TW434012B - Pharmaceutical composition for treating airway diseases in mammals - Google Patents

Abstract

The present invention pertains to compositions for reducing and treating the disease state in mammals caused by undesired inflammatory response comprising: an infla-mmatory response mediator; and a carrier composition; wherein the inflammatory response mediator is an anti-oxidant and capable of reducing undesired inflammatory response in mammalian cells.

Description

Printed by the Consumers' Cooperative of the Central Bureau of the Ministry of Economic Affairs of the People's Republic of China 4340 12. ^ A7 _____B7 _____ ^^ V. Description of the invention (1) '' Background of the invention 丨. The invention of this invention is related to undesired breathing urges, enzymes and cells The production of signal factors is related to the inflammatory response of mammalian cells, and the prevention of damage and disease states in mammals is related to the treatment. The invention also relates to the composition used in this medical method. Description of the prior art Reactive oxygen atoms are cells that respond to internal aerobic metabolism, the breakdown of drugs, toxins and other foreign microorganisms, ultraviolet and X-rays, and breathing to kill invading bacteria and respond to foreign bodies Produced by forcing cells to swallow (like white blood cells). Hydrogen peroxide, for example, is produced when most living microorganisms breathe, especially living cells under stress. These reactive oxygen atom classes can harm cells. An important example of this type of injury is fat peroxidation, which is related to oxidatine degradation of unsaturated fats. Fat peroxidation is highly detrimental to the structure and function of the membrane, and can cause severe cellular pathological effects. Cells counteract fat peroxidation by producing atomic scavengers such as peroxide dismutase, catalase, and peroxidation squatgers. The ability of injured cells to produce atomic sleep scavengers decreases. Too much nitrogen peroxide will react with DNA, causing the body to break and cause mutations, and—3— This paper size applies to the China Standard® (CNS) A4 size (210X297 mm) * nn (please first (Read the note on the back ^^ items really fill in this page)

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.I A7 B7 434012 V. Description of the invention (2). Change and release test basis. Hydrogen peroxide can also interact with pyrimidine and open 5, 6-double bonds. This reaction inhibits the ability of Yado to bind to basic bases through hydrogen bonding. Hallaender et al. (1971). Such oxidative biochemical damage can lead to the loss of cell membrane integrity, reduce enzyme activity, and change the motive force of transport. Change the content of membrane fat and leakage of potassium ions, ammonia ions and other cellular substances. The production of reactive oxygen atom intermediates is thought to cause many things like allergies, photoaging, wrinkles, actinic keratosis, tumor formation, cancer, hypertension, and Parkinson's disease Diseases of the skin, tissues, and organs such as lung disease, heart disease, and heart disease. Reactive oxygen atom groups have been proposed to play a role in promoting tumor growth. This is based on the increase of active oxygen radicals by active tumor promoters. (B) Many free radical generating systems promote tumor production. And (c) the discovery that specific antioxidants inhibit the biochemical effects of tumor promoters. The intermediates of reactive oxygen atoms in the test tube can be produced in the cell culture medium through the components of the culture medium by auto-oxidation (autoxidion) and photooxidation (photooxidantion). During the period when the transplanted organ is excised and stored, it will be damaged by oxidation, resulting in the loss of the integrity of the cell wall and the shortened useful life of the organ. When cells are urgently damaged by oxidative damage, a step of recovery is needed to repair the cells. Antioxidants have been shown to inhibit injuries related to reactive oxygen atoms. For example, it has been reported that pyruvate and other α-ketoacids react quickly and chemically with hydrogen peroxide in order to protect the size of fine paper. CNS M size (210X297 mm) m · 11. JIL —JT V One (Please read the notes on the back before filling this page) Order

