Pharmaceutical composition containing ilex asprella, heat-clearing and inflammation-eliminating preparation and preparation method thereof

Abstract

The application discloses a medicine composition containing Ilex hainanensis, a heat-clearing and inflammation-resolving preparation and a preparation method thereof, and the medicine composition containing Ilex hainanensis comprises the following raw material components in parts by weight: Ilex hainanensis dry extract powder 100 parts; sucralose 0.30-0.40 parts; stevioside 1.00-1.20 parts; citric acid 0.05-0.15 parts. The medicine composition containing Ilex hainanensis and the heat-clearing and inflammation-resolving preparation provided by the application use sucralose, stevioside and citric acid as a composite flavoring agent, the three components are mutually coordinated, the oral compliance of the preparation is successfully improved, the bitterness and astringency of the heat-clearing and inflammation-resolving preparation obtained after the composite flavoring agent is added according to the amount are well improved, there is no bad smell, and the overall taste is good.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical preparations, in particular, a kind of drug composition containing Ilex hainanensis, heat-clearing and inflammation-eliminating Ning preparation and its preparation method. BACKGROUND

[0002] Ilex hainanensis is the aboveground part of grass coral plant of Chiman family, also known as Zhongjie Feng, which has the effects of clearing heat and detoxifying, antibacterial and anti-inflammatory, clearing lung and relieving cough, expelling wind and dampness, relaxing sinews and activating collaterals, promoting blood circulation and relieving pain, setting bone and healing injury, etc. Heat-clearing and inflammation-eliminating Ning preparation developed by the applicant is a traditional Chinese medicine preparation prepared from natural medicinal material Ilex hainanensis according to the traditional Chinese medicine principle of "treating heat with cold and treating warm with clear".

[0003] Cold is a very common disease, especially the infants, the elderly or some people with underlying diseases who have weak resistance are particularly susceptible to cold virus infection. Cold virus invades the respiratory tract, causing acute upper respiratory tract infection, and causing symptoms such as sore throat, cough, fever, etc. There are still many problems in the treatment of acute upper respiratory tract infection, such as the abuse of antibiotics, antiviral drugs, compound cold medicines, traditional Chinese medicines, and excessive dependence on intravenous drugs, non-standard treatment, etc. Based on the clinical needs of acute upper respiratory tract infection and the safety and effectiveness of heat-clearing and inflammation-eliminating Ning preparation, the applicant provides a new drug composition containing Ilex hainanensis, heat-clearing and inflammation-eliminating Ning preparation, in order to better solve the problems existing in the prior art and meet the needs of clinical treatment of upper respiratory tract infection and other diseases.

[0004] Oral administration is the most commonly used administration method in clinical practice at present. Taste is one of the important factors affecting the clinical application of oral preparations. Adverse taste may affect the patient's medication compliance, leading to difficulty in achieving or maintaining ideal therapeutic effect, and may also lead to unstable drug exposure in the body, thereby causing safety hazards. Therefore, taste evaluation is usually a very important special research content in the process of drug development.

[0005] The dry paste powder prepared from the medicinal Ilex hainanensis Merr. has extremely bitter taste, astringency and bad smell after brewing, and most of its oral preparations have strong bitter taste and other unpleasant taste, which can easily cause taste discomfort in patients, especially children, and can lead to delayed treatment due to non-compliance with medication, that is, low medication compliance, affecting patients to take medicine. Because the taste buds of children are more sensitive to different tastes, especially bitter taste, bitter components are more easily perceived by taste receptors in the mouth, causing bad taste, and the risk of adverse medication behavior caused by bad taste is also correspondingly increased. Therefore, compared with adult medication, the study of taste of children's medication has stronger clinical significance and value, and also has greater technical challenge. However, it is not easy to mask the bitter taste, and the perception threshold of bitter taste is very small. How to effectively mask the bitter taste of the drug and improve the quality of the preparation is a big challenge for pharmaceutical workers. With the progress of preparation technology, taste masking technology is developing, and the addition of flavoring agents and coating is still the most commonly used two taste masking methods. However, it is still very challenging to mask the taste of the medicinal Ilex hainanensis Merr. with strong bitter taste and large dose, which requires researchers to design and research the physicochemical properties, dose and other properties of Ilex hainanensis Merr. with precision, integrate innovative concepts, and flexibly use taste masking technology. There is no related report in the prior art. SUMMARY

