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WO2016068607A1 - Composition antitussive et expectorante contenant, en tant que principe actif, un extrait de mélange de rhizoma coptidis et de pelargonium sidoides - Google Patents

Composition antitussive et expectorante contenant, en tant que principe actif, un extrait de mélange de rhizoma coptidis et de pelargonium sidoides Download PDF

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Publication number
WO2016068607A1
WO2016068607A1 PCT/KR2015/011468 KR2015011468W WO2016068607A1 WO 2016068607 A1 WO2016068607 A1 WO 2016068607A1 KR 2015011468 W KR2015011468 W KR 2015011468W WO 2016068607 A1 WO2016068607 A1 WO 2016068607A1
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Prior art keywords
extract
pelargonium sidoides
pharmaceutical composition
pelargonium
sulfur
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PCT/KR2015/011468
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English (en)
Korean (ko)
Inventor
최연웅
민병구
하대철
조상민
송희용
박희찬
기도형
정원태
남규열
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Korea United Pharm Inc
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Korea United Pharm Inc
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Publication of WO2016068607A1 publication Critical patent/WO2016068607A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A61K36/718—Coptis (goldthread)

Definitions

  • the present invention relates to the use of Coptidis rhizome and Pelargonium Sidoides mixed extracts as antitussive or expectorant and for the prevention or treatment of respiratory diseases or airway infections.
  • Coughing is one of our body's most important defensive actions, preventing harmful substances such as bacteria and other substances from entering our airways.
  • Cough is the most common symptom of respiratory illness, and if excessive, reduces and worsens the patient's quality of life. Therefore, cough suppression treatment is needed to reduce cough.
  • Sputum is a mucous substance secreted from the respiratory tract and is an element of the defense mechanism that protects the airway epithelium and removes external aspirants.
  • sputum is not conscious, but it is continuously produced and processed through the larynx and swallowed by the gastrointestinal tract.However, if secretion and discharge increase due to lung disease, sputum is retained in the airways, which can cause symptoms such as coughing and shortness of breath. . Therefore, there has been a need for the development of therapeutic agents that can effectively ameliorate such cough or sputum.
  • Coptidis rhizome is an evergreen perennial plant of the dicotyledonous plant, the herbaceous perennial herbaceous plant, also known as the honeysuckle . It is known to be distributed in Korea, Japan, and China, and its name comes from the yellow color of the stem and the stem of the ground. These yellow lotuses have long been known to have efficacy in tonic, arteriosclerosis, disease weakness or stroke. Also, Pelargonium Sidoides is a plant native to the highlands of the inland and coastal areas of South Africa, and is known to be effective for acute bronchitis, sore throat and colds (Planta Medica 2008 74: 6 (661-666). )), Currently sold as umkaron syrup. However, there is no known example of using the Pelargonium sidoides and the yellow lotus together for Jinhae expectorant.
  • the present inventors have made intensive efforts to develop a drug having an antitussive expectorant effect, and therefore, when using a mixed extract of rhubarb and pelargonium sidoides, the present inventors compared to the antitussive expectorant as compared to the rhubarb extract and the pelargonium sidoides extract alone. It was confirmed that it shows a synergistic effect, and through this it was confirmed that the mixed herbal extracts of the barberry and pelargonium sidoides can be usefully used as a prophylactic or therapeutic agent for antitussives or respiratory diseases, and completed the present invention.
  • One object of the present invention is to provide a pharmaceutical composition for antitussive or expectorant, comprising a Coptidis rhizome and Pelargonium Sidoides mixed extract as an active ingredient.
  • Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of respiratory diseases, comprising a mixture of rhubarb and pelargonium sidoides as an active ingredient.
  • Still another object of the present invention is to provide a pharmaceutical composition for preventing or treating respiratory tract infections, which comprises a mixture of rhubarb and pelargonium sidoides as an active ingredient.
  • Still another object of the present invention is to provide a tablet for oral administration comprising the composition.
  • Another object of the present invention to provide a liquid formulation for oral administration comprising the composition.
  • Still another object of the present invention comprises a mixture of rhubarb and pelargonium sidoides as an active ingredient, for Jinhae or expectorant; Or to provide a health functional food for preventing or improving respiratory diseases or airway infections.
