regenerative capacity exist in the liver, nervous system (especially the central nervous system such as the brain), skin, adipose tissue, retina, cornea, skeletal muscle and even the heart (Garry DJ et al.: Ponce de Leon 's fountain: stem cel ls and the regenerating heart. Am J Med Sci. 329(4): 190-201, 2005).
- Intrinsic stem cells are currently considered to be present in all organs and tissues (Weissman IL: Translating stem and progenitor cel lbi I o I gy to the cl inic: Barriers and opportunities. Science.
- neural stem cells When neural stem cells are cultured in the presence of a neurotrophic factor or a growth factor, they form a single cell-derived colony called a neurosphere (ie, self-replication), and these nerves
- the spheres differentiate into neurons, astrocytes, and oligodendrocytes (ie, multi potency) depending on the induced microenvironment.
- another neurosphere can be formed from a single cell derived from a neurosphere (Reyno I ds BA and We i ss S: Generation of neurons and astrocytes from isolated cel ls of the adult mammal ian centra I nervous system. Science. 255:1707-1710, 1992);
- neural stem cells can only differentiate into glial cells when they are transplanted into the spinal cord of another adult rat, they can be differentiated into hippocampal dentate gyrus. Neuron (Shihabuddin LS et al.: Adult spinal cord stem ce II s generate neurons after transplantation in the adult dentate gyrus. The J Neuroscience. 20: 8727 - 8735, 2000);
- neural stem cells When neural stem cells are cultured with vascular endothelial cells, they can promote the proliferation of neural stem cells and differentiate into neurons (Shen Q et al.: Endothelial cel ls stimulate self-renewal and expand neurogenesis of neural stem ce I Is. Science 304: 1338-1440, 2004);
- BM-MSCS Bone marrow-derived mesenchymal stem cells
- BM-MSCs can differentiate into epidermal cells, cytokeratins and glandular cells, and promote angiogenesis to enhance capillaries.
- Density (Yaoj iongWu et al.: Mesenchymal Stem Ce I Is Enhance Wound Heal ing Through Differentiation and Angiogenesis. STEM CELLS. Vo I ume 25, Issue 10, 2648-2659, October 2007).
- a known promotion method for increasing intrinsic stem cells, or/and blood source or bone marrow-derived stem cells, for the purpose of regenerative medicine using self-organized stem cell regeneration is as follows:
- EGF When EGF is administered to a model animal of cerebral ischemia, the proliferation of neural stem cells can be promoted, and about 20% of the cells in the infarcted area are regenerated (Teramoto T et al.: EGF ampl stratifies the replacement of parva I bum in-expressing striatal i nterneurons after Ischemia. The J Cl inical Investigation. 111 : 1125-1132, 2003) ;
- statin 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor
- EGF vascular endothelial growth factor
- FGF FGF
- PDGF PDGF
- NGF vascular endothelial growth factor
- HGF HGF
- cytokines such as G-CSF, GM-CSF, erythropoietin (EP0)
- EP0 erythropoietin
- estrogens and lipids have also been reported to increase stem cells ( Takeyama K, Ohto H: PBSC mobi ization. Transf useApher SCI 31 : 233-243, 2004; Aicher A, Zeiher AM, Dimmeler S: Mobi lizing endothel Ial progenitor cel ls. Hypertension 45:321-325, 2005).
- G-CSF is at risk of carcinogenesis
- b-FGF is at risk of side effects such as occlusion of the blood vessel during intravenous injection.
- VEGF and b-FGF have been developed as growth factors with few targeted cell types, but have not been obtained in clinical studies. Adequate efficacy.
- EP0 has side effects including an increase in blood pressure.
- tissue regeneration Obviously, it is clinically necessary to make use of the "in situ tissue regeneration” method to rationally and conveniently utilize the stem cells of the body itself, which are widely distributed throughout all organ tissues, specifically to enable the proliferation, migration and differentiation of these stem cells.
- Stem cells play a leading role in tissue regeneration and are readily recognized by those skilled in the art.
- tissue regeneration dominated by stem cells also has an immunomodulatory effect, so those skilled in the art naturally conclude that stem cells can be used for treatment.
- Allergic reactions Hypersens itivi ty
- diseases including allergic diseases (A ll erg icdi seases) and autoimmune diseases).
- the mechanism of allergic diseases is very complicated.
- the clinical practice is often mixed, but it is mainly based on a certain type, such as type I and type III, and type II and type III can also occur at the same time, even II.
- Types III and IV can also appear at the same time.
- Allergic diseases are the interpretation of foreign antigens as harmful objects (such as bacteria, viruses, pollen, dust, etc.) and allergic reactions, which will activate the phagocytic cells in immune cells, release histamine and prostaglandins, histamine and Prostaglandins have a series of effects such as microvascular dilatation, increased vascular permeability, itching, smooth muscle contraction and reflex. Small erythematosus on the skin and inflammatory characterization such as swelling and fever. Allergies refer to these abnormal reactions, also known as type I allergic reactions (ie, A l l energy ).
- Type I allergic reactions often do not cause tissue or organ damage, but some type I allergic reactions change to chronic symptoms (even if desensitization treatment does not change the symptoms) or with other types of allergic reactions can cause tissue or organ damage, and not easy Heal.
- glucocorticoids, immunosuppressive drugs and other drugs for treatment if the allergic reaction turns chronic, the general treatment is not effective, and more effective tissue regeneration therapy is needed.
- Autoimmune disease tissue damage is mostly caused by type I I, III, IV allergic reactions: the role of autoantibodies; the role of immune complexes; the role of T cells; the role of macrophages, NK cells.
- autoimmune diseases The amount of autoantibodies and/or autoreactive T cells present is parallel to the severity; the range of involvement is mainly the distribution of autoantigens or sensitized lymphocytes to their own antigens; passive transfer; The cause of most autoimmune diseases is unknown; the course of disease is prolonged, the onset and remission are alternate; the patients are more common in women, the incidence rate increases with age, there is a genetic tendency; the disease overlaps; the treatment with immunosuppressive agents has certain curative effect.
- An autoimmune disease refers to any disease caused by immune cells that are incorrectly directed to healthy cells and/or tissues of the body.
- Autoimmune diseases are characterized by: T and B lymphocytes that abnormally target their own proteins, self-polypeptides, self-peptides, and/or other self-molecules cause organ, tissue, or tissue types in the body (eg, skin, pancreas, brain, thyroid) Or gastrointestinal tract damage and/or dysfunction, causing clinical manifestations of the disease (Mar rack et al I, Nat Med 7, 899-905, 2001).
- Autoimmune diseases include diseases affecting specific tissues and/or organs (organ specific) and affecting multiple tissues And/or organ diseases (non-organ specific diseases).
- tissue-specific autoimmunity is the selective targeting of a single tissue or a single cell type.
- certain autoimmune diseases that target ubiquitous self-proteins can also affect specific organs. For example, in polymyositis, the autoimmune response targets the widely existing proteomic-tRNA synthetase, but the primary clinical manifestation is the autoimmune destruction of muscle.
- the body's immune system has the ability to recognize "self” and "non-self” antigenic substances. Under normal circumstances, the immune system does not produce an immune response to its own tissue antigen, or it produces only a very weak immune response. This phenomenon is called itself. Tolerance. Self-tolerance is maintained by the active regulation of the immune system through a variety of mechanisms to ensure that the tissue components of the tissue are not attacked by an immune response. In some cases, self-tolerance is disrupted, and the immune system produces a significant immune response to its own tissue components, that is, antibodies or sensitized lymphocytes against its own tissue components are produced in the body, called autoimmunity.
- autoimmune diseases a common treatment for autoimmune diseases is the use of glucocorticoids or the use of immunosuppressive drugs to alleviate the inflammatory response caused by the immune system attacking tissues and suppress the immune system.
- these methods can cause serious adverse reactions, such as severe infections, myelosuppression, etc., and these treatments can only slow the progression of the disease, rather than cure the disease.
- placental stem cells to treat autoimmune diseases
- Chose Patent, Publication No.: CN101657206A Treatment of type 1 diabetes with human body fat-derived stem cells
- Intestinal progenitor cells are used to produce insulin-secreting cells in the intestine for the treatment of type 1 diabetes ( Chut i ma
- Ta I cha i et al. Generat i on of f unct i ona I i nsu I i n-produc i ng ce II s in the gut by Foxol ablation. Nature Genet i cs.
- the treatment of autoimmune diseases by stem cells mainly utilizes two functions of stem cells: immunomodulatory effects and tissue regeneration.
- mesenchymal stem cells Mesenchymal Stromal Cel l
- MSCs Single-molecule regulation of immunosuppressive agents commonly used in clinical practice, MSCs are achieved through multi-molecular participation, multi-pathway regulation and its paracrine effects, and their immunomodulatory effects interact with the microenvironment of the body's inflammation (Pittenger, MF, Mart in, BJ: Mesenchyma I stem cel ls and their potential as cardiac therapeutics. Circ. Res., 2004, 95, 9-20).
- stem cell hair Dynamic tissue regeneration has natural immunomodulatory capacity (because the body's immune system recognizes the new organization as "self").
- Chlorine dioxide is an internationally recognized new generation of high-efficiency, broad-spectrum, safe sterilization and preservatives. It is an ideal substitute for chlorine preparations and has been widely used in developed countries around the world. Relevant organizations in developed countries such as the United States, Western Europe, Canada, and Japan, such as the US Environmental Protection Agency, the Food and Drug Administration, and the US Department of Agriculture, have approved and recommended the use of chlorine dioxide for disinfection of food, food processing, pharmaceuticals, hospitals, public environments, etc. , anti-mold and anti-corrosion preservation of food. The World Health Organization (WHO) and the World Food Organization (FAO) have also classified chlorine dioxide as a Class A1 safe and effective disinfectant.
- WHO World Health Organization
- FEO World Food Organization
- chlorine dioxide has been widely used in developed countries in Europe and America to disinfect drinking water.
- chlorine dioxide has not been accepted by the market as a medicine.
- some patents relate to the use of chlorine dioxide to treat some diseases (for example,
- Another object of the present invention is to provide the use of chlorine dioxide in the preparation of a medicament for initiating stem cell proliferation, migration and differentiation.
- a drug for initiating stem cell proliferation, migration and differentiation has a chlorine dioxide-containing stem cell promoter which can initiate the proliferation, migration and differentiation of the existing stem cells in the patient, and can function quickly and moderately. And can continue to promote The effect, with little side effects or no side effects, is less burdensome for the patient.
- the present invention adopts a technical solution: a method for initiating proliferation, migration and differentiation of mammalian stem cells, the method comprising: preparing a chlorine dioxide-containing stem cell promoter and administering the stem cells to a mammalian target tissue A step of activating agent, wherein the stem cell promoter is administered an effective amount of chlorine dioxide when administered to a mammalian target tissue.
- the method for preparing a chlorine cell-containing stem cell promoter is: dissolving chlorine dioxide gas in an acidic solution A containing an acidic pH adjuster at a pH of 1.5 to 6.5, preparing 500 to 2900 ppm of two Chlorine oxide solution.
- the method for preparing a chlorine cell-containing stem cell starter is: preparing a chlorine dioxide precursor in water to prepare an aqueous solution of 1% to 40%, and adding an acidic solution B containing an acidic pH adjuster to the aqueous solution, adjusting 5 ⁇ 6. 5 ⁇ The pH of the mixed solution is 1. 5 ⁇ 6.
- the method for preparing a chlorine cell-containing stem cell starter is: dissolving a chlorine dioxide precursor in water to prepare an aqueous solution C having a concentration of 1% to 40%; and dissolving the acidic pH adjuster in water to prepare an acidic solution. 5 ⁇ 6. 5 ⁇ The pH of the mixed solution was adjusted to 1. 5 ⁇ 6.
- the chlorine dioxide precursor is sodium chlorite, chlorite clock, lithium chlorite, calcium chlorite, bismuth chlorite and bismuth chlorite.
- the acidic pH adjuster is citric acid, acetic acid or sodium dihydrogen phosphate.
- the stem cell promoter is directly administered by arterial injection, intramuscular injection, subcutaneous injection, intracardiac injection, intrathecal injection, intra-articular injection, puncture injection, rectal administration, nasal administration, transdermal administration or inhalation administration. Go to the damaged organ or tissue.
- the stem cell promoter is prepared as an injection, an ointment, an inhalant, a nasal drop, a lotion, a suppository, a patch, a paste, a tablet, an oral solution, a capsule, a granule, a granule, a pill or a syrup.
- the present invention provides the use of chlorine dioxide for the preparation of a medicament for initiating stem cell proliferation, migration and differentiation, wherein the medicament is for treating a disease treated by regenerative medicine which initiates stem cell proliferation, migration and differentiation. Further, the medicament comprises the above-described stem cell promoter for use in a method for initiating proliferation, migration and differentiation of mammalian stem cells.
- the stem cells are cells used in regenerative medicine using in situ tissue regeneration.
- the regenerative medicine is about skin diseases, sports system diseases, endocrine diseases, respiratory diseases, urology diseases, gastrointestinal diseases, ophthalmic diseases, nervous system diseases, cardiovascular diseases, Damaged tissue regeneration during vascular disease treatment.
- skin diseases include burns, skin ulcers, acne, dry skin disease, diabetic skin ulcers, androgen alopecia, paronychia, gastrointestinal mucosal erosion, peptic ulcer, corneal ulcer, pulpitis, recurrent aphthous ulcer, Oral mucosal ulcer;
- the nervous system diseases include stroke, Alzheimer's disease, Parkinson's disease, myelitis, multiple peripheral neuropathy, and hearing impairment;
- the cardiovascular diseases include myocardial infarction, angina pectoris, viral myocarditis , atherosclerosis, valvular heart disease, infective endocarditis, pericarditis;
- the gastrointestinal diseases including chronic gastritis, gastric ulcer, duodenal ulcer, appendicitis, ulcerative colitis, intestinal tuberculosis, viral Hepatitis, alcoholic hepatitis, pancreatitis;
- the respiratory diseases include bacterial bronchitis, infectious pneumonia, aspiration pneumonia;
- the urological diseases
- the regenerative medicine relates to tissue healing in cosmetic plastic surgery, wound healing of surgical or accidental tissue damage, regeneration of inflammatory tissues caused by various causes, and regeneration of damaged tissues in various cancers.
- the drug for initiating stem cell proliferation, migration and differentiation is applied to a disease treated by the tissue regeneration ability and immunomodulatory ability of stem cells.
