WO2015056897A1 - Composition de lavage intestinal - Google Patents

Composition de lavage intestinal Download PDF

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Publication number
WO2015056897A1
WO2015056897A1 PCT/KR2014/008893 KR2014008893W WO2015056897A1 WO 2015056897 A1 WO2015056897 A1 WO 2015056897A1 KR 2014008893 W KR2014008893 W KR 2014008893W WO 2015056897 A1 WO2015056897 A1 WO 2015056897A1
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WO
WIPO (PCT)
Prior art keywords
composition
cleansing
intestinal
ascorbic acid
water
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Application number
PCT/KR2014/008893
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English (en)
Korean (ko)
Inventor
강윤식
신정윤
강현석
강현이
Original Assignee
강윤식
신정윤
강현석
강현이
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.)
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Publication date
Priority claimed from KR20140081087A external-priority patent/KR101508464B1/ko
Application filed by 강윤식, 신정윤, 강현석, 강현이 filed Critical 강윤식
Priority to JP2016548986A priority Critical patent/JP6570533B2/ja
Priority to CA2927719A priority patent/CA2927719A1/fr
Priority to CN201480043216.4A priority patent/CN105658212B/zh
Priority to US14/903,779 priority patent/US20160151340A1/en
Priority to EP14854467.9A priority patent/EP3015102B1/fr
Priority to CN201910207622.4A priority patent/CN109908142B/zh
Publication of WO2015056897A1 publication Critical patent/WO2015056897A1/fr
Priority to US15/843,070 priority patent/US10973808B2/en
Priority to US17/219,733 priority patent/US20210353603A1/en

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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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

  • the present invention relates to an intestinal cleansing composition, and more specifically, by containing a high concentration of specific sugar alcohols and ascorbic acid in laxative phycosulfate, the overall dosage is reduced, and the intestinal cleanability is further improved, It relates to a novel intestinal cleansing composition also ensured safety.
  • Colorectal cancer is the third most common cancer worldwide, according to a report by the World Cancer Research Fund International.In 2012, it is estimated that 1.4 million new colorectal cancer patients worldwide, and by 2035 It is estimated that 2.4 million new colorectal cancer patients will occur each year. Colonoscopy is essential to diagnose such colon cancer. Furthermore, colonoscopy is very important because colonic polyps, which can be called precursor lesions of colon cancer, can be blocked at the time of colonoscopy.
  • PEG polyethylene glycol
  • PEG preparations The main problem with PEG preparations is that the dosage reaches 41 ⁇ and the disgusting taste of PEG preparations makes them very difficult to take. Because of this difficulty in taking, there is a widespread negative perception of the bowel cleansing process, which eventually leads people to fear or avoid colonoscopy.
  • phycosulfate-containing intestinal cleansers do not contain electrolytes, resulting in rare cases of hyponatremia and hypokalemia due to high doses, but serious side effects such as convulsions have been reported. Magnesium can cause hypermagnesemia, which is contraindicated in people with renal impairment.
  • Picosulfate-containing intestinal cleansers developed to address the difficulty of taking these most commonly used PEG preparations have improved dosage compliance, but have poor intestinal cleansing ability, and as a result still take large amounts of 2.3-3.5L. In addition, the situation has problems such as electrolyte abnormalities and side effects of hypermagnesemia.
  • the present invention is to solve the problems of the prior art as described above, the object of the present invention, while having both the ease of taking through the improvement of taste and safety for the human body is still up to 70% It is to provide a novel bowel cleansing composition with excellent cleansing power that greatly enhances the provision of adequate bowel preparation.
  • Another object of the present invention is to provide a novel bowel cleansing composition which can be economically mass produced and commercialized.
  • the bowel cleansing composition according to the present invention is composed of xylitol, consumption, glycerol, erytholi, tri, arabi, ribi, manny, galacta, fusi, eidi, and inoji as first cleaning components.
  • At least one sugar alcohol selected from blemy, isomalt, malty, lacty, maltotri, maltotegra, and polyglyci; Ascorbic acid or a mixture of ascorbic acid and ascorbic acid as a second cleaning component; Picosulfate as a third cleaning component; And a water-soluble solvent, wherein the content of the first cleaning component is 10 g / L to 500 g / L based on the total composition, the content of the second cleaning component is 15 g / L to 500 g / L based on the total composition, and the third The content of the cleaning component is lmg / L to 100mg / L, and the capacity of the water-soluble solvent is 0.1L to 1.0L.
  • Intestinal cleansing composition according to the present invention by using a specific concentration of sugar alcohol, ascorbic acid, and picosulfate, while improving the taste and at the same time exhibited a superior bowel cleansing power than conventional bowel cleansing.
  • the bowel cleansing composition according to the present invention greatly reduced the dose, thereby greatly improving the ease of taking and mildness.
  • the bowel cleansing composition according to the present invention minimizes discomfort such as discomfort, abdominal pain and vomiting in the course of taking, thereby improving discomfort symptoms, and by containing bicarbonates such as sodium bicarbonate and potassium bicarbonate, It can prevent electrolyte abnormalities such as hyponatremia and hypokalemia, which can occur in detergents, and because it does not contain magnesium, it can be safely used in patients with kidney disorders without serious side effects due to hypermagnesemia.