X Printed by the Central Consumers ’Cooperative Bureau of the Ministry of Economy 4 3 4 0 1 2 :! Printed by the Central Ministry of Economy ’s Consumer Cooperatives of the Ministry of Economy A7 __B7_____ 5. Explanation of the invention (3), the cell is free from dissolution, O 'Donnell-Tormey et al., J. ExP. Med_, 165, pp. 500-514 (1987). U.S. Patent No. 5,210,098, issued by Nath, shows a method ' by administering non-toxic pyruvate to patients in need of such treatment in order to prevent or prevent acute renal failure. The treatment provided by Nath's invention is to administer a certain amount of pyruvate to a patient who is experiencing acute kidney failure or is at risk. Of the pyruvates, sodium pyruvate is preferred, and it is best dispersed or dissolved in a pharmaceutically acceptable liquid carrier, and in an amount effective to prevent or prevent the above-mentioned acute renal failure, Do parenteral administration, so normal kidney function is restored. In some cases, gadolinium pyruvate is injected directly into the renal or near renal artery circulation. This method is effective for preventing or combating acute renal failure caused by various causes, but the damage of trauma, including burns and obstructions, ischemia, inflammatory glomerulonephritis, and sepsis, such as Gram-negative Bacterial infections are not included. Martin et al., In 1994, U.S. Patent No. 5,296,370, published therapeutic compositions that prevent and reduce mammalian cell damage and increase the rate of recovery of mammalian injured cells. In a specific example, the therapeutic composition contains (a) a propionate selected from the group consisting of pyruvate, a pharmaceutically acceptable pyruvate, and mixtures thereof, (b) an antioxidant, and (c) ) A mixture of saturated or unsaturated fatty acids, where fatty acids are those needed to repair injured mammalian cells. US Patent No. 5,256,697 issued by Miller et al. Shows a -5-______ r .__ rr ^ ^ __ \ (Please read the note on the back before filling out this page) Order ^ 1 This paper size is applicable to the Chinese Standard for Crisis (CNS) A4 specification (210X297 mm) 4 3 4 0 12 at Β7 V. Description of the invention (4). By oral administration, a curative dose of propionic acid precursor is administered to mammals to improve insulin resistance Reduce the amount of persistent insulin, and reduce fat gain. U.S. Patent Nos. 3,92,835, 3,984,556, and 3,988,470, all issued by Vanscott et al., Show methods for treating acne, dandruff, and palmar keratosis, respectively. This method includes the The main composition of the pharmaceutically acceptable excipient is applied to the affected area. This composition contains from about 1% to 20%, from α-oxo acid, α_moeic acid and its lipids, and 3-class The lower lipid compounds of two to six carbon atoms selected from the group consisting of butyric acid. This lipid compound contains propionate and lactic acid. Two U.S. Pat. Nos. 4,105,783 and 4,197,316 issued by Yu et al. Each show a method and composition for treating dry skin, which include a pharmaceutically acceptable agent The main composition of the formulation is applied to the injured area. This composition contains from about 1% to 20% of the ammonium and ammonium salts of (X-oxo acid, β-oxo acid, and α-keto acid The selected compound in the composed category. This compound contains pyruvate and ammonium salts of lactic acid and ammonium salts. Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please note the note on the back of Mt # before filling out this page) ) .Fei ——. N) r US Case No. 4: 234,599, published by Van scott et al., Shows a method for treating actinic and non-actinic skin keratosis, including the The main composition of pharmaceutically acceptable excipients is applied to the injured area. This composition contains a selected one of the categories consisting of α_oxo acids, β_oxo acids, and α-keto acids. Effective amount of compound. Such acidic compounds include pyruvate and lactic acid. —6- This paper size is applicable to the Chinese national standard (CNS > Λ4 specification (210X297 mm) 1 '434012 Printed A7 B7 by the Consumers' Cooperatives of the Central Procurement Bureau of the Ministry of Economic Affairs __ 5. Description of the invention (5)' by Wildnauer Published U.S. Patent No. 4,294,852 shows a composition for treating the skin, which composition contains α-oxo acid, β-oxo acid, which is bound to C3-C8, as disclosed by Van scott et al. Above. And α · arsinic acid. U.S. Patent No. 4,663,166, issued by Veech et al., Shows an electrolyte solution containing L-lactate and pyruvate in a ratio of 20: 1 to 1: 1, Or a mixture of D-β-hydroxybutyric acid and acetamidine acetate in a ratio of 6: 1 to 0-5: 1. It has been reported that sodium pyruvate can reduce acetamylsalicylic acid in guinea pigs and rats. Erosion, ulcers, and bleeding on the gastric mucosa. Acetosalicylic acid's analgesic and antipyretic effects will not be diminished by sodium pyruvate. 1 ^^ 111 ^ 1111, 8 1 ^ 6 Ruchu 61 Negative (^ 11 Qiu. Issue 33. 410 ~ 415 and 415 ~ 416 (1983). It has been reported that after a short period of time, After the stage of coronary occlusion that caused irreversible damage, pyruvate has the effect of increasing contraction of the myocardium, which is weak due to prolonged ventricular dysfunction, Mentzzer et al., Ann. Sug. 209, 629 ~ 633 pages (1989). It has been reported that pyruvate can produce fairly stable left atrial pressure and operational variables, and can reduce the size of infarcts. Pyruvate enhances the recovery of the heart's fairly stable natural beating and normal rate And recovery from stress development. Bunger et al., Journal of Molecular Cell Cardiology (J_Mol .. celUardiol), 18th issue, 423 ~ 438 (1986), Mochizuk 丨 et al., Journal of Physiology (Paris), No. Issue 76, pp. 805 ~ 812 This paper uses China National Standard (CNS) A4 size (2 丨 〇 < 297 mm) ----- L--Γχλ ^-V (please first (Notes on the back of the M feed are stored in the yellow book.) If fl 4 4 4 0 12 A7 B7 V. Description of the invention (6) '(1980), Regitz et al., Cardiovascular Research (Cardivascu · Res.) 15th Issue, pp. 652-658 (1976), Giannill et al., Thoracic Surgery Issue No. 22, Issue 3 ~ 396 (1976). It has been reported that sodium pyruvate plays a role in antagonizing cyanide poisoning (inferred to be the formation of cyanohydrin), Moreover, it is protected from the lethal effects of sodium sulfide, and the functional, morphological, and biochemical measurement of the axonal axon pathway is initiated and performed. Schwartz et al., Pharmacology of Toxicology, Issue 50, pp. 437-442 (1979). Sabri et al. Brain Res_, 483, p. 11 (1989). Chemotherapy for severe L1210 leukemia has been proposed and repaired with sodium propionate to make abnormally deformed red blood cells normal. Deformed red blood cells prevent proper drug delivery to the tumor. Cohen et al. Cancer Chemother. Pharmcol., No. 5, pp. 175-179 (1981). Printed by the Central Labor Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperatives (please read the "Notes on the back" and fill out this page). Some people have proposed to be exposed to 7,12-dibenzylbenzene (7,12_ dimethylbenz) in vivo. (a) Primary culture of heterotopic transplantation of anthracene) can be alone and stimulated to produce peripheral blood lymphocytes of interleukin-2 and plasmacytoma and hybridoma, pig embryo and human blastocyst cells , Successfully maintained in nutrient-rich medium supplemented with sodium pyruvate.

