WO2021039975A1 - Préparation de gelée contenant de la lévocarnitine à concentration élevée - Google Patents

Préparation de gelée contenant de la lévocarnitine à concentration élevée Download PDF

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Publication number
WO2021039975A1
WO2021039975A1 PCT/JP2020/032648 JP2020032648W WO2021039975A1 WO 2021039975 A1 WO2021039975 A1 WO 2021039975A1 JP 2020032648 W JP2020032648 W JP 2020032648W WO 2021039975 A1 WO2021039975 A1 WO 2021039975A1
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Prior art keywords
jelly
jelly agent
levocarnitine
weight
agent according
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PCT/JP2020/032648
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English (en)
Japanese (ja)
Inventor
仁 松瀬
一毅 岡本
真健 大樂
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丸石製薬株式会社
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Publication of WO2021039975A1 publication Critical patent/WO2021039975A1/fr

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    • 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
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals

Definitions

  • the present invention relates to a high-concentration levocarnitine-containing jelly agent in which adverse effects on patients who need to take Levocarnitine and whose dietary standards such as drinking water should be considered, for example, patients with renal disease are suppressed. ..
  • Levocarnitine is an essential nutrient for energy metabolism of muscle exercise, and about 75% of the required amount is ingested from food, and the rest is synthesized in the body. Ingestion from food is usually sufficient, but for example, in patients with carnitine deficiency, carnitine deficiency reduces the activity of organs such as the liver, brain, skeletal muscle, and myocardium, and in severe cases, it is accompanied by a hypoglycemic attack. , It may be in a coma, so it is necessary to supplement with levocarnitine.
  • Levocarnitine supplementation treatment is usually taken in 3 divided doses of 1500 mg to 3000 mg daily.
  • the amount of water intake for swallowing multiple tablets with water in the case of patients with renal disease undergoing dialysis treatment who have (restriction of nutritional intake of various minerals such as protein, water, energy (calories), salt, potassium and phosphorus).
  • self-management that does not exceed dietary standards becomes a major problem.
  • the taste of the liquid preparation remains in the mouth, and some patients drink water to eliminate the taste, which exceeds the dietary standard.
  • the dissolution test method specified by the Japanese Pharmacopoeia is also an index for judgment. Since the levocarnitine preparation is a normal preparation, elution of 85% or more is required in 15 minutes, but as a reference, when the dissolution test of confectionery jelly containing carnitine (Paddle method, 50 rpm Japanese Pharmacopoeia) is performed, 85% in 15 minutes. The above elution was not observed (see also Reference Example 1 below). A gel of carnitine is also known (Patent Document 1), but no problem with elution is recognized.
  • a high-concentration levocarnitine-containing jelly agent suitable as a pharmaceutical product has not been provided so far.
  • An object of the present invention is to provide a high-concentration levocarnitine jelly agent.
  • the present invention further (1) restricts the intake of water and energy (specifically, restricts the intake of various minerals such as protein, water, energy (calories), salt, potassium and phosphorus) by efficiently ingesting levocarnitine. ), That is, adverse effects on patients who should consider the dietary standards edited by the Japanese Society of Nephrology, such as patients with renal disease, are suppressed, (2) easy to take, and / or (3) physical properties and storage stability.
  • the challenge is to provide a high-concentration levocarnitine jelly agent for pharmaceuticals with excellent properties.
  • the present inventors have been able to provide a high-concentration levocarnitine-containing jelly agent by containing levocarnitine and a specific component (gelling agent, one or more polyhydric alcohols, etc.). Furthermore, it has been found that such a jelly agent can solve the above-mentioned problems and the like. Based on such findings, the present inventors have further advanced research and have completed the present invention.
  • the present invention includes the following inventions in order to solve the above problems.
  • High-concentration revo containing (a) levocarnitine, (b) gelling agent, and (c) one or more polyhydric alcohols to suppress adverse effects on patients for whom dietary criteria should be considered.
