A processed dried tangerine peel product, its preparation method and uses

Abstract

This invention belongs to the field of traditional Chinese medicine processing technology, specifically relating to a processed tangerine peel product, its preparation method, and its uses. The processed tangerine peel product of this invention is prepared from the following raw materials in the indicated weight ratios: 6-48 parts tangerine peel, 1.5-12 parts fennel, 1.5-12 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum pulp, 0.1875-1.5 parts sandalwood, and 0-24 parts coarse salt. This invention revives and clarifies the processing technology of "processed tangerine peel," optimizes the selection of tangerine peel raw materials, and optimizes the amount of water added, soaking time, decoction time, and number of decoctions during the decoction process. The water content of the intermediate product of processed tangerine peel before mixing with powder after decoction can maximize the preservation of the chemical components of the processed tangerine peel, significantly improve the quality of the finished product, and digitize and standardize the ancient processing technology of processed tangerine peel, making it suitable for large-scale industrial production. It protects and explores the unique processing techniques of tangerine peel, a traditional Chinese medicine from Sichuan Province, which is conducive to the inheritance and innovation of traditional Chinese medicine processing techniques and the protection of tangerine peel germplasm resources.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine processing, and particularly relates to a legalized tangerine peel processed product, its preparation method and uses. Background Art

[0002] Tangerine peel is the dried ripe pericarp of the citrus plant Citrus reticulata Blanco and its cultivated varieties. It has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm, and is used for abdominal distension, anorexia, vomiting and diarrhea, cough with copious phlegm. The cultivated varieties of tangerine peel mainly include Citrus reticulata ‘Chachi’ (Guangdong tangerine peel), Citrus reticulata‘Dahongpao’, Citrus reticulata ‘Unshiu’, Citrus reticulata‘Tangerina’.

[0003] In terms of drug quality, in actual use, as long as it is the peel of citrus and its cultivated varieties, it is used as tangerine peel, resulting in a large number of sources of tangerine peel. In the processing of tangerine peel slices and drug production, the source is not differentiated, which causes certain difficulties in the quality control and traceability of drugs.

[0004] In terms of processing, as a common traditional Chinese medicine that can be used both as medicine and food, tangerine peel has a very wide range of applications and there are also many processing methods. The processing methods in past dynasties include cleaning, cutting, frying, baking, boiling, steaming, carbonizing, stir-frying with bran, wine processing, honey processing, processing with rice water, vinegar processing, processing with children's urine, black bean processing, ginger processing, salt processing, croton processing, carp skin processing, alum processing, rice processing, flour processing, cyperus processing, etc., more than 20 kinds. And the modern processing methods are mainly included in local processing specifications such as cleaning, cutting, pulverizing, carbonizing by frying, steaming, stir-frying with bran, stir-frying, stir-frying with earth, honey processing, salt processing, stir-frying with bran, vinegar processing, etc.

[0005] Legalized tangerine peel is a characteristic processed variety of tangerine peel. There is no standard in China for its processing method. This variety has a relatively clear historical evolution of processing. At present, it is still seen in various empirical prescriptions and treatises. The processing of legalized tangerine peel was first seen in the "Prescriptions of the Imperial Pharmacy" in the Yuan Dynasty. Many medical books or classic works on Chinese materia medica such as the "General Prescription of Universal Relief", "Classified Collection of Medical Prescriptions", "Song's Health Preservation", "Recipe for Planting Apricots", "Classified Prescriptions in the Standards for Diagnosis and Treatment", "Complete Works of Jingyue", "New Compilation of Materia Medica" in later generations all have records on "legalized tangerine peel". By sorting out the processing methods of "legalized tangerine peel" in different historical periods, it is found that in different periods, it is based on the medicinal flavors and processing methods recorded in the "Prescriptions of the Imperial Pharmacy".

[0006] The technical solution provided by the inventor is mainly based on the record of processed tangerine peel in the Yuan Dynasty's *Imperial Pharmacy Prescriptions*: "Half a catty of tangerine peel (remove the pith, 4 taels, cut into strips), 2 taels of fennel, 4 taels of rock salt, 2 taels of licorice root (roasted), half a tael of dried ginger, half a tael of dried plum flesh, and 2.5 mace of white sandalwood. Except for the tangerine peel, grind everything into a fine powder. Add a large bowl of water and 3 taels of the powdered medicine, and simmer together with the tangerine peel over a low heat. After the tangerine peel is very soft, drain it. After a short while, mix it with the dry powdered medicine and bake it dry." However, the original text of *Imperial Pharmacy Prescriptions* only mentions the processing procedure, but does not specify the process parameters. Neither the *Chinese Pharmacopoeia* nor the processing standards of various regions contain relevant standards for "processed tangerine peel."

[0007] In terms of clinical needs and processing characteristics, "processed tangerine peel" adds fennel seeds, coarse salt, roasted licorice root, dried ginger, dried plum pulp, and sandalwood to the base of tangerine peel. This transforms the function and indications of tangerine peel from "regulating qi and strengthening the spleen, drying dampness and resolving phlegm. Used for abdominal distension, poor appetite, vomiting and diarrhea, cough with excessive phlegm" to "aiding digestion and regulating qi, relieving chest congestion and diaphragm obstruction. Used for food stagnation, phlegm and dampness obstructing the middle jiao, qi stagnation and discomfort, chest and diaphragm distension, belching with a foul odor and acid reflux, discomfort after drinking alcohol, and loss of appetite." This creates new functions and indications based on tangerine peel, providing new options for clinical practice.

[0008] This invention aims to utilize modern technology to achieve quality control of processed products and overcome the difficulties in traceability. It provides a method for processing dried tangerine peel and its processed products that, based on traditional processing methods, utilizes modern technology to study the process steps and parameters in the preparation process. Summary of the Invention

[0009] To address the aforementioned problems, the purpose of this invention is to provide a processed tangerine peel product and its preparation process, reviving and clarifying the processing technique of "processed tangerine peel," and modernizing, standardizing, and digitizing the ancient formula.

[0010] This invention provides a processed dried tangerine peel product, which is prepared from the following raw materials in the indicated weight ratios:

[0011] 6-48 parts dried tangerine peel, 1.5-12 parts fennel seeds, 1.5-12 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum flesh, 0.1875-1.5 parts sandalwood, and 0-24 parts coarse salt.

[0012] Furthermore, the ingredients are: 6-24 parts dried tangerine peel, 1.5-6 parts fennel seeds, 1.5-6 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum pulp, 0.1875-1.5 parts sandalwood, and 0-24 parts coarse salt.

[0013] Further, add 6-18 parts dried tangerine peel, 1.5-4.5 parts fennel seeds, 1.5-4.5 parts roasted licorice root, 0.375-1.5 parts dried ginger, 0.375-1.5 parts dried plum pulp, 0.1875-1 part sandalwood, and 0-12 parts coarse salt.

[0014] More preferably, it is prepared from the following raw materials in the indicated weight ratios:

[0015] 12 parts dried tangerine peel, 3 parts fennel seeds, 3 parts roasted licorice root, 0.75 parts dried ginger, 0.75 parts dried plum flesh, 0.375 parts sandalwood, and 6 parts coarse salt.

[0016] This invention produces processed tangerine peel using dried, mature peels of Citrus reticulata Blanco and its cultivated varieties, including Chachi tangerine peel, Dahongpao tangerine peel, Wenzhou mandarin orange peel, and Tangerine peel. Dahongpao tangerine peel is a high-quality representative of Sichuan tangerine peel, with a long history of use and high content of indicators such as hesperidin, nosocomialis, and citrus peel. Dahongpao tangerine peel is the preferred variety.

[0017] The dried tangerine peel used in the processing of tangerine peel according to this invention is unremoved white pith (original ancient texts record that the white pith of tangerine peel needs to be removed). According to the 2025 edition of the Chinese Pharmacopoeia, tangerine peel is "the dried, mature peel of Citrus reticulata Blanco and its cultivated varieties, belonging to the Rutaceae family. Mature fruits are harvested, the peel is removed, and then sun-dried or dried at low temperature." Therefore, the tangerine peel used in the processing of tangerine peel according to this invention is unremoved white pith.

[0018] The salt used in the processing of dried tangerine peel according to this invention is coarse salt.

[0019] The processed tangerine peel product of this invention is a traditional Chinese medicine decoction piece made from tangerine peel, fennel, roasted licorice root, dried ginger, dried plum pulp, sandalwood, and coarse salt.

[0020] This invention also provides a process for preparing the aforementioned processed product. This process uses the content of key components, yield, tightness of the powder coating, and powder loss rate (impurities) of the processed tangerine peel as quality control indicators. The process for achieving these quality control indicators includes the following steps:

[0021] S1. Take dried tangerine peel, remove impurities, moisten it, and then cut it.

[0022] S2. Take fennel seeds, roasted licorice root, dried ginger, dried plum flesh, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix well.

[0023] S3. Take the dried tangerine peel obtained in S1 and some of the medicinal powder obtained in S2, and soak them in water.