[0006] The application provides a Qingre Xiaoyanning and a preparation method thereof, to solve the technical problem that the Qingre Xiaoyanning has extremely bitter taste, astringency and bad smell due to the medicinal Ilex hainanensis Merr., and causes taste discomfort in patients when taken, affecting the medication compliance of patients (especially children).

[0007] According to one aspect of the application, a pharmaceutical composition containing Ilex hainanensis Merr. is provided, which comprises the following raw material components in parts by weight: 100 parts of Ilex hainanensis Merr. dry paste powder, 0.30-0.40 parts of sucralose, 1.00-1.20 parts of steviol glycoside, and 0.05-0.15 parts of citric acid.

[0008] Further, the pharmaceutical composition containing Ilex hainanensis Merr. comprises the following raw material components in parts by weight: 100 parts of Ilex hainanensis Merr. dry paste powder, 0.35-0.36 parts of sucralose, 1.00-1.20 parts of steviol glycoside, and 0.05-0.15 parts of citric acid.

[0009] Further, the pharmaceutical composition containing Ilex hainanensis Merr. comprises the following raw material components in parts by weight: 100 parts of Ilex hainanensis Merr. dry paste powder, 0.36 parts of sucralose, 1.00-1.20 parts of steviol glycoside, and 0.10 parts of citric acid.

[0010] Further, the nine-stemmed tea-containing pharmaceutical composition comprises the following raw material components by weight: 100 parts of nine-stemmed tea dry extract powder; 0.36 parts of sucralose; 1.1 parts of stevioside; and 0.10 parts of citric acid.

[0011] According to another aspect of the present application, there is also provided a Qingre Xiaoyanning preparation comprising the nine-stemmed tea-containing pharmaceutical composition and other pharmaceutically acceptable excipients.

[0012] Further, the acceptable excipients comprise 4-50 parts of a filler.

[0013] Further, the filler comprises malt dextrin, starch or lactose.

[0014] According to still another aspect of the present application, there is also provided a preparation method of Qingre Xiaoyanning granules, comprising the following steps:

[0015] The nine-stemmed tea is extracted, concentrated, dried and pulverized to obtain nine-stemmed tea dry extract powder, wherein the relative density of the concentrated thick extract at 60-70 DEG C is 1.25-1.30.

[0016] The nine-stemmed tea dry extract powder is mixed with other raw materials according to the weight of the raw material components to obtain a mixed powder.

[0017] The mixed powder is granulated by a dry method to obtain Qingre Xiaoyanning granules.

[0018] Further, the extraction comprises heating reflux extraction or decocting and filtering extraction.

[0019] The present application has the following beneficial effects:

[0020] The nine-stemmed tea-containing pharmaceutical composition and the Qingre Xiaoyanning preparation provided by the present application use sucralose, stevioside and citric acid as a composite flavoring agent, and the three components synergistically improve the oral compliance of the preparation.

[0021] The present application is based on the fact that there are five basic tastes in human body, i.e., sweet, salty, sour, bitter and umami, and the taste of these tastes depends on the interaction between molecules in food and specific taste receptor proteins on the taste buds of the tongue, the taste receptors recognize the corresponding food molecules, trigger a cascade signal, cause the release of chemical substances (neurotransmitters), and activate specific areas in the brain that perceive and process taste. Studies have found that type II taste cells contain receptors that distinguish sweet substances and bitter substances, i.e., T1R2, T1R3 and T2R, which belong to the G protein-coupled receptor family. Sweet and bitter use similar signal pathways in cells. Therefore, when a sweetener is added, the competition of sweet taste for specific proteins can be increased, thereby weakening the perception of bitterness in the human body. In the present prescription, stevioside and sucralose compete with each other for bitter taste perception through this mechanism, thereby weakening the bitter taste.

