TW201266B - A production method of smokeless and ordorless medicine used in moxibustion - Google Patents

Abstract

A production method of smokeless and ordorless medicine used in moxibustion, which is characterized by cutting or grinding into powder of dried plant leaves, fumigating them until no white smoke is produced, adding water into the plant leaves which had been fumigated, selecting and molding the semi-carbonated material which is floated on the upper part of the solution, and drying the material to a water content of less than 4 %.

Description

Fix 82, l._9

20U66 μ Fangben + month B V. Description of the invention (1) Medical active ingredient flupiridine (chemically named as 2-amino-3-pyridoxamine-6- (4-octanylmonoamine) -shame Dian) like a painkiller. The preparation of this compound and its physiologically acceptable compounds are described in German Patent 1,795,858 and German Patent 3,133,591. It is now found that flupirtine also has a skeletal muscle relaxation effect and is suitable for antagonizing clinical signs, clinical diseases and diseases based on the development of muscle tension or muscle tension. The present invention is falsely directed to an agent for antagonizing diseases and / or clinical conditions based on muscle tension or the development of such muscle tension. Therefore, for example, in addition to the analgesic effect of flupiridine during the measurement of the resistance of the flexors and extensors of the hind legs of rats, it also shows a good skeletal muscle relaxation effect. Experimental method: 1 60 g to 200 g of female SI V50-rats were used as experimental animals. These animals are maintained at 2 0t: to a room temperature of 241C, printed by the Beigong Consumer Cooperative of the Central Bureau of Economics of the Ministry of Economic Affairs (please listen to the precautions on the game surface before playing 1 page) 6 0% to 70% relative Humidity and light to dark time ratio of 12 to 12 hours. Feed (Atromin «, mature rye) and water supply are unlimited. Flupirtine is used in its maleic acid form. The muscle relaxation effect is measured by continuously measuring the resistance of the flexor and extensor muscles of the hind legs of the rat. To achieve this, the foot of the right hind leg of the mouse is moved up and down quickly. This is achieved by using a 30-second electronically driven automatic motor to achieve the cost of paper. The standard of the Chinese National Standard (CNS) A 4 (210 X 297 Cli) —3 — 201266 A 6 B6 Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Beigongxiao #Cooperative V. Invention description (2). The relaxation response of the flexor and extensor muscles of rats was stimulated by the forced movement of the rat feet, and the relaxation response was transmitted to a forced transducer and evaluated using a computer (I B M / PC). Parallel to the online evaluation, the data is drawn with a general plotter and recorded on a tape at the same time. Before the experiment started, the experimental instrument was calibrated by providing a calibrated 50 gram weight on the mandatory transducer. Thereafter, the animals were placed in the experimental unit for 30 minutes to adjust the unit. After measuring the resistance of the original rat flexor and extensor muscles (control value), flupiridine maleate was administered intraperitoneally and recorded and stored, and the effect of the compound on the flexor and extensor muscles was evaluated online9. Minutes, the average value is calculated every 10 minutes. The Student's T test was used to check the magnitude of the difference between the mean values of the experimental animal groups. Muscle tone effect was noted after intraperitoneal administration of flupiridine in an analgesic effective dose range. In animals treated with chipiridine in the investigated dose range, there were no significant side effects such as ataxia or immediate motility The reduction was observed. For example, in the above experimental method with a dose of 1 mg / kg body weight of rats, the value of skeletal muscle in sober rats caused by drugs was reduced by 50%. In the above animal tests, the lowest effective dose is, for example: 1 mg / kg orally. 1 mg / kg intraperitoneally. For this effect, the general dose range is considered, for example, 1-100 mg / kg, orally, holding Don't be 10 to 40 mg / kg, Taigu.Zhang Chiming ii «Xianzhong Min H House 揼 m (CNS1 A 4 report (210x297 public goods) ~ 4 ~ (Please read the notes on the back before filling this page ) I amended ^ 82. -¾ A6 B6 201266

Benquay month B