[0024] S4. After soaking in water, heat and boil until the decoction is almost gone. Remove and let cool to obtain the intermediate product of processed tangerine peel; or after soaking in water, heat and boil until the tangerine peel is very soft (boil until the core is thoroughly cooked), drain to obtain the intermediate product of processed tangerine peel.

[0025] S5. Take the intermediate product of processed tangerine peel from S4 and mix it with the remaining medicinal powder in S2 after S3.

[0026] S6. After mixing, dry at a temperature not exceeding 60℃. The finished product is any one or more of the following: powder, flakes, segments, blocks, shreds, strips, and lumps.

[0027] The tangerine peel mentioned in step S1 can be cut tangerine peel and / or crushed tangerine peel before being processed in step S1, or it can be unprocessed raw tangerine peel.

[0028] Furthermore, in step S1, the raw material for dried tangerine peel is the dried, mature peel of Citrus reticulata Blanco and its cultivated varieties, including Citrus reticulata 'Chachi' (Guangdong tangerine peel), Citrus reticulata 'Dahongpao', Citrus reticulata 'Unshiu', and Citrus reticulata 'Tangerina'. Dahongpao is a high-quality representative of Sichuan tangerine peel, with a long history of use and high content of indicator components such as hesperidin, nosocomialis, and citrus peel. Citrus reticulata 'Dahongpao' tangerine peel is preferred.

[0029] Furthermore, in step S1, the cut products of dried tangerine peel include any one or more of the following: powder, slices, segments, blocks, shreds, and strips.

[0030] Preferably, the powder includes coarsest powder, coarse powder, medium powder, fine powder, finest powder, and ultrafine powder; wherein: coarsest powder (meaning that all of it can pass through sieve No. 1, but mixed with no more than 20% of the powder that can pass through sieve No. 3), coarse powder (meaning that all of it can pass through sieve No. 2, but mixed with no more than 40% of the powder that can pass through sieve No. 4), medium powder (meaning that all of it can pass through sieve No. 4, but mixed with no more than 60% of the powder that can pass through sieve No. 5), fine powder (meaning that all of it can pass through sieve No. 5, and contains no less than 95% of the powder that can pass through sieve No. 6), finest powder (meaning that all of it can pass through sieve No. 6, and contains no less than 95% of the powder that can pass through sieve No. 7), and ultrafine powder (meaning that all of it can pass through sieve No. 8, and contains no less than 95% of the powder that can pass through sieve No. 9). The specific sieve sizes are as follows: Sieve No. 1 (average inner diameter of sieve openings 2000μm ± 70μm, mesh size 10), Sieve No. 2 (average inner diameter of sieve openings 850μm ± 29μm, mesh size 24), Sieve No. 3 (average inner diameter of sieve openings 355μm ± 13μm, mesh size 50), Sieve No. 4 (average inner diameter of sieve openings 250μm ± 9.9μm, mesh size 65), and Sieve No. 5 (average inner diameter of sieve openings 18...). 0μm±7.6μm, 80 mesh), No. 6 sieve (average inner diameter of sieve opening 150μm±6.6μm, 100 mesh), No. 7 sieve (average inner diameter of sieve opening 125μm±5.8μm, 120 mesh), No. 8 sieve (average inner diameter of sieve opening 90μm±4.6μm, 150 mesh), No. 9 sieve (average inner diameter of sieve opening 75μm±4.1μm, 200 mesh).

[0031] Preferably, the sheet thickness is 0-6 mm;

[0032] Preferably, the thickness of the segment is 3 to 17 mm;

[0033] Preferably, the block is a cube with a thickness of 6-14 mm;

[0034] Preferably, the thickness of the wire is 0-12 mm.

[0035] More preferably, the thickness of the shreds is 0-12mm (shredding increases the contact area with other medicinal ingredients during processing, allowing more active ingredients to participate in the reaction; the moisture in the finished product is more easily evaporated after shredding, making it less prone to mold and dampness, which is beneficial for the drying and long-term preservation of the finished product).

[0036] Furthermore, the pulverization described in step S2 is performed by pulverizing the medicinal materials individually or pulverizing a mixture of the medicinal materials.

[0037] Furthermore, the fine powder mentioned in step S2 refers to powder that can completely pass through a No. 5 sieve and contains at least 95% of the powder that can pass through a No. 6 sieve. Specifically, the No. 5 sieve has an average inner diameter of 180μm ± 7.6μm and a mesh size of 80 mesh; the No. 6 sieve has an average inner diameter of 150μm ± 6.6μm and a mesh size of 100 mesh. Pulverizing the medicinal materials into a fine powder facilitates the uniform distribution of the powder during subsequent decoction and mixing processes, and improves the quality control of the finished product.

[0038] Furthermore, in step S3, the weight of the powder taken is 10 / 37 to 15 / 37 of the total weight of the powder in step S2, preferably 12 / 37.

[0039] Furthermore, in step S3, the amount of water added is 4-12 times the weight of the medicinal materials in step S3, preferably 6 times the weight of the medicinal materials.

[0040] Furthermore, in step S3, the soaking time after adding water is 15 minutes to 1 hour, preferably 1 hour.

[0041] Furthermore, in step S4, the tangerine peel is extremely soft and needs to be simmered until it is thoroughly cooked.

[0042] Furthermore, in step S4, the decocting is performed 1-3 times; preferably once.

[0043] Furthermore, before mixing the remaining medicinal powder in step S5, the moisture content of the processed tangerine peel intermediate is controlled to be 50%~85%. This ensures that the viscosity of the processed tangerine peel intermediate is moderate during subsequent mixing, making it easier for the medicinal powder to adhere during mixing, resulting in a uniform distribution of medicinal powder on the surface of the dried finished product, thus guaranteeing the effectiveness and quality stability of the finished product.

[0044] Preferably, before mixing with the remaining medicinal powder in step S5, the moisture content of the processed tangerine peel intermediate is controlled at 50%~55%. The powder loss rate (impurities) is approximately 20%~30%.

[0045] In a further optimized step, before mixing the processed tangerine peel with the remaining medicinal powder in step S5, the moisture content of the intermediate product is controlled to be 55%~65%. The powder loss rate (impurities) is approximately 10%~15%.

[0046] In the most preferred case, before mixing the remaining medicinal powder in step S5, the moisture content of the intermediate product of processed tangerine peel is controlled to be 65%~85%, and the powder loss rate (impurities) is not higher than 5%.

[0047] Furthermore, in step S5, the ratio of the remaining medicinal powder used to the medicinal powder used in step S3 is 27:10 to 22:15, preferably 25:12, and the remaining medicinal powder used accounts for 22 / 37 to 27 / 37 of the total weight of the medicinal powder in step S2, preferably 25 / 37.

[0048] Furthermore, in step S6, the drying temperature is no more than 60°C to avoid the loss of volatile components in the processed tangerine peel product of the present invention due to high temperature, thus ensuring the quality of the medicine.

[0049] Furthermore, the finished product in step S6 can be any one or more of the following: powder, flakes, segments, blocks, shreds, strips, and lumps.

[0050] The present invention also provides a new use for the above-mentioned processed tangerine peel, namely, the use of the processed tangerine peel of the present invention in the preparation of medicines for improving discomfort after drinking alcohol.

[0051] The advantages of this invention compared to the prior art are as follows:

[0052] 1. Through the optimized processing technology designed in this invention, such as optimizing the selection of tangerine peel raw materials, optimizing the amount of water added, soaking time, decoction time, number of decoctions, moisture content of the intermediate product of processed tangerine peel before mixing with powder after decoction, and drying temperature, the chemical components of the processed tangerine peel can be preserved to the maximum extent, significantly improving the quality of the finished product of processed tangerine peel. This makes the processing technology of processed tangerine peel data-driven and standardized, suitable for large-scale industrial production, and ensures the safety, effectiveness, and quality control of clinical use.

[0053] 2. The processed tangerine peel obtained through this invention gives it new functions and indications. The original function of tangerine peel, "regulating qi and strengthening the spleen, drying dampness and resolving phlegm, used for abdominal distension, poor appetite, vomiting and diarrhea, cough with excessive phlegm," is transformed into "aiding digestion and regulating qi, relieving chest congestion and diaphragm discomfort, used for food stagnation, phlegm and dampness obstructing the middle jiao, qi stagnation and discomfort, chest and diaphragm distension, belching with a foul odor and acid reflux, discomfort after drinking alcohol, and loss of appetite," providing more options for clinical use.

[0054] 3. The processed tangerine peel obtained by this invention can be used in the clinical treatment of "post-drinking discomfort", which improves the current predicament of drugs used for this symptom having a single effect, being unable to provide overall conditioning, and having many side effects and contraindications.

[0055] 4. This invention revives the processing technique of processed tangerine peel, protects and explores the unique processing techniques of tangerine peel, a traditional Chinese medicine from Sichuan Province, which is conducive to the inheritance and innovation of traditional Chinese medicine processing techniques and the protection of tangerine peel germplasm resources. Attached Figure Description

[0056] Figure 1 Specificity assessment.