[0022] Applicants found that too little or too much sweetener would result in poor bitterness suppression or excessive sweetness. In addition, when only sweetener is used, bitterness and sweetness can be perceived simultaneously, and the bitterness cannot be completely eliminated, resulting in unnatural mouthfeel. To address this, applicants added an acidifier, citric acid, which can offset some of the sweetness and bitterness, impart a moderate sour taste, and improve the flavor and mouthfeel of the product.

[0023] However, it is still a great challenge to achieve a universally acceptable taste or neutral taste for pharmaceutical compositions containing Ilex hainanensis, such as Qingre Xiaoyanning granules. In the research process, applicants found that, when using a single flavoring agent other than high-sweetness flavoring agents or low-sweetness sweeteners, there was little improvement in the mouthfeel of the product. This indicates that, in order to achieve the purpose of masking the bitterness of the preparation through flavoring means, high-sweetness sweeteners or a large amount of other flavoring agents need to be added. Based on the consideration of the dosage of the preparation, applicants prefer to use a large-sweetness sweetener, sucralose, and found that, when used alone, it still cannot achieve the desired goal. Therefore, a second high-sweetness sweetener, steviol glycoside, was introduced. The combination of the two significantly reduced the bitterness of the product, but there was still a lingering bitter aftertaste, and the bitter and sweet tastes coexisted, resulting in an obvious off-taste and mouthfeel. Therefore, in order to further improve the flavor and mouthfeel, applicants added acidifiers, flavors, and salty agents for testing. After extensive testing, applicants found that acidifiers, flavors, and salty agents had a significant impact on the improvement of bitter taste by sweeteners. As the number of auxiliary materials increased, the uncontrollability of the flavoring effect increased. Specifically, in the first case, when sodium chloride, a salty agent, was added alone on the basis of double sweeteners, the entry bitterness decreased slightly, but the lingering bitterness increased. When the proportion of sodium chloride was increased, both the entry bitterness and the lingering bitterness increased. In the second case, when a flavor was added alone on the basis of double sweeteners, the odor was optimized, but the mouthfeel was worse. In the third case, when citric acid was added alone on the basis of double sweeteners, the mouthfeel and entry bitterness were improved to some extent, but the amount of citric acid had a significant impact on the improvement effect, and the impact showed irregular changes. When the amount of citric acid was less than or greater than the optimal amount in the prescription, the bitterness and lingering bitterness were stronger. In the fourth case, when two or more acidifiers, salty agents, and flavors were added simultaneously on the basis of double sweeteners, the mouthfeel was strange, and there was no adjustment regularity.

[0024] Finally, the applicant accidentally found that when the contents of sucralose, stevioside and citric acid were selected, the three components showed a synergistic effect: in this scheme, the two high-intensity sweeteners were retained while an appropriate amount of citric acid was introduced, which weakened the bitter taste of the preparation while processing the after-bitterness and the problem of bitter taste existing with sweetness, and did not bring other unpleasant taste. Compared with the introduction of other types of flavoring agents and the effect of other amounts of citric acid, the ratio of the prescription has more improvement advantages, significantly weakens the bitter taste while introducing less unpleasant taste, and greatly enhances the palatability. Especially when the following weight parts of raw material components are used: 100 parts of Kuzhu tea dry extract powder; 0.36 parts of sucralose; 1.00-1.20 parts of stevioside; 0.10 parts of citric acid, the comprehensive score can be as high as 9 points, the bitter and astringent taste of Kuzhu tea pharmaceutical composition and its Redian Ning preparation has been greatly improved, there is no unpleasant odor, the overall taste is good, and the patient's (especially children) compliance can be effectively improved. DETAILED DESCRIPTION

[0025] In order to make the invention purposes, technical solutions and beneficial technical effects of the present application clearer, the present application will be further described in detail below in combination with examples. It should be understood that the examples described in the present specification are only for the purpose of explaining the present application, and are not intended to limit the present application.

