WO2010150930A1 - Film à dissolution rapide administré par voie orale qui permet de prévenir efficacement tout goût désagréable - Google Patents

Film à dissolution rapide administré par voie orale qui permet de prévenir efficacement tout goût désagréable Download PDF

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Publication number
WO2010150930A1
WO2010150930A1 PCT/KR2009/003451 KR2009003451W WO2010150930A1 WO 2010150930 A1 WO2010150930 A1 WO 2010150930A1 KR 2009003451 W KR2009003451 W KR 2009003451W WO 2010150930 A1 WO2010150930 A1 WO 2010150930A1
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Prior art keywords
film
oral
sweetener
acid
group
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PCT/KR2009/003451
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English (en)
Korean (ko)
Inventor
박진규
양원석
정경태
Original Assignee
(주)벡스코아
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Priority to PCT/KR2009/003451 priority Critical patent/WO2010150930A1/fr
Publication of WO2010150930A1 publication Critical patent/WO2010150930A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A23L27/33—Artificial sweetening agents containing sugars or derivatives
    • A23L27/36—Terpene glycosides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/70—Fixation, conservation, or encapsulation of flavouring agents
    • A23L27/79—Fixation, conservation, or encapsulation of flavouring agents in the form of films
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Definitions

  • the present invention relates to a film for oral use effectively concealing an unpleasant taste, more specifically, stevioside-based sweeteners and high sweeteners are contained in a ratio (w / w) of 1: 3-3: 1, drug It effectively masks the unpleasant taste of, and relates to the oral film for oral use, which enhances the patient's dose compliance, that is, the after-improving effect that can be dissolved quickly in the oral cavity without water.
  • the disintegrating film easily disintegrates or dissolves in the mouth, it can be taken without water, so it is very useful for children with disabilities, patients lying in bed, and busy modern people, as well as elderly people who have difficulty taking tablets or capsules. to be. While it is possible to prescribe liquid solutions in place of tablets or capsules for the elderly and children, liquid formulations have the disadvantage of poor stability and inaccurate dosage.
  • the liver can also be avoided, so the fast-release film can be applied to drugs that are highly metabolized among the drugs absorbed from the digestive tract.
  • the film formulations that dissolve easily in the oral cavity absorb the drug through the oral mucosa, and therefore, a method of shielding the taste and discomfort upon absorption of the drug is required.
  • WO 2003/070227 masks the taste by containing a carbon dioxide forming material such as sodium bicarbonate.
  • a carbon dioxide forming material such as sodium bicarbonate.
  • sodium bicarbonate a drug with a strong bitter taste has a limit on concealment.
  • US 2008/0044454 discloses a uniform film by coating an active material using various coating techniques and injecting it into a film former. This also makes the coating process cumbersome.
  • the present inventors have tried to solve the above disadvantages, as a result of using aspartame, acesulfame potassium, sucralose, neotime in combination with stevioside and its derivatives to mask the bitter and unpleasant taste without significant change in the manufacturing method could.
  • the present inventors solved the problems of the prior art, and as a result of research to develop the most preferred form of the active ingredient-containing oral film, as a result of the high sweetness sweetener is particularly known as steviosides and derivatives thereof
  • the unpleasant taste can be effectively shielded without a separate coating process, and completed the present invention.
  • an object of the present invention to provide an oral fast-acting film containing a therapeutically effective amount of a medically active ingredient, steviosides and stevioside derivatives, and at least one high sweetener, film former and one or more pharmaceutically acceptable additives. It is.
  • Another object of the present invention is to provide an oral cavity film that effectively masks the unpleasant taste of a therapeutically effective amount of a medically active ingredient and dissolves quickly in the oral cavity.
  • the present invention has been made in order to achieve the above object, at least one water-soluble polymer, at least one medical active ingredient, stevioside-based sweetener as a tail enhancer, and at least one high sweetener as a taste blocker (first sweetener) It provides an oral rapid use film comprising a.
  • Oral quick-release film of the present invention is not only excellent in the unpleasant taste blocking effect, but also can be easily produced by a low cost and simplified recipe, oral cleansers, bad breath removers, nutritional supplements for oral and gastrointestinal tract cleaning It can be usefully used as a snow-soluble agent for the absorption of the drug in.