Shacter, J. Immuno Methods, 99, pp. 259-270 (1987), Marchok et al. Cancer Research (Cancer R_es), 37, pp. 1811-1821 (1977), Davis, Journal of Reproduction and Insemination _ Supplement (J. Reprod. Ferti). Suppl., Issue 34, U5 ~ 124 The paper size is applicable to China National Sample Rate (CNS) Α4 Washer (210 × 297 mm) Ministry of Economic Affairs 4340 12 A7 ____ B7__ Printed by the Central Government Bureau of Standards and Technology Co., Ltd. V. Description of Invention (7), page, (1985). Okamoto et al., No To Shinkei, No. 38, Nos. 593-598, (1986). Cohen Journal of In vitro Fertilization and Embryo Transfer (J.

In vitro Fert. Embryo. Transfer.), No. 2, pp. 59-64, (1985). U.S. Patent Nos. 4,158,057, 4,351,835, 4,415,576, and 4,645,764, all issued by Stanko, have shown that preventing the accumulation of fat in the liver due to alcohol consumption in mammals, controlling mammals' weight, and inhibiting the body's body when mammals have increased protein concentrations Fat, and methods for controlling the distribution of body fat in the body. This method consists of administering pyruvate and dihydroxyacetone to a mammal, and optionally a vitamin B2 therapeutic mixture. U.S. Patent No. 4,548,937 issued by Stanko shows a method that can control the weight gain of mammals, which comprises administering to the mammal a therapeutically effective amount of pyruvate and optionally vitamin B2 and pyruvate. It has been reported that the rats fed with oxalic acid containing sodium pyruvate to cause calculus-induced food intake are more prone to generate calculus than the control group not given sodium pyruvate. Ogawa et al., Hinovokika Kivo, No. 32, pp. 1341 ~ 1347 (1986). U.S. Patent No. 4,521,375 issued by Houlsbii shows a method for disinfecting surfaces that come into contact with living tissue. This method uses water-based hydrogen peroxide to disinfect the surface, and then uses pyruvate to neutralize the surface.

U.S. Patent No. 4,416,982, published by Tauda et al., Shows a method for trans-9 using hydrogen peroxide and an aniline or aniline derivative containing catalase. This paper is applicable to the Chinese impurity ratio (CNS) A4 «^ (210X297 Mm) '-1 LK-— «Li If I (please read the" $ "on the back side before filling out this page) Order f · Central Government Bureau of the Ministry of Economic Affairs, Consumer Consumption Du Yinye 4 3 4 0 1 2 * a? __B7 ____ 5. Description of the invention (8) " Should be used to decompose hydrogen peroxide.