  • Carnitine-containing jelly agent [2] The jelly agent according to the above [1], wherein the concentration of levocarnitine with respect to the entire jelly agent is about 10 to 30% by weight.
  • the gelling agent is carrageenan and / or locust bean gum.
  • the content of glycerin is less than about 15% by weight based on the total jelly agent, and / or the content of propylene glycol and / or macrogol is less than about 10% by weight based on the total amount of jelly agent.
  • the jelly agent according to any one of the above [1] to [7] which is for oral medicine.
  • the jelly agent of the present invention has a high content of levocarnitine, but the jelly does not diffuse into the mouth and is easy to take. Furthermore, since the present invention is a jelly agent, unlike tablets and the like, it does not require water to be taken, and unlike powders and powders, jelly does not disperse in the mouth, and unlike liquid agents and the like. The convenience of patients who should consider dietary standards, such as patients with renal disease, such as not having to drink extra water, is immeasurable. It is an excellent jelly agent that has been long-awaited for the emergence of carnitine preparations that are close to the physical administration problems of such patients.
  • levocarnitine ((A) Active ingredient: levocarnitine (L-carnitine))
  • L-carnitine ((A) Active ingredient: levocarnitine (L-carnitine)
  • the structure of levocarnitine (L-carnitine), which is the active ingredient, is shown below.
  • Levocarnitine is usually a white crystalline powder having a molecular formula: C 7 H 15 NO 3 , a molecular weight: 161.20 g / mol, and a melting point of 197 to 198 ° C.
  • the content (concentration) of levocarnitine in the jelly agent of the present invention is, for example, preferably about 10 to about 30% by weight, more preferably about 18 to about 30% by weight, and about 23 to about 30% by weight based on the entire composition.
  • the weight may be about 11 to about 30% by weight, about 12 to about 30% by weight, about 13 to about 30% by weight, and about 14 to about 30%. It may be% by weight, about 15 to about 30% by weight, about 16 to about 30% by weight, about 17 to about 30% by weight, about 19 to about 19 to. It may be about 30% by weight, about 20 to about 30% by weight, about 21 to about 30% by weight, about 22 to about 30% by weight, and about.
  • the levocarnitine concentration is lower than these ranges, the intake capacity of the jelly agent ingested by the patient becomes large, and the patient who should consider the dietary standard, for example, the renal disease patient who has restricted intake of water and nutrition. Etc. may not be suitable.
  • the concentration of levocarnitine is higher than these ranges, it may be difficult to prepare a jelly agent that meets the requirements of pharmaceutical products due to the relationship between the hydration power of levocarnitine and the water content or other components in the jelly agent. There is sex.
  • Levocarnitine may be in any form, for example, a free base, a crystalline polymorph (eg, anhydrous crystals), a hydrate, a pharmacologically acceptable salt (eg, an acid addition salt, etc.). It is good, but it is preferably a free form (a state in which no salt is formed).
  • the reason why the free form is preferable is that, for example, when trying to prepare a jelly agent using a hydrochloride of carnitine, the carnitine chloride chloride is acidic, but such an acidic carnitine is used as an easy-to-take jelly agent. In order to impart good dissolution property, it is necessary to adjust the pH to 5 or more with a pH adjuster or a buffering agent.
  • Levocarnitine can be produced by a known method, and levocarnitine can be obtained by purchasing a reagent such as Tokyo Chemical Industry Co., Ltd. It can be obtained from commercially available levocarnitine foods according to a method known per se.
  • levocarnitine it is usually preferable to orally administer about 1500 to 3000 mg of levocarnitine to an adult in 3 divided doses a day, but it may be administered in 1 to 6 divided doses a day, or 2 to 6 times a day. It may be administered in 4 divided doses.
  • about 500 to 2000 mg of levocarnitine or 2000 to 5000 mg of levocarnitine may be administered daily depending on the symptoms.
