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EP2991624A1 - Formulation orale comprenant un extrait de rhizome de coptide présentant un goût amer masqué - Google Patents

Formulation orale comprenant un extrait de rhizome de coptide présentant un goût amer masqué

Info

Publication number
EP2991624A1
EP2991624A1 EP14791495.6A EP14791495A EP2991624A1 EP 2991624 A1 EP2991624 A1 EP 2991624A1 EP 14791495 A EP14791495 A EP 14791495A EP 2991624 A1 EP2991624 A1 EP 2991624A1
Authority
EP
European Patent Office
Prior art keywords
extract
coptis rhizome
exchange resin
formulation
cation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP14791495.6A
Other languages
German (de)
English (en)
Other versions
EP2991624A4 (fr
Inventor
Youn Woong Choi
Byung Gu Min
Dea Chul HA
Sang Min Cho
Hee Yong Song
Hee Chan Park
Ji Hyun Ahn
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Korea United Pharm Inc
Original Assignee
Korea United Pharm Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Korea United Pharm Inc filed Critical Korea United Pharm Inc
Publication of EP2991624A1 publication Critical patent/EP2991624A1/fr
Publication of EP2991624A4 publication Critical patent/EP2991624A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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)
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents

Definitions

  • the present invention relates to an oral formulation having masked bitter taste, which comprises an extract of Coptis rhizome and a cation-exchange resin having a sulfonic acid group, and to a preparation method thereof.
  • Taste is an important factor in administering drugs orally. In the preparation of formulations, it is important to mask unpleasant tastes. Particularly, it is important in the pharmaceutical industry to mask the bitter taste of drugs so that drugs have an acceptable taste. Thus, many pharmaceutical companies address the issue of taste masking from the initial stage of product development and have made various efforts to develop formulations having masking of bitter taste while still exhibiting medicinal effects. Examples of methods developed by such efforts include a method of minimizing the dissolution of drugs by saliva to reduce the bitter taste, a method of coating drug particles, a method of using amino acid and protein hydrolysates, and a method of forming molecular complexes between drugs and other chemicals.
  • Components having a bitter taste are very diverse. Also, in structural terms, whether a particular substance has a bitter taste may vary depending on the type of structural isomer or enantiomer. For example, L-tryptophan is bitter, but a D-enantiomer thereof is sweet, and hesperidin is tasteless, but neohesperidin, a positional isomer thereof, has a very strong bitter taste. Examples of components known to have bitter taste include sodium sulfate, peptides, polyphenols, terpenoids, flavonoids, alkaloids, and other various components.
  • Coptis rhizome is an evergreen perennial dicotyledonous plant belonging to the family Ranunculaceae of the order Ranunculales .
  • Coptis rhizome is known to be distributed in Korea, Japan and China, and the cross section of the rhizome thereof is yellow in color. It has been known that Coptis rhizome has a tonic effect, is effective against arteriosclerosis, weakness after illness, or palsy, and is cold in nature and bitter in taste.
  • oral syrup formulations prepared using Coptis rhizome have a disadvantage in that they are not easily taken by patients, particularly children and people sensitive to bitter taste, due to their strong bitter taste that cannot be masked even by sweeteners or the like.
  • the present inventors have made extensive efforts to develop an oral formulation comprising a Coptis rhizome extract having masked bitter taste, and as a result, have found, when a cation-exchange resin having a sulfonic acid group is added to a Coptis rhizome extract to prepare an oral formulation, the bitter taste of the Coptis rhizome extract is more effectively masked compared to when a sweetener or cyclodextrin is used, and also have found that, even if the cation-exchange resin having a sulfonic acid group is used in a smaller amount than a cation-exchange resin or anion-exchange resin having a carboxyl group, it has an excellent effect of masking the bitter taste, thereby completing the present invention.
  • It is an object of the present invention to provide an oral formulation comprising an extract of Coptis rhizome and a cation-exchange resin having a sulfonic acid group.
  • Another object of the present invention is to provide an oral formulation, comprising an extract mixture of Coptis rhizome and Pelargonium sidoides; and a cation-exchange resin having a sulfonic acid group.
  • Still another object of the present invention is to provide an oral formulation, comprising an extract mixture of Coptis rhizome and ivy leaves; and a cation-exchange resin having a sulfonic acid group.
