[go: up one dir, main page]

WO2013119002A1 - Composition laxative contenant du polyéthylène glycol et de la vitamine c - Google Patents

Composition laxative contenant du polyéthylène glycol et de la vitamine c Download PDF

Info

Publication number
WO2013119002A1
WO2013119002A1 PCT/KR2013/000857 KR2013000857W WO2013119002A1 WO 2013119002 A1 WO2013119002 A1 WO 2013119002A1 KR 2013000857 W KR2013000857 W KR 2013000857W WO 2013119002 A1 WO2013119002 A1 WO 2013119002A1
Authority
WO
WIPO (PCT)
Prior art keywords
laxative composition
polyethylene glycol
enteric
composition
laxative
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.)
Ceased
Application number
PCT/KR2013/000857
Other languages
English (en)
Korean (ko)
Inventor
한태희
장우영
채준호
한승희
이준엽
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.)
Taejoon Pharm Co Ltd
Original Assignee
Taejoon Pharm Co Ltd
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 Taejoon Pharm Co Ltd filed Critical Taejoon Pharm Co Ltd
Publication of WO2013119002A1 publication Critical patent/WO2013119002A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • 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
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • the present invention relates to enteric laxative compositions containing polyethylene glycol and vitamin C and pharmaceutical formulations comprising the same.
  • Intestinal lavage has been used in endoscopy, diagnostic or surgical measures such as colonoscopy, barium enema X-rays and intravenous renal angiography, and first aid, for which intestinal laxative compositions are used. do.
  • the intestinal laxative composition as described above is characterized by constipation caused by strict constipation, rigid constipation, functional constipation such as rectal constipation, stenosis due to postoperative adhesion, and organic constipation caused by intestinal disease, drug-induced constipation It can also be used to treat and relieve symptoms.
  • pretreatment enteric cleaner In the diagnosis and treatment of intestinal disease, sufficient pretreatment must be preceded in order to provide a safe and effective test in the endoscopy, diagnostic or surgical measures, and the ideal pretreatment enteric cleaner is safe, simple and patient compliance. It should be good and excellent in the cleansing effect.
  • an enteric laxative composition for this purpose, a method of inducing diarrhea by ingesting a large amount of isotonic water containing only an electrolyte was used.
  • An example of this is an aqueous formulation consisting of phosphate salts, in which the phosphate salt solution produces an osmotic effect, inducing a significant amount of water into the intestine to promote bowel movement.
  • the preparations cannot be used in patients with nephropathy, heart disorders or hypertension.
  • enteric laxative compositions comprising polyethyleneglycol / electrolyte consisting of sodium sulfate, potassium chloride, sodium chloride, sodium bicarbonate and the like, and water-bound polyethyleneglycol are most commonly used.
  • enteric laxative compositions containing polyethyleneglycol / electrolyte have to drink about 4 L of solution within 2-3 hours cycle (Afridi et al., Gastrointest. Endosc., 1995, 41, 485-489).
  • side effects such as discomfort, nausea, cramps and vomiting due to overdose (Dipalma et al., Am. J. Gastroenterol., 2003, 98, 2187-2191) It may also be offensive. Therefore, there have been attempts to reduce the amount of salt or add flavors to solve these side effects or discomfort.
  • US Patent No.7169381 provides a polyethylene glycol / electrolyte enteric laxative composition containing vitamin C, which increases the osmotic effect to reduce the weight of polyethylene glycol, thereby reducing the weight of the liquid state immediately before administration. There is an effect that can reduce the volume of the composition. In addition, it protects the intestinal cells, mitigates some of the toxicity that may be caused by excessive use of polyethylene glycol, and protects the intestines by inhibiting the death of intestinal useful bacteria. It can be said that the effect of compensating for the disadvantages of the composition is great.
  • the polyethylene glycol / electrolyte enteric laxative composition containing vitamin C is unstable in heat, light, moisture, etc., and is easily destroyed during storage or distribution, or an oxidation reaction and a browning reaction occur, and thus its utility is significantly lower than immediately after preparation.
  • the United States Patent No. 7169381 also proposed to separate or separate the components of the intestinal laxative composition, such as vitamin C, from the mixture of other pharmaceutical ingredients, but the management and manufacturing costs according to the packaging There is a disadvantage of being increased.
  • US Patent No. 5274001 provides a single mixture of enteric laxative compositions in which the least stable vitamin C of the components of the enteric laxative composition is coated with silicone or ethyl cellulose. .
  • the intestinal laxative composition disclosed in the patent has a disadvantage in that the overall manufacturing cost according to the coating cost is increased because the total composition ratio of vitamin C is high. There is also a controversy that vitamin C can be easily destroyed by the heat generated during coating, resulting in lower stability.