^ 1L 5. Description of the invention (3) (Please read the notes on the back and then this page) Ο. 1-30 mg / kg, intraperitoneally, especially 1 to 20 mg / kg. Compared with other active compounds with the same effect, flupiridine shows the following differences: flupiridine does not cause dependence and has a significant analgesic effect. 0 The muscle relaxation effect of flupiridine also leads to anti-Bakinson's disease agents Reserpine (molecular formula c 4.0 SN 2) in a similar way caused a hard reduction. The combination of air-pyridine with this type of anti-Bakinson's disease agent provides a super-additive, enhanced skeletal muscle relaxation effect. Therefore, flupiridine also reduces the tension in the middle skeletal muscles in diseases such as Mobaskin's disease, and the muscle tension in the disease is increased. The effective dose for this purpose is given. Gaspiridine alone or in combination with other known anti-Bakinson's disease building agents such as (I) —N, oc —dimethyl-N — 2 -propynylphenethylamine, α — 5 — probornene-2 —The effect of the base of a base of α-phenyl-1-pyridinyl propanol and L-dopa to dorsalpine (dopa) is listed in the following table. Printed by R Industrial and Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs-5- This paper scale is applicable to China National Standards (CNS) A 4 specifications (210 X 297 mm); 0105395

PL &lt; No. Of application for the application of the Chinese language in the revised version I3 6 Amendment in January 1981 V. Description of the invention (4) J-value hard reducing substance dose> Flexor extensor mg / kg ip% effect% effect Ministry of Economy Central Printed by quasi-bureau employee consumer cooperatives 5 53 ± 0.5 0.5 ± 0.5 (-) N, «—dimethyl-1 18 ± 0.5 14 ± 0.5 N-2 — propynyl phenylethylamine gas Dian 5 + + 96 soil 0.5 93 ± 0.5 (1) N, α-dimethyl-1 N-2-propynylphenethylamine, 1 'α-5—probornene-1—0.1 12 ± 0.5 16 ± 0.5 base-10 [-phenyl-1 1-monopropanol flupiridine 5 + + 89 ± 0 · 5 96 ± 0.5 α-5—orbornene-2—0.1 base-1 ot—phenyl-1 _Edylpropanol L _Dopa 5 17 soil 0.5 11 soil 0.5 flupiridine 5 + + 93 ± 0.5 88 ± 0.5 L one-dopa 5 (CNS) Specifications (210X297 (please read the precautions before filling out this page) installed-201266 Ministry of Economic Affairs Central Standards Bureau employee consumption cooperation du printing to reduce stiffness by the rat described The ore-holding measurement of the resistance of the flexor and extensor muscles of the hind legs. The only difference in the determination of the reduction in stiffness is that the animal is given an intraperitoneal dose of 2.5 mg / mouse weight kg 16 hours before the start of the experiment. Reserpine. Reserpine leads to a hard value. The reduction or elimination of stiffness caused by the combination of flupiridine, different anti-Bakinson's agents, and flupiridine and the latter is determined in the manner described. The indications of flupiridine according to the new effect of the present invention can be regarded as: All diseases related to muscle tension (stubbornness) and its subsequent symptoms, such as neuralgia, arthritis, arthropathy, chronic or primary tension headache , Post-operative weakness, generalized tendon muscle paralysis, attached tendon muscle paralysis, and Bajinsheng's disease (especially the stiffness associated with Bajinsheng's disease). Taboo emblem: Myasthenia gravis. The pharmaceutical formula usually contains 50 mg to 500 mg , Preferably 100 mg to 200 mg of flupirtine base. Available in tablets, capsules, pills, coated tablets, drug, sound, gum, milk, powder, micropowder, aerosol or liquid dosage forms The form is put into service. The type can be regarded as, for example: oil, alcohol or aqueous solution and suspension and emulsion. The preferred application form is capsule or tablet, which contains 100 mg to 200 mg of flupiridine, or it is a solution containing 0.1 to 10 wt% The single dose of flupirtine can be, for example: a) In the case of oral pharmaceutical dosage forms, it is between 70 mg and 300 mg, preferably 100 mg to 20 mg, b) In the non-menstrual period Intestinal medicine dosage form (for example, intravenous or intramuscular) (please read the precautions on the back before filling out this page). Packed.-Line · -7-201266 A 6 B6 Printed by Beigong Consumer Cooperative, Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention i6) The lower difference Λ is from 8 mg to 80 mg, preferably from 10 mg to 100 mg. _ (In each case, the dose is equivalent to the free base of flupirtine) If possible, the recommended dosage is, for example, 3 times a day, 1 to 2 each time contains 50 to 2 mg of active substance Capsules or tablets. If flupiridine and anti-Bakinson's disease agent are used together in a combination or dosage form, the weight ratio of flupiridine against the anti-Bakinson's disease agent is, for example, 1: 0.01 to 1: 1. In related products, flupirtine and anti-Bakinson's disease agents are therefore present in, for example, such a ratio. Acute toxicity of flupiridine in mice (like expressed in LD50 mg / kg, the method is in accordance with Miller and Tainter ♦ PrOC · S〇C. Exper., Biol.A. Med. 5 7 (1944) 261), in For example, in the case of oral administration, it is 60 mg / kg to 800 mg / kg (or greater than 500 mg / kg). The present invention also, for example, relates to the following method for the production of a drug containing fluoropiperidine as a main active agent. (a)-A method for preparing a medicine that antagonizes muscle tension or a disease or condition where the development of muscle tension is predominant, the special emblem of which is flupiridine or a pharmacologically acceptable class thereof, optionally with anti-Bakinson's disease agents It is formulated with the general pharmaceutical carrier, adjuvant and / or diluent to treat the diseases listed above. (b)-This preparation mainly antagonizes the development of muscle tension or muscle tension. Use of Minpu Dingmu m (CNS) A 4 phase, m〇y297 common alkyne) -8-(please read the precautions on the back before filling this page) 201266 A 6 B6 Ministry of Economic Affairs Printed by the Industrial and Consumer Cooperatives V. Description of the invention (7) The imitation of the medicine for the disease or condition, which is characterized by at least the pharmaceutically acceptable salt of pipidine or flupiridine, optionally with an anti-Bakinson's The disease agent is mixed together and homogenized with a general carrier and / or diluent or adjuvant material at 0 to 120¾ (preferably 20 to 80Ό), and the resulting mixture (which is used to prepare 50 to 500 mg / Each unit of flupiridine or pharmacologically acceptable formula of flupiridine is poured into an empty capsule of suitable size, or compressed into tablets or filled into capsules of suitable size or granulated and then compressed into Tablets or optionally with additional general adjuvant substances are added to the capsule. (c) A method of preparing a medicine that antagonizes muscle tension or a disease or condition where the development of muscle tension is predominant, which is characterized by flupiridine or a pharmacologically acceptable class of flupiridine, optionally with an anti-pakinson Syndrome is mixed with one or more of the following substances: starch, cyclodextrin, urea, cellulose, lactose, formaldehyde-casein, modified starch magnesium stearate, talc, phenoxyethanol, and the resulting mixture is arbitrarily Granulated with an aqueous solution containing at least gelatin, starch, polyvinylpyrrolidone, ethylvinylpyrrolidone ethyl acetate copolymer and / or polygaseous ethylene sorbitan monooleate as ingredients, the granules optionally with one or more of the above The adjuvant materials are granulated together and the mixture is compressed into tablets or filled with gum, and in each case, the pharmaceutical unit of the tablet or capsule contains 50 to 500 mg of the active substance flupiridine or its (please first Read the precautions on the back and fill in this page) Printed by the Employee Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs £ 01C66 A6 _ B6 V. Description of Invention ^ 8) (d)-A preparation that antagonizes the development of muscle tension or muscle tension The method of the medicine for the disease or the disease, which is characterized by the pharmacologically acceptable class of amphetidine or flupiridine, is optionally suspended with a primary anti-Bakinson's disease agent in a melting temperature of 3 1 to 6 5 C In stearin or other mixtures containing fatty acid glycerol and one or more of the following adjunct substances are homogenized together: soybean egg yolk fat, oxynex, phenoxyethanol, and the mixture is poured into an empty capsule or into a capsule, dosage unit Contains 50 to 50 mg of active flupirtine or its salt. (e)-A method of preparing a medicine that antagonizes muscle tension or a disease or condition that is mainly the development of muscle tension, which is to be treated with flupiridine or the pharmacologically acceptable flupiridine, optionally with primary antibody bakin Synergistic and / or emulsified together with at least one of the following substances at a temperature between 20 and 120 1C, and optionally in the presence of one or more emulsifiers and / or compound precursors Glycerin, stone beetle, vaseline Ci2-C25-aliphatic alcohol, Cu-C2. Aliphatic monocarboxylic acid, sorbitan monopalmitate, polyoxyethylene polyol fatty acid ester, mono- or polyvalent low molecular weight aliphatic alcohol, fatty acid glyceride, pan, silicon, polyethylene glycol, dioxide Silicon. (f) A method of preparing a drug (solution) that antagonizes muscle tension or a disease or condition where the development of muscle tension is predominant, and its special emblem lies in flupiridine or the pharmaceutically acceptable salt of flupiridine. Read the precautions on the back and then fill out this page) Outfit · Thread · Too 蚯 疳 iSIII Φ due to national