  • Still another object of the present invention is to provide a method for treating a respiratory disease or airway infection, comprising administering a mixture of barberry and pelargonium sidoides to an individual suspected of respiratory disease or airway infection.
  • Coptidis rhizome and Pelargonium sidoides Sidoides Provides a pharmaceutical composition for antitussive or expectorant, comprising a mixed extract as an active ingredient.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of respiratory diseases, comprising as an active ingredient extracts of sulfur and pelargonium sidoides.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of respiratory tract infection, comprising a mixture of sulfur and pelargonium sidoides as an active ingredient.
  • the present invention provides a tablet for oral administration comprising the composition.
  • the present invention provides a liquid formulation for oral administration comprising the composition.
  • the present invention comprises a rye and pelargonium sidoides mixed extract as an active ingredient, for Jinhae or expectorant; Or it provides a health functional food for preventing or improving respiratory diseases or airway infections.
  • the present invention provides a method of treating a respiratory disease or airway infection, comprising administering a mixture of the barberry and pelargonium sidoides to a suspected respiratory disease or airway infection.
  • the present invention provides a method for alleviating cough or sputum, comprising administering a mixture of sulfur and pelargonium sidoides to a subject.
  • composition comprising the mixed herbal extract of the barberry and pelargonium sidoides of the present invention in a predetermined ratio is superior to the antitussive expectorant in comparison with the same dose of the barberry and pelargonium sidoides extract, which have fewer side effects as a natural product. Since it shows a synergistic effect, it can be usefully used as an antitussive expectorant or a therapeutic agent for respiratory diseases.
  • 1 is a diagram showing the sputum excretion of the dosage of the extract of the barberry or Pelargonium sidoides alone and 1: 1 mixture thereof.
  • A represents the rhubarb extract
  • B represents the Pelargonium sidoides extract
  • a + B represents the 1: 1 mixture thereof.
  • Staging numbers are the total dose (mg / kg) calculated based on the dry matter of the 1: 1 mixed extract.
  • Figure 2 is a diagram showing the sputum discharge capacity according to the mixing ratio of the rhubarb and pelargonium sidoides extract when the total dose is fixed to 200 mg / kg.
  • A represents the rhubarb extract
  • B represents the Pelargonium sidoides extract
  • the number is the dosage of each extract calculated based on the dry matter.
  • the present invention is Coptidis rhizome and Pelargonium sidoides Sidoides ) Provides a pharmaceutical composition for antitussive or expectorant, comprising a mixed extract as an active ingredient.
  • Coptidis rhizome refers to Ranuculaceae. A plant belonging to a family).
  • the nasturtium is specifically known as Coffis chinensis Franch, Coptis del Toides ( Coptis). dltoides ), Coptis japonica or dried rhizome of other species of the same species, including berberine.
  • the yellow lotus used in the composition of the present invention may be purchased commercially, or may be used collected or cultivated in nature.
  • the pelargonium sidoides Is a plant having an antitussive or expectorant effect, and its extract may be used in a composition for antitussive or expectorant
  • the pelargonium sidoides may be purchased commercially, collected from nature, or may be used. There is no limitation to this, and flowers, seeds, stems, roots or outposts may be used as raw materials.
  • the composition of the present invention comprising a mixed herbal extract of rhubarb and pelargonium sidoides can be usefully used as an antitussive or expectorant.
  • the term "mixed extract” refers to a form of an extract obtained by mixing natural products and then extracting with one or more solvents, or a mixture of extracts obtained by extracting each natural product with a solvent.
  • the mixed extract may be a mixture including rhubarb and pelargonium sidoides as an extraction solvent, or a mixture of the rhubarb extract and pelargonium sidoides extract may be mixed with each other.
  • the mixed extract includes all of the crude extract or a specific solvent soluble extract (fraction) form, may be an extract extracted using an extraction method such as hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction, and further The resultant was filtered under reduced pressure, and the filtrate was concentrated under reduced pressure to obtain an extract available in water, alcohol or a mixed solvent thereof, but the present invention is not limited thereto, and the extract, the dilution or concentrate of the extract, and the extract are dried. It includes all the dried products obtained, or these modifiers or purified products.