Lindstrom et al., U.S. Patent No. 4,696,917, shows an Eag 丨 e's minimal minimal medium containing Earle's salts, chondroitin sulfate, buffer, 2-acetone and pyruvate injection Wash the solution. This injection and washing solution preferably contains vitamin C and α-tocopherol. U.S. Patent No. 4,725,586, issued by Lisndstrom et al., Shows a solution containing a balanced salt solution, chondroitin sulfate, buffer, 2-salted ethanol, sodium carbonate or dextrose, pyruvate, sodium phosphate and Flushing system and injection solution of cystine. This injection and washing solution preferably contains vitamin C and γ-vitamin E. U.S. Patent No. 4,847,069 issued by Bissett et al. Shows a photoprotective composition containing (a) a sorbohydroxamic acid, and (b) an anti-inflammatory agent selected from the group consisting of Steroid anti-inflammatory agents and a natural anti-inflammatory agent, and (c) a typical excipient. Use fatty acids as softeners. U.S. Patent No. 4,847,071 issued by Bisset et al. Shows a photoprotective composition containing (a) vitamin E and (b) an anti-inflammatory agent selected from steroidal anti-inflammatory agents and A natural anti-inflammatory agent, and (c) a typical excipient. U.S. Patent No. 4,847,072, issued by Bissett et al., Shows a typical composition that contains no more than 25% of vitamins in a typical excipient. E ° It has been reported that the addition of pyruvate steel to bacterial or yeast systems can inhibit the generation of hydrogen peroxide, promote growth, and protect the entire system against the toxic effects of reactive oxygen atom intermediates. Contains -10 in chicken fat-This paper size is suitable for Chinese National Samples (CNS > Α4 now (210X297 mm) ----- * — Λ ^ —I (Please read the note on the back ^! ^ Please fill in this page again) Order 4340 12 A7 B7 printed by the Central Laboratories of the Ministry of Economic Affairs Shellfish Consumer Cooperative V. Description of the invention (9) 'The best ratio of unsaturated fatty acid and saturated fatty acid can improve the membrane Repair and reduce the effects of cell toxicity. Antioxidants and acetyl acetates reduce the damage caused by oxygen atomic groups. Martin ’s doctoral dissertation, (1987-1989). However, the therapeutic composition and methods in the above report only There is no composition and method for inhibiting reactive oxygen atom intermediate products, and it is used to treat the damage and disease states caused by undesired breathing urges, the production of enzymes and cell signaling factors in mammalian cells, and mammals. Brief Description of the Invention The present invention relates to a method for treating a disease state caused by mammalian cells associated with an inflammatory response in a mammal, and an effective composition therefor. A method related to the disease state caused by mammalian cells in mammals, including: using an inflammation mediator to contact mammalian cells involved in an inflammatory response, the amount of the inflammation mediator here can reduce the unwanted inflammation response, and it is an antioxidant In addition to reducing the undesired inflammatory response, the inflammatory mediator is an antioxidant that can further provide a source of cellular energy and act as a building block in the cellular synthesis of other cellular components. The inflammatory mediator can also increase the rate of cellular metabolism The present invention relates to a composition for reducing and treating a disease state caused by an undesired inflammatory response in a mammal, which contains a mediator of an inflammatory response; and an excipient composition in which an inflammatory response Harmonize the national standard rate (CNS) A4 specification of this paper (210X297 mm) H. 11 · ϋ----· ----- mn 〆. (Please read the precautions on the back before filling in this Page).) Τ y A7 4340 1 2 V. Description of the invention (10) " The substance is an antioxidant and can reduce the An allergic reaction is desired. The inflammatory response mediator can be used alone or further with antibacterial agents, antivirals, antimycotics, proteins, enzymes, antihistamines, hormones, nonsteroidal antiinflammatory agents, cytokines, and steroids. The therapeutic agents are used in combination. A better method of applying the inflammatory mediators is by inhalation. The present invention details mammalian cells that are related to the inflammatory response, and therapeutic compositions and methods for treating disease states caused by mammals. It was found that the mammalian cells that primarily respond to the inflammatory response are white blood cells or white blood cells. 0 Mammalian cells associated with the inflammatory response. In the treatment of mammalian-induced disease states, mammalian cells are a mediator of inflammation. contact. Inflammatory blends are present in an amount that reduces unwanted inflammatory reactions and are an antioxidant. Inflammatory reactions, often related to shortness of breath, are defensive mammalian cells, mainly white blood cells or white blood cells. Normally, these cells respond to injury or foreign body invasion in mammals by releasing activated components at the injured or invaded area. Among the released components, there are protein enzymes like enzymes, and active oxygen atoms like hydrogen peroxide. Standards of this paper use two standards of Zhonggu (CNS > A4 size (2 丨 0X297 mm) (Please read the precautions on the back before filling out this page). Binding and ordering-Central Ministry of Economic Affairs Printed by the Industrial and Consumer Cooperatives 4 3 4 0 1 2 * A7 _____B7__ 5. Description of the invention (11) The purpose of shortness of breath is to provide a set of devices that can be used to destroy foreign cells, viruses, particles, and some white blood cells. Or the stimulants of toxins ingested by nearby white blood cells, which respond to oxidants. The word "shortness of breath" is related to a series of coordinated metabolic events. When white blood cells are exposed to appropriate stimuli, this group of metabolic effects will occur. This set of metabolic events is the basis of all oxygen-related killing actions by white blood cells. The first of these events is that when the stimulation of white blood cells occurs, the oxygen atoms will rise sharply. However, the dormant white blood cells of various cell types Oxygen consumption, all will respond to an increase in oxygen uptake when stimulated properly. 0 Hexose monophosphate shunting can also increase glucose oxidation by stimulating white blood cells. Hexose monophosphate shunt is a metabolic pathway, this pathway of glucose is oxidized to carbon dioxide and pentoses, while NAE) p + role as the electron acceptor. Therefore, the activation of hexose monophosphate shunting means that the NADP becomes an oxidative effect of NADP + when breathing is short. The Central Bureau of Economic Affairs, the Ministry of Economic Affairs and the Ministry of Economic Affairs of the Ministry of Economic Affairs of the United States of America have printed LI · ^ 丨 — ^^ 1 · ϋ m In — ^ Γ τ, --n »—1 (Please read the note f on the back before filling out this page ) I · Respiratory pressure produces peroxide and hydrogen peroxide. Oxygen taken as a result of shortness of breath is converted into peroxides. When breathing is short, tritium peroxide appears and rises, mainly due to the dismutation of peroxide ions. 〇2 * + 02 · + 2Η + ^ Η 202- + 02 has been proven by Root and Metcalf and also reported in the 60th volume of the Journal of Clinical Investigation (j Clin. Invest ·), page 1260, 80% _ 13-^ The paper size is applicable to national standards (CNS > A4 size (210X297 mm) ^^ 434012

