Traditional Chinese medicine compound gegenqinlian decoction placebo, preparation method and application thereof

Abstract

This application provides a placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction. The placebo comprises a matrix, pigments, flavorings, and flavoring agents: the matrix includes buckwheat flour, sodium carboxymethyl cellulose, and potassium sorbate; the pigments include caramel coloring, yellow pigment, and carmine red pigment; the flavorings include kudzu root flavoring, caramel flavoring, and green tea flavoring; and the flavoring agents include sucrose octaacetate, disodium inosinate, and sugar alcohols. This placebo is similar in color, odor, and taste to the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, meeting the blinding requirements in clinical trials. Even if patients are exposed to the investigational drug, it is unlikely that the blinding will be broken, making it suitable for clinical trials treating type 2 diabetes.

Description

Technical Field

[0001] This invention generally relates to the field of pharmaceutical technology, and specifically to a placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, its preparation method, and its application. Background Technology

[0002] A placebo is a simulated drug that contains little or no pharmacologically active ingredients, has no therapeutic effect on the observed physiological or pathological phenomena, and is identical or similar to the test drug in appearance, color, and taste. Researchers cannot distinguish between the drug and the placebo, thus eliminating the interference of additional psychological factors such as the participants' expectations and the doctor's suggestions caused by the intervention itself, improving the authenticity and reliability of the results. Traditional Chinese medicine (TCM) compound decoctions are diverse, and the composition and content of Chinese herbs are complex and variable. The sensory characteristics exhibited by different combinations of Chinese herbs are difficult to predict. TCM compound decoctions contain many herbs with flexible and varied compositions, and many herbs have unique sensory characteristics, making the preparation of TCM placebos extremely difficult. Current research on TCM placebos has made some progress, but most are placebos in the form of granules, capsules, and pills, with few placebos prepared from TCM decoctions. Furthermore, there is currently a lack of mature placebos available for the TCM compound decoction, Ge Gen Qin Lian Tang. Summary of the Invention

[0003] In view of the above-mentioned defects or deficiencies in the prior art, it is desirable to provide a placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, its preparation method and application. The placebo is similar in color, smell and taste to the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction. Patients are not likely to break blindness even if they are exposed to the test drug, and it will not affect the patient's blood sugar. It can be used in clinical trials involving diabetic patients.

[0004] In a first aspect, the present invention provides a placebo of a traditional Chinese medicine compound, Ge Gen Qin Lian Tang, the placebo comprising a base, a pigment, a flavoring agent, and a taster:

[0005] The matrix includes buckwheat flour, sodium carboxymethyl cellulose, and potassium sorbate;

[0006] Pigments include caramel color, yellow pigment, and carmine red pigment;

[0007] Flavorings include kudzu root flavoring, caramel flavoring, and green tea flavoring;

[0008] Flavoring agents include sucrose octaacetate, disodium inosinate, and sugar alcohols.

[0009] As an alternative, the yellow pigments include lemon yellow and citrus yellow, and the sugar alcohols include xylitol or maltitol.

[0010] As an optional option, the placebo comprises the following components by weight:

[0011] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, citrus yellow pigment 0.2-0.4 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, xylitol 12-14 parts.

[0012] As an optional option, the placebo comprises the following components by weight:

[0013] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, citrus yellow pigment 0.2-0.4 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, maltitol 9-10 parts.

[0014] As an alternative, the yellow pigments include lemon yellow and sunset yellow, and the sugar alcohols include xylitol or maltitol.

[0015] As an optional option, the placebo comprises the following components by weight:

[0016] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, sunset yellow pigment 0.02-0.03 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, xylitol 12-14 parts.

[0017] As an optional option, the placebo comprises the following components by weight:

[0018] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, sunset yellow pigment 0.02-0.03 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, maltitol 9-10 parts.

[0019] As an alternative, the placebo comprises the following components:

[0020] 8 parts of buckwheat flour, 0.5 part of sodium carboxymethylcellulose, 0.25 part of potassium sorbate, 0.4 part of caramel color, 0.1 part of tartrazine, 0.25 part of citrus yellow pigment, 0.07 part of carmine pigment, 0.3 part of sucrose octaacetate, 13 parts of xylitol, 0.15 part of disodium 5'-ribonucleotide, 2 parts of kudzu root essence, 0.5 part of caramel essence, and 0.2 part of green tea essence.