[0057] In Figure A, the mixed reference solution is shown; in Figure B, the negative control solution is shown; and in Figure C, the test solution is shown. The values ​​in Figure A represent 1: glycyrrhizin; 2: hesperidin; 3: norihesperidin; and 4: citrinin.

[0058] Figure 2 Physical diagram of orthogonal experiment.

[0059] Figure 3 Orthogonal design verification sample physical image.

[0060] Where A represents the physical image of the first batch of samples for orthogonal design verification, B represents the physical image of the second batch of samples for orthogonal design verification, and C represents the physical image of the third batch of samples for orthogonal design verification.

[0061] Figure 4 Photos of products dried using different methods.

[0062] In the image, A represents a product that has been air-dried for 1 hour, B represents a product that has been dried at 50℃ for 2 hours, and C represents a product that has been dried at 50℃ for 4 hours.

[0063] Figure 5 Photos of intermediate products before and after mixing powder with different moisture levels.

[0064] In the figures, A, E, and E represent the intermediate products before mixing and the finished products after mixing when the moisture content is 84.35%, 68.4%, 57.43%, 57.08%, and 50.66%, respectively.

[0065] Figure 6 A picture of a legally produced dried tangerine peel.

[0066] In this diagram, A represents the first batch of pilot-scale samples of processed tangerine peel, B represents the second batch of pilot-scale samples of processed tangerine peel, and C represents the third batch of pilot-scale samples of processed tangerine peel.

[0067] Figure 7 Photos of actual samples showing the results of an investigation into the "extremely soft" texture of processed dried tangerine peel after different boiling times.

[0068] Where A represents simmering for 30 minutes, B represents simmering for 45 minutes, and C represents simmering for 60 minutes.

[0069] Figure 8 Images showing the characteristics of processed tangerine peel products made using different techniques.

[0070] Where A represents the original processing method, and B represents the processing method of A.

[0071] Figure 9 Thin-layer identification diagram of two types of processed tangerine peel.

[0072] Wherein 1-8 represent: 1. Test sample (original processing method); 2. Test sample (original processing method); 3. Test sample (original processing method); 4. Test sample (processing method A); 5. Test sample (processing method A); 6. Test sample (processing method A); 7. Tangerine peel reference material; 8. Hesperidin reference standard.

[0073] Figure 10 Thin-layer chromatography diagrams for different methods of processing dried tangerine peel and roasted licorice.

[0074] Wherein 1-8 represent: 1. Test sample (original processing method); 2. Test sample (original processing method); 3. Test sample (original processing method); 4. Test sample (processing method A); 5. Test sample (processing method A); 6. Test sample (processing method A); 7. Licorice reference material; 8. Glycyrrhizin reference standard. Detailed Implementation

[0075] The present invention will be explained and described below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0076] In the following embodiments, the processed tangerine peel of the present invention is based on the record of processed tangerine peel in the Yuan Dynasty's "Imperial Pharmacy Prescriptions": "Half a catty of tangerine peel (remove the pith, 4 taels, cut into strips), 2 taels of fennel, 4 taels of rock salt, 2 taels of licorice (roasted), half a tael of dried ginger, half a tael of dried plum pulp, and 2.5 mace of white sandalwood. Except for the tangerine peel, all other ingredients are ground into a fine powder. Add a large bowl of water and 3 taels of the powdered medicine, and simmer together with the tangerine peel over a low heat. After the tangerine peel is very soft, drain it and mix it with the dry powdered medicine. Then dry it." Modern technology is used to modernize and standardize the processing of this product, achieving quality control and overcoming the difficulty of traceability.

[0077] Based on the records of processed tangerine peel in the Imperial Pharmacy Formulary, and after verification of the raw materials and calculation of the dosage, this invention produces a processed tangerine peel product, which is prepared from the following raw materials in the indicated weight ratios:

[0078] 6-48 parts dried tangerine peel, 1.5-12 parts fennel seeds, 1.5-12 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum flesh, 0.1875-1.5 parts sandalwood, and 0-24 parts coarse salt.

[0079] Furthermore, the ingredients are: 6-24 parts dried tangerine peel, 1.5-6 parts fennel seeds, 1.5-6 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum pulp, 0.1875-1.5 parts sandalwood, and 0-24 parts coarse salt.

[0080] Further, add 6-18 parts dried tangerine peel, 1.5-4.5 parts fennel seeds, 1.5-4.5 parts roasted licorice root, 0.375-1.5 parts dried ginger, 0.375-1.5 parts dried plum pulp, 0.1875-1 part sandalwood, and 0-12 parts coarse salt.

[0081] More preferably, it is prepared from the following raw materials in the indicated weight ratios:

[0082] 12 parts dried tangerine peel, 3 parts fennel seeds, 3 parts roasted licorice root, 0.75 parts dried ginger, 0.75 parts dried plum flesh, 0.375 parts sandalwood, and 6 parts coarse salt.

[0083] The processed tangerine peel of this invention uses dried, mature peel of Citrus reticulata Blanco and its cultivated varieties, including Citrus reticulata 'Chachi' (Guangdong tangerine peel), Citrus reticulata 'Dahongpao', Citrus reticulata 'Unshiu', and Citrus reticulata 'Tangerina', with Citrus reticulata 'Dahongpao' being the preferred variety.

[0084] The salt used in the processing of dried tangerine peel according to this invention is coarse salt.

[0085] According to the processing method of processed tangerine peel recorded in the Imperial Pharmacy Formulary, "Except for the tangerine peel, all other ingredients are ground into a fine powder. A large bowl of water and three ounces of the powder are added together with the tangerine peel and simmered over low heat until the tangerine peel is very soft. After draining, it is separately mixed with the dry powder and then dried." Through verification and screening of the processing method, it has been confirmed that the preparation method of the processed product of this invention includes the following steps:

[0086] S1. Take dried tangerine peel, remove impurities, moisten it, and then cut it.

[0087] S2. Take fennel seeds, roasted licorice root, dried ginger, dried plum flesh, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix well.

[0088] S3. Take the dried tangerine peel obtained in S1 and some of the medicinal powder obtained in S2, and soak them in water.

[0089] S4. After soaking in water, heat and boil until the decoction is almost gone. Remove and let cool to obtain the intermediate product of processed tangerine peel; or after soaking in water, heat and boil until the tangerine peel is very soft (boil until the core is thoroughly cooked), drain to obtain the intermediate product of processed tangerine peel.

[0090] S5. Take the intermediate product of processed tangerine peel and mix it with the remaining medicinal powder in S2 after S3.

[0091] S6. After mixing, dry at a temperature not exceeding 60℃. The finished product is any one or more of the following: powder, flakes, segments, blocks, shreds, strips, and lumps.

[0092] The inventors of this invention focused on modernizing and standardizing the decoction process conditions corresponding to "slow cooking" and the drying methods and degrees corresponding to "controlling the drying and mixing with dry medicinal powder for a short time" in the process of reviving the method of processing tangerine peel.

[0093] In the following experiment, the proportions of the raw materials used were as follows: 12 parts dried tangerine peel, 3 parts fennel seeds, 3 parts roasted licorice root, 0.75 parts dried ginger, 0.75 parts dried plum pulp, 0.375 parts sandalwood, and 6 parts coarse salt. The dried tangerine peel samples were prepared according to the following method for the experiment:

[0094] S1. Take dried tangerine peel, remove impurities, moisten it, and then cut it into strips;

[0095] S2. Take fennel seeds, roasted licorice root, dried ginger, dried plum flesh, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix well.

[0096] S3. Take the dried tangerine peel obtained in S1 and a portion of the medicinal powder obtained in S2 (12 / 37 of the total weight of the medicinal powder), and soak them in water.

[0097] S4. After soaking in water, heat and boil until the decoction is almost gone. Remove and let cool to obtain the intermediate product of processed tangerine peel; or after soaking in water, heat and boil until the tangerine peel is very soft (boil until the core is thoroughly cooked), drain to obtain the intermediate product of processed tangerine peel.

[0098] S5. Take the intermediate product of dried tangerine peel prepared by method S4 and mix it with the remaining medicinal powder (25 / 37 of the total weight of the medicinal powder) after use in S3.

[0099] S6. After mixing, dry at a temperature not exceeding 60℃.

[0100] The technical parameters involved in the decoction conditions include the amount of water added and the soaking time in step S3, and the number of decoctions and the decoction time in step S4. The technical parameters involved in the drying process include the control of the moisture content of the processed tangerine peel intermediate before mixing it with the remaining medicinal powder in step S5.

[0101] I. Screening Experiment for Decoction Conditions of Processed Tangerine Peel

[0102] 1. Determination of evaluation indicators

[0103] The contents of hesperidin, norihesperidin, tangeretin, and glycyrrhizin were determined. Based on this, the content of extracts from processed tangerine peel was included in the evaluation index. A comprehensive evaluation method was used to screen the processing technology of processed tangerine peel and determine the specific process parameters.

[0104] 2. Establishment of methods for determining the content of hesperidin, nonotrimonin, tangeretin, and glycyrrhizin.