  • Example 1 is a diagram showing the results of comparative dissolution experiments of oral fast-acting film prepared according to Example 9 at pH 1.2 and the control drug (zofran tablet, GlaxoSmithKline, 8 mg).
  • the sweetness expression rate is slow in the order of acesulfame potassium (ACK), aspartame (AST), stevioside (STS).
  • ACK acesulfame potassium
  • AST aspartame
  • STS stevioside
  • the present invention relates to an oral cavity film composition containing a pharmaceutically active ingredient, effectively masking an unpleasant taste and dissolving rapidly in the oral cavity.
  • Preferred fast-acting films according to the present invention comprise a pharmaceutical active agent, stevioside and / or stevioside derivatives, one or more high sweetener (first sweetener), a film former and one or more of the following additional ingredients.
  • the additional components consist of pharmaceutically acceptable additives such as saliva stimulants, thickeners, fillers, plasticizers, second sweeteners, acidulants, flavors, emulsifiers, surfactants, binders, preservatives, colorants, coolants and the like.
  • pharmaceutically acceptable additives such as saliva stimulants, thickeners, fillers, plasticizers, second sweeteners, acidulants, flavors, emulsifiers, surfactants, binders, preservatives, colorants, coolants and the like.
  • a drug having a high taste and a high sweetener (first sweetener) and stevioside and its derivatives which improve the aftertaste are dissolved in water or oil, emulsified and mixed with a water-soluble polymer and other additives to form a rapid film.
  • the fast-drying film of this invention contains the 1st sweetener which is a high sweetness sweetener.
  • the high sweetening sweetener (first sweetener) is in the group consisting of aspartame, acesulfame salt, sucralose, saccharin salt, neotime, cyclate salt, tau martine, Nahan fruit extract, licorice extract It may be one or more high sweetening sweeteners selected. More preferably, at least one high sweetener sweetener selected from aspartame, sucralose, neotime, acesulfame salts.
  • stevioside examples include stevittenite (over 98% stevioside), stevitenrich (100% enzymatically treated stevia) and stevia extract REB-A73% (rebaudioside A 73% or more) produced by Daepyung ), And the like.
  • the enzyme-treated stevia is a product in which glucose is added to the stevia extract by using a sugar transfer enzyme, which is a microporous improvement product that reduces the intrinsic bitter taste of stevioside and enhances solubility.
  • the stevia extract REB-A 73% is the highest sweetness and excellent sweetness of the seven sweet components of stevia, is produced through a separate separation operation in stevia.
  • the maximum sweetness of the high-sweetness sweetener over time is expressed in acesulfame potassium first, and the maximum sweetness is expressed in the order of aspartame, sucralose and stevioside. Therefore, steviosides with a late sweetness are preferred for the control of the unpleasant taste that is felt when the drug is absorbed and left in the oral cavity.
  • Oral rapid-release film of the present invention contains a water-soluble polymer.
  • the water-soluble polymer is pullulan, gelatin, pectin, low viscosity pectin, hydroxypropyl methyl cellulose, low viscosity hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, polyacrylic acid, Methyl methacrylate copolymer, carboxyvinyl polymer, polyethylene glycol, alginic acid, low viscosity alginic acid, sodium alginate, carrageenan, modified starch, casein, whey protein isolate, soy protein isolate, zein, levan, elcinane, gluten, acacia At least one water-soluble polymer selected from the group consisting of gums, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum, gellan gum and agar.
  • the water-soluble polymer may be at least one water-soluble polymer selected from the group consisting of pullulan, gelatin, pectin, low viscosity pectin, low viscosity alginic acid, hydroxypropylmethylcellulose and modified starch.
  • the water-soluble polymer may contain 50 to 90% by weight, preferably 60 to 80% by weight, and more preferably 60 to 70% by weight, based on the total weight of the flux film.
  • the pharmacologically active ingredient used in the rapid-release film of the present invention may be a pharmacologically active ingredient orally administered, but particularly, a drug capable of quickly exhibiting medicinal effects by exhibiting rapid dissolution is preferable.