regulations miCNS) A 4 twisted grid (210x297 public repair) -10-201266 A 6 B6 Printed by Beigong Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs Preparation 5. Description of the invention (9) Intentionally and firstly anti-Bakinson's disease agent and optionally dissolved in a physiologically harmless alcohol with a temperature of 30 to 100¾ in the presence of a composite precursor and / or emulsifier, Polyethylene glycol, polyglycol derivatives, dimethyl ink, triglycerides, partial esters of glycerol, pandan or oils or mixtures thereof and the resulting solution is arbitrarily supplemented with the solvents named above so that The final solution, final suspension or final emulsion contains 0.1 to 10% by weight of the active substance flupiridine. The pharmaceutical composition or medicament contains apiridine or a physiologically acceptable substance as an active substance. The active substance is optionally present in the mixture with other pharmacologically or pharmaceutically acceptable active substances. The preparation of drugs is carried out in a general manner, and it is also possible to use general traditional pharmaceutical adjuvants and other general carriers and diluents. Examples of substances that can be considered as carriers and adjuvants are the adjuvant substances used in pharmaceuticals, cosmetics and related fields, which are pushed or described in the following documents *, Lllmanns Encyklopadie der techischen Ch_efflie々, 4 vendors (1953 ), 1 to 39 pages; Journal ot Pharmaceuntical Sciences, 52 distributors (1963), after 9 1 8 pages; HVCzetsch'Lindenwald, 'Hifsstoffe fu r Phermazie und angrenzende Gebiete' '; Pharm · Ind.issue 2 (196 1), after 72 pages; Dr. HP · Fied-ler, ', Lexikon der Hi Ifsstoffe fur Pharmaz ie, Kosmetik und angrenzende Gobiete' 'Cantor KG * Au 1 ~ endorf in Wirt t temberg 19 8 1. Too earthworm is used in the size of kappa kimchi karaoke w (CNS) in the 4 specifications (210x297 male bitch) -11-(please read the precautions on the back before filling out this page) Pack. Order-line-201266 A 6 B6 Printed by the Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (θ Examples in this article are gelatin, natural carbohydrates such as unrefined sugar or lactose, lecithin, pectin, starch (for example, corn starch), and cyclodextrin Refined and cyclodextrin derivatives, polyvinylpyrrolidone, polyvinyl acetate, gelatin, gum arabic, alginic acid, cellulose-based sodium acetate, talc, lycopine, silicone rubber (such as gum), cellulose, cellulose-derived Substances such as cellulose ethers, in which cellulose hydroxyl groups are partially esterified by lower saturated aliphatic alcohols and / or lower saturated aliphatic oxyalcohols, for example methoxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose Element, hydroxypropyl methylcellulose phthalate); 0〃_ (: 22 fatty acids and magnesium, calcium or aluminum fatty acids, especially saturated ones (such as stearic acid), emulsifiers, oils and fats , Don't be vegetable oil (such as peanut oil, sesame oil, olive oil, sesame oil Cottonseed oil, corn oil, wheat gum oil, Xiangyue sunflower oil, cod liver oil, also hydrogenated in each case; saturated fatty acids C2 Η24〇2 to (: ^^ 13 <; 〇2 single, double and Triglycerides and their mixtures, pharmaceutically acceptable mono- or di- or polyhydric alcohols and polyethylene glycols such as polyethylene glycol and its derivatives, aliphatic saturated or unsaturated fatty acids (C 2-C 2 2, especially Cu- u) Esters with mono-aliphatic alcohols (C / -C2.), or esters with polyols such as glycol, glycerol, diethylene glycol, pentaerythritol, sorbitol, mannitol, etc. Etherification, esters of citric acid and primary alcohols, acetic acid, benzoyl benzoate, dioxane, glycerol formaldehyde, tetrahydrofuran alcohol, polyglycol ethers with C, monoCu alcohols, dimethyl ethyl Acetamide, internal amide, lactate, ethyl masterate, silicone (especially polydimethylsiloxane with intermediate viscosity), calcium masterate, sodium masterate, calcium phosphate, phosphoric acid, magnesium phosphate Etc. Other adjuvant materials that can be used are those that help disinfection (the disinfectant that is given is too long. Λ 疳 ιΛϊίΐΦΚΙΜ Zhaijige (210 to 297 public avoidance)-12 -(Please read the precautions on the back before filling in this page) Pack ·-line. 201266 A 6 B6 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention () Such as: cross-linked therapy of vinylpyrrolidone, carboxyl Sodium methyl starch, sodium carboxymethylcellulose or microcrystalline ferricin. Known coating materials can also be used. Examples include acrylic acid and / or methacrylic acid and / or ester polymers And copolymers; copolymers of acrylic acid and methacrylic acid esters with low ammonium content (such as Fudragits Rs), copolymers of acrylic acid and methacrylic acid esters