  • the silicone or ethyl cellulose-coated vitamin C has low solubility in aqueous solution, and thus it is difficult to use as a component of intestinal laxatives in which powder components are dissolved in water and drinkable.
  • the inventors of the present invention while studying a method for producing a highly safe intestinal laxative composition during storage or distribution, when some of the components included in the intestinal laxative composition is separated from the mixture of the other pharmaceutical ingredients and the layer, It was found that there is little change in the composition of the composition, it was confirmed that the stability even when mixed packaging, it was possible to complete the present invention by confirming that the production cost for this can be significantly reduced.
  • the present invention provides a mixed packaged intestinal laxative composition containing polyethylene glycol and vitamin C.
  • the present invention polyethylene glycol, the first pharmaceutical component
  • Vitamin C second pharmaceutical ingredient
  • a third pharmaceutical ingredient consisting of a sweetener
  • It relates to a pharmaceutical enteric laxative composition or a pharmaceutical formulation comprising the same, characterized in that one of the first to third pharmaceutical ingredients is separated in order to minimize direct contact with the enteric laxative mixture of the present invention.
  • One of the first to third pharmaceutical ingredients such as coating powder (powder), coating granules, coating tablets, capsules and uncoated tablets to minimize physical contact with the mixture of other pharmaceutical ingredients It may be a sweetener prepared in more than one state.
  • the mixed-packed enteral laxative composition of the present invention is prepared by separating the third pharmaceutical component in consideration of each part by weight, manufacturing process, and production cost of the first to third pharmaceutical ingredients of the enteric laxative composition of the present invention. to provide.
  • a single or a mixture of coating bases selected from the group consisting of methacrylate copolymer (Eudragit) series, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) may be used.
  • PVP polyvinylpyrrolidone
  • PVA polyvinyl alcohol
  • the coating agent it is best to use a coating base consisting of a mixture of a polyvinyl alcohol and a methacrylate copolymer which are water-soluble agents.
  • the coating layer if necessary, pharmaceutically acceptable additives,
  • PEG polyethylene glycol
  • the light-shielding agent may include titanium dioxide (TiO 2 ), etc. in the pigment, but is not significantly limited.
  • the enteric laxative composition may further include an electrolyte supply salt, a flavoring agent, and other pharmaceutical excipients, more preferably, the enteric laxative composition may be 5 to 15 parts by weight of vitamin C, based on 100 parts by weight of polyethylene glycol, 5-15 parts by weight of the salt for the electrolyte supply, 0.01-3 parts by weight of the sweetener, 0.01-3 parts by weight of the flavoring agent and other pharmaceutical excipients may be mixed.
  • the 'Purgative' is a drug that acts to excrete the contents of the intestine, and when the colon (X-ray, endoscopy) is examined through a strong bowel (Stronger Catharsis) that completely or completely emptyes the large intestine (complete purgation). It can lead to mild catharsis that causes diarrhea (partial purgation) as well as pretreatment intestinal lavage, leading to weakening or releasing feces.
  • the enteric laxative composition of the present invention contains polyethylene glycol, vitamin C and salts for supplying electrolyte as main components,
  • the polyethylene glycol is a high osmotic laxative, and in the case of a polymer having a large molecular weight, it is not absorbed by the intestine but remains in solution and is transferred to the large intestine. It serves to facilitate bowel movement in the form of a liquid.
  • the electrolyte supply salts are active ions or molecules that act as osmosis, are not absorbed in the intestinal tract, move water in the intestinal tract to facilitate bowel movement, and are rarely absorbed in the intestine. Used as a salt.
  • the vitamin C can be used in amorphous, crystalline or chloride form, and can be used alone or in combination of one or more.
  • the function of vitamin C is to increase the osmotic effect of polyethylene glycol has the effect of reducing the amount of polyethylene glycol, protects the intestinal cells, and serves to protect the intestines by inhibiting the death of intestinal useful bacteria.
  • Polyethylene glycol of the present invention is a relatively stable, non-toxic substance having different properties according to the molecular weight, the average molecular weight of about 200 to 35,000 is used, polyethylene glycol 400 (PEG 400) is a somewhat tacky transparent liquid, polyethylene glycol 1,500 (PEG 1,500) is a soft solid, polyethylene glycol 4,000-20,000 (PEG 4,000-20,000) is a white, light solid in the form of flakes or powders.
  • polyethylene glycol 3,350 PEG 3,350
  • polyethylene glycol 4,000 PEG 4,000
  • polyethylene glycol 6,000 PEG 6,000
  • polyethylene Glycol 8,000 PEG 8,000
  • the salt for electrolyte supply of the intestinal laxative composition of the present invention includes at least one electrolyte.
  • Polyethyleneglycol may remain in solution rather than absorbed by the intestinal tract, altering the concentration of electrolytes in the patient's body, preventing the absorption of water into the body due to increased osmotic pressure in the colon.
