Compound scutellaria baicalensis and orchid oral liquid placebo and preparation method thereof

Abstract

The invention discloses a compound scutellaria baicalensis and orchid oral liquid placebo and a preparation method thereof, and belongs to the technical field of medicines. The technical problem to be solved is to provide the compound scutellaria baicalensis and orchid oral liquid placebo which is good in taste, similar in appearance and free of peculiar smell. According to the technical scheme, the compound scutellaria baicalensis and orchid oral liquid placebo is characterized by being prepared from, by weight, 60-70 parts of compound scutellaria baicalensis and orchid extract, 45-55 parts of thickening agent, 0.4-0.6 part of bitter agent, 45-55 parts of sweetening agent, 3-4 parts of coloring agent and 2.7-3 parts of preservative, and the bitter agent is sucrose octaacetate.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a placebo of compound Scutellaria baicalensis and Lanhua oral liquid and its preparation method. Background Technology

[0002] Traditional Chinese medicine (TCM) placebos are drug preparations without pharmacological components, which can stabilize the mood of people who have experienced adverse effects from long-term use of a certain drug. With the development of modern medicine, TCM placebos are becoming increasingly indispensable as control drugs in large-scale randomized, double-blind clinical trials to verify the therapeutic effects of experimental drugs. Successful placebo preparation can improve patient adherence to medication. The difficulty in preparing TCM placebos lies in their diverse dosage forms, complex ingredients, and significant differences in color, odor, and taste between different preparations. The specific selection and proportions of raw materials for each variety are also different. Therefore, it is necessary to choose reasonable formulas and preparation methods to prevent unblinding and reduce bias in clinical trials, thus ensuring the smooth progress of the clinical trials.

[0003] There are few reports on the development of placebos for oral Chinese medicine in clinical trials in my country, so the development of placebos for oral Chinese medicine is of great significance.

[0004] Relevant patent documents retrieved: For example, Chinese patent CN106267142A, published on January 4, 2022, discloses a process for preparing a placebo of compound traditional Chinese medicine (TCM) formula granules. This process includes the following steps: 1) mixing the original prescription formula granules; 2) recording relevant parameters of the mixed formula granules; 3) examining excipients; 4) producing colorant granules; 5) weighing the original prescription mixed formula granules; and 6) preparing the compound formula granule placebo. This process addresses the issue of color differences between single-formula granule placebos and the original TCM decoction when combined, based on the principle of multi-herb compatibility in TCM clinical practice. It also achieves a visual effect of multiple formula granule colors in the placebo, allowing researchers and subjects to more directly assess the difference between the treatment drug and the placebo under experimental conditions, eliminating bias caused by factors such as color and taste, and improving the reliability of the trial.

[0005] Relevant non-patent literature retrieved: The journal or book title is *Xinjiang Journal of Traditional Chinese Medicine*, and the article title is "Preparation, Simulated Effect Evaluation, and Quality Standard Formulation of Placebo for Snow Lotus Oral Liquid," published in Volume 13, Issue 3, 2025. This article uses single-factor experiments to screen colorants and flavoring agents in the Snow Lotus Oral Liquid placebo formulation to determine the optimal placebo formulation. The placebo's appearance, odor, color, and taste were evaluated manually to simulate its effects. Three small-scale trials were conducted, and quality standards for the Snow Lotus Oral Liquid placebo were established. The results showed that the placebo had a high similarity to the Snow Lotus Oral Liquid, being essentially identical to the original drug in appearance, color, odor, and taste. The development of the Snow Lotus Oral Liquid placebo fills a gap in the current preparation of oral liquid placebos. This placebo meets the requirements for placebos in randomized controlled clinical trials and provides a reference method and approach for the preparation, simulated effect evaluation, and quality standard formulation of traditional Chinese medicine placebos.

[0006] The prior art represented by the aforementioned documents has at least the following unresolved technical problems or defects: Patent CN106267142A may not be suitable for clinical applications of oral liquids, and patient compliance regarding its taste needs improvement. While the literature "Preparation of Placebo, Evaluation of Simulated Effects, and Formulation of Quality Standards for Traditional Chinese Medicine Snow Lotus Oral Liquid" fills the gap in the preparation of placebos for traditional Chinese medicine oral liquid dosage forms, its screening of bittering agents has certain limitations.