and trimethylammonium methacrylate (such as Fudragits RL); poly Vinyl acetate; Fatty oils, waxes, fatty alcohols; hydroxypropyl methylcellulose phthalate or acetate ester; cellulose-, starch- and polyvinyl acetate phthalate; carboxymethyl cellulose ; Methylcellulose phthalate, monosuccinate, monophthalate succinate and -phthalate acid half ester; zein; ethyl cellulose and succinic acid; schell ac; gluten; Ethyl carboxyethyl cellulose; ethyl acrylate-maleic anhydride copolymer; maleic acid Anhydride-vinyl methyl ether copolymer; styrene-maleic acid copolymer; 2-ethyl-hexyl-acrylate maleic anhydride copolymer; keto acid-vinyl acetate copolymer; glutamic acid / glutamic acid Ester copolymer; carboxymethyl ethyl cellulose glycerol monocaprylate; cellulose acetate succinate; polyarginine. Plasticizers used for coating materials can be considered as: citric acid and tartaric acid ester (ethyl triethyl mono, ethyl tributyl mono, tributyl, -triethyl citrate); Glycerin and glycerides (glycerol diacetate, triacetate, acetylated monoglyceride, castor oil); phthalates (dibutyl mono, dipentyl, diethyl, dimethyl, dipropylene Phthalate), D- (2-methoxy or ethoxyethyl) monophthalate, ethyl phthaloyl, butyl phthaloyl ethyl and butyl glycol ester; alcohols (propylene glycol, Polyethylene glycol with different bond lengths), adipic acid ester (diethyl adipate), diyi (Taiyao Baotang Tang Ji used in the regulation of the housekeeping dimension (CMS) A 4 槻 grid (210x297) f)-13-(Please read the precautions on the back before filling in this page) 201266 A6 __B6___ printed by the Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention (Θ 2—Methyl and Ethyl Adipic Acid Ester); benzophenone; diethyl mono- and dibutyl sebacate, succinate, tartrate, diethylene glycol dibutyrate; tributyl phosphate, tributyrin; polyethylene Sorbitol Monooleate (polysorbates such as polysorbates 80); sorbitan monooleate. For the production of solutions or suspensions, it is possible to use, for example, water or physiologically acceptable organic solvents such as, for example, ethanol, propyl ether, isobutanol, 1,2-propanediol, polydiol and derivatives thereof, dimethyl Inkstones, fatty alcohols, triglycerides, partial esters of glycerin, stone pan, etc. For injection solutions or suspensions, it is possible to use, for example, non-toxic parenterally acceptable diluents or solvents such as, for example, water, 1,3-butanediol, ethylene glycol, 1,2-propanediol, and more Mixtures of glycols in water, Ringer &lt; s solutions, isotonic solutions or solidified oils include synthetic mono- or diglycerides or fatty acids such as oleic acid. When manufacturing the formulation, it is possible to use, for example, known general solubilizers or emulsifiers. The solubilizers and emulsifiers that can be used are, for example: polyvinyl pyrrole, sorbitan fatty acid esters such as sorbitan oleate, phosphorus esters such as lecithin, acacia gum, xanthan gum, poly Gas ethylated sorbitan monooleate and other ethyl gasified fatty acid esters or sorbitan, polyoxyethylated fats, poly gas ethylated oleic triglyceride, sub Oleated triglycerides of oleic acid, concentrated products of fatty alcohol polygasified ethylene, alkylphenols or fatty acids or 1-methyl-2- (2-hydroxyethyl-imidazolidone- (2). In this case, Poly-gas ethylation means that the substance concerned contains poly-gas ethyl chains, and the degree of polymerization is usually between 2 and 40, especially 10 to Tai Guihuo. Regulations (210x297 public +; »·)-14-(please read the notes on the back before filling in this page) 201266 A6 B6 Printed by the Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economy V. Invention Instructions (1: ^ 2 Between 0. Polyoxyethylated substances of this kind may include, for example, hydroxyl-containing compounds (for example, mono- or diglycerides or not And compounds such as those containing oleic acid residues) and gasified ethylene (for example, 40 moles of gasified ethylene per mole of glyceride). Examples of oleic acid triglycerides are olive oil, peanut oil, sesame oil, Sesame oil, cottonseed oil, corn oil, see also Dr. HPFiedler * Lex ikon de r Hi Ifsstoffe fur Pharmazie, Kosmetik und angrenzende Gebiete &quot; 1 9 7 1, 1 9 1 — 1 9 5 pages. In addition, it may be added Preservatives, stabilizers, buffer substances such as calcium hydrogen phosphate, gelled aluminum hydroxide, flavoring substances, sweeteners, pigments, anti-gasification agents and compound precursors such as ethylenediaminetetraacetic acid), etc. It is possible to arbitrarily use physiologically acceptable acids or buffers to adjust the pH to about 3 to 7 to stabilize the molecule of the active substance. Generally, a neutral to weakly acidic pH value (minimum about PH5) is preferred. For the preparation of formulations for transdermal administration, the above-mentioned