An oral gel of wogonin and a preparation method thereof

Abstract

The application provides a wogonoside oral gel which is prepared by adding gel excipients to wogonoside extract as an active ingredient, wherein the gel excipients comprise: a bitter taste inhibitor, a sweetening agent; the bitter taste inhibitor comprises: xanthan gum, micronized-i-kappa-carrageenan; the bitter taste inhibitor is used in an amount of not more than 0.5% w / w of the total amount of the gel; and the sweetening agent comprises: sucralose, mogroside, and is used in an amount of 0.3% w / w of the total amount of the gel. The oral gel is used for oral administration, has a fixed shape and volume, presents a weakly flowing gel state, is prepared by mixing and swelling the active ingredient, the gel matrix and excipients, has soft and smooth texture, reduces the risk of laryngeal obstruction and asphyxia, and improves the safety of medicine taking of children, the elderly and other patients with swallowing difficulties.

Description

Technical Field

[0001] This invention relates to an oral gel containing Scutellaria baicalensis. Background Technology

[0002] Traditional Chinese medicine oral liquid preparations are widely used in clinical practice, especially in pediatrics and geriatrics, due to their advantages such as rapid onset of action, accurate dosage, and convenient production. Lanqin Oral Liquid, a compound preparation composed of five classic heat-clearing Chinese herbs—Isatis root, Scutellaria baicalensis, Gardenia, Phellodendron bark, and Sterculia lychnophora—has proven efficacy in clearing heat and detoxifying, relieving sore throat and reducing swelling, and has become a commonly used drug for treating acute pharyngitis, upper respiratory tract infections, and other diseases. Pharmacological studies have confirmed that the active ingredients in this preparation, such as baicalin, geniposide, and berberine, have significant antiviral, antibacterial, anti-inflammatory, and immunomodulatory effects, specifically relieving sore throat, inhibiting pathogen proliferation, and controlling inflammatory responses, resulting in significant clinical efficacy. However, the oral liquid itself has a distinctly unpleasant odor, a strong bitter taste, a lingering bitterness, and a slightly astringent taste, causing many patients, children whose swallowing function is not yet fully developed, and the elderly with diminished swallowing reflexes to develop significant resistance to taking the medication. Insufficient dosage, treatment interruption, or irregular medication due to taste issues not only directly affect clinical efficacy but may also increase the risk of disease recurrence or chronicity due to incomplete treatment. Wu Fan et al., using high-resolution mass spectrometry to characterize the multiple components of Lanqin oral liquid, identified 16 active ingredients, including baicalin, scutellarin, isovitexin, geniposide, palmatine, berberine, magnoflorine, berberine, guanosine, baicalein, adenosine, cytidine, epigallocatechin, gardenin, and chlorogenic acid. Based on the structural characteristics of common bitter substances, it can be inferred that the bitterness in Lanqin oral liquid may be caused by alkaloids, flavonoids, and saponins. Therefore, masking the unpleasant odor and strong bitterness / astringency present in Lanqin oral liquid is a pressing challenge that needs to be overcome.

[0003] Application No.: CN202310560822.4, Invention Title: A Traditional Chinese Medicine Taste-Mask Composition and Its Application in Oral Preparations of Scutellaria baicalensis. This invention provides a traditional Chinese medicine taste-masking composition that resolves the contradiction between the large volume of traditional Chinese medicine compound preparations and the low drug loading of cyclodextrin. It improves the taste-masking effect while reducing the amount of excipients, achieving synergistic effects. The traditional Chinese medicine taste-masking composition includes sulfobutyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin in a mass ratio of 1:1. The composition also contains methyl-β-cyclodextrin and α-cyclodextrin; or it may further contain polymeric-β-cyclodextrin, cationic-β-cyclodextrin, and methyl-β-cyclodextrin. The above-mentioned cyclodextrins and their derivatives, as pharmaceutical excipients, have low production costs and are suitable for industrial promotion. Furthermore, this invention also provides the application of the traditional Chinese medicine taste-masking composition in oral preparations of Scutellaria baicalensis. Although the method disclosed in this document can achieve the purpose of taste masking, its application in the field of traditional Chinese medicine is currently limited and it is not suitable for children, the elderly, or patients with swallowing difficulties. Summary of the Invention

[0004] This invention provides an oral gel containing Scutellaria baicalensis suitable for children or the elderly with swallowing difficulties, and a method for preparing the same.

[0005] This invention provides an oral gel containing Scutellaria baicalensis, which is prepared by adding gel excipients to Scutellaria baicalensis extract as the active ingredient. The gel excipients include: bitterness inhibitors and sweeteners.

[0006] The bitterness inhibitors include xanthan gum and micronized 1-carrageenan; the amount of bitterness inhibitors used does not exceed 0.5% w / w of the total gel volume;

[0007] The sweeteners include sucralose and mogroside, used at 0.3% w / w of the total gel volume.

[0008] The excipients also include peppermint oil.