  • the solvent used in the preparation of the mixed extract may be water, various alcohols, or a mixture thereof.
  • the alcohol may be a linear or branched alcohol having 1 (C 1 ) to 4 (C 4 ) carbon atoms, preferably methanol, ethanol or butanol, or a mixed solvent thereof, but is not limited thereto.
  • the extraction method may be a solvent extraction, hot water extraction, cold needle extraction, reflux cooling extraction, ultrasonic extraction, or steam extraction, but is not limited thereto.
  • the extracts include, without limitation, extracts, fractions of the extracts, all of the crude or purified thereof.
  • the extract, fractions of the extract, the crude or purified product thereof may be used as it is in the form of a liquid, or concentrated and / or dried it.
  • concentration and / or drying methods include, but are not limited to, methods such as freeze drying, vacuum drying, hot air drying, spray drying, reduced pressure drying, foam drying, high frequency drying, infrared drying, and the like.
  • the term "naphtha extract” refers to an extract obtained by extracting the yellow lotus.
  • the yellow lotus may specifically be a root portion of the yellow lotus.
  • the sulfur extract is obtained by extracting pulverulent pulverized with water, alcohols of various carbon atoms, such as linear or branched alcohols having 1 (C 1 ) to 4 (C 4 ) carbon atoms, or a mixed solvent thereof as an extraction solvent. It may be, but is not limited thereto.
  • the alcohol is preferably ethanol, methanol or butanol, but is not limited thereto.
  • the yellow lotus extract may be a water extract, specifically, a hydrothermal extract, which may be used in the form of a dried product, but is not limited thereto.
  • the term "pelargonium sidoides extract” means an extract obtained by extracting the pelargonium sidoides.
  • the pelargonium sidoides extract extracts pelargonium sidoides pulverized water, alcohols having various carbon atoms, such as linear or branched alcohols having 1 (C 1 ) to 4 (C 4 ) carbon atoms, or a mixed solvent thereof. It may be obtained by extraction using a solvent. It may be in the form of a mixture of other solvents such as glycerol, such as pelargonium sidoides 11% ethanol extract (1 ⁇ 8 ⁇ 10) and glycerol (8: 2) mixture (w: w).
  • the Pelargonium sidoides extract may be a Pelargonium sidoides 11% ethanol extract (1 ⁇ 8 ⁇ 10) glycerol (8: 2) mixture (w: w) or the ethanol extract of Pelargonium sidoides have.
  • the extract may be dried to be used in the form of a dried product, but is not limited thereto.
  • the extract may be included in 0.001 to 50% by weight, more preferably 0.01 to 10% by weight relative to the total weight of the pharmaceutical composition.
  • sputum in the present invention refers to the release of sputum, which includes alleviating, ameliorating or treating the retention of mucus in the airways.
  • the expectorant acts to remove the sputum in the airway, such as the peripheral airway, into the central airway to remove it by coughing, and / or to increase mucus secretion to induce coughing, and / or to dissolve mucus.
  • the concept includes both reducing the viscosity to facilitate sputum discharge.
  • the expectorant activity was confirmed by administering the composition according to the present invention to mice and measuring sputum excretion using a phenol red solution, and according to the specific dosage and / or the mixing ratio of the total extract dose and / or dosage of the mixed extract, It was confirmed that the synergistic expectorant activity was significantly increased compared to using the same extract alone in the same ratio (Fig. 1 and 2).
  • the present invention provides a pharmaceutical composition for the prevention or treatment of respiratory diseases, comprising as an active ingredient extracts of sulfur and pelargonium sidoides.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of respiratory tract infection, comprising a mixture of sulfur and pelargonium sidoides as an active ingredient.
  • the sulfur, pelargonium sidoides, mixed extract and the pharmaceutical composition are as described above.
  • the term "respiratory disease” refers to a disease accompanied by symptoms such as coughing, bronchial spasms, dyspnea, or sputum, for example, emphysema accompanied by bronchitis, asthma, whooping cough, pneumonia, cough, or sputum. Colds, flu, and the like, but are not limited thereto.