Oxides are converted to hydrogen peroxide and disproportionation is the only important source of hydrogen peroxide during shortness of breath. Hydrogen peroxide and peroxide are thought to respond to killer white blood cells. Many are soluble and particulate vehicles ' that can activate shortness of breath. Particulate activation media include bacteria, viruses, and molds in organ regions of the body, as well as the lungs, skin, digestion and excretion of organs such as body cavities and open to the environment. Bacteria, viruses, fungi, fibers, smoke, dust , Ash, pollen, exhaust, and the like. Soluble mediators can be toxins, medicinal ingredients, and soluble excretion of bacteria, molds, infected mammals, and the like. Less than a minute after exposure to the stimulus, often a rapid activation of the white blood cells breaths. Under the stimulation of shortness of breath, the oxygen consumption of white blood cells will increase by 100 times, resulting in the production of peroxides and hydrogen peroxide in other cases. As used herein, the terms white blood cells include lymphocytes, phagocytic cells, macrophages, and Auxiliary cells. Printed by Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs -------- Γ .---- Please read the notes on the back before filling out this page) ^ Usually after the shortness of breath, the irritants and / Or the stimulus mechanism is suspended to return the white blood cells to its normal dormant state. When the breaks in breathing are not stopped, the inflammatory effects of white blood cells will continue unchecked and cause some disease states. When compounds produced by white blood cells attack, injure and kill tissue cells and other white blood cells, further disease states occur. It is useless to treat the disease state caused by the respiratory damage and the subsequent damage of surrounding tissue cells, blood cells, other leukocytes and injured cells. When the inflammatory response causes damage to the host cells and this damage forms an independent threat to the host, the unwanted inflammatory response will be -14-New Paper CNS (2iQX297 mm) " "-Central Bureau of Standards, Ministry of Economic Affairs Printed by the employee consumer cooperative 4340 1 2-A7 B7 V. Description of the invention (13 >, Occurrence. In a better specific example, this therapeutic composition contains an inflammation mediator, which is applied topically to the inflamed area. In another preferred embodiment, the therapeutic composition is administered in a systemic manner. However, in another preferred embodiment, the therapeutic composition can be administered in both a local and a systemic manner. In a preferred embodiment, the therapeutic composition is administered by inhalation. The therapeutic composition is first sprayed in a suitable manner. The therapeutic composition can be stored in a liquid or solid form, and the liquid droplets are inhaled. Or particles that are small enough to easily reach the lung tissue. In the preferred embodiment, the sterile solution of the therapeutic agent is sprayed out and inhaled by the patient. The inflammatory mediator is effective The amount is inhaled. This is accompanied by a single breathing action or a repeated breathing action that is basically one to thirty minutes long. It is better to complete the breathing action in less than twenty minutes. To complete the breathing in less than fifteen minutes The action is even better. The term "injured cell" as used herein refers to a cell with some or all of the following conditions: (a) the injured cell membrane reduces transport through the membrane, and can cause one or more of the following The situation described above, that is, the increase of toxins and normal cellular waste in the cells and / or the reduction of nutrients and other components required for intracellular repair, (b) the ability of cells to produce antioxidants and enzymes is reduced, resulting in intracellular Increase in oxygen atom plutonium. (C) Damaged DNA, RNA, and nuclear callus that must be repaired or replaced before normal cell function can be restarted. This paper is applicable to the standard β home ladder (CNS > Α4 Specifications (210X297 mm) (please read the note on the back before filling this page)-. A7 B7 434012 V. Invention February (14)-Tian was brought into contact with mammalian cells, and sent It is better for the mediator to provide cell energy sources and building blocks in the cell synthesis of other cellular components. Please first listen to the note of A. The reduced inflammatory response is at least one of the following: the production of oxygen atom plutonium, the production of peroxides , Production of cytokines and / or protein enzymes, production of erythema, histamine, and interleukin and similar responses known in the art of inflammatory response techniques.