[0007] In solving the above problems or overcoming the above defects, the present invention encountered the following difficulties and obstacles: In the process of optimizing the screening of bittering agents, sucrose octaacetate has low solubility, while maltodextrin and sucrose are easily soluble in hot water. Therefore, sucrose octaacetate, maltodextrin and sucrose are added at the same time and boiled. The solution is basically dissolved 5 minutes after the water boils, thus shortening the dissolution time. Summary of the Invention

[0008] The purpose of this invention is to provide a compound Scutellaria baicalensis and Lanhua oral liquid placebo, and related technologies, to solve technical problems such as poor patient compliance in terms of appearance, taste, color, and smell of oral liquid placebos, or combinations thereof.

[0009] Terminology Explanation: Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0010] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of the invention in any way. In this invention, the singular is used in conjunction with the plural unless otherwise specifically stated. It should also be noted that, unless otherwise stated, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0011] The definition of the standard chemical term can be found in the reference "Standard for Evaluation of Placebo Simulation Effect of Traditional Chinese Medicine Preparations", formulated by the China Association of Traditional Chinese Medicine, edited by Gao Rui, June 2025.

[0012] Unless specifically defined herein, the use of all commercially available products herein employs standard techniques. For example, it may be carried out using the manufacturer's instructions for use with the kit, or in accordance with methods known in the art or the description of this invention. The techniques and methods described herein can generally be implemented according to conventional methods well known in the art, based on the descriptions in the various summary and more specific documents cited and discussed in this specification.

[0013] In a first aspect, the present invention provides a compound Scutellaria baicalensis oral liquid placebo, comprising, by weight, 60-70 parts of compound Scutellaria baicalensis extract, 45-55 parts of thickener, 0.4-0.6 parts of bittering agent, 45-55 parts of sweetener, 3-4 parts of coloring agent, and 2.7-3 parts of preservative. Other specific values ​​within the above range can be selected, all of which can achieve the technical effects of the present invention. For example, the thickener includes, but is not limited to, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, and 55 parts.

[0014] Preferably, the compound Scutellaria baicalensis oral liquid placebo comprises, by weight, 66.88 parts of compound Scutellaria baicalensis extract, 50 parts of thickener, 0.5 parts of bittering agent, 50.75 parts of sweetener, 4 parts of coloring agent and 2.7 parts of preservative.

[0015] Preferably, the thickener is maltodextrin.

[0016] Preferably, the bittering agent is sucrose octaacetic acid ester.

[0017] Preferably, the sweetener is sucrose and steviol glycosides, with a mass ratio of 45-55:0.5-1. Other specific values ​​within the above range can be selected to achieve the technical effect of the present invention, including but not limited to 45:0.5, 45:1, 50:0.75, 50:0.5, 50:1, 55:0.5, and 55:1.

[0018] More preferably, the mass ratio of sucrose to steviol glycosides is 50:0.75.

[0019] Preferably, the colorant is a mixture of caramel color, caramel color and milk chocolate brown, or a mixture of caramel color and lemon yellow.

[0020] Preferably, the mass ratio of caramel color to milk chocolate brown is 1.5-2.5:1.

[0021] More preferably, the mass ratio of caramel color to milk chocolate brown is 2:1.

[0022] Preferably, the mass ratio of caramel color to lemon yellow is 1.5-2.5:1.

[0023] More preferably, the mass ratio of caramel color to lemon yellow is 2:1.

[0024] Preferably, the preservative is sodium benzoate.

[0025] As a preferred embodiment, the compound Scutellaria baicalensis oral liquid placebo comprises, by weight, 66.88 parts of compound Scutellaria baicalensis extract, 50 parts of maltodextrin, 0.5 parts of sucrose octaacetate, 50 parts of sucrose, 0.75 parts of steviol glycosides, 4 parts of caramel color, and 3 parts of sodium benzoate.

[0026] Secondly, the present invention provides a method for preparing the above-mentioned compound Scutellaria baicalensis oral liquid placebo, comprising the following steps: After filtering the compound Scutellaria baicalensis extract, add water and heat to boiling to obtain a compound Scutellaria baicalensis extract solution for later use. Dissolve the prescribed amounts of sucrose octaacetate, sucrose, and maltodextrin in water, heat to boiling, cool, add steviol glycosides, sodium benzoate, and caramel color, stir until fully dissolved, mix evenly, let stand at room temperature, add the compound Scutellaria baicalensis extract solution, add water to make up the volume, stir evenly, coarsely filter, finely filter, fill, and sterilize to obtain the final product.

