TW200404550A - Cepharospolin formulation for oral use - Google Patents

Abstract

The present invention relates to an oral cephalosporin preparation with improved bittering, which characterized by that it contains a sugar alcohol and a strawberry flavoring.

Description

200404550 (1) Description of the invention: (Technical field) The present invention relates to an oral cephalosporin preparation for improving bitterness. (Prior art) As a method for improving the bitterness of a drug, a method of compounding sugars, artificial sweeteners, sugar alcohols, sour agents, amino acids, glutamates, and flavors is known. However, depending on the chemical structure of the drug, the type of bitterness also changes. Therefore, it is not easy to find a prescription for the optimal improvement of the inherent bitterness of the drug. Cephalosporin compounds for oral use (especially the ester prodrug type cephalosporins) have a strong bitterness unique to their compound groups. Preparations that are sensitive to bitterness by dispersing drugs such as dry syrup in the oral cavity are formulated to improve the bitterness in order to make it easier to take. (Summary of the Invention) The inventors have repeatedly reviewed the bitterness improvement of oral cephalosporins for many years. The combination of sugar alcohol and strawberry flavor showed a particularly excellent bitterness improvement effect than before, and finally completed the present invention. The present invention is an oral cephalosporin preparation for improving bitterness as follows. (1) An oral cephalosporin preparation is characterized by containing sugar alcohol and strawberry flavor. (2) If (1) the oral cephalosporin preparation, wherein the oral cephalosporin is an ester prodrug type cephalosporin ° (3) If (1) the oral cephalosporin preparation 'wherein Oral cephalosporins are selected from the group consisting of Cefpodoxime proxetil, Cefotiam Hexetil, and Chevrolet Bieber-6-200404550 Cefteram Pivoxil, Cefuroxime Acetil, Ceferetaniet Pivoxil, Cefditoren West Road Pivoxil) and Cefcapene Pivoxil (U.S.) were prepared orally using cephalosporins. (4) The cephalosporin preparation for oral use as described in (1), wherein the cephalosporin for oral use is Shefportic Simeon Prokaryostasis. (5) The cephalosporin preparation for oral use according to any one of (1) to (4), wherein the sugar alcohol is selected from the group consisting of erythritol, xylitol, mannitol and sorbitol. (6) The cephalosporin preparation for oral use according to any one of (1) to (4), wherein the sugar alcohol is D-mannitol. (7) The oral cephalosporin preparation according to any one of (1) to (6), wherein the preparation is selected from the group consisting of a dry syrup, a chewable tablet, an orally disintegrating tablet, a tongue tablet, a powder, and Granules. (8) The cephalosporin preparation for oral use according to any one of (1) to (6), wherein the preparation is a dry syrup. (9) The cephalosporin preparation for oral use according to (1), wherein the preparation is a dry syrup containing D-mannitol and strawberry flavor. (10) The cephalosporin preparation for oral use as described in (1), wherein the preparation is a dry syrup preparation containing D-mannitol and strawberry flavor, which is characterized by Chevrolet's Cixi Prometheus blood serum. The sugar alcohol used in the present invention is not particularly limited as long as it is a polyvalent alcohol whose carbonyl group is reduced, such as erythritol, xylitol, mannitol, and sorbitol. Chase some Zhongyi mannitol, the most suitable is D_mannitol. 200404550 The compounding amount of sugar alcohol in oral cephalosporin preparations is usually preferably 20 to 80% by weight, and most preferably 30 to 60% by weight. When D-mannitol is used, it is preferred that the weight of the strawberry flavor used in the present invention is, for example, strawberry particles, strawberry fragrant, strawberry powder, and strawberry flavor, and strawberry fragrant strawberry particles are preferred. The blending amount of strawberry flavor in oral cephalosporin preparations is generally preferably 0.001 to 5% by weight, and most preferably 0.05 to 2% by weight. When strawberry fragrant is used, it is preferably 0.05 to 0.1% by weight. The cephalosporin for oral use used in the present invention is not specific as long as it is an effective beta compound for oral administration, and an ester prodrug type cephalosporin with a 4-carboxyl group protected by an ester is preferred. The cephalosporin ester prodrugs may be, for example, Chevrolet Potchiximum Pro-stage Blood Gypsy, Xuefuqi Amu Black-phase Blood Gypsy, Chevron Tiram Bieber Stage West Road, Chevroch Ximu Ah Kuo Xue Ji, Shepherd also has Delta Dobberth West Road, Shepherds Dorian Bieber Road West and Shef Cabin Bieber Road West, the most suitable is Shepherd's Potsy Simeon Proton Blood Kyrgyzstan. The amount of the oral cephalosporin in the oral cephalosporin preparation is usually preferably 5 to 40% by weight, and most preferably 5 to 15% by weight. When using Shepherd's Potsy® Female Provencal Blood Gyro, it is optimally 5 to 10% by weight. The preparations applicable to the present invention are not specific as long as they are administered orally, and are suitable for preparations in which the drug is dispersed in the oral cavity and are susceptible to bitter taste, such as dry syrups, chewable tablets, orally disintegrating tablets, tongue tablets, Powder or granules. Especially dry syrup. The preparation of the present invention is characterized by oral cephalosporin combined with sugar alcohol and strawberry flavor. It can use excipients, disintegrating agents, binding agents 200404550, flavoring agents, sweeteners, coloring agents, suspensions commonly used in formulations. Agents, pH adjusters, antifoaming agents, preservatives, flavoring agents, perfumes, fluidizers, solvents, water, etc. are suitably blended according to methods well known to the industry, such as the general prescription of the Japanese Pharmacy or the like . As the excipient, lactose, crystalline cellulose, corn starch, sugar, and the like can be used. The disintegrating agents can be sodium carboxymethyl starch, carboxymethyl ether cellulose, carboxymethyl ether cellulose calcium, carboxymethyl ether sodium, polyvinylpolypyrrolidone, low-substitution hydroxypropyl cellulose, and partially alpha starch. , Corn starch, etc. As the binding agent, α-starch, ethyl cellulose, polyvinylpyrrolidone, copolyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinylpyrrolidone and the like can be used. As the flavoring agent, L-aspartate, sarcosinate, glycyrrhizin, L_glutamate, sodium L-melamine, sodium chloride, glycyrrhizin, and the like can be used. As the sweetener, aspartame, glycyrrhizinate, white sugar, fructose, refined essence and the like can be used. Examples of the colorant include yellow osmium trioxide, caramel, titanium oxide, iron trioxide, copper chlorophyll, riboflavin, and the like. As the suspending agent, sodium carboxymethylcellulose, sodium alginate, methylcellulose, Lu polysorbate 80, tragacanth gum, carrageenan, Sanxian gum and the like can be used. As the pH adjusting agent, sodium carbonate, citric acid, succinic acid, tartaric acid, sodium bicarbonate, maleic acid, citric anhydride and the like can be used. As the defoaming agent, ethanol, sorbitol trioleate, polysorbate 80, sucrose fatty acid ester and the like can be used. Preservatives use benzoic acid, sodium benzoate, peroxybenzoate, and so on. Perfumes and fragrances include orange essential oil, orange oil, cherry flavor, pine oil, pectin, lemon powder, and the like. -9-200404550 As the fluidizer, light-weight liver silicate, stearic acid, magnesium stearate, calcium stearate, talc, etc. can be used. The solvent can be ethanol, purified water, water for injection and the like. (Embodiment) The dry syrup of the present invention can be added to the cephalosporin compound, sugar alcohol and strawberry flavor with the above-mentioned excipients, disintegrating agents, binding agents, flavoring agents, coloring agents, antifoaming agents, pH adjusting agents, sweetness After mixing the agent, etc., the fluidized layer is granulated while spraying the binder solution and dried, and then classified and granulated. The obtained granules are produced by adding extra-granular components and mixing if necessary. (Example 1) Formulation of dry syrup with D-mannitol and strawberry flavor Weight per mg (mg) 5 0 m g Force value 27.18 3 0 10 5 25 20