At least one compound selected from the group consisting of pyruvate and pyruvate precursors, lactate precursors, and lactate is preferred among at least one compound. A precursor is a substance from which other substances are formed, and salts are also included in this article. Propionate includes propionate, propionate, sodium propionate, pyruvate, magnesium propionate, propionate, zinc propionate, silver propionate, and the like or a mixture of the foregoing . Sodium pyruvate is preferred. Consumption cooperation between employees of the Central Bureau of Standards and Economics of the Ministry of Economic Affairs of the People's Republic of China should be based on the use of salt-based inflammatory mediators. Preferable inflammatory mediators include pyruvyl-glycene, pyruvyl-alanine, and propionate. Pyruvyl-leucine, Pyruvyl-valine, Pyruvyl-isoleucine, Pyruvyl-phenylalanine, Pyruvate (pyruvamide), dihydroxypropane, and propylene glycol. When a salt-based inflammatory mediator is used, a preferred inflammatory mediator salt is a salt that does not produce unwanted effects in mammalian cells. Typical salts can be lithium, sodium, potassium, aluminum, magnesium, calcium, zinc, manganese, ammonium ions, and -16-this paper size is common Chinese National Standard (CNS) A4 specification (21〇297297) 4 3 4 0 1 2 1 A7 B7 V. Description of the invention (15) '' or the like, or a mixture of the above. The precursor of lactate is preferably selected from the group consisting of lactyl-glycene, lactyl-alanine, lactyl-leucine, and lactyl -valine), lactyl-isoleucine, lactyl-phenylalanine, lactamide, and various lactates. Compositions of ingredients that reduce and treat mammalian disease states caused by undesired inflammatory reactions: cancer-generating response mediators; excipients. The composition of this excipient is selected from the group consisting of lozenges, capsules, liquids, isotonic solutions, isotonic bases, enteral lozenges and capsules, parenteral administration, topical medications, creams, gels, Creams, chewing gum, confections and the like. The inflammatory mediator is administered in a therapeutically effective amount to reduce the adverse inflammatory response. Each dose is preferably from 0.001 to 10 grams. 0.001 to 1 g per dose is preferred, and 0.001 to 0.25 g per dose is even better. It is now understood that the method of application and treatment will greatly affect the dose required to achieve efficacy. Printed by ni-aa ^ i κϋ ftn —l · — m · UK— 1 ^ 1 I (Please read the note on the back before filling out this page) " Available at present This composition and method treats typical respiratory diseases, but is not limited to asthma, acute bronchitis, emphysema, panacinous emphysema, chronic obstructive bronchitis, reactive respiratory disease, cysts Sexual fibrosis (cystic fibrosis), bronchiectasis, this paper size applies Chinese National Standards (CMS > A4 Washer (210X297 mm) 434012 A7 B7 Printed by the Central Ministry of Economic Affairs, Zhuhai, Beibei Consumer Cooperatives) Description of the invention (16) 'Acquired bronchiectasis, Kartaagenor's symdroms, acute insufficiency, chronic insufficiency, pneumonia, primary hyperplasia, Reginagliosis disease), crane disease (Psittacosis), fiber dust disease, diseases caused by organic dust, diseases caused by irritating gases and chemicals, allergic diseases of the lung, primary osmotic diseases of the lung, and The specific diseases to be treated are emphysema and asthma. The inflammatory mediators of the present invention can be administered before, after and / or together with other therapeutic agents. Typical therapeutic agents are antibacterial agents, antivirals, antimycotics Agents, antihistamines, proteins, enzymes, hormones, non-steroidal anti-inflammatory agents, cytokines, steroids, and the like. Obviously, many changes and differences in the present invention may be as described above, and the present invention is not limited to this. It is therefore understood that in the scope of the attached order, this creation is actually more limp than the one specifically described in this article. Illustrative patient:-fifty-nine who are suffering from emphysema and restrictive respiratory diseases The aged male was treated with the following methods for three months. Before treatment, the patient's biting ability was limited, he did not respond to any other treatment, he used oxygen every day, and he did not rely on operation (it was during rest) Lung lobes). After a leap month of treatment, he showed a marked improvement. In fact, a dramatic result was observed in Inmachi within two weeks. —18 -一 —in (Please read the note on the back before filling this page) Order _ ψ «κ ^ — C CNS) Α4Ά ^ ^ 210X297 ^) 4340 1 2 A7 B7 V. Description of the invention (17) 'Treatment: treatment The method is as follows: Five milliliters of a five millimolar volume (mM) sodium pyruvate solution are filtered through a 0.2 millimeter filter. A sterile pyruvate solution was placed in a "Pulmo aid" -sprayer manufactured by Devilbiss, Somerset, Pennsylvania 15501-0635. This sterile pyruvate solution is sprayed out 'by a disposable sprayer "Purple Moped Device" and is inhaled by the patient. The patient normally inhales from the "Pur Moped" sprayer until all the solution is ejected and inhaled. This inhalation step takes about ten to twenty minutes. Patients are treated periodically with this inhalation therapy. At the beginning, treatment was performed four times a day at six-hour intervals. Thirty days after treatment, the treatment was reduced to three times a day, with an interval of eight hours each. Six days after the start of treatment