[0009] The preparation method of the Scutellaria baicalensis extract is as follows:

[0010] Take 250 parts of Scutellaria baicalensis, 300 parts of Isatis indigotica, 300 parts of Gardenia jasminoides, 100 parts of Phellodendron chinense, and 100 parts of Sterculia lychnophora and grind them into coarse powder. Add water and decoct. Filter and concentrate the filtrate to a relative density of 1.15. Set aside for later use. Add chitosan clarifying agent to clarify and obtain Scutellaria baicalensis extract.

[0011] The amount of the gel excipient used is as follows:

[0012] Xanthan gum (XG) 0.2%, micronized ι-carrageenan (Micro-ι-CA) 0.3%, sucralose (TGS) 0.15%, mogroside (MG) 0.15%, peppermint oil (PEO) 0.05%.

[0013] The present invention also provides a method for preparing the above-mentioned Scutellaria baicalensis oral gel, which includes the following steps:

[0014] a. Take 250 parts of Scutellaria baicalensis, 300 parts of Isatis indigotica, 300 parts of Gardenia jasminoides, 100 parts of Phellodendron chinense, and 100 parts of Sterculia lychnophora and grind them into coarse powder. Add water and decoct. Filter and concentrate the filtrate to a relative density of 1.15. Set aside for later use. Add chitosan clarifying agent to clarify and obtain Scutellaria baicalensis extract.

[0015] b. Take the Scutellaria baicalensis extract, heat it to 80 ℃ with a magnetic stirrer, and slowly add the pre-mixed gelling excipients, namely 0.2% xanthan gum and 0.3% micronized carrageenan, while stirring slowly. Then add the sweetener excipients, namely 0.15% sucralose and 0.15% mogroside. After the excipients are completely dissolved and mixed, add 0.05% peppermint oil and finally cool it at room temperature to obtain the final product.

[0016] The present invention also provides the use of the above-mentioned Scutellaria baicalensis oral gel in the preparation of gels for children, the elderly, or patients with dysphagia.

[0017] This invention employs UPLC-MS and molecular docking techniques to analyze the compound composition and key bitter substances in Scutellaria baicalensis extract. Based on the characteristics of these bitter substances, a taste-masking and flavor-correcting method is developed. Volunteer sensory evaluation and electronic tongue measurement are used to screen the flavor-correcting formula through a subjective-objective correlation. Based on this, a novel dosage form, Scutellaria baicalensis oral gel (LQOG), is prepared to further improve the swallowing performance of the drug. The oral gel is intended for oral administration, maintaining a fixed shape and volume, exhibiting a weakly flowing gel state. It is prepared by mixing and swelling the active ingredient with the gel matrix and excipients. Its soft and smooth texture reduces the risk of choking and suffocation, improving the safety of medication administration for children, the elderly, and other patients with swallowing difficulties. Attached Figure Description

[0018] Figure 1 Schematic diagram of IDDSI swallowing function classification and assessment method;

[0019] Figure 2 Results of docking between bitter substances and receptor molecules;

[0020] Figure 3 morphological diagrams of different gel excipient formulations;

[0021] Figure 4 Sensory evaluation results of volunteers using Scutellaria baicalensis oral gel;

[0022] Figure 5 Results of electronic tongue measurement. Detailed Implementation

[0023] Example 1: Preparation of the Scutellaria baicalensis oral gel of the present invention

[0024] (1) Preparation of Scutellaria baicalensis extract:

[0025] ① Extraction of concentrated solution: Crush 250 g of Scutellaria baicalensis, 300 g of Isatis indigotica, 300 g of Gardenia jasminoides, 100 g of Phellodendron chinense, and 100 g of Sterculia lychnophora into coarse powder, place them in a beaker, add an appropriate amount of water and decoct 3 times, the first time for 2 hours, the second and third times for 1 hour each, filter and combine them separately, place them in a designated container, concentrate to a relative density of 1.15, and set aside for later use.

[0026] ② Preparation of chitosan clarifying agent: Weigh 1g of chitosan, add 50mL of water and 2mL of glacial acetic acid, stir well, heat to 80℃, add water to 100mL, keep warm for 45min, and set aside.

[0027] ③ Oral liquid preparation: Add the prepared chitosan clarifying agent to the concentrate, heat in a 70 ℃ water bath while stirring for 30 min, remove and let stand at 0~5 ℃. Take the supernatant, add an appropriate amount of purified water to adjust the volume to about 6 times the amount of medicinal material, bottle, sterilize, and the finished product is obtained.

[0028] (2) Preparation of Scutellaria baicalensis oral gel:

[0029] Take 10 mL of Scutellaria baicalensis extract, heat it to 80 ℃ with a magnetic stirrer, and slowly add the pre-mixed gelling excipients, namely 0.2% xanthan gum and 0.3% micronized carrageenan, while stirring slowly. Then add the sweetener excipients, namely 0.15% sucralose and 0.15% mogroside. After the excipients are completely dissolved and mixed, finally add 0.05% peppermint oil and cool at room temperature to obtain the final product.

