Silkworm excrement traditional Chinese medicine formula granules with good solubility and preparation method of silkworm excrement traditional Chinese medicine formula granules

Abstract

The invention discloses silkworm excrement traditional Chinese medicine formula granules with good solubility and a preparation method thereof, and the preparation method comprises the following steps: S1, packaging silkworm excrement decoction pieces by using a single-layer non-woven fabric bag, then adding a certain amount of purified water, decocting for a period of time, and filtering by using a duplex filter to obtain silkworm excrement decoction liquid; s2, concentrating the decoction to a certain solid content, and cooling; s3, adding a certain amount of compound enzyme into the concentrated solution, carrying out heat preservation and enzymolysis for a period of time, then heating and carrying out enzyme deactivation treatment, and collecting permeate after passing through a 300-mesh filter screen; s4, putting the silkworm excrement extraction concentrated solution subjected to enzymolysis into an inverted conical container, standing for a period of time, and then collecting supernate; s5, concentrating the supernate to obtain silkworm excrement extract, adding auxiliary materials, and performing spray drying; and S6, granulating the obtained silkworm excrement dry paste powder to obtain the silkworm excrement traditional Chinese medicine formula granules. Compared with a traditional silkworm excrement traditional Chinese medicine decoction, the silkworm excrement traditional Chinese medicine formula granules have the advantages of being good in solubility and free of sediment.

Description

Technical Field

[0001] The invention relates to the field of preparation of traditional Chinese medicine formula granules, and in particular to silkworm excrement traditional Chinese medicine formula granules with good solubility and a preparation method thereof. Background Art

[0002] Silkworm excrement is a formula granule made from the dried excrement of the silkworm (Bombyx mori Linnaeus), an insect of the Bombydae family, which is processed and made according to the main quality indicators of standard decoctions. Silkworm excrement tastes sweet and spicy, is warm in nature, and enters the liver and spleen meridians. It is rich in active ingredients such as flavonoids, polyphenols, vitamins, and alkaloids. It has the effects of dispelling wind and dampness, promoting blood circulation and dredges the menstruation, and can relieve rheumatic pain, amenorrhea, and urticaria pruritus.

[0003] However, silkworm excrement contains a large amount of toxic, harmful or anti-nutritional substances such as microorganisms, cellulose, tannins, pectin, phytic acid, etc., which lead to more precipitation in the traditional Chinese medicine decoction prepared by the conventional silkworm excrement decoction method, affecting the efficacy of the traditional Chinese medicine decoction and giving patients a poor taking experience. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides a silkworm excrement Chinese medicine formula granule with good solubility and a preparation method thereof, wherein enzymatic hydrolysis technology is used to decompose the insoluble impurities in the silkworm excrement decoction, and then the insoluble precipitates in the decoction are further removed by standing, thereby improving the solubility of the silkworm excrement formula granule in pure water and solving the turbidity problem of the silkworm excrement formula granule to a certain extent, so that the final silkworm excrement formula granule has the characteristic of good solubility.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for preparing silkworm excrement Chinese medicine formula granules with good solubility comprises the following steps:

[0007] Step 1: Decocting: decoct the silkworm excrement slices with purified water, filter, and obtain silkworm excrement decoction;

[0008] Step 2, concentration: Concentrate the silkworm excrement decoction and cool it to 30-65°C;

[0009] Step 3, enzymolysis: add 0.1-0.2% of the compound enzyme to the silkworm excrement concentrate, keep the temperature at 30-65℃ for 1-3h, then heat to 95-100℃ to inactivate the enzyme for 15-20min, and collect the permeate after filtering through a 300-mesh filter;

[0010] Step 4, standing and removing impurities: placing the silkworm excrement extract concentrate after enzymatic hydrolysis in an inverted conical container and standing for 5-10 hours, and then collecting the supernatant;

[0011] Step 5, secondary concentration and drying: taking the supernatant and concentrating it to a solid content of 20-30%, adding auxiliary materials of 3-10% of the amount of silkworm excrement medicinal materials, and spray drying to obtain silkworm excrement dry paste powder;

[0012] Step six, granulation: granulate the obtained silkworm excrement dry paste powder into granules to obtain the finished silkworm excrement traditional Chinese medicine formula granules.