- diseases which are treated by stem cell tissue regeneration ability and immunomodulatory ability are type I allergic diseases and autoimmune diseases.
- the type I allergic reaction diseases include: allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic exogenous asthma, rubella; the autoimmune diseases including thrombocytopenic purpura, leukopenia Symptoms, herpes zoster, herpes zoster, Graves disease, myasthenia gravis, urticaria vasculitis, systemic lupus erythematosus, rheumatoid arthritis; polyarteritis, contact dermatitis, discoid lupus erythematosus, vasculitis, Type I diabetes, multiple sclerosis, psoriasis, psoriatic arthritis, scleroderma, encephalomyelitis, alopecia areata, amyotrophic lateral sclerosis, ankylosing spondylitis, self Immune urticaria, bullous pemphigoid, chronic obstructive pulmonary disease
- the present invention provides a novel use of chlorine dioxide, including two aspects: In one aspect, the present invention provides a method for initiating proliferation, migration and differentiation of stem cells in a mammal using a chlorine dioxide-containing stem cell promoter, and The step of administering the stem cell promoter to the mammalian target tissue; on the other hand, the use of chlorine dioxide in the preparation of a medicament for initiating stem cell proliferation, migration and differentiation is provided.
- the chlorine dioxide-containing stem cell promoter of the present invention is capable of initiating proliferation, migration and differentiation of stem cells.
- the invention can therefore be advantageously used in regenerative medicine, in particular in regenerative medicine using stem cells in situ tissue.
- the regenerative medicine using stem cells in the in situ tissue using the chlorine dioxide-containing stem cell promoter of the present invention uses the stem cells originally present in the body of the patient, it is not necessary to introduce the cells from the outside of the patient's body. Therefore, there is no need for complicated processes such as separation and culture of cells outside the body, and the burden on the patient is light and the risk of infection such as during cell transplantation does not exist, and as a result, regenerative medicine using stem cells in in situ tissue is superior to Regenerative medicine that introduces cells from outside the body of a patient. And does not involve medical ethics issues.
- regenerative medicine using in situ tissue regeneration using the chlorine dioxide-containing stem cell promoter of the present invention the initiation of stem cells specifically occurs in the diseased part of the patient (ie, the damaged organ and/or tissue). And the tissue regeneration occurs only depending on the degree required. Therefore, regenerative medicine using in situ tissue regeneration does not cause excessive regeneration and/or over-repair of cell transplantation, or complications due to immune rejection, which is the main method of traditional regenerative medicine introduced from the outside of the patient's body. Danger.
- the chlorine dioxide-containing stem cell promoter has little side effects or no side effects, and can quickly and appropriately function according to the progress state and degree of the damaged organ and/or the damaged tissue applied by the regenerative medicine. It also has a sustained promotion of stem cell proliferation, migration and differentiation. Therefore, it can be advantageously used for regenerative medicine. Therefore, the present invention can be used in regenerative medicine, particularly in regenerative medicine using in situ tissue regeneration, and has high applicability.
- NCT01341041 Chlorine Dioxide Versus Sa I i ne for Wound I rri gat i on, reported in Rhode I s I and Hosp i ta I ) shows that compared to saline, dioxide Chlorine has the following effects on general wounds: Accelerate wound healing and reduce scar formation. In animal body tests, it has been reported that chlorine dioxide has a rapid effect on hemostasis and accelerated wound healing in wounds (Jin Wei et al., Experimental study on the effect of chlorine dioxide sustained-release gel on wound healing in rabbits, Journal of Shanxi Medical University ⁇ 2011, Volume 42, Issue 07).
- wound healing is initiated by stem cells, and if the tissue loses stem cells, it is impossible for any wound of the tissue to heal.
- the wounds of human tissues will be able to heal normally.
- the root cause is that stem cells are present near the wounds on the tissue, and stem cells will grow intact new tissue through proliferation, migration and differentiation. Once the number of stem cells or the ability to differentiate is insufficient, scarring may occur during wound healing or the wound may not heal for a long time. For example, a degree I burn can naturally heal without leaving scars; a second degree burn scar is healed; a third degree burn cannot heal naturally.
- ASCs are considered to be the source of new tissue during wound healing, including skin wound healing, liver regeneration, lung regeneration, renal function repair, corneal epithelial healing, nerve regeneration, cardiomyopathy, and ischemic brain injury. Repair is accomplished by stem cell proliferation, migration, and differentiation in in situ tissue. Bone marrow mesenchymal stem cells (BM-MSC) have been shown to be involved in all stages of wound healing (Kather i ne Lau et al., Exploring the role of stem ce II s in cutaneous wound heal ing, Experimental Dermatology, Volume 18, Issue 11, Pages 921 - 933, November 2009).
- BM-MSC Bone marrow mesenchymal stem cells
- chlorine dioxide solutions have a significant accelerated healing ability for skin wounds, and rarely leave scars, such as greater inflammatory wound healing and wound healing of diabetic foot.
- Inflammatory pain Nociceptive pain protects the body from the outside world and protects the body (Cl ifford J. Woo If , What is this thing cal led pain? J Cl in Invest. 2010 November 1 ; 120(11): 3742 - 3744) ; Inflammatory pain plays a role in promoting healing of damaged tissues (Cl ifford ⁇ Wool, Pain: Moving from Symptom Control toward Mechan i sm-Spec i ficPharmaco I og ic Management , Anna I s of Internal Medicine (2004) , Volume: 140, Issue: 6, Pages: 441-451 ). Therefore, pain is beneficial for the repair of tissue damage, and it should also be through various stimulating factors to promote stem cell differentiation to regenerate in response to tissue damage.
- the present inventors have also found that a chlorine dioxide solution is applied to organ tissues, has a micro-resistance effect thereon, and causes a short-term pain sensation.
- the inventors believe that the creation of micro-wounds, in one aspect, has a clearing effect to remove necrotic tissue; on the other hand, it acts to induce tissue regeneration of stem cells, and the stimulation of pain promotes this effect.
- the inventors have found that a suitable concentration of chlorine dioxide solution is used in the hair loss area, and has the following phenomenon: a chlorine dioxide solution is applied externally every day, and a wound-like erythema appears in the medicated area around the third to fifth day, still New hair is found in the hair loss area of the hair, and new hair appears in the all-light hair loss area in about 20 days. Only the ability of stem cells to regenerate tissue can explain this phenomenon.
- stem cells Fetal wounds heal quickly and without scars, and adult wound healing increases with age, which may represent changes in the functional status of stem cells (Ceci I ia Roh et al.: Cutaneous Stem Cel ls and Wound Healing, Pediatric Research (2006) . 59, 100R- 103R). This also indicates that stem cell regeneration has the potential to age.
- the "microenvironment" of stem cells plays a key role in the loss of stem cells caused by aging. Stem cells are localized in the microenvironment of other cells, and microenvironments are known to play an important role in stem cell function.
- the inventors have also found that the same wounds (with the same area and depth) are treated with chlorine dioxide solution, and the healing ability of people over 60 years old is significantly lower than that of people under 30 years old. It is indicated that the effect of chlorine dioxide on stem cells is basically consistent with the results predicted by the above theory.
- the inventors have found that the chlorine dioxide solution has a significant promoting effect on tissue repair from the viewpoint of wound healing, and it can be seen that the newborn tissue is younger.
- Chlorine dioxide gives five electrons an oxidation-reduction potential of 1.5, which exceeds 1.2 of oxygen, and is a strong oxidant due to its strong electron-accepting ability.
- chlorine dioxide relies on strong oxidative capacity to destroy normal cells, similar to causing wounds in tissue or removing necrotic tissue, and producing pain The body will automatically initiate stem cells to heal the wound; chlorine dioxide is a water-soluble gas, like nitric oxide (N0) and hydrogen sulfide (H2S), chlorine dioxide can be used as a signal molecule. After entering or infiltrating into the body tissues, the special ability of the gas signal molecules is exerted, and the stem cells are activated to proliferate, migrate and differentiate to complete tissue regeneration.
- N0 nitric oxide
- H2S hydrogen sulfide
- Nitric oxide to promote wound healing
- Nitric oxide gives two electron oxygen under acidic conditions
- the reduction potential is 1.6, which is close to chlorine dioxide, and both are soluble in water (the former is slightly soluble).
- chlorine dioxide can act as an exogenous signaling molecule on the body and can act as a stem cell promoter in in situ tissue regeneration.
- the chlorine dioxide-containing preparation of the present invention can remove the necrotic part of the damaged tissue, provides space for the stem cell to start and complete the tissue repair, and also stimulates the body automatically due to the abundant spatial and tissue specific suggestion. Repair damaged tissue.
- the Chinese patent "Infectious Skin and Mucosal Disease Therapeutic Drugs" as disclosed in CN1 01 641 1 04A utilizes a broad spectrum of pathogenic microbial killing action by chlorine dioxide for skin diseases caused by partially pathogenic microorganisms.
- the chlorine dioxide preparation of the present invention can effectively kill pathogenic microorganisms, and has the functions of exogenous substances such as debridement, infection prevention, and elimination of allergens (which are themselves, and/or regarded by the immune system). .
- the chlorine dioxide-containing preparation of the present invention can produce micro-wounds distributed in the damaged tissue, and cause pain to stimulate the body to activate various factors and cells to repair the wound, and repair in a relatively early mode, so that The repaired tissue can be restored as new and younger, including restoring a new tissue that is recognized by the immune system as "self", which is immune-modulating.
- the chlorine dioxide-containing preparation of the present invention enhances the activity of stem cells, and promotes the repair of damaged tissues by initiating the differentiation, migration and differentiation of stem cells.
- chlorine dioxide as a gas signal molecule also has an indirect immunomodulatory effect either directly or through stem cells.
- the role of chlorine dioxide preparations should be complex and comprehensive.
- the present invention is based on the above findings, and therefore the chlorine dioxide-containing preparation of the present invention as a stem cell promoter can not only utilize stem cell-derived tissue regeneration ability to treat diseases, but also utilize the immunomodulatory ability accompanying stem cell tissue regeneration to treat diseases. At the same time, the use of chlorine dioxide to remove necrotic tissue to clear the creative and kill the pathogenic microorganisms against infection.
- Stem cells are undifferentiated cells that have self-replication and multipotency that differentiate into multiple cells.
- Specific examples of stem cells include embryonic stem cells (ES cells), embryonic germ cells (EG cells), adult stem cells, hemangioblasts, neural stem cells, hematopoietic stem cells, mesenchymal stem cells, and stem cells of other cells (including bone cells, Chondrocytes, several cells, cardiac cells, neurons, sputum cells, fat cells, J3 ⁇ 4J spring cells (pancreocytes), hepatocytes, kidney cells, and hair follicle cells, etc.
- ES cells embryonic stem cells
- EG cells embryonic germ cells
- adult stem cells include hemangioblasts, neural stem cells, hematopoietic stem cells, mesenchymal stem cells, and stem cells of other cells (including bone cells, Chondrocytes, several cells, cardiac cells, neurons, sputum cells, fat cells, J3 ⁇ 4J spring cells (pancreocytes), hepatocytes,
- the stem cell promoter of the present invention wherein the differentiation initiation phase comprises the whole process of down-differentiating from stem cells to terminally differentiated cells, that is, including differentiation of stem cells into progenitor cells (progenitor cells are defined as daughter cells of stem cells, and their differentiation Potential or self-replication ability or both are more limited), including the whole process of differentiation of progenitor cells into differentiated cells, and then into terminal cells, or at a certain stage.
- the entire phase represents a common pattern of stem cell repair of damaged tissue. Stem cells are in the body, leading to the maintenance and repair functions of the tissue. In order to accomplish such functions, the life cycle can be divided into prol iferation, migration and differentiation. (differentiation).
- the pattern of stem cell self-renewal and cloning behavior is correspondingly Three types: symmetric division, stem cells achieve proliferation; stem cells in adjacent tissues symmetrically divide and migrate; asymmetric division, stem cells self-renew and differentiate into daughter cells (Al lon M. Klei et al.: Universal patterns of stem cel l fate In cycl ing adult tissues , Development, August 1, 2011, 138, 3103-3111 ).
- the chlorine dioxide-containing stem cell promoter of the present invention, wherein "starting” comprises a whole process of starting and repairing a tissue such as stem cell proliferation, migration and differentiation, and is not limited to a specific one of them.
- the present invention defines transdifferentiation of stem cells as cells in which tissue-specific stem cells are transformed into other lineages. If a tissue-specific stem cell has lost the ability to regenerate the tissue, then the regeneration of the tissue requires the transdifferentiation of adjacent stem cells. There is a small amount of stem cell transdifferentiation in the body tissues, and the present invention includes this transdifferentiation definition in the definition of stem cell differentiation.
- Stem cells present in the adult body can be divided into intrinsic stem cells, blood-derived stem cells, and bone marrow-derived stem cells based on their origin and location.
- An intrinsic stem cell is defined as a cell having self-replication ability and pluripotency existing in a specific organ or tissue, and in the case where the organ or tissue is damaged, the cell contributes to regeneration of the organ or tissue.
- Specific examples of these intrinsic stem cells include corneal stem cells, cardiac stem cells, neural stem cells, blood vessel EPC, and the like. From the foregoing description, those skilled in the art can also easily understand that intrinsic stem cells are widely distributed in the human body, in almost all organs or tissues, and can be used for in situ tissue regeneration.
- Blood-derived stem cells are defined as cells having self-replication ability and pluripotency present in circulating blood. In the case where an organ or tissue is damaged, the cell migrates and accumulates in the organ or tissue, thereby contributing to the regeneration of the organ or tissue.
- the blood in this case includes peripheral blood, placental blood, arterial blood, venous blood, blood from the heart, or blood from the fundus.
- Specific examples of blood-derived stem cells include blood vessel EPC, mesenchymal stem cells, and the like.
- a bone marrow-derived stem cell is defined as a cell having self-replication ability and pluripotency existing in the bone marrow, in the case where the organ or tissue is damaged, the cell migrates through the blood circulation and accumulates in the organ or In the tissue, thereby contributing to the regeneration of the organ or tissue.
- Specific examples of bone marrow-derived stem cells include vascular EPC, mesenchymal stem cells, and the like.
- the stem cell promoter of the present invention is capable of initiating these internal stem cells, blood-derived stem cells, and Proliferation, migration and differentiation of each of bone marrow-derived stem cells.
- stem cells can be divided into activated state cells (cells in this state undergoing proliferation, migration, and differentiation) and non-activated cells (cells in this state are not undergoing proliferation, migration, and differentiation).