  • bicarbonates such as sodium bicarbonate and potassium bicarbonate
  • electrolyte abnormalities such as hyponatremia and hypokalemia, which can occur in detergents, and because it does not contain magnesium, it can be safely used in patients with kidney disorders without serious side effects due to hypermagnesemia.
  • hyponatremia and hypokalemia which can occur in detergents, and because it does not contain magnesium
  • it can be safely used in patients with kidney disorders without serious side effects due to hypermagnesemia.
  • by using a combination of sugar alcohol and ascorbic acid in a certain concentration it has excellent cleaning and
  • the most difficult reason for the intestinal cleansing from the patient's point of view is the inconvenience of large doses, poor detergent taste, abdominal pain, vomiting, etc.
  • the poor symptoms of taking Due to the poor cleaning ability, many hospitals still have the inconvenience of taking a large amount of solution, totaling 3.51 ⁇ .
  • the present invention contains sugar alcohol and ascorbic acid as a specific content instead of magnesium citrate, which is used in addition to the conventional picosulfate preparation, to increase intestinal cleansing and reduce the total dose including water to 2L or less, the purity of the dose Was raised.
  • the bowel cleansing composition according to the present invention makes the bowel cleansing process much easier and safer, thereby greatly contributing to the activation of colorectal endoscopy, and as a result, early detection of colorectal cancer as well as resection of colorectal polyps. Maximize the prevention effect of colon like.
  • the intestinal cleansing composition according to the present invention can be utilized for the treatment of constipation, etc. and symptom relief. According to the production method according to the present invention, it is possible to economically mass-produce and commercialize the intestinal cleansing composition.
  • 1 and 2 are photographs showing the results of culturing intestinal bacteria with respect to the composition for enteric cleaning according to one embodiment and comparative reference example of the present invention for each test organization.
  • Figure 3 is a photograph for showing the intestinal cleanliness after taking the intestinal cleansing composition according to one embodiment and comparative examples of the present invention.
  • 4A and 4B are graphs showing the results of investigations on the ratio of clean bowel cleansing and unstable bowel cleansing after taking the bowel cleansing composition according to one embodiment and comparative examples of the present invention.
  • FIG. 5 is a photograph showing a state in which a lot of bubbles occurred in the intestine after taking the intestinal cleansing composition prepared according to the prior art of the present invention.
  • Intestinal cleansing composition Xylitol, consumption (Sorbitol), glycerol (Glycerol), erythritol, Thritol (Threitol), Arabido (Arabitol) Ribitol, Mannitol, Galactitol, Fucitol, Iditol, Inositol, Volemitol, Isomalt At least one sugar alcohol selected from Maltitol, Lactitol, Maltotriitol, Maltote gradol, and Polyglycitol; Ascorbic acid or a mixture of ascorbic acid and ascorbic acid as a second cleaning component; Picosulfate as a third cleaning component; And a water-soluble solvent, wherein the content of the first cleaning component is 10 g / L to 500 g / L based on the total composition, the content of the second cleaning component is 15 g / L to 500 g / L based on the
  • the sugar alcohol used as the first cleaning component in the present invention is a cleaning component that functions as a laxative by using at a high concentration.
  • the sugar alcohols used as the first cleaning ingredient in the present invention are Xyl, consumption, glycerol, erythri, thrice, arabic, riboni, mantle, galacti, fusi, and eidiol. It is at least one selected from Remyl, Isomalt, Malty, Lactitol, Maltotritle, Maltotegrai and Polyglycile.
  • the sugar alcohol as the first cleaning component may include, for example, a consumption or a mixture of xyllets or consumption and xyllets.
  • Ladas et al.'S review found that the explosion was not limited to Mannier's or consumption frame, but also after intestinal lavage with PEG or phosphate.
  • Ladas et al reported a total of 20 gas explosions involving intestinal lavage between 1952 and 2006. Of these, two of four accidents during colon polypectomy were PEG and one was phosphate.
  • the sugar alcohol is used in combination with a specific content together with a second cleaning component such as ascorbic acid and a third cleaning component of picosulfate as the first cleaning component to have an excellent intestinal cleansing and antimicrobial activity compared to the dosage.
  • a second cleaning component such as ascorbic acid
  • a third cleaning component of picosulfate as the first cleaning component
  • the content of the first cleaning component used in the present invention is in the range of 10 g / L to 500 g / L, 20 g / L to 200 g / L, 50 g / L to 150 g / L based on the total composition, but is not limited thereto.
  • generation of hydrogen gas and methane gas, which are combustible gases may be increased.
  • bowel cleansing may be incomplete when the content of the first cleansing component is out of the above range and the concentration is low.
  • Silver ascorbic acid used as the second cleaning ingredient in the present invention Water-soluble vitamin known as c is an essential vitamin that plays various roles in maintaining human health. Recently, as interest in ascorbic acid has increased, various kinds of health drinks including ascorbic acid have been released. By the way, the concentration of ascorbic acid contained in such health drinks and the like is prepared up to 10 mg / mL (ie, 10 g / L) or less.