[0030] Example 2: Screening test of the gel excipients of the present invention

[0031] 1. Experimental Instruments and Materials

[0032] Experimental instruments: BT25S type 1 / 100,000 electronic analytical balance (Sartorius GmbH, Germany), UPR-11-5T type pure water system (Sichuan Youpu Ultrapure Technology Co., Ltd., China); 85-2A type digital display constant temperature and speed measuring magnetic stirrer (Changzhou Yuexin Instrument Manufacturing Co., Ltd.).

[0033] Experimental materials: Isatis root, Scutellaria baicalensis, Gardenia jasminoides, Phellodendron chinense, and Sterculia lychnophora (all purchased from Hehuachi Traditional Chinese Medicine Market, Chengdu, Sichuan Province); ι-carrageenan (batch number: 20220401), sulfate ester content 24.4%, purchased from Qingdao Longrun Food Co., Ltd.; xanthan gum (batch number: C12899675), purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; sodium carboxymethyl cellulose (batch number: 20230322), purchased from Henan Qinuo Food Ingredients Co., Ltd.; sodium alginate (batch number: 20221118), purchased from Qingdao Longrun Food Co., Ltd.; gellan gum (batch number: 20... Items 221ND103 (batch number: 221ND103) were purchased from Qingdao Longrun Food Co., Ltd.; hydroxypropyl methylcellulose (batch number: 20230510) was purchased from Henan Food Ingredients Co., Ltd.; konjac gum (batch number: 220601130301) was purchased from Hubei Qiangsen Konjac Technology Co., Ltd.; locust bean gum (batch number: SK30031364) was purchased from Qingdao Longrun Food Co., Ltd.; carboxymethyl chitosan (batch number: G2305657) was purchased from Aladdin Reagent (Shanghai) Co., Ltd.; pectin (batch number: C12846999) was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.; mogrosides (batch number: LHGE-250217) were purchased from Hunan Huacheng Biological Resources Co., Ltd.; sucralose (batch number: Y25061501) was purchased from Yancheng Jiekang Sucralose Manufacturing Co., Ltd. Fruit flavorings (batch numbers: 124539, 124540, 124541, 124542, 124543, 124544, 124545) and liquid essential oils (batch numbers: 125013, 125014, 125015) were all purchased from Senxin Flavor & Pigment Technology (China) Co., Ltd.

[0034] 2 Experimental Methods

[0035] 2.1 UPLC-MS analysis of Scutellaria baicalensis extract

[0036] 2.1.1 Chromatographic conditions

[0037] The chromatographic column was an ACQUITY UPLC BEH C18 1.7 μm; the mobile phase was 0.1% formic acid aqueous solution (A)-acetonitrile (B), with gradient elution (0~2 min, 95% A; 2~5 min, 92%→85% A; 5~7 min, 85%→70% A; 7~10 min, 70%→65% A; 10~11 min, 65%→60% A; 11~12 min, 60%→30% A; 12~13 min, 30%→5% A; 13~15 min, 5% A; 15~15.1 min, 5%→95% A; 15.1~18 min, 95% A); the flow rate was 0.3 mL / min; the column temperature was 40 ℃; the total run time was 18 min; and the injection volume was 5 μL.

[0038] 2.1.2 Mass Spectrometry Conditions

[0039] Desolventizing gas: nitrogen (600 L / h); capillary voltage: 2.5 kV (positive ion mode) and 2.0 kV (negative ion mode); ion source: ESI source; ion source temperature: 150 ℃; desolventizing temperature: 550 ℃. Quantitative analysis was performed using multiple reaction detection (MRM).

[0040] 2.1.3 Preparation of test solution

[0041] Accurately measure 3 mL of Scutellaria baicalensis extract and place it in a 100 mL volumetric flask. Dissolve and dilute to the mark with methanol, and shake well. Filter the solution through a 0.22 μm filter membrane before injection for analysis.

[0042] 2.1.4 Data Processing

[0043] The collected raw data were imported into Compound Discoverer 3.0 software, and the identification process for unknown compounds was established using the software wizard and method templates. After peak alignment and extraction, molecular formula fitting was performed on the extracted molecular ion chromatographic peaks and isotope peaks. Secondary fragment spectra were matched with the mzVault and mzCloud online databases, with matching parameters set as follows: peak area not less than 100,000, mass deviation not exceeding 5 ppm, and matching degree greater than 80%. Finally, the compounds were identified by combining compound information from the databases and relevant literature.

[0044] 2.2 Prediction of Bitter Components in Scutellaria baicalensis Extract Based on Data Mining Analysis

[0045] 2.2.1 Molecular docking technology for predicting bitter substances and bitter taste receptors

[0046] UPLC-MS results of Scutellaria baicalensis extract were analyzed to predict its bitter compounds and screen for high-affinity bitter receptors. Eight major bitter compounds were identified: 6-O-methylbaicalin, apigenin, baicalin, berberine, cryptotanshinone, wogonin, isoleucine, and geniposide. Their common broad-spectrum bitter receptors, TAS2R39, TAS2R14, and TAS2R46, were selected as docking bitter receptors. The MM2 algorithm in ChemBio3D 14.0 was used to minimize the energy of the bitter compounds. After pretreatment including receptor hydrogenation, dehydration, and charge addition, as well as ligand hydrogenation and charge addition, a semi-flexible molecular docking was performed using a genetic algorithm in Autodock software to calculate the binding energy between the receptor and the bitter compounds. The optimal configuration obtained from the docking was plotted and displayed using PyMol 14.0 software.

