A flavor-correcting formula for improving the taste of Qinxiang Qingjie oral liquid

Through the flavor correction strategy of "sour, cool, spicy, strong, sweet and bitter," combined with citric acid, menthol and sweetener, the problem of bitter and spicy taste of Qinxiangqingjie oral liquid is solved, which improves the taste and stability and improves the patient's medication compliance.

CN116392597BActive Publication Date: 2025-08-15GUANGZHOU UNIRISE PHARM CO LTD +3
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Patent Information

Application Number
CN202310093424.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-02-07
Publication Date
2025-08-15
Estimated Expiration
2043-02-07

AI Technical Summary

Technical Problem

Due to the strong bitterness and spicy taste of Qinxiang Qingjie Oral Liquid, it affects the medication compliance of pediatric patients. The existing flavor correction methods are poor, making it difficult to effectively improve its taste.

Method used

The flavoring strategy of "acid, cool, spicy, strong, sweet, and bitter, overall optimization, and stability" is adopted. Citric acid is used to reduce the spicyness, menthol improves the burning sensation, and sweeteners such as xinli and saccharin are combined to inhibit bitterness and optimize sweetness and stability.

Benefits of technology

It significantly improved the taste of Qinxiang Qingjie Oral Liquid, improved the patient's medication compliance, while maintaining the stability of the drug and the content of active ingredients.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention provides a flavor-correcting formula for improving the taste of Qinxiang Qingjie oral liquid, comprising citric acid, menthol, essence, and a sweetener. The flavor-correcting formula disclosed in the present invention is screened using a sensory evaluation method conducted by volunteers. Based on the actual human taste as a screening criterion, the formula aims to improve the unpleasant taste of Qinxiang Qingjie oral liquid to the greatest extent possible without affecting its efficacy, thereby enhancing patient compliance.
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Description

Technical Field

[0001] The invention belongs to the field of medicine, and particularly relates to a flavor-correcting formula for improving the taste of Qinxiang Qingjie oral liquid. Background Art

[0002] Qinxiang Qingjie Oral Liquid is composed of 12 herbs: Scutellaria baicalensis, Patchouli, Cicadae Periostracum, Gypsum, Pueraria lobata, Rhubarb, Red Peony Root, Platycodon grandiflorum, Isatis root, Scrophularia ningpoensis, Sophora flavescens, and Licorice. It has the effects of dispelling wind and relieving fever, clearing internal heat, and detoxifying and relieving sore throats. It is commonly used for children with upper respiratory tract infections characterized by both internal and external heat, with symptoms such as fever, nasal congestion, runny nose, cough, red and sore throat, constipation, thirst and irritability, red tongue with a yellow coating, and a slippery and rapid pulse. However, it has a complex taste, with unpleasant bitter and spicy notes.

[0003] As an oral liquid preparation of traditional Chinese medicine, it has high bioavailability and rapid effect, but its high dispersion makes the unpleasant-tasting drug components dissolve and diffuse instantly after entering the mouth. The unpleasant taste is produced quickly and with high intensity, which seriously affects the medication compliance of pediatric patients.

[0004] Currently, there are three main approaches to improving the taste of oral liquid preparations of traditional Chinese medicine: 1. Preventing or reducing contact between the drug and taste receptors, primarily through physical coating, thickening, resin exchange, bitterness quenching, and masking techniques; 2. Blocking the pathways of taste signal transmission, primarily through anesthetizing taste receptors and blocking nerve signal transmission; and 3. Interfering with the integration of taste nerve centers, primarily through the use of sweeteners, fragrances, cooling agents, and other ingredients to reduce the sensitivity of taste receptors to unpleasant taste components. However, single flavor correction and masking methods are ineffective and are unable to reduce or eliminate the unpleasant taste and odor of the drug itself.

[0005] Therefore, improving the unpleasant taste of Qinxiang Qingjie oral liquid and increasing patient compliance are important issues that need to be addressed urgently. Summary of the Invention

[0006] In order to solve the above technical problems, the present invention provides a flavor-correcting formula for improving the taste of Qinxiang Qingjie oral liquid.

[0007] The true taste of Qinxiang Qingjie oral liquid is primarily composed of bitterness, spiciness, and a complex mouthfeel resulting from the superposition of multiple drugs. Baicalein (a flavonoid), rhubarb anthraquinone (anthraquinone), platycodin (a saponin), and matrine (an alkaloid) are the primary bittering substances in the oral liquid, while terpenoids (such as β-caryophyllene) in patchouli volatile oil are the primary material basis for its pungent, pungent taste. The present invention provides targeted flavor correction for the different mouthfeels within this true taste.