[0013] Preferably, in the step one, a single-layer non-woven bag with a mesh size of 300-400 is used to encapsulate 1 / 2-1 / 3 of the volume of the silkworm excrement slices in the non-woven bag, and then 7-14 times the amount of pure water is added and boiled for 1-1.5 hours, 1-3 times of boiling, and the boiling temperature is 60-85°C, and then the silkworm excrement decoction is obtained after filtering through a double filter with a pore size of 100-200.

[0014] Preferably, in step 2, the decoction is concentrated to a solid content of 10-20%.

[0015] Preferably, in step three, the type and mass ratio of the complex enzyme are neutral protease: cellulase: pectinase = 1:1:1.

[0016] Preferably, in the step five, the auxiliary material is maltodextrin, and the spray drying parameters are the induced draft fan frequency of 30 Hz to 50 Hz, the atomizer frequency of 30 Hz to 50 Hz, the purge air temperature of 50°C to 85°C, the conveying air temperature of 40°C to 60°C, the inlet air temperature of 180°C to 200°C, and the outlet air temperature of 100°C to 120°C.

[0017] Preferably, in step six, the silkworm excrement Chinese medicine formula granules obtained have a paste yield of 11% to 20%.

[0018] The present invention also provides silkworm excrement Chinese medicine formula granules prepared by the method. The obtained silkworm excrement formula granules are subjected to chromatographic detection. Five characteristic peaks should be presented in the chromatogram, and the retention times should correspond to the five characteristic peaks in the chromatogram of the reference medicinal material. The peak corresponding to the protocatechuic acid reference peak is the S peak. The relative retention time of each characteristic peak and the S peak is calculated, wherein the relative retention time of peak 1, peak 3 and peak 4 should be within the range of ±10% of the specified value, and the relative retention time of peak 5 should be within the range of ±15% of the specified value. The specified values ​​are: 0.39 (peak 1), 1.12 (peak 3), 1.40 (peak 4), and 2.23 (peak 5).

[0019] The beneficial effects produced by the present invention are:

[0020] 1. Compared with the traditional silkworm excrement decoction, the silkworm excrement formula granules in the present invention have the characteristics of being ready to take and easy to carry.

[0021] 2. The present invention utilizes enzymatic hydrolysis technology and an inverted cone container static sedimentation impurity removal method to specifically remove insoluble impurities in the silkworm excrement decoction, so that the obtained silkworm excrement formula granules have the characteristics of being easy to dissolve and having no precipitation.

[0022] 3. The present invention does not use organic solvents in the process of preparing the silkworm excrement formula granules, and the whole process is green and safe. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is the comparative characteristic spectrum of the silkworm excrement formula granules in the present invention. DETAILED DESCRIPTION

[0024] The present application is further explained below in conjunction with specific implementation methods, but the embodiments do not limit the present application in any form.

[0025] Example 1

[0026] This embodiment discloses a silkworm excrement Chinese medicine formula granule with good solubility and a preparation method thereof, and the method steps are specifically as follows:

[0027] (1) A 300-mesh single-layer non-woven bag is filled with 1 / 3 of the volume of silkworm excrement slices, with a total amount of 5000 g of the slices, and then decocted with 35 L of pure water at 60° C. for 1 h, and then filtered with a 100-mesh double filter to obtain a silkworm excrement decoction. The silkworm excrement decoction is concentrated to a solid content of 10%, and then cooled to 30° C. 5 g of a composite enzyme (neutral protease: cellulase: pectinase = 1:1:1) is added to the silkworm excrement concentrate, and then the temperature is kept at 30° C. for 1 h, and then the temperature is raised to 95° C. for enzyme inactivation treatment for 15 min, and the permeate is collected after passing through a 300-mesh filter. The permeate after enzymolysis is placed in an inverted conical container and allowed to stand for 5 h, and then the supernatant is collected.