I Ten days, the treatment was further reduced to once a day. After ninety days, the treatment is three to five times a week. The following data show the results of different lung volume and lung function application tests before and two months after the recommended treatment. ^^-1 HI n a- 丨 w.-1 (》------ ϋ (Please read the precautions on the back before filling out this page)-Order the printing test of the Shellfish Consumer Cooperative of the Central Bureau of the Ministry of Economic Affairs SVC slow lung capacity after treatment before treatment 63 83 (slow vital capacity) ic Inspiratory capacity 64 69 (inspiratory capacity) This paper is used for the standard rate of medium-to-solid fixation (CNS > A4 size (2 丨 0X297 mm) 3 4 CM 2 A7 B7 V. Description of the invention (18) ERV expiratory reserve volume 62 110 (expirtotry reserve volume) MVV maximum ventilation volume 19 25 (maximum ventiatory volume) DCO carbon monoxide diffusion 27 27 (diffusion of carbon monooxide) DSB Diffusion single breath 42 52 (diffusion single breath) 0 SAT oxygen saturation 91 95 (oxygen saturation) (Please read the precautions on the back before filling this page) 'C. Observation: Twenty to thirty minutes after starting treatment, Increased tidal volume, asthma cessation, and increased exercise tolerance were observed. During the first two weeks of treatment, reliance on Proventil (manufactured by Albuterol " by Schering) changed from daily Six hundred cents Reduced to four hundred milligrams. When treatment is started, immediately eliminate the use of oxygen. Conclusion: The treatment can do the following: (1) Improve lung function by about 20%. (2) Reduce some doses and discontinue the use of oxygen. (3) Reduce reactive respiratory diseases until routine use of inhalers is not required. (4) Increased exercise tolerance has been tested and determined as -20-This paper size applies China National Kneading Rate (CNS) A4 specifications (210 × 297 mm) Order printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs ^ 340 1 2 v A7 ___________B7 _ V. Description of the invention (19) _, which is similar to a non-emphysema and restrictive respiratory disease The condition of the person. The patient can resume all the work schedules of the previous work. (5) The reduced lung function is no longer recurring. (6) The mental attitude is gradually greatly improved. However, the treatment described in the article is related to the lactation-related breastfeeding. The method for the disease state of animal cells, the composition of which is more suitable for the specific examples of the present invention. It is understood that the present invention is not limited to the precise form of the method, and the changes caused by it do not deviate from the The scope of the invention as defined in the patent application. (Please read the note ^^ on the back before filling out this page> Order _ Γ Printed by the Ministry of Economic Affairs of the Bureau of Quasi-Bureau Consumer Cooperatives, L. -21-This paper is applicable to SS home standards (CNS > A4 specification (2 丨 〇x297mm) _ This year is 丨 43 such as 2 supplement ^ A7 B7 V. Description of the invention () ROC Patent Appln. No. 85111379 Supplementary test data Chinese text —Annex ㈠ Supplemental Test Data in Chinese-Enel. (I) (Submitted on December 5th, 1989) (Submitted on December 5 ", 2000) Mild asthma response to pyruvate treatment 15 patients with mild bronchial asthma Complete the following research report. Patients with mild bronchial asthma were clinically diagnosed for the disease, and at the screening visit (Visit 1), it was confirmed that after inhaling the bronchodilator, FEV-1 of 60-80% of the expected value could be achieved Or a 12% increase in FEV-1. Report: 15 patients with mild bronchial asthma first inhaled a single 5 ml dose of normal saline at baseline (pre-dose) and 15 minutes and 30 minutes after administration , 1 hour, 2 hours, and 4 hours, Pulmonary function assessment and vital signs. At the return visit (visit 2), 'each patient inhaled a single 5 ml dose of 0.5 mM sodium pyruvate in physiological saline'. The assessed physiological function included forced expiratory volume within one second ( FEV-1) and peak expiratory airflow (PEF). FEV-1 and PEF values obtained through general lung breathing test. FEV-1 is a self-sufficient inspiratory forced expiratory air that is expelled from the air within the first second. Because of the objectivity and reproducibility of the data, it has been widely accepted as an indicator of obstructive pulmonary disease and is widely used. PEF is the maximum for 10 milliseconds of forced exhalation from fullness of the lungs. Flow rate. Generally speaking, a change of greater than 10% FEV-1 and a change of PEF greater than 25% are considered clinically relevant and used as the standard for evaluating the data in this study. Cellu85407.rpt-ch Paper size Applicable to China National Standard (CNS) A4 Specification < 210 X 297 Public Love) ----— 1 ·-? Bu-'! ^^^ · --------- Order ------ --- line ^ N- (please read the note $ on the back and fill in this page first)