[0026] For simplicity, only some numerical ranges are explicitly disclosed herein. However, any lower limit can be combined with any upper limit to form a range not explicitly recited; and any lower limit can be combined with other lower limits to form a range not explicitly recited, and likewise any upper limit can be combined with any other upper limit to form a range not explicitly recited. Furthermore, although not explicitly recited, every point or individual number within a range is included in the range. Thus, every point or individual number can serve as its own lower limit or upper limit to combine with another point or individual number or to combine with other lower limits or upper limits to form a range not explicitly recited.

[0027] In the description herein, it should be noted that, unless otherwise specified, "above", "below" include the number, and the meaning of "multiple" in "one or more" is two or more, and the meaning of "multiple" in "one or more" is two or more.

[0028] The problem of flavoring and taste masking of traditional Chinese medicine and preparations has always been a difficult problem faced by the preparation science. Domestic and foreign scholars have conducted more research on the problem of drug taste. At present, the mechanism of flavoring and taste masking of drugs mainly includes the following aspects: ① adding flavoring agents to change the sensitivity of taste buds to unpleasant taste; ② directly isolating the direct contact of drugs with taste buds by coating, adsorption and inclusion; ③ modifying the molecular structure of drugs.

[0029] For example, flavoring agents are classified into various types, including high-intensity sweeteners, bitter blockers, flavorings, sour agents, etc. The type of flavoring agent, the amount of flavoring agent, and the amount of a certain flavoring agent can all bring about great changes in sensory results. In addition, different traditional Chinese medicines and preparations have different active ingredients, and there are great differences in the flavoring or taste-masking research of different traditional Chinese medicines and preparations, and there is no fundamental commonality or regularity, which has been puzzling researchers in the field of pharmaceutical science for a long time. The main reason is that the chemical composition of traditional Chinese medicines is complex. A bitter medicinal material usually contains multiple bitter substances and other off-taste sensations such as astringency, sourness, etc. It is difficult to determine the specific components of the drug that cause adverse taste, making it difficult to use corresponding flavoring and taste-masking techniques. For example, the selectivity of cyclodextrin to the inclusion compound limits the use of inclusion technology in the taste-masking of traditional Chinese medicine compounds. Some methods commonly used in the food and chemical medicine fields, such as adding bitter eliminating agents or using macroporous ion exchange resin method, are relatively mature techniques in the field of taste-masking of oral liquid preparations at home and abroad at present, but these methods are mainly for chemical drugs with very clear composition. In the field of chemical drugs, prodrugs are also an effective flavoring and taste-masking technology, but in the field of traditional Chinese medicines, the complexity of the components makes it difficult to use this new technology. When using fluidized bed coating to mask the taste, the particle size of the drug powder is too small to affect the coating due to static electricity, and the particle size is too large to affect the taste effect, and the quality is not easy to control. In addition, there is a non-standard phenomenon in the use of flavoring and taste-masking materials. Some pharmaceutical excipients have been used in the laboratory without approval by the pharmaceutical regulatory department, and the relevant flavoring and taste-masking techniques obtained are limited to experimental research and are difficult to apply to actual industrial production. The first aspect of the embodiments of the present application provides a pharmaceutical composition containing Ilex hainanensis, which comprises the following raw material components by weight: Ilex hainanensis dry extract powder 100 parts; sucralose 0.30-0.40 parts; steviol glycoside 1.00-1.20 parts; citric acid 0.05-0.15 parts.

[0030] The pharmaceutical composition containing Ilex hainanensis provided by the embodiments of the present application uses sucralose, steviol glycoside and citric acid as a composite flavoring agent, which successfully improves the oral compliance of the preparation. The bitter taste and astringency of the Ilex hainanensis preparation Qingre Xiaoyanning obtained after adding the composite flavoring agent according to the amount are well improved, there is no unpleasant odor, and the overall taste is good.