- the stem cell promoter of the present invention is capable of promoting proliferation, migration and differentiation of activated cells in an activated state and an inactivated state.
- the stem cell promoter of the present invention can promote the repair of damaged tissues by stem cells and achieve regeneration.
- start is defined as the three roles referred to below:
- Migration is defined as the movement of stem cells from the bone marrow, organs or tissues into the circulating blood; from the circulation of blood to the damaged organ or tissue; or within the organ or tissue.
- the chlorine dioxide-containing stem cell promoter of the present invention may comprise a single dosage form of chlorine dioxide alone or a combination of several parts comprising a chlorine dioxide precursor.
- a single dosage form in which chlorine dioxide alone is included can be made as follows:
- Method 1 Add a pH adjuster to water to prepare an acidic aqueous solution having a pH of 1.5 to 6.5.
- the chlorine dioxide gas is produced by a standard preparation method and a chlorine dioxide gas having a concentration of 99.9% or more (preferably chlorite reacts with an acid).
- a chlorine dioxide solution of 500 to 2900 ppm was prepared by bubbling and dissolving the chlorine dioxide gas into the above acidic aqueous solution.
- the solution should be stored in the dark and sealed at a temperature of 4 ° C to 15 ° C before being used in the treatment of the disease of the present invention.
- the method of preparing a chlorine dioxide-containing preparation is not necessarily an aqueous solution, and only the substance capable of functioning in the target tissue when applied to the target tissue is mainly chlorine dioxide.
- Method 2 A chlorine dioxide precursor is dissolved in water to prepare a 1% to 40% aqueous solution.
- An acidic solution containing a pH adjuster preferably 2% to 50% citric acid solution
- the solution should be stored in the dark and sealed at a temperature of 4 ° C to 15 ° C before being used in the treatment of the disease of the present invention.
- the method of preparing a chlorine dioxide-containing preparation is not necessarily an aqueous solution, and only the substance capable of functioning in the target tissue when applied to the target tissue is mainly chlorine dioxide.
- Several combinations of precursors comprising chlorine dioxide can be made as follows: Dissolving the chlorine dioxide precursor A 1% to 40% aqueous solution is prepared in water, which is the first solution; an acidic solution (preferably 2% to 50% citric acid solution) is prepared using a pH adjusting agent, which is a second solution. Before the treatment of the disease of the present invention, the above solution is mixed in the field, and the pH of the final mixed solution is adjusted to 1.5 to 6. 5, after the reaction produces chlorine dioxide, the solution is applied to the target tissue.
- the method of preparing a chlorine dioxide-containing preparation is not necessarily an aqueous solution, and only the substance capable of functioning in the target tissue when applied to the target tissue is mainly chlorine dioxide.
- the chlorine dioxide precursor which can be used in the present invention may, for example, be an alkali metal chlorite or an alkali metal chlorite.
- alkali metal chlorite include sodium chlorite, chlorite clock, and lithium chlorite.
- alkali metal chlorite salt include calcium chlorite and barium chlorite. , bismuth chlorite.
- sodium chlorite and chlorite clock are more preferable, and sodium chlorite is more preferable, from the viewpoint of obtaining an easy reason and excellent in the sustainability of chlorine dioxide activity.
- the pH adjusting agent which can be used in the present invention can be preferably used as long as it is a buffering acid.
- organic acid or a salt thereof examples include formic acid, acetic acid, propionic acid, butyric acid, lactic acid, pyruvic acid, citric acid, malic acid, tartaric acid, gluconic acid, glycolic acid, fumaric acid, malonic acid, and maleic acid. , oxalic acid, succinic acid, acrylic acid, crotonic acid, glutaric acid and their salts.
- Examples of the inorganic acid include phosphorus, boric acid, metaphosphoric acid, pyrophosphoric acid, and amino acid.
- Examples of the inorganic acid salt include a dihydrogen phosphate salt (sodium salt, a clock salt, the same applies hereinafter), a mixture of a dihydrogen phosphate salt and a hydrogen phosphate salt, and the PH regulator may be used singly or in combination of two. the above.
- the pH adjusting agent is preferably citric acid, acetic acid and sodium dihydrogen phosphate, more preferably citric acid.
- the final pH of the chlorine dioxide solution is preferably 1.5 to 5. 5, more preferably 1. 5 to 3. 5.
- the chlorine dioxide-containing stem cell promoter in the present invention is preferably a liquid.
- the dose of the stem cell promoter in the present invention varies depending on the age, body weight, disease nature and condition of the patient. However, in the case of an adult, for example, 1 mg to 5000 mg of chlorine dioxide per day, preferably 1 mg to 1 000 mg of chlorine dioxide per day.
- the chlorine dioxide-containing stem cell promoter of the present invention can be administered in a variety of ways.
- the chlorine dioxide-containing stem cell promoter can be administered systemically, such as by intravenous, intra-arterial or intraperitoneal administration; it can also be administered directly to a local affected area, which can be directly administered through transdermal, puncture, etc. Administered.
- the chlorine dioxide-containing stem cell promoter of the present invention can be administered by any route which can reach the intended tissue, for example, by intravenous drip, intravenous injection, intraarterial injection, intramuscular injection, subcutaneous injection, Intradermal, intracardiac, intraperitoneal, intrathecal, intraarticular, puncture, rectal, sublingual, nasal, transdermal, inhalation or topical administration to damaged organs or Organization, etc., but not limited to these.
- the effective amount of the stem cell promoter in the present invention ranges from 0.1 to 500 mg/kg of chlorine dioxide per day, and the area of the target tissue is more easily expressed.
- the effective range of the stem cell promoter in the invention is 0.1 to 500 mg / 1 00 cm 2 of chlorine dioxide per day, and is effective after at least 10 days when administered at the dose.
- the chlorine dioxide-containing stem cell promoter of the present invention only guarantees that the target effective dose of chlorine dioxide can be introduced into the target in a suitable manner to exert stem cell activation, and is not limited to any form or manner. And steps, and the help of other auxiliary substances.
- any of the preparations in the "Chinese Pharmacopoeia General Rules" can be used as a dosage form of the stem cell promoter in the present invention.
- Examples of the dry cell promoter in the method of the present invention as a pharmaceutical dosage form include injections (including suspensions, emulsions) for direct use in the body; ointments (including oily ointments, cream ointments (creams), water-soluble ointments, etc.) , inhalation, liquid preparation (including eye drops, nasal drops, etc.), suppositories, patches, pastes, lotions and other external preparations; or tablets (including sugar coatings, films, gel coats), liquid preparations, capsules Agents, granules, powders (including fine-grain grades), pills, syrups, tablets, and the like.
- These preparations can be prepared according to the general principles of Chinese Pharmacopoeia preparations.
- the stem cell promoters of the methods of the invention may also comprise a pharmaceutically acceptable solid or liquid carrier or interventional therapeutic material when administered.
- a pharmaceutically acceptable solid or liquid carrier there may be mentioned solvents, stabilizers, solubilizers, emulsifiers, suspensions, buffers, isotonic agents, colorants, bases, thickeners, excipients, lubricants. , but not limited to, binders, disintegrants, coating agents, flavoring agents, conditioning agents, foaming agents, superabsorbent resins, surfactants, penetration enhancers, and pH adjusters.
- deionized water lactose, white sugar, fructose, glucose, mannose, sorbitol, etc., sugar or sugar alcohol
- crystalline cellulose methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, low substituted hydroxyl Propylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, hydroxymethylcellulose, hydroxymethylcellulose Calcium, sodium carboxymethylcellulose, crosslinked hydroxymethylcellulose sodium, hydroxymethylethylcellulose, cellulose acetate phthalate
- cellulose and its related derivatives corn starch, wheat starch, rice starch, potato starch, cyclodextrin, amylopectin and other related derivatives
- agar sodium alginate, gum arabic, gelatin, collagen
- Natural polymers such as shellac, yellow potato gum and xanthan gum (seaweed, plant mucilage, protein, etc.); polyvinyl
- interventional treatment material examples include, but are not limited to, a syringe, a stent, an artificial blood vessel, a puncture syringe, a catheter, a balloon, and the like.
- the chlorine dioxide-containing stem cell promoter of the present invention may be administered an anesthetic according to the administration mode before administration, such as an injection type anesthetic such as barbiturate, an inhalation anesthetic such as nitrous oxide, lidocaine, etc.
- an injection type anesthetic such as barbiturate
- an inhalation anesthetic such as nitrous oxide, lidocaine, etc.
- Surface anesthetics, etc. are not limited to these.
- the stem cell promoter of the present invention can be applied to mammals having stem cells, and specific examples of mammals include humans, monkeys, dogs, pigs, cats, rabbits, rats, and mice. Among them, the person is the preferred one.
- the vast majority of end-stage cells in the body system are short-lived and must be replaced continuously during life.
- stem cells play the most important role (through the proliferation of differentiated cells, without the need for stem cells, this effect can be achieved). , but it is impossible to continue for a long time) Frequent cell replacement, other accidental or sporadic tissue trauma, is required to compensate for tissue regeneration initiated by stem cells, a process that can be induced by the injury process.
- stem cells play the most important role (through the proliferation of differentiated cells, without the need for stem cells, this effect can be achieved).
- Frequent cell replacement other accidental or sporadic tissue trauma, is required to compensate for tissue regeneration initiated by stem cells, a process that can be induced by the injury process.
- the main goal of regenerative medicine is to use stem cell proliferation, migration and differentiation to regenerate tissue to repair damaged tissues and organs, especially those that are not effectively repaired through natural regeneration processes.
- stem cells in the body can be initiated or activated to increase, migrate and differentiate, they can be regenerated under the induction of a damaged tissue-specific environment. Almost all body tissues (in terms of damaged tissue) can cure almost all diseases of tissue damage or functional disorders.
- the direct object of the present invention is to provide a method for initiating proliferation, migration and differentiation of stem cells, and thus can be used indirectly for the treatment of diseases requiring treatment with the tissue regeneration ability and immunomodulatory ability of stem cells, including the following two diseases.
- Type First, a treatable disease that simply utilizes the tissue regeneration ability of stem cells; 2.
- the unique properties of the stem cell promoters of the present invention such as the action of killing microorganisms and removing necrotic tissue by the strong oxidizing property of chlorine dioxide
- the unique properties of the stem cell promoters of the present invention are also utilized. And there is a repetition of the above two types of diseases in the range of use of the stem cell promoter as the drug in the description of the present invention.
- the type of the first type of disease (a treatable disease that simply utilizes the tissue regeneration ability of stem cells) will be described below.
- the diseases can be treated, and the therapeutic mechanism is to initiate normal stem cells (including intrinsic stem cells, blood-derived stem cells, and bone marrow-derived stem cells) in the injured tissue to proliferate, migrate, and differentiate to regenerate Functions such as new tissue to achieve repair of diseased tissues and organs.
- Stroke Alzheimer's disease, Parkinson's disease, various central nervous system diseases (eg, myelitis), various peripheral neurological diseases (eg, multiple peripheral neuropathy), nerve damage diseases caused by various causes ( For example, hearing nerve damage), myelopathy, and various types of encephalitis, etc., are not limited to these.
- Cardiovascular diseases are cardiovascular diseases.
- Myocardial infarction angina pectoris, unstable angina, various types of myocarditis (eg, viral myocarditis), acute cardiac insufficiency, chronic cardiac insufficiency, atherosclerosis, hypertension, rheumatic heart disease, arrhythmia, Valvular heart disease, infective endocarditis, pericarditis, percutaneous coronary intervention, and restenosis and reocclusion after PTCA, but are not limited to these.
- myocarditis eg, viral myocarditis
- acute cardiac insufficiency e.g, chronic cardiac insufficiency
- atherosclerosis e.g, atherosclerosis
- hypertension rheumatic heart disease
- arrhythmia arrhythmia
- Valvular heart disease infective endocarditis
- pericarditis percutaneous coronary intervention
- restenosis and reocclusion after PTCA but are not limited to these.
- Esophagitis acute gastritis, chronic gastritis, gastric ulcer, duodenal ulcer, appendicitis, various types of colitis (eg, ulcerative colitis), intestinal tuberculosis, viral hepatitis, alcoholic hepatitis, drug-induced hepatitis, Fatty liver, cirrhosis, pancreatitis, and organ diseases caused by surgery of various types of gastrointestinal cancers (for example, liver cancer, colon cancer, and gastric cancer), but are not limited thereto.
- Respiratory Diseases for example, liver cancer, colon cancer, and gastric cancer
- bronchitis for example, bacterial bronchitis
- infectious pneumonia infectious pneumonia
- aspiration pneumonia pulmonary embolism
- pneumothorax pulmonary embolism
- pulmonary insufficiency pulmonary insufficiency
- Cystitis various types of nephritis (eg, chronic nephritic syndrome, primary glomerular disease), adrenal inflammation, urethritis, bacterial and non-bacterial prostatitis, hypertensive nephropathy, diabetic nephropathy, renal insufficiency, etc. , but not limited to these.
- arthritis eg, rheumatoid arthritis
- muscular atrophy eg, amyotrophic lateral sclerosis
- bone defects after neurosurgical craniotomy e.g, spinal thelial growth factor (SLL)
- bone defects after orthopedic tumor resection e.g., spinal thelial growth factor (SLL)
- Bone defects after fracture bone defects caused by periodontal degeneration in the field of dentistry
- cartilage cartilage defects of various joints
- sputum damage caused by various injuries for example, trauma or distortion
- vascular disease eg, arteriosclerosis (AS0)
- Berg's disease occlusive thromboarteritis (TA0)
- various types of venous diseases eg, thrombophlebitis
- thrombosis Formation e.g., thrombophlebitis
- circulatory dysfunction e.g., thrombophlebitis
- DVT deep vein thrombosis
- diseases associated with peripheral circulatory disorders eg, sudden deafness and vibration
- restenosis and reocclusion after angioplasty but not Limited to these.
- Diabetes and its complications for example, diabetic peripheral neuropathy, diabetic foot and diabetic ulcer), hyperlipidemia, thyroiditis and obesity, etc., but are not limited to these.
- keratitis eg, keratitis and traumatic keratitis caused by alkaline or acidic compounds
- various retinal disorders eg, macular degeneration
- optic nerve damage eg, glaucoma
- dry eye syndrome And diabetic retinitis etc., but are not limited to these.
- the chlorine dioxide-containing stem cell promoter of the present invention can be preferably used as a medicine for the skin Tissue regeneration in the treatment of skin diseases, motor system diseases, endocrine diseases, respiratory diseases, urology diseases, gastrointestinal diseases, ophthalmic diseases, nervous system diseases, cardiovascular diseases and vascular diseases.