[0105] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the stationary phase; 99% acetonitrile as mobile phase A and 0.01% phosphoric acid water as mobile phase B, with gradient elution as specified in Table 1; the detection wavelength was 270 nm. The theoretical plate number, calculated based on the hesperidin peak and the nobiletin peak, should be no less than 2000.

[0106] Table 1. Mobile phase gradient for the determination of hesperidin, nonociterin, tangeretin, and glycyrrhizin content.

[0107]

[0108] Preparation of reference solution: Take appropriate amounts of hesperidin reference standard, norihesperidin reference standard, tangeretin reference standard, and glycyrrhizin reference standard, accurately weigh them, and add methanol to prepare a mixed solution containing 0.9650 mg of hesperidin, 1.0700 mg of norihesperidin, 2.2300 mg of tangeretin, and 0.2070 mg of glycyrrhizin per ml.

[0109] Preparation of the test solution: Take about 1.0 g of the coarse powder of this product (passed through a No. 2 sieve), accurately weigh it, place it in a stoppered conical flask, accurately add 10 ml of methanol, stopper tightly, shake well, weigh it, sonicate (power 250W, frequency 40kHz) for 60 minutes, cool it, weigh it again, make up the weight loss with methanol, shake well, filter it, and take the filtrate to obtain the test solution.

[0110] Methodological investigation

[0111] Our research group conducted a methodological review of the established content determination method, and the results are as follows:

[0112] (1) Specificity examination

[0113] Prepare the test solution, negative control solution, and reference solution separately, and inject them for analysis according to the above chromatographic conditions. Record the chromatograms as shown below. Figure 1 The results show that the spectral baseline is stable, the separation of each component is good, other components do not interfere with the analyte, and the specificity is good.

[0114] (2) Examination of linear range

[0115] The standard curve for hesperidin is Y = 1101.1x + 649.41, R0 2 =0.9999, linear range 0.0965~12.0625μg; standard curve of noriheptacortin Y=2698.6x+1577.8, R 2 =0.9995, linear range 0.1070~13.375μg; hesperidin standard curve Y=1306.5x+2388.6, R 2 =0.9992, linear range 0.2230~55.7500μg; glycyrrhizin standard curve Y=1806.9x+223.57, R 2 =0.9993, linear range 0.0207~2.0700μg; the detected components showed good linearity under these chromatographic conditions.

[0116] (3) Precision

[0117] The mean peak area precision of glycyrrhizin was 289.1750, with an RSD of 0.93%; the mean peak area precision of hesperidin was 3190.776, with an RSD of 0.90%; the mean peak area precision of norihesperidin was 11129.180, with an RSD of 0.80%; and the mean peak area precision of citrus reticulata was 4432.888, with an RSD of 0.77%.

[0118] (4) Repeatability

[0119] The mean content of glycyrrhizin was 0.0112%, with a repeatability RSD of 4.24%. The mean content of hesperidin was 0.7401%, with a repeatability RSD of 0.58%. The mean content of noriheptacortin was 0.4158%, with a repeatability RSD of 0.55%. The mean content of citric acid was 0.1884%, with a repeatability RSD of 1.16%.

[0120] (5) Stability

[0121] The glycyrrhizin, hesperidin, nobiletin, and tangeretin in the test sample showed good stability within 24 hours, with peak area RSD values ​​of 2.01%, 0.64%, 0.28%, and 0.34%, respectively.

[0122] (6) Accuracy

[0123] The average recoveries of glycyrrhizin, hesperidin, nobiletin, and citrusin were 100.42%, 102.67%, 102.11%, and 94.84%, respectively, with RSD values ​​of 2.06%, 4.54%, 1.53%, and 2.71%, respectively.

[0124] The assay involves precisely pipetting 10 μl each of the reference solution and the test solution into a liquid chromatograph and measuring the results.

[0125] 3. Determination of water-soluble extractives

[0126] The water-soluble extracts of processed tangerine peel were determined according to the hot immersion method in General Chapter 2201 of Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0127] 4. Orthogonal design for decocting processed tangerine peel

[0128] Using hesperidin, noriheptacortin, tangeretin, glycyrrhizin, and extract as evaluation indicators, the weights of each indicator were analyzed using the analytic hierarchy process (AHP). Combined with orthogonal design and comprehensive scoring, the decoction process in the processing of processed tangerine peel was optimized.

[0129] 4.1 AHP ​​Weight Analysis

[0130] The Analytic Hierarchy Process (AHP) is a systematic analytical method that treats the research object as a system and makes decisions based on decomposition, comparison, judgment, and synthesis, organically combining qualitative and quantitative methods. AHP primarily starts from the evaluator's understanding of the essence and elements of the evaluation problem, emphasizing qualitative analysis and judgment more than general quantitative methods. Based on the dosage proportions of medicinal ingredients involved in the processing of dried tangerine peel and the primary and secondary roles of each ingredient, the indicators were quantified and divided into three levels. The priority order of the indicators was determined as: hesperidin = nosenoside = tangeretin > glycyrrhizin > extractives. A pairwise comparison priority judgment matrix was constructed, and relative scores were assigned to each indicator. The judgment matrices and analysis results for each indicator are shown in Tables 2 and 3 below.

[0131] Table 2. 5-order judgment matrix for pairwise comparisons of each indicator.

[0132]

[0133] Table 3 Results of AHP (Analog-Philippines Hierarchical Analysis)

[0134]

[0135] As shown in Tables 2 and 3, the weight values ​​of hesperidin, nobiletin, tangeretin, glycyrrhizin, and extracts obtained from the 5-order judgment matrix established for the above 5 indicators are 0.2599, 0.2599, 0.2599, 0.1382, and 0.0820, respectively. The analytic hierarchy process consistency test results are passed, and the assigned indicator weights are effective.

[0136] 4.2 Orthogonal Design Optimization of the Decoction Process for Processed Tangerine Peel

[0137] Based on the determination that hesperidin, nobiletin, tangeretin, glycyrrhizin, and extracts are the evaluation indicators for optimizing the decoction process of processed tangerine peel, and assigning weights to these indicators, an orthogonal design was adopted, selecting 3 factors and 3 levels to optimize the soaking time, water volume, and number of decoctions affecting the decoction process, thus obtaining the optimal decoction process parameters. The orthogonal design factor level table and the orthogonal design experimental combination table are shown in Tables 4 and 5, and the results and analysis are shown in Tables 6-8. Images of the finished products from experiments 1-9 are shown in […]. Figure 2 .

[0138] Table 4. Orthogonal Design Factor Level Table

[0139]

[0140] Table 5 Orthogonal Design Experiment Combination Table

[0141]

[0142] Table 6. Results of Orthogonal Design Experiments

[0143]

[0144] Table 7. Visual Analysis of Orthogonal Experimental Design Results

[0145]

[0146] Table 8. Analysis of Variance of Orthogonal Experimental Design Results

[0147]

[0148] The intuitive analysis table of orthogonal experimental design results shows that the factor with the greatest impact on the overall score is the amount of water added, followed by the soaking time, and lastly the number of extractions. The optimal extraction process parameters are A1B3C2. According to the analysis of variance table, both the amount of water added and the soaking time have a significant impact on the decoction effect, while the number of decoctions has no significant impact. Considering the simplicity and energy saving in actual production, the process parameters are determined to be A1B3C1, i.e., adding 6 times the amount of water, soaking for 60 minutes, and decocting once.

[0149] 4.3 Orthogonal Design Optimization Process Verification

[0150] To confirm the feasibility and reliability of the optimized decoction process for processed tangerine peel selected by orthogonal design, three batches of production were carried out according to the optimized process, and the evaluation indicators were measured. The verification results are shown in Table 9 and the actual products. Figure 3 The RSD values ​​of all indicators were less than 6%, indicating that the optimized decoction process for processed tangerine peel is stable and feasible.

[0151] Table 9. Verification results of three batches of orthogonal designs.

[0152]

[0153] II. Examination of the Drying Process of Processed Tangerine Peel

[0154] The original text of the ancient book states, "Half a catty of dried tangerine peel...simmer it together with dried tangerine peel over a low fire until the tangerine peel is very soft. Drain it and mix it with dry medicinal powder after a short time. Then bake it dry." However, the drying time and degree of drying are not specified. Based on the optimized decoction process, we will study the drying process before mixing with powder.

[0155] 1. Investigate three drying methods

[0156] Process 1

[0157] Weigh out the medicinal ingredients according to the proportions, add 6 times the amount of water, soak for 60 minutes, decoct once, and when the decoction is almost gone, take it out, air dry at 25℃ for 1 hour, and then mix it with the remaining mixed powder.

[0158] Process 2

[0159] Weigh out the medicinal ingredients according to the proportions, add 6 times the amount of water, soak for 60 minutes, decoct once, and when the decoction is almost gone, remove it, dry it at 50℃ for 2 hours, remove it and let it cool for 10 minutes, and then mix it with the remaining powder.

