CN103948578A - Pyruvic acid medicine composition for stabilizing osmotic pressure, and detoxification function thereof in healthy people and patients with lung diseases - Google Patents
Pyruvic acid medicine composition for stabilizing osmotic pressure, and detoxification function thereof in healthy people and patients with lung diseases Download PDFInfo
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Abstract
The invention provides a method for detoxifying the lungs of healthy people and patients with lung diseases by virtue of a pyruvic acid medicine composition. Toxins accumulated by mammalian cells due to smoking and air pollution can be eliminated by contacting with an effective dose of pyruvic medicine composition; lung diseases comprise chronic obstructive pulmonary disease (COPD); the pyruvic acid medicine composition is selected from pyruvic acid, pyruvic acid pharmaceutical salt, pyruvic acid pharmaceutical precursors or the mixtures thereof. The method further comprises the step of using other medicine compositions while using the pyruvic medicine composition. The method provided by the invention has the following advantages: 1, the pyruvic acid medicine composition is higher in targeting because of directly acting on the focus part of the lung, and does not participate in the metabolism of the whole body; 2, the pyruvic acid medicine composition is lower in toxic and side effects, higher in safety and stable in medicine; 3, pyruvic acid is a natural substance in cells, has the effects of enhancing the functions of a cell movement system, promoting lung detoxification and promoting breathing, as well as is more comprehensive in curative effect compared with antibiotic medicines or steroid medicines and the like, and better in effect.
Description
Technical field
The invention provides utilize steady seepage press acetone acid ingredients get rid of pulmonary's toxin, improve pulmonary function and alleviate cough symptom method.The toxin causing because of smoking and air pollution finally can cause the pulmonary disease such as chronic obstructive pulmonary disease in the accumulation of pulmonary.The invention belongs to field of medical technology.The present invention also comprises preparation and uses the method for the acetone acid ingredients with medical effect.
Background technology
Air pollution or smoking meeting cause intracellular toxin accumulation.These toxin, such as benzene can be accumulated in bronchial wall or pneumonocyte.Most of COPD Patients are also smokers simultaneously.Chronic obstructive pulmonary disease is a class because smoking and air pollution cause pulmonary's toxin accumulation, and breathing is obstructed, decline in pulmonary function, the frequent and pulmonary disease that produces of cough.Chronic obstructive pulmonary disease mainly comprises chronic bronchitis and emphysema.Chronic bronchitis is trachea, and the chronic nonspecific inflammation of bronchial mucosa and surrounding tissue thereof causes air-flow to enter pulmonary and has some setbacks.Emphysema are that the alveolar tissue of terminal bronchiole far-end causes persistency expansion because residual volume increases, and then cause alveolar septum to destroy, and volume increases, so that affects the phenomenon of eupnea.The damage of lung tissue that chronic obstructive pulmonary disease causes is irreversible, but symptom and progression of disease can be by using such as antibiotic, expectorant, or the medicine such as bronchodilator is controlled.But these medicines can not be eliminated pneumonia.COPD has a series of complication, comprises respiratory tract infection, hypertension, and heart disease is such as heart attack or heart failure, pulmonary carcinoma and depression.At last decade, due to pollution, smoking and chronic pulmonary infection, the sickness rate of COPD has remarkable rising.
Various physiological processes can cause the generation of active oxygen, such as cell aerobic metabolism, drug metabolism, toxin and exogenous material, ultraviolet, X-radiation and phagocyte (such as leukocyte) are resisted the process of exogenous material such as toxin by respiratory burst.These toxin comprise anaphylactogen, the chemicals in medicated cigarette, air pollutants, dust particle, fine particle and toxic compounds etc.The harm of the size of these materials below 10 μ m time is particularly serious, because it can be deep into pulmonary.A lot of research shows, when the particle diameter of these microgranules approaches 2.5 μ m or more hour, these toxin can penetrate into gas exchange region and may have influence on other organs through pulmonary.In most of organism respiratory, can produce hydrogen peroxide for instance, in the situation that especially cell is under pressure.
These active oxygens can damaging cells.The generation that studies have shown that active oxygen can cause much skin, and the disease of tissue and organ, such as atherosclerosis, arthritis, cytotoxicity, scytitis, skin photoage, wrinkle of skin, actinic keratosis, tumor forms, cancer, hypertension, parkinson, pulmonary disease and heart disease etc.
In the time that cell oxide damages, antioxidant can play the effect of going back archeocyte.Antioxidant can stop the injury of active oxygen to cell and tissue.Such as acetone acid group and other 2-ketoacids have in quick and chemical dose ground and the ability of hydrogen peroxide, thereby Cell protection is not dissolved.
Acetone acid is the weak organic acid of a kind of acidity, has carbonyl and carboxyl Liang Ge functional group in molecule simultaneously, has carboxylic acid, the character of ketone and 2-ketoacid.Acetone acid is the three carbon keto acids that produce in body, and it is the end product of glycolytic pathway, or enters in mitochondrion and be oxidized to S-acetyl-coenzyme-A, enters tricarboxylic acid cycle, completes the aerobic oxidation energy supply process of glucose; Or in the time that oxygen is not enough, in cytoplasm, be reduced into lactic acid.Acetone acid also can be realized the mutual conversion between sugar, fat and aminoacid in body by S-acetyl-coenzyme-A and tricarboxylic acid cycle.Therefore, acetone acid plays important pivotal role in the metabolism contact of three major nutrient.
Acetone acid and pyruvate are antioxidants.In macrophage and other cell strains, Sodium Pyruvate can regulate generation and the level of inflammatory mediator such as oxygen-derived free radicals, can improve nitric oxide production synthetic simultaneously.Sodium Pyruvate can also reduce the excessively synthetic of superoxide anion.Sodium Pyruvate can improve the level of a kind of main antioxidant glutathion in cell.Acetone acid can enter cell by transmembrane transport system, and can penetrate blood brain barrier.All cells all have the transmembrane transport system that can concentrate the acetone acid that exceedes plasma concentration in cell.In and oxygen-derived free radicals after, excessive Sodium Pyruvate can enter bronchus and pneumonocyte.