- the type of the second type of disease (a treatable disease utilizing the tissue regeneration ability and immunomodulatory ability of stem cells) will be described below.
- the diseases can be treated, and the treatment mechanism is to initiate normal stem cells in damaged tissues (including internal Stem cells, blood-derived stem cells, and bone marrow-derived stem cells) proliferate, migrate, and differentiate to regenerate functions such as new tissues and achieve tolerance to the immune system, thereby enabling the repair of diseased tissues and organs.
- the present inventors have surprisingly found that the chlorine dioxide-containing stem cell promoter of the present invention has a positive effect on allergic diseases, particularly autoimmune diseases.
- allergic diseases include Type I allergic reaction diseases, Type I I allergic diseases, Type III allergic diseases, and Type IV allergic diseases.
- Type I allergic reactions are also known as immediate allergic reactions.
- Type I allergic reactions are mediated by I gE.
- the immediate allergic reaction is caused by the binding of antigen to IgE on mast cells or basophils.
- Atopic diseases are within the meaning of type I allergic diseases, such as, but not limited to, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic exogenous asthma, rubella, systemic allergies, etc., by I Allergies caused by allergic reactions are severe allergic reactions that are life threatening.
- Type 1 allergic or cytotoxic allergic reactions involve cytolysis mediated by antibodies, complement and/or cellular mechanisms. Anti-cell binding antigen antibodies destroy cells by activating complement or promoting phagocytosis.
- Type II allergic diseases in the scope of application of the present invention include, for example, Comm-positive hemolytic anemia, antibody-induced thrombocytopenic purpura, leukopenia, herpes zoster, herpes zoster, Gudpasch syndrome, and pernicious anemia .
- cold agglutinin syndrome also included are cold agglutinin syndrome, Graves disease, myasthenia gravis, narcolepsy, Devic syndrome, neuromuscular rigidity, rheumatic fever, urticaria vasculitis, panda syndrome, and fetal polycythemia.
- Type III allergic diseases involve reactions in which an antibody forms an immune complex with an antigen.
- the circulatory complex activates complement, adheres to the red blood cells, and the red blood cells are phagocytosed in the spleen, after which the complex leaves the circulatory system and triggers inflammation of the interstitial glands. This reaction is called the Arthus reaction.
- the complex is engulfed by antigen-presenting macrophages, releasing cytokines and activating B and T cells.
- l gE, l gA, I gG and I gM all form a complex with the antigen.
- Type III allergic reactions are usually caused by deposition of immune complexes on tissues, especially on the skin, joints, and kidneys.
- Type III allergic diseases in the scope of application of the present invention include, for example, serum diseases caused by serum, drugs or viral hepatitis antigens, systemic lupus erythematosus, rheumatoid arthritis, polyarteritis, cryoglobulinemia, hypersensitivity pneumonitis , bronchopulmonary aspergillosis, acute glomerulonephritis, chronic membrane proliferative glomerulonephritis. Also included are contact dermatitis, discoid lupus erythematosus, Meniere's disease, subacute bacterial endocarditis, vasculitis.
- Type IV allergic diseases involve cell-mediated responses that typically take 12 hours or more to occur.
- Type IV allergic diseases can include inflammation, and the result can be a chronic inflammatory disease.
- Type IV allergic reactions are also known as delayed type allergic reactions or DTH. Once the T cell is sensitized after the first contact, a second type of attack can cause a delayed type of allergic reaction. This reaction is a local inflammatory response that takes 2 to 3 days to take place in the clinic.
- Type IV allergic diseases in the scope of application of the present invention include celiac disease, type I diabetes, Guillain-Barré syndrome (GBS), Hashimoto's encephalopathy, Hashimoto's thyroiditis, multiple sclerosis, strabismus-encephalic ridge- Myoclonic syndrome (0MS), paraneoplastic cerebellar degeneration, psoriasis, psoriatic arthritis, nodular spasm, scleroderma, giant cell arteritis, ulcerative colitis.
- GRS Guillain-Barré syndrome
- Hashimoto's encephalopathy Hashimoto's thyroiditis
- multiple sclerosis multiple sclerosis
- strabismus-encephalic ridge- Myoclonic syndrome strabismus-encephalic ridge- Myoclonic syndrome
- paraneoplastic cerebellar degeneration paraneoplastic cerebellar degeneration
- psoriasis psoriatic arthritis
- nodular spasm sc
- type I and type III can occur at the same time.
- Types I I and III can also appear at the same time.
- Even type I I, III and IV can appear at the same time.
- autoimmune diseases cover most of the allergic diseases, and include some allergic diseases with clinically unknown etiology.
- autoimmune diseases in the scope of application of the present invention include: encephalomyelitis, Addison's disease, gamma globulinemia, alopecia areata, amyotrophic lateral sclerosis, ankylosing spondylitis, antiphospholipid syndrome, anti-synthesis Enzyme antibody syndrome, autoimmune aplastic anemia, autoimmune cardiomyopathy, autoimmune enteropathy, autoimmune hepatitis, autoimmune inner ear disease, autoimmune lymphoproliferative syndrome, autoimmune peripheral neuropathy, Autoimmune pancreatitis, autoimmune polyendocrine adenosis syndrome, autoimmune progesterone dermatitis, autoimmune urticaria, autoimmune urticaria, BAL0 concentric sclerosis, Behcet's disease, thromboembolic vasculature Inflammation, Bickstaff encephalitis, Blau syndrome, bullous pemphigoid, Cast l eman disease, Chagas disease, chronic inflammatory demyelinating poly
- the chlorine dioxide-containing stem cell promoter of the present invention can be preferably used as a medicament for the treatment of type I allergic diseases and autoimmune diseases which cause organ damage.
- stem cells used in regenerative medicine i.e., regenerating damaged organs and damaged tissues
- capable of treating diseases by initiating stem cell proliferation, migration, and differentiation are also chlorine dioxide-containing stem cells in the method of the present invention.
- the starter is used as a drug.
- the stem cell promoter of the present invention can rapidly and appropriately function as a drug according to the progress and degree of the damaged organ and/or the damaged tissue applied in the regenerative medicine.
- the stem cell promoter of the present invention has little or no side effects as a drug-related disease. Further, the chlorine dioxide-containing stem cell promoter of the present invention can continuously function for stem cells in in situ tissue regeneration.
- chlorine dioxide can be used to remove the necrotic tissue of the necrotic tissue and to kill the anti-infective effect of the pathogenic microorganism.
- Related embodiments of the invention are described below.
- This example is intended to illustrate a chlorine dioxide-containing stem cell promoter as a medicament for the treatment of androgen alopecia.
- Preparation of the drug a mixed solution of 7.47% sodium chlorite and 1.99% sodium chloride was prepared with deionized water to prepare a first solution; the concentration of deionized water was set to 16.7%. A citric acid solution was used to prepare a second solution.
- Dosage Take the same volume of solution from the different parts of the container, put it into a glass or plastic cup of the appropriate size, wait for the solution to mix for 3 to 5 minutes, then use 0. 22 ⁇ ( ⁇ Filter the double-layer filter, apply the cotton swab to the hair loss area, wait for 1 ⁇ 2 hours, then wash the head with water once a day.
- the first course of treatment is 1 5 ⁇ 25 days, 2 ⁇ 5 drugs are stopped. Month, then start the second course of treatment, starting from the second course of treatment for 10 to 1 5 days, then stopping the drug for 2 to 5 months, and then using the next course of treatment.
- the hair loss area accelerates hair loss, fine hair first
- the hair in the original hair loss area may be completely lost.
- the hairline is obviously moving forward. After taking a course of treatment, after 2 to 5 months of withdrawal, the hair can be judged to return to the previous level with the naked eye. For example, level 2 is restored to level 1,
- Level 4 is restored to level 3. After 1 to 2 months, start the second course of treatment, and the naked eye can be used to judge the hair to return to the next level.
- the drug begins to appear for 5 minutes, and the user describes a tingling sensation for about 15 to 30 minutes.
- a micro-wound is produced in the medication area, and the appearance is a piece of erythema, which is similar to wound hemorrhage and erythema.
- newborn hair has a higher density and is thicker.
- the chlorine dioxide-containing stem cell promoter promotes hair follicle stem cells to produce more hair follicle progenitor cells and subsequent hair follicle cells by proliferation, migration and differentiation, thereby remarkably producing new hair.
- the chlorine dioxide solution under acidic conditions can cause irritation to the skin, resulting in micro Wounds, and in areas where these wounds are concentrated, the hair growth effect is more pronounced than in other areas, which may indicate that the solution is sufficiently permeable and more capable of exerting the stem cell promoting ability of chlorine dioxide; or it may indicate that the wound is produced and the wound is healed.
- the stem cells will be differentiated in a more primitive procedure to produce more new hair (which should have been). Under normal circumstances, hair follicle stem cells do not differentiate into epidermal cells and are used for natural regeneration of human skin, but once the skin has a wound, the hair follicle stem cells will rapidly proliferate, migrate and differentiate to complete the healing of the wound.
- hair follicle stem cells were found to be involved in the regeneration of the epidermis (Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Mor ris RJ et a I: Stem ce II s in the ha irfo II ic I e bu I ge Contr i bute to wound heal ing, but not to homeostasis of the epidermis. Nat Med. 11 :1351-4.2005) .
- hair follicle stem cells can accelerate wound healing, and without hair follicle stem cells, there is a significant delay in wound healing time (Abigai l K Langton et al.: An Extended Epidermal Response Heals Cutaneous Wounds in the Absence of a Hair Folicle Stem Cel l Contribution. Journal of Investigative Dermatology. 128, 1311-1318, 2008).
- the wound healing delay is not seen, and the healing speed is fast.
- the chlorine dioxide-containing stem cell promoter of the present invention can promote proliferation, migration and differentiation of various stem cells to complete tissue regeneration such as wound healing and hair regeneration. process.
- tissue regeneration such as wound healing and hair regeneration.
- most users can produce new hair in 2 ⁇ 3 days, which can only be explained by the differentiation of stem cells, which is basically consistent with the time of general small wound healing.
- the chlorine dioxide-containing stem cell promoter of the present invention or the drug prepared therefrom as a main component can be used for treating various skin diseases, and the treatment mechanism is initiated.
- Stem cells promote tissue regeneration and repair diseased tissues and organs.
- a chlorine dioxide-containing stem cell promoter is used as a drug in a patient suffering from a vascular disease in the deep vein thrombosis of the lower extremity (DVT of the lower extremity) to illustrate a chlorine cell-containing stem cell promoter for peripheral blood.
- VE-Cadherin vascular endothelial-cadherin-positive cells
- CD34-positive mononuclear cells those cells present in peripheral blood that are considered to be CD34-positive mononuclear cells are vascular EPCs and mesenchymal stem cells (Zhao Y et al.: A human peripheral blood monocyte-der i ved multiple acts as p I Ur i potentstem ce I Is. ProcNatl AcadSci USA. 100: 2426-31, 2003). Therefore, it can be said that the CD34-positive mononuclear cells in the peripheral blood evaluated in the present example are vascular EPC and mesenchymal stem cells.
- endothelial progenitor cell expression marker is CD34 (Michejda M: Which stem ce II s hou I d be used for transp I antat i on? Feta ID i agnTher. 19:2-8, 2004 Fad ini GP et al. : C i rcu I at i ng endothe I ia I progen i tor ce I Is are reduced in peripheral vascular compl ications of tape 2 diabetes me II i tus. J American col lege of cardiology.
- vascular EPC which is known to be in the stage of differentiation progression and capable of adhering to the vascular state, can also express vascular endothelial calcium adhesion protein (Hri stov M, Weber C: Endothelial progen i tor ce I Is: character i zat i on, pathophysiology, and possible cl inical relevance. J Ce II Mo I Med. 8:498-508, 2004). Therefore, it can be said that CD34-positive/CD31-positive mononuclear cells and vascular endothelial-cadherin-positive mononuclear cells in the peripheral blood evaluated in the present example are vascular EPC.
- Test subject The subjects were 14 males and 6 female lower extremities aged 59-76 years (mean 67.2 years)
- DVT patient composition The patients were all unilateral limbs. Before the clinical trial, the purpose of the clinical trial was explained to all trial subjects and their consent was obtained.
- the first solution was prepared by dissolving a mixed solution of 7.47% sodium chlorite and 1.59% sodium chloride in deionized water; a citric acid solution having a concentration of 16.7% was prepared with deionized water to prepare a second solution. .
- the same volume of solution was taken from the containers of different solutions, mixed, and the solution was allowed to stand still for 3 to 5 minutes, diluted 5 times with physiological saline, and then filtered with 0.22 ⁇ (2 ⁇ m of double-layer filter, immediately loaded into the syringe. Prepare once for use.
- the chlorine dioxide solution configured by the above method was injected through the arterial puncture of the contralateral side (sick side) of the affected limb for 14 days at a dose of 10 ml per person per day. Before each injection, 2% lidocaine 2m I ⁇ 5m I was applied, and the anesthesia was infiltrated along the pre-puncture site at the puncture site.
- peripheral blood was collected from the median vein of the anterior hip joint of each patient before administration (before administration) and on days 7 and 14 after administration.
- the collected blood was immediately stored at 4 degrees Celsius and measured within 6 hours after collection.
- Blood was collected from all 20 lower extremity DVT patients before and 7 days after administration, and blood was collected from 15 of 20 lower extremity DVT patients on the 14th day after administration.
- CD34-positive mononuclear cells were isolated by immunofluorescence staining using a flow cytometer. 20 ⁇ l of phycoerythrin-labeled anti-CD34 antibody was added to the 100 ⁇ l mononuclear cell suspension obtained in the above method (5), and cultured at 4 ° C for 30 minutes under dark conditions. CD34 positive mononuclear cells were isolated and counted by flow cytometry. Calculate mononuclear cells according to the formula below Ratio of CD34-positive mononuclear cells (%):
- CD34/CD31 positive mononuclear cells were isolated by double immunofluorescence staining using flow cytometry. Add 20 ⁇ l of phycoerythrin-labeled anti-CD34 antibody and 20 ⁇ l of FITC-labeled anti-CD31 antibody to the 100 ⁇ l mononuclear cell suspension obtained in the above test method (5), and make it at 4 °C. Incubate for 30 minutes in the dark. Next, CD34/CD31 positive mononuclear cells were isolated and counted by flow cytometry. Calculate the ratio (%) of CD34/CD31 positive mononuclear cells in mononuclear cells according to the following formula:
- Vascular endothelial cadherin-positive mononuclear cells were isolated by immunofluorescence staining using a flow cytometer. 20 ⁇ of the ⁇ 0-labeled anti-VE cadherin antibody was added to the 100 ⁇ mononuclear cell suspension obtained in the above test method (5), and cultured at 4 ° C for 30 minutes under dark conditions. Next, VE calcium was separated. Adhesion protein-positive mononuclear cells were counted by flow cytometry. The ratio (%) of VE-cadherin-positive mononuclear cells in mononuclear cells was calculated according to the following formula:
- Vascular endothelial cadherin-positive mononuclear cells (vascular endothelial calcium adhesion protein-positive mononuclear cells / total number of mononuclear cells) X100
- Lower extremity edema is a typical and objective symptom of lower extremity DVT. Therefore, the extent of lower extremity edema was evaluated in 20 patients with a lower limb circumference of 20 cm at the knee and 15 cm below the knee measured before and after the injection of the chlorine dioxide solution through the femoral artery.