[0160] Process 3

[0161] Weigh out the medicinal ingredients according to the proportions, add 6 times the amount of water, soak for 60 minutes, decoct once, and when the decoction is almost gone, remove it, dry it at 50℃ for 4 hours, remove it and let it cool for 10 minutes, and then mix it with the remaining powder.

[0162] Recorded from Table 10 and physical samples of each process Figure 4 Analysis shows that during the drying process, drying at 25℃ for 1 hour and then mixing with the remaining powder can achieve a better mixing effect. The dried powder is less likely to fall off and has better properties.

[0163] Table 10 Comparison of different drying methods

[0164]

[0165] 2. Investigate the moisture content of intermediate processed tangerine peel before mixing with powder.

[0166] After decocting, processed tangerine peel needs to be drained before being mixed with powder to control moisture and achieve a better mixing effect. This part of the study investigates the moisture limit during mixing to provide a reference for actual production. The decocted processed tangerine peel is dried, and taken out at different drying time points to determine the moisture content. Medicinal powder is then mixed with it in a specific ratio, and the mixing state is observed and recorded. After mixing, drying continues until the moisture content is less than 13% (13% is the optimal moisture content for preserving the quality of processed tangerine peel, and it is also the lowest commercially cost-effective approach). The peel is then removed, and the powder loss rate (impurities) is measured (see Table 11). Photos of the moisture content of the intermediate processed tangerine peel before mixing and the finished product after mixing are shown in [Table 11]. Figure 5 .

[0167] Table 11 Study on moisture control of processed tangerine peel powder

[0168]

[0169] The above research indicates that the moisture content of the intermediate product of processed tangerine peel needs to be controlled after decocting and draining, and before mixing with powder. When the moisture content is below 50%, the viscosity of the intermediate product is poor, a large amount of medicinal powder is not adhered during mixing, and the surface of the dried finished product has less medicinal powder and a high powder loss rate (impurities). Furthermore, before mixing with the remaining medicinal powder in step S5, the moisture content of the intermediate product of processed tangerine peel should be controlled at 50%~55%, and the powder loss rate (impurities) should be approximately 20%~30%.

[0170] In a further preferred embodiment, before mixing the remaining medicinal powder in step S5, the moisture content of the intermediate product of processed tangerine peel is controlled to be 55%~65%, and the powder loss rate (impurities) is about 10%~15%.

[0171] Ideally, before mixing with the remaining medicinal powder in step S5, the moisture content of the intermediate product of processed tangerine peel should be controlled at 65%~85%. The powder loss rate (impurities) should not exceed 5%.

[0172] Based on literature review, this invention studies the amount of water added during decoction, soaking time, decoction time, number of decoctions, drying method and time, and moisture content control before mixing with powder in the processing of "processed tangerine peel," and draws the following conclusions:

[0173] 1. In the process of decocting tangerine peel and medicinal powder, the amount of water added, soaking time, decoction time and number of decoctions are important influencing factors. The results of orthogonal design study show that the amount of water added and soaking time have significant effects on the evaluation indicators of processed tangerine peel, while the number of decoctions has no significant effect. The optimized decoction process is as follows: add 6 times the amount of water, soak for 1 hour, and decoct once.

[0174] 2. The decoction process was validated according to the optimized orthogonal design. The results of each indicator were stable, and the optimized decoction process was stable and feasible.

[0175] 3. The moisture content of the intermediate product of processed tangerine peel before mixing with powder has a significant impact on the mixing effect. Using the mixing condition, powder loss rate (impurities), and finished product characteristics as evaluation indicators, the moisture content of the intermediate product of processed tangerine peel was optimized. The moisture content control requirements are as follows: the moisture content of the intermediate product of processed tangerine peel should be controlled at 50%~85%. For intermediate products with a moisture content of 50%~55%, the powder loss rate (impurities) is approximately 20%~30%; for intermediate products with a moisture content of 55%~65%, the powder loss rate (impurities) is approximately 10%~15%; and for intermediate products with a moisture content of 65%~85%, the powder loss rate (impurities) should not exceed 5%.

[0176] The above experiments determined the processing method of "processed tangerine peel" as follows: Take tangerine peel, remove impurities, moisten it, and cut it into strips according to the cutting method (General Rule 0213); separately take appropriate amounts of fennel seeds, roasted licorice root, dried ginger, dried plum pulp, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix them evenly. Soak the tangerine peel and appropriate amount of medicinal powder in water for 1 hour, decoct until the decoction is almost gone, remove it, cool it, control the moisture content of the intermediate product to 50%~85%, mix it evenly with the remaining medicinal powder, and dry it at no more than 60℃. For every 12kg of tangerine peel, use 3kg of fennel seeds, 3kg of roasted licorice root, 0.75kg of dried ginger, 0.75kg of dried plum pulp, 0.375kg of sandalwood, and 6kg of coarse salt. Use 4.5kg of medicinal powder when decocting, and 9.375kg of medicinal powder when mixing.

[0177] To verify the stability of the process method of this invention and to verify that the process method of this invention can standardize the reproduction of the processed products recorded in ancient prescriptions, the stability verification experiment is as follows:

[0178] Take dried tangerine peel, remove impurities, moisten it, and then shred it according to the cutting method (General Rule 0213). Separately, take appropriate amounts of fennel seeds, roasted licorice root, dried ginger, dried plum pulp, sandalwood, and coarse salt, remove impurities, grind them into a fine powder, and mix well. Soak the dried tangerine peel and appropriate amount of the medicinal powder in water for 1 hour, then decoct until the decoction is almost gone. Remove, cool (moisture content controlled at 50%~85%), mix with the remaining medicinal powder, and dry at no more than 60℃. Three batches were produced consecutively, and the test results are shown in Table 12 and... Figure 6 .

[0179] Table 12 Results of index determination for three batches of pilot-scale samples

[0180]

[0181] In summary, the optimal processing technique for processed tangerine peel is as follows: Take tangerine peel, remove impurities, moisten it, and then shred it according to the slicing method (General Rule 0213); separately take appropriate amounts of fennel seeds, roasted licorice root, dried ginger, dried plum pulp, sandalwood, and coarse salt, remove impurities, grind them into a fine powder, and mix well. Soak the tangerine peel and appropriate amount of medicinal powder in water for 1 hour, decoct until the decoction is almost gone, remove, cool, control the moisture content of the intermediate product to 50%~85%, mix it with the remaining medicinal powder, and dry it at no more than 60℃ until the moisture content does not exceed 13% (13% is the optimal moisture content to ensure the quality of processed tangerine peel, and it is also the lowest commercial cost), and package it. Pilot production has confirmed that this process is stable and feasible, and suitable for large-scale production.

[0182] III. Comparative Study of Two Processing Techniques for Dried Tangerine Peel (Decoction and Drying Processes)

[0183] Because the original text of the ancient book records that "half a catty of dried tangerine peel...simmered together with dried tangerine peel over a low flame until the tangerine peel is very soft, drained...and dried", the specific operation process of the decoction and drying process described in the above part of "...simmered over a low flame until the tangerine peel is very soft, drained" is "decoction until the decoction liquid is almost gone, take it out and let it cool".

[0184] This section proposes another decoction and drying process, namely, "decoction until the tangerine peel is extremely soft, then drain the water", and conducts a comparative study of the two processing methods.

[0185] 1. Examination of the "extremely soft" state of tangerine peel after decoction

[0186] The original text of the ancient book records, "Half a catty of dried tangerine peel...simmered together with the dried tangerine peel over a low flame until the peel is extremely soft, then drained...and dried." Regarding the characteristic of "extremely soft," "softness" and "whether it penetrates to the core" were used as evaluation indicators. The simmering time was studied to determine the simmering time required to achieve "extremely soft dried tangerine peel." The results are shown in Table 13 and... Figure 7 .

[0187] Table 13 Results of the investigation on the "extremely soft" state of processed tangerine peel at different boiling times.

[0188]

[0189] The results above show that when the simmering time reaches 30 minutes, the degree of "extreme softness" reaches the level described in the ancient text as "...simmered over low heat until the tangerine peel is extremely soft." The basis for judging "extreme softness" is simmering until the tangerine peel is "through the core."

[0190] 2. Comparative Study of Two Processing Techniques for Dried Tangerine Peel (Decoction and Drying Processes)

[0191] 2.1 Comparative Design of Decoction and Drying Processes in the Processing of Processed Tangerine Peel

[0192] Based on the determination that processed tangerine peel should be boiled until "extremely soft", another processing technique A for processed tangerine peel was obtained:

[0193] Process A: Take dried tangerine peel, remove impurities, moisten it, and cut it into shreds according to the cutting method (General Rule 0213); separately take appropriate amounts of fennel seeds, roasted licorice root, dried ginger, dried plum pulp, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix well. Soak the dried tangerine peel and an appropriate amount of medicinal powder in water for 1 hour, decoct until the tangerine peel is very soft, drain, control the moisture content of the intermediate product to 50%~85%, mix it with the remaining medicinal powder, and dry it at no more than 60℃.