  • ascorbic acid is a major cleaning component that functions as a laxative by being used at high concentrations, and also exhibits an antibacterial effect, thereby inhibiting the activity of intestinal bacteria and minimizing the generation of intestinal gas.
  • the second cleaning component is formulated in a high content of 15 g / L to 500 g / L, 20 g / L to 300 g / L, or 30 g / L to 200 g / L, based on the total composition.
  • the acidity of the solution may be excessively increased to make it difficult to take it by excessively sour taste, and it may cause severe stomach irritation, causing nausea, nausea, vomiting, heartburn, etc. May cause.
  • the content of the second cleaning component is out of the range of the low concentration, the antibacterial effect is low, there is a risk of excessive generation of intestinal combustible gas.
  • the ascorbic acid salt used as the second cleaning component in the present invention is an alkali metal or alkaline earth metal salt of ascorbic acid.
  • Alkali metals are for example sodium or potassium, and alkaline earth metals can be, for example, but not limited to.
  • Ascorbic acid salts used in the present invention are sodium ascorbate or calcium ascorbate.
  • Ascorbic acid salts can lower the acidity of the solution compared with the case of ascorbic acid alone, and further increase the intestinal cleansing effect by suppressing the absorption of ascorbic acid, which is known to increase absorption as the acidity is higher. It may be 1 to 60: 40: second cleaning component is ascorbic case of "Broken acid and ascorbic acid salt mixture, and ascorbic acid to the ascorbic acid salt weight ratio is 99. If the mass ratio of ascorbic acid to ascorbic acid is out of the above range, excess sodium, calcium, potassium or magnesium may be absorbed by the human body, leading to electrolyte abnormalities or to hypercalcemia or hypermagnesemia.
  • Picosulfate used as the third cleaning component in the present invention is a component used as an irritant laxative. Phycosulfate is usually taken at 7.5 mg once or twice a day.
  • the content of picosulfate as the third cleaning component used in the present invention may be 1 mg / L to 100 mg / L, 10 mg / L to 80 mg / L, or 15 mg / L to 70 mg / L based on the total composition.
  • Intestinal cleansing composition according to the present invention after intestinal gas removal or bowel cleaning may further comprise a bubble forming inhibitor to remove the intestinal bubbles that occur frequently.
  • a bubble forming inhibitor to remove the intestinal bubbles that occur frequently.
  • simethicone may be used as the bubble formation inhibitor, but is not limited thereto.
  • simethicone diluent is made and injected into the intestine through a small channel of the endoscope insert, or a separately provided simethicone preparation is the last step in taking an intestinal cleanser.
  • simethicone diluent is made and injected into the intestine through a small channel of the endoscope insert, or a separately provided simethicone preparation is the last step in taking an intestinal cleanser.
  • the range that the dimethicone diluent can be applied at a time is very limited. Therefore, when bubbles are formed over a wide range, there is a hassle of injecting dilution liquid more than a dozen times.
  • the simethicone preparation is separately taken at the end of the intestinal cleansing process, the dosage is usually about 10 ml, and thus there is a limit to suppressing bubble generation throughout the large intestine.
  • the bubble formation inhibitor such as simethicone in the intestinal cleansing composition to solve this problem, it is very effective to suppress the bubble formation over all the parts of the large intestine in contact with the bowel cleansing liquid even at a small dose.
  • the content of the bubble-forming inhibitor used in the present invention may be 100 mg / L to 2 g / L, 150 mg / L to 1.5 g / L, 200 mg / L to lg / L based on the total composition of simethicone, In the case of a bubble forming inhibitor other than ticon, it is not limited thereto. If the bubble formation inhibitor exceeds the upper limit of the above criteria, side effects such as abdominal pain, rash, facial or tongue edema or difficulty breathing may occur.
  • the water-soluble solvent used in the present invention may be, for example, water, carbonated water, alkaline ionized water, beverages and the like.
  • the kind for example drip coffee, various juices, cola, cider, gin and tonic.
  • carbonated water or alkaline ionized water may be used as the water-soluble solvent.
  • Carbonated water has a laxative effect on its own and is known to improve constipation in the elderly who suffer from chronic constipation.
  • Alkaline ionized water can enhance the cleaning effect by neutralizing a part of the acidity of the bowel cleansing composition according to the present invention to lower the absorption of ascorbic acid.
  • the capacity of the water-soluble solvent may be 0.1L to l.OL, 0.1L to 0.9L, 0.2L to 0.8L, 0.3L to 0.7L, but is not limited thereto. If the volume of the solvent is less than 0.1L contained components may not be completely dissolved in the solvent, 1) if the amount is greater than the dosage may be less dose compliance.
  • the bowel cleansing composition of the present invention may further include ingredients for increasing the degree of obesity of the dose and for alleviating upper gastrointestinal symptoms such as nausea, nausea, and vomiting that are commonly observed during intestinal cleansing.
  • the bowel cleansing composition of the present invention containing a large amount of ascorbic acid may have difficulty in taking due to excessive acidity, it may include bicarbonates such as sodium bicarbonate and potassium bicarbonate as neutralizing ingredients. Can be.