  • Antidiabetic agents such as, for example, glimepiride, pioglitazone, and the like; Agents for treating insomnia such as zolpidem, eszopiclone and the like; Urogenital therapeutics such as tolterodine, tropium and the like; Anti-obesity agents such as sibutramine and the like; Enzymes such as streptokinase and the like; Peptic ulcer solvents such as omeprazole; Antitussive expectorants such as theophylline, glenbuterol and the like; Skin disease treatment agents such as finasteride and the like; Antiemetic agents such as ondansetron; Antidepressants such as fluoxetine and the like; Antihistamines such as fexofen
  • the pharmaceutically active ingredient is triclosan, cetyl pyridium chloride, domiphen bromide, quaternary ammonium salt, zinc compound, acid guinarin, fluoride, alexidine, octonidine, EDTA, aspirin, acetaminophen, ibuprofen, ketoprofen, Diflunisal, Phenopropenecalcium, Naproxen, Tolmethinine Sodium, Indomethacin, Benzonatate, Caramiphene, Edsylate, Menthol, Dextromerophane, Hydrobromide, Hydrochloride, Cropedanol, Diphenhydra Min, pseudoephedrine, phenylephrine, phenylpropanolamine, pseudoephedrine sulfate, brompheniramine maleate, chlorpheniramine maleate, carbinoxamine maleate, clemastine fumarate, dexchlorpheniramine maleate, diphen
  • the active ingredient may contain 0.1 to 30% by weight, preferably 10 to 20% by weight, based on the total weight of the flux film.
  • the filler serves to reduce the slippery properties of the film in the oral cavity and to impart a backbone to the film. It also reduces the sticking properties of the films, and can control the sticking and dissolution rate of the film in the oral cavity and the dissolution rate of the drug.
  • the filler may be added in an amount of 1 to 15% by weight based on the total weight of the flux film.
  • the filler may be one or more components selected from the group consisting of microcrystalline cellulose, cellulose polymers, magnesium carbonate, calcium carbonate, limestone powder, silicates, clays, talc, titanium dioxide and calcium phosphate.
  • the plasticizer can be used to adjust the flexibility of the film.
  • the plasticizer may be added in an amount of 0.1 to 15 wt% based on the total weight of the flux film.
  • the plasticizer is at least one selected from the group consisting of sorbitol, maltitol, xylitol, glycerin, polyethylene glycol, propylene glycol, hydrogenated syrup, syrup, glycerin, triacetin, glycerololate, sucrose fatty acid ester, and medium chain fatty acid. It may be a component.
  • the fastener film of the present invention may include a second sweetener.
  • the second sweetener may be added 0.1 to 10% by weight based on the total weight of the edible film.
  • the sweetener is selected from the group consisting of sugar, glucose, maltose, oligosaccharides, dextrin, invert sugar, fructose, lactose, galactose, syrup, sorbitol, maltitol, xylitol, erythritol, hydrogenated syrup, mannitol, and trehalose It may be one or more components.
  • the oral rapid release film of the present invention may also further comprise an acidulant.
  • the acidulant together with the sweetener, controls the taste and may play a role in stimulating the generation of saliva so that the edible film can be dissolved well.
  • the acidulant may be added in an amount of 0.1 to 10% by weight based on the total weight of the flux film composition.
  • the acidulant may be at least one component selected from the group consisting of citric acid, malic acid, fumaric acid, tartaric acid, ascorbic acid, succinic acid, adipic acid and lactic acid.
  • the oral rapid release film of the present invention may also contain a fragrance. Since the rapid-release film of the present invention is a product that is dissolved and absorbed in the oral cavity, it is necessary to add an appropriate scent.
  • the flavor may be natural flavors, artificial flavors or mixtures thereof.
  • Natural flavors may be extracts from the leaves, flowers, fruits and the like of plants, oils of plants and the like.
  • Plant oils include spearmint oil, cinnamon oil, peppermint oil, lemon oil, clove oil, bay oil, thyme oil, cedar leaf oil, nutmeg oil and sage ( sage) oil, almond oil, and the like.
  • artificial flavors of fruits such as lemons, oranges, grapes, limes, strawberries and artificial synthetic flavors such as vanilla, chocolate, coffee, cocoa, pine needles, ginseng, red ginseng, citrus may be used.
  • the amount of fragrance used depends on a number of factors such as the type, type, and desired strength of the fragrance that is commonly used, and may generally comprise 1 to 15% by weight relative to the total weight of the generic film.
  • Perfume in oil form may be used together with an emulsifier to make it compatible with water-soluble substances.
  • the amount of the emulsifier may be adjusted according to the type and amount of the fragrance, and in general, 0.1 to 10% by weight based on the total weight of the film for the flux.
