Processing method for improving dissolution of medicinal components of taxus media reich f and application thereof

Abstract

The present application belongs to the technical field of traditional Chinese medicine processing, and particularly relates to a processing method for improving the dissolution of medicinal components of Taxus media and application thereof. The present application uses yellow rice wine to soak Taxus media, and then fries and roasts the soaked Taxus media with low heat to obtain wine Taxus media decoction pieces. Then, the wine Taxus media decoction pieces are processed with liquorice juice to obtain Taxus media decoction pieces with significantly increased content of paclitaxel, and enhanced anti-tumor effect. The processing method for Taxus media decoction pieces provided by the present application is simple, easy to realize industrial production, and has shorter processing time and higher efficiency than traditional replication processing. The method can efficiently prepare Taxus media decoction pieces with stable quality, increase the content of paclitaxel, and solve the problem of shortage of Taxus media resources.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine processing technology, specifically relating to a processing method for improving the dissolution rate of active ingredients in Taxus chinensis and its application. Background Technology

[0002] Taxus media, belonging to the genus Taxus in the family Taxaceae, is an important source for extracting the effective anticancer compound paclitaxel and its precursors. It is now included in the 2023 edition of the "Henan Province Standard for Traditional Chinese Medicine" and is widely used clinically to treat breast cancer, lung cancer, ovarian cancer, and esophageal cancer. However, Taxus plants grow slowly, have low taxane content, and purifying paclitaxel and its intermediates requires high costs. Therefore, both natural extraction and semi-synthetic chemical synthesis of paclitaxel are constrained by insufficient raw material sources, hindering the development of Taxus's advantageous medicinal resources and its widespread clinical application. New strategies to increase the supply of paclitaxel should be considered. Furthermore, paclitaxel has extremely poor solubility in water, resulting in low bioavailability and limiting its antitumor efficacy. Therefore, improving the bioavailability of paclitaxel and enhancing its antitumor efficacy can reduce the logging and exploitation of Taxus plants, representing a form of indirect protection of plant resources. Thus, it is necessary to innovate the processing methods of Taxus to improve the production efficiency of paclitaxel.

[0003] In clinical applications, paclitaxel is primarily administered via injection. However, injection administration has drawbacks such as significant toxic side effects, instability, and short-lived efficacy. Compared to injection, oral administration offers higher safety and is more suitable for long-term use. However, the paclitaxel derived from Taxus chinensis root slices currently used clinically exhibits poor water solubility and low oral bioavailability, severely limiting the application of its oral formulations in clinical treatment.

[0004] Currently, the processing methods for commercially available and clinically used Taxus chinensis involve cleaning or slicing. No other processing methods exist for Taxus chinensis slices, and research on processing methods for Taxus chinensis slices is lacking in existing technologies. Therefore, developing a new processing method for Taxus chinensis slices that can effectively increase the content of its anti-tumor active ingredients would be highly beneficial for both clinical applications and the promotion of the industrial production of Taxus chinensis slices. Summary of the Invention

[0005] The purpose of this invention is to provide a processing method that improves the dissolution rate of the active ingredients of Taxus chinensis, increases the paclitaxel content in processed Taxus chinensis products, and improves the bioavailability of paclitaxel in Taxus chinensis.

[0006] This invention provides a method for improving the dissolution rate of active ingredients in Taxus chinensis, comprising the following steps:

[0007] Mix Taxus chinensis slices with rice wine and let it steep.

[0008] After the Taxus chinensis leaves have been moistened, stir-fry them over a low heat until the moisture content is ≤13.0% to obtain wine-processed Taxus chinensis leaves.

[0009] Mix the prepared Taxus chinensis root slices with licorice juice, simmer over low heat until the medicine is fully absorbed and the juice is completely absorbed, then remove and dry to obtain Taxus chinensis root slices prepared with licorice juice.

[0010] Preferably, the mass ratio of the Taxus chinensis slices to the rice wine is 1:0.1 to 0.2.

[0011] Preferably, the alcohol content of the rice wine is 10-15% vol.

[0012] Preferably, the soaking time is 0.5 to 1.5 hours.

[0013] Preferably, during the simmering process, the temperature of the Taxus chinensis slices is 90–110°C; and the simmering time is 10–20 minutes.

[0014] Preferably, the mass ratio of the Taxus chinensis slices to the licorice juice is 1:10-15.

[0015] Preferably, the licorice juice is obtained by decocting licorice slices with water, and the mass ratio of licorice slices to water is 10-15:1.

[0016] Preferably, the drying temperature is 60-80°C and the drying time is 4-6 hours.

[0017] Preferably, the water content of the licorice juice-processed Taxus chinensis slices is ≤13.0%.

[0018] The present invention also provides the application of the processing method described in the above technical solution in the preparation of antitumor products.