  • the jelly agent of the present invention preferably contains carrageenan and locust bean gum (also known as carob bean gum) as gelling agents.
  • the carrageenan preferably contains ⁇ (iota) carrageenan and ⁇ (kappa) carrageenan.
  • a gelling agent such a jelly agent of the present invention has a hardness that is palatable and easy to swallow (for example, a jelly strength of 3000 to 30000 N / m 2 ), and is taken like food. Is possible.
  • the gelling agent contains both carrageenan and locust bean gum, and further, the physical properties (water separation and hardness) are stabilized by containing ⁇ carrageenan, ⁇ carrageenan and locust bean gum.
  • ⁇ carrageenan When ⁇ carrageenan is contained in the jelly agent of the present invention, it is preferably 0.4 to 2.0% by weight, more preferably 0.4 to 1.7% by weight, based on the entire jelly agent. It is preferably 0.5 to 1.5% by weight, even more preferably. When ⁇ carrageenan is contained, it is preferably 0.1 to 0.4% by weight, more preferably 0.15 to 0.35% by weight. The locust bean gum is preferably 0.1 to 0.4% by weight, more preferably 0.15 to 0.35% by weight. With these amounts, a jelly agent that is easier to swallow and has an appropriate hardness can be obtained.
  • the ratio of ⁇ carrageenan to ⁇ carrageenan in the jelly agent is preferably in the range of 2: 1 to 8: 1, and more preferably in the range of 3: 1 to 7: 1. Not limited. Further, the ratio of carrageenan (total of ⁇ carrageenan and ⁇ carrageenan) to locust bean gum in the jelly agent is preferably in the range of 2: 1 to 10: 1, and more preferably 4: 1 to 8 :. It is in the range of 1, but is not limited to these.
  • a gelling agent other than carrageenan and locust bean gum may be added to the jelly agent of the present invention, if necessary.
  • agar or agar powder may be added as long as the effect of the present invention is not hindered, such as the elution rate, but it is preferable that the jelly agent does not contain 0.05% by weight or more.
  • the case containing xanthan gum and / or guar gum may be excluded, and the case containing glucomannan may be excluded.
  • the total blending ratio of the gelling agent in the jelly agent of the present invention is not particularly limited as long as it does not interfere with the effect of the present invention, but for example, it is preferably 0.4 to 4.0% by weight based on the entire jelly agent. More preferably, it may be 0.8 to 3.0% by weight, and more preferably 1.0 to 2.0% by weight. By setting the blending ratio, a particularly excellent effect of the present invention (among others, the effect of good elution) can be obtained.
  • the one or more polyhydric alcohols contained in the jelly agent of the present invention are preferably one or more selected from the group consisting of glycerin, propylene glycol and macrogol as long as the effects of the present invention are not impaired.
  • the average molecular weight of macrogol may be, for example, 100, 200, 300, 400, 600, 1000, 1500, 1540, 4000, 6000, 20000, 35000 and the like, preferably 100, 200, 300, 400, 600. , 1000, 1500, 1540, 4000, more preferably 100, 200, 300, 400, 600.
  • glycerin contains 15% by weight or more, more preferably 12% by weight or more, still more preferably 10% by weight or more, including those contained as a sweetener. do not do.
  • Propylene glycol preferably does not contain 10% by weight or more, more preferably 5% by weight or more, and even more preferably 4% by weight or more.
  • the macrogol preferably does not contain 10% by weight or more, more preferably 5% by weight or more, and even more preferably 4% by weight or more.
  • the jelly agent of the present invention may contain a sweetening agent, but it is preferable not to add a sweetening agent. When used, it can be used in consideration of elution, jelly strength, and water separation rate.