substances and dispersible or liquid hydrocarbons such as petroleum jelly or scorpion or squalene hydrocarbons and polyethylene gums, plant or animal tissue fats and oils (which may also be partially hydrogenated) may be used ), Or artificial fats such as glycerol esters of Ce _C〃 fatty acids, as well as beetle, cetyl alcohol hexadecanoate, lanolin, lanolin alcohol; fatty alcohols such as cetyl alcohol, stearyl alcohol, molecular weight 200 to 20,000 Of polyethylene glycol; liquid flats such as isopropyl myristate, isopropyl stearate, ethyl oleate; emulsifiers and sodium, potassium, and ammonium stearate or hexadecanoic acid and Triethanolamine stearic acid too twisted m (CNS) flat 4 down grid (210x297 public repair) 15-(please read the precautions on the back and then fill in this page) f Pack. Order · Thread. 201266 A 6 B6 Central Ministry of Economic Affairs The Bureau of Standards and Technology ’s consumer cooperation du prints 5. Description of the invention (esters, oleic acid, aluminum bases, sulfurized fatty alcohols such as sodium lauryl sulfate, ethyl sodium sulfate, sodium stearate sulfate, 掊 酸Of the class, sterols such as cholesterol, and some fatty acid esters of polyvalent alcohols such as ethylene glycol mono-hard Ester, glycerol monostearate, pentaerythritol monostearate, partial fatty acid ester of sorbitan, partial fatty acid ester of polyoxyethylene sorbitan, polyoxyethylene sorbitan ether, polyoxyethylene Fatty acid esters of ethylene, fatty alcohol ethers of polyoxyethylene, fatty acid esters of sucrose, fatty acid esters of polyglycerol, lecithin. Antioxidants that can be considered are, for example, sodium metabisulfate, ascorbic acid, citric acid, Acid esters, butyl hydroxyanisole, ortho-dihydroguaiic acid, tocopherol, and tocopherol deco-synergist (those that bind heavy metals through the formation of complexes, such as lecithin, ascorbic acid, basal acid). The addition of it actually enhances the anti-gasification effect of tocopherol. Corcoline ’s preservatives are, for example, sorbic acid, parabens (such as lower esters), benzoic acid, sodium benzoate, trichloroisobutyl Alcohols, phenols, isophthalic acid, benzethonium gas and methylxer derivatives. The pharmacy and smelting treatment of the compounds of the present invention can be carried out according to the general standard methods. For example, the active substances and adjuvants and / or carrier substances are stirred Or homogenization (for example, using a general mixing device) and full mixing, this work is usually from 20 to 80 t :, preferably 20 to 50 Ό, especially at room temperature. In this regard, can Refer to the following standard writings: Sucker, Fuchs, Speiser, Pharmazeutische Technologie &quot; Vendor: Thieme-V er 1 ag S tu 11 gart, 1 9 7 8 〇 Can be applied to skin or mucous membranes or into the body, For example, mouth, intestine, and lung guinea in "囲 宅; sample miCNS) A 4 specifications (210x297 gong) -16-(please read the precautions on the back before writing this page) 201266 A 6 B6 Ministry of Economic Affairs Printed by the Central Bureau of Standards ’Staff Consumer Cooperative V. Invention Statement_ 明 （i 与 的 ， ί # 的 ， έ 的, vaginal, lingual, intravenous, intraarterial, intracardiac, intramuscular, intraperitoneal , Intradermal or subcutaneous. The parenteral dosage form of the preparation is particularly a sterile or sterilized preparation. Example: Ingot: In a general way, 1◦kg 2-amino-1-3-ethoxymethanamide-6- (4--gas amide) -Bit maleic acid vinegar and 2.5 kg of basic acid hydrogen Calcium is mixed with 2.5 kg of corn starch, and the mixture is granulated with 1 kg of polyvinylpyridine in 4 kg of demineralized water. After adding 1.3 kg of corn starch, 2 kg of crystalline cellulose, 0.6 kg of magnesium stearate and 0.1 kg of highly dispersed gasified silicon, the ingot is pressed to weigh 2 mg, 9 mm in diameter, and curvature It has a radius of 10 mm and is marked with a score. The bursting strength of the ingot is from 80 Newtons to 100 Newtons (Schleuniger bursting strength tester). The degradation time according to DAB8 is 5 minutes. Each capsule contains 100 mg of active substance. Capsules: Filled capsules are prepared in a manner similar to the above-mentioned method of preparing tablets, which are filled into hard gelatin capsules of suitable size. Filling volume per capsule: 200 mg. Each capsule contains 100 mg of active substance. Contains 15% flupiridine maleate. (Please read the precautions on the back before writing this page) f Pack · Order * Line-Tai K 埯 iA ffl Φ Κ Μ It 掸 m (CNS) Ψ4 specifications (210x297 male acetylene) -17-201266 A6 B6 Ministry of Economic Affairs Printed by the Beigong Consumer Cooperative of the Central Bureau of Standards V. Description of the invention (The following substance No. 1 is evenly suspended in 400 g of long-chain triglycerides (named by the merchant: Miglylol8 1 2 / Hiils Troisdort &quot;: 32.5 Gram high dispersion. Indefinite, hydrophobic digasification silicon (trade name: Aerosil R 972 / Degussa), 0.5 grams of dequantified sodium saccharin, 1.5 grams of finely ground sodium cyclohexane sulfonate, 0.1 Grams of vaporized iron, red 0.5 grams of strawberry flavor, 75 grams of flupiridine maleate and 0.3 7 5 grams of Oxynex LM (E. Merck / Darmstadt) suspension supplemented with medium- and long-chain triglycerides 500 grams and mix. One gram of suspension contains 150 mg of flupiridine. Injection solution This manufacturing method is like the batch method applied in 20 liters (= 6500 ampoules) 1. 