  • the content of sodium bicarbonate can be used in the range of O.lg / L to 10 g / L based on the total composition. Beyond this range, due to excessive salty taste, the dose of ungwoomyeon drop, may cause hypernatremia.
  • the content of potassium hydrogen carbonate may be 0.1 g / L to 20 g / L based on the total composition. Beyond this range, more potassium than the recommended daily intake can lead to hyperkalemia. Hyperkalemia can pose a risk, including heart failure.
  • the bowel cleansing composition of the present invention further contains an extract or powder or concentrate of ginger, peppermint, chamomile, or the like as an aqueous solution for the purpose of improving the nausea, vomiting, and abdominal pain. It may contain more.
  • These components function as gastrointestinal stabilizers and may be mixed in amounts of 5 g / L to 50 g / L based on the total bowel cleansing composition. If the content of these gastrointestinal stabilizer components is excessively high out of the above range, the bowel cleansing ability may be reduced by inhibiting bowel movement.
  • the bowel cleansing composition of the present invention may further contain known cleaning ingredients or auxiliary ingredients for enhancing the cleaning effect.
  • Additional cleaning and cleaning enhancement components include, for example, citric acid, magnesium such as magnesium oxide, docuate sodium, senna extracts (such as sennoside), aloe extracts (such as aloe), garlic extracts (such as aalli and allicin), and pectin. (pectin), zinc such as zinc oxide, caffeine, and the like.
  • Citric acid is a natural ingredient contained in high concentrations such as gamgle and gives a sour taste and is used as a preservative of various drinks and foods. Citric acid is classified as a very safe substance and is recognized by the FDA and FAO / WHO as it is almost harmless even when taken in large doses.
  • citric acid may be included as an additional cleansing ingredient that functions as a laxative.
  • the citric acid content used at this time is the whole composition Reference lg / L to 15g / L can be. Beyond this range, heartburn and strong sourness can reduce your dose.
  • the magnesium component is a substance having a function as a laxative.
  • the magnesium component when taking an overdose of 3g or more at a time may cause side effects due to hypermagnesemia, so people with renal impairment should be used with caution.
  • Pectin and zinc can inhibit the intestinal absorption of ascorbic acid and increase its function as a laxative.
  • the pectin content may be used in the range of O. lg / L to 2 g / L based on the total composition, and may not be dissolved when using a higher content.
  • Zinc oxide can be used in the range of 10 mg / L to 400 mg / L based on the total composition, vomiting, nausea and the like may occur when ingested in excess of this range.
  • Caffeine can be used to counteract the lethargy that may appear in the intestinal cleansing process and to enhance the intestinal cleansing effect and is used in the range of 30 mg or less based on the total composition. Excessive overdose can lead to tachycardia, anxiety, and sleep disorders in sensitive people.
  • Docutate Sodium (10 mg / L to 400 mg / L range, can cause vomiting and abdominal pain when ingested in excess), Senna extract (sennoside, 10 mg / L to 50 mg / L range, can cause vomiting and abdominal pain when ingested), aloe Extract (ingestion of aloein 10mg / L to 50mg / L for long periods of time may cause intestinal deterioration), garlic extract (to use allinin and allicin in the range of 10mg / L to 5g / L, severe ingestion of stomach pain and vomiting ) Can also be used as an auxiliary laxative.
  • the bowel cleansing composition of the present invention may include a sweetener to improve the taste, and usable sweeteners include, for example, sucralose, maltodextrin, glucose, sucrose, and text. Rox (Dextrose), Saccharin (Saccharin), Aspartame (Spartame), Stevia (Stevia) and the like, but are not limited thereto. These sweeteners may be used in the range of 0.01 mg / L to 10 g / L based on the total bowel cleansing composition. Excessive use beyond this range can lead to unpleasant symptoms such as nausea and nausea.
  • Intestinal cleansing composition of the present invention may be added to the appropriate amount of edible fruit flavor in order to increase the dose.
  • These fruit flavors may include strawberry flavor, orange flavor, apple flavor, grape flavor, lemon flavor, banana flavor, cherry flavor, and the like.
  • Enteric cleaning composition of the present invention to prevent the oxidation of ascorbic acid
  • antioxidants include, for example, ferrulic acid, glycine, histidine amino acids, hyaluronic acid, tocope, and the like, but are not limited thereto.
  • the bowel cleansing composition of the present invention may further include an adsorbent for adsorbing trace iron and copper ions that may be contained in the water-soluble solvent.
  • adsorbents include, for example, Versene CA chelating agent (Dow), but are not limited thereto.
  • the bowel cleansing composition according to the present invention may be one-part or two-part.
  • the bowel cleansing composition comprises a first cleansing component, a second cleansing component, and a third cleansing component, and, if necessary, all components of the bubble forming inhibitor, the gastrointestinal stabilizing agent 1, and other additives are water-soluble solvents. Can be packaged together in one component.
  • the bowel cleansing composition may be packaged in two-part form.