[0027] Preferably, the heating and boiling time is 5-15 minutes, the cooling temperature is 30-50°C, the coarse filtration uses three layers of filter paper, and the fine filtration uses a 0.8μm filter membrane.

[0028] More preferably, the heating and boiling time is 10 minutes, and the cooling temperature is 40°C.

[0029] Embodiments 1-5 of this invention at least support the protection scope of claim 1.

[0030] Regarding the claim 1: The technical feature “60-70 parts of compound Scutellaria baicalensis extract” is derived from the corresponding technical features 60, 66.88, and 70 parts in the foregoing explanation and / or Examples 1-5, summarized by the common feature “60-70 parts”. Therefore, those skilled in the art can reasonably infer that any point value within the range of 60-70 parts of the technical feature should fall within the protection scope of claim 1. For example, replacing 66.88 parts with 65 parts while keeping other technical features unchanged still falls within the protection scope of claim 1 of this invention.

[0031] The technical feature "45-55 parts of thickener" is derived from the aforementioned explanation and / or the corresponding technical features 45, 50, and 55 parts in Examples 1-5, summarized by the common feature "45-55 parts". Therefore, those skilled in the art can reasonably infer that any value within the range of 45-55 parts of technical feature should fall within the protection scope of claim 1. For example, replacing 50 parts with 51 parts while keeping other technical features unchanged still falls within the protection scope of claim 1 of this invention.

[0032] The technical feature "0.4-0.6 parts of bittering agent" is derived from the corresponding technical features of 0.4, 0.5, and 0.6 parts in the foregoing explanation and / or Examples 1-5, summarized by the common feature "0.4-0.6 parts". Therefore, those skilled in the art can reasonably infer that any value within the range of 0.4-0.6 parts of the technical feature should fall within the protection scope of claim 1. For example, replacing 0.5 parts with 0.55 parts while keeping other technical features unchanged still falls within the protection scope of claim 1 of this invention.

[0033] The technical feature "45-55 parts of sweetener" is derived from the corresponding technical features 45, 50, and 55 parts in the foregoing explanation and / or Examples 1-5, summarized by the common feature "45-55 parts". Therefore, those skilled in the art can reasonably infer that any value within the range of 45-55 parts of technical feature should fall within the protection scope of claim 1. For example, replacing 50 parts with 51 parts while keeping other technical features unchanged still falls within the protection scope of claim 1 of this invention.

[0034] The technical feature "3-4 parts of colorant" is derived from the aforementioned explanation and / or the corresponding technical features 3 and 4 parts in Examples 1-5, summarized by the common feature "3-4 parts". Therefore, those skilled in the art can reasonably infer that any point value within the range of 3-4 parts of technical feature should fall within the protection scope of claim 1. For example, replacing 4 parts with 3.5 parts while keeping other technical features unchanged still falls within the protection scope of claim 1 of this invention.

[0035] The technical feature "2.7-3 parts of preservative" is derived from the corresponding technical features 2.7 and 3 parts in the foregoing explanation and / or Examples 1-5, summarized by the common feature "2.7-3 parts". Therefore, those skilled in the art can reasonably infer that any value within the range of 2.7-3 parts of technical feature should fall within the protection scope of claim 1. For example, replacing 2.7 parts with 2.8 parts while keeping other technical features unchanged still falls within the protection scope of claim 1 of this invention.

[0036] The technical feature "the bittering agent is sucrose octaacetate" is derived from the foregoing explanation and / or the corresponding technical feature sucrose octaacetate in Examples 1-5, which is summarized by the common feature "sucrose octaacetate". Therefore, those skilled in the art can reasonably presume that the technical feature sucrose octaacetate should fall within the protection scope of claim 1.

[0037] The present invention has the following beneficial effects: Compared with existing technologies, the present invention has better technical effects in terms of appearance and taste.

[0038] Furthermore, based on the present invention: Based on the comparison of Examples 1-5 and Comparative Examples 1-24, this invention, through the rational selection of thickeners, bittering agents, coloring agents, and sweeteners, achieves new technical effects and provides a compound Scutellaria baicalensis oral liquid placebo with better effects in terms of color, appearance, and taste. The combined technical effect is superior to the sum of the effects of each individual technique. Attached Figure Description

[0039] Figure 1 The effect diagrams of the test drug and comparative examples 20-23 are shown (from left to right: test drug, comparative example 22, comparative example 20, comparative example 23, comparative example 21). Figure 2 This is a cross-sectional view of the filter in Comparative Example 20. Detailed Implementation

[0040] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0041] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all instruments, devices, equipment, reagents, products, etc., used in the embodiments of the present invention are obtained through conventional commercial means.