[0021] In a second aspect, the present invention provides a method for preparing a placebo of the traditional Chinese medicine compound Gegen Qinlian Decoction in the first aspect, which is characterized by comprising the following steps:

[0022] After preparing a mixed solution from a matrix, pigments, essence, and flavoring agents, fill it into traditional Chinese medicine bags and refrigerate.

[0023] As an alternative, the temperature for preparing the mixed solution is 85°C - 100°C, the volume of the mixed solution is 150 mL - 200 mL, and the refrigeration temperature is 0 - 4°C.

[0024] In a third aspect, the present invention provides the use of a placebo of the traditional Chinese medicine compound Gegen Qinlian Decoction in the first aspect in a clinical trial for treating type 2 diabetes.

[0025] The placebo of the traditional Chinese medicine compound Gegen Qinlian Decoction of the present invention uses buckwheat flour, sodium carboxymethylcellulose, and potassium sorbate as the matrix, and adds pigments to adjust the color of the mixed solution to make the color similar or even the same as that of the Gegen Qinlian Decoction. Essence and flavoring agents are added to adjust the smell and taste of the placebo respectively, so that the placebo is similar to the Gegen Qinlian Decoction in terms of color, smell, and taste. Researchers, volunteers, and type 2 diabetes patients cannot correctly identify which is the traditional Chinese medicine and which is the placebo, and their similarity scores are also sufficiently similar. The prepared Gegen Qinlian Decoction placebo meets the requirements of blinding in clinical trials, and patients are not easily unblinded even when exposed to the test drug. Moreover, the results of animal experiments and artificial evaluations of this placebo both show that the placebo is safe enough and does not affect the blood sugar of patients. The ingredients and preparation method of the placebo are consistent, and the quality of the placebo is controllable. Description of the Drawings

[0026] By reading the detailed description of the non-limiting embodiments with reference to the following drawings, other features, objectives, and advantages of the present application will become more obvious:

[0027] Figure 1 For the instantaneous blood glucose change of healthy mice;

[0028] Figure 2 For the area under the instantaneous blood glucose curve of healthy mice;

[0029] Figure 3 Line graph showing the changes in fasting blood glucose in diabetic model mice;

[0030] Figure 4 Line graph showing the changes in fasting blood glucose in healthy mice;

[0031] Figure 5 A graph showing the changes in blood glucose levels during an oral glucose tolerance test (OGTT) in healthy mice.

[0032] Figure 6 A graph showing the changes in ITT in diabetic model mice; Detailed Implementation

[0033] The present application will now be described in further detail with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and not intended to limit it. Furthermore, it should be noted that, for ease of description, only the parts relevant to the invention are shown in the accompanying drawings.

[0034] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. This application will now be described in detail with reference to the accompanying drawings and embodiments.

[0035] In a first aspect, embodiments of this application provide a placebo of a traditional Chinese medicine compound, Ge Gen Qin Lian Tang, the placebo comprising a base, pigment, flavoring agent, and taste-enhancing agent:

[0036] The matrix includes buckwheat flour, sodium carboxymethyl cellulose, and potassium sorbate;

[0037] Pigments include caramel color, yellow pigment, and carmine red pigment;

[0038] Flavorings include kudzu root flavoring, caramel flavoring, and green tea flavoring;

[0039] Flavoring agents include sucrose octaacetate, disodium inosinate, and sugar alcohols.

[0040] The matrix used in the embodiments of this application is similar in color to Ge Gen Qin Lian Tang and has good solubility. Combined with pigments, flavorings and taste-correcting agents, it can reliably adjust the color, smell and taste of the placebo, thereby making the placebo similar to Ge Gen Qin Lian Tang decoction. Moreover, buckwheat flour is beneficial for diabetic patients and reduces the impact on blood sugar.

[0041] As a means of achieving this, yellow pigments include lemon yellow and citrus yellow, and sugar alcohols include xylitol or maltitol.

[0042] The yellow pigment in this embodiment can reliably adjust the color of the placebo. In combination with caramel coloring and carmine pigment, the color of the placebo is similar to that of the Ge Gen Qin Lian Tang decoction. Furthermore, xylitol or maltitol, as natural sweeteners, can reliably correct bitterness, which helps the taste of the placebo to be close to that of the Ge Gen Qin Lian Tang decoction.

[0043] It is understood that the dosage of each component of the placebo in the embodiments of this application may be adjusted according to the actual dosage of each component of Ge Gen Qin Lian Tang.

[0044] For example, Ge Gen Qin Lian Tang includes 24g of kudzu root, 9g of scutellaria root, 9g of coptis root, and 6g of prepared licorice root. The decoction method is as follows: soak the herbs for 30 minutes, add water in an amount 10 times the weight of the herbs, heat over high heat until boiling, then simmer over low heat, maintaining a gentle boil. The first decoction is simmered for 30 minutes, and the second decoction is simmered for 20 minutes.

[0045] The embodiments of this application provide the following placebo for the above-mentioned Pueraria lobata and Scutellaria baicalensis:

[0046] In some embodiments, the placebo comprises, by weight, the following components:

[0047] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, citrus yellow pigment 0.2-0.4 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, xylitol 12-14 parts.

[0048] The placebo weight disclosed in this embodiment, by controlling the amount of buckwheat flour, sodium carboxymethyl cellulose, potassium sorbate, pigments, flavorings and tasters, is conducive to reliably adjusting the color, smell and taste of the mixture, so that the color, smell and taste are similar to or even the same as the color of the Ge Gen Qin Lian Tang decoction, which is beneficial to patients who are less likely to break blindness even if they are exposed to the test drug, and will not affect the patients' blood sugar.

[0049] In other embodiments, the placebo comprises, by weight, the following components:

[0050] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, citrus yellow pigment 0.2-0.4 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, maltitol 9-10 parts.

[0051] As a means of achieving this, yellow pigments include lemon yellow and sunset yellow, and sugar alcohols include xylitol or maltitol.

[0052] In some embodiments, the placebo comprises, by weight, the following components:

[0053] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, sunset yellow pigment 0.02-0.03 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, xylitol 12-14 parts.

[0054] In other embodiments, the placebo comprises, by weight, the following components:

[0055] Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, sunset yellow pigment 0.02-0.03 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, maltitol 9-10 parts.

[0056] In a preferred embodiment, the placebo comprises the following components:

[0057] 8 parts buckwheat flour, 0.5 parts sodium carboxymethyl cellulose, 0.25 parts potassium sorbate, 0.4 parts caramel color, 0.1 parts lemon yellow, 0.25 parts citrus yellow pigment, 0.07 parts carmine red pigment, 0.3 parts sucrose octaacetate, 13 parts xylitol, 0.15 parts disodium inosinate, 2 parts kudzu root flavoring, 0.5 parts caramel flavoring, and 0.2 parts green tea flavoring.

[0058] In summary, for the placebo of the traditional Chinese medicine compound Gegen Qinlian Decoction in the embodiments of the present application, by using buckwheat flour, sodium carboxymethylcellulose, and potassium sorbate as matrices, adding pigments to adjust the color of the mixture, making the color similar to or even the same as that of Gegen Qinlian Decoction, adding flavors and flavoring agents to adjust the smell and taste of the placebo respectively, so that the placebo is similar to Gegen Qinlian Decoction in terms of color, smell, and taste. Researchers, volunteers, and type 2 diabetic patients cannot correctly identify which is the traditional Chinese medicine and which is the placebo, and their similarity scores are also similar enough. The prepared Gegen Qinlian Decoction placebo meets the blinding requirements in clinical trials, and patients are not easily unblinded even when exposed to the test drug. Moreover, the results of animal experiments and artificial evaluations of this placebo show that the placebo is safe enough and does not affect the blood glucose of patients. The ingredients and preparation methods of the placebo are consistent, and the quality of the placebo is controllable.

[0059] In a second aspect, the present invention provides a preparation method for the placebo of the traditional Chinese medicine compound Gegen Qinlian Decoction in the first aspect, which is characterized by including the following steps:

[0060] After configuring the matrices, pigments, flavors, and flavoring agents into a mixture, fill it into traditional Chinese medicine bags and refrigerate.

[0061] It can be understood that the process of configuring the matrices, pigments, flavors, and flavoring agents into a mixture can be directly adding the matrices, pigments, flavors, and flavoring agents into hot water to obtain the mixture; it can also be adding the matrices, pigments, flavors, and flavoring agents into cold water and decocting to obtain the mixture. The embodiments of the present application do not make specific limitations on this.

[0062] As an implementable method, the configuration temperature of the mixture is 85°C - 100°C, and the volume of the mixture is 150 mL - 200 mL.

[0063] The configuration temperature of the mixture in this embodiment is beneficial to ensuring that the matrices, pigments, flavors, and flavoring agents are fully dissolved to obtain the mixture. The volume of the mixture in the present application is beneficial to ensuring that the color and taste of the placebo are consistent with those of Gegen Qinlian Decoction.

[0064] Specifically, the preparation temperature of the mixture can be, but is not limited to, 85℃, 90℃, 95℃, or 100℃. When the preparation temperature is below 85℃, the raw materials cannot dissolve completely. When the preparation temperature is above 100℃, the placebo's odor and color may change significantly, resulting in a significant difference from the odor and color of the traditional Chinese medicine compound Ge Gen Qin Lian Tang. The volume of the mixture can be, but is not limited to, 150mL, 160mL, 170mL, 180mL, 190mL, or 200mL. When the volume of the mixture is less than 150mL, the placebo will have a darker color and a stronger taste, resulting in a significant difference from the color and taste of the traditional Chinese medicine compound Ge Gen Qin Lian Tang. When the volume of the mixture is greater than 200mL, the placebo will have a lighter color and a milder taste, resulting in a significant difference from the color and taste of the traditional Chinese medicine compound Ge Gen Qin Lian Tang.

[0065] In some embodiments, the refrigeration temperature is 0-4°C, which is conducive to the storage of placebos, ensuring that the placebos remain stable in shape and do not precipitate or deteriorate.

[0066] In actual processing, the matrix, pigment, flavoring and flavoring agent are dissolved in 150mL of 100℃ hot water to obtain a mixed solution, which is then filled into Chinese medicine bags, sealed and refrigerated at 0-4℃.

[0067] For example, in practical applications, the placebo includes 1.6g of buckwheat flour, 0.1g of sodium carboxymethyl cellulose, 0.05g of potassium sorbate, 0.08g of caramel color, 0.02g of tartrazine, 0.05g of citrus yellow, 0.014g of carmine, 0.06g of sucrose octaacetate, 2.5g of sugar alcohol, 0.03g of disodium inosinate, 0.4g of kudzu root flavoring, 0.1g of caramel flavoring, and 0.04g of green tea flavoring.

[0068] In summary, the preparation method of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction according to the embodiments of this application is simple to operate, easy to process, and can ensure that the test items such as the properties, moisture content, and dosage difference of the placebo meet the requirements and reach the quality standard of the placebo. The obtained placebo is consistent with the color, smell and taste of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, and will not affect blood sugar.

[0069] Example

[0070] The placebo includes the following components:

[0071] 8 parts buckwheat flour, 0.5 parts sodium carboxymethyl cellulose, 0.25 parts potassium sorbate, 0.4 parts caramel color, 0.1 parts lemon yellow, 0.25 parts citrus yellow pigment, 0.07 parts carmine red pigment, 0.3 parts sucrose octaacetate, 13 parts xylitol, 0.15 parts disodium inosinate, 2 parts kudzu root flavoring, 0.5 parts caramel flavoring, and 0.2 parts green tea flavoring.

[0072] The placebo from the above embodiments was tested as follows:

[0073] 1. Conduct animal experiments to verify the safety of the placebo and its non-interference with glucose metabolism:

[0074] Experimental Methods: db / db mice and C57 mice were each divided into a placebo group and a control group. The placebo group was administered the placebo as described in the previous example via gavage, while the control group was administered the same volume of distilled water via gavage. The intervention lasted for 4 weeks. On the first day, the instantaneous blood glucose changes in both groups of C57 mice were measured after gavage. Fasting blood glucose was measured weekly in all four groups of mice during the experiment. db / db mice were diabetic model mice, and C57 mice were healthy mice. After the experiment, the db / db mouse groups underwent an intraperitoneal insulin resistance test, and the C57 mouse groups underwent an oral glucose tolerance test, with blood glucose changes measured in each mouse. Subsequently, all four groups of mice were anesthetized, and blood was collected from the eyeballs to measure liver and kidney function.

[0075] Statistical analysis: Measurement data that conform to a normal distribution are expressed as mean ± standard deviation (x ± s). For data with homogeneous variances, an independent samples t-test is used. For data with unequal variances or that do not conform to a normal distribution, the Mann-Whitney U test is used.

[0076] Experimental results:

[0077] 1.1 Safety observation in mice

[0078] During the intervention, no significant changes were observed in the appearance, behavior, mental state, respiration, or other general conditions of the mice in each group.

[0079] In diabetic model mice and healthy mice, there was no statistically significant difference in body weight between the intervention group and the control group (P>0.05), as shown in Tables 1 and 2.

[0080] Table 1. Changes in body weight (g) in diabetic model mice

[0081]

[0082] Table 2. Changes in body weight (g) of healthy mice

[0083]

[0084] 1.2 Effect of placebo on transient blood glucose changes in healthy mice

[0085] Table 3 shows the instantaneous blood glucose levels of healthy mice in the placebo group and the control group. Figure 1 and Figure 2Compared to the control group, at the 30-minute and 60-minute time points, the placebo group had slightly higher blood glucose levels, but the difference was small and not statistically significant (P>0.05). There were also no statistically significant differences in blood glucose levels and the area under the curve (AUC) at all time points (P>0.05).

[0086] Table 3. Instantaneous blood glucose changes in healthy mice (mmol / L)

[0087]

[0088] 1.3 Blood glucose changes

[0089] During the intervention, the changes in fasting blood glucose levels in diabetic model mice and healthy mice are shown in Table 4 below. Figure 3 and Table 5 and Figure 4 Compared with the control group, there were no statistically significant differences in fasting blood glucose levels at any time point in the intervention group (P>0.05).

[0090] Changes in OGTT in healthy mice are shown in Table 6 below. Figure 5 There were no statistically significant differences in blood glucose levels at any time point (P>0.05). Changes in ITT in diabetic model mice are shown in Table 7 below. Figure 6 There were no statistically significant differences in blood glucose levels at any time point (P>0.05).

[0091] There were no statistically significant differences in blood glucose levels at any time point among the groups of healthy mice and diabetic model mice. All of these results indicate that the placebo has no effect on blood glucose metabolism.

[0092] Table 4. Changes in fasting blood glucose levels (mmol / L) in diabetic model mice.

[0093]

[0094] Table 5. Changes in fasting blood glucose levels (mmol / L) in healthy mice.

[0095]

[0096] Table 6. Changes in OGTT in healthy mice (mmol / L)

[0097]

[0098] Table 7. Changes in ITT (mmol / L) in a Diabetic Model

[0099]

[0100] 1.4 Liver and kidney function

[0101] The liver and kidney function of diabetic model mice are shown in Table 8 below. There were no statistically significant differences between the two groups (P>0.05).

[0102] Table 8 Liver and kidney function in diabetic model mice

[0103]

[0104] The liver and kidney function of healthy mice are shown in Table 9 below. There were no statistically significant differences between the two groups (P>0.05).

[0105] Table 9 Liver and kidney function in healthy mice

[0106]

[0107] 2. Conduct a placebo similarity assessment:

[0108] 2.1 Researcher Evaluation

[0109] 2.1.1 Assessors

[0110] The evaluators were internal researchers from the research group.

[0111] 2.1.2 Evaluation Methods

[0112] A three-point test method was used: Each test kit contained three samples, which could be in six different configurations depending on their category (drug A / placebo B): ABB, AAB, ABA, BAA, BBA, and BAB. The three samples were coded from left to right with a three-digit format (e.g., 011, 012, 013), where the tens and hundreds digits represented the test kit number (e.g., 01), and the units digit represented the sample's sequence number from left to right (1, 2, 3). Each test kit was randomly distributed to evaluators, who were instructed to sample and evaluate the samples in ascending order of their numbers. Evaluators were also informed that each test kit contained two identical samples and one different sample. In a blinded state, evaluators compared the different sensory characteristics of the samples, identified the different sample, recorded its number on a questionnaire, and guessed whether the different sample was a drug or a placebo.

[0113] 2.1.3 Assessment Content

[0114] The sensory characteristics of traditional Chinese medicine and placebo were evaluated, including the following:

[0115] (1) Visual characteristics, including external shape, color and gloss, and texture;

[0116] (2) Taste characteristics, including flavor and texture;

[0117] (3) Odor characteristics.

[0118] Among them, the external shape refers to the external physical shape of the drug itself, such as round, oval, spherical, rhombic, etc., as well as the thickness and size; the texture is the real feeling that the drug itself gives people visually, and also includes, for example, the visual feeling given by the drug surface, etc.; the taste is the direct feeling produced by the drug in the oral cavity due to the touch of the tongue and chewing.

[0119] 2.1.4 Quality Control

[0120] Ensure that the assessors do not come into contact with items with strong pungent tastes or odors within 1 hour before the assessment. Before the evaluation starts, fully introduce the relevant concepts and evaluation methods to the assessors; during the evaluation, distribute the evaluation packages to the assessors by a dedicated person. During the evaluation process, except for specific personnel, do not give additional tendentious guidance to the assessors, and avoid the assessors communicating with each other or exchanging drugs. Let the assessors rinse their mouths with clean water during the interval between two drug tastings, and leave an interval of 30 seconds to reduce mutual interference. Ensure that the environment of the evaluation site is brightly lit and relatively quiet.

[0121] 2.1.5 Statistical Analysis

[0122] In the triangle test, count the number of people who guess correctly. When the number of people who guess correctly exceeds half, it can be considered that there are certain sensory differences between the placebo and the traditional Chinese medicine. In the analysis of guessing whether it is a drug or a placebo, calculate the relative ratio of placebo judgment (the calculation method is the proportion of placebo judged as "test drug" / the proportion of test drug judged as "test drug"). When it exceeds 60%, it can be considered that the simulation effect is qualified.

[0123] 2.1.6 Evaluation Results

[0124] A total of 14 evaluators participated in this evaluation, including 1 male and 13 females, all of whom are researchers in the field of traditional Chinese medicine. Among them, 12 people correctly identified different samples, and 2 people did not correctly identify. From the perspective of sensory evaluation, in the triangle test, more than 7 out of 14 evaluators gave the correct answer, and there are still certain sensory differences between the drug and the placebo.

[0125] Among these 12 people, 8 people misidentified the traditional Chinese medicine and the placebo, and 4 people correctly identified the traditional Chinese medicine and the placebo. Among the evaluators who correctly picked out different samples, 8 evaluators pointed out that there was a difference in smell, and 3 people thought the smell of the placebo was stronger. 8 people thought there was a difference in taste, 3 people thought the placebo was more bitter, 3 people thought the traditional Chinese medicine was more bitter, 1 person thought the placebo was sweeter, and 1 person thought the placebo only had a bitter taste. Considering that the bitterness of Gegen Qinlian Decoction is relatively persistent, the taste of the evaluators may be affected by the evaluation order and the previous evaluation, so there is a situation where more than half of the evaluators have different opinions. 3 people thought there was a difference in color.

[0126] From a blinded perspective, among the 14 evaluators, 10 guessed incorrectly, mistaking the placebo for traditional Chinese medicine, while 4 guessed correctly, identifying the traditional Chinese medicine. No one answered "don't know." The relative odds ratio for the placebo was 250%, indicating that the placebo effectively mimicked the effect of the test drug.

[0127] 2.2 Volunteer Evaluation

[0128] 2.2.1 Inclusion and Exclusion Criteria for Evaluators

[0129] ① Healthy people

[0130] Inclusion criteria:

[0131] (1) Normal sensory functions such as vision, smell and taste

[0132] (2) Has not suffered from a chronic disease requiring long-term medication within the past year;

[0133] (3) Age 18 years or older.

[0134] (4) Has not participated in other clinical studies within the past three months;

[0135] Exclusion criteria:

[0136] (1) Individuals with mental disorders and pregnant women;

[0137] (2) Those who cannot understand or cooperate.

[0138] ② Clinical trial participants

[0139] This group refers to individuals who meet the same inclusion and exclusion criteria as clinical trial participants but do not participate in formal clinical trials. Taking the randomized, double-blind, controlled clinical trial of Ge Gen Qin Lian Tang for the treatment of type 2 diabetes as an example, the inclusion and exclusion criteria are as follows:

[0140] Inclusion criteria:

[0141] (1) Clinically diagnosed with type 2 diabetes;

[0142] (2) Be 18 years of age or older;

[0143] (3) Has not participated in other clinical studies in the past three months.

[0144] Exclusion criteria:

[0145] (1) Comorbid severe cardiovascular and cerebrovascular diseases, tumors, etc.;

[0146] (2) Participated in clinical trials of Gegen Qinlian Decoction for the treatment of type 2 diabetes;

[0147] (3) People with mental disorders and pregnant women.

[0148] (4) Those who cannot understand or cooperate.

[0149] 2.2.2 Evaluation Methods

[0150] 2.2.2.1 Score Evaluation

[0151] In a simulated clinical trial scenario where participants were exposed to both a placebo and the investigational drug, evaluators conducted a comparative assessment of the placebo and Ge Gen Qin Lian Tang to determine the consistency between the placebo and Ge Gen Qin Lian Tang.

[0152] Each assessment kit contained two samples: "Ge Gen Qin Lian Tang + placebo" (Group C) and "2 Ge Gen Qin Lian Tang" samples (Group D). Assessors were randomly assigned to Groups C and D in a 1:1 ratio using a random number table. The sensory characteristics of the herbal medicine and the placebo were evaluated, including: visual characteristics such as shape, color, luster, and texture; taste characteristics such as flavor and mouthfeel; and odor characteristics. Assessors scored the similarity of the two samples within each kit on a scale of 0 to 10, with 10 points for identical samples and 0 points for completely different samples.

[0153] 2.2.2.2 Independent Evaluation

[0154] The participants were divided into a drug group (Group E) and a placebo group (Group F). Using a random number table, the participants were assigned to Group E and Group F in a 1:1 ratio to simulate the actual drug administration scenario in a clinical trial. The participants made an overall assessment based on sensory characteristics and subjectively judged whether the drug they were taking was a drug or a placebo, thereby judging the simulation effect of the placebo. The responses were: "real drug", "uncertain", and "placebo".

[0155] 2.2.3 Assessment Content

[0156] Same as above.

[0157] 2.2.4 Quality Control

[0158] Same as above.

[0159] 2.2.5 Statistical Analysis

[0160] For the score evaluation, SPSS 25.0 software was used to perform independent samples t-tests for statistical analysis. A p-value < 0.05 was considered statistically significant, indicating an identifiable difference between the placebo and Ge Gen Qin Lian Tang. Similarity scores for each dimension were calculated; scores ≥ 7 for visual and tactile similarity, and ≥ 6 for taste and smell similarity, were considered acceptable. For independent evaluation, the RR value was calculated, and the results were judged using a chi-square test.

[0161] 2.2.6 Evaluation Results

[0162] 2.2.6.1 Assessors

[0163] A total of 128 evaluators were recruited, including 64 healthy individuals and 64 diabetic patients, all of whom participated in the score evaluation and independent evaluation.

[0164] In the healthy population, there were 18 men and 46 women, almost all aged between 18 and 30, with only one participant aged 40. The average age was 20.08 (see Table 10). In the diabetic patient population, there were 28 men and 36 women, aged between 24 and 80, with an average age of 62.98. Their characteristics are shown in Table 11 below.

[0165] 2.2.6.1 Score Evaluation

[0166] A total of 128 evaluators were recruited, including 64 healthy individuals and 64 diabetic patients.

[0167] In the healthy population, 35 individuals received "Ge Gen Qin Lian Tang + placebo" (Group C1), and 29 individuals received "2 Ge Gen Qin Lian Tang" (Group D1). The appearance, color, and taste of the placebo were rated and compared. The results are shown in Table 3.20. There were no statistically significant differences in the similarity scores between Group C1 and Group D1 across all dimensions (P > 0.05). The similarity score for taste was less than 6 points, but not significantly different from the other group. The results are shown in Table 12.

[0168] In the diabetic subjects, 30 participants received "Ge Gen Qin Lian Tang + placebo" (Group C2), and 33 participants received "2 Ge Gen Qin Lian Tang" (Group D2). The appearance, color, and taste of the placebo were comprehensively compared. The results showed no statistically significant difference between the test drug and the placebo (P > 0.05), and the similarity scores for each dimension were all above 6. The results are shown in Table 13 below.

[0169] 2.2.6.2 Independent Evaluation

[0170] Table 14 shows the guesses for placebo and medication between diabetic and healthy individuals, and there was no statistically significant difference in the guesses (P = 0.705).

[0171] Table 10 Basic Information of Healthy Volunteers

[0172]

[0173] Table 11 Basic Information of Healthy Volunteers

[0174]

[0175] Table 12 Similarity scores of healthy individuals

[0176]

[0177] Table 13 Similarity scores among diabetic populations

[0178]

[0179] Table 14. Guessing results between diabetic and healthy individuals.

[0180]

[0181] Health assessment results:

[0182] In the healthy population, 29 individuals were assigned to the drug group (E1 group), of which 18 answered "drug," 8 answered "placebo," and 3 answered "don't know." In the placebo group (F1 group), 35 individuals were assigned to the drug group, of which 21 answered "drug," 13 answered "placebo," and 1 answered "don't know" (see Table 15). Using the chi-square test, no statistically significant difference was found between the two groups (P = 0.392), and the calculated RR value was 96.67%.

[0183] Table 15. Guessing results for healthy individuals

[0184]

[0185] Assessment results for people with diabetes:

[0186] In the diabetic population, 33 individuals were assigned to the medication group (E2 group), of which 28 answered "medication," 3 answered "placebo," and 2 answered "don't know." In the placebo group (F2 group), 30 individuals were assigned to the placebo group, of which 26 answered "medication," 4 answered "placebo," and 0 answered "don't know" (see Table 16 below). Using a chi-square test, no statistically significant difference was found between the two groups (P = 0.561). The calculated RR value was 102%.

[0187] Table 16. Guessing of the Diabetic Population

[0188]

[0189] Animal experiments and artificial evaluations showed that the placebo was safe enough and did not affect blood glucose metabolism. The ingredients and methods used to prepare the placebo were consistent, and the quality of the placebo was controllable. Researchers, volunteers and type 2 diabetes patients could not correctly identify which was the traditional Chinese medicine and which was the placebo. The similarity scores of the two were also similar enough. The prepared Ge Gen Qin Lian Tang placebo met the blinding requirements in clinical trials.

[0190] It should be understood that the terms "center," "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., used above to indicate orientation or positional relationships are based on the orientation or positional relationships shown in the accompanying drawings and are only for the convenience of describing the invention and simplifying the description, and do not indicate or imply that the panel or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined with "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of the invention, unless otherwise stated, "a plurality of" means two or more.

[0191] The above description is merely a preferred embodiment of this application and an explanation of the technical principles employed. Those skilled in the art should understand that the scope of the invention involved in this application is not limited to technical solutions formed by specific combinations of the above-described technical features, but should also cover other technical solutions formed by arbitrary combinations of the above-described technical features or their equivalents without departing from the inventive concept. For example, technical solutions formed by substituting the above features with (but not limited to) technical features with similar functions disclosed in this application.

Claims

1. A placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, characterized in that, The placebo consists of the following components in parts by weight: Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, citrus yellow pigment 0.2-0.4 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, xylitol 12-14 parts.

2. A placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, characterized in that, The placebo consists of the following components in parts by weight: Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, citrus yellow pigment 0.2-0.4 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, maltitol 9-10 parts.

3. A placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, characterized in that... The placebo consists of the following components in parts by weight: Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, sunset yellow pigment 0.02-0.03 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, xylitol 12-14 parts.

4. A placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, characterized in that, The placebo consists of the following components in parts by weight: Buckwheat flour 8-10 parts, sodium carboxymethyl cellulose 0.5-0.7 parts, potassium sorbate 0.2-0.4 parts, caramel color 0.4-0.6 parts, lemon yellow pigment 0.1-0.3 parts, sunset yellow pigment 0.02-0.03 parts, carmine red pigment 0.06-0.08 parts, kudzu root flavor 2-4 parts, caramel flavor 0.4-0.6 parts, green tea flavor 0.2-0.4 parts, sucrose octaacetate 0.3-0.5 parts, disodium inosinate 0.1-0.3 parts, maltitol 9-10 parts.

5. A placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang decoction, characterized in that, The placebo consists of the following components in parts by weight: 8 parts buckwheat flour, 0.5 parts sodium carboxymethyl cellulose, 0.25 parts potassium sorbate, 0.4 parts caramel color, 0.1 parts lemon yellow pigment, 0.25 parts citrus yellow pigment, 0.07 parts carmine red pigment, 0.3 parts sucrose octaacetate, 13 parts xylitol, 0.15 parts disodium inosinate, 2 parts kudzu root flavoring, 0.5 parts caramel flavoring, and 0.2 parts green tea flavoring.

6. A method for preparing a placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang according to any one of claims 1-5, characterized in that, Includes the following steps: After preparing the above components into a mixture, it is filled into Chinese medicine bags and refrigerated.

7. The method for preparing a placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang according to claim 6, characterized in that, The mixing solution is prepared at a temperature of 85℃-100℃, the volume of the mixing solution is 150mL-200mL, and the refrigeration temperature is 0-4℃.

8. Use of a placebo of the traditional Chinese medicine compound Ge Gen Qin Lian Tang according to any one of claims 1-5 in the preparation of a placebo for clinical trials for the treatment of type 2 diabetes.

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