- Table 3 lists the changes in CD34-positive mononuclear cells in the peripheral blood of patients with lower extremity DVT (mean value SD%).
- CD34-positive mononuclear cells 20 before administration 0.3 0.8 ⁇ 0 ⁇ 42
- ** indicates P ⁇ 0.01 compared to pre-dose.
- the chlorine dioxide solution activates CD34-positive mononuclear cells (i.e., vascular EPC and mesenchymal stem cells) in peripheral blood of patients with lower extremity DVT. Therefore, it can be considered that the stem cell action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote the proliferation and migration of CD34-positive mononuclear cells.
- CD34-positive mononuclear cells i.e., vascular EPC and mesenchymal stem cells
- Table 4 shows the changes in CD34-positive/CD31-positive mononuclear cells in peripheral blood of patients with lower extremity DVT (mean SD%).
- ** indicates P ⁇ 0.01 compared to pre-dose.
- the chlorine dioxide solution initiates CD34-positive/CD31-positive mononuclear cells (i.e., endothelial progenitor cells) in peripheral blood of patients with lower extremity DVT. Therefore, it can be considered that the stem cell action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote proliferation, migration and differentiation of CD34-positive/CD31-positive mononuclear cells.
- Table 5 lists the changes in the number of vascular endothelial cadherin-positive mononuclear cells in the peripheral blood of patients with lower extremity DVT (mean ⁇ 50%).
- ** means ⁇ 0.01.
- the chlorine dioxide solution initiates vascular endothelial adhesion protein-positive mononuclear cells (ie, vascular EPC) in peripheral blood of patients with lower extremity DVT. Therefore, it can be considered that the stem cell action of the chlorine dioxide-containing stem cell promoter of the present invention promotes proliferation, migration and differentiation of vascular endothelial cadherin-positive mononuclear cells.
- Table 6 shows the changes in the knee length and knee length of the lower extremity DVT patients (mean soil SD%).
- ** means ⁇ 0.01.
- the degree of edema of the lower extremities was evaluated by the length of the lower extremities at 20 cm on the knee and 15 cm below the knee. By giving the chlorine dioxide solution, the knee and knee lengths were significantly shortened (Table 6).
- stem cells were activated by administration of a chlorine dioxide solution. It is considered that the stem cell promoter of the chlorine dioxide-containing stem cell promoter of the present invention acts to promote the proliferation, migration and differentiation of stem cells, and as a result, the damaged blood vessels are regenerated and the symptoms of edema in the lower limb DVT are improved.
- APTT, PT, and TT parameters were analyzed before, after, and on the 7th and 14th days after the administration of the chlorine dioxide solution, there was no significant difference between before and after the chlorine dioxide solution was administered.
- the APTT, P T and T T parameters are used as indicators for monitoring side effects (e.g., bleeding) during administration to blood coagulation and fibrinolytic system formulations, including chlorine dioxide solutions. These results indicate that no side effects occurred in the administration of the chlorine dioxide solution. However, in the absence of an anesthetic (on the first day of administration), almost all patients had a strong tingling sensation after the injection of the chlorine dioxide solution, which disappeared after about 30 minutes.
- a stem cell promoter or a drug prepared therefrom as a main component can be used for treating various cardiovascular and cerebrovascular diseases, and the therapeutic mechanism is to activate stem cells to promote tissue regeneration and repair diseased tissues and organs.
- the rat brain ischemia/reperfusion injury model of the present invention illustrates the activation of neural stem cells by the chlorine dioxide-containing stem cell promoter of the present invention and the effect of the drug as a drug on the recovery of nerve function.
- the middle cerebral artery occlusion model was first established according to the method of Longa EZ et al. (Longa EZ et al.: Reversible middle cerebral artery occ I ust i on wi thoutcran i ectomy in rats. Stroke 20: 84-91, 1989). More specifically, 0.36 g/kg, 10% chloral hydrate was intraperitoneally administered to rats which had been fasted for 12 hours (but free of water) to anesthetize the rats. Next, a midline incision is made in the neck to expose the right common carotid artery.
- the internal carotid artery and the external carotid artery are separated, the posterior carotid artery (which is a branch of the external carotid artery) and the thyroid artery are electrocoagulated, and the external carotid artery is ligated at the branch of the lingual artery and the maxillary artery, and the external carotid artery is punctured.
- the length of the nylon suture is about 18 to 20 mm from the carotid artery branch.
- the middle cerebral artery was blocked with a nylon suture to maintain the ischemic state for 2 hours, and a model of middle cerebral artery occlusion was made.
- a model of cerebral ischemia/reperfusion injury was established by reperfusion of blood by pulling a nylon suture from the artery of the occlusion model.
- the first solution was prepared by dissolving a mixed solution of 7.47% sodium chlorite and 1.59% sodium chloride in deionized water; a citric acid solution having a concentration of 16.7% was prepared with deionized water to prepare a second solution. .
- the same volume of solution was taken from the containers of different solutions, mixed, and the solution was allowed to stand still for 3 to 5 minutes, diluted 5 times with physiological saline, and then filtered with 0.22 ⁇ (2 ⁇ m of double-layer filter, immediately loaded into the syringe. Prepare once and use once.
- Test group 120 rats: These animals have been modeled for cerebral ischemia/reperfusion injury. On the 2nd day after the establishment of the model of cerebral ischemia/reperfusion injury, the chlorine dioxide solution prepared by the step (3) was injected through the carotid artery at a dose of 2 ml/kg once a day for 10 days in total.
- Sham operation group 120 rats: The above procedure (2) was performed on the rats, and only the internal carotid artery and the external carotid artery were separated, and the subsequent middle cerebral artery occlusion and reperfusion procedures were not performed. At the same administration time as shown in the test group, the rats of this group were injected with the same volume of physiological saline through the carotid artery instead of the chlorine dioxide solution.
- Control group 120 rats: These animals have been modeled for cerebral ischemia/reperfusion injury. The same volume of physiological saline was administered to the carotid artery of the model rats in place of the chlorine dioxide solution at the same administration time as indicated in the test group.
- Neurological dysfunction scores were performed once a day for 15 rats in each group. Neurological dysfunction scores were performed according to the method of Longa EZ et al. (Longa EZ et al.: Reversible mi dd I e cerebra I artery occlustion without craniectomy in rats. Stroke 20: 84-91, 1989) using the following criteria. The results are expressed in median:
- Ten rats in each group were autopsied on the 7th, 14th and 21st day after the model was established (the total number of animals per animal was 30 rats). After preparing the tissue specimen, the neural stem cells were counted under a microscope.
- rat frozen brain sections were prepared on days 7, 14, and 21 after model establishment, and nestin was positive for subventricular zone (SVZ) by immunohistochemical staining using nestin markers expressed on neural stem cells. The presence of cells. The presence of nestin-positive cells was analyzed using a mouse anti-rat nestin monoclonal antibody.
- SVZ subventricular zone
- the presence of BrdU positive cells was analyzed using a mouse anti-rat BrdU monoclonal antibody.
- the presence of NeuN positive cells was analyzed using a goat anti-neuN monoclonal antibody.
- the presence of GFAP positive cells was analyzed using a goat anti-GFAP polyclonal antibody.
- a combination of a primary antibody of a mouse anti-rat BrdU monoclonal antibody and a second antibody of a Rho-labeled rabbit anti-mouse antibody, and a first antibody of a goat anti-GFAP polyclonal antibody and a FI TC-labeled rabbit anti-goat antibody The combination of the second antibody was analyzed for the presence of BrdU-positive/GFAP-positive cells by double immunofluorescence staining.
- the chlorine dioxide solution is capable of activating neural stem cells, and as a result contributes to the improvement of neurological dysfunction.
- stem cell priming action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote proliferation, migration and differentiation of neural stem cells, and the regeneration of damaged tissues is promoted by the priming action of the stem cells.
- Table 8 shows the number of nestin-positive cells in the SVZ region (mean SD, cell number/mm 2 )
- BRt (%): the percentage of nestin-positive cells in the test group at time t;
- Bt the average number of nestin-positive cells in the test group at time t
- St the average number of nestin-positive cells in the sham operation group at time t;
- Mt the average number of nestin-positive cells in the control group at time t;
- the number of nestin-positive cells in the control group increased compared with the sham-operated group (nestin is a marker of neural stem cells) (Table 8). This is believed to be due to the compensatory response induced by stimuli in cerebral ischemia/reperfusion injury in animals.
- the chlorine dioxide solution initiates nestin-positive cells (ie, neural stem cells). It is considered that the stem cell action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote proliferation and migration of neural stem cells.
- Table 9 shows the number of BrdU-positive cells in the SVZ region (mean SD, cell number/mm 2 ).
- BRt (%): The percentage of BrdU-positive cells in the test group at time t;
- Bt average number of BrdU-positive cells in the test group at time t;
- Mt average number of BrdU-positive cells in the control group at time t;
- NeuN positive cells were confirmed in the experimental group (data not shown). NeuN is a marker for expression of immature neurons differentiated from neural stem cells. Therefore, the results indicate that immature neurons differentiated from neural stem cells exist in the test group.
- GFAP is a marker of astrocyte expression in differentiation from neural stem cells. Therefore, the results indicate that astrocytes differentiated from neural stem cells exist in the test group. However, astrocytes are differentiated cells in neural tissue. Why is BrdU incorporated into them? It is considered that the detected BrdU is incorporated into the cells in the state of the stem cells before being differentiated into astrocytes, and the BrdU is present.
- Table 10 shows the number of GFAP-positive cells in the SVZ region (mean SD, cell number/mm 2 ).
- BRt The percentage of GFAP-positive cells in the test group at time t;
- Bt average number of GFAP-positive cells in the test group at time t;
- St the average number of GFAP-positive cells in the surgical group at time t;
- Mt the average number of GFAP-positive cells in the control group at time t;
- GFAP is a marker of astrocytes differentiated from neural stem cells
- the chlorine dioxide solution initiates GFAP-positive cells (ie, neural stem cells and/or neural progenitor cells). Therefore, it is considered that the start-up stem cell action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote proliferation, migration and differentiation of neural stem cells, in particular, to promote differentiation of the above cells into astrocytes.
- the chlorine dioxide solution was not administered after the model was established on the first day, the number of GFAP-positive cells in the test group was significantly increased on the 21st day after the model was established compared with the control group. This result indicates that the chlorine dioxide-containing stem cell promoter of the present invention has a sustained promoting effect on differentiation of neural stem cells into astrocytes.
- Table 1 1 shows the number of BrdU-positive cells in the SVZ region (average soil SD, cell number/mm 2 ).
- BRt (%): The percentage of BrdU-positive cells in the test group at time t;
- Bt average number of BrdU-positive cells in the test group at time t;
- Mt average number of BrdU-positive cells in the control group at time t;
- BrdU was administered intraperitoneally only twice within 24 hours after model establishment, and since BrdU was not given after this time, BrdU analyzed on days 7, 14, and 21 after model establishment. Positive cells are BrdU positive cells present at the time of BrdU administration. Therefore, the increase in the number of BrdU-positive cells in the SVZ region analyzed on days 7, 14, and 21 after model establishment reflects the number of BrdU-positive cells that have migrated to the SVZ region.
- BrdU-positive cells in the SVZ region consist only of neural stem cells and neural progenitor cells capable of incorporating BrdU with self-replication ability. Based on the above, Table 1 1 shows the state of migration of neural stem cells and neural progenitor cells in the SVZ region.
- the number of BrdU-positive cells in the control group was significantly increased compared with the sham-operated group (Table 1 1). This is attributed to the compensatory response induced by stimuli in cerebral ischemia/reperfusion injury in animals.
- the chlorine dioxide solution activates neural stem cells. It is considered that the stem cell action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote the migration of neural stem cells and/or neural progenitor cells.
- the chlorine dioxide solution was not administered after the first day of the model establishment, on the 21st day after the model was established, the number of BrdU-positive cells in the test group was significantly increased as compared with the control group. This result indicates that the chlorine dioxide-containing stem cell promoter of the present invention has a sustained promoting effect on the migration of neural stem cells and/or neural progenitor cells.
- BrdU-positive cells in the SVZ region between the control group and the test group was compared by immunochemical staining.
- BrdU-positive cells were only distributed on the surface of the SVZ region, but in the experimental group, BrdU-positive cells were widely distributed on the surface of the SVZ region to the inside thereof.
- the neural stem cells and/or neural progenitor cells migrate from the surface of the SVZ region to the inside due to the administration of the chlorine dioxide solution, that is, the chlorine dioxide-containing stem cell promoter of the present invention promotes neural stem cells and/or nerves in the brain tissue. Progenitor cells migrated nearby.
- Example 3 clearly show that the chlorine dioxide solution has a sustained priming effect on neural stem cells. It is considered that the stem cell priming action of the chlorine dioxide-containing stem cell promoter of the present invention is to promote proliferation, migration and differentiation of neural stem cells and/or neural progenitor cells, regenerate damaged tissues, and restore nerve function of the test animals.
- the chlorine dioxide-containing stem cell promoter of the present invention or a drug prepared therefrom as a main component can be used for treating diseases of various nervous systems and exercise systems.
- the treatment mechanism is to start stem cells to promote tissue regeneration, Repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug on alopecia areata.
- the first solution was prepared by dissolving a mixed solution of 7.47% sodium chlorite and 1.99% sodium chloride in deionized water; a citric acid solution having a concentration of 16.7% in deionized water was used. , prepare a second solution.