1 liter of water is heated to 7〇t: and the solution was added 156.2 g glucono S lactone, and allowed to stand at 70 C for 1 hour, in this procedure, the solution was applied with nitrogen. 2. Molecule The amount is 380 to 420 to 8000. ◦g of polyethylene glycol is measured into solution 1 and the solution is heated to 70 t and filled with nitrogen. 3. 30. 0 g of sodium bisulfite is dissolved in 500. 0 ml The water was filled with nitrogen. 4. Solution 3 was added to solution 2. 5. 666.6 g of flupiridine was screened through a sieve with a mesh size of 0.3 mm and dissolved in solution 4 accompanied by Strong nitrogen filling. (Please read the precautions on the back before filling the nest page) -install- line- too board? / IiA use ΨΜΚΙ house i «m (CNS) A 4 specifications ί210χ297 public bitch) -18-Economy The Ministry of Central Standards Administration of Beigong Xiaozhi cooperated to print and print the r6 201266. Amendment 81 · 1. -7 This month, the waiver V. Invention description (1 force 6. Solution 5 is cooled and filled with nitrogen-filled water to 20 liters. 7. Solution 6 was sterilized and filtered through a membrane filter paper with a pore size of 0.2 wm with glass fiber pre-filter paper. 8. Inspection during processing: the oxygen content of solution 7 was measured using an oxygen electrode, and the pH of solution 7 was measured. 9. The solution is filled into a colorless 3 ml ampoule under sterile and nitrogen gas filling conditions, one ampoule containing 164.5 mg of flupiridine gluconate dissolved in 3 ml . J In summary, the present invention relates to hinder: the use of a pharmaceutical disease or condition 1. fluoro pyridine or a pharmaceutically match therapeutically antagonist in the manufacture of Salt on the development of muscle tension or muscle tension of the. 2. A method for preparing a medicine that antagonizes the development of muscle tension or a disease or condition that is predominantly of muscle tension, the special emblem of which is flupiridine or its therapeutically acceptable class, optionally with anti-Bakinson's disease agents With general pharmaceutical carriers, adjuvants and / or diluents are formulated as drugs for the treatment of the diseases listed above.-A method of preparing drugs that antagonize the development of muscle tension or muscle tension. / Disease $ disease , The special emblem of which is at least flupiridine or pharmacologically acceptable flupirtine, arbitrarily mixed with an anti-Bakinson's disease agent and respectively with a general carrier and / or diluent or adjuvant substance: ! 0 to 丨 20t! (Preferably 20 to 8¾) under homogenization, and the resulting mixture (who is used to prepare 50 to 500 mg / each unit of flupiride; · or flupiridine pharmaceutical Acceptable formulas) are poured into an empty capsule of suitable size, or pressed into ingots or filled into a capsule of suitable size or made into granules. The paper is Λ-scale. 4 specifications (210X297 g *) (please read the precautions before writing this page)-installed. -Line &lt; -19-

Amendment 8ί. I.-7 This month B 201266 1 brother free Λ6_ V. Description of the invention (1¾ and then pressed into tablets or optionally added with additional general auxiliary substances into the capsule. 4. A preparation to antagonize muscle tension or muscle tension The method of developing a drug for the main disease or condition is characterized by flupiridine or the pharmaceutically acceptable class of flupiridine, optionally mixed with an anti-Bakinson's agent and one or more of the following substances: starch , Cyclodextrin, urea, cellulose, lactose, formaldehyde-casein, modified starch, magnesium stearate, talc, phenoxyethanol, the resulting mixture is optionally mixed with at least gelatin, starch, polyvinylpyrrole _ , Ethyl pyrrolidone ethyl acetate copolymer and / or polyoxyethylene sorbitan monooleate as an ingredient in an aqueous solution granulated together, the granules are optionally granulated together with one or more of the above-mentioned auxiliary substances and this mixture is Compressed tablets or capsules, and in each case, the pharmaceutical unit of the tablets or capsules contains 5 ◦ to 50 ◦ mg of the active substance flupiridine or its substrate. Beige Consumer Cooperation of the Central Standards Bureau of the Ministry of Economic Affairs Printed (please read the precautions before filling in this page) 5.