  • Yet another object of the present invention is to provide a method for preparing an oral formulation, comprising: (a) preparing a sample comprising an extract of Coptis rhizome ; and (b) mixing the sample comprising the extract of Coptis rhizome with a cation-exchange resin having a sulfonic acid group.
  • An oral formulation of the present invention which comprises an extract of Coptis rhizome as an active ingredient, comprises a cation-exchange resin having a sulfonic acid group, which significantly reduces the bitter taste of the Coptis rhizome extract.
  • the oral formulation of the present invention has an advantage in that it can be taken by children, old and feeble persons, and persons sensitive to bitter taste.
  • the present invention provides an oral formulation comprising an extract of Coptis rhizome and a cation-exchange resin having a sulfonic acid group.
  • Coptis rhizome is a medicinal herb having a strong bitter taste.
  • it is required to effectively mask the bitter taste of Coptis rhizome.
  • there was an attempt to mask the bitter taste of Coptis rhizome by adding a sweetener or the like to a formulation such as a syrup formulation but it was difficult to use the formulation as an oral formulation, because the degree of masking of the bitter taste of Coptis rhizome is low, even when the formulation contains a large amount of the sweetener.
  • the present inventors have made efforts to develop an oral formulation by effectively masking the bitter taste of Coptis rhizome using ion-exchange resins, and as a result, have found surprisingly found that, among various ion-exchange resins, a cation-exchange resin having a sulfonic acid group effectively masks the bitter taste of an extract of Coptis rhizome.
  • the extract of Coptis rhizome is not a drug consisting of a single component, but comprises various pharmacological components, it is difficult to identify the components attributable to the bitter taste of Coptis rhizome, and it is more difficult to select an ion-exchange resin suitable for the extract of Coptis rhizome as compared to the case of a drug consisting of a single component. For this reason, large amounts of time and effort are required to select a suitable ion-exchange resin that effectively masks the bitter taste of the Coptis rhizome extract.
  • the bitter taste of the Coptis rhizome extract is effectively masked by a cation-exchange resin having a sulfonic acid group.
  • a cation-exchange resin having a carboxyl group it was found that, in order to mask the bitter taste of Coptis rhizome using a cation-exchange resin having a carboxyl group, it should be used in significantly large amounts compared to a cation-exchange resin having a sulfonic acid group, and for this reason, the taste of the ion-exchange resin having a carboxyl group remains due to the large amounts thereof, suggesting that the use of the cation-exchange resin having a carboxyl group to mask the bitter taste of the Coptis rhizome extract is not suitable.
  • anion-exchange resins have low ability to mask the bitter taste of the Coptis rhizome extract, compared to cation-exchange resins, suggesting that the bitter taste of the Coptis rhizome extract is mainly attributable to cationic components.
  • the present invention is based on these findings.
  • Coptis rhizome refers to a perennial herbal plant belonging to the family Ranunculaceae , which is known to have pharmacological effects, including antimicrobial effects, blood pressure lowering effects and anti-inflammatory effects.
  • the Coptis rhizome includes the dried rhizome of Coptis chinensis Franch, Coptis deltoides C.Y. Cheng et Hsiao, Coptis japonica Makino (Ranunculaceae), or other berberine-containing species of the same genus, but is not limited thereto.
  • Coptis rhizome is known to have a unique strong bitter taste.
  • Coptis rhizome has a strong bitter taste due to the combined action of various components, including alkaloid components such as berberine, palmatine, coptisine or wornnine, which have bitter taste.
  • alkaloid components such as berberine, palmatine, coptisine or wornnine, which have bitter taste.
  • Coptis rhizome that is used in the formulation of the present invention is commercially available or can be obtained in nature or cultivated.
  • extract of Coptis rhizome refers to an extract obtained by extracting Coptis rhizome.
  • the extract of Coptis rhizome can be obtained by extracting crushed Coptis rhizome with an extraction solvent selected from among water, alcohols having various carbon chain lengths, for example, alcohols containing 1 to 4 carbon atoms, and mixed solvents thereof, but is not limited thereto.
  • the alcohol is preferably ethanol, methanol or butanol, but is not limited thereto.
  • the extract may be obtained using an extraction method such as hot-water extraction, cold maceration extraction, reflux cooling extraction or ultrasonic extraction.