[0042] The raw materials and manufacturers used in the following examples and comparative examples are shown in Table 1 below.

[0043] Table 1

[0044] Example 1: A placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid By weight, it consists of the following raw materials: Compound Scutellaria baicalensis extract 66.88 parts, maltodextrin 50 parts, sucrose octaacetate 0.5 parts, sucrose 50 parts, steviol glycosides 0.75 parts, caramel color 4 parts, sodium benzoate 3 parts.

[0045] Prepared according to the following method: Take 66.88g of compound Scutellaria baicalensis extract, filter it through 200-mesh silk cloth, add 400mL of purified water, heat to boiling, and obtain compound Scutellaria baicalensis extract solution for later use; take 400mL of purified water, add the above formula amount (1 part is calculated as 1g), sucrose octaacetate, sucrose, and maltodextrin, heat to boiling for 10min to fully dissolve, cool to 40℃, add steviol glycosides, sodium benzoate, and caramel color, stir to fully dissolve, mix evenly, cool to room temperature, add 400mL of the above compound Scutellaria baicalensis extract solution, add purified water to adjust the total volume to 1000mL, stir well, coarsely filter (three layers of filter paper), finely filter (0.8μm filter membrane), fill, and sterilize (105℃, 40 minutes) to obtain the final product.

[0046] Example 2: A placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid By weight, it consists of the following raw materials: Compound Scutellaria baicalensis extract 66.88 parts, maltodextrin 50 parts, sucrose octaacetate 0.5 parts, sucrose 50 parts, steviol glycosides 0.75 parts, caramel color 2 parts, milk chocolate brown 1 part, sodium benzoate 3 parts.

[0047] Prepared according to the following method: Take 66.88g of compound Scutellaria baicalensis extract, filter it through 200-mesh silk cloth, add 400mL of purified water, heat to boiling, and set aside. Take 400mL of purified water, add the above formula amount (1 part is calculated as 1g), sucrose octaacetate, sucrose, and maltodextrin, heat to boiling for 10 minutes to fully dissolve, cool to 40℃, add steviol glycosides, sodium benzoate, caramel color, and milk chocolate brown, stir to fully dissolve, mix evenly, cool to room temperature, add 400mL of compound Scutellaria baicalensis extract solution, add purified water to adjust the total volume to 1000mL, stir well, coarsely filter (three layers of filter paper), finely filter (0.8μm filter membrane), fill into bottles, and sterilize (105℃, 40 minutes) to obtain the final product.

[0048] Example 3: A placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid By weight, it consists of the following raw materials: Compound Scutellaria baicalensis extract 66.88 parts, maltodextrin 50 parts, sucrose octaacetate 0.5 parts, sucrose 50 parts, steviol glycosides 0.75 parts, caramel color 2 parts, lemon yellow 1 part, sodium benzoate 3 parts.

[0049] Prepared according to the following method: Take 66.88g of compound Scutellaria baicalensis extract, filter it through 200-mesh silk cloth, add 400mL of purified water, heat to boiling, and set aside. Take 400mL of purified water, add the above formula amount (1 part is calculated as 1g), sucrose octaacetate, sucrose, and maltodextrin, heat to boiling for 10 minutes to fully dissolve, cool to 40℃, add steviol glycosides, sodium benzoate, caramel color, and lemon yellow, stir to fully dissolve, mix evenly, cool to room temperature, add 400mL of compound Scutellaria baicalensis extract solution, add purified water to adjust the total volume to 1000mL, stir well, coarsely filter (three layers of filter paper), finely filter (0.8μm filter membrane), fill into bottles, and sterilize (105℃, 40 minutes) to obtain the final product.

[0050] Example 4: A placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid By weight, it consists of the following raw materials: Compound Scutellaria baicalensis extract 60 parts, maltodextrin 45 parts, sucrose octaacetate 0.4 parts, sucrose 45 parts, steviol glycosides 0.5 parts, caramel color 4 parts, sodium benzoate 2.7 parts.