[0028] (2) The supernatant was concentrated to a solid content of 20%, 150 g of maltodextrin was added, and the spray drying was performed under the spray drying parameters of induced draft fan frequency of 30 Hz, atomizer frequency of 30 Hz, purge air temperature of 50° C., conveying air temperature of 40° C., inlet air temperature of 180° C., and outlet air temperature of 100° C. to obtain silkworm excrement dry paste powder. The obtained silkworm excrement dry paste powder was granulated into granules to obtain 1000 g of silkworm excrement Chinese medicine formula granule finished product.

[0029] Example 2

[0030] This embodiment discloses a silkworm excrement Chinese medicine formula granule with good solubility and a preparation method thereof, and the method steps are specifically as follows:

[0031] (1) A 1 / 2 bag volume of silkworm excrement slices was placed in a 350-mesh single-layer non-woven bag, with a total amount of 5000 g of slices, and then decocted at 75°C for 1.2 h using 50 L of purified water, and then filtered through a 150-mesh double filter to obtain a silkworm excrement decoction. The silkworm excrement decoction was concentrated to a solid content of 15%, and then cooled to 50°C. 7.5 g of a composite enzyme (neutral protease: cellulase: pectinase = 1:1:1) was added to the silkworm excrement concentrate, and then the temperature was kept at 50°C for 2 h, then the temperature was raised to 98°C for enzyme inactivation treatment for 17 min, and the permeate was collected after passing through a 300-mesh filter. The permeate after enzymolysis was placed in an inverted conical container and allowed to stand for 8 h, and then the supernatant was collected.

[0032] (2) The supernatant was concentrated to a solid content of 25%, 250 g of maltodextrin was added, and the spray drying parameters were as follows: induced draft fan frequency of 40 Hz, atomizer frequency of 40 Hz, purge air temperature of 65° C., conveying air temperature of 50° C., inlet air temperature of 190° C., and outlet air temperature of 110° C., to obtain silkworm excrement powder. The obtained silkworm excrement powder was granulated into granules to obtain 1000 g of silkworm excrement Chinese medicine granules.

[0033] Example 3

[0034] This embodiment discloses a silkworm excrement Chinese medicine formula granule with good solubility and a preparation method thereof, and the method steps are specifically as follows:

[0035] (1) A 1 / 2 bag volume of silkworm excrement slices was placed in a 400-mesh single-layer non-woven bag, with a total amount of 5000 g of slices, and then decocted at 85°C for 1.5 h using 70 L of purified water, and then filtered through a 200-mesh double filter to obtain a silkworm excrement decoction. The silkworm excrement decoction was concentrated to a solid content of 20%, and then cooled to 65°C. 10 g of a composite enzyme (neutral protease: cellulase: pectinase = 1:1:1) was added to the silkworm excrement concentrate, and then the temperature was kept at 65°C for 3 h, and then the temperature was raised to 100°C for enzyme inactivation treatment for 20 min, and the permeate was collected after passing through a 300-mesh filter. The permeate after enzymolysis was placed in an inverted conical container and allowed to stand for 10 h, and then the supernatant was collected.

[0036] (2) The supernatant was concentrated to a solid content of 30%, 300 g of maltodextrin was added, and the spray drying parameters were as follows: induced draft fan frequency of 50 Hz, atomizer frequency of 50 Hz, purge air temperature of 85° C., conveying air temperature of 60° C., inlet air temperature of 200° C., and outlet air temperature of 120° C., to obtain silkworm excrement powder. The obtained silkworm excrement powder was granulated into granules to obtain 1000 g of silkworm excrement Chinese medicine granules.

[0037] Comparative Example 1

[0038] In this comparative example, the steps of Example 1 were followed, except for the enzymatic treatment in step 3, and the remaining steps remained unchanged. The specific steps are as follows:

[0039] (1) A 300-mesh single-layer non-woven bag is filled with 1 / 3 of the bag volume of silkworm excrement slices, with a total amount of 5000 g of the slices, and then decocted with 35 L of purified water at 60° C. for 1 h, and then filtered with a 100-mesh double filter to obtain a silkworm excrement decoction. The silkworm excrement decoction is concentrated to a solid content of 10%, and then cooled to 30° C. The silkworm excrement concentrate is placed in an inverted conical container and allowed to stand for 5 h, and then the supernatant is collected.