  • the extract of Coptis rhizome may be filtered under reduced, and the filtrate may be concentrated under reduced pressure and solubilized in water, alcohol or a mixed solvent thereof, but is not limited thereto.
  • extract as used herein also includes an extract, a dilution or concentrate of the extract, a dried extract obtained by drying the extract, or a crude extract or purified extract.
  • an extract obtained by drying a water extract of Coptis rhizome was used (Example 1).
  • the extract of Coptis rhizome has various effects, including an antitussive or expectorant effect, a bowel cleansing effect, and effects against diarrhea, anadypsia, gastrointestinal bleeding, gum bleeding, and jaundice caused by excessive drinking, inflammation, cancer, and diabetes.
  • the oral formulation of the present invention which comprises the extract of Coptis rhizome, can be used as a formulation having various effects as described above.
  • the oral formulation of the present invention is characterized in that it comprises a cation-exchange resin having a sulfonic acid group in order to effectively mask the bitter taste of the Coptis rhizome extract.
  • ion-exchange resin refers to a synthetic resin capable of ion exchange.
  • the ion-exchange resin may have an ion-exchange functional group on the inner surface thereof, and examples thereof include cation-exchange resins, anion-exchange resins, resins having cation and anion exchange groups, electron-exchange redox resins, and chelate resins coordinated with specific metal ions, but not limited thereto.
  • a preferred ion-exchange resin that is used to mask the bitter taste of the Coptis rhizome extract is a cation-exchange resin having a sulfonic acid group.
  • the cation-exchange resin include styrene sulfonate polymers, divinylbenzene styrene sulfonate copolymers and PolyAMPS (poly(2-acrylamido-2-methyl-1-propanesulfonic acid).
  • the styrene sulfonate polymers include sodium polystyrene sulfonate, calcium polystyrene sulfonate and polystyrene sulfonic acid.
  • sodium polystyrene sulfonate is more preferably used to mask the bitter taste of the Coptis rhizome extract, but is not limited thereto.
  • the Coptis rhizome extract and the cation-exchange resin having a sulfonic acid group are preferably contained at a ratio of 1:1 to 1:10 (w:w), more preferably 1:1.5 to 2.5 (w:w), and even more preferably 1:2 (w:w), based on the weight of solid content, in order to more effectively mask the bitter taste of the Coptis rhizome extract.
  • the cation-exchange resin having the sulfonic acid group which is contained in the oral formulation of the present invention, may interact with the nitrogen atoms of various components having bitter taste to form a complex to thereby mask the bitter taste, but is not limited thereto.
  • the interaction between the cation-exchange resin and the components of the Coptis rhizome extract can be performed by brining the resin into repeated contact with the Coptis rhizome extract in a chromatographic column or mixing the resin with a solution containing the Coptis rhizome extract, but is not limited thereto.
  • the components of the Coptis rhizome extract which formed a complex with the ion-exchange resin by the above-described process, may not be dissociated at the pH of the oral cavity, and thus can be taken in a state in which the bitter taste is masked.
  • the components of the Coptis rhizome extract can be exchanged with ions having a suitable charge so that they can be separated from the ion-exchange resin and absorbed in vivo , thereby exhibiting pharmacological effects.
  • the oral formulation of the present invention comprising the Coptis rhizome extract and the ion-exchange resin may be any oral formulation whose taste can be felt in the mouth.
  • it may be a liquid formulation, syrup, powder or granule.
  • liquid formulation means a liquid medicine that comprises a pharmacologically active ingredient dissolved in a solvent such as water or an organic solvent.
  • the liquid formulation has an advantage over a suspension or solid formulation in that the absorption of the active ingredient from the gastrointestinal tract into the systemic circulatory system is more effective.
  • the liquid formulation may comprise, in addition to the active ingredient, an additional solute, and may also comprise additives such as a colorant, a flavoring agent, a sweetener or a stabilizer.
  • the term "syrup" means a concentrated aqueous solution of sweetener.
  • the syrup is a formulation that comprises sweeteners and the cation-exchange resin to make it easy to take an active ingredient having unpleasant taste, for example, bitter taste, and is suitable to be taken by children.