[0051] Prepared according to the following method: Take 60g of compound Scutellaria baicalensis extract, filter it through 200-mesh silk cloth, add 400mL of purified water, heat to boiling, and set aside. Take 400mL of purified water, add the above formula amount (1 part is calculated as 1g), sucrose octaacetate, sucrose, and maltodextrin, heat to boiling for 10 minutes to fully dissolve, cool to 40℃, add steviol glycosides, sodium benzoate, and caramel color, stir to fully dissolve, mix evenly, cool to room temperature, add 400mL of compound Scutellaria baicalensis extract solution, add purified water to adjust the total volume to 1000mL, stir well, coarsely filter (three layers of filter paper), finely filter (0.8μm filter membrane), fill into bottles, and sterilize (105℃, 40 minutes) to obtain the final product.

[0052] Example 5: A placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid By weight, it consists of the following raw materials: The ingredients are: 70 parts of compound Scutellaria baicalensis extract, 55 parts of maltodextrin, 0.6 parts of sucrose octaacetate, 54 parts of sucrose, 1 part of steviol glycosides, 4 parts of caramel color, and 3 parts of sodium benzoate.

[0053] Prepared according to the following method: Take 70g of compound Scutellaria baicalensis extract, filter it through 200-mesh silk cloth, add 400mL of purified water, heat to boiling, and set aside. Take 400mL of purified water, add the above formula amount (1 part is calculated as 1g), sucrose octaacetate, sucrose, and maltodextrin, heat to boiling for 10 minutes to fully dissolve, cool to 40℃, add steviol glycosides, sodium benzoate, and caramel color, stir to fully dissolve, mix evenly, cool to room temperature, add 400mL of compound Scutellaria baicalensis extract solution, add purified water to adjust the total volume to 1000mL, stir well, coarsely filter (three layers of filter paper), finely filter (0.8μm filter membrane), fill into bottles, and sterilize (105℃, 40 minutes) to obtain the final product.

[0054] Comparative Example 1 The difference from Example 1 is that maltodextrin is replaced with soluble starch, while the rest is the same as in Example 1.

[0055] Comparative Example 2 The difference from Example 1 is that maltodextrin is replaced with dextrin, and everything else is the same as in Example 1.

[0056] Comparative Example 3 The difference from Example 1 is that 0.75 parts of steviol glycosides are replaced with 0.75 parts of sucrose, and the rest is the same as in Example 1.

[0057] Comparative Example 4 The difference from Example 1 is that 50 parts of sucrose are replaced with 50 parts of steviol glycosides, and the rest is the same as in Example 1.

[0058] Comparative Example 5 The difference from Example 1 is that 0.75 parts of steviol glycosides are replaced with 0.75 parts of lactitol, and the rest is the same as in Example 1.

[0059] Comparative Example 6 The difference from Example 1 is that 0.75 parts of steviol glycosides are replaced with 0.75 parts of sorbitol, and the rest is the same as in Example 1.

[0060] Comparative Example 7 The difference from Example 1 is that 0.5 parts of sucrose octaacetate are replaced with 0.5 parts of bittering, and the rest is the same as in Example 1.

[0061] Comparative Example 8 The difference from Comparative Example 7 is that 0.75 parts of steviol glycosides were replaced with 0.75 parts of lactitol, while the rest were the same as Comparative Example 7.

[0062] Comparative Example 9 The difference from Comparative Example 7 is that 0.75 parts of steviol glycosides were replaced with 0.75 parts of sorbitol, while the rest were the same as Comparative Example 7.

[0063] Comparative Example 10 The difference from Example 1 is that 0.5 parts of sucrose octaacetate are replaced with 0.5 parts of limonene, and the rest is the same as in Example 1.

[0064] Comparative Example 11 The difference from Comparative Example 10 is that 0.75 parts of steviol glycosides were replaced with 0.75 parts of lactitol, and the rest were the same as Comparative Example 10.

[0065] Comparative Example 12 The difference from Comparative Example 10 is that 0.75 parts of steviol glycosides were replaced with 0.75 parts of sorbitol, and the rest were the same as Comparative Example 10.

[0066] Comparative Example 13 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL capsicum oleoresin, and the rest is the same as in Example 1.

[0067] Comparative Example 14 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL patchouli oil, and the rest is the same as in Example 1.

[0068] Comparative Example 15 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL nutmeg oil, and the rest is the same as in Example 1.

[0069] Comparative Example 16 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL ginger oil, and the rest is the same as in Example 1.