  • the first cleaning component, the second cleaning component, and the third cleaning component are packaged together and the water-soluble solvent is packaged separately, or the second cleaning component and the water-soluble solvent are packaged together and the first cleaning component is A third cleaning component is packaged separately, or the first cleaning component, the third cleaning component and the water soluble solvent are packaged together and the second cleaning component is packaged separately, or the first cleaning component, the third cleaning component and the water soluble component A portion of the solvent is packaged together and a portion of the second cleaning component and the water-soluble solvent are packaged together, or the first cleaning component, the second cleaning component, the third cleaning component and a portion of the water-soluble solvent are packaged together and the water-soluble solvent is The remainder of the solvent may be packaged separately, but is not limited thereto.
  • foam forming inhibitors, gastrointestinal stabilizers, and other additives may be combined in various two-part forms as needed.
  • a method of packaging and using the bowel cleansing composition of the present invention in the form of a high concentration liquid and a vehicle as a two-part type will be described.
  • the bowel cleansing composition of the present invention in the form of a high concentration liquid and a vehicle as a two-part type.
  • the capacity of the water-soluble solvent to form a high concentration may be 0.05L to 0.2L
  • the amount of the beverage, the vehicle selected by the user may be the remaining capacity as a water-soluble solvent.
  • the solid components of the composition are packaged separately and a water-soluble solvent is After packaging, users can mix and use the whole ingredient at the time of taking it.
  • the form of the two-part composition is not limited to the above-described packaging method.
  • the first cleansing component, the second cleansing component, and the third cleansing component and, if necessary, all of the components, such as a bubble formation inhibitor, a gastrointestinal stabilizer, and other additives, are simultaneously mixed with a water-soluble solvent.
  • each component may be separately prepared and blended step by step.
  • the method for preparing a bowel cleansing composition comprises the steps of: forming a first blend comprising sugar alcohol as the first cleansing component; Forming at least 12 blends of ascorbic acid or ascorbic acid with ascorbic acid as a second cleaning component; Forming a nearly 13 blend comprising picosulfate as a third cleaning component; Forming a fourth blend comprising a bubble forming inhibitor as needed; Forming a fifth blend comprising a gastrointestinal stabilizer as needed; And combining the first to fifth blends with a water-soluble solvent to form a bowel cleansing composition.
  • the method for preparing the bowel cleansing composition according to the present invention comprises blending the first blend, the second blend, and the third blend with the fourth blend and the fifth blend as necessary in a water-soluble solvent. Prior to this, the method may further include pre-mixing the first to fifth blends in any combination.
  • a method for producing a bowel cleansing composition according to the present invention includes, for example, the first blend, the second blend, and the third blend, and, if necessary, the fourth blend. It is possible to prepare a high concentrate form containing a fifth formulation and a part of a water-soluble solvent in advance, and to drink by adjusting to the specific concentration and content by diluting to various drinks as a vehicle at the time of taking.
  • a beverage that can be selected by the user as a vehicle is not limited as long as it is a water-soluble solvent, and may be, for example, water, carbonated water, alkaline silver water, or beverage, and may be the same as or different from the water-soluble solvent in a high concentration liquid.
  • the effect of the present invention can be achieved as a beverage, there is no particular limitation on the kind thereof. Examples include drip coffee, various juices, cola, cider, gin and tonic.
  • a method of blending each component in the case of solids, particle shape and size, pH, preparation temperature, stirring condition, packaging container, packaging material, vacuum packaging or gas substitution packaging, etc.
  • the packaging method, etc. is the type, type, transportation, storage method, etc. Can be adjusted accordingly.
  • the method of taking the bowel cleansing composition according to the present invention takes into account the intestinal sensitivity of the subject. Begin taking 3-5 hours before colonoscopy and take 5-10 doses every 5-10 minutes, 50–lOOcc at a time, without limitation.
  • the ingestion time of the intestinal cleansing composition according to the present invention may be taken over an hour to 1 hour and 30 minutes, for example, but if thirst is added, an appropriate amount of mineral water may be additionally added, but is not limited thereto.
  • Intestinal cleansing composition according to the present invention by containing a certain concentration of sugar alcohol, ascorbic acid and picosulfate, not only shows an improved intestinal cleansing power even at a significantly reduced dose, but also provides the convenience of taking in a very small dose, It does not contain disgusting ingredients, and does not cause or minimize discomfort symptoms such as nausea, vomiting and gas bloating, and is safe by inhibiting the production of intestinal flammable gas in the human body.
  • the production method according to the present invention is economically capable of mass production and commercialization of a high performance bowel cleansing composition.
  • the bowel cleansing composition of the present invention has the ease and safety of taking excellent cleansing power, not only bowel cleansing for colonoscopy, but also bowel cleansing, pretreatment such as hemorrhoids, chronic constipation or acute constipation It can be used for treatment and prevention.
  • bowel cleansing composition of the present invention has the ease and safety of taking excellent cleansing power, not only bowel cleansing for colonoscopy, but also bowel cleansing, pretreatment such as hemorrhoids, chronic constipation or acute constipation It can be used for treatment and prevention.
  • pretreatment such as hemorrhoids, chronic constipation or acute constipation It can be used for treatment and prevention.
  • a solvent 45 g of Xyl, 25 g of ascorbic acid, 20 mg of picosulfate, 200 mg of simethicone, 200 mg of sodium bicarbonate, 1.4 g of potassium bicarbonate, and 20 mg of sucralose were prepared as a solvent to prepare a 150 ml high-concentrate solution.