  • berberine the main component of the sulfur extract, has an effect such as bronchial dilation, which can prevent or treat respiratory diseases.
  • the composition of the present invention since the composition of the present invention has an antitussive or expectorant effect, it can alleviate symptoms such as cough and sputum, and thus can be usefully used for the prevention or treatment of respiratory diseases involving these symptoms.
  • airway infection refers to a phenomenon in which a mucosa of the nose or pharynx of an individual who inhales pathogens scattered in the air mixed with saliva or sputum when another person coughs, sneezes, or talks is infected.
  • Non-limiting examples can include upper or lower respiratory tract infections such as acute or chronic rhinitis, sinusitis, sore throat, otitis media and bronchitis.
  • the pharmaceutical composition of the present invention includes the Pelargonium sidoides extract, the composition of the present invention containing it as an active ingredient can be used for the prevention or treatment of airway infection.
  • prevention refers to any action that inhibits or delays the development of a respiratory disease or airway infection by administration of the pharmaceutical composition
  • treatment refers to a respiratory disease or airway infection by administration of the composition. This means any action that improves or beneficially alters the symptoms of a suspicious or diseased individual.
  • prevention may be any action that inhibits or delays the storage of sputum in the airways by inhibiting cough, which is a representative symptom of respiratory disease, or by increasing sputum discharge, by administering the pharmaceutical composition
  • the treatment may be Administration of an antimicrobial composition may mean any action that improves or benefits from cough or sputum retention.
  • the mixture of the rhubarb extract and the Pelargonium sidoides extract showed a synergistic effect on the sputum discharge capacity than when using each of the rhubarb extract or Pelargonium sidoides extract alone.
  • the amount of the total mixture is determined by the weight ratio of the extracts administered alone and in the 1: 1 weight ratio of the Lactobacillus extract and Pelargonium sidoides extract.
  • the content ratio of the rhubarb extract and pelargonium sidoides in the mixed extract is not particularly limited thereto, but is not particularly limited to 1: 0.3 to 5 (based on the dry weight, the rhubarb extract weight: the pelargonium sidoides extract weight), or 1 : 0.5 to 3 may be.
  • the sulfur extract may include berberine or a pharmaceutically acceptable salt thereof.
  • the pharmaceutically acceptable salt of berberine may be berberine chloride, but is not limited thereto.
  • the sulfur extract may contain 1 to 30% by weight of berberine or a pharmaceutically acceptable salt thereof based on the dry matter. Preferably it may include 1.26 to 30% by weight, or 2 to 25% by weight, but is not limited thereto.
  • the pelargonium sidoides extract may include a phenolic compound including catechin or a pharmaceutically acceptable salt thereof.
  • the phenolic compound or a pharmaceutically acceptable salt thereof may include 25 to 45% by weight based on the dry matter of the Pelargonium sidoides extract.
  • the phenolic compound including catechin or a pharmaceutically acceptable salt thereof may include 30 to 40% by weight, but is not limited thereto.
  • Phenolic compounds including berberine and pelargonium sidoides extract contained in the sulfur extract may be present in the form of pharmaceutically acceptable salts.
  • salts are acid salts formed with pharmaceutically acceptable free acids.
  • pharmaceutically acceptable salt of the present invention is a concentration that has a relatively nontoxic and harmless effective action in a patient, and the side effects caused by this salt do not reduce the beneficial efficacy of phenolic compounds including berberine and / or catechin. Any organic or inorganic addition salt of any of the above compounds is meant.
  • Acid addition salts are prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equivalent molar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
  • a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile.
  • Equivalent molar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
  • organic acids and inorganic acids may be used as the free acid
  • hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. may be used as the inorganic acid
  • methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, and maleic acid may be used as the organic acid.
  • maleic acid succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid (gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid, etc. It is not limited to these.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • Alkali metal salts or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate.
  • the metal salt it is particularly suitable to prepare sodium, potassium, or calcium salt, but is not limited thereto.
  • Corresponding silver salts can also be obtained by reacting an alkali or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).
  • Pharmaceutically acceptable salts of the compounds of this invention include salts of acidic or basic groups which may be present in the phenolic compounds including berberine and / or catechin, unless otherwise indicated.
