TW201208715A - Dimemorfan oral liquid - Google Patents

Abstract

A sugar alcohol and/or trehalose and sucralose are added to a liquid preparation for internal administration or beverage containing dimemorfan and/or a salt thereof. In this manner, it becomes possible to reduce the bitterness inherent in dimemorfan and also reduce stimuli to the throat.

Description

201208715 VI. Description of the Invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to an internal liquid or beverage containing dimemorfan. [Prior Art] The dimethyl morphane has a strong coughing action of a morphinane (Morphinan) skeleton. Non-anesthetic agent without central dependence ‘Used in upper bronchitis, acute bronchitis, and pneumonia, it is used as a cough syrup for general medical use. The preparations for internal preparations and the like are easier to drink than solid preparations, and are easy to take for people who have reduced swallowing function such as children or elderly people or those who have symptoms such as cough. However, since the dimorphin tastes bitter, when it is used as a drink, the tasteability is deteriorated in terms of flavor. Therefore, it is necessary to reduce the bitterness and use the design by using a sweetener such as a sugar alcohol. To date, there has been a method of developing a taste improving effect by containing a drug exhibiting bitterness and the like. For example, by using stevia, a composition for colds which improves the bitter taste of Dihydrocodeine phosphate or bismuth maleate (Carbinoxamine Maleate) (refer to Patent Document 1), and reduction by using erythritol is achieved. Oral liquid of bitterness of Noscapine and Bromhexine (refer to Patent Document 2). Further, in the solid preparation for coughing which is taken up in the oral cavity to be broken or dissolved, there is a drug which has not only a bitter taste but also a sore throat when taken, but an example in which mannitol is added to reduce the pain in the throat ( Reference Patent Document-5-201208715 3) However, although the bitterness is improved by a known method for the agent containing cough suppressant, the problem of reducing throat irritation has not been solved. Therefore, it is sought to reduce the bitterness and the irritation of the throat or the irritation of the throat. CITATION LIST OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION The present invention has been made in the field of the invention. It has been confirmed that even in a liquid preparation or a beverage containing dimethorphan and/or a salt thereof, a high concentration of sugar alcohol is added, and bitterness and irritation to the throat cannot be reduced. The present invention is aimed at reducing the bitterness and throat irritation peculiar to dimemorfan and/or its salt in an internal liquid or beverage. In order to solve the above-mentioned problems, the inventors of the present invention have found that sugar alcohols and/or sugars are added together by an internal liquid preparation or a tanning material containing dimemorfan and/or a salt thereof. Trehalose, and sucralose (201208715)