Prior art (PriorArt)
U.S. the patent No. 5210098 (Nath) stops and prophylaxis of acute nephritis and acute renal failure with acetone acid;
U.S. the patent No. 5296370 (Martinetal.) stops and reduces the damage of mammalian cell with acetone acid, promotes the regeneration of damaging cells;
U.S. the patent No. 5256697 (Milleretal.) increases insulin resistance with the medicinal precursor of oral acetone acid, lowers long-term insulin level, and reducing fat increases;
U.S. the patent No. 3920835,3984556and3988470 (VanScottetal.) treats acne with the compound including acetone acid, dandruff and palm keratosis;
U.S. the patent No. 4105783,4197316 (Yuetal.) is treated xerosis cutis with the compound including acetone acid;
U.S. the patent No. 4234599 (VanScottetal.) is treated actinic keratosis and non-actinic keratosis with the compound including acetone acid;
U.S. the patent No. 4294852 (Wildnaueretal.) is treated dermatosis with the compound including acetone acid;
Sodium Pyruvate can reduce the gastric mucosal erosion being caused by aspirin in Cavia porcellus and rat, and ulcer and hemorrhage is conciliate hot property (Puschmann, Arzneimittelforschung, 1983) but do not reduce acetysalicylic analgesia;
But acetone acid can increase and time myocardium muscular strength.Press down the reversible symptom (Mentzeretal., Ann.Surg., 1989) that cardiac muscle is the lasting several hours cardiac insufficiencys to a couple of days after of short duration coronary occlusion;
Acetone acid has the effect of stable left ventricular pressure and running parameter, and reduces the coverage of myocardial infarction.Acetone acid can also help to recover spontaneous heart beating and normal heart rate and pressure (Bungeretal., J.Mol.Cell.Cardiol., 1986 after myocardial infarction; Mochizukietal., J.Physiol. (Paris), 1980; Regitzetal., Cardiovasc, Res., 1981; Giannellietal., Ann.Thorac.Surg., 1976);
Sodium Pyruvate can also suppress hydrogen peroxide and generate, and protection system is receptor 1 activity oxygen intermediate injury (Martin, thesis for the doctorate, 1987-1989) not.
Thereby above-mentioned description of the Prior Art suppress active oxygen with acetone acid and generate the method for a series of diseases for the treatment of, get rid of the especially method of chronic obstructive pulmonary disease portion toxin but do not mention with acetone acid.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art part, the method for utilizing the acetone acid ingredients of optimizing to get rid of pulmonary's toxin in Healthy People and COPD Patients is provided.This acetone acid ingredients produces curative effect by contact mammalian cell, and the acetone acid ingredients of wherein optimizing can be selected from acetone acid, acetone acid pharmaceutical salts, medicinal precursor or its mixture.
This invention comprises treats smoker and COPD Patients with the ingredients of acetone acid and pharmaceutical carrier.Wherein acetone acid is by promoting lung cells movement system function and decompose or discharging the pulmonary's toxin that causes decline in pulmonary function.Wherein pharmaceutical carrier can be selected from one or more in osmotic pressure regulator, acidity-basicity regulator, nutritional supplement and aromatic.
The method is also included in and uses acetone acid to use other drug simultaneously, such as one or more in antibiotic, antiviral agents, antifungal agent, antineoplastic agent, antihistaminic, protein-based, enzyme, hormones, non-steroidal anti-inflammatory drug, cytokines and steroid.Under ideal situation, acetone acid ingredients is by respiratory tract inhalation.
The present invention is the technology for the treatment of disease in mammal with acetone acid ingredients.Getting rid of pulmonary's toxin with acetone acid ingredients is a new invention.Toxin is such as benzene can reduce pulmonary function, and acetone acid ingredients can increase the function of lung cells movement system, gets rid of toxin and promotes the effect of enzyme system thereby play, and allows smooth breathing alleviate cough symptom.
Chronic obstructive pulmonary disease is mainly to be caused by pulmonary and bronchitis.Being promoted pulmonary function and alleviated cough symptom by eliminating toxin is a new technology.Chronic obstructive pulmonary disease mainly comprises chronic bronchitis and emphysema.Chronic bronchitis is trachea, and the chronic nonspecific inflammation of bronchial mucosa and surrounding tissue thereof causes air-flow to enter pulmonary and has some setbacks.Emphysema are that the alveolar tissue of terminal bronchiole far-end causes persistency expansion because residual volume increases, and then cause alveolar septum to destroy, and volume increases, so that affects the phenomenon of eupnea.
This type of respiratory inflammation derives from the physiological process that is known as respiratory burst.Respiratory burst is that mammal defense cell is such as leukocytic normal physiological reaction.These defense cells generally or quilt injured mammal are discharged a series of active substances at intrusion position after invading.These active substances comprise that protease and active oxygen are such as hydrogen peroxide.The object of respiratory burst is to provide and a series ofly can be used for eliminating external cell by leukocyte, virus, the active substance of granule and toxin.Respiratory burst refers to that leukocyte contacts a series of coordination metabolic responses that occur after suitable stimulus.These metabolic responses are that leukocyte utilizes oxidation reaction to kill the basis of exotic.
Respiratory burst was activated conventionally in one minute of leukocyte thigmic stimulus source.After respiratory burst is activated, leukocytic oxygen expenditure increase exceedes normal 100 times, causes super oxygen compound, the generation of per-compound and hydrogen peroxide etc.Leukocyte comprises lymphocyte herein, phagocyte, macrophage and accessory cell etc.
The stimulus that causes respiratory burst is generally toxin, comprises anaphylactogen, the chemicals in medicated cigarette, air pollutants, dust particle, fine particle and toxic compounds etc., object lesson includes but not limited to benzene, formaldehyde, ammonia, methanol, nicotine, tar, butane, acetone, acetic acid, arsenic, cadmium, carbon monoxide, lead, toluene, cyanide, oxysulfide, nitrogen oxide, fine particle (PM), persistency free radical, radioactive contaminant etc.
Under normal circumstances, after respiratory burst, along with the disappearance of stimulus, leukocyte also can return to normal state.If respiratory burst continues and do not stop, leukocytic lasting metabolic response can cause inflammation.Leukocyte constantly produces reactive compound, and these compounds finally can be attacked, and damages and kill normal histiocyte and other leukocyte, causes inflammation.The perienchyma causing because of the respiratory burst process that leukocyte is lasting, hemocyte and other leukocytic damages and death are the pathologic basis of chronic obstructive pulmonary disease.Utilize osmotic pressure balance acetone acid solution ingredients to alleviate pulmonary inflammatory method by eliminating stimulus and the toxin of these suctions, the invention provides.
The acetone acid ingredients that is used for eliminating toxin is by the mammiferous cell generation effect of contact, especially by contact respiratory tract administration.Acetone acid ingredients can be selected from acetone acid, acetone acid pharmaceutical salts, medicinal precursor or its mixture.Acetone acid ingredients has oxidation resistance, can Cell protection avoids the harm of oxide.Our research shows that acetone acid can eliminate the toxin of pulmonary.Under ideal situation, the concentration range of acetone acid ingredients is at 0.1-10.0mM, and more desirable concentration range is at 0.25-5.0mM, and more desirable concentration range is 0.5-4.0mM.