  • pharmaceutically acceptable salts may include sodium, calcium and potassium salts of the hydroxy group
  • other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate , Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts, and the like. It can be prepared through the method.
  • the pharmaceutical composition of the present invention may comprise 100 to 380 mg / kg, more preferably 150 to 300 mg / kg, based on the daily dose of the mixture of sulfur and pelargonium sidoides
  • the expectorant activity also increased up to a certain level as the dosage was increased, but when the dose was increased above a certain level, the expectorant activity was significantly decreased.
  • Table 4 when the pelargonium sidoides extract alone administration of 100 mpk and 200 mpk sputum discharge capacity is improved according to the dose, but when administered at 400 mpk it can be seen that significantly reduced there was.
  • the composition may be administered once a day or may be dividedly administered several times.
  • the composition may be administered three times a day, but is not limited thereto.
  • the dose per dose (dose) in the case of a liquid formulation is preferably 4 to 20 ml for convenience, but is not limited thereto.
  • composition of the present invention may further include a pharmaceutically acceptable diluent, excipient or carrier.
  • compositions comprising a pharmaceutically acceptable carrier may be in various oral or parenteral formulations.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may comprise at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin.
  • lubricants such as magnesium stearate, talc and the like are also used.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and the suspension solvent propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used.
  • the carrier may include a non-naturally occuring carrier.
  • the pharmaceutical composition may be administered in a pharmaceutically effective amount.
  • the term "administration" refers to introducing the pharmaceutical composition of the present invention to an individual in any suitable manner, and the route of administration of the composition may be various oral or nasal oral routes as long as the target tissue can be reached. And may be administered in a conventional manner, specifically via the oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, nasal, inhaled or intradermal routes.
  • the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level is defined as the type and severity, age, sex, Activity, sensitivity to drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts.
  • the compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art.
  • the composition may be administered to a variety of mammals, such as rats, livestock, humans, etc. by various routes.
  • a hot water extract and a dried product thereof were prepared as a representative yellow lotus extract (Example 1), and an ethanol extract of pelargonium sidoides as a representative pelargonium sidoides extract was obtained to obtain a glycerin mixed solution ( 8: 2) and in the form of dry matter (Example 2). Then, a mixture of the above-prepared rhubarb extract and pelargonium sidoides extract was prepared at various doses and / or mixing ratios to confirm the effect.
  • the pharmaceutical composition of the present invention exhibits an antihistamine effect.
  • H1 receptor blockade prevents endogenous histamine-mediated inflammatory reactions and bronchial smooth muscle contraction, thereby reducing capillary permeability, reducing edema, redness, pruritus, and suppressing bronchial spasms, resulting in mumps, rhinitis, conjunctivitis, pruritus. It can also be effective in the treatment of diseases such as asthma.
  • the present invention provides a tablet for oral administration comprising the pharmaceutical composition.
  • the present invention provides a liquid formulation for oral administration comprising the pharmaceutical composition.
  • tablette refers to a form of a medicine prepared by compressing a medicine into a certain shape as a kind of solid preparation, which is a dosage form having a certain shape.
  • the tablet may further include an excipient, a binder, a disintegrant, a lubricant, etc. in addition to the active ingredient.
  • the excipient serves to increase the volume to make a tablet of the desired size is not limited if the pharmaceutically acceptable type, and examples thereof include lactose, starch, white sugar, mannitol, sorbitol, microcrystalline cellulose and the like. . It may preferably be a lactose monohydrate, microcrystalline cellulose or a mixture thereof.
  • the binder serves to increase the adhesion between the particles to facilitate granulation and to maintain the physical form of the final molding, and the binder is not limited if it is pharmaceutically acceptable, and includes white sugar, glucose, starch, gelatin, and shamen rubber, povidone, etc. are mentioned. Preferably povidone.
  • the disintegrant absorbs moisture when the solid preparation is taken and promotes disintegration of the solid preparation into small particles, and the disintegrant is not limited if the pharmaceutically acceptable, crystal cellulose, starch, croscarmellose Sodium ossium and the like. Preferably may be croscarmellose sodium.