- Alopecia areata is a common disease in dermatology. It is more common in young adults, and it is round, oval, and varies in number. Alopecia areata is an autoimmune disease caused by lymphoid immune cells attacking its own hair follicles. Hair follicle stem cells in the alopecia areata are not destroyed and hair can be re-growth. About 80% of patients will develop hair again within 12 months after the onset of the disease. But usually it will repeat. Treatment with topical steroid injections stimulates hair growth but is prone to recurrence.
- the chlorine dioxide-containing stem cell promoter of the present invention can repair the alopecia areata immune response, regenerate the hair follicle and grow new hair, and completely cure the alopecia areata.
- those skilled in the art can generalize that the chlorine dioxide-containing stem cell promoter of the present invention or a drug prepared therefrom as a main component can be used for treating various autoimmune skin diseases, and the therapeutic mechanism Both start stem cells to promote tissue regeneration, and regulate immune mechanisms to repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug for osteoarthritis.
- the purpose of this test is to evaluate the therapeutic effect of intra-articular administration of a chlorine dioxide-containing stem cell promoter of the present invention in patients with hip osteoarthritis by evaluating cartilage thickness, pain intensity, and quality of life of patients before and after treatment. get on.
- VAS visual analog scale
- Severity of disease The Womac Osteoarthritis Index Questionnaire, the self-evaluation level of hip osteoarthritis, consists of 24 items used to test the progress of the disease and determine the treatment effect.
- Hip cartilage thickness measured by ultrasound scanning in the center, middle and side chambers.
- the results of this test are analyzed as follows:
- the chlorine dioxide-containing stem cell promoter of the present invention is sufficiently tolerated without a local or systemic allergic reaction. During the medication, there was a continuous itching sensation, but it disappeared completely after about 1 hour.
- VAS estimated pain value
- the estimated pain value (VAS) evaluated by the doctor at the beginning of the trial was 55.23 ( ⁇ 9.66); after 3 months, the mean was 20.03 ( ⁇ 7.32), and the percentage decreased to 63.7% (p ⁇ 0.05); 6 months , the average value is further reduced to 7.11 ( ⁇ 6.93), the percentage decreased to 87.12% (p ⁇ 0.05) 0
- Table 13 lists the clinical evaluations of patients who were examined at the start of the trial and at 3 and 6 months after the osmotic treatment.
- Table 14 lists the clinical evaluations of the percentage decline in clinical evaluations at 3 and 6 months after osmotic therapy.
- the mean lateral cartilage thickness at baseline was 0.61 ( ⁇ 0.09) mm; after 3 months, it had increased to 0.67 ( ⁇ 0.10) mm, with a percentage increase of 9.8% (p ⁇ 0.05); after 6 months, the thickness Further increase to 0.73 ( ⁇ 0.11) mm, the percentage increase was 8.9% (p ⁇ 0.05).
- the mean central cartilage thickness at baseline was 0.73 ( ⁇ 0.09) mm; after 3 months, it had increased to 0.79 ( ⁇ 0.11) mm, with a percentage increase of 8.2% (p ⁇ 0.05); after 6 months, the thickness Further increase to 0.89 ( ⁇ 0.09) mm, the percentage increase was 12.7% (p ⁇ 0.05).
- Table 15 lists the critical cartilage evaluation thicknesses at the beginning of the trial and 3 and 6 months after the osmotic treatment.
- the VAS pain value decreased significantly compared with the baseline, indicating that the drug not only enhanced the viscoelasticity of the synovial fluid, but also had a clear improvement in pain symptoms, thus providing a clear improvement in the patient's quality of life.
- the chlorine dioxide-containing stem cell promoter of the present invention has remarkable ability to regenerate inflammatory tissues as a drug.
- Stem cell promoters or drugs prepared therefrom as a main component can be used for the treatment of various inflammatory diseases and sports system diseases, and the therapeutic mechanism is to initiate stem cells to promote tissue regeneration and repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug on ankylosing spondylitis.
- Ankylosing spondylitis is a chronic, progressive, disabling autoimmune disease in which key hip involvement is the leading cause of AS disability in key peripheral lesions.
- the purpose of this test is to evaluate the therapeutic effect of intra-articular (s) administration of a chlorine dioxide-containing stem cell promoter of the present invention in a patient suffering from an autoimmune disease such as ankylosing spondylitis.
- the first solution was prepared by dissolving a mixed solution of 7.47% sodium chlorite and 1.59% sodium chloride in deionized water; a citric acid solution having a concentration of 16.7% was prepared with deionized water to prepare a second solution. . Remove the same volume of solution from the container of different solutions and place it in a glass or plastic cup of the appropriate size. Wait for the solution to mix for 3 to 5 minutes, then filter with 0.22 ⁇ ( ⁇ double filter). Add dimethyl sulfoxide according to the ratio of 1:1 of the volume. Immediately apply to the skin of the affected area of the hip joint once a day for 3 weeks, stop for 1 week, then continue treatment for 3 weeks, then stop the drug for 1 week. Repeat 4 cycles.
- stage 0 normal, 0 points
- stage I suspicious change, possibly local joint space narrowing, 25 points
- stage II mild abnormal, clear Joint space narrowed, joint space> 2 (11 (11, 50 points
- stage III moderate abnormality, joint space narrowing, joint space ⁇ 2 (11 (11 or local joint space disappeared, osteoarticular surface contact range ⁇ 2cm, 75 points
- Stage IV severe abnormalities, bone deformation, bone joint surface contact range> 2cm, 100 points.
- stage I and II lesions have the following three signs, namely erosion damage, callus formation and hip The two types of joint invagination are increased by one level.
- the corresponding BASRI evaluation is given according to the degree.
- Harris hip score Out of 100 points, including 44 degrees of hip pain, 47 points of hip function, 4 points of lower limb deformity, and 5 points of hip range (angle). The corresponding scores are given according to different degrees. AS disease activity and function were assessed using the Bath Ankylosing Spondylitis Function Index (BASFI), Bath Ankylosing Spondylitis Activity Index (BASDAI), ESR, and C-Reactive Protein (CRP).
- BASFI Bath Ankylosing Spondylitis Function Index
- BASDAI Bath Ankylosing Spondylitis Activity Index
- ESR ESR
- C-Reactive Protein C-Reactive Protein
- the chlorine dioxide-containing stem cell promoter of the present invention is sufficiently tolerated without a local or systemic allergic reaction. During the medication, there was a continuous itching sensation, but it disappeared completely after about 1 hour.
- the BASRI staging of hips involved in the 3 months after treatment was reduced by about half; the BASRI staging of hips involved in 6 months after treatment was reduced by about 1 grade.
- Table 16 shows the scores of the indices before and after AS treatment.
- AS is a systemic disease with unexplained sphincter arthritis and chronic inflammation of the spine. It can be classified as an autoimmune disease. 24% to 75% of patients have peripheral joints at the beginning or the course of the disease. Lesions, especially adolescents.
- the current standard of treatment is the use of hormones or certain biological agents. In theory, these treatments are based on the inhibition or alleviation of symptoms, and can not fundamentally eliminate the pathogenic factors.
- the chlorine dioxide-containing stem cell promoter in the present invention can be said to fundamentally solve the cause of the disease, and the mechanism and test results can be extended to other autoimmune diseases, especially the treatment of various types of arthritis.
- the chlorine dioxide-containing stem cell promoter of the present invention or the drug prepared therefrom as a main component can be used for treating various autoimmune diseases, and the treatment mechanism is To initiate stem cells to promote tissue regeneration, and to regulate immune mechanisms, repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug on eczema.
- the dry cell starter of the present invention is applied as follows:
- the first solution was prepared by dissolving a mixed solution of 8% sodium chlorite and 2% sodium chloride in deionized water; a citric acid solution having a concentration of 12% was prepared with deionized water to prepare a second portion.
- Solution Remove the same volume of solution from the different parts of the container (depending on the size of the treatment area, configure the corresponding volume of the solution, about 1 ⁇ 10 ml / 100 square centimeter), put the appropriate size of the glass prepared in advance Or in a plastic cup, wait for the solution to mix and stand still for 3 to 5 minutes, then filter with 0.22 ⁇ ( ⁇ double layer filter. Apply immediately to the affected area of the eczema, once a day for 10 to 15 days, then stop the drug. If the eczema recurs, apply as above.
- the chlorine dioxide-containing stem cell promoter of the present invention has the following effects on eczema: It has a certain tingling sensation and can immediately replace itching; the partial oxidation of the syrup can remove substances considered to be exogenous by the immune system.
- the active ingredient of the syrup can initiate stem cell differentiation of the wound in the affected area, can quickly heal the wound, and normalize the immune system to the affected area; the oxidizing ability of the medicinal water resists microorganisms such as bacteria, ensuring that the wound is not infected.
- a stem cell promoter or a drug prepared therefrom as a main component can be used for treating various types of autoimmune skin diseases, and the therapeutic mechanism is to activate stem cells to promote tissue regeneration, and to regulate immune mechanisms and repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug for psoriasis.
- Psoriasis is a T cell-mediated inflammatory disease that is considered to be one of the most common autoimmune diseases, affecting approximately 2% to 3% of adults.
- the purpose of this test is to evaluate the therapeutic effect of the chlorine dioxide-containing stem cell promoter of the present invention in patients suffering from autoimmune skin diseases such as psoriasis.
- Treatment group 29 males (74. 36%), 10 females (25. 64%); age (49 ⁇ 05 ⁇ 14.57); duration of disease (12 ⁇ 9) years.
- Control group 28 males (68.29%), 13 females (31.71%); age (47 ⁇ 05 ⁇ 16 ⁇ 25); duration of disease (12 ⁇ 10) years.
- the patient in the treatment group was treated with a mixed solution of 10% sodium chlorite and 2.5% sodium chloride in deionized water to prepare a first solution; a citric acid solution having a concentration of 22% was prepared with deionized water to prepare Take out the second solution.
- Remove the same volume of solution from the different parts of the container ((depending on the size of the treatment area, configure the corresponding volume of the solution, about 1 ⁇ 10 ml / 100 cm2), put the appropriate size of the glass or In the plastic cup, wait for the solution to mix and stand still for 3 to 5 minutes, then filter with 0.22 ⁇ (2 ⁇ m of double-layer filter. Apply immediately to the affected area, once a day for 10 to 15 days, then stop the drug. If relapse, follow the above method.
- This test is a count data, using the chi-square test to compare the cure rate and recurrence rate of the two groups.
- the chlorine dioxide-containing stem cell promoter of the present invention has the following effects on psoriasis: It has a certain tingling sensation and can immediately replace itching; the partial oxidation of the stem cell promoter can be eliminated by the immune system.
- Source material the active ingredient in the stem cell promoter can initiate stem cell differentiation of the wound in the affected area, can quickly heal the wound, regenerate the skin of the affected area, and normalize the immune system to the affected area; the oxidizing ability of the medicinal water resists microorganisms such as bacteria. Guarantee wound Not infected.
- the chlorine dioxide-containing stem cell promoter of the present invention or the drug prepared therefrom as a main component can be used for treating various autoimmune diseases, and the treatment mechanism is To initiate stem cells to promote tissue regeneration, and to regulate immune mechanisms, repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug for rhinitis.
- Rhinitis is a common disease with a high incidence rate. It is divided into chronic rhinitis and allergic rhinitis. There are not many treatments and it may be cured for a long time. The purpose of this test is to evaluate the therapeutic effect of the chlorine dioxide-containing stem cell promoter in the present invention in patients suffering from chronic rhinitis and allergic rhinitis.
- the patient in the treatment group was treated with a mixed solution of 7.47% sodium chlorite and 1.99% sodium chloride in deionized water to prepare a first solution; the concentration was set to 0.17 in deionized water.
- a second solution was prepared from a citric acid solution. The above two solutions were mixed to prepare a solution containing chlorine dioxide.
- Each patient was prepared 50 ml at a time, placed in a bottle and sealed in a refrigerator. Before use, take 2 ⁇ 5m l per person from the above configured solution and pour into the open cup. The patient aligns the nose with the solution cup, breathes the nose for 1 to 2 minutes, then dilutes the solution 5 to 100 times with physiological saline, and then puts it into the nasal spray, and sprays 3 to 5 times into each nasal cavity.
- Table 1 9 Group number of cases was effective, invalid, effective, recurrence, number of cases, recurrence rate, treatment group, 30 26 3 1 97%, 3 1 0%, control group, 30 1 0 1 3 7 77%, 27 90%, chlorine dioxide-containing stem cells in the present invention
- the agent has a significant therapeutic effect on chronic rhinitis and allergic rhinitis, in addition to significantly shrinking the nasal mucosa and reducing the secretion of nasal glands; it also exhibits significant anti-inflammatory and anti-allergic effects. Better than the products that are commonly used today.
- the chlorine dioxide-containing stem cell promoter of the present invention has the following effects on rhinitis: a certain tingling sensation, antihistamine, and reduced sneezing; partial oxidation of the medicinal water can be eliminated as an external source by the immune system Sexual substance; the active ingredient of the syrup can initiate the differentiation of stem cells in the affected area, can quickly eliminate inflammation, produce new tissue, and can normalize the immune system to the affected area, that is, anti-inflammatory and anti-allergic effects; Resists against microorganisms such as bacteria.
- the chlorine dioxide-containing stem cell promoter of the present invention or the drug prepared therefrom as a main component can be used for treating various inflammatory diseases, allergic diseases, and breathing.
- Systemic and ophthalmic diseases, and the treatment mechanism is to initiate stem cells to promote tissue regeneration, and regulate immune mechanisms to repair diseased tissues and organs.
- This example is intended to illustrate the test effect of the chlorine dioxide-containing stem cell promoter of the present invention as a drug in a type I diabetic mouse model.
- a first solution by dissolving a mixed solution of 4% sodium chlorite and 1% sodium chloride in deionized water; concentrating the citric acid solution at a concentration of 8% with deionized water to prepare a second solution . Remove the same volume of solution from the different parts of the solution, mix, wait for the solution to mix and stand still for 3 to 5 minutes, then filter with 0.22 ⁇ m ( ⁇ double filter) and load the syringe immediately.
- the type II diabetic mouse model which was purchased from Peking University Medical School, was randomly divided into two groups, sputum and sputum, each group of 10, group A was the above-mentioned configured stem cell starter treatment group, and group B was the same volume of 0.9%.
- the sodium chloride solution was in the control group.
- group A 0. 5m l of the above-mentioned configured stem cell promoter was injected on the 0th day of the mouse model, and the same dose was injected on the 7th day and the 14th day; the B group was infused at the same time point in the hepatic artery. 5 ml of saline and calculate the blood glucose level of the mouse model.