Sucralose), which improves the palatable taste characteristic of dimethylmorphan, and thus also reduces the irritation to the throat, and achieves the completion of the present invention. That is, the present invention (1) contains an a liquid or a liquid of a) dimem or fan and/or a salt thereof, b) a sugar alcohol and/or a trehalose, c) a sucralose. . (2) The liquid preparation or the beverage according to the above (1), wherein the component (b) component is 180 parts by mass or more with respect to 1 part by mass of the component a), and the component c) is 0.1 part by mass or more. (3) The liquid preparation or beverage according to the above (1) or (2), wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol and maltitol. EFFECTS OF THE INVENTION The present invention can reduce bitterness and irritation to the throat in an oral liquid or beverage containing dimemorfan and/or its salt. The preferred form for carrying out the invention is the "diphthyl salt" of the present invention, for example, an internal liquid such as a hydrochloride, a sulfate, a nitrate, a phosphate, a maleate or a fumarate. The salt allowed for the agent or beverage, but the most suitable is the dimethylmorphine phosphate. The "sugar alcohol" in the present invention may be erythritol, xylitol, maltitol, inositol, sorbitol, mannitol, maltitol or the like, but xylitol or sorbitol is preferred. 201208715 In order to fully achieve the effects of the present invention, the amount of the sugar alcohol and/or trehalose added in the present invention (the total amount when two or more kinds are added) is usually 180% with respect to 1 part by mass of the dimorphin. The amount is preferably 184 parts by mass or more, more preferably 30,000 parts by mass or more, and most preferably 260 parts by mass or more. In this case, the amount of sucralose added is preferably 1 part by mass or more based on 1 part by mass of the amount of dimorphin and/or a salt thereof. The "internal liquid" in the present invention is not particularly limited as long as it can be taken as an internal liquid. For example, medical preparations such as internal liquid preparations and oral preparations, and external medicines of the Ministry of Medicine may be mentioned. In addition, the "drinking" is, for example, various types of beverages in the food range such as nutritious functional foods and specific health foods. In the internal liquid preparation or the preparation of the present invention, vitamins, minerals, amino acids, crude drugs, crude drug extracts, caffeine, and the like may be appropriately added within the range which does not impair the efficacy of the present invention. In addition, if necessary, additives such as antioxidants, colorants, perfumes, flavoring agents, surfactants, solubilizers, preservatives, sugar alcohols, and trehalose may be appropriately added to the extent that the efficacy of the present invention is not impaired. Additives such as high-sweet sweeteners other than sucralose. These additives may be added alone or in combination of two or more. The method of preparing the internal liquid preparation or the dip material of the present invention is not particularly limited. Usually, if necessary, in the case of dimorphin and / or its salt, sugar alcohol and / or seaweed, sucralose and others, dissolve the other ingredients in appropriate refined water, and then further add purified water to adjust the capacity, if necessary, By applying a filtration or sterilization treatment, it is possible to provide an internal liquid preparation or a dip which contains dimorphin and/or a salt thereof. -8 - 201208715 [Embodiment] The present invention will be described in more detail with reference to test examples and the like, but the present invention is not limited to such test examples and the like. Test Example (1) Preparation of each internal liquid preparation or beverage Each of the internal liquid preparations or beverages of Reference Example 1-3, Example 1-7 and Comparative Example 1-3 shown below was prepared. Reference Example 1 Dissolve 60 mg of dimorphin salt and 1 6000 mg of xylitol in purified water for a total amount of 40 m 1 » Reference Example 2 Dissolve 3.3 mg of anhydrous caffeine and 16000 mg of xylitol in purified water. The total amount is 40 m 1 . Reference Example 3 60 mg of the dimorphin salt and 18,000 mg of xylitol were dissolved in purified water in a total amount of 40 ml. Example 1 -9 - 201208715 60 mg of dimorpholinate, I 6000 mg of xylitol and 6.6 mg of sucralose in a purified water were dissolved in a total amount of 40 ml. Example 2 60 mg of dimorpholinate, 14,000 mg of sorbitol, and 6.6 mg of sucralose were dissolved in purified water in a total amount of 40 ml. Example 3 60 mg of dimorphin salt, 16,000 mg of xylitol, 7.4 mg of stevia and 4.4 mg of sucralose were dissolved in purified water in a total amount of 40 ml. Example 4 60 mg of dimorpholinate, 8000 mg of erythritol and 4.4 mg of sucralose were dissolved in purified water in a total amount of 40 ml. Example 5 60 mg of dimorphin salt, 16,000 mg of maltitol and 4.4 mg of sucralose were dissolved in purified water in a total amount of 40 ml. Example 6 60 mg of dimorphin salt, 16,000 mg of trehalose, and 4.4 mg of sucralose were dissolved in purified water in a total amount of 40 ml. Example 7 -10- 8 201208715 Dissolved 60 mg of dimorpholinate, 4200 mg of xylitol, 10080 mg of sorbitol, 1500 mg of trehalose, and 10.6 mg of sucralose, 17.7 mg of stevia in refined water' The amount is 40 ml. Comparative Example 1 60 mg of the dimorphin salt and 33.3 nlg of sucralose