  • the lubricant is to facilitate the compression and release of the solid preparation prepared by improving the fluidity of the tablets to reduce the friction between the tablets and the tableting period, if the pharmaceutically acceptable is not limited, stearic acid, stearates And talc, carnauba wax, sodium stearyl fumarate, colloidal silicon oxide, magnesium silicate and the like.
  • the pharmaceutically acceptable is not limited, stearic acid, stearates And talc, carnauba wax, sodium stearyl fumarate, colloidal silicon oxide, magnesium silicate and the like.
  • sodium stearyl fumarate, colloidal silicon oxide, or mixtures thereof Preferably sodium stearyl fumarate, colloidal silicon oxide, or mixtures thereof.
  • liquid formulation refers to a form of medicine that is to be taken in the form of a potion dissolved in water or an organic solvent.
  • the liquid preparation is more effective in absorbing the drug into the systemic circulation in the intestinal tract than the suspension or solid preparation, and the liquid preparation may include additional solutes in addition to the medicine, and may include additives that impart color, odor, sammi, or stability. can do.
  • Non-limiting examples of the liquid formulation may include a syrup.
  • the syrup means a concentrated homemade sugar or sugar substitute.
  • the syrup is an unpleasant taste, such as a bitter taste of the medicine is easy to take as a liquid formulation, and is particularly suitable for children to take.
  • the syrup is 1) a surrogate of sucrose or sugar used for imparting sweetness and viscosity, 2) an antimicrobial preservative, 3) a flavor flavor, or 4, in addition to rhubarb and pelargonium sidoides extract and purified water. ) May include a colorant, but is not limited thereto.
  • sweeteners examples include, but are not limited to, sucrose, mannitol, sorbitol, xylitol, aspartame, stevioside, fructose, lactose, sucralose, saccharin or menthol.
  • the present invention comprises a rye and pelargonium sidoides mixed extract as an active ingredient, for Jinhae or expectorant; Or it provides a health functional food for preventing or improving respiratory diseases or airway infections.
  • the barberry, Pelargonium sidoides, mixed extract, Jinhae, expectorant, respiratory disease and airway infection are as described above.
  • the mixed extract When the mixed extract is used as a health functional food, the mixed extract may be added as it is or used in combination with other foods or ingredients, and may be appropriately used according to a conventional method.
  • the amount thereof is not particularly limited, but is, for example, 1 to 5% by weight, or 1 to 3% by weight based on the weight of the final food. Can be added. However, in the case of prolonged ingestion, the added amount may be below the above range, and since the mixed extract is a herbal ingredient, there is no problem in terms of safety, and thus the active ingredient may be used in an amount above the above range.
  • the type of health functional food of the present invention is not particularly limited.
  • foods that include all foods or beverages in a conventional sense and to which the extracts can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums and ice cream.
  • the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, Alcohol, a carbonation agent used for carbonated drinks, and the like.
  • Others may contain pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks.
  • the food may also be prepared in the form of tablets, granules, powders, capsules, liquid solutions and pills according to known production methods.
  • the present invention provides a method of treating a respiratory disease or airway infection, comprising administering a mixture of the barberry and pelargonium sidoides to a suspected respiratory disease or airway infection.
  • nasturtium, pelargonium sidoides, mixed herbal extract and respiratory disease are the same as described above.
  • the method of treatment of the present invention comprises administering the mixed extract of the barberry and pelargonium sidoides in the form of a pharmaceutical composition to a subject suspected of respiratory disease in a pharmaceutically effective amount.
  • the subject means an entire mammal including a dog, cow, horse, rabbit, mouse, rat, chicken or human, but the mammal of the present invention is not limited to the above examples.
  • the pharmaceutical composition may be administered orally, orally, subcutaneously, intraperitoneally, pulmonary, and intranasally, and may be administered by a suitable method including topical administration if necessary for local treatment.
  • Non-oral infusions include intramuscular, intravenous, intraarterial, intraperitoneal or subcutaneous administration.
  • oral administration is not limited thereto.
  • the preferred dosage of the pharmaceutical composition of the present invention may vary depending on the condition and weight of the individual, the extent of the disease, the form of the drug, the route of administration, and the duration, and may be appropriately selected by those skilled in the art.