[0008] In response to the bitter and spicy complex taste system of Qinxiang Qingjie Oral Liquid, the present invention proposes an innovative flavor correction strategy, namely "sour and cool to control spiciness, strong sweetness to suppress bitterness, overall optimization, and taking into account stability". Specifically, in response to the spicy and hot stimulation of patchouli volatile oil, acidulants such as citric acid are used to reduce the spiciness, while cooling agents such as menthol are used to improve the burning sensation of patchouli oil. Both aspects are indispensable. However, the use of acidulants brings two adverse effects: first, the use of acidulants will enhance the perceived intensity of bitterness and make the bitterness of the medicine stronger; second, the use of acidulants will lower the pH of the oral liquid, which may cause baicalin, one of the main ingredients in Qinxiang Qingjie Oral Liquid, to isomerize and precipitate during storage, reducing the clarity and stability of the system. Since baicalin is a quality control indicator of Qinxiang Qingjie Oral Liquid, a reduction in its content will affect the overall quality of the medicine. Therefore, for the flavor correction process of Qinxiang Qingjie oral liquid, there may be a narrow "dosage window" for the use of acidulants, that is, the amount of acidulants cannot be too much or too little.

[0009] Due to the use of acidifiers, the bitterness of the drug is more intense, requiring a more effective bitterness-reducing formula. Among them, alkaloids such as matrine are highly bitter and are a significant contributor to the peak bitterness of Qinxiang Qingjie Oral Liquid. Bitter saponins such as platycodin, due to their larger molecular weight and prolonged bitterness, are the primary source of the bitter aftertaste of Qinxiang Qingjie Oral Liquid. Therefore, in the process of flavor correction, it is necessary to control both the overall bitterness intensity of the oral liquid and the bitter aftertaste. Through comprehensive optimization, the combination of neotame + cyclamate or aspartame + mogroside is found to be more effective, with the combination of neotame and cyclamate being the most effective.

[0010] Based on this, the present invention provides a flavor-correcting formula for improving the taste of Qinxiang Qingjie oral liquid, wherein the flavor-correcting formula consists of citric acid, menthol, adenosine monophosphate and a sweetener.

[0011] In some embodiments, the sweetener is selected from one or more of neotame, cyclamate, aspartame, mogroside and steviol glycoside.

[0012] In some embodiments, the flavor is selected from one or more of orange flavor, strawberry flavor, lemon flavor, blueberry flavor, raspberry flavor, blackberry flavor, bayberry flavor, black plum flavor, and preserved plum flavor.

[0013] In some embodiments, the sweetener preferably consists of neotame and cyclamate.

[0014] In some embodiments, the sweetener preferably consists of aspartame and mogroside.

[0015] In some embodiments, the amount of citric acid is 0.06% to 0.1%; the amount of menthol is 0.01% to 0.03%; the amount of sweetener is 0.1% to 0.6%; and the amount of flavor is 0.1% to 0.5%.

[0016] In some embodiments, the flavoring formula consists of 0.06% to 0.1% citric acid, 0.01% to 0.03% menthol, 0.1% to 0.5% blueberry flavor, 0.005% to 0.02% neotame, and 0.15% to 0.4% cyclamate.

[0017] Preferably, the flavoring formula consists of 0.1% citric acid, 0.025% menthol, 0.4% blueberry flavor, 0.01% neotame and 0.25% cyclamate.

[0018] Preferably, the flavoring formula consists of 0.1% citric acid, 0.025% menthol, 0.4% blueberry flavor, 0.01% neotame and 0.35% cyclamate.

[0019] Preferably, the flavoring formula consists of 0.1% citric acid, 0.025% menthol, 0.4% blueberry flavor, 0.01% neotame and 0.4% cyclamate.

[0020] In some embodiments, the flavoring formula consists of 0.06% to 0.1% citric acid, 0.01% to 0.03% menthol, 0.1% to 0.5% blueberry flavor, 0.01% to 0.02% aspartame, and 0.1% to 0.5% mogroside.

[0021] Preferably, the flavoring formula consists of 0.1% citric acid, 0.025% menthol, 0.4% blueberry flavor, 0.02% aspartame and 0.2% mogroside.

[0022] Preferably, the flavoring formula consists of 0.1% citric acid, 0.025% menthol, 0.4% blueberry flavor, 0.02% aspartame and 0.5% mogroside.