434012 A7 B7 5. Description of the invention () Results: FEV-1 inhaled 0.5 mM sodium pyruvate for 15 minutes (ρ = 0.012), 30 minutes (ρ = 0.039), and 1 hour (ρ = 〇_〇54) After 2 hours (ρ = 0.001), a statistically significant improvement in FEV-1 percentage change (greater than 10 ° /.) Was observed compared to inhaled saline. (See Figure 1)

PEF inhalation of 0.5 mM sodium pyruvate for 15 minutes (P = 0.014), 30 minutes (ρ = 0.027), 1 hour (ρ = 0.012), 2 hours (ρ = 0.024), 4 hours ( ρ = 0.018), a statistically significant improvement (greater than 25%) in the percentage change in PEF compared to inhaled saline was observed. (Please see Figure 2) (Jingxian W read the note on the back and fill in this page) Printed by Shelley Consumer Cooperative, Intellectual Property Bureau, Ministry of Economic Affairs 2 cellu85407.rpt-ch This paper is applicable to the National Standard (CNS) A4 specification (210 X 297 mm)

Claims (1)

43 乜 12, f / ·, patent application scope A8 B8 C8 D8 Patent Application No. 85111379 ROC Patent Appln. No. 85111379 Amended Claims in Chinese-(Enel. I) (Submitted on October 20, 88) (Submitted on October 20, 1999) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. Two pharmaceutical compositions for the treatment of respiratory diseases in mammals, including effective amounts of pyruvate Salt and / or pyruvate precursor as Part A 'and a pharmaceutically acceptable carrier "" Properties 1 "2. The composition according to item 1 of the scope of patent application, wherein the propionate or propionate precursor When in contact with mammalian cells, it provides a cellular energy source and building block for the synthesis of cells containing cellular components. Danta 3. The composition according to item 2 of the scope of patent application, wherein the pyruvate test and / or the propionate precursor system can increase the metabolic rate of cells. 4. The composition according to item 1 of the scope of patent application, wherein the carrier is an isotonic substrate. 5. The composition according to item 1 of the patent application scope, wherein a propionate precursor is used as an active ingredient. 6_ The composition according to item 5 of the scope of patent application, wherein the pyruvate precursor is selected from the group consisting of acetone, glycine, acetone, alanine, propionate, acetone, valerate, and acetone Leucine, acetone, anilide, acetaminophen, dihydroxyacetone, and propylene glycol. 7. The composition according to item 1 of the scope of patent application, wherein the carrier is selected from the group consisting of isotonic solution, isotonic suspension and isotonic aerosol. '8. The composition according to item 1 of the scope of patent application, wherein the respiratory disease is emphysema. 9. A composition according to item 1 of the scope of patent application, wherein the respiratory disease is asthma. -22- This paper size is applicable to China National Standards (CNS). A4 size (210 X 297 male *) CE85407-CLAIM-CH (Please read the "Notes on the back" before ordering.