-A method of preparing a medicine that antagonizes muscle tension or the development of diseases or conditions that are mainly muscle tension, its specialty is flupiridine or flupiridine The pharmacologically acceptable compounds of pyridine, optionally with primary anti-Bakinson's disease agents, are suspended in molten stearin or other mixtures containing fatty acid glycerol at a temperature between 3 1 and 6 5 t: 1 or more of the following The adjuvant substances are homogenized together: soybean egg dish fat, oxynex, benzene gas ethanol, and then the mixture is poured into empty capsules or filled into capsules, the dosage unit contains 50 to 500 mg of active flupiride or its wall. 6 -A method of preparing a medicine that antagonizes muscle tension or the development of muscle tension-based diseases and diseases, whose treatment lies in the pharmacologically acceptable range of flupiridine or apipicidine, and arbitrarily anti-Bakinsheng Disease agent, at a temperature ranging from 20 to 120 t :, and arbitrarily used in one or more emulsifiers and the size of this paper. Chinese National Standard (CNS) A 4 specifications (210x29 '丨 public address)- 20-Printed by Beigong Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs Positive SI. 1 · -7 This month is 201266 Replenishment __ Λβ _______13_6 V. Description of the invention (19) In the presence of a compound precursor, homogenize and / or emulsify with at least one of the following substances: water, glycerin , Shi Pan, Vaseline, C, 2-C23 mono-aliphatic alcohol C 〃- C2. Aliphatic monocarboxylic acid, sorbitan monobranched acid ester • Polygasified ethylene polyol fatty acid ester, single or multivalent Low-molecular-weight aliphatic alcohols, glycerides of pickled fatty acids, pan, silicon, polyethylene glycol, silicon dioxide. 7.-a method of preparing medicines that antagonize muscle tension or diseases or conditions that are mainly the development of muscle tension, Its speciality lies in the pharmacologically acceptable salt of flupiridine or flupiridine, arbitrarily and primary anti-Bakinson's disease agent and optionally dissolved in the temperature between 30 in the presence of compound precursors and / or emulsifiers Water to 1001C physiologically harmless alcohols, polyglycols, polyglycol derivatives, dimethylstone, triglycerides, partial esters of glycerin, panax or oils or mixtures thereof and the resulting solution Be arbitrarily supplemented with the solvent named above so that the final solution, the final suspension The final solution or emulsion containing the active substance to a square-fluoro-piperidin 10wt% of the horses. (Please read the notes on the back # fill in this page first) ί Packing--order. Thread · This paper "standard use of Chinese national standards (CHS> T4 specifications (210 father 297 public solution) -21-

Claims (1)

Handle Factory Charge 1 ^ 801053955 Tiger Patent Shen Lujian Chinese Supplementary Enzyme Test In January, 1981, Kou Yuegen was administered to the rat to try the ihx for diacid, and the results are as follows: ^ cm | Q_S_IQ__P-0 _mg / kg weight 〇19.9 ± 0.5% 38.2 ± 0.5% 56.7 soil 0.5% muscle tightness 3R ^ S: P humble at the same time and calculate its E Dso value is 1 6 soil 1 mg, E Dso said Make the skeletal muscle tight, the lower the degree P, the lower the initial value is 50% #, and the test of the control group is listed in the table. I amended g2 丨 q 丨 Sister 2 cited 1 /, OX .. 1 · ζβ Supplement 6 of this year, the patent application group Annex A A: A7 B7 C7 D7 No. 80105395 Patent application case Chinese application patent range Amendment January 82 of the Republic of China Amendment 1. A pharmaceutical composition used to antagonize muscle tension, which commonly contains flupiridine (£ 1111 ^ 1 ^ 11 ^) or its therapeutically acceptable compound as an active substance and contains Generally a pharmaceutically acceptable carrier, adjuvant and / or diluent. 2. A medicinal composition for antagonizing muscle tension, the medicinal composition comprising (weight ratio): 88: 1 2 to 78: 22 flupirtine (flupirtine): (—) 一 Ν, α — 二Methyl-N — 2-propynylphenethylamine, or 99.5: 0.5 to 93: 7 of flupiridine: α—5—original ice olefin—2-yl—α—phenyl—1 Pyridine propanol, or flupiridine from 55: 45 to 45: 55: L-dopa (d〇Pa) 0 Please read the precautions on the back before filling in. • This page is bound by the Central Ministry of Economic Affairs. M, Pui The paper size printed by the Industrial and Consumer Cooperative Society uses the Chinese National Standard (CNS) A4 specification (210 X 297 mm) -1 _ 81.9.10,000