  • the present invention provides a method for alleviating cough or sputum, comprising administering to a subject a mixed herbal extract of rhubarb and pelargonium sidoides.
  • nasturtium, pelargonium sidoides, mixed herbal extract and respiratory disease are the same as described above.
  • the mixed extracts of the rhubarb and pelargonium sidoides of the present invention show excellent antitussive expectorant efficacy which is synergistically markedly increased compared to the same amount alone when mixed in a predetermined ratio, so that the mixed herbal extract coughs // And by administering to a subject in need of relief of sputum, the effect of relieving cough or sputum can be obtained.
  • Coptidis rhizome especially 1 kg of root diameter of hull , was selected and adjusted according to Pharmacopoeia's theft and powderiness. 10 times of water was added and extracted at 100 ° C for 3 hours, and the filtrate was concentrated under reduced pressure at 60 ° C. About 112 g of dry matter were obtained.
  • the dried product of the sulfur extract was tested for the concentration of heavy metals, microorganisms and residual pesticides contained in it to confirm that it is suitable for use as a pharmaceutical composition in all items.
  • Pelargonium Sipeides sidoides , Geraniaceae) cut the dried root to the appropriate size (> 10 mm or more, 95% or more), wet it with 35% ethanol (2 parts), add 5.3% ethanol (8 parts), and filter the extracted solution. 11 g of extract was obtained from about 1 g of dry roots as what was heated for a second. This solution was mixed with 85% glycerol in an 8: 2 (w / w) ratio (Example 2-1).
  • Example 2-2 As a result of quantifying the dried Pelargonium sidoides of Example 2-2 prepared as above, it was confirmed that 1 g of the dried Pelargonium sidoides contained 389 mg of epicatechin (38.9%). At this time, as confirmed by the Karl Fischer method, the dried material contained 8.86% moisture.
  • the dried product of the Pelargonium sidoides extract was tested for the concentration of heavy metals, microorganisms and residual pesticides contained in it to confirm that it is suitable for use as a pharmaceutical composition in all items.
  • In vivo expectorant activity evaluation was performed by measuring the sputum excretion capacity according to the dose and / or composition ratio of the mixture of the rye extract and pelargonium sidoides extract.
  • test substance was prepared by weighing the dried product obtained in Examples 1 and 2-2 as it was, adding some excipient to dissolve, and then adding the excipient to a prescribed concentration. The test substance dissolved in the excipient was filtered and sterilized and then treated in the experimental animal. Preparation was carried out on the day of administration.
  • each experimental group was administered with 100, 200 or 400 mg / kg (G1 to G3, respectively). And G4 to G6) and the experimental groups (G7 to G10) administered so that the total amount of the mixture of these extracts mixed 1: 1 was 50, 100, 200 or 400 mg / kg, respectively (Table 1). Ambroxol was used as a control.
  • G1 Huangshan administration group 1 100 10 G2 Huangshan administration group 2 200 10 G3 Huangshan administered group 3 400 10 G4 Pelargonium sidoides group 1 100 10 G5 Pelargonium sidoides group 2 200 10 G6 Pelargonium sidoides group 3 400 10 G7 Mixture administration group 1 50 (25 + 25) 10 G8 Mix dose group 2 100 (50 + 50) 10 G9 Mix dose group 3 200 (100 + 100) 10 G10 Mix dose group 4 400 (200 + 200) 10 G11 Positive control group (ambroxol) 250 10
  • Radiation-sterilized rat animal feed (TEKLAD CERTIFIED IRRADIATED GLOBAL 18% PROTEIN RODENT DIET, 2918C, Harlan Laboratories Inc., USA) was supplied from Coatech and freely ingested and watered with UV sterilizers and microfiltration equipment. Free bottle ingestion. Immediately after administration of the test substance and the control substance, the test animals were observed prior to administration of the phenol red solution and before organ extraction to confirm death. When the animals died during the observation period, the autopsy examined the symptoms.
  • phenol red solution (w / v) prepared at 10% concentration in physiological saline was intraperitoneally administered to ICR mice at a dose of 0.2 mg / morning, and after 30 minutes, euthanized with carbon dioxide gas to trachea (trachea) was extracted.