[0047] 2.3 Screening of Scutellaria baicalensis oral gel formulation

[0048] 2.3.1 Preparation of Scutellaria baicalensis oral gel

[0049] Sample preparation: Take 10 mL of Scutellaria baicalensis extract, heat it to 80 ℃ with a magnetic stirrer, and slowly add the pre-mixed sweetener and gelling excipients while stirring slowly. After the excipients are completely dissolved and mixed, cool it at room temperature to obtain the sample.

[0050] Gel excipient screening: Gel excipients with good bitterness inhibition and gel morphology were screened from 10 commonly used excipients, including konjac gum, sodium carboxymethyl cellulose, locust bean gum, pectin, gellan gum, ι-carrageenan, sodium alginate, xanthan gum, carboxymethyl chitosan, and hydroxypropyl methylcellulose, as candidates. Based on previous laboratory research, micronized ι-carrageenan excipients were included in the screening to ensure a broader and more comprehensive screening scope.

[0051] Screening of excipient ratio and total amount for gel excipients: Through preliminary experiments, XG and Micro-ι-CA were selected as superior excipients. The two excipients were compounded and three gradients were set up. The optimal excipient ratio and total amount for gel excipients were screened based on the degree of bitterness inhibition and oral gel form.

[0052] Table 1 Screening of gel excipient ratios and total amounts

[0053]

[0054] Sweetener excipient selection: Due to the strong initial bitterness and aftertaste of Scutellaria baicalensis extract, based on the optimal gel excipient ratio, a high-concentration sweetener TGS and a sweet-aftertaste-promoting MG were selected for combination to effectively suppress the bitterness of the oral liquid. Three gradients were set up to screen the optimal sweetener ratio and total amount based on the degree of bitterness suppression.

[0055] Table 2 Screening of Sweetener Proportion and Total Amount

[0056]

[0057] Fragrance selection: Common fruit flavorings and essential oils were screened to mask unpleasant odors. This invention selected strawberry, blueberry, lemon, peach, sweet orange, chocolate, and tangerine peel flavorings and peppermint, sweet orange, and lemon essential oils, and selected the optimal formula through sensory evaluation by volunteers (S7).

[0058] The formulas for S1-S7 are as follows:

[0059] S1: 0.2% xanthan gum + 0.2% micronized carrageenan

[0060] S2: 0.2% xanthan gum + 0.3% micronized carrageenan

[0061] S3: 0.2% xanthan gum + 0.4% micronized carrageenan

[0062] S4: 0.2% xanthan gum + 0.3% micronized α-carrageenan + 0.1% sucralose + 0.15% mogrosides

[0063] S5: 0.2% xanthan gum + 0.3% micronized α-carrageenan + 0.15% sucralose + 0.15% mogrosides

[0064] S6: 0.2% xanthan gum + 0.3% micronized 1-carrageenan + 0.2% sucralose + 0.15% mogrosides

[0065] S7: 0.2% xanthan gum + 0.3% micronized α-carrageenan + 0.15% sucralose + 0.15% mogroside + 0.05% peppermint oil

[0066] 2.3.2 Volunteer Sensory Evaluation

[0067] The inclusion criteria for volunteers are as follows: age 20-28 years; no history of severe allergies, hereditary diseases, cholecystitis, or oral and pharyngeal diseases; no smoking, drinking, or other unhealthy lifestyle habits. A standard taste solution was prepared using quinine sulfate (bitter), tannic acid (astringent), citric acid (acidic), capsaicin (spicy), and sucrose (sweet) to initially screen volunteers' taste recognition abilities. Only those with normal taste function were eligible for standardized training. The training used five concentration gradients of quinine sulfate solutions (0, 0.05, 0.3, 0.5, and 1 mg / mL) as bitterness references, corresponding to bitterness scores of 0, 2.5, 5, 7.5, and 10, respectively representing no bitterness, slight bitterness, noticeable bitterness, severe bitterness, and intense bitterness. Volunteers needed to master the bitterness intensity levels and scores corresponding to each concentration solution. A single-blind test was then conducted, where one sample was randomly selected from the five bitterness standard solutions for volunteers to taste. Those who answered correctly passed the test. All volunteers voluntarily signed informed consent forms, and all procedures performed on the volunteers were approved by the Medical Ethics Committee of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. (Approval No.: 2024KL-090)

[0068] Sample preparation: Take 200 mL of Scutellaria baicalensis extract, heat it to 80 ℃ with a magnetic stirrer, and slowly add the pre-mixed sweetener and gelling excipients while stirring slowly. The optimal ratio of gelling excipients and sweeteners was screened by single-factor screening.