  • the syrup may comprise, in addition to purified water, the Coptis rhizome extract and the sweetener such as sugar or a sugar substitute that is used to give sweetness and viscosity, (1) an antimicrobial preservative, (2) a flavor, or (3) a colorant, but is not limited thereto.
  • sweetener examples include, but are not limited to, white sugar, mannitol, sorbitol, xylitol, aspartame, stevioside, fructose, lactose, sucralose, saccharin and menthol.
  • the term "powder” means a mixture of finely divided, relatively dry, particulate matter comprising one or more substances. Powder as a dosage form is in a ground state, and thus when it is administered orally, the unpleasant taste of the drug can be strongly felt. For this reason, if the Coptis rhizome extract is formulated into a powder form without separate treatment, it will give an unpleasant feeling to the patient due to the strong bitter taste of Coptis rhizome , suggesting that the use of the Coptis rhizome extract in a powder form without separate treatment can be unsuitable.
  • granule refers to a small particle or grain comprising a medicinal agent in a dry mixture.
  • Granules are generally produced by wetting powder or a powder mixture and passing the resulting masses through a sieve or granulator having a suitable mesh size depending on a desired granule size.
  • the granule formulation is in a particle state, like the powder formulation, and thus the degree of contact of the drug with the tongue is great. For this reason, if a medicinal agent having bitter taste is formulated into a granule form, it can give an unpleasant feeling to the patient, particularly a child or an old and feeble person.
  • the Coptis rhizome extract having bitter taste into a liquid, syrup, powder or granule form, it is necessarily required to mask the bitter taste in order for the extract to be commercially used as a formulation.
  • a cation-exchange resin having a sulfonic acid group was used to mask the bitter taste of the Coptis rhizome extract, thereby developing a medical formulation that masks the bitter taste of Coptis rhizome extract while exhibiting the pharmacological effects of the Coptis rhizome extract.
  • an ion-exchange resin having a sulfonic acid group when added to an oral solution formulation comprising an extract of Coptis rhizome, it had a significantly higher ability to mask the bitter taste of Coptis rhizome, compared to a sweetener or cyclodextrin, and it also had a high effect of masking the bitter taste, compared to an anion-exchange resin and an ion-exchange resin having a carboxyl group.
  • the present invention provides an oral formulation comprising an extract mixture of Coptis rhizome and Pelargonium sidoides, and a cation-exchange resin having a sulfonic acid group.
  • Coptis rhizome and the cation-exchange resin having the sulfonic acid group are as described above.
  • the oral formulation comprises anextract mixture of Coptis rhizome and Pelargonium sidoides .
  • the extract mixture may be an extract obtained by mixing a Coptis rhizome extract with a Pelargonium sidoides extract or may be an extract obtained by mixing Coptis rhizome with Pelargonium sidoides and extracting the mixture, but is not limited thereto.
  • Pelargonium sidoides refers to a plant known to grow naturally in the alpine region of the inland and coastal areas of the Republic of South Africa and is also named kaloba, umcka or zucol. Pelargonium sidoides has an antitussive or expectorant effect, and thus a formulation comprising an extract of Pelargonium sidoides can be used as an oral formulation having an antitussive or expectorant effect. Pelargonium sidoides that is used in the present invention is commercially available or can be obtained in nature or cultivated.
  • extract of Pelargonium sidoides means an extract obtained by extracting Pelargonium sidoides .
  • the extract of Pelargonium sidoides can be obtained by extracting crushed Pelargonium sidoides with an extraction solvent selected from among water, alcohols having various carbon chain lengths, for example, alcohols containing 1 to 4 carbon atoms, and mixed solvents thereof, but is not limited thereto.
  • the alcohol is preferably ethanol, methanol or butanol, but is not limited thereto.
  • the extract may be obtained using an extraction method such as hot-water extraction, cold maceration extraction, reflux cooling extraction or ultrasonic extraction.
  • the extract of Pelargonium sidoides may be filtered under reduced pressure, and the filtrate may be concentrated under reduced pressure and solubilized in water, alcohol or a mixed solvent thereof, but is not limited thereto.
  • extract as used herein includes an extract, a dilution or concentrate of the extract, a dried extract obtained by drying the extract, or a crude extract or purified extract.