- the fasting blood glucose levels of the murine model were measured on the 7th day, the 14th day, the 21st day, and the 28th day after the last injection, and the results are shown in Table 20 below. Table 20
- chlorine dioxide-containing stem cell promoter of the present invention or a drug prepared therefrom as a main component can be used for treating various urinary and endocrine diseases, and the therapeutic mechanism Both start stem cells to promote tissue regeneration and repair diseased tissues and organs.
- Example 1 1 the chlorine dioxide-containing stem cell promoter of the present invention or a drug prepared therefrom as a main component can be used for treating various urinary and endocrine diseases, and the therapeutic mechanism Both start stem cells to promote tissue regeneration and repair diseased tissues and organs.
- This example is intended to illustrate the therapeutic effect of a chlorine dioxide-containing stem cell promoter as a drug on gastric ulcer.
- Gastric ulcer is a common and frequently-occurring disease in internal medicine, and there are many causes. Among them, Helicobacter pylori (HP) infection is a major factor. A large number of studies have shown that about 80% of gastric ulcers are caused by HP infection. The occurrence of gastric ulcer is the result of the imbalance of mucosal invasion factors and defense factors, and is a typical gastric tissue damage disease.
- HP Helicobacter pylori
- the first solution was prepared by dissolving a mixed solution of 20% sodium chlorite and 5% sodium chloride in deionized water; a citric acid solution having a concentration of 30% was prepared with deionized water to prepare a second solution. . Remove the same volume of solution from the container of different parts of solution, put it into a glass or plastic cup of appropriate size and clean, and wait for the solution to mix for 3 to 5 minutes. Fill the mixed solution with No. 0 in a syringe. Soft capsules, capsules containing the stem cell promoter of the present invention are prepared.
- Soft capsules of cell starter one capsule each time; control group 1 patient 30 minutes before meals, oral colloidal pectin ⁇ 15 mg and tinidazole 100 mg, 3 times / d, oral omeprazole 20 mg, 2 times / d; Group 2 patients received oral amoxicillin 1.0 g, clindamycin 500 mg, 3 times / d, esomeprazole 20 mg, 2 times / do each group for 1 week. The clinical symptoms of abdominal pain, nausea and acid reflux were observed 2 weeks after taking the drug in three groups. After 30 days, gastroscopy and gastric mucosal urease test were performed to observe ulcer healing and HP eradication.
- Efficacy judgment criteria Accurately record changes in the condition before and after treatment and the disappearance of symptoms.
- the diagnostic criteria are as follows: 1) Complete healing criteria: Pain, heartburn, nausea, acid reflux, bloating and other symptoms disappear; endoscopic ulcers heal completely, peripheral inflammation disappears; Helicobacter pylori test negative; 2) basic healing criteria: consciousness symptoms disappear, Gastroscopic ulcer healing >90%, peripheral inflammation is basically eliminated; 3) Effective criteria: ulcer surface shrinkage >50%, or ulcer number reduction >50%; 4) Invalid criteria: ulcer healing 50% or no change, even ulcer surface or The number of ulcers increases. A mucosal specimen was taken from the gastric antrum and the corpus corpus for a rapid urease test. Both results were negative and the HP was negative.
- the HP conversion rate of the treatment group is substantially equivalent to the HP conversion rate of the control group 1, which indicates that the chlorine dioxide in the stem cell promoter of the present invention exerts an obvious effect of killing pathogenic microorganisms in the body;
- the effect of HP eradication is similar, the rate of complete healing of gastric ulcer is higher after the drug prepared using the stem cell promoter of the present invention, indicating that the stem cell promoter of the present invention promotes tissue regeneration of stem cells and accelerates gastric ulcer. healing.
- the chlorine dioxide-containing stem cell promoter of the present invention or a medicament prepared therefrom as a main component can be used for treating various gastrointestinal diseases and excluding skin.
- In vivo organ tissues are infected with diseases caused by pathogenic microorganisms, and the therapeutic mechanism is to initiate stem cells to promote tissue regeneration, repair diseased tissues and organs, and also include chlorine dioxide to kill pathogenic microorganisms in vivo.
- This example is intended to illustrate the preventive effect of a chlorine dioxide-containing stem cell promoter as a drug on post-operative complications of lung cancer.
- Surgical treatment is the first choice for lung cancer treatment, but surgical treatment is more traumatic and can easily lead to a series of postoperative complications.
- the more common complications are: 1) bronchial anastomotic leakage and bronchopleural fistula; 2) intrathoracic hemorrhage after lung cancer surgery; 3) respiratory complications; 4) cardiovascular system complications.
- a pH of 3 acidic aqueous solution of 15 liters was prepared with citric acid and deionized water.
- a 30% aqueous solution of 500 m I was made with deionized water and sodium chlorite, and a 50% aqueous solution of 500 ml was prepared with deionized water and citric acid.
- the above two solutions were mixed in a 2-liter triangular beaker and bottled.
- the plastic conduit of the plug (closed beaker mouth) is connected to the configured acidic aqueous solution.
- the chlorine dioxide gas was bubbled into the acidic aqueous solution for 40 minutes to prepare a chlorine dioxide-containing stem cell promoter, which was then packaged in 150 plastic bottles having a capacity of 100 ml and stored in a refrigerator.
- the stem cell promoter containing chlorine dioxide has a significant preventive effect on the postoperative complications of lung cancer, indicating that the stem cell promoter of the present invention can promote the regeneration of damaged tissue caused by cancer and restore the normal function of the tissue. An aid to cancer treatment.
- Stem cell promoters or drugs prepared from them as main components can be used to promote tissue regeneration and treat various respiratory diseases in various types of cancer, and the drug mechanism is to initiate stem cells to promote tissue regeneration, and to reconstitute diseased tissues and organs.
- This example is intended to illustrate the effect of a chlorine dioxide-containing stem cell promoter as a drug on skin scar removal.
- Scars are physical, biological, chemical and other factors that damage the soft tissues of human skin, leading to serious damage to the soft tissues of the skin and cannot be completely repaired by themselves.
- the essence of scar is an abnormal, unsound tissue that does not have normal skin tissue structure and physiological functions, and loses normal tissue vitality.
- the scar tissue can be replaced by normal tissue to achieve the cosmetic or therapeutic effect of removing scars.
- Twenty patients with scars were screened as subjects, including 7 males and 13 females with an average age of 33 years; 5 cases of burn scars, 7 cases of scars left by accidental wound healing, 5 cases of surgical scars, and residual skin diseases 3 cases of scars under; the average duration of scars is about 3 years.
- the first solution by using a mixed solution of 10% sodium chlorite and 2.5% sodium chloride in deionized water; prepare a citric acid solution with a concentration of 20% in deionized water to prepare the first Two parts solution.
- Remove the same volume of solution from the different parts of the solution (( according to the size of the treatment area, configure the corresponding volume of the solution, about 1 ⁇ 10 ml / 100 square centimeter), put it in the appropriate size In a glass or plastic cup, wait for the solution to mix and stand still for 3 to 5 minutes, then filter with a double layer membrane of 0.22 ⁇ , and add dimethyl sulfoxide according to the ratio of 1:1. Apply immediately to the scar, daily Once, for 10 to 1 5 consecutive days, then discontinue the drug; the first dose is started 1-2 months after the first drug is stopped, once a day for 5 to 10 days.
- the chlorine dioxide-containing stem cell promoter of the present invention is used as a medicine for treating scars, and the effective rate is 45%, and the effective rate is 30%, which is 1 month after the second administration. Efficiency has increased to 75%. It can be seen that the chlorine dioxide-containing stem cell promoter of the present invention is useful as a medicine for treating scars in human skin, and the effect is remarkable. It has been found that the chlorine dioxide-containing stem cell promoter of the present invention first utilizes its unique clearing action to clear scar tissue, and then initiates stem cells for tissue regeneration to grow intact and functionally new skin. The chlorine dioxide-containing stem cell promoter of the present invention can be used for tissue regeneration in cosmetic surgery.
- the chlorine dioxide-containing stem cell promoter of the present invention or the drug prepared therefrom as a main component can be used for tissue regeneration in cosmetic surgery, and can also treat generality.
- the skin disease, and the drug mechanism is to initiate stem cells to promote tissue regeneration and repair damaged tissues and organs.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Ophthalmology & Optometry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Inorganic Chemistry (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015544328A JP6141997B2 (ja) | 2012-11-29 | 2013-10-26 | 哺乳類の幹細胞に作用する方法と、哺乳類の幹細胞に作用する薬物の応用において調製、使用される二酸化塩素 |
US14/647,698 US20150335678A1 (en) | 2012-11-29 | 2013-10-26 | Method of activating stem cells in an animal and the use of chlorine dioxide for preparing medicines for activating stem cells in an animal |
EP13858112.9A EP2926819B1 (en) | 2012-11-29 | 2013-10-26 | Method for initiating stem cells of mammals and use of chlorine dioxide in preparation of drug for initiating stem cells of mammals |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210499300.XA CN103040860B (zh) | 2012-11-29 | 2012-11-29 | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 |
CN201210499300.X | 2012-11-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2014082514A1 true WO2014082514A1 (zh) | 2014-06-05 |
Family
ID=48053871
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2013/086018 WO2014082514A1 (zh) | 2012-11-29 | 2013-10-26 | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20150335678A1 (zh) |
EP (1) | EP2926819B1 (zh) |
JP (1) | JP6141997B2 (zh) |
CN (1) | CN103040860B (zh) |
WO (1) | WO2014082514A1 (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014121322A (ja) * | 2012-12-21 | 2014-07-03 | Stembios Technologies Inc | 幹細胞による行為効果を評価する方法 |
US10143710B2 (en) | 2010-08-04 | 2018-12-04 | StemBios Technologies, Inc. | Somatic stem cells |
US11492592B2 (en) | 2012-12-06 | 2022-11-08 | StemBios Technologies, Inc. | Lgr5+ somatic stem cells |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103040860B (zh) * | 2012-11-29 | 2018-08-14 | 刘学武 | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 |
CN103720709A (zh) * | 2013-12-12 | 2014-04-16 | 刘学武 | 包含二氧化氯的细胞凋亡诱导剂及其在制备化妆品或抗衰老或抗肿瘤药物中的用途 |
CN105726469A (zh) * | 2016-03-08 | 2016-07-06 | 刘学武 | 包含二氧化氯的注射剂及其制备方法 |
CH713095B1 (de) * | 2017-04-07 | 2018-04-30 | Schweizer Zentrum Fuer Wss Forschung Innovation Und Entwicklung | Pharmazeutische Zusammensetzung zur Behandlung von Entzündungen. |
CH713711B1 (de) * | 2017-04-07 | 2019-02-15 | Schweizer Zentrum Fuer Wss Forschung Innovation Und Entwicklung | Pharmazeutische Zusammensetzung zur Behandlung von Infektionskrankheiten. |
CN108888636A (zh) * | 2018-08-14 | 2018-11-27 | 东营凤起生物科技发展有限公司 | 一种治疗糖尿病和动脉粥样硬化的方法 |
WO2021255646A1 (en) * | 2020-06-15 | 2021-12-23 | Margana Bio Technologies Ltd. | A copper based composition for animal consumption |
CN113398248B (zh) * | 2021-07-27 | 2023-08-15 | 上海交通大学医学院附属第九人民医院 | 一种改善皮瓣血运的外用药及其制备方法 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5750108A (en) | 1995-09-18 | 1998-05-12 | Regenix Marketing Systems, Inc. | Hair treatment system and kit for invigorating hair growth |
CN1199633C (zh) | 1996-07-29 | 2005-05-04 | 罗伯特·埃里克·蒙哥马利 | 二氧化氯牙齿增白组合物 |
CN101278045A (zh) | 2005-09-30 | 2008-10-01 | 东菱药品工业株式会社 | 干细胞和/或祖细胞的赋活剂 |
CN101405021A (zh) | 2006-03-17 | 2009-04-08 | 干细胞治疗公司 | 神经干细胞增殖试剂和神经干细胞分化试剂的连续给药方案 |
CN101641104A (zh) | 2007-03-27 | 2010-02-03 | 大幸药品株式会社 | 感染性皮肤和粘膜疾病治疗药 |
CN101657206A (zh) | 2007-02-12 | 2010-02-24 | 人类起源公司 | 利用胎盘干细胞治疗炎性疾病 |
CN102137651A (zh) | 2008-07-15 | 2011-07-27 | 巴斯夫公司 | 非细胞毒性的二氧化氯流体 |
CN102441006A (zh) | 2011-12-01 | 2012-05-09 | 刘学武 | 一种含二氧化氯的生发溶液及其制备和使用方法 |