  • Such sweeteners include, for example, sucralose, acesulfame potassium, aspartame, fructose glucose syrup, saccharin, saccharin sodium, stevia, somatin, erythritol, sorbitol, sorbitol solution, lactose, honey, xylitol, glycerin, concentrated glycerin, martitol
  • a maltitol solution or the like or a mixture of two or more of these can be mentioned, preferably sucralose, or acesulfame potassium or a mixture of two or more of these, but patients who should consider dietary criteria as much as possible, such as , Preferably used in consideration of patients with renal disease, etc., and is not limited there
  • reduced maltose starch syrup or powdered reduced maltose starch syrup may be added as long as the effect of the present invention is not hindered, such as the elution rate, but it is preferable that the jelly agent does not contain 5% by weight or more.
  • the jelly agent of the present invention preferably has a pH of about 6 to 8, more preferably about 6 to 7.5, and even more preferably about 6 to 7.
  • the jelly agent of the present invention preferably adjusts its pH by containing a pH adjusting agent.
  • a pH adjuster it is preferable to use an organic acid or an inorganic acid that does not contain phosphoric acid or a metal salt.
  • Organic acids include, for example, citric acid, malic acid, lactic acid, acetic acid, trifluoroacetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, L-tartaric acid, D-tartaric acid, oxalic acid, benzoic acid, besilic acid.
  • Ascorbic acid methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid and the like
  • examples of the inorganic acid include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitrate and sulfuric acid, etc. or their hydration. Examples thereof include, but it is preferable and not limited to use in consideration of patients who should consider dietary standards as much as possible, for example, patients with renal disease.
  • fragrance It is not necessary to add a fragrance to the jelly agent of the present invention, but if necessary, for example, a fragrance preferred by children and the like may be added as a flavor. As such a flavor, for example, orange flavor, banana flavor, strawberry flavor, vanilla flavor and each essence may be added. These may be used individually by 1 type, or may be used by mixing 2 or more types.
  • the blending amount of the fragrance in the jelly agent of the present invention is not particularly limited as long as it does not interfere with the effect of the present invention, but it is preferably used in consideration of patients who should consider dietary standards as much as possible, for example, patients with renal disease.
  • Preservative A preservative may be added to the jelly agent of the present invention, if necessary.
  • the preservative is not limited as long as it is usually used for pharmaceutical purposes, but for example, methyl paraoxybenzoate (methylparaben), ethyl paraoxybenzoate (ethylparaben), propyl paraoxybenzoate (propyl).
  • Paraben isopropyl paraoxybenzoate (isopropylparaben), butyl paraoxybenzoate (butylparaben), isobutyl paraoxybenzoate (isobutylparaben), benzyl paraoxybenzoate (benzylparaben), sodium benzoate, benzoate, benzyl benzoate, Examples thereof include benzalkonium chloride, cetylpyridinium chloride, benzethonium chloride, aminoethylsulfonic acid, sorbic acid, sorbate, dehydroacetic acid, and dehydroacetate. These may be used individually by 1 type, or may be used by mixing 2 or more types.
  • the amount of the preservative compounded in the jelly agent of the present invention is not particularly limited as long as it does not interfere with the effect of the present invention, but it is preferably used in consideration of patients who should consider dietary standards as much as possible, for example, patients with renal disease. ..
  • any additive that can be orally administered is not particularly limited, and a thickener, a thickener, a solvent, a stabilizer, a stabilizer, an isotonic agent, an isotonic agent, and the like.
  • a plasticizer, a solubilizer, and other additives can be added to improve the productability.
  • “Salt” The daily dose is about 6g or less. "Potassium”: The daily dose is about 2g or less.
  • the adverse effect on the dietary standard for the above-mentioned renal disease patient is suppressed by efficiently ingesting levocarnitine, and dialysis treatment is performed. It is more preferable that the adverse effects on the dietary standards for patients with renal disease are suppressed, and the adverse effects on the dietary standards for patients with renal disease who are undergoing peritoneal dialysis treatment and / or hemodialysis treatment are suppressed. Is even more preferable.