[0040] (2) The supernatant was concentrated to a solid content of 20%, 140 g of maltodextrin was added, and the spray drying parameters were as follows: induced draft fan frequency of 30 Hz, atomizer frequency of 30 Hz, purge air temperature of 50° C., conveying air temperature of 40° C., inlet air temperature of 180° C., and outlet air temperature of 100° C., to obtain silkworm excrement powder. The obtained silkworm excrement powder was granulated into granules to obtain 1000 g of silkworm excrement Chinese medicine granules.

[0041] Comparative Example 2

[0042] In this comparative example, the steps of Example 1 were followed except for the step of placing the silkworm excrement concentrate in an inverted conical container for standing to remove impurities. The remaining steps remained unchanged. The specific steps are as follows:

[0043] (1) A 300-mesh single-layer non-woven bag is filled with 1 / 3 of the volume of silkworm excrement slices, with a total amount of 5000 g of the slices, and then decocted with 35 L of purified water at 60° C. for 1 h, and then filtered through a 100-mesh double filter to obtain a silkworm excrement decoction. The silkworm excrement decoction is concentrated to a solid content of 10%, and then cooled to 30° C. 5 g of a composite enzyme (neutral protease: cellulase: pectinase = 1:1:1) is added to the silkworm excrement concentrate, and then the enzymatic hydrolysis is kept at 30° C. for 1 h, and then the temperature is raised to 95° C. for enzyme inactivation treatment for 15 min, and the permeate is collected after passing through a 300-mesh filter.

[0044] (2) The permeate was concentrated to a solid content of 20%, 130 g of maltodextrin was added, and the permeate was spray-dried under the spray drying parameters of induced draft fan frequency of 30 Hz, atomizer frequency of 30 Hz, purge air temperature of 50° C., conveying air temperature of 40° C., inlet air temperature of 180° C., and outlet air temperature of 100° C. to obtain silkworm excrement dry paste powder. The obtained silkworm excrement dry paste powder was granulated into granules to obtain 1000 g of silkworm excrement traditional Chinese medicine formula granule finished product.

[0045] Test example

[0046] 1. Determination of the yield of silkworm excrement slices

[0047] Paste yield = (a×b) / (A×B)×100%

[0048] Where a represents the mass of the dry paste of silkworm excrement (g), B represents the sampling volume (mL), A represents the initial mass of the silkworm excrement (g), and b represents the volume of the silkworm excrement decoction (mL).

[0049] The yield of silkworm feces slices in each embodiment and comparative example was determined according to the method under General Chapter 2201 of the Chinese Pharmacopoeia (2020 edition), and the results are shown in Table 1.

[0050] Table 1 The yield of silkworm excrement slices in different embodiments and comparative examples

[0051]

[0052] As can be seen from Table 1, the yield of the silkworm excrement slices in Examples 1-3 is between 11% and 20%. Compared with Example 1, Comparative Examples 1 and 2 do not use the enzymatic hydrolysis step and the step of standing and removing impurities in the inverted conical container respectively, resulting in the yield of the silkworm excrement slices exceeding the specified value range. This shows that the enzymatic hydrolysis step and the step of standing and removing impurities in the inverted conical container in the present invention are integral, and the lack of any step cannot make the yield of the silkworm excrement slices within the specified range.

[0053] 2. Characteristic spectra of silkworm excrement granules in various embodiments and comparative examples

[0054] 2.1 Chromatographic conditions and system suitability test

[0055] Octadecylsilane bonded silica gel was used as the filler (column length: 250 mm, inner diameter: 4.6 mm, particle size: 5 μm); acetonitrile was used as mobile phase A, 0.1% formic acid solution was used as mobile phase B, and gradient elution was performed according to the provisions in Table 2; the flow rate was 1 mL per minute; the column temperature was 30°C; the detection wavelength was 259 nm. The theoretical plate number calculated based on the protocatechuic acid peak should not be less than 20,000.