[0069] 2.3.3 Evaluation of Electronic Tongue

[0070] Preparation of reference solution: Accurately weigh 2.24 g potassium chloride and 0.05 g tartaric acid, add 500 mL distilled water, stir to dissolve, transfer to a 1000 mL volumetric flask, and make up to volume.

[0071] Preparation of positive electrode cleaning solution: Accurately weigh 7.46 g of potassium chloride, add 500 mL of distilled water, stir to dissolve, accurately add 300 mL of anhydrous ethanol, and while stirring, add 0.56 g of accurately weighed potassium hydroxide. After dissolving, transfer to a 1000 mL volumetric flask and make up to volume.

[0072] Preparation of negative electrode cleaning solution: Accurately weigh 300 mL of anhydrous ethanol, shake and mix with 500 mL of distilled water, add 8.3 mL of concentrated hydrochloric acid, stir and mix, then transfer to a 1000 mL volumetric flask and make up to volume.

[0073] Preparation of test solution: Scutellaria baicalensis extract was diluted 8 times and different amounts of gelling excipients and sweeteners were added to prepare Scutellaria baicalensis oral gel as an electronic tongue evaluation sample.

[0074] Electronic tongue testing method: The electrode is cleaned in the cleaning solution for 90 seconds and then cleaned twice with the reference solution. The sensor is zeroed at the equilibrium position for 30 seconds. After reaching equilibrium, the test begins and lasts for 30 seconds. The electrode is briefly cleaned in two sets of reference solutions for 3 seconds each. The sensor is then inserted into a new reference solution for a 30-second aftertaste test. This cycle is repeated 4 times. The first cycle is discarded, and the average of the last three tests is taken as the test result.

[0075] 2.3.4 Swallowing performance

[0076] Refer to the traffic testing methods of the IDSI framework ( Figure 1 To evaluate the swallowing performance of each compound formulation: Take a 10mL syringe, fix it vertically, and block the lower end with your finger. Add the sample to be tested until the upper liquid level is level with the 10mL mark. Remove your finger when the timer starts, observe the flow behavior of each sample within 10 seconds, and record the amount of gel remaining in the syringe when the timer ends.

[0077] 2.3.5 Weighted Algorithm

[0078] Box plots were used to perform iterative testing and outlier removal on the oral data. The data after outlier removal were calculated as follows:

[0079] The formula for calculating the bitterness score (I) is shown in Formula 1-1:

[0080] I = (I1 + I2 + I3 + ... + I) n ) / n (Formula 1-1)

[0081] Where I1, I2, …, I n The bitterness value is given to each volunteer, and n is the number of volunteers who participated in the sensory evaluation.

[0082] The formulas for calculating the improvement in bitterness, sweetness, and astringency (∆I%) are as shown in Formula 1-2:

[0083] ∆I%=[(I a -I b ) / I a ]×100% (Formula 1-2)

[0084] Among them, I a To score the bitterness, sweetness, and astringency of the sample before flavoring, I b The bitterness, sweetness, and astringency of the samples were scored after flavoring. Quantitative scores were assigned based on the degree of bitterness improvement, swallowing performance, and appearance of each compound sample. The specific scoring criteria are shown in Table 3.

[0085] Table 3 Weighted Algorithm Scoring Indicators

[0086]

[0087] The formula for calculating the weighted total is shown in Formula 1-3:

[0088] Total value = Y1×20%+Y2×20%+Y3×15%+Y4×10%+Y5×15%+Y6×20% (Formula 1-3)

[0089] Among them, Y1 is the improvement score of initial bitterness, Y2 is the improvement score of aftertaste bitterness, Y3 is the improvement score of sweetness, Y4 is the improvement score of astringency, Y5 is the swallowing performance score, and Y6 is the character score.

[0090] 2.4 Data Processing

[0091] Compounds and related bitter substances in Scutellaria baicalensis extract were identified using Compound Discoverer 3.0 and the BitterX database (https: / / mdl.shsmu.edu.cn / BitterX / ). Data were processed, analyzed, and plotted using software such as Origin2024, SPSS 24.0, ChemBio3D14.0, Autodock, and PyMol 14.0. For the data in the figures, error bars represent the standard deviation.

[0092] 3 Experimental Results

[0093] 3.1 Results of compound composition analysis of Scutellaria baicalensis extract

[0094] UPLC-MS analysis was performed on the extract of *Scutellaria baicalensis* to determine its compound composition. A total of 54 compounds were detected, and the results are shown in Table 4. The results indicate that the chemical composition of *Scutellaria baicalensis* extract is complex and diverse, encompassing multiple active ingredients and metabolism-related substances. Ketones were the most numerous, totaling 16, accounting for 30.2% of the identified compounds. These mainly include flavonoids such as baicalin and wogonin, which is consistent with the chemical characteristics of *Scutellaria baicalensis* and *Gardenia jasminoides* in the formula and is one of the material bases for the heat-clearing and detoxifying effects of this preparation. Nitrogen-containing compounds totaled 17, accounting for 32.1% of the total, including alkaloids such as berberine and amino acid derivatives. In addition, the analysis also revealed the presence of 4 sugar compounds, 6 acid compounds, and 4 amino acids. These components may participate in regulating the taste, stability, or in vivo metabolic processes of the preparation; their specific sources and pharmacological effects require further investigation.