  • renal diseases include, but are not limited to, chronic renal failure, acute renal failure, chronic nephritis, acute nephritis, diabetic nephropathy, nephrotic syndrome, and the like.
  • Patients who need levocarnitine administration or supplementation are not limited to patients with carnitine deficiency, for example, dialysis treatment patients for the treatment of renal failure, patients with congenital metabolic disorders, epilepsy, valproic acid after mental illness or brain surgery.
  • TPN parenteral nutrition
  • TPN total parenteral nutrition
  • anticancer drugs such as platinum preparations, anthracycline preparations and alkylating agents, pivoxil groups
  • Patients receiving antibacterial drugs, patients with liver cirrhosis, liver failure, patients with neuromuscular disorders such as muscular dystrophy and atrophic lateral sclerosis, elderly patients, patients with severe illness, patients with suspected carnitine deficiency such as undernourishment, or carnitine Patients who are considered to be more likely to develop deficiency include, but are not limited to.
  • the jelly agent of the present invention may be administered or supplemented to a patient or the like for the purpose of supplementing tube feeding, TPN, enteral nutritional supplement or the like.
  • the efficient intake of levocarnitine suppresses adverse effects on the dietary standard, but this is not limited to the above-mentioned renal disease patients, for example, patients who require levocarnitine administration or supplementation. It is also useful for nutritional management and dietary restrictions in Japan.
  • the jelly agent of the present invention is preferably for pharmaceutical use and is administered either orally or parenterally, but is preferably administered orally.
  • the animal to which the jelly agent of the present invention is administered is not particularly limited, but may be, for example, a human or a non-human animal. Since the jelly agent of the present invention is in the form of jelly, it is easy to administer to any animal.
  • non-human animals are not particularly limited, but treatment according to veterinary instructions includes dogs, cats, mice, rats, hamsters, cows, horses, pigs, sheep, rabbits, foxes, gorillas, chickens, pigeons, and hawks.
  • the jelly agent of the present invention is in the form of jelly, it is easy to mix with feed and is also suitable for mixing with animal feed and the like.
  • the jelly agent of the present invention is orally administered to an adult in an amount of about 500 to 5000 mg of levocarnitine daily in 1 to 6 divided doses, a single dose of the jelly agent is taken.
  • the amount is preferably about 10 g or less, more preferably about 8 g or less, still more preferably about 5 g or less, but may be about 9 g or less, about 8 g or less, or about 7 g or less. It may be about 6 g or less, may be about 4 g or less, and may be about 2 g or less, but is not limited thereto.
  • the single dose of the jelly agent of the present invention is preferably about 2 to about 10 g, more preferably about 2 to about 5 g, still more preferably about 2 to about 3 g, but about 2 to about 9 g. It may be about 2 to about 8 g, about 2 to about 7 g, about 2 to about 6 g, or about 2 to about 4 g. Within these ranges, it is considered that adverse effects on patients for whom dietary criteria should be considered, such as patients with renal disease, are suppressed.
  • Jellies jelly strength present invention preferably has a jelly strength of 3000 ⁇ 30000N / m 2, more preferably from 3000 ⁇ 28000N / m 2, still more preferably 3000 ⁇ 24000N / m 2.
  • the strength may be measured by using a strength measuring device under the condition of a plunger speed of 60 mm / min made of stainless steel having a diameter of 5 mm.
  • a strength measuring device for example, EZTest manufactured by Shimadzu Corporation may be used.
  • the jelly strength may be measured based on the method described in the EZTest instruction manual.
  • the jelly agent of the present invention preferably has a water separation rate of about 0.1 to 10%, more preferably about 0.5 to 10%, based on the weight ratio of the jelly after storage at 40 ° C. for 1 month. It is preferably about 1-9%, even more preferably.
  • the water separation rate may be measured by weight deduction.