Acetone acid pharmaceutical salts refers to the pyruvates that can not produce toxic and side effects in mammalian cell.Typical pyruvate is selected from acetone acid lithium, Sodium Pyruvate, Potassium pyruvate., acetone acid magnesium, calcium pyruvate, acetone acid zinc, acetone acid manganese or its mixture.
Acetone acid group exists with number of chemical form, and these chemical specieses are called as precursor, discharges acetone acid group by reacting with mammalian cell.Medicinal precursor, refers to that those must could produce by biochemical reaction in body the compound of drug effect.Enter in body to from compound the delay that produces drug effect and be called medicine incubation period.Have bioactive compound to form a kind of new compound by chemical modification, this noval chemical compound can discharge the former bioactive compound that has by enzyme reaction in vivo.The main purpose of this chemical modification is to improve the physico-chemical property of former compound, comprises absorption, distributes and enzymes metabolism.Medicine also can comprise the non-enzyme regeneration of former compound incubation period.The medicinal precursor of acetone acid is selected from ethyl pyruvate, pyruvoyl glycine, pyruvoyl alanine, pyruvoyl leucine, pyruvoyl valine, pyruvoyl isoleucine, acetylbenzoyl alanine, pyroracemamide, pyruvate or its mixture.
Acetone acid ingredients also comprises pharmaceutical carrier, comprises osmotic pressure regulator and acid-base modifier.Osmotic pressure regulator comprises and is not restricted to one or more in sodium chloride, glucose, sorbitol, glycerol, Polyethylene Glycol, propylene glycol and mannitol.Wherein desirable osmotic pressure regulator is sodium chloride.The optimization mass concentration of sodium chloride is 0.05%-8%, and more optimal mass concentration is 0.2%-5%, and more optimal mass concentration is 0.45%-1.8%.
Acid-base modifier comprises and is not limited to one or more in hydrochloric acid, sodium hydroxide, citric acid, sodium citrate, tartaric acid, sodium tartrate and potassium hydroxide.In addition, pharmaceutical carrier is also selected from and is not restricted to traditional normal saline such as bicarbonate solution, acetic acid ringer's solution, Lactated Ringer'S Solution, phosphate buffered solution, TRIS buffer solution, HEPES buffer solution, standard saline citrate (SSC), Han Keshi balanced salt solution (HBSS), E Ershi balanced salt solution (EBSS) or gey's balanced salt solution (GBSS).The concentration of osmotic pressure regulator should be in physiology tolerance interval.Ideally, the osmotic pressure scope of final solution is 1-2800Osm/L, and more desirable osmotic pressure scope is 154-1800Osm/L, and more desirable osmotic pressure scope is 308-1027Osm/L.Ideally, the acid-base value scope of final solution is pH2.5-11, and more desirable acid-base value scope is pH4.0-10, and more desirable acid-base value scope is pH5.0-9.0.
In addition, ingredients can also comprise nutritional supplement, aromatic and composition thereof.Such as nutritional supplement is selected from one or more in leucine, vitamin D, vitamin E, glutamic acid, folic acid and nicotiamide.
Acetone acid ingredients both can, in the local use of focus, can systematically use at whole body again.Can also systematically use in focus part and whole body simultaneously.
Ideally, acetone acid ingredients carrys out administration by the method sucking.Administration after acetone acid ingredients can first make to nebulize by suitable method, acetone acid ingredients can be liquid or solid form, and the size of drop or solid solid particle can be absorbed smoothly by lung tissue must be small enough to inhalation time.Ideal situation be delivery of particulate between 0.01-10 μ m, more ideal situation be delivery of particulate between 0.1-7 μ m, ideal situation is that delivery of particulate is between 0.5-5 μ m more.
The suction of acetone acid ingredients can be the course for the treatment of one or many suck.Each in typical case suction can continue 1 to 30 minute, more preferably continues in 20 minutes, more preferably continues in 15 minutes.
Administration after the sterile solution of acetone acid ingredients can use nebulizer to make to nebulize in the time for the treatment of, or also can use aerosol apparatus administration.The method inhalation that the form of all right dry powder of ingredients is used dry powder to suck.When with dry powder doses inhalation, a kind of ideal situation be every dose of weight range between 0.0001-10mg, more preferably situation be every dose of weight range between 0.005-5mg, ideal situation is that every dose of weight range is between 0.01-0.275mg more.
Acetone acid ingredients can also use together with other drug.Described medicine can be selected from one or more in antibiotic, antiviral agents, antifungal agent, antineoplastic agent, antihistaminic, protein-based, enzyme, hormones, non-steroidal anti-inflammatory drug, cytokines and steroid.The use amount of medicine should be medical effective dose.Medical treatment effective dose refers to normally used dosage when treating particular condition, depends in treated disease and ingredients other composition, and main purpose is to obtain therapeutic effect.Concrete dosage should determine by the healthcare givers who sees service, and this is not the scope that the present invention is concerned about.These medicines can, before using acetone acid, use simultaneously or afterwards.
Operable antibiotic can be selected from multiple water solublity or non-water-soluble medicine, or their acid or salt.Salt can be organic salt or inorganic salt.Antibiotic can be various slow release or extend releasing pattern.Antibiotic example comprises and is not restricted to bismuth-containing compound, sulfa drugs, nitrofuran, metronidazole, tinidazole, nimorazole, benzoic acid, aminoglycoside, Macrolide, penicillin, polypeptide class, tetracycline, cephalosporin, chloromycetin and clindamycin etc.
The antibiotic consumption using in the present invention depends on concrete antibiotic recommendation consumption or safe level.Ideally, antibiotic consumption is approximately 0.01%-10% weight, and more preferably consumption is 0.1%-5% weight, and more preferably consumption is 1%-3% weight.
Operable antiviral agents can be selected from multiple water solublity or non-water-soluble medicine, or their acid or salt.Salt can be organic salt or inorganic salt.Antiviral agents can be various slow release or extend releasing pattern.The example of antiviral agents comprises and is not restricted to rna synthesis inhibitor, protein synthesis inhibitor, immunostimulant, protease inhibitor, and cytokines.Concrete example comprises and is not restricted to acyclovir, foscarnet sodium, ribavirin, vidarabine, ganciclovir sodium, zidovudine, carbolic acid, amantadine hydrochloride, Alferon N.