[0095] Table 4. Compound analysis of Scutellaria baicalensis extract.

[0096]

[0097]

[0098]

[0099]

[0100]

[0101]

[0102] Note: "-" in the table indicates that the data for that part is not yet clear. a represents amino acids; b represents sugars; c represents aldehydes; d represents ketones; e represents acids; f represents nitrogen-containing compounds; g represents ethers; and h represents esters.

[0103] 3.2 Analysis of Molecular Docking Results

[0104] The molecular docking results of the bitterness-contributing components in LQOL, including 6-O-methylbaicalin, apigenin, baicalin, berberine, cryptotanshinone, wogonin, isoleucine, and geniposide, with bitterness receptors TAS2R14, TAS2R39, and TAS2R14 are as follows: Figure 2 As shown in the figure. It is generally believed that the greater the absolute value of the binding energy between bitter components and bitter taste receptors, the stronger the binding force between them. An absolute value of binding energy > 5 kcal / mol indicates a strong binding ability. The binding energies of apigenin to TAS2R14 and TAS2R46 receptors were -5.51 kcal / mol and -5.8 kcal / mol, respectively; those of baicalin to TAS2R14 and TAS2R46 were -5.74 kcal / mol and 5.73 kcal / mol, respectively; those of berberine to TAS2R14, TAS2R39, and TAS2R14 were -6.58 kcal / mol, -7.06 kcal / mol, and -7.26 kcal / mol, respectively; those of cryptotanshinone to TAS2R14, TAS2R39, and TAS2R14 receptors were -7.73 kcal / mol, -7.11 kcal / mol, and -7.9 kcal / mol, respectively; and those of baicalin to TAS2R14, TAS2R39, and TAS2R14 receptors were -6.09 kcal / mol and -6.09 kcal / mol, respectively. The values ​​of kcal / mol, -6.12 kcal / mol, and 6.92 kcal / mol indicate that it has a strong binding capacity. Therefore, the compounds in Scutellaria baicalensis extract that produce bitterness are apigenin, baicalin, berberine, cryptotanshinone, and wogonin, and the -OH or -O- groups in their structures are important groups that contribute to the bitterness of Scutellaria baicalensis extract.

[0105] Table 5. Results of Molecular Docking Binding Energy

[0106]

[0107] 3.3 Results of the screening of Scutellaria baicalensis oral gel formulation

[0108] 3.3.1 Screening of gel excipients

[0109] Screening was conducted on 10 common gels, and the results are shown in Table 6. ι-carrageenan and XG exhibited good bitterness-inhibiting effects, but the gel formed by ι-carrageenan was hard and brittle with almost no flowability, resulting in low patient acceptance. Existing research reports that chemical modification can improve the gel properties of carrageenan. Our research group previously micronized carrageenan to investigate its physical and chemical changes. The results showed that micronization technology, without altering the functional groups and molecular skeleton of carrageenan, can not only reduce the hardness of the carrageenan gel but also improve water-holding capacity, swallowing performance, mouthfeel, and bitterness-inhibiting effect. Based on this, this invention included Micro-ι-CA in the screening scope. The screening results are as follows: among the 11 gel excipients, XG and Micro-ι-CA showed strong flowability and significant bitterness-inhibiting effects, and can be used as excipients for preparing LQOG. Since Micro-ι-CA can enhance the dispersibility of XG, and both have a certain inhibitory effect on bitter substances in LQOG, it is advisable to combine the two to reduce the bitterness of LQOG while making the excipients more uniformly mixed, thus exerting a synergistic effect.

[0110] Table 6 Screening of 11 Gel Excipients

[0111]

[0112] Depend on Figure 3 It was found that when the total amount of XG and Micro-ι-CA exceeded 0.5%, the oral gel of Scutellaria baicalensis had poor flowability, making it unsuitable for children, the elderly, and other people with swallowing difficulties, potentially posing risks such as choking and coughing. Considering both its bitterness suppression and gel flowability, the optimal gel formulation for preparing the oral gel of Scutellaria baicalensis was selected as an XG to Micro-ι-CA ratio of 0.2%:0.3% and a total gel content of 0.5%.

[0113] Preliminary experiments screened out two sweeteners: TGS and MG. TGS is approximately 600 times sweeter than sucrose, with a pure sweetness, primarily improving the peak bitterness of LQOG. MG is 150-300 times sweeter than sucrose, with a longer-lasting sweetness, primarily improving the aftertaste of LQOG. The combination of the two synergistically improves bitterness. Regarding masking the unpleasant herbal flavor in the oral gel, preliminary results showed that essential oils, due to their stronger aroma, were more effective than liquid fragrances. Therefore, a trace amount of peppermint essential oil was chosen to mask the unpleasant odor in LQOG.