  • Sodium ions, magnesium ions, and calcium ions are suitable to alleviate this. These ions may be present in the form of suitable salts, for example their chlorides, bicarbonates, acetates, carbonates, citrates, fumarates, gluconates, malates, nitrates, phosphates, succinates, or sulfates. Chlorides and sulphates such as sodium chloride, potassium chloride and sodium sulfate are particularly preferred.
  • the electrolyte feed salt is selected from sodium chloride, potassium chloride and sodium sulfate.
  • the composition of the present invention comprises both of these electrolytes.
  • the sweetener of the intestinal laxative composition of the present invention comprises at least one sweetener.
  • at least one sweetener In addition to the usual sugars Glucose, Sucrose, Dextrose, Fructose and Maltose, saccharin and saccharin exhibit sweetness and fast solubility even in small amounts.
  • sucralose may be used in combination with one or more sweeteners selected from the group consisting of, preferably the sweetener based on 100 parts by weight of polyethylene glycol 0.01 3 parts by weight may be included.
  • the intestinal laxative composition may be prepared by adding a flavoring agent in addition to the sweetening agent to improve the medication compliance of the patient, preferably the flavoring agent may be included 0.01 to 3 parts by weight based on 100 parts by weight of polyethylene glycol.
  • the flavoring agent may include a liquid or powder (powder) or clathrate form.
  • Enteric laxative compositions of the present invention may be prepared in the form of powders, granules, or tablets. At this time, when prepared in a powder (powder) or granular composition,
  • the sweetener By separating the intestinal laxative composition and the layer of the present invention, only the sweetener can be prepared in powder or coated granules or coated tablets with a separate coating, even in uncoated or capsule-filled sweeteners. Can be prepared.
  • the above example is an example of the layered enteric laxative composition of the present invention, which does not limit the spirit of the present invention, and the same by the layer separation of polyethylene glycol (PEG), one of the main components, or the layer separation of vitamin C. You can expect the effect.
  • PEG polyethylene glycol
  • the enteric laxative compositions of the present invention may include additional ingredients to enhance the characteristics of the solid dosage form, to maintain the particle state of the active substance during the formulation process, or to increase the safety of the composition.
  • the additional component may be mixed with other components of the enteric laxative composition of the present invention, and may be one that does not adversely affect the osmotic pressure of the enteric laxative composition of the present invention.
  • Additional ingredients that may be used in the formulations of the invention may include, for example, diluents, binders, glidants, glidants, colorants, disintegrants, flavoring agents, functional polymers or waxes.
  • the formulation of the enteric laxative compositions of the present invention may comprise a glidant.
  • lubricants include, but are not limited to, magnesium stearate, potassium stearate, talc, stearic acid, sodium lauryl sulfate and paraffin. Lubricants facilitate the preparation of solid dosage forms.
  • carriers such as sodium citrate and di-calcium phosphate, stearates, silica, gypsum, starch, lactose, sucrose, glucose, mannitol, talc, and fillers or extenders such as silicic acid, hydroxypropylmethylcellulose, hydride Binders such as oxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone and acacia, moisturizers such as glycerol, agar, calcium carbonate, potato starch, tapioca starch, alginic acid, certain silicates, colloidal silicon dioxide, sodium starch glycolate , Disintegrants such as crospovidone and sodium carbonate, dissolution retardants such as paraffin, absorption accelerators such as quaternary ammonium compounds, wetting agents such as cetyl alcohol and glycerol monostearate, absorbents such as kaolin and bentonite clay, stables such as fumaric acid Topical, Colorant, Bu
  • the enteric laxative composition of the present invention can be used as a solid dosage form dissolved in water immediately before administration.
  • the appropriate dosage of the intestinal laxative compositions of the present invention can be varied depending on the individual to be treated and the purpose. For example, age, weight, medical history of the individual patient, and the like may affect the therapeutic effect of the treatment. Induction of mild catharsis may require low dose administration of the composition, whereas complete bowel movement for preoperative intestinal cleansing during colon (X-ray, endoscopic) examination may require higher doses. .
  • the enteric laxative composition of the present invention is provided in a mixed or separately packaged state as needed, preferably a mixed-packaged enteral laxative composition, 5-15 parts by weight of vitamin C, based on 100 parts by weight of polyethylene glycol, a compound for supplying an electrolyte 5 to 15 parts by weight and 0.01 to 3 parts by weight of sweetener, 0.01 to 3 parts by weight of flavoring agent and additional pharmaceutical ingredients, more specifically, 100 g of polyethylene glycol 3,350 (PEG 3,350), vitamin C (amorphous, crystalline) Or 10.6 g of chloride form alone or in a mixture of one or more thereof, 11.206 g of an electrolyte supply salt (mixed form of sodium sulfate, sodium chloride, potassium chloride), sweetener (0.317 g of aspartame and one or more mixed forms), complex Flavor and pharmaceutical additives and coating base polyvinyl alcohol / methacrylate copolymer mixtures.