[0019] Beneficial effects

[0020] This invention utilizes rice wine to moisten Taxus chinensis, followed by gentle stir-frying to obtain wine-processed Taxus chinensis slices. These slices are then further processed with licorice juice. The resulting Taxus chinensis slices exhibit a significantly increased paclitaxel content, enhancing the anti-tumor efficacy of Taxus chinensis. The processing method for Taxus chinensis slices provided by this invention is simple, easily scalable for industrial production, and compared to traditional methods, it is faster and more efficient. It can efficiently produce high-quality, stable Taxus chinensis slices, increasing paclitaxel content and addressing the shortage of Taxus chinensis resources. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the embodiments will be briefly described below.

[0022] Figure 1 The flowchart shows the processing method for improving the dissolution rate of the active ingredients of Taxus chinensis provided by the present invention. Detailed Implementation

[0023] This invention provides a method for improving the dissolution rate of active ingredients in Taxus chinensis, comprising the following steps:

[0024] Mix Taxus chinensis slices with rice wine and let it steep.

[0025] After the Taxus chinensis leaves have been moistened, they are stir-fried over a low heat until dry to obtain wine-processed Taxus chinensis leaves.

[0026] Mix the Taxus chinensis slices with licorice juice, simmer over low heat until the medicine is fully absorbed and the juice is completely used up, then remove the Taxus chinensis slices and dry them a second time.

[0027] This invention involves mixing Taxus chinensis slices with rice wine and then allowing them to steep.

[0028] In this invention, the soaking time is preferably 0.5 to 1.5 hours, more preferably 1.5 hours. The Taxus chinensis slices used in this invention are preferably cleaned or sliced ​​Taxus chinensis slices.

[0029] In this invention, the alcohol content of the rice wine is preferably 10-15% vol, more preferably 14-15% vol, and even more preferably 15% vol. The mass ratio of the Taxus chinensis slices to the rice wine is preferably 1:0.1-0.2, and even more preferably 1:0.15. Rice wine is very hot in nature, sweet and pungent in taste. It has a fragrant aroma, can promote the upward and downward movement of the medicine, and has the effects of activating blood circulation, dispelling wind and cold, and removing foul odors. Soaking Taxus chinensis in rice wine can guide the medicine upward and enhance the effects of Taxus chinensis in reducing swelling and lumps, relieving dysmenorrhea, and promoting diuresis; moreover, rice wine itself has a certain bactericidal and preservative effect. Taxus chinensis soaked in rice wine can be stored for a long time without easily spoiling, as long as it is properly prepared and stored in a dark and sealed container.

[0030] After being moistened, the present invention stir-fries the moistened Taxus chinensis slices over a low heat until the moisture content is ≤13.0%, thus obtaining the wine-processed Taxus chinensis slices.

[0031] In this invention, during the simmering process, the temperature of the Taxus chinensis slices is preferably 90-110°C, and the simmering time is preferably 10-20 minutes. During the simmering process, a vessel is used for simmering. In this invention, it is preferred that the vessel is heated first before adding the Taxus chinensis slices for simmering, and the temperature when adding the Taxus chinensis slices to the vessel is preferably 60-70°C.

[0032] After obtaining the Taxus chinensis slices, the present invention mixes the Taxus chinensis slices with licorice juice, simmers them over low heat until the medicine is fully absorbed and the juice is completely absorbed, and then removes the Taxus chinensis slices and dries them.

[0033] In this invention, the preferred mass ratio of the Taxus chinensis slices to licorice juice is 1:10-15, more preferably 1:15; the Taxus chinensis slices are preferably cooled to room temperature before mixing with licorice juice; the licorice juice is preferably obtained by decocting licorice slices with water, and the mass ratio of licorice slices to water is 10-15:1; the licorice slices are preferably soaked for 20-30 minutes before decocting with water. Glycyrrhizic acid in licorice exhibits characteristics of an amphiphilic surfactant. When the concentration reaches the critical micelle concentration, non-covalent bonds drive the formation of a core from hydrophobic segments (glycosidic structures) and a shell from hydrophilic segments (glycans), resulting in self-assembly of micelles, which effectively increases drug solubility. Paclitaxel and glycyrrhizic acid both belong to terpenoids and have similar relative molecular masses. Based on the principle of "like dissolves like," glycyrrhizic acid is miscible with paclitaxel. This invention uses licorice juice to replicate Taxus chinensis root slices, which can effectively improve the water solubility of paclitaxel in Taxus chinensis root slices. On the other hand, paclitaxel suffers from low intestinal permeability due to P-gp efflux, while the pharmacological functions of glycyrrhizic acid (such as the function of inhibiting P-gp) can effectively improve the bioavailability of paclitaxel by using glycyrrhizic acid as a carrier in the paclitaxel solubilization system.