were dissolved in purified water in a total amount of 40 ml. Comparative Example 2 60 mg of the dimethyl morphane salt and 11 〇 8 mg of stevia were dissolved in purified water in a total amount of 40 ml. Comparative Example 3 60 mg of dimorpholinate, 16 mg of xylitol and 22 mg of stevia were dissolved in purified water in a total amount of 40 ml. (2) Test method The internal liquid preparations or beverages prepared according to the evaluation criteria of Table 1 were evaluated by four panelists to evaluate the bitterness and the stimulation of the throat. The results are shown in Table 2: 0 -11 · 201208715 [1] ® Evaluation benchmark is very weak, coffee is weak, slightly uncertain, slightly stronger <πι SS Very strong cs inch VO Bu CO I i2 S ο 1 16000 1 ο ο ο ο ο 1 0.17 1 § 〇m 00 — CO — OJ m SS ο ο ο ο ο ο 1 110.8 1 ο 1 0.17 1 ο 〇in 00 cd in CnJ rH base £ g ο ο ο ο ο ο ο CO CO CO 1 0.17 1 ο g CO cd CO CSJ (0 s 瘥聃s ο ο ο ο ο 116000 1 ο — 1 0J7 I 1 22.6 1 ο 一 m CO in i Grip ms ο ο ο ο 1 16000 1 ο ο 寸 1 〇·17 1 § 1 38.6 1 00 CO o CO Grip s ο ο ο 1 8000 1 ο ο ο 1 0·17 1 1 20.6 1 00 CO CO eo CO i Grip s ο 1 16000 1 ο ο ο ο 守 · 1 0.17 1 § ο Ift ο CO 00 CM mus mus ο ο 1 14000 1 ο ο ο ο (Ο cd 10.17 1 leaf CO CO CO CO eg rH § 挨铖s ο 1 16000 1 ο ο ο ο ο i〇CD 10.17 ι § g in CN3 CO CO CO extract fir 璐s ο 1 18000 1 ο ο ο ο ο ο 1 0.17 1 ΙΛ CO in 00 03 匡lo CO CO 1 16000 1 ο ο ο ο ο ο 1 0·17 1 in in CO rH m You § ο 1 16000 1 ο ο ο ο ο ο 丨 0-17 I § 5 CO iri 00 — 1 Ingredient name | B $ JJ $ J "52 J "3 JJJJ 1 Miscellaneous Mohr Wave MOmL ι 1 Sugar Alcohol Wave (%) | 1 Sweetness (9) | 1 I 喉 喉 喉 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 (%) is defined as the sweetness equivalent to the sucrose (sucrose) concentration [w/ν%] in l〇〇ml, and the sweetness 1% corresponds to the sweetness of the 1% sucrose aqueous solution. (3) The results are shown in Table 2. As can be seen from the results of Reference Examples 1 and 2, the addition of sugar alcohol to the caffeine containing the drug having a bitter taste as described by the Japanese Pharmacopoeia can reduce bitterness even if sugar alcohol is added. For internal liquid preparations containing dimorphin, the bitterness cannot be reduced. Further, it was found that the beverage containing dimorphin was more irritating to the throat than the beverage containing caffeine. From the results of Reference Example 3, it was found that in the oral liquid preparation or the beverage containing dimorphin, even if sugar alcohol was further added, the sweetness was adjusted to 45%, and compared with Reference Example 1, the bitterness and the irritation to the throat could not be reduced. From the results of Example 1, it was found that an internal liquid solution containing dimorphin and a sugar alcohol was added together with sucralose to reduce bitterness and irritation to the throat. From the results of Comparative Example 1, it was found that sucrose was added to the dimethyl morphane without adding sugar alcohol, and when the same sweetness as in Example 1 was adjusted, the irritation to the throat was reduced, but the bitterness was not reduced. Similarly, from the results of Comparative Example 2, it was found that the addition of stevia to dimethyl morpha did not reduce the bitterness even when the same sweetness as in Example 1 was adjusted. Further, from the results of Examples 2, 4, and 5, it can be seen that, as a sugar alcohol, in addition to the xylitol added in Example 1, when sorbitol, erythritol, and maltitol are added, the bitter taste of dimethylmorphin can be reduced. Stimulation of the throat. Further, from the results of Example 6, it was found that, in place of the sugar alcohol added in Examples 1, 2, and 4'-13 to 201208715, when trehalose was added, the bitter taste of the dimethylmorphin and the irritation to the throat were also reduced. From the results of Example 3, it was found that the oral liquid preparation containing dimorphin, sugar alcohol and sucrose could be added in the same degree as in Example 1 even if stevia was added, and the bitterness and irritation to the throat were the same. From the results of Comparative Example 3, it was found that in place of the sucralose added in Example 1, when the stevia was added, the bitterness and the irritation to the throat could not be reduced. Industrial Applicability According to the present invention, it is possible to reduce bitterness and throat irritation of a dimethylmorphanin-containing material, and therefore, it is possible to provide a commercially available diterpene-containing dip in the pharmaceutical product "medical products" and foods. 8 -14-

Claims (1)

201208715 VII. Application for Patent Park: • 1· An internal liquid or beverage characterized by a) dimemorfan and/or its salt, b) sugar alcohol and/or trehalose, c) sucrose Sucralose. 2. In the case of the liquid preparation or the dip in the first item of the patent application, wherein the component b) is more than 180 parts by mass and the component c) is 0.1 part by mass or more with respect to 1 part by mass of the component a). 3. The liquid medication or beverage according to item 1 or item 2 of the patent application, wherein the sugar alcohol is at least one selected from the group consisting of xylitol, sorbitol, erythritol and maltitol. -15- 201208715 IV. Designated representative map: (1) The representative representative of the case is: No (2) The symbol of the representative figure is simple: No 201208715 If there is a chemical formula in the case, please disclose the chemical formula that best shows the characteristics of the invention. :no