[0031] In embodiments, the trichlorosucrose is 0.30-0.40 parts by weight, for example, 0.3 parts, 0.35 parts, 0.36 parts, or 0.4 parts, etc., and can also be any combination of the above weight parts; the steviol glycoside is 1.00-1.20 parts by weight, for example, 1.00 parts, 1.05 parts, 1.10 parts, 1.15 parts, or 1.20 parts, etc., and can also be any combination of the above weight parts; the citric acid is 0.05-0.15 parts by weight, for example, 0.05 parts, 0.08 parts, 0.10 parts, 0.12 parts, or 0.15 parts, and can also be any combination of the above weight parts.

[0032] In embodiments, the dosage form of the pharmaceutical composition containing Kudafolia can be granules, liquid, or tablets, etc., wherein the granules and liquid can be used as a dosage form for children aged 2-13 years.

[0033] In embodiments of the present application, the use of steviol glycoside alone cannot improve the bitter taste, and the use of trichlorosucrose alone can improve the bitter taste to a certain extent, but the bitter taste and sweet taste coexist; the use of citric acid alone can significantly improve the astringent taste, but the improvement of the bitter taste is not obvious. The simultaneous use of trichlorosucrose, steviol glycoside, and steviol glycoside in the present application can not only improve the bitter taste well, but also significantly improve the astringent taste. However, if the amount of trichlorosucrose or steviol glycoside is less than the above minimum value, the effect of reducing bitter taste will be significantly affected; if the amount of steviol glycoside is greater than the above maximum value, the overall improvement effect of the sweetener (trichlorosucrose and steviol glycoside) on the bitter taste will be weakened, and the taste will be too sour; if the amount of citric acid is greater than the above maximum value, the taste will be sour while the taste is improved, and the improvement effect of the sweetener on the bitter taste will be weakened.

[0034] The pharmaceutical composition containing Kudafolia provided in embodiments of the present application has a significantly reduced bitter and astringent taste, and the taste is acceptable, more acceptable, or easily acceptable (acceptable: bitter / strange taste; more acceptable: slightly bitter / strange taste; easily acceptable: no bitter / strange taste).

[0035] In order to further improve the taste of the pharmaceutical composition containing Kudafolia, embodiments of the present application include the following weight parts of raw material components: Kudafolia dry extract powder 100 parts; trichlorosucrose 0.35-0.36 parts; steviol glycoside 1.00-1.20 parts; citric acid 0.05-0.10 parts.

[0036] The dry paste powder obtained by extracting, concentrating and drying of the medicinal herb Artemisia japonica has extremely bitter taste, with astringent taste and bad smell. Especially children patients are more sensitive to taste, and have poor compliance to medicine, which may lead to delayed treatment due to the bad taste of medicine. In order to further improve the taste of the Qingre Xiaoyanning, and make it more acceptable to children, the embodiment of the present application comprises the following raw material components by weight: Artemisia japonica dry paste powder 100 parts; sucralose 0.36 parts; steviol glycoside 1.00-1.20 parts; citric acid 0.10 parts.

[0037] In order to further improve the taste of the Artemisia japonica-containing pharmaceutical composition, and make it acceptable to all people (including children), the embodiment of the present application comprises the following raw material components by weight: Artemisia japonica dry paste powder 100 parts; sucralose 0.36 parts; steviol glycoside 1.1 parts; citric acid 0.10 parts.

[0038] There are many problems in the drug treatment of acute upper respiratory tract infection in children, including the abuse of antibiotics, antiviral drugs, compound cold medicines and traditional Chinese medicines, in addition, there is excessive dependence on intravenous drugs and non-standard treatment methods. The applicant develops Qingre Xiaoyanning granules as an acute upper respiratory tract infection drug specially designed for children aged 2-13 years, which significantly improves the taste and increases the compliance of children patients. At the same time, the Qingre Xiaoyanning granules are designed for the treatment of acute upper respiratory tract infection, and the function is to "clear heat and detoxify, and relieve inflammation and pain", which is used for the treatment of acute upper respiratory tract infection in children, with symptoms of headache, sore throat, muscle soreness, fever, cough, nasal congestion and runny nose. In the embodiment of the present application, the Artemisia japonica-containing pharmaceutical composition with the above raw material composition is made into granules with slightly sweet and slightly sour taste, reduced bitter taste and reduced strange taste, smooth taste, and the comprehensive score reaches 9 points, which is especially suitable for children aged 2-13 years.