[0070] Comparative Example 17 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL chrysanthemum oil, and the rest is the same as in Example 1.

[0071] Comparative Example 18 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL licorice tincture, and the rest is the same as in Example 1.

[0072] Comparative Example 19 The difference from Example 1 is that the 400 mL compound Scutellaria baicalensis extract solution in the preparation method is replaced with 0.1 mL of menthol ice, and the rest is the same as in Example 1.

[0073] Comparative Example 20 The difference from Example 1 is that 4 parts caramel color are replaced with 4 parts sorghum red, and the rest is the same as Example 1.

[0074] Comparative Example 21 The difference from Example 1 is that 4 parts caramel coloring is replaced with 4 parts lemon yellow, and the rest is the same as Example 1.

[0075] Comparative Example 22 The difference from Example 1 is that 4 parts caramel color are replaced with 4 parts milk chocolate brown, and the rest is the same as Example 1.

[0076] Comparative Example 23 The difference from Example 1 is that 4 parts caramel coloring is replaced with 5 parts caramel coloring, and the rest is the same as Example 1.

[0077] Comparative Example 24 The difference from Example 1 is that the mass ratio of sucrose to steviol glycosides is 20:0.5, while the rest is the same as in Example 1.

[0078] Comparative Example 25 The difference from Example 1 is that the mass ratio of sucrose to steviol glycosides is 120:1, while the rest is the same as in Example 1.

[0079] Comparative Example 26 The difference from Example 1 lies in the preparation method, as detailed below: Take 600mL of purified water, add the above formula amount (1 part is calculated as 1g) of sucrose octaacetate, sucrose, and maltodextrin, heat to boiling for 10 minutes to fully dissolve, cool to 40℃, add steviol glycosides, sodium benzoate (2.7g), and caramel color, stir to fully dissolve, mix evenly, cool to room temperature, add 100mL of compound scutellaria oral liquid, add purified water to adjust the total volume to 1000mL, stir well, coarsely filter (three layers of filter paper), finely filter (0.8μm filter membrane), fill into bottles, and sterilize (sterilize at 105℃ for 40 minutes) to obtain the product.

[0080] Detection Example 1 The placebos obtained from the examples and comparative examples were evaluated for appearance, color, taste, and odor using a manual scoring method. Compound Scutellaria baicalensis oral liquid (Heilongjiang Zhenbaodao Pharmaceutical Co., Ltd.) was used as the control sample. Ten evaluators aged 18-50 years were randomly selected and scored the samples by smelling, looking, and tasting. A score of 10 was given for samples that were completely identical to the sample, and a score of 0 was given for samples that were completely different. Evaluators scored the samples within the range of 0-10 based on the actual situation.

[0081] The results are shown in Table 2. Table 2

[0082] The results in Table 2 show that: 1. Thickener screening experiment Appearance evaluation of Example 1 and Comparative Examples 1-2 revealed that Comparative Example 1 exhibited sedimentation and stratification; Comparative Example 2 had an astringent taste.

[0083] 2. Screening experiments for bittering agents and sweeteners Comparative studies of Examples 1, 4, 5 and Comparative Examples 3-12 revealed that the bitterness of the samples containing limonene was significantly weaker than that of Compound Scutellaria baicalensis Oral Liquid; the sweetness of the samples containing lactitol or sorbitol was significantly different from that of the test drug, and they had their own unique sweetness; the taste of the samples containing sucrose octaacetate or bittering and sucrose or steviol glycosides was similar to that of the test drug.

[0084] Selection of bittering agent: The excipients used in placebos should generally meet pharmaceutical standards. Sucrose octaacetate is included in the Chinese Pharmacopoeia and has clear quality requirements. For safety reasons, sucrose octaacetate was selected as the bittering agent.

[0085] Sweetener selection: Sucrose can enhance the taste and texture of the oral liquid, while also increasing its relative density. Steviosides, used as an excipient in the production of the experimental drug, can more closely resemble the taste of the drug. Therefore, sucrose and steviol glycosides were chosen together as sweeteners.

[0086] Comparing Examples 1, 4, 5, 24, and 25, it was found that: Comparative Example 24 was weaker than the test drug in both bitterness and sweetness; Examples 1, 4, and 5 were closer to the test drug in both bitterness and sweetness; and Comparative Example 25 was stronger than the test drug in both bitterness and sweetness.