20 5 3 80 3 92.4 5 10 Shepherd's Cixi Promum Blood Gelatose Carboxymethyl Carboxylate Cellulose Calcium Hydroxypropyl Cellulose Sodium Branate Sodium Aspartame Ferric Oxide Carboxymethyl Ether Fiber Sodium citric acid (anhydrous) D-mannitol white sugar trioleate sorbitol sodium benzoate strawberry vanillin talc powder light silicic anhydride _ Total -10, 200404550 (Example 2) Blended with D-mannitol and strawberry flavor Prescription of dry syrup of microparticles (1) Weight per 1 dose (mg) Shepherd's Pot Cixi Promethoxone 50mg Lipolactose 13.15 Carboxymethylcellulose calcium 30 Hydroxypropyl cellulose 10 Sodium chloride 5 Sodium glutamate 25 Aspartame 20 Ferric trioxide 0.2 Sodium carboxymethyl ether cellulose 20 Citric acid (anhydrous) 5 D-mannitol 3 80 White sugar 3 92.4 Sorbitol trioleate 5 Sodium benzoate 10 Strawberry Microparticles 15 Talc powder 1 Light silicic acid anhydride 3 Total 1 0 0 0 mg 200404550 (Example 3) Formulation of dry syrup with D-mannitol and strawberry aroma particles (2) Weight per mg (mg) Snow Fupotchixi Promethalactose Carboxymethyl Ether Cellulose Calcium Hydroxypropyl Cellulose Chloride Sodium glutamate, aspartame, ferric oxide, carboxymethylcellulose sodium, citric acid (anhydrous), D-mannitol, sugar, sorbitol trioleate, sodium benzoate, strawberry particles, talcum powder, light silicic acid _ Total blood Ji 5 0 mg power price 13.15 3 0 10 5 25 20 0.2 20 5 5 00 2 72.4 5 10 15 1 3 1 0 0 0 mg