[0114] 3.3.1 Analysis of Volunteer Sensory Evaluation Results

[0115] According to volunteer evaluations, the original extract of Scutellaria baicalensis had a high bitterness score of 7.08, a bitter aftertaste score of 5.46, a sweetness score of 2.17, and an astringent score of 2.33. In the gel dosage screening group (S1~S3), the bitterness, bitter aftertaste, and astringent scores of sample S2 decreased to 4.29, 2.96, and 1.54, respectively, and the sweetness score was 3.75, with improvements of 39.38%, 45.82%, and 33.83%, respectively, and an increase in sweetness of 42.4%. This was significantly better than sample S1, with corresponding improvement rates of 6.25%, 3.83%, and 21.32%, and an increase in sweetness of 24.87%. Therefore, the optimal gel dosage ratio is 0.2%:0.3% for XG and Micro-ι-CA, which achieves a nearly 50% improvement in bitterness and bitter aftertaste while maintaining a good gel morphology. In the sweetener dosage screening group (S4~S6), the bitterness, aftertaste, and astringency scores of sample S5 decreased to 2.88, 2.5, and 1.13, respectively, while the sweetness score was 3.58, with improvements of 59.39%, 54.21%, and 51.72%, respectively, and a sweetness increase of 39.72%, significantly better than sample S4. The corresponding improvement rates were 29.97%, 63.37%, and 39.20%, respectively, with a sweetness increase of 51.09%. Therefore, the optimal sweetener dosage ratio is 0.15%:0.15%. Sample S7, based on the optimal ratio of gelling excipients and sweeteners, had a trace amount of 0.05% peppermint essential oil added. Data showed that its bitterness, aftertaste, and astringency scores decreased to 1.58, 1.54, and 0.67 respectively, while the sweetness score was 4.08, representing improvements of 77.64%, 71.77%, and 71.39% respectively, and an increase in sweetness of 47.10%. The improved bitterness, aftertaste, and astringency scores by peppermint essential oil were further enhanced, possibly due to its ability to lower tongue surface temperature and inhibit bitterness perception. This formulation improved unpleasant tastes in LQOG by over 70%, appropriately increased sweetness, and the peppermint aroma significantly improved the herbal taste in the oral gel. The combined improvement in taste and aroma significantly enhanced the palatability of the Lanqin oral gel (e.g., ...). Figure 4 (As shown).

[0116] 3.3.2 Analysis of Electronic Tongue Evaluation Results

[0117] The electronic tongue sensor is essentially an electrochemical detector. Peppermint essential oil may cause drift or abnormal fluctuations in the sensor's potential or current signal. This signal may be incorrectly interpreted by the system as a "bitter" or "astringent" taste, or even an unrecognizable noise signal. Therefore, this experiment selected samples S1-S6 for electronic tongue measurement to further screen and verify the amount and ratio of gel excipients and sweeteners. The results are as follows: Figure 5As shown, the original extract of Scutellaria baicalensis had a high bitterness score of 12.28, a bitter aftertaste score of 3.59, a sweetness score of 3.5, and an astringent score of 14.91. In the gel dosage screening group (S1~S3), the bitterness, bitter aftertaste, and astringent scores of sample S2 decreased to 8.23, 2.17, and 13.41, respectively, and the sweetness score was 3.61, with improvements of 32.95%, 39.65%, and 10.06%, respectively, and an increase in sweetness of 3.05%, which was higher than that of sample S1, with corresponding improvements of 27.82%, 29.71%, and 9.61%, and an increase in sweetness of 2.5%. In the sweetener dosage screening groups (S4~S6), the bitterness, aftertaste, and astringency scores of sample S5 decreased to 7.83, 0.92, and 13.44, respectively, while the sweetness score was 3.95, representing improvements of 36.21%, 74.37%, and 9.86%, respectively, with a sweetness increase of 11.47%, higher than sample S4, whose corresponding improvements were 29.34%, 61.93%, and 9.52%, respectively, with a sweetness increase of 4.8%. The optimal ratio of XG to Micro-ι-CA was 0.2%:0.3%, and the optimal ratio of CTS to MG was 0.15%:0.15%, consistent with the sensory evaluation results from volunteers.