The consumption of the antiviral agents using in the present invention depends on recommendation consumption or the safe level of concrete antiviral agents.Ideally, the consumption of antiviral agents is approximately 0.1%-20% weight, and more preferably consumption is 1%-10% weight, and more preferably consumption is 2%-7% weight.
Operable antifungal agent can be selected from multiple water solublity or non-water-soluble medicine, or their acid or salt.Salt can be organic salt or inorganic salt.Antifungal agent can be various slow release or extend releasing pattern.The concrete example of antifungal agent comprises and is not restricted to miconazole, clotrimazole, tioconazole, terconazole (triaconazole), povidone iodine and Butoconazole.Other antifungal agent also comprise lactic acid, sorbic acid.Wherein miconazole and clotrimazole are desirable antifungal agent.
The consumption of the antifungal agent using in the present invention depends on recommendation consumption or the safe level of concrete antifungal agent.Ideally, the consumption of antifungal agent is approximately 0.05%-10% weight, and more preferably consumption is 0.1%-5% weight, and more preferably consumption is 0.2%-4% weight.
Operable antineoplastic agent can be selected from multiple water solublity or non-water-soluble medicine, or their acid or salt.Salt can be organic salt or inorganic salt.Antineoplastic agent can be various slow release or extend releasing pattern.The example of antineoplastic agent comprises and is not restricted to antimetabolite, antibiotic, plant product, hormone and various chemotherapeutics.Nonspecific medicine comprises alkylating agent and N-alkyl-N-nitroso compound.Alkylating agent comprises chlormethine, Ethylenimine, sulphonic acid ester and epoxy.Antimetabolite refers to and disturbs the formation of normal cell metabolite or the compound of utilization, comprise the antagonist of the synthetic metabolite of amino acid antagonists, vitamin and voenzyme antagonist and participation nucleic acid, as glutamine antagonist, antifol, pyrimidine antagonist and purine antagonist.Antibiotic is that the D actinomycin D comprising and associated antibiotic, glutarimide antibiotic, (R)-2-methylene-3-oxocyclopentanecarboxylic acid., Amebacilin, streptonigrin, tenuazonic acid, actinogan, pepsinogen and anthracycline antibiotic are such as amycin by the compound with the energy for growth that suppresses other biological of microorganisms.Plant product comprises colchicine, podophyllotoxin and vinca alkaloids.Hormones comprises the steroid hormone for breast carcinoma and carcinoma of prostate, and for leukemia and lymphadenomatous corticosteroid.Other chemotherapeutant comprises urethanes, hydroxyurea and relevant compound; Thiosemicarbazones and related compound; Phthalyl diphenylamines and related compound; And Triazenes and hydrazine.Antineoplastic agent can be also monoclonal antibody or X ray.
The consumption of the antineoplastic agent using in the present invention depends on recommendation consumption or the safe level of concrete antineoplastic agent.Ideally, the consumption of antineoplastic agent is approximately 1%-50% weight, and more preferably consumption is 10%-30% weight, and more preferably consumption is 20%-25% weight.
The invention provides the method for utilizing the acetone acid ingredients of optimizing to get rid of pulmonary's toxin in Healthy People and COPD Patients.This acetone acid ingredients produces curative effect by contact mammalian cell, and the acetone acid ingredients of wherein optimizing is selected from acetone acid, acetone acid pharmaceutical salts, medicinal precursor or its mixture.This invention comprises treats smoker and COPD Patients with the ingredients of acetone acid and pharmaceutical carrier.Wherein acetone acid is by promoting lung cells movement system function and decompose or discharging the pulmonary's toxin that causes decline in pulmonary function.Wherein pharmaceutical carrier can be selected from one or more in osmotic pressure regulator, acidity-basicity regulator, nutritional supplement and aromatic.The method is also included in and uses acetone acid to use other drug simultaneously, such as one or more in antibiotic, antiviral agents, antifungal agent, antineoplastic agent, antihistaminic, protein-based, enzyme, hormones, non-steroidal anti-inflammatory drug, cytokines and steroid.Under ideal situation, acetone acid ingredients is by respiratory tract inhalation.
The present invention has following advantage:
1, directly act on pulmonary lesions position and have more targeting, do not participate in general metabolism.
2, acetone acid toxic and side effects is less, and safety is higher, and medicine is stable.
3, acetone acid is intracellular natural materials, has the cell traffic of enhancement systemic-function, promotes pulmonary's toxin expelling, is beneficial to the effect of breathing, and its curative effect is more comprehensive than antibiotic or steroid medicine etc., and effect is better.
Brief description of the drawings
Fig. 1: after COPD Patients suction normal saline or 0.5mM Sodium Pyruvate, the percentage ratio of FEV1 changes;
Fig. 2: after COPD Patients suction normal saline or 1.5mM Sodium Pyruvate, the percentage ratio of FEV1 changes;
Fig. 3: after COPD Patients suction normal saline or 2.5mM Sodium Pyruvate, the percentage ratio of FEV1 changes;
Fig. 4: after COPD Patients suction normal saline or 5.0mM Sodium Pyruvate, the percentage ratio of FEV1 changes;
Fig. 5: after COPD Patients suction normal saline or 0.5mM Sodium Pyruvate, the percentage ratio of PEF changes;
Fig. 6: after COPD Patients suction normal saline or 1.5mM Sodium Pyruvate, the percentage ratio of PEF changes;
Fig. 7: after COPD Patients suction normal saline or 2.5mM Sodium Pyruvate, the percentage ratio of PEF changes;
Fig. 8: after COPD Patients suction normal saline or 5.0mM Sodium Pyruvate, the percentage ratio of PEF changes;
Detailed description of the invention
Embodiment 1: carry out toxin study in tissue culture
We utilize MatTekEpiDerm to test to investigate acetone acid stabilized cell, eliminate the ability of toxin and increase cell survival.EpiDerm cell and pneumonocyte are almost just the same.We process EpiDerm tissue samples with the Sodium Pyruvate of various concentration.In Sodium Pyruvate solution, after balance after an hour, EpiDerm cell, at 37 DEG C, is cultivated with culture fluid in 5%CO2 calorstat.Replace old culture fluid with fresh medium, and in culture fluid, add tested material at this moment.The time of tested material and cells contacting is respectively 1 hour, 4 hours and 20 hours.Wherein main tested material is smoke from cigarette.Smoke from cigarette is extracted after condensing on filter paper and adds in cell culture fluid.Undressed sample is used to do negative control.After tested material is processed, cell culture fluid is used to check cell survival rate and cellular stress (by checking the level of cytokines IL-1 and IL-8).Repeating this tests once.