  • a mixed-packaged enteral laxative composition 5-15
  • the total daily dose for light bowel movement is, for example, from about 60 g (58-62 g) / 500 mL to about 120 g (116-124 g) / 1 L of enteric laxative composition in which the layer of the present invention is dissolved in water You can be the best.
  • the total dose used for complete bowel movement for pretreatment intestinal cleansing during colon (X-ray, endoscopy) examination is about 240 g (232-248) / intestinal laxative composition in which the layer of the present invention is dissolved in water. It can be 2L of laxative and is taken with or without splitting.
  • the intestinal laxative composition according to the present invention provides a method for treating gastrointestinal disorders such as constipation when provided in low doses, and when provided in high doses, the colon is examined for colon (X-ray, endoscopy) examination or surgical operation. Provides a method of completing a toilet to pretreat.
  • Intestinal laxative compositions of the present invention may be prepared in pharmaceutical formulations conventional in the art such as powders, granules, capsules, pills, tablets, multi-layered tablets, suspensions and the like until the desired effect is achieved and up to a daily maximum Undivided or divided doses may be taken within dose limits.
  • Water is added to the mixed packaged laxative composition of the present invention in a container and shaken well to prepare a homogeneous solution. If necessary, the solution can be refrigerated before drinking. Prepared solutions should be stored refrigerated and used within 24 hours.
  • Non-split administration (evening administration) Method At 6 pm the day before colonoscopy, take 1L of the preparation solution for 1 hour (1 cup of 250mL every 15 minutes), and 1L of the preparation solution for 1 hour after 1.5 hours. Also take an additional 1 liter of water during the evening.
  • Intestinal laxative compositions of the invention can be administered via a variety of routes.
  • the laxative composition may be administered orally or may be administered via a tube such as a feeding tube or a feeding tube on the nose.
  • the present invention relates to a mixed packaged intestinal laxative composition containing polyethylene glycol and vitamin C, wherein the phase change of the intestinal laxative composition is obtained by separating some of the components included in the intestinal laxative composition from a mixture of other pharmaceutical ingredients and the layer.
  • the vitamin C content is maintained, thereby maintaining stability during storage or distribution and maintaining an intestinal cleaning or constipation removal effect for diagnostic tests and surgery during shelf life.
  • Figure 2 is a photograph confirming the stability test results of Comparative Examples 29-34 and Comparative Example test results (acceleration day 10) for the cross-test of the salt for the electrolyte supply to the mixture of the first to third pharmaceutical ingredients as a result of the formulation compatibility test to be.
  • Figure 3 is a photograph showing the change in the appearance of the properties of the intestinal laxative composition of the present invention comprising a sweetener powder or granules coated with a mixed coating base of polyvinyl alcohol and methacrylate copolymer and stability results for 6 months of acceleration.
  • Figure 4 is a photograph showing the change in the appearance of the properties of the intestinal laxative composition of the present invention comprising a sweetener tablet or uncoated tablet coated with a mixed coating base of polyvinyl alcohol and methacrylate copolymer and stability results for 6 months of acceleration.
  • Figure 5 shows the appearance of the change in appearance and stability of the intestinal laxative composition of the present invention comprising a capsule filled with a sweetener powder or granules coated with a mixed coating base of polyvinyl alcohol and methacrylate copolymer It is a photograph.
  • Figure 6 is a photograph showing the change in the appearance of the properties of the intestinal laxative composition of the present invention comprising a capsule filled with sweetener powder or granules and stability results for 6 months of acceleration.
  • FIG. 7 shows a composition of the present invention mixed packaged in one or more of a powder, coated granules, coated tablets, capsules and uncoated tablets to minimize physical contact with the mixture of pharmaceutical ingredients. It is a schematic diagram about.
  • Enteric laxative compositions containing polyethylene glycol and vitamin C are known to be unstable in heat, light, and moisture, so that vitamin C is easily destroyed during storage or distribution, and oxidation and browning reactions occur. It is distributed in the market in a separately packaged form.
  • the present inventors conducted an experiment to determine the suitability of the mixed packaging according to vitamin C and other main ingredients and pharmaceutical excipients as a main component in order to make a vitamin C mixed package form.
  • various combinations of experimental groups were prepared and mixed as shown in ⁇ Table 1>.