[0034] In this invention, the drying temperature is 60–80°C, more preferably 60°C; the drying time is preferably 4–6 hours, more preferably 4 hours; and the moisture content of the licorice juice-processed Taxus chinensis slices is preferably ≤13.0%. This invention does not specifically limit the drying method, as long as the moisture content of the licorice juice-processed Taxus chinensis slices is ≤13.0%.

[0035] This invention selects a replication method using two excipients to process Taxus chinensis slices, which can effectively promote the solubility of paclitaxel in Taxus chinensis and enhance its anti-tumor pharmacological effect.

[0036] The present invention also provides the application of the processing method described in the above technical solution or the licorice juice-processed Taxus chinensis slices prepared by the processing method described in the above technical solution in the preparation of antitumor products.

[0037] To further illustrate the present invention, the following detailed description, in conjunction with the accompanying drawings and embodiments, provides a method for improving the dissolution rate of active ingredients in Taxus chinensis and its application, but these descriptions should not be construed as limiting the scope of protection of the present invention.

[0038] Example 1

[0039] according to Figure 1 The flowchart describes the processing of Taxus chinensis slices, specifically:

[0040] The medicinal material of Taxus chinensis was sorted to obtain Taxus chinensis decoction pieces;

[0041] Spread 100g of pure Taxus chinensis slices evenly on the bottom of a plate, with a thickness of 5mm. Add 15g of 15% vol Shaoxing wine and seal the plate to allow it to moisten.

[0042] Stir-fry the moistened Taxus chinensis slices over a low heat until the moisture content is ≤13.0%. The temperature of the low heat is 90-110℃. Stir-fry until the color deepens and the aroma is released. Remove and let cool to room temperature to obtain the Taxus chinensis slices for wine.

[0043] Separately, decoct licorice slices with water at a mass ratio of 15:1. Remove the licorice residue to obtain licorice juice.

[0044] Add licorice juice to Taxus chinensis slices (in a mass ratio of 15:1). Simmer over low heat until the juice is fully extracted, then remove and place in an oven to dry. Start timing when the temperature reaches 60℃ and dry at a constant temperature of 60℃ for 4 hours. This yields Taxus chinensis slices prepared with licorice juice.

[0045] Comparative Example 1

[0046] Same as Example 1, except that licorice juice is not used to process the Taxus chinensis slices, and the final product is Taxus chinensis slices in wine.

[0047] Comparative Example 2

[0048] Same as Example 1, except that rice wine is not used to process the Taxus chinensis slices, and the final product is Taxus chinensis slices processed with licorice juice.

[0049] Test Example 1

[0050] The unprocessed Taxus chinensis slices, Taxus chinensis slices prepared in Example 1, Comparative Example 1, and Comparative Example 2 were used as test samples. An octadecylsilane-bonded silica column with a length of 250 mm and an inner diameter of 4.6 mm was used as the chromatographic column. Acetonitrile (A)-0.1% trifluoroacetic acid aqueous solution (B) was used as the mobile phase, with a flow rate of 1 mL / min; the column temperature was 30 °C; the detection wavelength was 232 nm; and the injection volume was 10 μL. Gradient elution was performed to test the samples.

[0051] The gradient elution procedure is as follows:

[0052] 0~14min, 40%~65%A, 60%~35%B;

[0053] 14~15min, 65%~68%A, 35%~32%B;

[0054] 15~30min, 68%~100%A, 32%~0%B;

[0055] Accurately weigh paclitaxel reference standard, dissolve it in methanol and dilute to volume to prepare a solution with a mass concentration of 131.25 μg / mL. Accurately pipette 0.05 mL, 0.25 mL, 0.5 mL, 0.75 mL and 1 mL of the paclitaxel reference standard solution, respectively, and dilute to 1 mL. Inject a fixed volume of 10 μL and determine the chromatographic conditions as described above. Plot a standard curve with the reference standard concentration as the abscissa (X) and the peak area as the ordinate (Y).

[0056] The final paclitaxel standard curve was obtained as Y = 32017x - 92244, with a linear range of 65.625 μg to 1325 μg. Three parallel determinations were performed on each sample group, and the average value was taken as the paclitaxel peak area Y. The measured paclitaxel peak area Y was substituted into the equation to calculate the X value, thus determining the paclitaxel content. The results are shown in Table 1 below.

[0057] Table 1 Results of Paclitaxel Content Determination

[0058]

[0059] As shown in Table 1, the paclitaxel content test results indicate that the wine-processed Taxus chinensis and licorice-processed Taxus chinensis provided by this invention can effectively increase the paclitaxel content in Taxus chinensis, which is 28.06% higher than that of raw Taxus chinensis.

[0060] Comparative Example 3

[0061] The preparation method is the same as in Example 1, the only difference being that 52% vol white wine is used to moisten the Taxus chinensis slices.