  • a solvent 45 g of Xyl, 25 g of ascorbic acid, 20 mg of picosulfate, 200 mg of simethicone, 200 mg of sodium bicarbonate, 1.4 g of potassium bicarbonate, and 20 mg of sucralose were prepared as a solvent to prepare a 150 ml high-concentrate solution.
  • 350 ml of carbonated water was prepared to prepare a two-component bowel cleansing composition.
  • Comparative Reference Example 1 was prepared as a comparative sample for the solution of Example 1 for an in vitro experiment for confirming the safety of the sugar alcohol used as the first cleaning component in the present invention.
  • Comparative Reference Example 1 is 10 ml of a picoliteite solution, and the picoliteite solution is diluted in bottled water according to the recommended dosage method.
  • the concentration of the active ingredient is the same as that used for intestinal lavage.
  • Example 1 Comparative Reference Example 1, the control (bottled water), the solution obtained by diluting the stools obtained from five persons was mixed, stored in a 500 ml container, 20 ml, and stored at room temperature for 18 hours. Gas concentration in each container was measured. At this time, the diluted solution of the stool was taken from five different people, and each person's 3g side was diluted with 100 ml of bottled water to make five kinds of fecal lime solution.
  • the stool dilution made from the stools collected from five people was divided into 10 ml each of three containers for each individual to make three containers containing the same stool limestone solution. was prepared.
  • Example 1 Comparative Reference Example 1 (picolite), and control group (bottled water) were added.
  • the Geotech GA5000 gas meter can measure m0 gas in V0 l% and hydrogen gas up to 0–100 ppm.
  • the bowel cleansing composition of Example 1 was not detected at all, and the methane gas concentration was 0.13%, lower than that of the control, and lower than the bowel cleansing solution of the picosulfate formulation of Comparative Reference Example 1. That is, it can be confirmed that the bowel cleansing composition according to the present invention is the safest in relation to the intestinal combustible gas generation.
  • the average number of strains grown for each experimental solution is shown in the table below.
  • the intestinal bacteria culture results for Example 1, Comparative Reference Example 1 and the control in Figures 1 and 2 are shown for each test institution.
  • Example 1 (Unit 10 5 CFU / ml)
  • the strain number measurement result confirms more clearly the antimicrobial effect of the bowel cleansing composition according to the present invention.
  • Example 1 As a result of culturing all five stool dilutions, not only Comparative Reference Example 1 using picolite, but also fewer strains than the control group. That is, in the case of Example 1, it can be seen that the bacteria capable of generating combustible gases such as hydrogen gas and methane gas are substantially suppressed.
  • these results are the result of in vitro in vitro experiments, it is confirmed that the bowel cleansing composition according to the present invention is safer than any conventional bowel cleansers in relation to intestinal combustible gas generation.
  • the composition of Example 1 containing xylitol, ascorbic acid, and physulfate as a main component is a very safe composition with respect to intestinal bacterial growth and consequent intestinal flammable gas generation risk.
  • the result of this excellent antimicrobial effect suggests that when the bowel cleansing composition according to the present invention is used as a laxative for pre- bowel treatment, it can make a great contribution to reducing the incidence of post-operative infection.
  • contamination due to intestinal contents may occur, and therefore, antibiotics are pre-administered before surgery to prevent infection at the surgical site.
  • the intestinal treatment with the bowel cleansing composition according to the present invention the bacteria in the intestinal contents are suppressed, thereby reducing the possibility of infection even when contamination due to the intestinal contents occurs.
  • This effect is more effective in the bowel cleansing composition according to the present invention, considering that the conventional bowel cleansing liquid is not only used for bowel cleansing before colonoscopy, but also as a causative agent for bowel treatment before colorectal surgery. It can be increased. From the above two in vitro safety experiments, a novel The bowel cleansing composition has the lowest risk by minimizing the generation of hydrogen gas and methane gas, which are combustible gases, and inhibiting bacterial growth, compared to other bowel cleansers.
  • Comparative Examples 1 and 2 were prepared for comparative experiments on the ease of taking the intestinal cleansing composition according to the present invention, the effect of cleaning each bowel, and safety.
  • the intestinal three compositions in which the conventional commercial enteric cleaner picolite and coolprep were mixed with water in the recommended blending amounts were prepared as Comparative Examples 1 and 2, respectively.
  • the kind of each enteric detergent given in Comparative Examples 1 and 2 and the amount of water blended are shown in Table 3 below.
  • Clap 56.402 g of serving content per package, manufactured by Taejun Pharmaceutical Co., Ltd.
  • the cleaning performance analysis and dose compliance of the bowel cleansing compositions prepared in Example 1 and Comparative Examples 1 and 2 were performed.
  • Comparative Example 1 for each colonoscopy subject was cited.
  • Example 1 and Comparative Examples 1 and 2 the specific taking method is as follows.
  • Dosing method of Example 1 starts 5 hours before the scheduled time of the test
  • enteric lavage solution 500 ml was taken five times every 30 minutes, one half cup of 100 mK5 sip paper cups at a time. After drinking 100 ml of intestinal lavage solution, an additional 200 ml of drinking water was added every 15 minutes. This took a total of 120 minutes to take the cleaner.