CN103040860A (zh) * | 2012-11-29 | 2013-04-17 | 刘学武 | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5857308A (ja) * | 1981-09-30 | 1983-04-05 | Masumi Inaba | 発毛,養毛剤 |
US4818519A (en) * | 1986-12-29 | 1989-04-04 | Ratcliff Perry A | Method and composition for prevention of plaque formation and plaque dependent diseases |
US4956184A (en) * | 1988-05-06 | 1990-09-11 | Alcide Corporation | Topical treatment of genital herpes lesions |
US6350438B1 (en) * | 1998-02-27 | 2002-02-26 | The Procter & Gamble Company | Oral care compositions comprising chlorite and methods |
DE19949297A1 (de) * | 1999-10-13 | 2001-04-26 | Steag Encotec Gmbh | Lagerhalle für mit wärmeerzeugendem radioaktivem Material gefüllte Behälter |
JP2005097225A (ja) * | 2003-09-24 | 2005-04-14 | Sukegawa Chemical Co Ltd | 活性化二酸化塩素による家畜子宮炎の予防と治療 |
JP5313874B2 (ja) * | 2007-03-22 | 2013-10-09 | 大幸薬品株式会社 | アレルゲン不活性化剤 |
BRPI0916446A2 (pt) * | 2008-07-15 | 2018-09-11 | Basf Corp | dispositivo, sistema, composição e método para a distribuição de uma composição de dióxido de cloro substancialmente isenta de ânion de oxi- cloro a um tecido |
US8311625B2 (en) * | 2009-02-04 | 2012-11-13 | Basf Corporation | Chlorine dioxide treatment for biological tissue |
CA2756695A1 (en) * | 2009-03-23 | 2010-09-30 | Kross-Link Laboratories | Method for suppressing or preventing fibrous adhesion formation using a multicomponent aqueous oxychlorine composition prepared on-site |
WO2011090932A2 (en) * | 2010-01-19 | 2011-07-28 | Sinox Corporation | A method of treating sinusitis, including chronic sinusitis |
-
2012
- 2012-11-29 CN CN201210499300.XA patent/CN103040860B/zh not_active Expired - Fee Related
-
2013
- 2013-10-26 US US14/647,698 patent/US20150335678A1/en not_active Abandoned
- 2013-10-26 EP EP13858112.9A patent/EP2926819B1/en not_active Not-in-force
- 2013-10-26 WO PCT/CN2013/086018 patent/WO2014082514A1/zh active Application Filing
- 2013-10-26 JP JP2015544328A patent/JP6141997B2/ja not_active Expired - Fee Related
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5750108A (en) | 1995-09-18 | 1998-05-12 | Regenix Marketing Systems, Inc. | Hair treatment system and kit for invigorating hair growth |
CN1199633C (zh) | 1996-07-29 | 2005-05-04 | 罗伯特·埃里克·蒙哥马利 | 二氧化氯牙齿增白组合物 |
CN101278045A (zh) | 2005-09-30 | 2008-10-01 | 东菱药品工业株式会社 | 干细胞和/或祖细胞的赋活剂 |
CN101405021A (zh) | 2006-03-17 | 2009-04-08 | 干细胞治疗公司 | 神经干细胞增殖试剂和神经干细胞分化试剂的连续给药方案 |
CN101657206A (zh) | 2007-02-12 | 2010-02-24 | 人类起源公司 | 利用胎盘干细胞治疗炎性疾病 |
CN101641104A (zh) | 2007-03-27 | 2010-02-03 | 大幸药品株式会社 | 感染性皮肤和粘膜疾病治疗药 |
CN102137651A (zh) | 2008-07-15 | 2011-07-27 | 巴斯夫公司 | 非细胞毒性的二氧化氯流体 |
CN102441006A (zh) | 2011-12-01 | 2012-05-09 | 刘学武 | 一种含二氧化氯的生发溶液及其制备和使用方法 |
CN103040860A (zh) * | 2012-11-29 | 2013-04-17 | 刘学武 | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 |
Non-Patent Citations (51)
Title |
---|
"Stem Cell Antholgy", 2010, ELSEVIER INC. |
ABIGAIL K LANGTON ET AL.: "An Extended Epidermal Response Heals Cutaneous Wounds in the Absence of a Hair Follicle Stem Cell Contribution", JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 128, 2008, pages 1311 - 1318 |
AICHER A; ZEIHER A M; DIMMELER S: "Mobilizing endothelial progenitor cells", HYPERTENSION, vol. 45, 2005, pages 321 - 325 |
ALLON M. KLEI ET AL.: "Universal patterns of stem cell fate in cycling adult tissues", DEVELOPMENT, vol. 138, 1 August 2011 (2011-08-01), pages 3103 - 3111 |
ASAHARA T ET AL.: "Isolation of putative progenitor endothelial cells for angiogenesis", SCIENCE, vol. 275, 1997, pages 964 - 967 |
CAI, WEILING ET AL.: "Observation on effect of patients with nasopharyngeal radioactivity oral cavity mucositis prevented and treated by moerlun gargarism.", CHINESE NURSING RESEARCH, vol. 26, no. 3B, 31 March 2012 (2012-03-31), pages 720 - 721, XP055259872 * |
CECILIA ROH ET AL.: "Cutaneous Stem Cells and Wound Healing", PEDIATRIC RESEARCH, vol. 59, 2006, pages 100R - 103R |
CHUTIMA TALCHAI ET AL.: "Generation of functional insulin-producing cells in the gut by Foxol ablation", NATURE GENETICS, vol. 44, 2012, pages 406 - 412 |
CLIFFORD J. WOOLF: "What is this thing called pain?", J CLIN INVEST., vol. 120, no. 11, 1 November 2010 (2010-11-01), pages 3742 - 3744 |
CLIFFORD J.: "Annals of Internal Medicine", vol. 140, 2004, article "Wool. Pain: Moving from Symptom Control toward Mechanism-Specific Pharmacologic Management", pages: 441 - 451 |
FADINI G P ET AL.: "Circulating endothelial progenitor cells are reduced in peripheral vascular complications of tape 2 diabetes mellitus", J AMERICAN COLLEGE OF CARDIOLOGY, vol. 45, 2005, pages 1449 - 1457 |
GARRY D J ET AL.: "Ponce de Leon's fountain: stem cells and the regenerating heart", AM J MED SCI, vol. 329, no. 4, 2005, pages 190 - 201 |
GARRY DJ ET AL.: "Ponce de Leon's fountain: stem cells and the regenerating heart", AM J MED SCI., vol. 329, no. 4, 2005, pages 190 - 201 |
HILA TOLEDANO ET AL.: "The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche", NATURE, 23 May 2012 (2012-05-23) |
HRISTOV M; WEBER C: "Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance", J CELL MOL MED, vol. 8, 2004, pages 498 - 508 |
ITO M ET AL.: "Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding", NATURE, vol. 447, no. 7142, 17 May 2007 (2007-05-17), pages 316 - 20 |
ITO M; LIU Y; YANG Z; NGUYEN J; LIANG F; MORRIS RJ ET AL.: "Stem cells in the hair follicle bulge contributed to wound healing, but not to homeostasis of the epidermis", NAT MED., vol. 11, 2005, pages 1351 - 4 |
JIN WEI ET AL.: "the trial study on promotion of chlorine dioxide on wound healing of rabbit", SHANXI MEDICAL UNIVERSITY JOURNAL, vol. 42, no. 7, 2011 |
JULIA M. RUCKH ET AL.: "Rejuvenation of Regeneration in the Aging Central Nervous System", CELL STEM CELL, vol. 10, no. 1, 6 January 2012 (2012-01-06), pages 96 - 103 |
KATHERINE LAU ET AL.: "Exploring the role of stem cells in cutaneous wound healing", EXPERIMENTAL DERMATOLOGY, vol. 18, no. 11, November 2009 (2009-11-01), pages 921 - 933 |
KATHERINE LAU ET AL.: "xploring the role of stem cells in cutaneous wound healing", EXPERIMENTAL DERMATOLOGY, vol. 18, no. 11, November 2009 (2009-11-01), pages 921 - 933 |
KENTARO AKIYAMA ET AL.: "Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis", CELL STEM CELL, vol. 10, no. 5, 26 April 2012 (2012-04-26), pages 544 - 444 |
KUWANA M ET AL.: "Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation", J LEUKOC BIOL, vol. 74, 2003, pages 833 - 845 |
LONGA E Z ET AL.: "Reversible middle cerebral artery occlusion without craniectomy in rats", STROKE, vol. 20, 1989, pages 84 - 91 |
LORD; WRIGHT, BLOOD CELLS, vol. 6, 1980, pages 581 - 593 |
LUIS A. GARZA ET AL.: "Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells", J CLIN INVEST., vol. 121, no. 2, 1 February 2011 (2011-02-01), pages 613 - 622 |
M. B. WITTE ET AL.: "Nitric oxide enhances experimental wound healing in diabetes", BRITISH JOURNAL OF SURGERY, vol. 89, no. 12, December 2002 (2002-12-01), pages 1594 - 1601 |
MAJIDA RIZK ET AL.: "Nitric Oxide and Wound Healing", WORLD JOURNAL OF SURGERY, vol. 28, no. 3, 2004, pages 301 - 306 |
MARRACK ET AL., NAT MED, vol. 7, 2001, pages 899 - 905 |
MARSHAL LAND LORD, INT REV. CYT., vol. 167, 1996, pages 185 - 261 |
MCCLOSKEY K E ET AL.: "Use of embryonic stem cell-derived endothelial cells as a cell source to generate vessel structures in vitro", TISSUE ENG, vol. 11, 2005, pages 497 - 505 |
MICHEJDA M: "Which stem cells should be used for transplantation?", FETAL DIAGN THER, vol. 19, 2004, pages 2 - 8 |
PITTENGER, M.F.; MARTIN, B.J.: "Mesenchymal stem cells and their potential as cardiac therapeutics", CIRC. RES., vol. 95, 2004, pages 9 - 20 |
QU RUO ET AL.: "Stability of chlorine dioxide treat of severe corneal ulcers efficacy.", CHINESE OURNAL OF CRITICAL CARE MEDICINE., vol. 19, no. 9, 30 September 1999 (1999-09-30), pages 521, XP008179573 * |
REYNOLDS B A; WEISS S: "Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system", SCIENCE, vol. 255, 1992, pages 1707 - 1710 |
SATO Y ET AL.: "Can a bone marrow cell contribute to organ regeneration? In vivo analysis using transgenic rats with reporter genes", TRANSPLANTATION PROCEEDINGS, vol. 37, 2005, pages 273 - 275 |
SHEN Q ET AL.: "Endothehal cells stimulate self-renewal and expand neurogenesis of neural stem cells", SCIENCE, vol. 304, 2004, pages 1338 - 1440 |
SHIHABUDDIN L S ET AL.: "Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus", THE J NEUROSCIENCE, vol. 20, 2000, pages 8727 - 8735 |
TAKEYAMA K; OHTO H: "PBSC mobilization", TRANSFUS APHER SCI, vol. 31, 2004, pages 233 - 243 |
TERAMOTO T ET AL.: "EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia", THE J CLINICAL INVESTIGATION, vol. 111, 2003, pages 1125 - 1132 |
VIKASH CHANDRA ET AL.: "Islet-Like Cell Aggregates Generated from Human Adipose Tissue Derived Stem Cells Ameliorate Experimental Diabetes in Mice", PLOS ONE, vol. 6, no. 6, 7 June 2011 (2011-06-07), pages E20615 |
WALTER D H ET AL.: "Statin therapy accelerates reendothelialization: A novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells", CIRCULATION, vol. 105, 2002, pages 3017 - 3024 |
WEI CAO ET AL.: "Leukemia Inhibitory Factor Inhibits T Helper 17 Cell Differentiation and Confers Treatment Effects of Neural Progenitor Cell Therapy in Autoimmune Disease", IMMUNITY, vol. 35, no. 2, 11 August 2011 (2011-08-11), pages 273 - 284 |
WEISSMAN I L: "Translating stem and progenitor cell biology to the clinic: Barriers and opportunities", SCIENCE, vol. 287, 2000, pages 1442 - 1446 |
WEISSMAN IL: "Translating stem and progenitor cell bilolgy to the clinic: Barriers and opportunities", SCIENCE, vol. 287, 2000, pages 1442 - 1446 |
WRIGHT; LORIMORE, CELL TISSUE KINET, vol. 20, 1987, pages 191 - 203 |
XUE, GUANGBO ET AL.: "Prospect stable cholrine dioxide.", SHANGHAI LABORATORY ANIMAL SCIENCE, vol. 14, no. 3, 4, 31 December 1994 (1994-12-31), pages 133 - 134, XP008179563 * |
YAOJIONG WU ET AL.: "Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis", STEM CELLS, vol. 25, no. 10, October 2007 (2007-10-01), pages 2648 - 2659 |
YONG ZHAO; ZHAOSHUN JIANG; TINGBAO ZHAO; MINGLIANG YE; CHENGJIN HU; ZHAOHUI YIN ET AL.: "Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells.", BMC MEDICINE, vol. 10, 10 January 2012 (2012-01-10), pages 3 |
YU, J ET AL.: "Intravenous Administration of Bone Marrow Mesenchymal Stem Cells Benefits Experimental Autoimmune Myasthenia Gravis Mice Through an ImmunomodulatoryAction", SCANDINAVIAN JOURNAL OF IMMUNOLOGY, vol. 72, no. 3, 2010, pages 242 |
ZHAO Y ET AL.: "A human peripheral blood monocyte-derived subset acts as pleuripotent stem cells", PROC NATL ACAD SCI USA, vol. 100, 2003, pages 2426 - 31 |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10143710B2 (en) | 2010-08-04 | 2018-12-04 | StemBios Technologies, Inc. | Somatic stem cells |
US11492592B2 (en) | 2012-12-06 | 2022-11-08 | StemBios Technologies, Inc. | Lgr5+ somatic stem cells |
JP2014121322A (ja) * | 2012-12-21 | 2014-07-03 | Stembios Technologies Inc | 幹細胞による行為効果を評価する方法 |
Also Published As
Publication number | Publication date |
---|---|
EP2926819A1 (en) | 2015-10-07 |
EP2926819A4 (en) | 2016-06-29 |
US20150335678A1 (en) | 2015-11-26 |
CN103040860A (zh) | 2013-04-17 |
JP2016500114A (ja) | 2016-01-07 |
CN103040860B (zh) | 2018-08-14 |
EP2926819B1 (en) | 2018-02-28 |
JP6141997B2 (ja) | 2017-06-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2014082514A1 (zh) | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 | |
Xie et al. | What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment? | |
JP5649786B2 (ja) | ヒト胚性幹細胞およびそれらの誘導体を含む組成物、使用方法、ならびに調製方法 | |
JP2019513136A (ja) | 羊水による治療の組成物及び方法 | |
US11351190B2 (en) | Composition for treating tissue lesions | |
JP2023521064A (ja) | 疼痛調節因子を含む幹細胞由来エクソソーム及びその用途 | |
JP5602364B2 (ja) | 幹細胞及び/又は前駆細胞の賦活剤 | |
Yan et al. | A novel conductive polypyrrole‐chitosan hydrogel containing human endometrial mesenchymal stem cell‐derived exosomes facilitated sustained release for cardiac repair | |
US20230172994A1 (en) | Methods of promoting vasculogenesis | |
CN111566204B (zh) | 培养细胞的制造方法、脊髓损伤疾病的治疗剂的制造方法 | |
US20210386791A1 (en) | Methods of cellular reprogramming | |
TWI468184B (zh) | 藥學組成物及使用其之藥用化妝品 | |
JP5251873B2 (ja) | 脂肪組織細胞画分の照射後組織再生への使用 | |
Zinovyev et al. | Experience of stem cell use in treatment of skin burns | |
TWI382090B (zh) | 幹細胞及/或前驅細胞的賦活劑 | |
Wawryk-Gawda et al. | Application of mesenchymal stem cells in paediatrics | |
Li et al. | MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of spinal cord injury by alleviating neuroinflammation | |
JP2023089978A (ja) | デキストランまたはポロキサマーを含む、関節疾患または結合組織疾患の治療用組成物 | |
CN116059246A (zh) | MSCs和AMP在制备干预特应性皮炎产品中的应用和制剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13858112 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2015544328 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 14647698 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2013858112 Country of ref document: EP |