The Sodium Pyruvate of 5 milliliters of 0.5mM comprises 0.28 milligram of Sodium Pyruvate; The Sodium Pyruvate of 5 milliliters of 10mM comprises 5.6 milligrams of Sodium Pyruvates; The Sodium Pyruvate of 5 milliliters of 20mM comprises 11.2 milligrams of Sodium Pyruvates; The Sodium Pyruvate of 5 milliliters of 40mM comprises 22.4 milligrams of Sodium Pyruvates.
Result:
It is main test data that the level of IL-1 and IL-8 changes.These two kinds of interleukin all have the effect that promotes inflammatory reaction.In medicated cigarette, toxin increases IL-1 and IL-8 horizontal exceeding 200%.Use separately Sodium Pyruvate solution to fail to cause the rising of IL-1 and IL-8.When but in Sodium Pyruvate solution and medicated cigarette, toxin exists simultaneously, IL-8 is significantly reduced by least 200%, IL-1 and is significantly reduced by least 200%.This experimental results show that Sodium Pyruvate has the effect that promotes pneumonocyte toxin expelling.Compare with undressed cell, in medicated cigarette, toxin can reduce cell survival rate and reaches 72%, once after adding acetone acid, cell survival rate increases by 15% on the contrary.This digital proof Sodium Pyruvate can improve cell survival rate.
Embodiment 2: the present embodiment is Sodium Pyruvate clinical research data.
In this clinical research, use health volunteer and COPD Patients to be once all or be smoker now, and cough every day and suffer air pollution.Their symptom comprises cough, rapid breathing and decline in pulmonary function.Each patient has the cough diary that is recorded in Sodium Pyruvate treatment front and back.
Object:
1 detects the safety in health volunteer and slight patients with chronic obstructive pulmonary diseases of Sodium Pyruvate inhalant and the effectiveness for the treatment of;
Whether 2 measure Sodium Pyruvate inhalant can effectively reduce these experimenters' cough symptom.
Method:
We have used the Sodium Pyruvate solution of four kinds of concentration; 0.5mM, 1.5mM, 2.5mM and 5.0mM.80 experimenters are by 20 normal healthy controls individualities, and 60 individual compositions of slight chronic obstructive pulmonary disease.Normal healthy controls individuality is divided into 4 groups, every group of 5 experimenters; Accept respectively the Sodium Pyruvate of four kinds of concentration for every group.Slight chronic obstructive pulmonary disease individuality is divided into 4 groups, every group of 15 experimenters; Accept respectively the Sodium Pyruvate of four kinds of concentration for every group.Every experimenter sucks the Sodium Pyruvate of the variable concentrations of single dose 5.0mL.Sodium Pyruvate, by atomised form administration, approximately sucks 15-20 minute at every turn.
Test:
Started to carry out breath test the same day in administration.First day, all experimenters comprise that health volunteer and slight patients with chronic obstructive pulmonary diseases only suck normal saline.Conventionally the sensitive indicator that is used as clinically chronic obstructive pulmonary disease by PEF and two kinds of indexs of FEV1, PEF is forced expiration peak flow, FEV1 be one second FEC.Before normal saline sucks, test these two kinds of indexs, and suck latter 15 minutes at normal saline, 30 minutes, 1 hour, when 2 hours and 4 hours, again test.These test datas are base-line data.Second day, same experimenter accepted the treatment of the Sodium Pyruvate solution of variable concentrations.Then carry out in the same way the test of PEF and FEV1.These test datas are experimental data.
Result:
The percentage ratio delta data of 1.FEV1 is in table 1, and 0.5mM Sodium Pyruvate concentration is shown in Fig. 1, and 1.5mM Sodium Pyruvate concentration is shown in Fig. 2, and 2.5mM Sodium Pyruvate concentration is shown in Fig. 3, and 5.0mM Sodium Pyruvate concentration is shown in Fig. 4;
The percentage ratio delta data of 2.PEF is in table 2, and 0.5mM Sodium Pyruvate concentration is shown in Fig. 5, and 1.5mM Sodium Pyruvate concentration is shown in Fig. 6, and 2.5mM Sodium Pyruvate concentration is shown in Fig. 7, and 5.0mM Sodium Pyruvate concentration is shown in Fig. 8.
Table 1: the percentage ratio that after normal saline contrast or Sodium Pyruvate suck, FEV1 measures
Table 2: the percentage ratio that after normal saline contrast or Sodium Pyruvate suck, PEF measures
Conclusion:
A. safety: all experimenters all show well tolerable to the suction of Sodium Pyruvate.In any experimenter, all do not observe because Sodium Pyruvate sucks the serious adverse events and the physiological change that need to stop research.
B. effectiveness: prove that according to the variation of measuring FEV1 and PEF Sodium Pyruvate can help patients with chronic obstructive pulmonary diseases to breathe more smooth and easy.In addition, clinical data shows that the Sodium Pyruvate solution of concentration between 0.5-1.5mM is preventing and treating slight chronic obstructive pulmonary disease have significant curative effect by atomization inhalation.Meanwhile, experimenter's cough diary shows, sucks Sodium Pyruvate and can also reduce every day and cough number of times and reach 45%.Patient obviously experiences alleviating of cough symptom after representing to suck Sodium Pyruvate, and sucking normal saline does not have this variation.The result of measuring shows, normal subjects sucks normal saline or Sodium Pyruvate solution FEV1 and PEF index to be and to see and increase or reduce, but the number of times of cough has reduced by 50%, only has COPD patient's FEV1 or the increase of PEF value, especially for smoker, all the more so.
Embodiment 3: Sodium Pyruvate inhalant stability study
Prescription is in table 3
Table 3: Sodium Pyruvate inhalant prescription
Sodium Pyruvate inhalant prepared by prescription 1-12 is put into 40 DEG C of stability test casees and is carried out 6 months accelerated tests, the results are shown in Table 4.Same Sodium Pyruvate solution at room temperature can keep still there is at least 97% residue after 3 years.
Table 4: stability data (percentage ratio is Sodium Pyruvate surplus in solution)
Conclusion:
Can prove that from table 4 Sodium Pyruvate is that chemical stability between 0.5mM-6.0mM is good in concentration.
Embodiment 4: preparation is containing the inhalant of 0.5mM Sodium Pyruvate
Prescription:
Technique: by the acetone acid of recipe quantity, sodium chloride is dissolved in appropriate purified water, the osmotic pressure of regulator solution, to 308-1027Osm/L, regulates pH to 5-9, uses BFS technology to prepare the Sodium Pyruvate inhalant of single dose 0.5mM.