-12- 200404550 (Reference Example 1) Weight per mg of dry syrup formulation with orange microparticles (mg) Shepherd's Potassium, Simeon Pro-stage Blood Gypsum 5 Omg, Lactose 13.17 Carboxymethyl Cellulose Calcium 3 0 Hydroxypropyl cellulose 7.5 Sodium chloride 5 Bonded sodium amine 25 Aspartame 25 Iron dioxide 0.1 Carboxymethyl cellulose sodium 20 Citric acid (anhydrous) 5 White sugar 7 6 5.0 Sorbitol trioleate 5 Sodium benzoate 10 Orange particles 20 Talc powder 1 Light silicic acid anhydride 3 Total 1 0 0 0 mg

200404550 (Reference Example 2) Formulation of dry syrup containing D-mannitol and orange granules, weight per dose (mg) Chevrolet Portcixi Promethoxine 50mg potency lactose 13.15 carboxymethyl ether cellulose Calcium 30 Hydroxypropyl cellulose 10 Sodium chloride 5 Sodium glutamate 25 Aspartame 20 Iron trioxide 0.2 Sodium carboxymethyl cellulose 2 0

Citric acid (anhydrous) 5 D-mannitol 380 White sugar 3 9 2.4 Sorbitol trioleate 5 Sodium benzoate 10

Orange granules 20 talc powder 1 Light silicic acid anhydride_3 Total 1 0 5 mg (Test Example 1) Comparative test of bitterness For the preparations of Example 1, Example 2, Reference Example 1 and Reference Example 2, 3 8 For healthy people (21 males and 17 females), the evaluation test of taste 1 to 3 was performed. The preparation of Chevrolet Potassium Simeon Pro-stage Blood Gypsum 50mg Power Formula -14-200404550 was included in the mouth ’s crumble to evaluate the degree of improvement of bitterness. Test 1 · Comparison of Example 1 and Example 2 (strawberry flavor comparison with each other) Test 2: Comparison of Reference Example 1 and Reference Example 2 (comparison of orange flavor with each other) S-type test 3 · g 1 and winner of Test 2 Comparison (comparison between strawberry flavor and orange flavor) (Result of test 1) Example 1 is better or slightly better〗 8 examples 2 are better or slightly better 17

Cannot judge 3 (result of test 2) Reference example 1 is better or slightly better 1 reference example 2 is better or better 3 5 cannot be judged 2 (result of test 3) strawberry taste is better 2 1 orange Better 1 4

Unable to judge 3 people From the results of Test 1, it was found that the formulations containing D-mannitol had the same flavor in the strawberry fragrant preparation and the strawberry fine particle preparation. From the results of Test 2, it is known that the formulation containing D_mannitol in the orange particle preparation has a better taste than the formulation without D_mannitol. From the results of Test 3, it was found that the formulations containing D-mannitol had better strawberry flavor than orange flavor. CONCLUSION: The combination of D-mannitol and strawberry flavor can improve the bitterness of Chevrolet's Cixi Promethoxine preparation. -15- 200404550 (Possibility of industrial utilization) Oral use of cephalosporin preparations (especially dry syrup containing ester prodrug type cephalosporins) combined with sugar alcohol (especially D-mannitol) and strawberry flavor, found It has an exceptionally better bitterness improvement effect than ever before. (Schematic description) None

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Claims (1)

200404550 The scope of patent application: 1. A cephalosporin preparation for oral use, characterized by containing sugar alcohol and strawberry flavor. 2. An oral cephalosporin preparation according to item 1 of the scope of patent application, wherein the oral cephalosporin is an ester prodrug type cephalosporin. 3. The oral cephalosporin preparation according to item 1 of the scope of patent application, wherein the oral cephalosporin is selected from the group consisting of Cefpodoxime proxetil and Xuefuqi Amu black Cefotiam H e X eti 1), Cefte ι · am P iv ο X i 1), Cefuiroxime Acetil ), Chevrolet Delta Mebbe West Road (C efetamet P ivoxi 1), Chevrote Dolomite West Road (Cefditoren Pivoxil), and Cefcapene Pivoxil Road (Cefcapene Pivoxil) Cephalosporin preparation for oral use. 4. The cephalosporin preparation for oral use according to item 1 of the patent application scope, wherein the cephalosporin for oral use is Shepherd's Potassium Simeon Pro-stage Blood Gill. 5. The cephalosporin preparation for oral use according to any one of claims 1 to 4, wherein the sugar alcohol is selected from the group consisting of erythritol, xylitol, mannitol, and sorbitan furfuryl alcohol. 6. The cephalosporin preparation for oral use according to any one of claims 1 to 4, wherein the sugar alcohol is D-mannitol. 7. The cephalosporin preparation for oral use according to any one of claims 1 to 6, wherein the preparation is selected from the group consisting of dry syrup, chewable tablets, orally disintegrating tablets, tongue tablets, powders, and Granules. 8. The cephalosporin preparation for oral use according to any one of claims 1 to 6, wherein the preparation is a dry syrup. -17, 200404550 (1) Designated representative map: (1) The designated representative map in this case is: (). (2) Brief description of the element representative symbols in this representative map: 捌 If there is a chemical formula in this case, please disclose the chemical formula that can best show the characteristics of the invention: