Traditional Chinese medicine compound pueraria qinlian decoction placebo as well as preparation method and application thereof

Abstract

The invention provides a traditional Chinese medicine compound pueraria qinlian decoction placebo, the placebo comprises the following components: a matrix, a pigment, an essence and a flavoring agent, the matrix comprises buckwheat flour, sodium carboxymethyl cellulose and potassium sorbate; the pigments comprise caramel pigment, yellow pigment and carmine pigment; the essence comprises radix puerariae essence, caramel essence and green tea essence; the flavoring agent comprises sucrose octaacetate, disodium 5 '-ribonucleotide and sugar alcohol. The color, smell and taste of the placebo provided by the invention are similar to those of a traditional Chinese medicine compound Gegen Qinlian decoction, the requirements of blindness setting in clinical tests are met, the blindness of a patient is not easy to break even if the patient is in contact with a test medicine, and the placebo can be used for clinical tests for treating type 2 diabetes mellitus.

Description

Technical Field

[0001] The present invention generally relates to the field of medical technology, and in particular to a Chinese medicine compound Gegenqinlian decoction placebo and a preparation method and application thereof. Background Art

[0002] Placebo refers to a simulated drug that contains no or a small amount of pharmacologically active ingredients, but has no therapeutic effect on the observed physiological and pathological phenomena, and is the same or similar to the test drug in appearance, color, taste, etc. The test personnel cannot distinguish between drugs and placebos, so as to eliminate the interference of additional psychological factors such as the inner expectations of the subjects and the doctor's suggestions caused by the intervention itself on the test results, and improve the authenticity and reliability of the test results. However, there are many kinds of Chinese herbal compound decoctions, and the composition and content of Chinese medicine are complex and changeable. The sensory characteristics of the prescriptions composed of different combinations of Chinese medicines are even more difficult to predict. Chinese herbal compound decoctions contain many kinds of herbs and the composition is flexible and changeable, and most Chinese herbal medicines have unique sensory characteristics, which brings great difficulties to the preparation of Chinese herbal placebos. At present, the research on Chinese herbal placebos has made some progress, but most of them are placebos in the form of Chinese herbal granules, capsules, pills, etc., and there are few placebos made in Chinese herbal decoctions. For the Chinese herbal compound decoction of Gegenqinlian Decoction, there is currently a lack of mature placebos available. Summary of the invention

[0003] In view of the above-mentioned defects or deficiencies in the prior art, it is desired to provide a placebo of a Chinese medicine compound Gegenqinlian decoction and a preparation method and application thereof. The placebo is similar to the color, smell and taste of the Chinese medicine compound Gegenqinlian decoction, and the patient is not easily blinded even if he is exposed to the test drug, and it will not affect the patient's blood sugar, so it can be used in clinical trials involving diabetic patients.

[0004] In a first aspect, the present invention provides a traditional Chinese medicine compound Gegenqinlian decoction placebo, the placebo comprising a matrix, a pigment, an essence and a flavoring agent: The matrix includes buckwheat flour, sodium carboxymethyl cellulose, and potassium sorbate; Pigments include caramel, yellow, and carmine; Fragrances include kudzu root, caramel, and green tea; Flavoring agents include sucrose octaacetate, disodium ribonucleotides, and sugar alcohols.

[0005] As an alternative, the yellow pigment includes lemon yellow pigment and citrus yellow pigment, and the sugar alcohol includes xylitol or maltitol.

[0006] As an optional solution, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.2-0.4 parts of citrus yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium flavor nucleotides, and 12-14 parts of xylitol.

[0007] As an optional solution, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.2-0.4 parts of citrus yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium flavor nucleotides, and 9-10 parts of maltitol.

[0008] As an alternative, the yellow pigment includes tartrazine and sunset yellow, and the sugar alcohol includes xylitol or maltitol.

[0009] As an optional solution, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.02-0.03 parts of sunset yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium nucleotides, and 12-14 parts of xylitol.

[0010] As an optional solution, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.02-0.03 parts of sunset yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium nucleotides, and 9-10 parts of maltitol.

[0011] As an alternative, placebo may include the following components: 8 parts of buckwheat flour, 0.5 parts of sodium carboxymethyl cellulose, 0.25 parts of potassium sorbate, 0.4 parts of caramel color, 0.1 parts of lemon yellow, 0.25 parts of citrus yellow pigment, 0.07 parts of carmine pigment, 0.3 parts of sucrose octaacetate, 13 parts of xylitol, 0.15 parts of disodium nucleotides, 2 parts of kudzu flavor, 0.5 parts of caramel flavor, and 0.2 parts of green tea flavor.

[0012] In a second aspect, the present invention provides a method for preparing a placebo of the Chinese medicinal compound Gegenqinlian decoction according to the first aspect, characterized in that it comprises the following steps: After the base, pigment, essence and flavoring agent are prepared into a mixed liquid, it is filled into a Chinese medicine bag and refrigerated.

[0013] As an optional solution, the preparation temperature of the mixed liquid is 85°C-100°C, the volume of the mixed liquid is 150mL-200mL, and the refrigeration temperature is 0-4°C.

[0014] In a third aspect, the present invention provides use of the Chinese herbal compound Gegenqinlian decoction placebo of the first aspect in a clinical trial for the treatment of type 2 diabetes.

[0015] The Chinese medicine compound Gegenqinlian decoction placebo of the present invention adopts buckwheat flour, sodium carboxymethyl cellulose and potassium sorbate as a matrix, adds pigment to adjust the color of the mixed solution, so that the color is similar to or even the same as the color of the Gegenqinlian decoction, adds flavor and flavoring agent to adjust the smell and taste of the placebo respectively, and then makes the color, smell and taste of the placebo similar to the Chinese medicine compound Gegenqinlian decoction, researchers, volunteers and type 2 diabetes patients cannot correctly identify which is the Chinese medicine and which is the placebo, and the similarity scores of the two are also similar enough, and the Gegenqinlian decoction placebo produced meets the needs of blinding in clinical trials, and patients are not easy to break the blind even when exposed to the test drug. In addition, the results of animal experiments and manual evaluations of the placebo all show that the placebo is safe enough and does not affect the patient's blood sugar. The preparation materials and methods of the placebo are consistent, and the quality of the placebo is controllable. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Other features, objects and advantages of the present application will become more apparent by reading the detailed description of non-limiting embodiments made with reference to the following drawings: Figure 1 This is the instantaneous blood sugar changes in healthy mice; Figure 2 is the area under the instantaneous blood glucose curve of healthy mice; Figure 3 This is a line graph of fasting blood glucose changes in diabetic model mice; Figure 4 This is a line graph of fasting blood glucose changes in healthy mice; Figure 5This is the blood sugar change diagram of healthy mice during OGTT; Figure 6 This is the ITT change diagram of diabetic model mice; DETAILED DESCRIPTION The present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are only used to explain the relevant invention, rather than to limit the invention. It is also necessary to explain that, for ease of description, only the parts related to the invention are shown in the accompanying drawings.

[0017] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present application will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0018] In a first aspect, an embodiment of the present application provides a placebo of a traditional Chinese medicine compound Gegenqinlian decoction, the placebo comprising a matrix, a pigment, an essence and a flavoring agent: The matrix includes buckwheat flour, sodium carboxymethyl cellulose, and potassium sorbate; Pigments include caramel, yellow, and carmine; Fragrances include kudzu root, caramel, and green tea; Flavoring agents include sucrose octaacetate, disodium ribonucleotides, and sugar alcohols.

[0019] The matrix used in the embodiments of the present application is similar in color to Gegen Qinlian Decoction and has good solubility. Together with pigments, flavors and correctives, it can reliably adjust the color, smell and taste of the placebo, thereby making the placebo similar to the Gegen Qinlian Decoction decoction. Buckwheat flour is beneficial for diabetic patients to use and reduces the impact on blood sugar.

[0020] As an achievable manner, the yellow pigment includes lemon yellow pigment and citrus yellow pigment, and the sugar alcohol includes xylitol or maltitol.

[0021] The yellow pigment of this embodiment can reliably adjust the color of the placebo, and cooperate with caramel pigment and carmine pigment to make the color of the placebo close to the color of the Gegen Qinlian Decoction; and xylitol or maltitol, as a natural sweetener, can reliably correct the bitterness, which is conducive to the placebo having a taste close to that of the Gegen Qinlian Decoction.

[0022] It can be understood that the dosage of each component of the placebo in the examples of the present application can be adjusted according to the actual dosage of each component of Gegenqinlian Decoction.

[0023] For example, Gegenqinlian Decoction includes 24g of Pueraria root, 9g of Scutellaria baicalensis, 9g of Coptis chinensis, and 6g of Radix Glycyrrhizae; the decoction method is: soak the medicinal materials for 30 minutes, add water in an amount 10 times the weight of the medicinal materials, first heat with high heat to reach boiling, then switch to low heat to slowly decoct and maintain a slight boil, decoct for 30 minutes for the first decoction and 20 minutes for the second decoction.

[0024] The placebo provided in the embodiments of the present application for the above-mentioned Radix Puerariae and Radix Qinlian includes: In some embodiments, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.2-0.4 parts of citrus yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium flavor nucleotides, and 12-14 parts of xylitol.

[0025] The weight portion of the placebo disclosed in this embodiment is conducive to reliably adjusting the color, smell and taste of the mixed solution by controlling the amount of buckwheat flour, sodium carboxymethyl cellulose, potassium sorbate, pigments, flavors and flavoring agents, so that the color, smell and taste are similar to or even the same as the color of the Gegenqinlian Decoction, which is conducive to the patient not being easily blinded even if he or she is exposed to the test drug, and will not affect the patient's blood sugar.

[0026] In some other embodiments, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.2-0.4 parts of citrus yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium flavor nucleotides, and 9-10 parts of maltitol.

[0027] As an achievable manner, the yellow pigment includes lemon yellow pigment and sunset yellow pigment, and the sugar alcohol includes xylitol or maltitol.

[0028] In some embodiments, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.02-0.03 parts of sunset yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium nucleotides, and 12-14 parts of xylitol.

[0029] In some other embodiments, the placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.02-0.03 parts of sunset yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium nucleotides, and 9-10 parts of maltitol.

[0030] In a preferred embodiment, the placebo comprises the following components: 8 parts of buckwheat flour, 0.5 parts of sodium carboxymethyl cellulose, 0.25 parts of potassium sorbate, 0.4 parts of caramel color, 0.1 parts of lemon yellow, 0.25 parts of citrus yellow pigment, 0.07 parts of carmine pigment, 0.3 parts of sucrose octaacetate, 13 parts of xylitol, 0.15 parts of disodium nucleotides, 2 parts of kudzu flavor, 0.5 parts of caramel flavor, and 0.2 parts of green tea flavor.

[0031] In summary, the traditional Chinese medicine compound Gegenqinlian decoction placebo of the embodiment of the present application adopts buckwheat flour, sodium carboxymethyl cellulose and potassium sorbate as the matrix, adds pigment to adjust the color of the mixed solution, so that the color is similar to or even the same as the color of the Gegenqinlian decoction, adds flavors and flavoring agents to adjust the smell and taste of the placebo respectively, and then makes the placebo and the traditional Chinese medicine compound Gegenqinlian decoction color, smell and taste similar, researchers, volunteers and type 2 diabetes patients can not correctly identify which is the traditional Chinese medicine and which is the placebo, the similarity score of the two is also similar enough, the Gegenqinlian decoction placebo produced meets the needs of blinding in clinical trials, and patients are not easy to break the blind even if they are exposed to the test drug. In addition, the results of animal experiments and manual evaluations of the placebo show that the placebo is safe enough and does not affect the patient's blood sugar. The preparation materials and methods of the placebo are consistent, and the quality of the placebo is controllable.

[0032] In a second aspect, the present invention provides a method for preparing a placebo of the Chinese medicinal compound Gegenqinlian decoction according to the first aspect, characterized in that it comprises the following steps: After the base, pigment, essence and flavoring agent are prepared into a mixed liquid, it is filled into a Chinese medicine bag and refrigerated.

[0033] It is understandable that the process of configuring the matrix, pigment, flavor and flavoring agent into a mixed liquid can be to directly add the matrix, pigment, flavor and flavoring agent into hot water to obtain the mixed liquid; or it can be to add the matrix, pigment, flavor and flavoring agent into cold water and boil them to obtain the mixed liquid. The embodiments of the present application do not specifically limit this.

[0034] As an achievable manner, the configuration temperature of the mixed liquid is 85° C.-100° C., and the volume of the mixed liquid is 150 mL-200 mL.

[0035] The configuration temperature of the mixed liquid of this embodiment is conducive to ensuring that the matrix, pigment, flavor and flavoring agent are fully dissolved to obtain a mixed liquid, and the volume of the mixed liquid of this application is conducive to ensuring that the color and taste of the placebo are consistent with the color and taste of the traditional Chinese medicine compound Gegenqinlian decoction.

[0036] Specifically, the preparation temperature of the mixed solution can be but is not limited to 85°C, 90°C, 95°C or 100°C, etc. When the preparation temperature is lower than 85°C, the raw materials cannot be fully dissolved; when the preparation temperature is higher than 100°C, the smell and color of the placebo may change significantly, which is quite different from the smell and color of the compound Chinese medicine Gegen Qinlian Decoction; the volume of the mixed solution can be but is not limited to 150mL, 160mL, 170mL, 180mL, 190mL or 200mL, etc. When the volume of the mixed solution is less than 150mL, the color of the placebo will be darker and the taste will be heavier, which is quite different from the color and taste of the compound Chinese medicine Gegen Qinlian Decoction; when the volume of the mixed solution is greater than 200mL, the color of the placebo will be lighter and the taste will become lighter, which is quite different from the color and taste of the compound Chinese medicine Gegen Qinlian Decoction.

[0037] In some embodiments, the refrigeration temperature is 0-4°C, which is conducive to the storage of the placebo, so that the shape of the placebo is stable and no precipitation, deterioration or other problems occur.

[0038] In actual processing, the matrix, pigment, flavor and corrective are added to 150 mL of 100° C. hot water to dissolve to obtain a mixed solution, which is then filled into a Chinese medicine bag, sealed and refrigerated at 0-4° C.

[0039] For example, in actual application, the placebo includes 1.6g buckwheat flour, 0.1g sodium carboxymethyl cellulose, 0.05g potassium sorbate, 0.08g caramel color, 0.02g lemon yellow, 0.05g orange yellow, 0.014g carmine, 0.06g sucrose octaacetate, 2.5g sugar alcohol, 0.03g disodium flavor nucleotides, 0.4g kudzu root flavor, 0.1g caramel flavor and 0.04g green tea flavor.

[0040] In summary, the preparation method of the Chinese herbal compound Gegenqinlian decoction of the embodiment of the present application is simple to operate, easy to process, and can ensure that the properties, moisture content, filling volume difference and other inspection items of the placebo meet the requirements and meet the quality standards of the placebo. The obtained placebo is consistent with the color, smell and taste of the Chinese herbal compound Gegenqinlian decoction and will not affect blood sugar.

[0041] Example The placebo consisted of the following components: 8 parts of buckwheat flour, 0.5 parts of sodium carboxymethyl cellulose, 0.25 parts of potassium sorbate, 0.4 parts of caramel color, 0.1 parts of lemon yellow, 0.25 parts of citrus yellow pigment, 0.07 parts of carmine pigment, 0.3 parts of sucrose octaacetate, 13 parts of xylitol, 0.15 parts of disodium nucleotides, 2 parts of kudzu flavor, 0.5 parts of caramel flavor, and 0.2 parts of green tea flavor.

[0042] The placebo of the above example was tested as follows: 1. Conduct animal experiments to verify the safety of placebo and its non-interference in blood sugar metabolism: Experimental method: The db / db mice and C57 mice were divided into two groups, respectively, a placebo group and a control group. The placebo group was given the placebo of the above embodiment by oral gavage, and the control group was given the same volume of distilled water by oral gavage. The intervention lasted for 4 weeks. On the first day, the instantaneous blood glucose changes of the two groups of C57 mice after oral gavage were measured. During the experiment, the fasting blood glucose of the four groups of mice was measured every week. The db / db mice are diabetic model mice, and the C57 mice are healthy mice. After the experiment, the two groups of db / db mice underwent intraperitoneal injection insulin resistance test, and the two groups of C57 mice underwent oral glucose tolerance test, and the blood glucose changes of each mouse were measured. Subsequently, the four groups of mice were anesthetized, and blood was drawn from the eyeballs to measure liver and kidney function; Statistical analysis: The measured data were expressed as mean ± standard deviation (x ± s) when they were in accordance with normal distribution. The independent sample t test was used for homogeneous variance, and the Mann-Whitney U test was used for unequal variance or non-normal distribution.

[0043] Experimental results: 1.1 Safety observation in mice During the intervention, no significant changes were observed in the general conditions of mice in each group, including physical signs, behavioral activities, mental state, and respiration.

[0044] 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.

[0045] Table 1 Body weight changes of diabetic model mice (g)

[0046] Table 2. Changes in body weight of healthy mice (g)

[0047] 1.2 Effects of placebo on transient blood glucose changes in healthy mice The instantaneous blood glucose values ​​of the healthy mice placebo group and control group are shown in Table 3. Figure 1 and Figure 2 . Compared with the two groups, the blood glucose level in the placebo group was slightly higher than that in the control group at 30min and 60min, but the difference was small and there was no statistical difference (P>0.05). There was also no statistical difference in blood glucose values ​​and the area under the time-blood glucose curve (AUC) at all time points (P>0.05).

[0048] Table 3 Changes of instantaneous blood glucose in healthy mice (mmol / L)

[0049] 1.3 Changes in blood sugar During the intervention, the changes in fasting blood glucose of diabetic model mice and healthy mice are shown in Table 4 and Figure 3 , and Table 5 and Figure 4 There was no statistically significant difference in the fasting blood glucose values ​​of mice in the intervention group at each time point compared with the control group (P>0.05).

[0050] The changes of OGTT in healthy mice are shown in Table 6 and Figure 5 The blood glucose values ​​at each time point were not statistically significant (P>0.05). The changes in ITT of diabetic model mice are shown in Table 7 and Figure 6 There was no statistically significant difference in blood glucose levels at each time point (P>0.05).

[0051] There was no statistical difference in the blood glucose levels of healthy mice and diabetic model mice in each group at each time point. The above results indicate that placebo has no effect on blood glucose metabolism.

[0052] Table 4 Fasting blood glucose changes in diabetic model mice (mmol / L)

[0053] Table 5 Fasting blood glucose changes in healthy mice (mmol / L)

[0054] Table 6 OGTT changes in healthy mice (mmol / L)

[0055] Table 7 Diabetes model ITT changes (mmol / L)

[0056] 1.4 Liver and kidney function The liver and kidney functions of diabetic model mice are shown in Table 8 below. There was no statistically significant difference between the two groups (P>0.05).

[0057] Table 8 Liver and kidney function of diabetic model mice

[0058] The liver and kidney functions of healthy mice are shown in Table 9 below. There was no statistically significant difference between the two groups (P>0.05).

[0059] Table 9 Liver and kidney function of healthy mice

[0060] 2 Conducting placebo similarity evaluation: 2.1 Researcher evaluation 2.1.1 Evaluators The evaluators for this study are internal researchers of the research group.

[0061] 2.1.2 Evaluation Method The three-point inspection method is used: there are 3 samples in each evaluation package. There are 6 cases for these 3 samples according to the sample category (drug A / placebo B) and the order of arrangement: ABB, AAB, ABA, BAA, BBA, BAB. The 3 content samples are coded in a 3-digit format (for example, 011, 012, 013) from left to right, where the tens and hundreds digits represent the test package number, such as 01, and the ones digit represents the sequence number of the samples in the test package from left to right (1, 2, 3 respectively). Each evaluation package is randomly distributed to the evaluators, and the evaluators are informed to uniformly sample and evaluate in the order of the sample numbers in the evaluation package from small to large. The evaluators are also informed that each evaluation package has two identical samples and one different sample. The evaluators comprehensively compare the different sensory characteristics of the samples in a blind state, find the different sample, and record the sample number on the evaluation questionnaire to guess whether the different samples are drugs or placebos.

[0062] 2.1.3 Evaluation Content The sensory properties of Chinese medicine and placebo were evaluated, including: (1) Visual characteristics, including external shape, color, gloss, and texture; (2) Taste characteristics, including flavor and mouthfeel; (3) Odor characteristics.

[0063] The external shape refers to the external physical shape of the drug itself, such as circle, ellipse, sphere, diamond, etc., as well as thickness and size; texture refers to the real visual feeling of the drug itself, and also includes, for example, the visual feeling of the drug surface; taste refers to the direct feeling of the drug in the human mouth caused by tongue touch and chewing.

[0064] 2.1.4 Quality Control Ensure that the assessors have not come into contact with items with strong irritating tastes or odors within 1 hour before the assessment. Fully introduce the relevant concepts and assessment methods to the assessors before the assessment begins; during the assessment, a dedicated person will distribute the assessment package to the assessors. During the assessment process, except for specific personnel, no additional biased guidance will be given to the assessors to avoid communication or exchange of drugs between assessors. In between two drug tastings, the assessors will rinse their mouths with clean water, and the interval will be 30 seconds to reduce mutual interference. Ensure that the assessment site is brightly lit and relatively quiet.

[0065] 2.1.5 Statistical analysis In the three-point test method, the number of people who guessed correctly is counted. When more than half of them guessed correctly, it can be considered that there is a certain sensory difference between the placebo and the Chinese medicine. In the analysis of guessing whether it is a drug or a placebo, the relative ratio of the placebo judgment is calculated (the calculation method is the proportion of placebos judged as "test drugs" / the proportion of test drugs judged as "test drugs"), and when it exceeds 60%, the simulation effect is considered qualified.

[0066] 2.1.6 Evaluation Results A total of 14 evaluators participated in this evaluation, including 1 male and 13 female researchers in the field of traditional Chinese medicine. Among them, 12 people correctly identified different samples, and 2 people did not correctly identify them. From the perspective of sensory evaluation, in the three-point test method, more than 7 of the 14 evaluators gave correct answers, and there were still certain sensory differences between the drug and the placebo.

[0067] Among these 12 people, 8 people misidentified the Chinese medicine and the placebo, and 4 people correctly identified the Chinese medicine and the placebo. Among the evaluators who correctly picked out different samples, 8 of them suggested that there was a difference in smell, and 3 people thought that the placebo smelled stronger. 8 people thought that there was a difference in taste, 3 people thought that the placebo was more bitter, 3 people thought that the Chinese medicine was more bitter, 1 person thought that the placebo was sweeter, and 1 person thought that the placebo was only bitter. Considering that the bitterness of Gegenqinlian Decoction is more persistent, the taste of the evaluators may be affected by the evaluation order and the previous evaluation, so more than half of the evaluators disagreed. 3 people thought that there was a difference in color.

[0068] From the perspective of blind method, among the 14 evaluators, 10 people made wrong guesses and identified the placebo as the Chinese medicine, and 4 people made correct guesses and correctly identified the Chinese medicine. No one answered "I don't know". The relative ratio of the placebo judgment was 250%, which can be considered that the placebo achieved the effect of simulating the test drug.

[0069] 2.2 Volunteer Evaluation 2.2.1 Inclusion and Exclusion Criteria of Evaluators ① Healthy people Inclusion criteria: (1) Normal sensory functions such as vision, smell and taste (2) No chronic disease requiring long-term medication in the past year; (3) Aged 18 and above.

[0070] (4) Have not participated in other clinical research in the past three months; Exclusion criteria: (1) People with mental disorders and pregnant women; (2) Those who are unable to understand or cooperate.

[0071] ② Clinical trial subjects This group of people refers to those who have the same exclusion criteria as the subjects of the clinical trial, but do not participate in the formal clinical trial. Taking the randomized double-blind controlled clinical trial of Gegenqinlian Decoction for the treatment of type 2 diabetes as an example, the exclusion criteria are as follows: Inclusion criteria: (1) Clinical diagnosis of type 2 diabetes; (2) Aged 18 or above; (3) Have not participated in other clinical research in the past three months.

[0072] Exclusion criteria: (1) Patients with severe cardiovascular and cerebrovascular diseases, tumors, etc. (2) Participate in clinical trials of Gegenqinlian decoction for the treatment of type 2 diabetes; (3) People with mental disorders and pregnant women.

[0073] (4) Those who are unable to understand or cooperate.

[0074] 2.2.2 Evaluation methods 2.2.2.1 Score evaluation In a simulated clinical trial scenario where patients are exposed to both a placebo and a test drug at the same time, the evaluators were asked to conduct a comparative evaluation between the placebo and Gegenqinlian decoction to determine their consistency.

[0075] There are 2 samples in each evaluation package, namely "Gegenqinlian Decoction + Placebo" (Group C) and "2 Gegenqinlian Decoctions" (Group D). Using the random number table method, the evaluators were assigned to Groups C and D at a ratio of 1:1. The sensory properties of Chinese medicine and placebo were evaluated, including: visual properties, such as external shape, color and gloss, texture; taste characteristics, such as taste and mouthfeel; odor characteristics. Comparing the 2 samples in the evaluation package, the evaluators scored the similarity of different sensory characteristics, with a score of 0 to 10 points, 10 points for completely the same, and 0 points for completely different.

[0076] 2.2.2.2 Independent evaluation The patients were divided into a drug group (Group E) and a placebo group (Group F). The evaluators were assigned to Group E and Group F at a ratio of 1:1 using a random number table to simulate the actual medication scenario in a clinical trial. The evaluators conducted an overall evaluation based on the sensory characteristics and subjectively determined whether the drug they were taking was a drug or a placebo, in order to judge the simulated effect of the placebo. There were three possible answers: "real drug", "uncertain", and "placebo".

[0077] 2.2.3 Evaluation Content Same as above.

[0078] 2.2.4 Quality Control Same as above.

[0079] 2.2.5 Statistical analysis For the score evaluation, the independent sample t-test was used for statistical analysis using SPSS 25.0 software. When P < 0.05, the difference was statistically significant, that is, there was a recognizable difference between the placebo and Gegenqinlian decoction. The similarity scores of each dimension were calculated. When the scores of visual and tactile similarity were ≥ 7 points, and the scores of taste and olfactory similarity were ≥ 6 points, they were considered qualified. For independent evaluation, the RR value was calculated, and the chi-square test was used to judge the results.

[0080] 2.2.6 Evaluation Results 2.2.6.1 Evaluators A total of 128 evaluators were recruited, including 64 healthy subjects and 64 diabetic subjects, who all participated in the score evaluation and independent evaluation.

[0081] Among the healthy population, there were 18 males and 46 females, almost all of whom were aged between 18 and 30, with only one 40-year-old, and the average age was 20.08, as shown in Table 10. Among the diabetic subjects, there were 28 males and 36 females, aged between 24 and 80, with an average age of 62.98. The characteristics of the subjects are shown in Table 11 below.

[0082] 2.2.6.1 Score evaluation A total of 128 evaluators were recruited, including 64 healthy people and 64 diabetic patients. Among the healthy population, there were 35 people who took "Gegenqinlian Decoction + Placebo" (Group C1) and 29 people who took "2 Gegenqinlian Decoctions" (Group D1). The appearance, color, and taste of the placebo were scored and compared. The results are shown in Table 3.20. There was no statistical difference in the similarity scores of Group C1 and Group D1 in each dimension (P>0.05). The similarity score in taste was less than 6 points, but it was not much different from the score of the other group. The results are shown in Table 12 Among the diabetic subjects, there were 30 people in the "Gegenqinlian Decoction + Placebo" (C2 group) and 33 people in the "2 Gegenqinlian Decoctions" (D2 group). The appearance, color, and taste of the placebo were scored and compared comprehensively. The results showed that there was no statistically significant difference between the test drug and the placebo (P>0.05), and the similarity of each dimension was above 6 points. The results are shown in Table 13 below.

[0083] 2.2.6.2 Independent evaluation The predictions for placebo and drug in the diabetic population and the healthy population are shown in Table 14 , and there was no statistical difference in the prediction results ( P = 0.705).

[0084] Table 10 Basic information of healthy volunteers

[0085] Table 11 Basic information of healthy volunteers

[0086] Table 12 Similarity scores of healthy people

[0087] Table 13 Similarity scores of diabetic population

[0088] Table 14 Speculations of diabetic and healthy people

[0089] Health Personnel Assessment Results: Among the healthy population, 29 people were assigned to the drug group (E1 group), of which 18 answered "drug", 8 answered "placebo", and 3 "did not know"; 35 people were assigned to the placebo group (F1 group), of which 21 answered "drug", 13 answered "placebo", and 1 "did not know", see Table 15. Using the chi-square test, there was no statistical difference in the guesses between the two groups (P = 0.392), and the calculated RR value was 96.67%.

[0090] Table 15 Speculations of healthy people

[0091] Diabetes population assessment results: Among the diabetic population, 33 people were assigned to the medication group (E2 group), of which 28 answered "medication", 3 answered "placebo", and 2 "did not know"; 30 people were assigned to the placebo group (F2 group), of which 26 answered "medication", 4 answered "placebo", and 0 "did not know", see Table 16 below. Using the chi-square test, there was no statistical difference between the two groups (P = 0.561). The calculated RR value was 102%.

[0092] Table 16 Speculations of diabetes population

[0093] The results of animal experiments and manual evaluations show that the placebo is safe enough and does not affect blood sugar metabolism; the preparation materials and methods of the placebo are consistent, and the quality of the placebo is controllable; researchers, volunteers, and type 2 diabetes patients cannot correctly identify which is the traditional Chinese medicine and which is the placebo, and the similarity scores of the two are similar enough. The Gegenqinlian Decoction placebo produced meets the requirements of blinding in clinical trials.

[0094] It should be understood that the terms "center", "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like used above to indicate orientations or positional relationships are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the panel or component referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, unless otherwise specified, "multiple" means two or more.

[0095] The above description is only a preferred embodiment of the present application and an explanation of the technical principles used. Those skilled in the art should understand that the scope of the invention involved in the present application is not limited to the technical solution formed by a specific combination of the above technical features, but should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the inventive concept. For example, the above features are replaced with (but not limited to) technical features with similar functions disclosed in the present application.

Claims

1. A Chinese medicine compound Gegenqinlian decoction placebo, characterized in that: The placebo includes base, color, flavor and corrective agent: Wherein, the matrix comprises buckwheat flour, sodium carboxymethyl cellulose and potassium sorbate; The pigments include caramel pigment, yellow pigment and carmine pigment; The flavors include kudzu root flavor, caramel flavor, and green tea flavor; The flavoring agent includes sucrose octaacetate, disodium flavor nucleotides, and sugar alcohol.

2. The placebo according to claim 1, characterized in that The yellow pigment includes lemon yellow pigment and citrus yellow pigment, and the sugar alcohol includes xylitol or maltitol.

3. The placebo according to claim 2, characterized in that The placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.2-0.4 parts of citrus yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium flavor nucleotides, and 12-14 parts of xylitol.

4. The placebo according to claim 2, characterized in that The placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.2-0.4 parts of citrus yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium flavor nucleotides, and 9-10 parts of maltitol.

5. The placebo according to claim 1, characterized in that The yellow pigment includes lemon yellow pigment and sunset yellow pigment, and the sugar alcohol includes xylitol or maltitol.

6. The placebo according to claim 5, characterized in that The placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.02-0.03 parts of sunset yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium nucleotides, and 12-14 parts of xylitol.

7. The placebo according to claim 5, characterized in that The placebo comprises the following components by weight: 8-10 parts of buckwheat flour, 0.5-0.7 parts of sodium carboxymethyl cellulose, 0.2-0.4 parts of potassium sorbate, 0.4-0.6 parts of caramel pigment, 0.1-0.3 parts of lemon yellow pigment, 0.02-0.03 parts of sunset yellow pigment, 0.06-0.08 parts of carmine pigment, 2-4 parts of kudzu root flavor, 0.4-0.6 parts of caramel flavor, 0.2-0.4 parts of green tea flavor, 0.3-0.5 parts of sucrose octaacetate, 0.1-0.3 parts of disodium nucleotides, and 9-10 parts of maltitol.

8. The placebo according to claim 2, characterized in that The placebo comprises the following components: 8 parts of buckwheat flour, 0.5 parts of sodium carboxymethyl cellulose, 0.25 parts of potassium sorbate, 0.4 parts of caramel color, 0.1 parts of lemon yellow, 0.25 parts of citrus yellow pigment, 0.07 parts of carmine pigment, 0.3 parts of sucrose octaacetate, 13 parts of xylitol, 0.15 parts of disodium nucleotides, 2 parts of kudzu flavor, 0.5 parts of caramel flavor, and 0.2 parts of green tea flavor.

9. A method for preparing the placebo of the Chinese medicinal compound Gegenqinlian decoction according to any one of claims 1 to 7, characterized in that: The steps include: After the matrix, the pigment, the flavor and the flavoring agent are prepared into a mixed liquid, the mixed liquid is filled into a traditional Chinese medicine bag and refrigerated; Preferably, the preparation temperature of the mixed liquid is 85°C-100°C, the volume of the mixed liquid is 150mL-200mL, and the refrigeration temperature is 0-4°C.

10. Use of the traditional Chinese medicine compound Gegenqinlian decoction placebo according to any one of claims 1 to 7 in a clinical trial for the treatment of type 2 diabetes.

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