There is good curative effect by clinical research this product to treating slight chronic obstructive pulmonary disease.
Embodiment 5: the Sodium Pyruvate inhalant (1000) of preparation 1.5mM
Prescription:
Technique: the Sodium Pyruvate of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the Sodium Pyruvate inhalant of 1.5mM.
There is good curative effect by clinical research this product to treating slight chronic obstructive pulmonary disease.
Embodiment 6: the Sodium Pyruvate inhalant (1000) of preparation 2.5mM
Prescription:
Technique: the Sodium Pyruvate of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the Sodium Pyruvate inhalant of 2.5mM.
There is certain curative effect by clinical research this product to treating slight chronic obstructive pulmonary disease, be more used for the treatment of severe chronic obstructive pulmonary disease.
Embodiment 7: the Sodium Pyruvate inhalant (1000) of preparation 5.0mM
Prescription:
Technique: the Sodium Pyruvate of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the Sodium Pyruvate inhalant of 5.0mM.
By clinical research this product, treatment severe chronic obstructive pulmonary disease is had to good curative effect.
Embodiment 8: the Sodium Pyruvate inhalant (1000) of preparation 6.0mM
Prescription:
Technique: the Sodium Pyruvate of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the Sodium Pyruvate inhalant of 6.0mMol.
By clinical research this product, treatment severe chronic obstructive pulmonary disease is had to good curative effect.
The inhalant relating in above-described embodiment uses 5ml liquid at every turn, and liquid is poured in nebulizer and produced water smoke, by the general breathing of pulmonary's power, water smoke is sucked to pulmonary, uses 15 minutes at every turn.
Embodiment 9: preparation is containing the inhalant (this liquid of lactated Ringer's) of 0.5mM Sodium Pyruvate
Prescription:
Technique: the acetone acid of recipe quantity is dissolved in this liquid of appropriate lactated Ringer's, and the osmotic pressure of regulator solution, to 273-1027Osm/L, regulates pH to 5-9, adopts aseptic technique to prepare the Sodium Pyruvate spray of single dose containing 0.5mM.
Embodiment 10: preparation is containing the inhalant (HBSS solution) of 1.5mM Sodium Pyruvate
Prescription:
Technique: the acetone acid of recipe quantity is dissolved in appropriate HBSS solution, and the osmotic pressure to 275 (± 50Osm/L) of regulator solution, regulates pH to 7.1-7.5, and this solution can use patient by aerosol apparatus.
Embodiment 11: preparation is containing the Foradil Aerolizer formoterol fumarate of Sodium Pyruvate
Prescription:
Technique: by the Sodium Pyruvate of recipe quantity, glucose, after leucine mix homogeneously, be dissolved in appropriate water, and with osmotic pressure regulator regulate osmotic pressure to 308-1027Osm/L, regulate pH to 5-9, filtration sterilization, spray be dried after, pack in dust cloud ejector, single delivery dosage is 0.275mg.
Embodiment 12: the metered dose inhaler that preparation contains Potassium pyruvate.
Prescription:
Technique: by the Potassium pyruvate. of recipe quantity, after sorbitol and nicotiamide mix homogeneously, be dissolved in appropriate sterilized water, and with osmotic pressure regulator regulate osmotic pressure to 308-1027Osm/L, regulate pH to 5-9, after filtration sterilization, pack in metered-dose inhaler, the single delivery dosage of Potassium pyruvate. is 0.825mg.
The preparation (1000) of the pyruvoyl glycine inhalant of embodiment 13:0.1mM
Prescription:
Technique: the pyruvoyl glycine of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the pyruvoyl glycine inhalant of 0.1mM, and its osmotic pressure is controlled at 145 ± 50Osm/L, and pH value is 5-9.
By clinical research this product, treatment severe chronic obstructive pulmonary disease is had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl glycine is the precursor substance of Sodium Pyruvate, have and the identical pharmacological action of acetone acid, can use with Sodium Pyruvate simultaneously, or use before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl glycine of embodiment 14:0.1mM and antibiotic (azithromycin) compound recipe inhalant
Prescription:
Technique: pyruvoyl glycine, sodium chloride and the azithromycin of recipe quantity are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained pyruvoyl glycine and the azithromycin compound recipe inhalant of 0.1mM, and its osmotic pressure is controlled at 485 ± 50Osm/L, and pH value is 5-9.
By clinical research this product, treatment chronic obstructive pulmonary disease and the infection of concurrent antibacterial are had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl glycine is the precursor substance of Sodium Pyruvate, there is the identical pharmacological action with acetone acid, and azithromycin stable in properties, therefore this product can be used with Sodium Pyruvate simultaneously, or uses before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl alanine inhalant of embodiment 15:0.5mM
Prescription:
Technique: the pyruvoyl alanine of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the pyruvoyl alanine inhalant of 0.5mMol, and its osmotic pressure is controlled at 845 ± 50Osm/L, and pH value is 5-9.
By clinical research this product, treatment chronic obstructive pulmonary disease is had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl alanine is the precursor substance of Sodium Pyruvate, have and the identical pharmacological action of acetone acid, can use with Sodium Pyruvate simultaneously, or use before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl alanine of embodiment 16:0.5mM and antiviral agents (Moroxydine) compound recipe inhalant
Prescription:
Technique: pyruvoyl glycine, sodium chloride and the Moroxydine of recipe quantity are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained pyruvoyl glycine and the Moroxydine compound recipe inhalant of 0.5mM, and its osmotic pressure is controlled at 985 ± 50Osm/L, and pH value is 5-9.
By clinical research this product, treatment chronic obstructive pulmonary disease and concurrent viral infection are had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl glycine is the precursor substance of Sodium Pyruvate, there is the identical pharmacological action with acetone acid, and Moroxydine stable in properties, therefore this product can be used with Sodium Pyruvate simultaneously, or uses before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl leucine inhalant of embodiment 17:2
Prescription:
Technique: the pyruvoyl leucine of recipe quantity and sodium chloride are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the pyruvoyl alanine inhalant of 2mMol, and its osmotic pressure is controlled at 1344 ± 50Osm/L, and adjusting pH value is 5-9.