[0039] The embodiment of the second aspect of the present application provides a Qingre Xiaoyanning preparation, which comprises the Artemisia japonica-containing pharmaceutical composition and other pharmaceutically acceptable excipients.

[0040] In the embodiment of the present application, the raw material of the Qingre Xiaoyanning preparation further comprises a filler 4-50 parts. In order to facilitate production, the raw material of the Qingre Xiaoyanning preparation can further comprise the following fillers: starch, lactose, malt dextrin, etc.

[0041] The embodiment of the third aspect of the present application provides a preparation method of Qingre Xiaoyanning granules, which comprises the following steps:

[0042] Artemisia japonica is extracted, concentrated, dried and crushed to obtain Artemisia japonica dry paste powder, wherein the relative density of the thick paste after concentration is 1.25-1.30 at 60-70°C;

[0043] According to the weight parts of the raw material components, the Uncariae Ramulus Cum Uncis dry extract powder is crushed, passed through a 100-mesh sieve, and mixed with other auxiliary materials to obtain a mixed powder.

[0044] The mixed powder is granulated by dry granulation and sieved through a 12-mesh sieve to obtain Qingre Xiaoyan Ning granules.

[0045] In some embodiments, the extraction includes heating reflux extraction, or decocting and filtering extraction.

[0046] In some embodiments, the concentration is reduced pressure concentration.

[0047] According to the embodiments of the present application, the preparation process of Qingre Xiaoyan Ning granules has simple equipment, convenient operation, high automation degree, low labor intensity, and high production efficiency.

[0048] In some embodiments, the preparation method of Qingre Xiaoyan Ning granules includes the following steps:

[0049] S1, extraction: Uncariae Ramulus Cum Uncis decoction pieces are extracted twice with a solvent, and the extract is obtained by filtering, wherein the solvent is water, and the extraction is heating reflux extraction;

[0050] S2, concentration: the extract is concentrated to obtain an extract;

[0051] S3, drying: the Uncariae Ramulus Cum Uncis dry extract powder after drying and crushing;

[0052] S4, mixing and flavoring: Uncariae Ramulus Cum Uncis dry extract powder, fillers, and sucralose, stevioside, and citric acid are mixed and flavored to obtain a mixed powder after flavoring;

[0053] S5, granulation: the mixed powder is granulated by dry granulation to obtain Qingre Xiaoyan Ning granules.

[0054] Embodiments

[0055] The following examples more specifically describe the disclosure of the present application, which are only used for illustrative purposes, because various modifications and changes within the scope of the disclosure of the present application are obvious to those skilled in the art. Unless otherwise stated, all parts, percentages, and ratios reported in the following examples are based on weight, and all reagents used in the examples are commercially available or synthesized according to conventional methods and can be used directly without further treatment, and the instruments used in the examples are commercially available.

[0056] The Qingre Xiaoyan Ning granules of the examples and comparative examples are based on the principle of maximum addition amount of a single flavoring agent and relatively small amount of auxiliary materials, and the flavoring agent is added for flavoring in 2.9g of Uncariae Ramulus Cum Uncis dry extract powder.

[0057] Preparation of dry powder of Ilex hainanensis Merr. : Ilex hainanensis Merr. was decocted twice with water, 1.5 hours for the first time and 1 hour for the second time. The decoction was filtered, and the filtrate was combined and concentrated under reduced pressure to a thick paste with a relative density of 1.25-1.30 (60-70 °C). The paste was dried and pulverized to obtain the dry powder of Ilex hainanensis Merr.

[0058] Mixing and flavoring: 2.9 g of the dry powder of Ilex hainanensis Merr. and flavoring agents were mixed and flavored. Finally, maltodextrin was added to make up 3 g. The mixed powder was dry granulated to obtain granules. The specific amount of the flavoring agents is shown in Table 2. The amount of each raw material in Table 2 is in mg, and the mass percentage is based on the amount of each raw material added / the mass of the dry powder of Ilex hainanensis Merr. (2.9 g).