[0023] The "amount" mentioned in the present invention refers to the mass volume percentage of the flavoring agent to the Qinxiang Qingjie oral liquid, and the unit of mass volume percentage is g / 100mL. For example, 0.1% citric acid means adding 0.1g of citric acid to 100mL of Qinxiang Qingjie oral liquid.

[0024] The flavor correction formula is screened based on a volunteer sensory evaluation method, which includes the following steps:

[0025] Step 1: Establish relevant standards for sensory evaluation by volunteers;

[0026] Step 2: preparing a flavor correction sample of Qinxiang Qingjie oral liquid;

[0027] Step 3: Based on the above criteria, evaluate the flavor correction samples and obtain the optimal taste and flavor correction formula.

[0028] The flavor correction formula of the present invention is preferably obtained by the following steps:

[0029] Step 1: Establish evaluation criteria for sensory evaluation by volunteers;

[0030] 1. Volunteer screening and training

[0031] The following criteria were met for screening volunteers: age 20-28, no history of severe allergies or genetic diseases, no cholecystitis, no smoking, alcoholism, or other negative habits, no recent oral or pharyngeal diseases, and normal sense of taste. After a brief training session, 10 qualified volunteers were selected, with a near 1:1 male-to-female ratio, for the formal sensory test. Training method: Quinine sulfate solutions were prepared at 0.001 mg / ml, 0.15 mg / ml, 0.3 mg / ml, 0.5 mg / ml, and 0.8 mg / ml, with bitterness scores set at 0 (no bitterness), 2-3 (slightly bitter), 5 (clearly bitter), 7-8 (severely bitter), and 10 (extremely bitter). Volunteers tasted each sample solution and were asked to memorize the bitterness scores corresponding to the five concentration gradients of the different samples. A single-blind test was then conducted, with one sample solution randomly selected from the four bitter drug solutions. Volunteers who correctly scored the solution were considered successful.

[0032] Table 1 Sensory evaluation scoring criteria

[0033]

[0034] 2. Sensory evaluation method

[0035] Each volunteer took 10-15 ml of the sample solution and placed it in their mouth. They then gargled to allow their tongue and mouth to fully experience the taste of the drug. A timer began at the moment of entry, and sensory scores were performed according to the scoring criteria, with the start and end times of each taste sensation recorded. After 15 seconds, the drug solution was spit out. Rinse the mouth with purified water five times until the bitter taste disappeared. The next sample was evaluated after 0.5-1 hour.

[0036] Step 2: preparing a flavor correction sample of Qinxiang Qingjie oral liquid;

[0037] Step 3: Use the volunteer sensory evaluation method to evaluate the flavor correction samples and screen out the optimal flavor correction formula.

[0038] The evaluation standard indicators of the volunteers' sensory evaluation are bitterness, sweetness, pungency and odor.

[0039] In some embodiments, the number of volunteers for the sensory evaluation is 10, with a male to female ratio of approximately 1:1.

[0040] The present invention has achieved the following beneficial effects:

[0041] 1) In response to the unique bitter and spicy complex flavor system of Qinxiang Qingjie Oral Liquid, the present invention creatively proposes a flavor correction strategy of "sour and cool to control spiciness, strong sweetness to suppress bitterness, overall optimization, and taking into account stability." To address the spicy and hot stimulation of patchouli volatile oil, citric acid is used to reduce the spiciness, while menthol is used to improve the burning sensation of patchouli oil. Both are indispensable.

[0042] 2) The addition of citric acid will lower the pH of the oral solution, causing baicalin, the main component of Qinxiang Qingjie oral solution, to isomerize and precipitate during storage, reducing the clarity and stability of the system. The present invention screened and obtained an appropriate citric acid dosage of 0.06% to 0.1%. Specific implementation method:

[0043] The embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and intended to be used to explain the present invention, but should not be understood as limiting the present invention.

[0044] The endpoints and any values of the ranges described herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed herein.

[0045] The reagents and materials involved in the present invention are as follows:

[0046] Citric acid, malic acid, menthol, blueberry, neotame, cyclamate, aspartame, and mogroside are all substances that comply with relevant safety regulations in the pharmaceutical and food fields and are commercially available.

[0047] Qinxiang Qingjie oral liquid was produced by Guangzhou Yipinhong Biopharmaceutical Co., Ltd. (batch number 10741031)

[0048] Example 1: Screening of the flavor-correcting formula of Qinxiang Qingjie oral liquid

[0049] 1) Preparation of flavor correction samples

[0050] Each flavor-correcting formula was added to Qinxiang Qingjie oral liquid (100 mL), stirred at 500 rpm for 15 min using a magnetic stirrer to completely dissolve it, and then sterilized under high pressure for 35 min to obtain five flavor-correcting samples with different formulas. Volunteers conducted sensory evaluation, and the best flavor-correcting formula was screened out based on the results.