  • An accelerated stability test was conducted, and the results are shown in FIG. 1.
  • the vitamin C 15g was packaged and stored for 10 days and then visually confirmed.
  • Test Example 11 in which polyethylene glycol 266.7g is mixed with 15g of vitamin C
  • 20 g, 7.2 g, and 2.7 g of anhydrous sodium sulfate, sodium chloride, and potassium chloride alone or in addition to each other were added according to the above conditions, and the appearance change was visually confirmed after storage for 10 days under long-term and accelerated conditions.
  • the blending amount of polyethylene glycol and salts in the enteric laxative composition was mixed twice the maximum weight of the present enteric laxative.
  • the intestinal laxative composition is mixed according to the conditions of ⁇ Table 2>, and after storage for 10 days under long-term and accelerated conditions It was visually confirmed whether there was a change. The control for this was that all components were mixed. Properties of the test results 29 to 34 is the same as FIG.
  • ⁇ Comparative Example 02> was packaged and mixed with the same composition as the ⁇ Comparative Example 01> in order to compare the changes in the properties of some of the ⁇ Test Examples 01 ⁇ 34>, and after storage for 10 days under long-term and accelerated conditions It was visually confirmed whether there was a change.
  • test example and the comparative example of the present invention are merely illustrative to help understanding, the content of the present invention is not limited thereto.
  • enteric laxative composition of the present invention polyethylene glycol and the components of the remaining enteric laxative composition were separately mixed, and then visually checked for changes in properties. In the comparison group, all components were mixed. After storage for 10 days under long-term and accelerated conditions, the appearance change was visually confirmed.
  • vitamin C and the components of the remaining enteric laxative composition were separately mixed according to the conditions of ⁇ Table 4>, and then visually confirmed whether there was a change in appearance after storage for 10 days under accelerated conditions.
  • enteric laxative composition of the present invention polyethylene glycol, vitamin C and the components of the remaining enteric laxative composition were separately mixed according to the conditions of ⁇ Table 5>, and then the change in appearance after 10 days storage under long-term and accelerated conditions was visually confirmed. In the comparison group, all components were mixed.
  • Example 17 and Comparative Example 02 it was found that the change in appearance in the accelerated conditions in Example 17 and Comparative Example 02 is severe, the intestinal laxative composition at this time was confirmed to have a red or yellow. Therefore, when mixed with the other components of each of the components of polyethylene glycol and vitamin C, as in Examples 13 to 16, it can be seen that there is no change in appearance compared to the initial properties.
  • Super sweetener is a small amount, and general sweetener was set up by tasting evaluation of the amount of sweetness similar to the super sweetener.
  • each component of the intestinal laxative composition of the present invention was prepared in the form of a coating powder or granules using a fluidized bed coater, and then all the components were mixed under the conditions of ⁇ Table 8>, under accelerated conditions After storage for 10 days, the change of appearance was visually confirmed. In the comparison group, all components were mixed.
  • polyethylene glycol 3,350 1,000 g was placed in a fluidized bed coater and coated with a polyvinyl alcohol (PVA) composition as a coating base.
  • PVA polyvinyl alcohol
  • the polyvinyl alcohol (PVA) composition was prepared by dissolving or dispersing 500 g of purified water in 25 g of polyvinyl alcohol.
  • the coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 28 °C, inlet air temperature 29 °C, flow 8, outlet air flat 40%.
  • 1,120.6 g of salt 750 g of sodium sulfate anhydride, 269.1 g of sodium chloride and 101.5 g of potassium chloride
  • PVA polyvinyl alcohol
  • This polyvinyl alcohol (PVA) composition was prepared by dissolving or dispersing 560 g of purified water in 28 g of polyvinyl alcohol. The coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 35 °C, inlet air temperature 37 °C, flow 8, outlet air flat 40%.
  • 1,000 g of the flavoring agent was placed in a fluidized bed coater and coated with a polyvinyl alcohol (PVA) composition as a coating base.
  • PVA polyvinyl alcohol
  • This polyvinyl alcohol (PVA) composition was prepared by dissolving or dispersing 500 g of purified water in 25 g of polyvinyl alcohol. The coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 35 °C, inlet air temperature 37 °C, flow 8, outlet air flat 40%.
  • the polyvinyl alcohol (PVA) composition was prepared by dissolving or dispersing 475 g of purified water in 23.78 g of polyvinyl alcohol.
  • the coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 37 °C, inlet air temperature 38 °C, flow 8, outlet air flat 40%.
  • the polyvinyl alcohol (PVA) composition was prepared by dissolving or dispersing 4.756 g of methacrylate and 950 g of purified water in 42.80 g of polyvinyl alcohol.
  • the coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 37 °C, inlet air temperature 38 °C, flow 8, outlet air flat 40%.