[0059] Establishment of scoring system (reference: Technical Guidelines for Taste Design and Evaluation of Medicines for Children): The granules of Qingre Xiaoyan Ning obtained in each example or comparative example were dissolved in 50 ml of hot water (to observe the solubility) to obtain a medicinal liquid, which was kept in a constant-temperature water bath at 35 ± 5 °C.

[0060] The tasters (without smoking or drinking within two days, and without eating for 2 hours before tasting) were selected to taste. Before tasting, the tasters rinsed their mouths with warm water. Each solution was contained in the mouth for 10 seconds and then spit out. The taste was suitable for the degree of taste (the main off-taste of the product was bitter. The final judgment was based on the degree of bitterness and the overall taste). The overall sensory evaluation was scored. The sensory evaluation grade score for tasting is shown in Table 1. A score of 5 or more indicates successful flavoring, which does not affect the patient's compliance with medication; a score of 7 or more meets the standard for medicines for children.

[0061] Table 1 Sensory evaluation grade score table for tasting

[0062]

[0063]

[0064] Ten tasters were selected for each experiment of the present application to score. After removing one highest score and one lowest score, the average was taken, and the integer was obtained after rounding off to the nearest whole number, as shown in Table 2.

[0065] 1. Comparison of three flavoring agents (Examples 1-6) with two flavoring agents (Comparative Examples 1-9).

[0066] Table 2 Examples 1-6 and Comparative Examples 1-9

[0067]

[0068]

[0069] Note: The values in parentheses in the table for each component are the mass percentage of the component in the granules of Qingre Xiaoyan Ning.

[0070] The solubility of the above examples and comparative examples is qualified, and from the above results, it can be seen that examples 1-6 can all at least achieve a significant reduction in bitter taste and off-taste, and the taste is acceptable, that is, the comprehensive score is more than 5. Among them, the overall taste in example 2 is the best, the bitter taste is significantly reduced, the taste is relatively smooth, and the standard for children's medication is met (a comprehensive score greater than 7 is considered to meet the standard for children's medication). At the same time, it can be seen from the results that when the amount of sucralose or steviol glycoside is reduced, the bitter taste reduction effect is reduced; when the amount of steviol glycoside exceeds a certain limit, the bitter taste reduction effect and overall taste are also reduced; when the amount of citric acid is too large, the taste is improved, but there is a situation of being too sour, and the sweetener reduces the bitter taste.

[0071] 2. Comparison of four flavoring agents

[0072] In this experiment, 2.9 g of intermediate dry powder was added to four types of flavoring agents, and maltodextrin was added to make up to 3.0 g. The preparation method was the same as above, and the results are shown in Table 3.

[0073] Table 3 Comparative examples 10-15

[0074]

[0075]

[0076] Note: The numbers in parentheses in the table are the mass percentage of the component in Qingre Xiaoyanling Granules.

[0077] The solubility of the above comparative examples is qualified, and from the results, it can be seen that when the composite flavoring agent is steviol glycoside + sucralose + citric acid + sodium chloride, part of the saltiness is introduced, and the sensory is not good, especially after introducing different amounts of sodium chloride based on example 2, the sensory is significantly decreased. When the composite flavoring agent is steviol glycoside + sucralose + citric acid + lemon powder essence, the bitter taste improvement effect is not good, especially after introducing a certain amount of lemon powder essence based on example 2, the sensory is significantly decreased.

[0078] 3. Comparison of single flavoring agents

[0079] In this experiment, 2.9 g of intermediate dry powder was added to a single type of flavoring agent, and maltodextrin was added to make up to 3.0 g. The preparation method was the same as above.

[0080] Among them, mannitol, steviol glycoside or sucralose was taken as a sweetener (dose 10.5 mg), or L-malic acid or citric acid was taken as a sour agent (dose 2.9 mg), respectively, and the taste improvement evaluation was carried out according to the evaluation method of the evaluation system. The mixed powder without adding flavoring agents was used as a control, and the results are shown in Table 4:

[0081] Table 4 Comparative Examples 16-21

[0082]

[0083]

[0084] Note: The values in parentheses in the table are the mass percentage of the component in Qingre Xiaoyanning granules.