[0194] For every 12 kg of dried tangerine peel, use 3 kg of fennel seeds, 3 kg of roasted licorice root, 0.75 kg of dried ginger, 0.75 kg of dried plum pulp, 0.375 kg of sandalwood, and 6 kg of coarse salt. Use 4.5 kg of the powdered herbs when decocting, and 9.375 kg when mixing.

[0195] Original processing method: Take dried tangerine peel, remove impurities, moisten it, and cut it into shreds according to the cutting method (General Rule 0213); separately take appropriate amounts of fennel seeds, roasted licorice root, dried ginger, dried plum pulp, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix them evenly. Soak the dried tangerine peel and appropriate amount of medicinal powder in water for 1 hour, decoct until the decoction is almost gone, remove it, let it cool, control the moisture content of the intermediate product to 50%~85%, mix it with the remaining medicinal powder, and dry it at no more than 60℃.

[0196] For every 12 kg of dried tangerine peel, use 3 kg of fennel seeds, 3 kg of roasted licorice root, 0.75 kg of dried ginger, 0.75 kg of dried plum pulp, 0.375 kg of sandalwood, and 6 kg of coarse salt. Use 4.5 kg of the powdered herbs when decocting, and 9.375 kg when mixing.

[0197] Production was scaled up according to the original processing method and process A, respectively. In process A, the tangerine peel was removed after simmering for 30 minutes, drained, and the hesperidin content in the filtrate was measured to determine the hesperidin content in the decoction and to examine the effect of draining on the composition.

[0198] 2.2 Establishment of a method for determining hesperidin content in aqueous decoction

[0199] Chromatographic conditions and system suitability tests were performed using octadecylsilane-bonded silica gel as the stationary phase; 99% acetonitrile as mobile phase A and 0.1% phosphoric acid solution as mobile phase B, with gradient elution as specified in Table 14; the detection wavelength was 270 nm. The theoretical plate number, calculated based on the hesperidin peak, should be no less than 2000.

[0200] Table 14 Mobile phase gradient for hesperidin content determination

[0201]

[0202] Preparation of the reference solution: Take an appropriate amount of hesperidin reference standard, accurately weigh it, and add methanol to prepare a solution containing 0.2416 mg per ml.

[0203] Preparation of the test solution: Accurately measure 5 mL of the decoction and place it in a 10 mL volumetric flask. Add methanol to the mark, shake well, filter, and collect the filtrate to obtain the test solution.

[0204] The assay involves precisely pipetting 5 μl of both the reference solution and the test solution into a liquid chromatograph and measuring the results.

[0205] 2.3 Results of hesperidin content determination in aqueous decoction

[0206] Content determination revealed that, when processed using the A-process, a total of 2600ml of decoction was filtered out, containing 0.53g of hesperidin.

[0207] 3. Comparative Study on the Quality of Two Methods of Processing Tangerine Peel

[0208] The quality of processed tangerine peel produced using two different processing methods was analyzed using previously established quality standard research projects, and the quality differences between the two processed products were compared.

[0209] 3.1 Inspection Items and Contents

[0210] 3.1.1 Characteristics

[0211] This product appears in irregular strips or lumps. The outer surface is reddish-brown or brownish-red. The inner surface is yellowish-brown, rough, and covered with powder. It is slightly hard and brittle. It has a fragrant odor and a pungent, bitter, and salty taste.

[0212] 3.1.2 Identification

[0213] (1) The powder of this product is yellowish-brown. Calcium oxalate crystals are found in sheets within the parenchyma cells of the mesocarp, appearing as polyhedral, rhomboid, or bipyramidal shapes, with a diameter of 3–34 μm and a length of 5–53 μm. Some cells contain parallel twins composed of two polyhedra or 3–5 square crystals. Hesperidin crystals are mostly found in parenchyma cells, yellow or colorless, appearing as round or amorphous clumps, some showing radial stripes (dried tangerine peel). Non-glandular trichomes are unicellular, slightly curved or hook-shaped, and the cell lumen often contains yellowish-brown substances (dried plum flesh).

[0214] (2) Take 0.3g of the powder, add 10ml of methanol, sonicate for 20 minutes, filter, take 5ml of the filtrate, concentrate to 1ml, and use as the test solution. Take 0.3g of the reference herb tangerine peel, and prepare the reference herb solution in the same way. Take the hesperidin reference standard, add methanol to prepare a saturated solution, and use as the reference standard solution. Perform the thin-layer chromatography test (General Rule 0502), take 4μl of each of the above three solutions, and spot them separately on the same silica gel G thin-layer plate prepared with 0.5% sodium hydroxide solution. Use ethyl acetate-formic acid-water (8:1:1) as the developing solvent, develop to about 8cm, remove, air dry, spray with aluminum trichloride test solution, and examine under ultraviolet light (365nm). In the chromatogram of the test sample, fluorescent spots of the same color appear at the corresponding positions as in the chromatograms of the reference herb and the reference standard.

[0215] (3) Take 10g of the powder, add 40ml of ether, heat under reflux for 1 hour, filter, discard the ether, add 30ml of methanol to the residue, heat under reflux for 1 hour, filter, evaporate the filtrate to dryness, add 40ml of water to dissolve the residue, extract with n-butanol 3 times, 20ml each time, combine the n-butanol extracts, wash with water 3 times, discard the aqueous solution, evaporate the n-butanol extract to dryness, add 5ml of methanol to dissolve the residue, and use this as the test solution. Take 1g of licorice reference material and prepare a reference material solution using the same method. Take glycyrrhizin reference standard and add methanol to prepare a solution containing 2mg per ml, and use this as the reference solution. Perform the thin-layer chromatography test (General Rule 0502). Apply 2 μl of each of the three solutions described above to the same silica gel G thin-layer plate prepared with 0.5% sodium hydroxide solution. Develop the plate using ethyl acetate-formic acid-glacial acetic acid-water (15:1:1:2) as the developing solvent. Remove the plate, air dry, spray with 10% sulfuric acid ethanol solution, and heat at 105℃ until the spots are clearly visible. Examine under ultraviolet light (365 nm). The chromatogram of the test sample should show fluorescent spots of the same color at the corresponding positions as those of the reference medicinal material and the reference standard.

[0216] 3.1.3 Inspection

[0217] Moisture content shall not exceed 13.0% (General Rule 0832, Method IV).

[0218] The aflatoxin content of this product per 1000g shall not exceed 5μg of aflatoxin B1, and the total amount of aflatoxin G2, aflatoxin G1, aflatoxin B2 and aflatoxin B1 shall not exceed 10μg.

[0219] 3.1.4 Content Determination

[0220] This product, calculated on a dried basis, contains hesperidin (C). 28 H 34 O 15 (It shall not be less than 1.2%).

[0221] 3.2 Test Results

[0222] 3.2.1 Characteristics

[0223] A comparison of the two types of processed tangerine peel products is shown in the following figures. Figure 8 Their actual characteristics are consistent.

[0224] 3.2.2 Identification

[0225] The results of thin-layer chromatography identification of two types of processed tangerine peel are as follows: Figure 9 .

[0226] Comparing the two processed tangerine peel products, their thin-layer chromatographic identification was consistent. In the chromatogram of the test sample, fluorescent spots of the same color appeared at the corresponding positions as in the chromatograms of the reference medicinal material and the reference standard.

[0227] Thin-layer chromatography results of two methods of processing tangerine peel and roasted licorice: Figure 10 .

[0228] Comparing the two processed tangerine peel products, the thin-layer chromatography identification of the roasted licorice root was consistent. In the chromatogram of the test sample, fluorescent spots of the same color appeared at the corresponding positions as in the chromatograms of the reference medicinal material and the reference substance.

[0229] 3.2.3 Inspection

[0230] The two types of processed dried tangerine peel products were compared, and their inspection results both met the standard requirements.

[0231] 3.2.4 Content determination

[0232] The results of the content determination of the two methods of processed tangerine peel are shown in Table 15.

[0233] Table 15 Content determination results (mean, n=2)

[0234]

[0235] Comparing the processed tangerine peel products obtained from the two processing methods, the content determination results of both products met the standard requirements, and the difference between the two was minimal.

[0236] The results of the quality study on the two methods of processing dried tangerine peel are summarized as follows:

[0237] 1. Characteristics

[0238] The quality standard for processed dried tangerine peel stipulates that this product is in irregular strip or clump shape. The outer surface is reddish-brown or brownish-red. The inner surface is yellowish-brown, rough, and covered with powder. It is slightly hard and brittle. It has a fragrant aroma and a pungent, bitter, and salty taste.

[0239] The analysis results of the quality differences between the two processed tangerine peels, namely, the original process method and the A process method, are consistent and meet the quality standards for processed tangerine peels.