By clinical research this product, treatment chronic obstructive pulmonary disease is had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl leucine is the precursor substance of Sodium Pyruvate, have and the identical pharmacological action of acetone acid, can use with Sodium Pyruvate simultaneously, or use before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl leucine of embodiment 18:2mM and antifungal agent (terbinafine) compound recipe inhalant
Prescription:
Technique: pyruvoyl glycine, sodium chloride and the terbinafine of recipe quantity are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained pyruvoyl glycine and the terbinafine compound recipe inhalant of 2mM, and its osmotic pressure is controlled at 2798 ± 50Osm/L, and regulating pH value by acid-base modifier is 8-11.
By clinical research this product, treatment chronic obstructive pulmonary disease and Complicated With Mycotic Infection are had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl glycine is the precursor substance of Sodium Pyruvate, there is the identical pharmacological action with acetone acid, and terbinafine stable in properties, therefore this product can be used with Sodium Pyruvate simultaneously, or uses before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl valine inhalant of embodiment 19:4mM
Prescription:
Technique: pyruvoyl valine, glucose and the vitamin D of recipe quantity are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained the pyruvoyl valine inhalant of 4mM, and its osmotic pressure is controlled at 988 ± 50Osm/L, taking acid-base modifier pH value as 8-10.
By clinical research this product, treatment chronic obstructive pulmonary disease is had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl valine is the precursor substance of Sodium Pyruvate, have and the identical pharmacological action of acetone acid, can use with Sodium Pyruvate simultaneously, or use before acetone acid or afterwards.
The preparation (1000) of the pyruvoyl valine of embodiment 20:8mM and antineoplastic agent (paclitaxel) compound recipe inhalant
Prescription
Technique: pyruvoyl valine, sorbitol and the paclitaxel of recipe quantity are added respectively and add again 5% surplus purified water to stir after stirring in 95% surplus purified water.After aseptic filtration, carry out sterile filling, subpackage had both obtained pyruvoyl valine and the paclitaxel compound recipe inhalant of 8mM, and its osmotic pressure is controlled at 1021 ± 50Osm/L, and regulating pH value by acid-base modifier is 8-10.
By clinical research this product, treatment chronic obstructive pulmonary disease and concurrent tumor (especially benign tumor) are had to good curative effect, treatment according to the order of severity of disease, according to respiratory time difference, its dosage is between 0.001～10mg, by changing atomization frequency, droplet is controlled between 0.01～10 μ m, pyruvoyl valine is the precursor substance of Sodium Pyruvate, there is the identical pharmacological action with acetone acid, and paclitaxel stable in properties, therefore this product can be used with Sodium Pyruvate simultaneously, or uses before acetone acid or afterwards.
Embodiment 21
The medicinal front physical ability of acetone acid increases cell survival rate
The object of this experiment is to weigh the medicinal precursor of acetone acid to increasing the effect of cell survival rate.Density with 1x105 cells/ml in 6 porocyte culture plates is inoculated fibroblast.Cultivate after 24 hours and add hydrogen peroxide (H2O2) solution, make hydrogen peroxide ultimate density at 0.01mM between 0.03mM.Hydrogen peroxide can cause cellular oxidation stress.Cell survival rate is to weigh by test cell membrane permeability.
As experimental group, in the cell of crossing in above hydrogen peroxide treatment, add pyruvoyl leucine, make its concentration between 0.1-50mM.In the time that pyruvoyl leucine concentration is between 2-20mM, significantly (P<0.05) and effectively increase cell survival rate and reach 10-30% of pyruvoyl leucine.This experimental results show that the medicinal precursor of acetone acid can improve cell survival rate.
Claims (29)
1. acetone acid ingredients comprises the purposes of chronic obstructive pulmonary disease (COPD) patient pulmonary toxin medicine for the preparation of removing Healthy People and lung disease, the acetone acid ingredients using produces therapeutical effect by contact human body, wherein pneumonopathy comprises chronic obstructive pulmonary disease (COPD), a class because smoking and air pollution cause pulmonary's toxin accumulation, breathing is obstructed, decline in pulmonary function, frequent and the pulmonary disease that produces of cough, chronic obstructive pulmonary disease mainly comprises chronic bronchitis and emphysema, chronic bronchitis is trachea, the chronic nonspecific inflammation of bronchial mucosa and surrounding tissue thereof, causing air-flow to enter pulmonary has some setbacks, emphysema are that the alveolar tissue of terminal bronchiole far-end causes persistency expansion because residual volume increases, and then cause alveolar septum to destroy, volume increases, so that affect the phenomenon of eupnea, lung tissue's damage that chronic obstructive pulmonary disease causes is irreversible, but symptom and progression of disease can be controlled by toxin expelling.
2. there is the compositions of purposes as claimed in claim 1, it is characterized in that the acetone acid ingredients in described compositions is selected from acetone acid, acetone acid pharmaceutical salts, medicinal precursor or its mixture.
3. compositions according to claim 2, is characterized in that described acetone acid pharmaceutical salts is selected from Sodium Pyruvate, Potassium pyruvate., acetone acid lithium, acetone acid magnesium, calcium pyruvate, acetone acid zinc, acetone acid manganese or its mixture.
4. compositions according to claim 2, is characterized in that the described medicinal precursor of acetone acid is selected from acetone acid second fat, pyruvoyl glycine, pyruvoyl alanine, pyruvoyl leucine, pyruvoyl valine, pyruvoyl isoleucine, acetylbenzoyl alanine, pyroracemamide, pyruvate or its mixture.
5. compositions according to claim 2, is characterized in that, the molar concentration of described acetone acid, acetone acid pharmaceutical salts or medicinal precursor is 0.1 ~ 10 mM.
6. compositions according to claim 5, is characterized in that, the molar concentration of described acetone acid, acetone acid pharmaceutical salts or medicinal precursor is 0.15 ~ 5 mM.
7. compositions according to claim 6, is characterized in that, the molar concentration of described acetone acid, acetone acid pharmaceutical salts or medicinal precursor is 0.5 ~ 4.0 mM.
8. compositions according to claim 2, it is characterized in that, in described compositions, also comprise pharmaceutical carrier or medical accessory drugs and purified water, wherein pharmaceutical carrier or medical accessory drugs can be osmotic pressure regulators, acid-base modifier, one or more in nutritional supplement and aromatic.
9. compositions according to claim 8, is characterized in that, described osmotic pressure regulator is one or more in sodium chloride, glucose, sorbitol, glycerol, Polyethylene Glycol, propylene glycol and mannitol.
10. compositions according to claim 9, is characterized in that, described osmotic pressure regulator is sodium chloride, and the mass body volume concentrations of sodium chloride is 0.05% ~ 8%.
11. according to the compositions described in claim 10, it is characterized in that, described osmotic pressure regulator is sodium chloride, and the mass body volume concentrations of sodium chloride is 0.2 ~ 5%.