[0087] 3. Masking agent screening test Volunteers evaluated Example 1 and Comparative Examples 13-19 and found that Comparative Examples 13-19 had a significantly different odor from the test drug (lacking the unique aroma of traditional Chinese medicine). Therefore, they considered adding Compound Scutellaria and Ligusticum Oral Liquid for preparation (as in Comparative Example 26), but the result was that it had an off-odor after sterilization.

[0088] 4. Colorant Screening Experiment Comparative examples 20-23 were examined, such as Figure 1 As shown, Comparative Example 23 is closest to the test drug, therefore caramel color was used in the experiment. Comparative Example 20 was difficult to filter, and residues remained after filtration (such as...). Figure 2 ).

[0089] Detection Example 2 Three hundred and twenty volunteers were selected to evaluate Compound Scutellaria and Lan Oral Liquid and each group of simulated placebos in terms of appearance, color, taste, and smell, according to the requirements of the "Standard for Evaluation of Placebo Simulation Effect of Traditional Chinese Medicine".

[0090] After all evaluators completed the evaluation forms and the data entry and cleaning were finished, the data were unblinded and analyzed by a statistician. The relative ratio (RR) was used as the outcome indicator for independent evaluation. During the analysis, the ordinal rating results were converted into the number of people who judged it as the investigational drug (including those who selected "definitely the investigational drug" and "possibly the investigational drug"). The RR value of Compound Scutellaria baicalensis placebo relative to Compound Scutellaria baicalensis oral liquid was calculated separately. The minimum standard for passing independent evaluation was an RR value of not less than 60% (i.e., relative ratio (RR) ≥ 60%). The calculation formula is as follows: ×100% ×100% The results are shown in Table 3.

[0091] Table 3

[0092] As can be seen from the data in Tables 2 and 3, the placebo prepared in the embodiments of the present invention has the same color, smell and taste as Compound Scutellaria baicalensis and Oral Solution, and patients are less likely to lose their blindness even when exposed to the test drug.

[0093] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid, characterized in that, By weight, it includes 60-70 parts of compound Scutellaria baicalensis extract, 45-55 parts of thickener, 0.4-0.6 parts of bittering agent, 45-55 parts of sweetener, 3-4 parts of colorant and 2.7-3 parts of preservative, wherein the bittering agent is sucrose octaacetate.

2. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 1, characterized in that, By weight, it includes 66.88 parts of compound Scutellaria baicalensis extract, 50 parts of thickener, 0.5 parts of bittering agent, 50.75 parts of sweetener, 4 parts of coloring agent and 3 parts of preservative.

3. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 1, characterized in that, The thickener is maltodextrin.

4. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 1, characterized in that, The sweetener is sucrose and steviol glycosides, with a mass ratio of 45-55:0.5-1.

5. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 4, characterized in that, The mass ratio of sucrose to steviol glycosides is 50:0.

75.

6. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 1, characterized in that, The colorant is a mixture of caramel color, caramel color and milk chocolate brown, or a mixture of caramel color and lemon yellow.

7. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 1, characterized in that, The colorant is caramel color.

8. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 1, characterized in that, The preservative mentioned is sodium benzoate.

9. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral liquid according to claim 2, characterized in that, The thickener is maltodextrin, the sweetener is sucrose and steviol glycosides, the colorant is caramel color, and the preservative is sodium benzoate. By weight, it includes 66.88 parts of compound Scutellaria baicalensis extract, 50 parts of maltodextrin, 0.5 parts of sucrose octaacetate, 50 parts of sucrose, 0.75 parts of steviol glycosides, 4 parts of caramel color, and 3 parts of sodium benzoate.

10. The placebo of compound Scutellaria baicalensis and Scutellaria baicalensis oral solution according to claim 9, characterized in that, The preparation method of the compound Scutellaria baicalensis oral liquid placebo includes the following steps: After filtering the compound Scutellaria baicalensis extract, add water and heat to boiling to obtain a compound Scutellaria baicalensis extract solution for later use. Dissolve the prescribed amounts of sucrose octaacetate, sucrose, and maltodextrin in water, heat to boiling, cool, add steviol glycosides, sodium benzoate, and caramel color, stir until fully dissolved, mix evenly, let stand at room temperature, add the compound Scutellaria baicalensis extract solution, add water to make up the volume, stir evenly, coarsely filter, finely filter, fill, and sterilize to obtain the final product.

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