  • the jelly agent of the present invention is preferably eluted in 15 minutes by the general test method dissolution test method (paddle method) described in the Japanese Pharmacopoeia, in accordance with the bioequivalence guidelines for generic drugs.
  • the dissolution tester may be any equipment in which the conditions described in the dissolution test method and the equipment management (calibration) are sufficiently performed.
  • NTR-6200AC22 manufactured by Toyama Sangyo Co., Ltd. or another company may be used.
  • the analysis of the elution rate may also be performed by using a spectrophotometer similarly controlled by an instrument.
  • UV1800 manufactured by Shimadzu Corporation may be used.
  • the jelly agent of the present invention can be produced by a known method or a method known per se. Since the jelly manufacturing means has been sufficiently disclosed in the past, the present invention may follow the same. Specifically, for example, each component is weighed in a desired amount, heated and dissolved while stirring, and then a desired glass container or plastic container or, for example, polyethylene, nylon, polypropylene, polyvinylidene chloride fiber, polyethylene terephthalate. , A mixture of each component heated and dissolved in various molded films such as acrylic, polycarbonate, aluminum foil, or a multilayer container having a vapor-deposited film such as gold, silver, aluminum, silica, etc. to which barrier properties of various films are imparted.
  • the melting temperature is, for example, preferably 75 to 95 ° C, more preferably 75 to 90 ° C, but is not limited thereto.
  • the stirring time, including the sterilization step is preferably about 30 minutes to 1 hour, and the filling temperature is preferably 60 to 90 ° C., and is preferably in the range of about 60 to 80 ° C. Is more preferable, and it is more preferable to carry out in the range of about 60 to 70 ° C., but the present invention is not limited thereto.
  • the jelly agent of the present invention can also be produced by a method of adding a pre-dissolved solution of levocarnitine and water after heating and dissolving a gelling agent, a polyhydric alcohol or the like.
  • Example 1 Each component other than levocarnitine (L-carnitine) shown in Table 1 was mixed all at once, and then stirred at 80 ° C. for 30 minutes to be heated and dissolved. After adding levocarnitine (L-carnitine) to this, the mixture was stirred at 80 ° C. for 30 minutes and dissolved by heating to obtain a mixture.
  • the obtained mixture was filled in an appropriate aluminum stick packaging material having the shape of the desired jelly agent at 70 ° C., left to cool at room temperature, and after confirming that it had solidified, it was taken out from the container and taken out from Example 1.
  • the jelly agent of No. 1 was obtained, it was in the form of a colorless semi-solid jelly that maintained its shape along the inside of the container, and had a good appearance.
  • Examples 2 to 6 The jelly agents of Examples 2 to 6 were obtained in the same procedure as in Example 1 except that the amounts of each component were as shown in Table 1. Similar to Example 1, the appearance was good.
  • dissolution test In the dissolution test, the dissolution rate (%) after 15 minutes was measured based on the paddle method (50 rpm, 37 ⁇ 0.5 ° C., 900 mL of water) of the Japanese Pharmacopoeia.
  • the equipment used was NTR-6200AC22 manufactured by Toyama Sangyo Co., Ltd., and a spectrophotometer (UV1800 manufactured by Shimadzu Corporation) was used for the analysis of the elution rate.
  • the jelly strength test was carried out with an EZTest manufactured by Shimadzu Corporation and a stainless steel plunger having a diameter of 5 mm at a speed of 60 mm / min and measured at a temperature of 20 to 30 ° C. (measured value unit is N / m 2 ).
  • the jelly strength was measured according to the description in the EZTest instruction manual.
  • the jelly agent of the example having good appearance, dissolution test and jelly strength immediately after production was subjected to a water separation test at 40 ° C. storage. If the appearance is in a sol state immediately after production or after storage at 40 ° C., or if the dissolution test is less than 85% at a 15-minute value, or if the jelly strength is less than 3000 N / m 2 , the test can be carried out. Although it is difficult, there was no applicable example, and the water separation test could be performed for all the examples.