  • the extract of Pelargonium sidoides also includes a 8:2 (a weight of a pelargonium sidoides extract: a weight of glycerol) mixture of a 11% ethanol extract (1->8 ⁇ 10) of Pelargonium sidoides and glycerol.
  • the extract mixture comprises the Coptis rhizome extract and the 8:2 (w:w) mixture of a 11% ethanol extract (1->8 ⁇ 10) of Pelargonium sidoides and glycerol, it may comprise these extracts at a weight ratio of 1:50 to 1:1,500 (w:w), but is not limited thereto.
  • an oral solution formulation comprising, in addition to the Coptis rhizome extract and the 8:2 (w:w) mixture of a 11% ethanol extract (1->8 ⁇ 10) of Pelargonium sidoides and glycerol, a cation-exchange resin having a sulfonic acid group, effectively masked the bitter taste of the Coptis rhizome extract, suggesting that the cation-exchange resin is suitable for use as an oral formulation comprising the extract of the coptis rhizome (Example 6).
  • the present invention provides an oral formulation, comprising an extract mixture of Coptis rhizome and ivy leave; and a cation-exchange resin having a sulfonic acid group.
  • Coptis rhizome the cation-exchange resin having the sulfonic acid group, and the oral formulation, are as described above.
  • the oral formulation comprises a mixed extract of Coptis rhizome and ivy leaves.
  • the mixed extract may be an extract obtained by mixing a Coptis rhizome extract with an ivy leaf extract or may be an extract obtained by mixing Coptis rhizome with an ivy leaf and extracting the mixture, but is not limited thereto.
  • the term "ivy” means a plant ( Hedera spp.) belonging to the genus Hedera of the family Araliaceae .
  • Examples of the ivy plant include, but are not limited to, Hedera algeriensis , Hedera azorica , Hedera canariensis , Hedera colchica , Hedera helix , Hedera hibernica , Hedera maderensis , Hedera nepalensis , Hedera pastuchowii, and Hedera rhombea .
  • the ivy leaf has an effect of promoting mucus secretion and an antitussive effect, and thus when the oral formulation of the present invention comprises an extract of the ivy leaf, it can be used as an oral formulation having an antitussive or expectorant effect.
  • the ivy that is used in the present invention is commercially available or can be obtained in nature or cultivated.
  • extract of ivy leaves refers to an extract obtained by extracting ivy extracts.
  • the extract of ivy leaves can be obtained by extracting crushed ivy leaves with an extraction solvent selected from among water, alcohols having various carbon chain lengths, for example, alcohols containing 1 to 4 carbon atoms, and mixed solvents thereof, but is not limited thereto.
  • the alcohol is preferably ethanol, methanol or butanol, but is not limited thereto.
  • the extract may be obtained using an extraction method such as hot-water extraction, cold maceration extraction, reflux cooling extraction or ultrasonic extraction.
  • extract of ivy leaves may be filtered under reduced pressure, and the filtrate may be concentrated under reduced pressure and solubilized in water, alcohol or a mixed solvent thereof, but is not limited thereto.
  • extract of ivy leaves includes an extract, a dilution or concentrate of the extract, a dried extract obtained by drying the extract, or a crude extract or purified extract.
  • the Coptis rhizome extract and the ivy leaf extract may be contained at a weight ratio of 1:1 to 1:10 (a weight of the coptis rhizome extract : a weight of the ivy leaf extract) based on the weight of solid content, but is not limited thereto.
  • an oral solution formulation was prepared by adding a cation-exchange resin having a sulfonic acid group to the Coptis rhizome extract and the ivy leaf extract, and it was shown that the oral solution formulation comprising the cation-exchange resin could effectively mask the bitter taste of the Coptis rhizome extract, suggesting that the cation-exchange resinis suitable for use as an oral formulation comprising the extract of the Coptis rhizome (Example 7).
  • the present invention provides a method for preparing an oral formulation, the method comprising: (a) preparing a sample comprising an extract of Coptis rhizome ; and (b) mixing the sample with a cation-exchange resin having a sulfonic acid group.
  • the extract of Coptis rhizome and the cation-exchange resin having the sulfonic acid group are as described above.
  • step (a) is a step of preparing a sample comprising an extract of Coptis rhizome
  • step (b) is a step of mixing the sample with the cation-exchange resin having the sulfonic acid group, prepared in step (a).