[0240] 2. Identification

[0241] The quality standard for processed tangerine peel stipulates: (1) The powder of this product is yellowish-brown. Calcium oxalate crystals are found in sheets in the parenchyma cells of the mesocarp, in the form of polyhedral, rhomboid, or bipyramidal shapes, with a diameter of 3-34 μm and a length of 5-53 μm. Some cells contain parallel twins composed of two polyhedra or 3-5 square crystals. Hesperidin crystals are mostly found in parenchyma cells, yellow or colorless, in the form of round or amorphous clumps, some with visible radial stripes (tangerine peel). Non-glandular trichomes are unicellular, slightly curved or hook-shaped, and the cell lumen often contains yellowish-brown substances (dried plum flesh).

[0242] (2) Take 0.3g of the powder, add 10ml of methanol, sonicate for 20 minutes, filter, take 5ml of the filtrate, concentrate to 1ml, and use as the test solution. Take 0.3g of the reference herb tangerine peel, and prepare the reference herb solution in the same way. Take the hesperidin reference standard, add methanol to prepare a saturated solution, and use as the reference standard solution. Perform the thin-layer chromatography test (General Rule 0502), take 4μl of each of the above three solutions, and spot them separately on the same silica gel G thin-layer plate prepared with 0.5% sodium hydroxide solution. Use ethyl acetate-formic acid-water (8:1:1) as the developing solvent, develop to about 8cm, remove, air dry, spray with aluminum trichloride test solution, and examine under ultraviolet light (365nm). In the chromatogram of the test sample, fluorescent spots of the same color appear at the corresponding positions as in the chromatograms of the reference herb and the reference standard.

[0243] (3) Take 10g of the powder, add 40ml of ether, heat under reflux for 1 hour, filter, discard the ether, add 30ml of methanol to the residue, heat under reflux for 1 hour, filter, evaporate the filtrate to dryness, add 40ml of water to dissolve the residue, extract with n-butanol 3 times, 20ml each time, combine the n-butanol extracts, wash with water 3 times, discard the aqueous solution, evaporate the n-butanol extract to dryness, add 5ml of methanol to dissolve the residue, and use this as the test solution. Take 1g of licorice reference material and prepare a reference material solution using the same method. Take glycyrrhizin reference standard and add methanol to prepare a solution containing 2mg per ml, and use this as the reference solution. Perform the thin-layer chromatography test (General Rule 0502). Apply 2 μl of each of the three solutions described above to the same silica gel G thin-layer plate prepared with 0.5% sodium hydroxide solution. Develop the plate using ethyl acetate-formic acid-glacial acetic acid-water (15:1:1:2) as the developing solvent. Remove the plate, air dry, spray with 10% sulfuric acid ethanol solution, and heat at 105℃ until the spots are clearly visible. Examine under ultraviolet light (365 nm). The chromatogram of the test sample should show fluorescent spots of the same color at the corresponding positions as those of the reference medicinal material and the reference standard.

[0244] The analysis results of the quality differences between the two processed tangerine peels, namely, the original process method and the A process method, are consistent and meet the quality standards for processed tangerine peels.

[0245] 3. Moisture

[0246] The quality standard for legally produced dried tangerine peel stipulates that it shall not exceed 13.0% (General Rule 0832, Law IV).

[0247] Both the original process method and the A process method of processed tangerine peel products meet the regulations, and the quality difference analysis results are consistent, which meets the quality standards for processed tangerine peel.

[0248] 4. Aflatoxin

[0249] The quality standard for processed dried tangerine peel stipulates that: per 1000g of this product, the content of aflatoxin B1 shall not exceed 5μg, and the total amount of aflatoxin G2, aflatoxin G1, aflatoxin B2 and aflatoxin B1 shall not exceed 10μg.

[0250] The original process method for processing tangerine peel contained no detectable aflatoxin B1 per 1000g, and the total amount of aflatoxin G2, aflatoxin G1, aflatoxin B2, and aflatoxin B1 was also undetectable. The A process method for processing tangerine peel contained no detectable aflatoxin B1 per 1000g, and the total amount of aflatoxin G2, aflatoxin G1, aflatoxin B2, and aflatoxin B1 was also undetectable. The quality difference analysis results for both methods are consistent and comply with the quality standards for processed tangerine peel.

[0251] 5. Content determination

[0252] The quality standard for processed dried tangerine peel stipulates that this product, calculated on a dried basis, contains hesperidin (C...). 28 H 34 O 15 (It shall not be less than 1.2%).

[0253] The original process method for processing dried tangerine peel yielded a purity of 1.59%, while the A process method yielded a purity of 1.55%. Both met the standard requirements, with minimal difference.

[0254] 4. Conclusion

[0255] In summary, during the decoction process of processed tangerine peel, the "extremely soft" and "drying" control in processing technique A is proposed to be "decoct until the tangerine peel is extremely soft, then drain." The decoction after draining contains very little hesperidin, approximately 1 / 47th of the hesperidin content in processed tangerine peel, indicating that the "draining" operation has little impact on the indicator components. The processed tangerine peel products obtained using the above two processing techniques show little difference in quality and both meet the proposed quality standards for processed tangerine peel.

[0256] IV. Research on the hangover-relieving effects of processed dried tangerine peel

[0257] 1. Experimental Design and Methods

[0258] 1.1 Model Replication Principle

[0259] A mouse alcohol intoxication model was established by gavage with edible alcohol.

[0260] 1.2 Laboratory Animals

[0261] Two hundred and forty male SPF mice, weighing 18-22g and aged 6-8 weeks, were used. The mice were fed a standard animal diet for 7 days at an ambient temperature of 20-24℃ and humidity of 40%-70%. The mice were observed for any abnormalities in their appearance, behavior, and feeding. Mice without abnormalities were selected for subsequent experiments.

[0262] 1.3 Experimental Methods

[0263] This study was divided into an alcohol group, a processed tangerine peel group, and a positive control group, with 8 animals in each group.

[0264] The alcohol group was administered a 35% (v / v) edible alcohol solution via gavage. 1 L of 95% (v / v) premium edible alcohol was mixed with 2.17 L of purified water and allowed to return to room temperature before being filtered through a 0.45 µm microporous membrane for later use.

[0265] The group of processed tangerine peel was administered a 35% (v / v) ethanol solution containing processed tangerine peel by gavage: processed tangerine peel was taken, crushed, extracted by hot reflux and concentrated into an extract, and then dissolved in a 35% (v / v) ethanol solution to prepare a drug solution with a crude drug concentration of 0.1 g / mL, which was used as the test solution for the group of processed tangerine peel.

[0266] The positive control group was administered a 35% ethanol solution containing Haiwang Jinzun tablets via gavage: 100g of Haiwang Jinzun tablets were weighed and 1000mL of 35% ethanol solution was measured to prepare a 0.1g / mL solution as the test solution for the positive control group.

[0267] 1.3.1 Mouse intoxication experiment

[0268] SPF mice that had undergone adaptive feeding were fasted and given free access to water for 12-16 hours prior to gavage. All mice were weighed and randomly divided into three groups (n=8 per group): an alcohol group, a positive control group, and a processed tangerine peel group. Each group was administered the corresponding test substance via gavage. The alcohol group received 0.15 ml / 10g of the test substance; the positive control group received 0.15 ml / 10g (equivalent to 10 times the daily dose of 9 g for a 60 kg adult, calculated based on mouse body weight); and the processed tangerine peel group received 0.15 ml / 10g (equivalent to 10 times the daily dose of 9 g for a 60 kg adult, calculated based on mouse body weight). The test substance was administered according to body weight, and the administration was repeated sequentially. The latency period (from the start of gavage to falling asleep, i.e., the disappearance of the righting reflex) and the intoxication period (from falling asleep to waking up, i.e., the recovery of the righting reflex) of mice were observed over a 5-hour period. The disappearance of the righting reflex was defined as mice exhibiting lethargy and failing to roll over within 30 seconds, at which point the intoxication time and latency period were recorded. The recovery of the righting reflex was defined as mice becoming agile, reacting freely, and rolling over twice consecutively within 60 seconds, at which point the sobering-up time and intoxication period were recorded. A mouse intoxication model was considered successfully established if the intoxication rate was higher than 90% and the mortality rate was 0% during the treatment period.

[0269] 1.3.2 Mouse Ethanol Metabolism Rate Experiment

[0270] SPF mice that had undergone adaptive feeding were fasted and given free access to water for 12-16 hours prior to gavage. All mice were randomly divided into an alcohol group, a processed tangerine peel group, and a positive control group, with 64 mice in each group. Ethanol levels in the mice were recorded at eight time points, with eight mice in each time point: 0, 0.25, 0.5, 0.75, 1, 6, 10, and 12 hours after alcohol gavage. Mice in the alcohol group that received alcohol gavage at 0 hours were given purified water and deprived of water, while other mice were given the corresponding test substance and deprived of water. The time of gavage was recorded. The gavage volume for all mice was based on the mouse intoxication experiment (calculated by mouse body weight). No mice died after gavage with the alcohol-containing test substance; however, all mice exhibited significant restlessness, incoordination, followed by paralysis and drowsiness, indicative of intoxication. During the experiment, blood was collected from the eyes of mice in each group at corresponding time points. After the blood samples from each group of mice were left to stand at room temperature for 30 minutes, they were centrifuged at 3500 rpm for 15 minutes. The serum samples from the upper layer were taken, frozen, and the ethanol content in the serum was detected.