  • the emulsifier may be at least one component selected from the group consisting of glycerin fatty acid ester, sucrose fatty acid ester, lecithin, enzyme treated lecithin, polysorbate, sorbitan fatty acid ester and propylene glycol.
  • the oral film for oral use of the present invention may contain a pigment suitable for the product.
  • the pigment may be appropriately adjusted in its content as needed, and generally 0.01 to 10% by weight based on the total weight of the edible film.
  • the pigment may be a natural or synthetic pigment.
  • the oral rapid release film of the present invention may also further comprise a freshener.
  • the coolant may be, for example, but not limited to, WS3, WS23 or Questais-L.
  • the freshener can be appropriately adjusted in its content as needed, and generally can be added in an amount of 0.01 to 5% by weight, based on the total weight of the film for fastening.
  • the present invention also provides a flux film comprising the oral flux film composition.
  • the oral rapid-release film of the present invention will preferably form a thin film that maintains an appropriate range of tensile strength and toughness in a very thin film state.
  • the thickness of the rapid-release film of this invention is 20 micrometers-200 micrometers, Preferably it is 40 micrometers-100 micrometers.
  • the present invention also provides a method for producing the oral flux film.
  • the method for producing a rapid-release film of the present invention is a rapid-release film of the present invention.
  • (3) may comprise aging the molded film at a relative humidity of 50 to 70% for 1 to 10 days.
  • the method for producing an edible film according to the present invention can be carried out through, for example, the following process.
  • 2nd solution manufacturing process The 2nd solution which mixed additives, such as a pigment, a sweetener, an acidulant, and a filler, is prepared.
  • 3rd solution manufacturing process The 3rd solution is prepared by mixing an active ingredient, menthol, a fragrance, and a freshener with an emulsifier.
  • the 4th solution is prepared by mixing the said 2nd solution and the said 3rd solution.
  • e) 5th solution manufacturing process It raises the temperature to 60 degreeC or more, and mixes the said 1st solution and the said 4th solution, and manufactures a 5th solution.
  • the fifth solution is filtered and then introduced into a molding machine to form a film.
  • the temperature of the molding machine is 50 to 80 °C and manufactured in roll form through a belt drum dryer.
  • the molded film contains moisture suitable for slitting or cutting through a aging process of about 1 to 10 days at a relative humidity of 50 to 70%. At this time, the water content is appropriately 8 to 12%.
  • the following process may be further performed as a subsequent process of the manufacturing method.
  • the aged rolls are slits into small rolls, cut into appropriate sizes and filled into small containers or aluminum wrappers.
  • Filled small containers or aluminum bags are repackaged in small boxes or blistered into products.
  • the rapid-release film prepared by the method of the present invention is rapidly disintegrated and dissolved by saliva in the oral cavity without eating extra water, and thus can be easily administered to patients or elderly and children who have difficulty in swallowing tablets.
  • Meloxycam was added as a pharmaceutically active ingredient to prepare a film according to the composition shown in Table 1 below.
  • Aspartame and starch oxide were used by Daesang Co., Ltd., Acesulfame potassium was manufactured by Nutrinova, Sucralose was produced by Tate & Lyle, Carrageenan was manufactured by MSC, and Polysorbate was manufactured by Ilshin Wells. The product, pullulan was used by Hayashibara, and peppermint oil and lemon by Borax.
  • Low viscosity pectin is CIPIKELCO's GENU pectin DSS
  • gelatin is Geltech's 100 Bloom product
  • hydroxypropylmethylcellulose is Demasa's demacol HE 5/6 BV
  • low viscosity alginic acid is MSC's login
  • hydroxypropyl starch Grain Processing Corp. used the product.
  • Films were prepared according to the compositions described in Tables 6 and 7, and placed in the mouths of six adult men and women, the time at which the film completely disintegrated by the saliva of the oral cavity was measured, and the sensory test was performed. Sensory tests were performed randomly and are described in Table 8 below.
  • Oral quick-release film of the present invention is not only excellent in the unpleasant taste blocking effect, but also can be easily produced by a low cost and simplified recipe, so that oral cleansers, bad breath removers, nutritional supplements for oral cleanliness and oral and gastrointestinal tract It can be usefully used as a snow-soluble agent for the absorption of the drug.