  • step (b) mixing of the sample comprising the Coptis rhizome extract with the cation-exchange resin having the sulfonic acid group can be performed using a suitable mixing method known in the art depending on the type of oral formulation.
  • a suitable mixing method known in the art depending on the type of oral formulation.
  • the sample comprising Coptis rhizome extract and the cation-exchange resin having the sulfonic acid group may be added to a sterile aqueous solution and stirred
  • the sample comprising Coptis rhizome extract and the cation-exchange resin having the sulfonic acid group may be added to a solution comprising the sweeteners and stirred, but is not limited thereto.
  • the Coptis rhizome extract and the cation-exchange resin having the sulfonic acid group may be mixed with each other at a weight ratio of 1:1 to 1:10 (a weight of the coptis rhizome extract : a weight of the cation-exchange resin), and preferably 1:2 (a weight of the coptis rhizome extract : a weight of the cation-exchange resin), on solid basis, but is not limited thereto.
  • step (b) may be a step of mixing a sample comprising an extract mixture of Coptis rhizome and Pelargonium sidoides with the cation-exchange resin having the sulfonic acid group, but is not limited thereto.
  • step (b) may be a step of mixing a sample comprising an extract mixture of Coptis rhizome and ivy leaves with the cation-exchange resin having the sulfonic acid group, but is not limited thereto.
  • the dry root of Pelargonium sidoides ( Geraniaceae ) was cut to a suitable size (10 mm or less, 95% or more), and then wet with 35% ethanol (2-fold amount), after which 5.3% ethanol (8-fold amount) was added to the plant which was then extracted.
  • the extract was filtered at a temperature of 120 ⁇ 121 °C for 30 seconds, whereby 9-11 g of an extract was obtained from about 1 g of the plant.
  • the extract was mixed with 85% glycerol at a ratio of 8:2 (a weight of the extract : a weight of the extract).
  • Example 4 Preparation of mixtures of Coptis rhizome extract and sweetener, cyclodextrin or ion-exchange resin and comparison of bitter taste masking effect
  • composition of the present invention comprising the Coptis rhizome extract of Example 1 and an ion-exchange resin with that of cyclodextrin or a sweetener and to compare the effect of masking the bitter taste of the Coptis rhizome extract between a cation-exchange resin having a sulfonic acid group, a cation-exchange resin having a carboxyl group and an anion-exchange resin, the following experiment was performed.
  • cyclodextrins ⁇ -cyclodextrin and ⁇ -cyclodextrin were used, and as the sweeteners, high-fructose and D-sorbitol were used.
  • ion-exchange resins sodium polystyrene sulfonate that is a representative ion-exchange resin having a sulfonic acid group, polacrilin potassium that is a representative ion-exchange resin having a carboxyl group, and cholestyramine that is a representative anion-exchange resin, were used to compare their effects of masking the bitter taste of the Coptis rhizome extract.
  • the Coptis rhizome extract as an active ingredient and the sweetener, the cyclodextrin or the ion-exchange resin were dissolved in water to prepare oral solution formulations.
  • Each of the prepared oral solution formulations had a total volume of 200 mL.
  • the anion-exchange resin cholestyramine showed a slight masking effect and did not completely mask the bitter taste of the Coptis rhizome extract (#7).
  • the cation-exchange resin having the carboxyl group showed the effect of masking the bitter taste when it was used in amounts of 0.3 g and 0.6 g for 0.1 g of the Coptis rhizome extract, but the taste thereof remained due to the use of large amounts of the resin (#5 and #6).
  • the groups (#8 and #9) comprising the cation-exchange resin having the sulfonic acid group
  • a high masking effect appeared even when the ion-exchange resin was used in the same amount as the Coptis rhizome extract (0.1 g).
  • 0.2 g of the ion-exchange resin was used, it showed a very high masking effect, suggesting that the cation-exchange resin having the sulfonic acid resin is most suitable to effectively mask the bitter taste of the Coptis rhizome extract using a relatively small amount of the ion-exchange resin.
  • the anion-exchange resin showed a slight masking effect, suggesting that the bitter taste of the Coptis rhizome extract is mostly attributable to cationic compounds having bitter taste.