12. compositionss according to claim 11, is characterized in that, described osmotic pressure regulator is sodium chloride, and the mass body volume concentrations of sodium chloride is 0.45 ~ 1.8%.
13. compositionss according to claim 8, is characterized in that, described acid-base modifier is selected from one or more in hydrochloric acid, sodium hydroxide, citric acid, sodium citrate, tartaric acid, sodium tartrate and potassium hydroxide.
14. compositionss according to claim 8, is characterized in that, described nutritional supplement is selected from one or more in leucine, vitamin D, vitamin E, glutamic acid, folic acid and nicotiamide.
15. compositionss according to claim 8, wherein said pharmaceutical carrier is selected from but is not limited to bicarbonate solution, acetic acid ringer's solution, Lactated Ringer'S Solution, phosphate buffered solution, TRIS buffer solution, HEPES buffer solution, standard saline citrate, Han Keshi balanced salt solution, E Ershi balanced salt solution or gey's balanced salt solution.
16. compositionss according to claim 2, is characterized in that, described pharmaceutical composition is by polar liquid as carrier administration, and the osmotic pressure of described carrier is 1 ~ 2800 Osm/L, and acid-base value is pH 2.5 ~ 11.
17. compositionss according to claim 16, is characterized in that, the more optimal osmotic pressure of described carrier is 154 ~ 1800 Osm/L, and acid-base value is pH 4.0 ~ 10.
18. compositionss according to claim 17, is characterized in that, the more optimal osmotic pressure of described carrier is 308 ~ 1027 Osm/L, and acid-base value is pH 5.0 ~ 9.0.
19. compositionss according to claim 2, is characterized in that, described contact method is selected from atomized inhalation, Foradil Aerolizer formoterol fumarate or spray.
20. compositionss according to claim 19, is characterized in that, described acetone acid and pharmaceutical salts thereof or medicinal precursor dosage are 0.0001 ~ 10 mg.
21. compositionss according to claim 20, is characterized in that, described acetone acid and pharmaceutical salts thereof or the more optimal dosage of medicinal precursor are 0.0005 ~ 5 mg.
22. according to compositions described in claim 21, it is characterized in that, described acetone acid and pharmaceutical salts thereof or the more optimal dosage of medicinal precursor are 0.001 ~ 0.825 mg.
23. compositionss according to claim 2, is characterized in that, wherein acetone acid and pharmaceutical salts thereof or medicinal precursor form the fine droplet that can be penetrated into deep lung, and described droplet size is 0.01 ~ 10 μ m.
24. compositionss according to claim 23, is characterized in that, described droplet size is 0.1 ~ 7 μ m.
25. compositionss according to claim 24, is characterized in that, described droplet size is 0.5 ~ 5 μ m.
26. compositionss according to claim 2, it is characterized in that, in the time using acetone acid and pharmaceutical salts and medicinal precursor, use another kind or multi-medicament simultaneously, described medicine is selected from antibiotic, antiviral agents, antifungal agent, antineoplastic agent, antihistaminic, one or more in protein-based, enzyme, hormones, non-steroidal anti-inflammatory drug, cytokines and steroid.
27. according to compositions described in claim 26, it is characterized in that, wherein another kind or multi-medicament used before using acetone acid and pharmaceutical salts and medicinal precursor.
28. according to compositions described in claim 26, it is characterized in that, wherein another kind or multi-medicament are using acetone acid and pharmaceutical salts thereof and medicinal precursor to use simultaneously.
29. according to compositions described in claim 26, it is characterized in that, wherein another kind or multi-medicament use after using acetone acid and pharmaceutical salts and medicinal precursor.
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| CN201410175073.4A CN103948578A (en) | 2013-08-02 | 2014-04-28 | Pyruvic acid medicine composition for stabilizing osmotic pressure, and detoxification function thereof in healthy people and patients with lung diseases |
| PCT/CN2014/082185 WO2015014209A1 (en) | 2013-08-02 | 2014-07-15 | Pyruvate pharmaceutical compositions for osmotic stability and detoxification effect thereof in healthy human beings and lung disease patients |
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| CN2013103355699A CN103385868A (en) | 2013-08-02 | 2013-08-02 | Application of sodium pyruvate in preparing medicine for treating chronic obstructive pulmonary disease |
| CN201410032871.1A CN103720682A (en) | 2013-08-02 | 2014-01-23 | Pyruvic acid medicinal composition and application thereof in preparation of medicament for treating chronic obstructive pulmonary diseases |
| CN201410032871.1 | 2014-01-23 | ||
| CN201410175073.4A CN103948578A (en) | 2013-08-02 | 2014-04-28 | Pyruvic acid medicine composition for stabilizing osmotic pressure, and detoxification function thereof in healthy people and patients with lung diseases |
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| CN201410032871.1A Pending CN103720682A (en) | 2013-08-02 | 2014-01-23 | Pyruvic acid medicinal composition and application thereof in preparation of medicament for treating chronic obstructive pulmonary diseases |
| CN201410175073.4A Pending CN103948578A (en) | 2013-08-02 | 2014-04-28 | Pyruvic acid medicine composition for stabilizing osmotic pressure, and detoxification function thereof in healthy people and patients with lung diseases |
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| CN106727320A (en) * | 2017-01-13 | 2017-05-31 | 江苏长泰药业有限公司 | A kind of composition for repairing schneiderian membrane, reducing allergic reaction, antiinflammatory action |
| CN109771398B (en) * | 2019-02-25 | 2019-09-20 | 广州南鑫药业有限公司 | A kind of Peramivir solution-type inhalant and preparation method thereof |
| CN110859307A (en) * | 2019-12-10 | 2020-03-06 | 周方强 | Composition containing sodium pyruvate and use thereof |
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| CN103385868A (en) * | 2013-08-02 | 2013-11-13 | 江苏长泰药业有限公司 | Application of sodium pyruvate in preparing medicine for treating chronic obstructive pulmonary disease |
| CN103610671A (en) * | 2013-12-10 | 2014-03-05 | 江苏长泰药业有限公司 | Pyruvic acid medicinal composition and application thereof in preparing medicament for treating lung cancer |
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Non-Patent Citations (1)
| Title |
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| VOTTO ET AL: "Inhaled Sodium Pyruvate Improved FEV1 and Decreased Expired Breath Levels of Nitric Oxide in Patients with Chronic Obstructive Pulmonary Disease", 《JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY》, vol. 21, no. 4, 31 December 2008 (2008-12-31), pages 329 - 334 * |
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