  • the extracted organ was placed in a microcentrifuge tube and subjected to sonication for 15 minutes by adding 1 ml of physiological saline and centrifuged (10,000 rpm, 5 minutes). 0.5 ml of supernatant was taken and placed in a new centrifuge tube and 0.5 ml of 1N sodium hydroxide was added.
  • the supernatant of the solution to which sodium hydroxide was added was stirred with a vortex mixer, and then 0.2 ml of the solution was dispensed into a 96-well plate.
  • the sputum discharge capacity of the test substance was calculated by substituting the following formula.
  • the rhubarb extract showed an expectorant effect, and the effect was increased in proportion to the dose, but the increase rate was decreased as the dose was increased.
  • the expectorant effect increased as the dose was increased, but when the dose was increased to 400 mg, the effect was significantly reduced.
  • the two extracts were mixed in the same weight (1: 1 weight ratio, on a dry basis), but the total extract amount was from 50 mg to 400 Mice were dosed with increasing up to mg.
  • the sputum ejection capacity thus measured was evaluated in comparison with the values measured for the same amount of the single extract administration group (Tables 2 and 3), and more when the mixed extract was used compared to the same amount of the single extract. Dosages showing high activity were identified. The measured results are shown in FIG. 1 and Table 4 below. As a positive control, 250 mg of ambroxol was used.
  • the total dose was 200 mg / kg showed an increased sputum discharge capacity of about 60% and 53%, respectively, compared with the 200 mg of each alone extract. Furthermore, the sputum excretion capacity measured by the administration of 100 mg of each showed more than 15% higher activity than the simply summed value. In addition, it was confirmed that the activity was more than two times higher than the positive control group administered with Ambroxol 250 mg / kg. This is because the combination of the rhubarb extract and the pelargonium sidoides extract according to the present invention showed a markedly increased activity compared to the case where each of them was used alone or the value of each activity simply added. Induce synergistic increase.
  • the total 200 mg confirmed to have the best sputum discharge ability through Example 3 (5)
  • the dose was set and a sample was prepared while adjusting the ratio (dry basis weight ratio) of the extract of Pelargonium sidoides (dry weight basis) from 1: 2 to 1: 0.2, and the sputum discharge capacity was measured.
  • the composition and measured sputum discharge capacity of the mixed extract are shown in Table 5 and FIG. 2.
  • the ratio of pelargonium sidoides extract to rhubarb extract was the highest when the ratio of sputum was 2, and even if the ratio was reduced to 0.3, the sputum was still higher than when the same amount of the single extract was administered. Emission capacity is shown (see results for Table 2 G2 and Table 3 G5).
  • the component contents shown in Table 6 as an active ingredient, it comprises a rhubarb extract and a pelargonium sidoides extract, further mixed with microcrystalline cellulose, lactose monohydrate, povidone, calcium silicate, and then fed and granulated by adding purified water And dried at a temperature of 50-60 ° C. in a cabinet drier (LOD 2% or less). After sizing, the remaining disintegrant and glidants were mixed.
  • bilayer tablet including two active ingredients in separate layers As described above, it is possible to prevent undesirable phenomena that may occur due to the mixing of the respective active ingredients during manufacture, storage and / or distribution.

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Abstract

La présente invention concerne l'utilisation d'un extrait de mélange de Rhizoma Coptidis et de Pelargonium Sidoides en tant qu'agent antitussif ou expectorant, et son utilisation pour prévenir ou traiter des maladies des voies respiratoires ou une infection respiratoire.<i />
PCT/KR2015/011468 2014-10-28 2015-10-28 Composition antitussive et expectorante contenant, en tant que principe actif, un extrait de mélange de rhizoma coptidis et de pelargonium sidoides Ceased WO2016068607A1 (fr)

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KR20200004178A (ko) * 2018-07-03 2020-01-13 한국유나이티드제약 주식회사 펠라고니움 시도이데스 추출물을 포함하는 약학 조성물 및 이의 제조방법
KR20220078762A (ko) 2020-12-03 2022-06-13 (주)에스디생명공학 무궁화 꽃 추출물을 유효성분으로 포함하는 진해 및 거담용 조성물

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