[0085] The solubility of the above comparative examples is qualified, and the results show that after adding sucralose, the bitter taste and the improvement effect of the taste are more obvious, but considering the maximum daily usage (WHO stipulates that the daily intake can reach 13 mg / kg), the improvement effect of using the sweetener alone cannot achieve the expected effect. The bitter taste of adding mannitol alone is unbearable, and the overall taste is not improved; the overall taste is improved by adding stevioside alone, but the bitter taste is obvious; the overall taste is improved by adding L-malic acid alone, but the bitter taste is unbearable; the overall taste is improved by adding citric acid, but the bitter taste is unbearable.

[0086] In summary, the Qingre Xiaoyanning provided by the present application uses sucralose, stevioside and citric acid as a composite flavoring agent, which successfully improves the oral compliance of the preparation, and the bitter taste and astringent taste of the Qingre Xiaoyanning preparation are well improved, there is no unpleasant odor, and the overall taste is good.

[0087] Although the present application has been described with reference to the preferred embodiments, various modifications can be made to it without departing from the scope of the application, and equivalent substitutions can be made to the components thereof, and in particular, the technical features mentioned in each embodiment can be combined in any manner as long as there is no structural conflict. The present application is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.

Claims

1. A pharmaceutical composition comprising Kuzhu, characterized in that, The nine-stemmed tea dry powder is prepared from the following raw material components by weight: 100 parts of nine-stemmed tea dry powder; 0.35-0.40 parts of sucralose; 1.00-1.20 parts of stevioside; and 0.05-0.15 parts of citric acid.

2. The Gynostemma-containing pharmaceutical composition according to claim 1, characterized in that, The nine-stemmed tea dry powder is prepared from the following raw material components by weight: 100 parts of nine-stemmed tea dry powder; 0.35-0.36 parts of sucralose; 1.00-1.20 parts of stevioside; and 0.05-0.15 parts of citric acid.

3. The Gynostemma-containing pharmaceutical composition according to claim 1, characterized in that, The nine-stemmed tea dry powder is prepared from the following raw material components by weight: 100 parts of nine-stemmed tea dry powder; 0.36 parts of sucralose; 1.00-1.20 parts of stevioside; and 0.10 parts of citric acid.

4. The Gynostemma-containing pharmaceutical composition according to claim 1, characterized in that, The nine-stemmed tea dry powder is prepared from the following raw material components by weight: 100 parts of nine-stemmed tea dry powder; 0.36 parts of sucralose; 1.00-1.20 parts of stevioside; and 0.10 parts of citric acid.

5. A preparation of Qingre Xiaoyan Ning, characterized in that, The nine-stemmed tea dry powder is prepared from the following raw material components by weight: 100 parts of nine-stemmed tea dry powder; 0.36 parts of sucralose; 1.00-1.20 parts of stevioside; and 0.10 parts of citric acid.

6. The Qingre Xiaoyan Ning preparation according to claim 5, characterized in that, The acceptable excipients include 4-50 parts of fillers.

7. The Gynostemma-containing pharmaceutical composition according to claim 6, characterized in that, The fillers include malt dextrin, starch or lactose.

8. The dosage form of the Qingre Xiaoyan Ning preparation according to any one of claims 5-7 comprises granules or tablets.

9. The method for preparing Qingre Xiaoyan Ning granules according to claim 8, characterized in that, The method comprises the following steps: The nine-stemmed tea is extracted, concentrated, dried and pulverized to obtain the nine-stemmed tea dry powder, wherein the relative density of the concentrated thick paste at 60-70°C is 1.25-1.30; The nine-stemmed tea dry powder is mixed with other raw materials according to the weight of the raw material components to obtain a mixed powder; The mixed powder is granulated by dry granulation to obtain the Qingre Xiaoyan Ning granules.

10. The method of claim 9, wherein, The extraction includes heating reflux extraction or decocting and filtering extraction.

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