  • the test results of the jelly agent (Example) of the present invention are shown in Table 1. Since the jelly agent of the example contains a high concentration of levocarnitine in particular, adverse effects on the dietary standard of, for example, renal disease patients are suppressed. Further, the jelly agent of the example was eluted at 85% or more in the elution test 15 minutes value, the jelly strength was 3000 N / m 2 or more, and the water separation rate was 8% or less even after storage at 40 ° C. for 1 month. It was a jelly agent with good physical characteristics and met the standards as a pharmaceutical product.
  • a jelly agent containing a high concentration of levocarnitine for example, about 10 to 30% by weight, etc.
  • the balance between levocarnitine having strong hydration power and water and other components is a problem. Therefore, it is considered that a good jelly agent was obtained by containing a specific gelling agent and one or more polyhydric alcohols as in the present invention.
  • the present invention completely satisfies the requirements of pharmaceutical products, and high-concentration levocarnitine in consideration of the diet standard (intake limit value) of patients who should consider the diet standard, for example, patients with renal disease. It has been shown that a contained jelly can be provided.
  • the pharmaceutical jelly agent of the present invention has optimum pH and physical properties (dissolution rate, jelly strength, water separation rate, etc.), and adverse effects on dietary standards are suppressed. It is useful because it is easy to take and has excellent storage stability.

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Abstract

Le problème décrit par la présente invention est de fournir une préparation de gelée contenant de la lévocarnitine à une concentration élevée. La présente invention aborde également le problème de la fourniture d'une préparation de gelée riche en lévocarnitine destinée à être utilisée dans des médicaments, (1) qui est réduite en termes d'effets secondaires indésirables sur un patient soumis à la restriction de l'apport en eau ou en énergie (plus spécifiquement, la restriction de l'apport d'un nutriment tel qu'une protéine, de l'eau, une énergie (calorie), un sel commun et un minéral comprenant du potassium et du phosphore), c'est-à-dire, un patient qui devrait prendre en compte les "Recommandations Alimentaires" éditées par la Société Japonaise de Néphrologie tel qu'un patient atteint d'une maladie rénale, afin de permettre au patient d'ingérer efficacement et en toute sécurité la lévocarnitine, (2) qui est facile à ingérer, et/ou (3) qui présente d'excellentes propriétés physiques et une excellente stabilité au stockage. La solution selon l'invention porte sur une préparation de gelée contenant de la lévocarnitine à une concentration élevée, la préparation de gelée ayant une composition spécifiée.
PCT/JP2020/032648 2019-08-30 2020-08-28 Préparation de gelée contenant de la lévocarnitine à concentration élevée WO2021039975A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005187362A (ja) * 2003-12-25 2005-07-14 Ominedo Yakuhin Kogyo Kk 液体ゼリー状経口医薬組成物
JP2009100667A (ja) * 2007-10-22 2009-05-14 Nipro Corp ゲル状組成物の製造方法
JP2011246407A (ja) * 2010-05-28 2011-12-08 Zeria Pharmaceutical Co Ltd 経口ゼリー剤
JP2016020383A (ja) * 2010-07-29 2016-02-04 帝人ファーマ株式会社 ビスホスホン酸の経口ゼリー状製剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005187362A (ja) * 2003-12-25 2005-07-14 Ominedo Yakuhin Kogyo Kk 液体ゼリー状経口医薬組成物
JP2009100667A (ja) * 2007-10-22 2009-05-14 Nipro Corp ゲル状組成物の製造方法
JP2011246407A (ja) * 2010-05-28 2011-12-08 Zeria Pharmaceutical Co Ltd 経口ゼリー剤
JP2016020383A (ja) * 2010-07-29 2016-02-04 帝人ファーマ株式会社 ビスホスホン酸の経口ゼリー状製剤

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