  • Comparative Example 1 namely, 2.3L of picolite, was drank at 150 ml of water by drinking one packet provided 5 hours before the test day at 7:00 p.m. on the day before the test, followed by additional drinking of 1 L of water over 1 hour. I took it one more time in the same way before.
  • Comparative Example 2 that is, 3L of Cleprep, 1L of the preparation solution at 7 pm the day before the test The method was taken for 1 hour (250 ml every 15 minutes), and drinking 1 L of the preparation solution again for 1 hour 5 hours before the test day. After the evening and the day after drinking the dilution solution, they were asked to drink another 500 mL of water.
  • Intestinal cleanliness is determined by the surgeon based on the criteria shown in Table 4 and FIG. 3, based on the criteria of Excellence, Good, Fair, Poor and Fail. Evaluation was divided into stages. Intestinal cleanliness evaluation was conducted by blind test without any information about the bowel cleansing composition that the patient drank for the fair evaluation without exposing it to the surgeon performing the colonoscopy. Table 4
  • Comparative Example 2 (Cool Wrap) 16.3 51 22.5 10.2 0
  • the results are classified into 'clean bowel cleansing', which is suitable for intestinal endoscopy, and 'unstable bowel cleansing,' which is insufficient or impossible to perform an accurate test, and is shown in FIGS. 4A and 4B.
  • 'Clean bowel cleansing' includes excellent and excellent condition.
  • 'Fouled bowel cleansing' usually includes inadequate and untestable condition.
  • Example 1 As shown in the above results, in Example 1, no bubbles were generated in 92.8%, but in Comparative Examples 1 and 2, the ratio of no bubbles was only about one third, especially one of three persons. In more than one person, a large amount of bubbles were generated, which greatly disturbed the test. Bubbles can be washed off with medication during colonoscopy, but they require considerable effort and time because of the limited scope of washing at one time. In other words, the occurrence of excessive bubbles not only interferes with the smooth colonoscopy, but also causes missing small lesions.
  • the bowel cleansing composition of Example 1 almost completely prevents the occurrence of air bubbles, shortens the inspection time and at the same time allows more time to observe the lesions, and also makes it easier to find small lesions due to the clear view. It can increase the diagnosis of disease.
  • Ease of taking was evaluated in four categories: 1 taste of detergent, 2 discomfort after taking, 3 whether to recommend to family, and 4 need for improvement.
  • the taste of the detergent is divided into three stages of very turtles, little turtles, alright, and subjectively judged the degree through a questionnaire, and obtained the percentage of the evaluation value is shown in Table 7 below.
  • Comparative Example 2 (Clep Prep) 14.3 53.1 32.6 As shown in the results, in Example 1, 95.1% of the taste of the detergent was good, and Comparative Example 1 was 93.9%, but Comparative Example 2 was only 32.6%.
  • Example 1 can be seen that all of the items such as abdominal pain, gas distension, vomiting and thirst lower than or similar to the conventional intestinal detergents exhibited discomfort symptoms.
  • Comparative Example 2 the frequency of vomiting was quite high, which seems to be related to the disgusting taste of the PEG formulation.
  • Comparative Example 1 was relatively low as 7% of the non-recommended ratio was a little higher than Example 1. This can be seen as a result of the 2.3 L dose have.
  • Example 1 Among the subjects using the bowel cleansing composition of Example 1, 89 patients with past bowel cleansing experience were surveyed whether the ease of taking was improved compared to the previous bowel cleansing experience, and the results are shown in Table 11 below. Indicated.
  • Example 1 About 78.7% said it was easier to take the bowel cleansing composition of Example 1, and no one was more difficult. This result can be said to be an indirect comparison between Comparative Examples 1 and 2, and Example 1, which is a conventional enteric cleaner, and it can be seen that the preference for Example 1 is very high.
  • each intestinal cleanser was determined by blood test. Ascorbic acid concentrations and other hematological tests were performed to evaluate.
  • Reference values for blood ascorbic acid concentrations range from 2 to 20 pg / mL.
  • Comparative Example 3 in which 21.2 g of ascorbic acid is mixed and in Example 1 containing 25 g of ascorbic acid, it is foreseeable that the blood ascorbic acid concentration temporarily rises above the reference value.
  • ascorbic acid is water-soluble, it is known that blood ascorbic acid exceeding the reference value is excreted immediately through the kidneys, thereby normalizing blood levels.
  • ascorbic acid can be safely administered intravenously up to 1.5 g / kg in healthy individuals, except in patients with G6PD deficiency, kidney disease or people with urinary tract stones ⁇ "Vitamin C pharmacokinetics: implications for oral and intravenous use", Padayatty SJ, Sun H, Wang Y, et al., Ann Intern Med 140 (7), 533-7, 2004; "Phase I clinical trial of iv ascorbic acid in advanced malignancy", Hoffer LJ, Levine M, Assouline S, et al., Ann Oncol 19 (11), 1969-74, 2008.
  • Moviprep® the same ingredient as the product Kulprep (used in Comparative 2), which has been found to temporarily increase the concentration of ascorbic acid in the blood, seems to have been approved by the US FDA as an intestinal cleanser without any problems.