  • the polyvinylpyrrolidone (PVP K-25) composition was prepared by dissolving or dispersing 570 g of purified water in 28.53 g of polyvinylpyrrolidone (PVP K-25). The coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 37 °C, inlet air temperature 38 °C, flow 8, outlet air flat 40%.
  • a sweetener 600 g of aspartame, 351 g of acesulfame potassium was placed in a fluidized bed coater and coated with a hydroxypropylmethylcellulose (HPMC 2910, 50 cps) composition.
  • HPMC 2910, 50 cps hydroxypropylmethylcellulose
  • This hydroxypropyl methyl cellulose composition was prepared by dissolving or dispersing 760 g of purified water in 38.04 g of hydroxypropyl methyl cellulose (HPMC 2910, 50 cps). The coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 37 °C, inlet air temperature 38 °C, flow 8, outlet air flat 40%.
  • This methacrylic acid copolymer (PMMA) composition was prepared by dissolving or dispersing 570 g of purified water in 28.53 g of methacrylate copolymer (PMMA). The coating process was carried out under the conditions of inlet air 4.2 bar, spray air 1.8 bar, outlet air temperature 37 °C, inlet air temperature 38 °C, flow 8, outlet air flat 40%.
  • Example 42 and Examples 45 to 49 there is little or no change in the appearance, the polyethylene glycol of the uncoated powder (Powder) state or the coated state
  • the sweetener was added, it was observed that there was almost no change in appearance regardless of the type, and the intestinal laxative composition of the present invention was able to be mixed and packaged in a stable state even when one of the components of polyethylene glycol and sweetener was separated (coated). It was confirmed.
  • Example 42 the proportion of the total weight part of the enteric laxative composition is high, and in the case of polyethylene glycol, since the melting point should be set at a low temperature during coating, there is a disadvantage in that the manufacturing time is long and the coating yield is low. In terms of manufacturing, it can be seen that the sweetener coating is more preferred.
  • each component of the enteric laxative composition of the present invention is packaged in the form of a coated powder or coated granules (Examples 45 to 59), it is carried out to ensure the variety and potential of the formulation.
  • each component was mixed under the conditions of the following ⁇ Table 9>, and the change in appearance after 30 days storage under long-term and accelerated conditions was visually confirmed. The control for this was that all components were mixed.
  • Granules are granulated and placed in a dryer to dry.
  • Granules are granulated and placed in a dryer to dry.
  • Granules are granulated and placed in a dryer to dry.
  • the sweetener uncoated tablet of Example 50 was water-coated with PVA to prepare a film-coated tablet (2.5% coating of the sweetener uncoated weight).
  • the sweetener uncoated tablet of Example 51 was water-coated with PVA to prepare a film-coated tablet (2.5% coating of the sweetener uncoated weight).
  • the sweetener uncoated tablet of Example 52 was water-coated with PVA to prepare a film-coated tablet (2.5% coating of the sweetener uncoated weight).
  • the sweetener uncoated tablet of Example 50 was water-coated with a PVA / PMMA copolymer mixture to prepare a film-coated tablet. (2.5% coating of sweetener uncoated weight)
  • the sweetener uncoated tablet of Example 51 was water-coated with a PVA / PMMA copolymer mixture to prepare a film-coated tablet. (2.5% coating of sweetener uncoated weight)
  • the sweetener uncoated tablet of Example 52 was water-coated with a PVA / PMMA copolymer mixture to prepare a film-coated tablet. (2.5% coating of sweetener uncoated weight)
  • the sweetener uncoated tablet of Example 52 was water-coated with a PVA / PMMA Copolymer mixture to prepare a film-coated tablet form (5.0% coating of sweetener uncoated weight).
  • One of the components of the intestinal laxative composition of the present invention was prepared in the form of a powder or granule in which a sweetener was not coated and filled in a hard capsule, and then each component was prepared under the conditions of the following ⁇ Table 10>. All were mixed, and after 30 days of storage under long-term and accelerated conditions, the appearance change was visually confirmed. The control for this was that all components were mixed.
  • the sweetener is prepared in the form of a powder (coated powder) or coated granules filled in a hard capsule, and then each component is the conditions of the following ⁇ Table 10> All of them were mixed, and after 30 days of storage under long-term and accelerated conditions, the appearance change was visually confirmed. The control for this was that all components were mixed.
  • Example 60-68 enteric laxative composition prepared in the form of a sweetener capsule was observed that almost no change in appearance under accelerated conditions, the layer of the present invention through a mixed packaging in a separate formulation When the contact area was reduced and the reactivity was suppressed, it was observed that the possibility of change of properties was low.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/KR2013/000857 2012-02-10 2013-02-04 Composition laxative contenant du polyéthylène glycol et de la vitamine c Ceased WO2013119002A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2012-0013997 2012-02-10
KR1020120013997A KR101210831B1 (ko) 2012-02-10 2012-02-10 폴리에틸렌글리콜과 비타민 씨를 함유하는 장관 하제 조성물