[0051] Table 2 Amount of flavoring agents added in different flavoring formulas

[0052]

[0053]

[0054] 2) Volunteer sensory evaluation

[0055] The volunteers scored the bitterness, sweetness, pungency and peculiar taste of the samples shown in Table 2 according to the taste evaluation criteria. The score was the weighted value of the four scoring items (assuming that the mean values of the bitterness, sweetness, pungency and peculiar taste scores were A, B, C and D respectively, and the weighted value I0 = A×50%+|B-5|×30%+C×10%+D×10%). The lower the score, the better the flavor correction effect of the formula.

[0056] The results are shown in Table 3. The results show that the flavor correction formula of the present invention has the best taste improvement effect, while when other acidulants such as malic acid are used instead of citric acid, the taste improvement effect is not good. In addition, the taste effect is closely related to the amount of citric acid used.

[0057] Table 3 Volunteers' oral evaluation scores

[0058] serial number 1 2 3 4 5 6 7 8 9 10 11 12 13 Score 9.43 4.31 3.56 3.07 2.13 1.71 1.17 1.74 3.14 4.01 2.95 6.35 5.53

[0059] Example 2: Effect of citric acid dosage on pH, baicalin content, and stability of Qinxiang Qingjie oral liquid:

[0060] Different amounts of citric acid were added to Qinxiang Qingjie oral liquid to adjust the pH to approximately 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, and 7.0, respectively. After sterilization, the samples were allowed to stand for one week, and the stability of the samples and the baicalin content in the oral liquid were observed. The results are shown in Table 4.

[0061] Table 4 Stability and baicalin content under different pH conditions

[0062]

[0063] As shown in Table 4, the pH of the Qinxiang Qingjie oral liquid decreases to varying degrees after sterilization. After citric acid is used to adjust the taste of the Qinxiang Qingjie oral liquid, different citric acid dosages have a significant effect on the baicalin content and stability. When the pH is below 4.0, a small amount of precipitation begins to appear, mainly due to the decrease in baicalin solubility, and the baicalin content in the oral liquid begins to decrease. When the pH is above 6.5, although the oral liquid does not precipitate, the baicalin content begins to decrease due to the pH approaching alkaline. This is mainly due to the easy ring-opening isomerization of baicalin under near-neutral or alkaline conditions. Therefore, the pH of the Qinxiang Qingjie oral liquid (before sterilization) should be controlled between 4.5 and 6.0, which is more suitable. The corresponding citric acid dosage is 0.06% to 0.1%.

[0064] The above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A flavor-correcting composition for improving the mouthfeel of Qinxiang Qingjie oral liquid, characterized in that: The flavoring composition consists of citric acid, menthol, essence and sweetener; The sweetener consists of neotame and cyclamate; Or the sweetener consists of aspartame and mogroside; The dosage of citric acid is 0.06% to 0.1%; the dosage of menthol is 0.01% to 0.03%; the dosage of sweetener is 0.1% to 0.6%; the dosage of flavor is 0.1% to 0.5%; The "amount" mentioned above refers to the mass volume percentage of the flavoring agent and the Qinxiang Qingjie oral liquid, and the unit of mass volume percentage is g / 100mL.

2. The flavor-correcting composition according to claim 1, wherein: The flavor is selected from one or more of orange flavor, strawberry flavor, lemon flavor, blueberry flavor, raspberry flavor, blackberry flavor, bayberry flavor, black plum flavor, and preserved plum flavor.

3. The flavor-correcting composition according to claim 1, wherein: The flavoring composition consists of 0.06% to 0.1% of citric acid, 0.01% to 0.03% of menthol, 0.1% to 0.5% of blueberry essence, 0.005% to 0.02% of neotame and 0.15% to 0.4% of cyclamate.

4. The flavor-correcting composition according to claim 3, wherein: The flavoring composition consists of 0.1% of citric acid, 0.025% of menthol, 0.4% of blueberry essence, 0.01% of neotame and 0.25% of cyclamate.

5. The flavor-correcting composition according to claim 1, wherein: The flavoring composition consists of 0.06% to 0.1% of citric acid, 0.01% to 0.03% of menthol, 0.1% to 0.5% of blueberry essence, 0.01% to 0.02% of aspartame and 0.1% to 0.5% of mogroside.

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