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Abstract

La présente invention concerne un film à dissolution rapide administré par voie orale qui se dissout rapidement dans la bouche. L’invention porte plus particulièrement sur un film à dissolution rapide administré par voie orale qui comprend un édulcorant à base de stévioside et un édulcorant intense selon un rapport (p/p) compris entre 1:3 et 3:1. Le film à dissolution rapide administré par voie orale selon la présente invention prévient efficacement le goût désagréable des médicaments et améliore l’arrière-goût laissé par les médicaments. De plus, les patients peuvent dissoudre rapidement le film dans la bouche sans eau, et ainsi les patients acceptent plus facilement de prendre des médicaments.
PCT/KR2009/003451 2009-06-25 2009-06-25 Film à dissolution rapide administré par voie orale qui permet de prévenir efficacement tout goût désagréable WO2010150930A1 (fr)

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PCT/KR2009/003451 WO2010150930A1 (fr) 2009-06-25 2009-06-25 Film à dissolution rapide administré par voie orale qui permet de prévenir efficacement tout goût désagréable

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WO2012104726A2 (fr) * 2011-02-01 2012-08-09 E.P.C. (Beijing) Plant Pharmaceutical Technology Co., Ltd Edulcorant à base de stevia ayant un agent tensioactif
CN104125822A (zh) * 2011-12-23 2014-10-29 欧莱雅 甜菊醇、甜菊醇糖苷衍生物或其异构体之一用于刺激、修复或调节皮肤和半粘膜的细胞新陈代谢的美容用途
US9131718B2 (en) 2009-06-16 2015-09-15 Epc (Beijing) Natural Products Co., Ltd. Process for rebaudioside D
WO2016048059A1 (fr) * 2014-09-24 2016-03-31 주식회사 태준제약 Composition pour le traitement de maladies gastro-intestinales, contenant de l'acide alginique ou un alginate et un extrait de glycyrrhiza uralensis fischer
US9492444B2 (en) 2013-12-17 2016-11-15 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US9578895B2 (en) 2010-08-23 2017-02-28 Epc (Beijing) Natural Products Co., Ltd. Rebaudioside A and stevioside compositions
US9707184B2 (en) 2014-07-17 2017-07-18 Pharmaceutical Manufacturing Research Services, Inc. Immediate release abuse deterrent liquid fill dosage form
US9795156B2 (en) 2011-03-17 2017-10-24 E.P.C (Beijing) Plant Pharmaceutical Technology Co., Ltd Rebaudioside B and derivatives
CN108813630A (zh) * 2018-07-04 2018-11-16 上海海洋大学 一种可直接口服并速溶的自乳化膜剂及其制备方法
US10172797B2 (en) 2013-12-17 2019-01-08 Pharmaceutical Manufacturing Research Services, Inc. Extruded extended release abuse deterrent pill
US10195153B2 (en) 2013-08-12 2019-02-05 Pharmaceutical Manufacturing Research Services, Inc. Extruded immediate release abuse deterrent pill
US10264811B2 (en) 2014-05-19 2019-04-23 Epc Natural Products Co., Ltd. Stevia sweetener with improved solubility
US10357052B2 (en) 2014-06-16 2019-07-23 Sweet Green Fields USA LLC Rebaudioside A and stevioside with improved solubilities
US10485256B2 (en) 2014-06-20 2019-11-26 Sweet Green Fields International Co., Limited Stevia sweetener with improved solubility with a cyclodextrin
CN111012762A (zh) * 2019-11-05 2020-04-17 浙江工业大学 一种氢溴酸加兰他敏口腔速溶膜剂及其制备方法
US10959958B2 (en) 2014-10-20 2021-03-30 Pharmaceutical Manufacturing Research Services, Inc. Extended release abuse deterrent liquid fill dosage form
US11179331B1 (en) 2020-04-21 2021-11-23 Cure Pharmaceutcai Holding Corp Oral soluble film containing sildenafil citrate
CN115624530A (zh) * 2022-09-22 2023-01-20 广西纯正堂制药有限公司 枸地氯雷他定口腔黏附片及其制备方法
CN116270487A (zh) * 2023-03-15 2023-06-23 南京中医药大学 一种小儿氨酚黄那敏颗粒及制备方法

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WO2016048059A1 (fr) * 2014-09-24 2016-03-31 주식회사 태준제약 Composition pour le traitement de maladies gastro-intestinales, contenant de l'acide alginique ou un alginate et un extrait de glycyrrhiza uralensis fischer
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