  • Example 5 Preparation of oral solution formulations comprising Coptis rhizome extract and cation-exchange resin having sulfonic acid group and examination of bitter taste masking effect
  • Example 4 Based on the results of Example 4, the mixing ratio between the Coptis rhizome extract and the cation-exchange resin having the sulfonic acid was adjusted, and the bitter taste masking effect was examined.
  • the Coptis rhizome extract as an active ingredient and sodium polystyrene sulfonate as the cation-exchange resin having the sulfonic acid group were dissolved in water to prepare oral solution formulations.
  • Each of the prepared oral solution formulations had a total volume of 200 mL.
  • a sensory test was performed. Specifically, 5 mL of each of formulations #10 to #14 was taken by each of a total of thirty men and women, and then the degree of masking of the bitter taste was evaluated by questionnaire. The results of the evaluation are shown in Table 2 below.
  • Example 6 Preparation of oral solution formulations comprising an extract mixture of Coptis rhizome and Pelargonium sidoides and a cation-exchange resin having sulfonic acid group and the examination of bitter taste masking effect
  • an extract obtained by drying a water extract of Coptis rhizome , and a 8:2 (w:w) mixture of a 11% ethanol extract (1 ⁇ 8 ⁇ 10) of Pelargonium sidoides and glycerol, were mixed at a weight of 1: 50 to 1: 1500 (w:w), and sodium polystyrene sulfonate that is a cation-exchange resin having a sulfonic acid group was mixed with the extract mixture in water according to the compositions shown in Table 3 below, thereby preparing formulations #15 to #19.
  • Each of the prepared formulations #15 to #19 had a total volume of 200 mL and had a composition shown in Table 3 below.
  • Example 7 Preparation of oral solution formulations comprising an extract mixture of Coptis rhizome and ivy leaves and a cation-exchange resin having sulfonic acid group and the examination of bitter taste masking effect
  • an extract obtained by drying a water extract of Coptis rhizome , and an extract obtained by drying a 30% ethanol extract of ivy leaves, were mixed at a weight of 1: 1 to 1: 10 (w:w), and sodium polystyrene sulfonate that is a cation-exchange resin having a sulfonic acid group was mixed with the mixed extract in water according to the compositions shown in Table 4 below, thereby preparing formulations #20 to #24.
  • Each of the prepared formulations #20 to #24 had a total volume of 200 mL and had a composition shown in Table 4 below.
  • each component was added to and dissolved in purified water, and a suitable amount of lemon fragrance was added thereto. Next, the above components were mixed, and the resulting solution was adjusted to a total volume of 100 mL by addition of purified water, after which it was filled into a brown bottle and sterilized, thereby preparing a liquid formulation.
  • Lactose 1 g
  • Lactose 1 g
  • the above components were mixed, granulated according to a conventional method, and then filled in an airtight sac to prepare a granule formulation.

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Abstract

La présente invention concerne une formulation orale présentant un goût amer masqué et comprenant un extrait de rhizome de Coptide et une résine échangeuse de cations possédant un groupe d'acide sulfonique, l'invention concernant également un procédé de préparation de cette formulation.
EP14791495.6A 2013-04-29 2014-04-29 Formulation orale comprenant un extrait de rhizome de coptide présentant un goût amer masqué Withdrawn EP2991624A4 (fr)

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KR1020130047566A KR101580119B1 (ko) 2013-04-29 2013-04-29 쓴맛이 차폐된 황련 추출물을 포함하는 경구투여용 제제
PCT/KR2014/003797 WO2014178617A1 (fr) 2013-04-29 2014-04-29 Formulation orale comprenant un extrait de rhizome de coptide présentant un goût amer masqué

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KR102528183B1 (ko) * 2021-01-27 2023-05-03 충북대학교 산학협력단 중머리풀 추출물과 이온교환수지를 포함하는 습식과립 제제 및 이의 제조방법

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KR20140129459A (ko) 2014-11-07
BR112015026635A2 (pt) 2017-07-25
CN105188669A (zh) 2015-12-23
MX2015014623A (es) 2016-03-01
RU2667638C2 (ru) 2018-09-21
EP2991624A4 (fr) 2016-12-07
PH12015502316A1 (en) 2016-02-10
RU2015142432A (ru) 2017-06-05
KR101580119B1 (ko) 2015-12-29
WO2014178617A1 (fr) 2014-11-06

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