Publications (1)

Publication Number Publication Date
WO2013119002A1 true WO2013119002A1 (fr) 2013-08-15

Family

ID=47907372

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2013/000857 Ceased WO2013119002A1 (fr) 2012-02-10 2013-02-04 Composition laxative contenant du polyéthylène glycol et de la vitamine c

Country Status (2)

Country Link
KR (1) KR101210831B1 (fr)
WO (1) WO2013119002A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8999313B2 (en) 2012-09-11 2015-04-07 Norgine Bv Compositions
US9592252B2 (en) 2011-03-11 2017-03-14 Norgine Bv Colonoscopy—preparation

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20220033810A (ko) * 2020-09-10 2022-03-17 강윤식 장 정결용 보조 음료

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5997906A (en) * 1996-11-13 1999-12-07 C.B. Fleet Company, Inc. Coated sodium phosphate bowel cleanser
JP2006507281A (ja) * 2002-10-25 2006-03-02 ノージーン ヨーロピ ビーブイ 結腸洗浄組成物
US20090053304A1 (en) * 2007-08-23 2009-02-26 Jinling Chen Composition and method of producing a taste masking formulation of laxatives for bowel cleaning preparation prior to colonoscopy
JP2011162549A (ja) * 2011-03-28 2011-08-25 Ajinomoto Co Inc 腸管洗浄用組成物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5997906A (en) * 1996-11-13 1999-12-07 C.B. Fleet Company, Inc. Coated sodium phosphate bowel cleanser
JP2006507281A (ja) * 2002-10-25 2006-03-02 ノージーン ヨーロピ ビーブイ 結腸洗浄組成物
US20090053304A1 (en) * 2007-08-23 2009-02-26 Jinling Chen Composition and method of producing a taste masking formulation of laxatives for bowel cleaning preparation prior to colonoscopy
JP2011162549A (ja) * 2011-03-28 2011-08-25 Ajinomoto Co Inc 腸管洗浄用組成物

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9592252B2 (en) 2011-03-11 2017-03-14 Norgine Bv Colonoscopy—preparation
US10646512B2 (en) 2011-03-11 2020-05-12 Norgine Bv Colonoscopy - preparation
US10780112B2 (en) 2011-03-11 2020-09-22 Norgine Bv Colonoscopy-preparation
US10792306B2 (en) 2011-03-11 2020-10-06 Norgine Bv Colonoscopy—preparation
US11529368B2 (en) 2011-03-11 2022-12-20 Norgine Bv Colonoscopy—preparation
US8999313B2 (en) 2012-09-11 2015-04-07 Norgine Bv Compositions
US9326969B2 (en) 2012-09-11 2016-05-03 Norgine Bv Compositions
US9707297B2 (en) 2012-09-11 2017-07-18 Norgine Bv Compositions
US10016504B2 (en) 2012-09-11 2018-07-10 Norgine Bv Compositions
US10918723B2 (en) 2012-09-11 2021-02-16 Norgine Bv Colon cleansing compositions and methods of use
US12083179B2 (en) 2012-09-11 2024-09-10 Norgine Bv Colon cleansing compositions and method of use

Also Published As

Publication number Publication date
KR101210831B1 (ko) 2012-12-11

Similar Documents

Publication Publication Date Title
CZ2002724A3 (cs) Farmaceutický přípravek obsahující derivát benzamidu se zlepąenou rozpustností a orální absorptivitou
BR112012028857B1 (pt) Composições farmacêuticas administráveis por via oral que compreendem derivados de 1- (beta-d glucopiranosil)-2-tienil-metilbenzeno como inibidores de sglt
WO2014054880A1 (fr) Nouvelle composition laxative à stabilité améliorée, contenant du polyéthylène glycol et de la vitamine c
WO2020040438A1 (fr) Préparation pharmaceutique ayant d'excellentes propriétés de dissolution, contenant de l'ésoméprazole et du bicarbonate de sodium
WO2020130502A1 (fr) Composition pharmaceutique comprenant l'empagliflozine et la sitagliptine
ES2319292T3 (es) Composicion medicinal solida estable, de administracion por via oral de ramosetron.
WO2017119801A1 (fr) Préparation pharmaceutique à usage oral et goût masqué contenant de la varénicline ou un sel pharmaceutiquement acceptable de celle-ci
WO2023172065A1 (fr) Composition antivirale ou anticancéreuse contenant du niclosamide ou un sel pharmaceutiquement acceptable de celui-ci, et son procédé de préparation
JP6168673B2 (ja) アリールアルキルアミン化合物含有医薬組成物
WO2013119002A1 (fr) Composition laxative contenant du polyéthylène glycol et de la vitamine c
WO2022146089A1 (fr) Formulation orale solide pour le nettoyage du côlon
WO2017146286A1 (fr) Composition pharmaceutique à base d'extrait de feuille de ginkgo biloba utilisant une matrice de polymère hydrophile pour libération prolongée, et préparation à libération prolongée utilisant cette dernière
CN115245487A (zh) 美沙拉嗪与马来酸共晶物及制备方法和其组合物与用途
CN111718258B (zh) 蓓萨罗丁与聚乙烯吡咯烷酮共无定型物及制备方法和其组合物与用途
WO2018062964A1 (fr) Capsule composite contenant de la vitamine d ou un dérivé de celle-ci, et du raloxifène ayant un taux de dissolution amélioré, et son procédé de préparation
WO2022211460A1 (fr) Composition pharmaceutique pour le traitement d'une infection au sras-cov-2
WO2023171894A1 (fr) Composition pharmaceutique comprenant du docétaxel ou un sel pharmaceutiquement acceptable de celui-ci et son procédé de préparation
WO2022095913A1 (fr) Formulation solide
WO2015130110A1 (fr) Composition de dispersion solide à stabilité accrue, contenant de la solifénacine amorphe ou un sel de celui-ci, et son procédé de préparation
WO2015115853A1 (fr) Composition pharmaceutique comprenant de la 5-{4-(aminosulfonyl)phényl}-2,2-diméthyl-4-(3(fluorophényl)-3(2h)-furanone et capsule comprenant la composition pharmaceutique
WO2014163215A1 (fr) Composition pharmaceutique ayant un goût amer masqué
WO2012064130A2 (fr) Composé précurseur du célécoxib ciblant le côlon et composition pharmaceutique contenant le composé comme principe actif pour le traitement ou la prévention des maladies du côlon
WO2024063537A1 (fr) Composition pharmaceutique comprenant du sel de calcium sacubitrilㆍvalsartan
WO2013169082A1 (fr) Préparation orale à libération contrôlée de bosentan
WO2010150984A2 (fr) Dispersion solide d'adefovir dipivoxil amorphe présentant une stabilité améliorée et son procédé de préparation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13747133

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13747133

Country of ref document: EP

Kind code of ref document: A1