[0118] 3.3.3 Weighted Algorithm for Selecting the Optimal Recipe

[0119] This invention aims to improve the overall palatability and swallowing compliance of LQOG. It comprehensively evaluates multiple indicators, including bitterness, aftertaste, sweetness, astringency, swallowing performance, and properties, to screen for the optimal preparation formula. The results are shown in Table 7, where bitterness, aftertaste, and properties are the key factors affecting the overall taste. Considering that the bitterness and aftertaste of LQOG raw materials are quite prominent, simply increasing the amount of sweetener can easily lead to an uncoordinated blending of sweetness and bitterness, resulting in a separate sweet and bitter taste. Therefore, a balance between sweetness and bitterness can be explored, significantly alleviating bitterness while providing a moderate sweetness. Furthermore, LQOG is suitable for children and the elderly who may have swallowing difficulties. An overly firm gel may pose a choking risk, while an overly thin texture will affect the taste experience and drug adhesion. Therefore, a gel with moderate consistency is chosen, balancing good flowability and taste. Based on the comprehensive experimental results, the S7 formulation achieved the highest overall evaluation score, and its composition was determined to be: 0.3% Mircor-ι-CA + 0.2% XG + 0.15% TGS + 0.15% MG + 0.05% PEO.

[0120] Table 7 Results of the weighted algorithm

[0121]

[0122] 4. Summary and Discussion

[0123] The results of this chapter indicate that the main components of Scutellaria baicalensis extract are nitrogen-containing compounds and ketones, among which geniposide, baicalin, baicalein, and wogonin are the main active ingredients. By screening bitter compounds and corresponding bitter receptors in a database and combining this with molecular docking technology, key bitter substances in Scutellaria baicalensis extract were identified: berberine, cryptotanshinone, and wogonin. The -OH or -O- groups in their structures are important groups contributing to the bitterness of Scutellaria baicalensis extract.

[0124] To address the unpleasant odor and persistent bitterness associated with Scutellaria baicalensis extract, this study screened 10 common gelling excipients, initially identifying carrageenan and xanthan gum as the superior excipients. Based on previous laboratory research, carrageenan was processed using micronization technology to enhance its bitterness-masking effect and optimize the oral gel's morphology, giving it a certain degree of fluidity and reducing the risk of choking when swallowed by children and the elderly. Based on a comprehensive analysis of volunteer sensory evaluations, electronic tongue measurements, and a series of swallowing performance and appearance assessments, the optimal formulation for Scutellaria baicalensis oral gel was determined to be: 0.3% Mircor-1-CA + 0.2% XG + 0.15% TGS + 0.15% MG + 0.05% PEO. The resulting LQOG (Limited-Quality Ointment) has a mild, refreshing minty flavor, a noticeable sweetness upon entry, a moderate sweet-bitter taste, a slightly sweet aftertaste, almost no bitterness, and appropriate fluidity, thus improving patient compliance.

Claims

1. A kind of Scutellaria baicalensis oral gel, characterized in that: It is prepared by adding gelling excipients, with Scutellaria baicalensis extract as the active ingredient. The gelling excipients include: bitterness inhibitors and sweeteners. The bitterness inhibitors include xanthan gum and micronized 1-carrageenan; the amount of bitterness inhibitors used does not exceed 0.5% w / w of the total gel volume; The sweeteners include sucralose and mogroside, used at 0.3% w / w of the total gel volume.

2. The Scutellaria baicalensis oral gel according to claim 1, characterized in that: The excipients also include peppermint oil.

3. The Scutellaria baicalensis oral gel according to claim 2, characterized in that: The preparation method of the Scutellaria baicalensis extract is as follows: Take 250 parts of Scutellaria baicalensis, 300 parts of Isatis indigotica, 300 parts of Gardenia jasminoides, 100 parts of Phellodendron chinense, and 100 parts of Sterculia lychnophora and grind them into coarse powder. Add water and decoct. Filter and concentrate the filtrate to a relative density of 1.

15. Set aside for later use. Add chitosan clarifying agent to clarify and obtain Scutellaria baicalensis extract.

4. The Scutellaria baicalensis oral gel according to any one of claims 1-3, characterized in that: The amount of the gel excipient used is: Xanthan gum (XG) 0.2%, micronized ι-carrageenan (Micro-ι-CA) 0.3%, sucralose (TGS) 0.15%, mogroside (MG) 0.15%, peppermint oil (PEO) 0.05%.

5. A method for preparing the Scutellaria baicalensis oral gel according to any one of claims 1-4, characterized in that: It includes the following steps: a. Take 250 parts of Scutellaria baicalensis, 300 parts of Isatis indigotica, 300 parts of Gardenia jasminoides, 100 parts of Phellodendron chinense, and 100 parts of Sterculia lychnophora and grind them into coarse powder. Add water and decoct. Filter and concentrate the filtrate to a relative density of 1.

15. Set aside for later use. Add chitosan clarifying agent to clarify and obtain Scutellaria baicalensis extract. b. Take the Scutellaria baicalensis extract, heat it to 80 ℃ with a magnetic stirrer, and slowly add the pre-mixed gelling excipients, namely 0.2% xanthan gum and 0.3% micronized carrageenan, while stirring slowly. Then add the sweetener excipients, namely 0.15% sucralose and 0.15% mogroside. After the excipients are completely dissolved and mixed, add 0.05% peppermint oil and finally cool it at room temperature to obtain the final product.

6. The use of the Scutellaria baicalensis oral gel according to any one of claims 1-4 in the preparation of a gel for children, the elderly, or patients with dysphagia.

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