[0062] Comparative Examples 4-6

[0063] The preparation methods for Comparative Examples 4 to 6 are the same as those for Example 1, except that the alcohol content of the rice wine used is different, as shown in Table 2 below.

[0064] Table 2 shows the alcohol content of the rice wine used in Comparative Examples 4-6.

[0065]

[0066] Test Example 2

[0067] The unprocessed Taxus chinensis slices, Taxus chinensis slices prepared in Example 1, and Taxus chinensis slices prepared in Comparative Examples 3 to 6 were used as test samples. The paclitaxel content was determined according to the method described in Test Example 1. The results are shown in Table 3 below.

[0068] Table 3 Results of Paclitaxel Content Determination

[0069]

[0070] As shown in Table 3, the paclitaxel content in the samples was higher when processed with rice wine than when processed with baijiu; and the highest paclitaxel content was obtained when processed with 15% vol rice wine.

[0071] Comparative Examples 7–14

[0072] The processing methods for Comparative Examples 7-14 are the same as those for Example 1, except that the drying conditions are different, as shown in Table 4 below.

[0073] Table 4 shows the conditions for the second drying in Comparative Examples 7–14.

[0074]

[0075] Test Example 3

[0076] The unprocessed Taxus chinensis slices, Taxus chinensis slices prepared in Example 1, and Taxus chinensis slices prepared in Comparative Examples 7 to 14 were used as test samples. The paclitaxel content was determined according to the method described in Test Example 1. The results are shown in Table 3 below.

[0077] Table 5 Results of Paclitaxel Content Determination

[0078]

[0079] As shown in Table 5, the highest paclitaxel content was found in the Taxus chinensis slices prepared from licorice juice when the drying temperature was 60℃ and the drying time was 4h.

[0080] Test Example 4

[0081] Using the licorice juice-based wine-making process of Taxus chinensis slices prepared in Example 1 as a sample, 1g of sample was accurately weighed, passed through a No. 5 sieve, placed in a stoppered conical flask, and treated with 50mL of methanol via ultrasonication (500W power, 50Hz frequency).

[0082] The sample was filtered twice, 30 min each time, and the filtrates were combined and evaporated to dryness in a water bath. The residue was dissolved in methanol and transferred to a 10 mL volumetric flask. Methanol was added to the mark, and the solution was shaken well and filtered through a 0.22 μm microporous membrane to obtain the test solution. The solution was injected for determination after standing for 0 h, 2 h, 4 h, 8 h, 12 h, and 24 h. The mass fraction of paclitaxel was calculated, and the results are shown in Table 6 below. The RSD values ​​for each group were 0.99%.

[0083] Table 6 Results of Paclitaxel Concentration Determination in Test Solution

[0084]

[0085] As shown in Table 6, the paclitaxel content in the test solution prepared from the licorice juice-based wine-making Taxus chinensis slices prepared in Example 1 did not change significantly within 24 hours of standing, indicating that the test solution was stable within 24 hours.

[0086] As can be seen from the above, the processing method for Taxus chinensis slices using the two excipients provided by this invention can significantly improve the solubility of the antitumor active ingredients in Taxus chinensis, alleviating the problem of Taxus chinensis resource scarcity. The processing method for Taxus chinensis provided by this invention is simple, easy to operate, and suitable for large-scale production and promotion.

[0087] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for processing Taxus chinensis slices to improve the content and dissolution rate of medicinal components, characterized in that, Includes the following steps: Mix Taxus chinensis slices with rice wine and let it steep. After the Taxus chinensis leaves have been moistened, stir-fry them over a low heat until the moisture content is ≤13.0% to obtain wine-processed Taxus chinensis leaves. Mix the prepared Taxus chinensis slices with licorice juice, simmer over low heat until the medicine is fully absorbed and the juice is completely removed, then remove and dry to obtain Taxus chinensis slices prepared with licorice juice. The mass ratio of the Taxus chinensis slices to the rice wine is 1:0.1-0.2; The alcohol content of the rice wine is 15% vol; The soaking time is 0.5 to 1.5 hours; The mass ratio of the Taxus chinensis slices to the licorice juice is 1:10-15; The licorice juice is obtained by decocting licorice slices with water, and the mass ratio of licorice slices to water is 10-15:

1. During the simmering process, the temperature of the Taxus chinensis slices is 90-110℃. The drying temperature is 60–80°C; the drying time is 4–6 hours.

2. The processing method according to claim 1, characterized in that, The simmering time is 10 to 20 minutes.

3. The processing method according to claim 1 or 2, characterized in that, The water content of the licorice juice-processed Taxus chinensis slices is ≤13.0%.

4. The application of the processing method according to any one of claims 1 to 3 in the preparation of antitumor products.

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