[0271] 1.4 Statistical Methods

[0272] Data analysis was performed using SPSS statistical software. All data were expressed as mean plus or minus standard deviation. The mean ± standard deviation (±s) indicates that if homogeneity of variance is satisfied, the LSD test is used; if homogeneity of variance is not satisfied, the Dunnett test is used. ， The s-T3 test was performed. All analytical results were considered statistically significant with P < 0.05.

[0273] 2. The experimental results are shown in Tables 16 and 17.

[0274] Table 16 Analysis of intoxication time in mice (minutes, ±s)

[0275]

[0276] Table 17 Experimental data on changes in serum ethanol content in mice (mmol / L, ±s)

[0277]

[0278] As shown in Tables 16 and 17, compared with the alcohol group, the incubation period of the processed tangerine peel group and the positive control group was longer, and the difference was statistically significant. Compared with the alcohol group, the intoxication period in the processed tangerine peel group and the positive control group was shorter, and the difference was statistically significant. ).

[0279] One hour after oral administration of alcohol, serum ethanol levels in all groups of mice reached their peak. At 0.25, 0.5, 1, 6, and 10 hours, serum ethanol levels in both the processed tangerine peel group and the positive control group were lower than those in the alcohol group. There were no statistically significant differences in serum ethanol levels at 0 and 12 hours among the groups. ).

[0280] In summary, this invention, through its optimized processing techniques, such as optimizing the selection of dried tangerine peel raw materials, and adjusting the amount of water added, soaking time, decoction time, number of decoctions, and the moisture content of the intermediate dried tangerine peel before powdering after decoction, can maximize the preservation of the chemical components of the processed dried tangerine peel, significantly improve the quality of the finished product, and digitize and standardize the processing technology, making it suitable for large-scale industrial production while ensuring the safety, effectiveness, and quality control of clinical use. The processed dried tangerine peel of this invention can be used in the clinical treatment of "post-alcohol discomfort," improving upon the current limitations of drugs used for this symptom, which often have limited efficacy, cannot provide holistic treatment, and have numerous side effects and contraindications. This invention revitalizes the processing technology of dried tangerine peel, protects and explores the unique processing techniques of dried tangerine peel, a traditional medicinal material from Sichuan Province, and is conducive to the inheritance and innovation of traditional Chinese medicine processing techniques and the protection of dried tangerine peel germplasm resources.

Claims

1. Processed dried tangerine peel, characterized by: It is prepared from the following raw materials in the following weight ratio: 6-48 parts dried tangerine peel, 1.5-12 parts fennel seeds, 1.5-12 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum pulp, 0.1875-1.5 parts sandalwood, 0-24 parts coarse salt; Preferably, it is prepared from the following raw materials in the indicated weight ratios: 6-24 parts dried tangerine peel, 1.5-6 parts fennel seeds, 1.5-6 parts roasted licorice root, 0.375-3 parts dried ginger, 0.375-3 parts dried plum pulp, 0.1875-1.5 parts sandalwood, and 0-24 parts coarse salt. Further optimized, it is prepared from the following raw materials in the indicated weight ratios: 6-18 parts dried tangerine peel, 1.5-4.5 parts fennel seeds, 1.5-4.5 parts roasted licorice root, 0.375-1.5 parts dried ginger, 0.375-1.5 parts dried plum pulp, 0.1875-1 part sandalwood, and 0-12 parts coarse salt; Further preferred, it is prepared from the following raw materials in the indicated weight ratios: 12 parts dried tangerine peel, 3 parts fennel seeds, 3 parts roasted licorice root, 0.75 parts dried ginger, 0.75 parts dried plum pulp, 0.375 parts sandalwood, and 6 parts coarse salt.

2. The processed dried tangerine peel product according to claim 1, characterized in that: It satisfies at least one of the following: The raw material for the dried tangerine peel is the dried, mature peel of Citrus reticulata Blanco, a plant of the Rutaceae family, and its cultivated varieties. Alternatively, more preferably, the Rutaceae plant Citrus reticulata Blanco and its cultivated varieties include Citrus reticulata 'Chachi' (Guangdong Chenpi), Citrus reticulata 'Dahongpao', Citrus reticulata 'Unshiu', and Citrus reticulata 'Tangerina'. Alternatively, most preferably, the Rutaceae plant Citrus reticulata Blanco and its cultivated varieties are Citrus reticulata 'Dahongpao'.

3. The process method for producing processed dried tangerine peel according to claim 1 or 2, characterized in that: Includes the following steps: S1. Take dried tangerine peel, remove impurities, moisten it, and then cut it. S2. Take fennel seeds, roasted licorice root, dried ginger, dried plum flesh, sandalwood, and coarse salt, remove impurities, grind them into fine powder, and mix well. S3. Take the dried tangerine peel obtained in S1 and some of the medicinal powder obtained in S2, and soak them in water. S4. After soaking in water, heat and boil until the decoction is almost gone. Remove and let cool to obtain the intermediate product of processed tangerine peel. Alternatively, after soaking in water, heat and boil until the tangerine peel is very soft, then drain to obtain the intermediate product of processed tangerine peel. S5. Take the intermediate product of processed tangerine peel from S4 and mix it with the remaining medicinal powder in S2 after S3. S6. After mixing, dry at a temperature not exceeding 60℃.

4. The processing method for the prepared dried tangerine peel according to claim 3, characterized in that: At least one of the following must be met: The dried tangerine peel mentioned in step S1, before being processed in step S1, is either cut dried tangerine peel and / or crushed dried tangerine peel, or unprocessed dried tangerine peel raw material. Alternatively, in step S1, the cut products of dried tangerine peel include any one or more of the following: powder, slices, segments, blocks, shreds, and strips; Alternatively, preferably, the powder includes coarsest powder, coarse powder, medium powder, fine powder, finest powder, and extra-fine powder; Alternatively, preferably, the sheet thickness is 0–6 mm; Alternatively, preferably, the thickness of the segment is 3 to 17 mm; Alternatively, preferably, the block is a cube with a thickness of 6-14 mm; Alternatively, preferably, the thickness of the wire is 0-12 mm; Alternatively, more preferably, the thickness of the wire is 0-12 mm.

5. The processing method for the prepared dried tangerine peel according to claim 3, characterized in that: At least one of the following must be met: The pulverization described in step S2 refers to pulverizing the medicinal materials individually or pulverizing a mixture of medicinal materials. Alternatively, the fine powder mentioned in step S2 refers to powder that can pass through a No. 5 sieve completely and contains at least 95% of powder that can pass through a No. 6 sieve.

6. The processing method for the prepared dried tangerine peel according to claim 3, characterized in that: At least one of the following must be met: In step S3, the weight of the medicinal powder taken is 10 / 37 to 15 / 37 of the total weight of the medicinal powder in step S2; Alternatively, preferably, in step S3, the weight of the powder taken is 12 / 37 of the total weight of the powder in step S2; Alternatively, in step S3, the amount of water added is 4-12 times the weight of the medicinal materials in step S3; Alternatively, preferably, in step S3, the amount of water added is 6 times the weight of the medicinal materials in step S3; Alternatively, in step S3, the soaking time after adding water is 15 minutes to 1 hour; Alternatively, preferably, in step S3, the soaking time after adding water is 1 hour.

7. The processing method for the prepared dried tangerine peel according to claim 3, characterized in that: At least one of the following must be met: In step S4, the dried tangerine peel is very soft and needs to be simmered until it is thoroughly cooked. Alternatively, in step S4, the decoction is performed 1-3 times; Alternatively, preferably, in step S4, the frying is performed once.

8. The processing method for the prepared dried tangerine peel according to claim 3, characterized in that: At least one of the following must be met: In step S5, before mixing with the remaining medicinal powder, the moisture content of the intermediate product of processed tangerine peel is controlled to be 50%~85%. Alternatively, in step S5, the ratio of the remaining powder used to the powder used in step S3 is 27:10 to 22:15; Alternatively, preferably, in step S5, the ratio of the remaining powder used to the powder used in step S3 is 25:12; Alternatively, in step S5, the remaining medicinal powder used accounts for 22 / 37 to 27 / 37 of the total weight of the medicinal powder in step S2; Alternatively, preferably, in step S5, the remaining powder used accounts for 25 / 37 of the total weight of the powder used in step S2.

9. The processing method for the prepared dried tangerine peel according to claim 3, characterized in that: At least one of the following must be met: In step S6, the drying temperature is: not exceeding 60℃; Alternatively, the finished product in step S6 may be any one or more of the following: powder, flakes, segments, blocks, shreds, strips, or lumps.

10. Use of the processed tangerine peel product according to claim 1 or 2 in the preparation of a medicine for improving discomfort after drinking alcohol. It is used for food stagnation, phlegm and dampness obstructing the middle jiao, qi stagnation and discomfort, chest and diaphragm distension, belching with a foul odor and acid reflux, discomfort after drinking alcohol, and loss of appetite.

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