  • urea nitrogen (BUN), creatinine, and liver enzymes AST (( ) T) and ALT which measure magnesium levels, electrolyte levels, and kidney function.
  • BUN urea nitrogen
  • AST ( ) T)
  • ALT liver enzymes
  • the concentration of (GPT) was measured and the results are shown in Tables 13 to 16 below. Blood was collected immediately before colonoscopy and measured according to a routine test at the Department of Diagnostic Laboratory, Joy Hospital. Table 13
  • the reason for the increase in magnesium blood concentration near the upper limit in the test subject using the bowel cleansing composition of Comparative Example 1 is that a large amount of magnesium oxide (10.5 g) is included in the picoliteite component.
  • the bowel cleansing composition according to Example 1 is a safe drug that does not cause abnormal conditions in blood chemistry.
  • Intestinal cleansing composition according to the present invention by using a certain concentration of sugar alcohol, ascorbic acid, and picosulfate in combination, while improving the taste at the same time exerted a superior bowel cleansing power compared to the existing three tablets.
  • the bowel cleansing composition according to the present invention greatly reduced the dose, thereby greatly improving the ease of taking and wooseong.
  • the bowel cleansing composition according to the present invention minimizes discomfort such as discomfort, abdominal pain and vomiting in the course of taking, thereby improving discomfort symptoms, and by including bicarbonate such as sodium bicarbonate and potassium bicarbonate, the existing picosulfate is included. It can prevent electrolyte abnormalities such as hyponatremia and hypokalemia, which can occur in intestinal cleansers, and do not contain magnesium, so it can be safely used in patients with kidney disorders without serious side effects due to hypermagnesemia.

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Abstract

La présente invention concerne une composition de lavage intestinal comprenant : un polyol particulier, comme le xylitol ou le sorbitol, en tant que premier ingrédient de lavage ; de l'acide ascorbique ou un mélange d'acide ascorbique et d'un sel de l'acide ascorbique en tant que second ingrédient de lavage ; du picosulfate en tant que troisième ingrédient ; et un solvant soluble dans l'eau, dans laquelle, relativement à la composition totale, la teneur en le premier ingrédient de lavage est de 10 à 500 g/L, la teneur en le second ingrédient de lavage est de 1 à 100 mg/L, la teneur en le troisième ingrédient de lavage est de 15 à 500 g/L, et le volume de solvant soluble dans l'eau est de 0,1 à 1,0 L, la composition de lavage intestinal ayant une capacité de lavage intestinal étonnante, étant facile à administrer et présentant une tolérance améliorée, et pouvant ainsi être utilisée à des fins de lavage intestinal pour : une colonoscopie, des chirurgies endoscopiques et équivalents ; un lavage intestinal avant des chirurgies abdominales ; un traitement intestinal avant une chirurgie anale, par exemple pour les hémorroïdes ; ainsi que le traitement et le soulagement de maladies telles que la constipation aiguë et chronique.
PCT/KR2014/008893 2013-10-17 2014-09-24 Composition de lavage intestinal WO2015056897A1 (fr)

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JP2016548986A JP6570533B2 (ja) 2013-10-17 2014-09-24 腸洗浄用組成物
CA2927719A CA2927719A1 (fr) 2013-10-17 2014-09-24 Composition de lavage intestinal
CN201480043216.4A CN105658212B (zh) 2013-10-17 2014-09-24 肠清洁组合物
US14/903,779 US20160151340A1 (en) 2013-10-17 2014-09-24 Bowel cleansing composition
EP14854467.9A EP3015102B1 (fr) 2013-10-17 2014-09-24 Composition de lavage intestinal
CN201910207622.4A CN109908142B (zh) 2013-10-17 2014-09-24 肠清洁组合物
US15/843,070 US10973808B2 (en) 2013-10-17 2017-12-15 Bowel cleansing composition
US17/219,733 US20210353603A1 (en) 2013-10-17 2021-03-31 Bowel cleansing composition

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WO2016208781A1 (fr) * 2015-06-22 2016-12-29 주식회사 씨티씨바이오 Composition purgative pour le lavage du tractus intestinal
CN111544436A (zh) * 2020-04-16 2020-08-18 唐传生物科技（厦门）有限公司 一种清洁肠道的肠道准备药物组合物及其制备方法
CN116585261A (zh) * 2023-05-17 2023-08-15 深圳市贝美药业有限公司 药物液体组合物及其制备方法和应用

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Publication number Priority date Publication date Assignee Title
WO2016208781A1 (fr) * 2015-06-22 2016-12-29 주식회사 씨티씨바이오 Composition purgative pour le lavage du tractus intestinal
CN111544436A (zh) * 2020-04-16 2020-08-18 唐传生物科技（厦门）有限公司 一种清洁肠道的肠道准备药物组合物及其制备方法
CN116585261A (zh) * 2023-05-17 2023-08-15 深圳市贝美药业有限公司 药物液体组合物及其制备方法和应用
CN116585261B (zh) * 2023-05-17 2024-05-14 深圳市贝美药业有限公司 药物液体组合物及其制备方法和应用

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