[0056] Table 2 Gradient elution conditions

[0057]

[0058] 2.2 Preparation of reference solution

[0059] Take 2g of silkworm excrement control medicinal material, add 25mL of water, ultrasonically treat (power 300W, frequency 40kHz) for 30 minutes, cool, filter, and take the filtrate as the control medicinal material reference solution. Take an appropriate amount of protocatechuic acid reference substance, add methanol to make a solution containing 20μg per 1mL, as the control substance reference solution.

[0060] 2.3 Preparation of test solution

[0061] Take 2 g of this product, add 25 mL of water, and treat with ultrasound (power 300 W, frequency 40 kHz) for 30 minutes. Filter and take the filtrate to obtain the product.

[0062] 2.4 Determination method

[0063] Accurately pipette 10 μL of the reference solution and the test solution respectively, inject into the liquid chromatograph, and measure. There should be 5 characteristic peaks in the chromatogram of the test sample, and the retention time should correspond to the 5 characteristic peaks in the chromatogram of the reference medicinal material. The peak corresponding to the protocatechuic acid reference peak is the S peak. Calculate the relative retention time of each characteristic peak and the S peak. The relative retention time of peak 1, peak 3, and peak 4 should be within the range of ±10% of the specified value, and the relative retention time of peak 5 should be within the range of ±15% of the specified value. The specified values ​​are: 0.39 (peak 1), 1.12 (peak 3), 1.40 (peak 4), 2.23 (peak 5).

[0064] 2.5 Analysis of measurement results

[0065] Table 3 Relative retention time of control medicinal materials

[0066]

[0067] Table 4 Relative retention time of silkworm excrement granules in Examples 1-3 and Comparative Examples 1-2

[0068]

[0069] From the attached Figure 1 As can be seen from Table 3 and Table 4, the characteristic spectra of the silkworm feces formula granules in Examples 1-3 and Comparative Examples 1-2 all show 5 characteristic peaks, which correspond to the retention times of the 5 characteristic peaks in the chromatogram of the control medicinal material reference, and the relative retention time of each peak is within the range, which meets the requirements.

[0070] 3. Solubility of Silkworm Excrement Granules in Different Examples and Comparative Examples

[0071] 2.5 g of the silkworm excrement formula granules in different embodiments and comparative examples were accurately weighed, dissolved in 50 mL of pure water, shaken at a speed of 100 rpm / min for 2 min, and the precipitation of the solution was observed.

[0072] Table 5 Solubility of silkworm excrement granules in different embodiments and comparative examples

[0073]

[0074] As can be seen from Table 5, no precipitation occurs after the silkworm excrement formula granules in Examples 1-3 are dissolved, while obvious precipitation occurs in the silkworm excrement formula granules in Comparative Examples 1-2. Precipitation is a key indicator for measuring the dissolution stability of formula granules. The less precipitation, the higher the dissolution stability of the formula granules. The above results show that the enzymatic hydrolysis step and the static impurity removal step in the inverted cone container can significantly improve the solubility of the silkworm excrement formula granule solution and improve the patient's sensory experience of taking it.

[0075] Based on the above data analysis results, the silkworm excrement formula granules prepared in the embodiment of the present invention have the characteristics of good solubility. On the other hand, the silkworm excrement formula granules obtained by the present invention remove toxic, harmful or anti-nutritional substances such as cellulose, tannin, pectin, phytic acid, etc. during the preparation process, which is beneficial to improve the clinical efficacy of the silkworm excrement formula granules.

[0076] In summary, the above embodiments are only examples of the preferred embodiments of the present invention and do not include all the implementation scopes of the invention. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, the protection scope of the present invention shall be based on the scope defined in the claims.

Claims

1. A method for preparing silkworm excrement Chinese medicine granules with good solubility, characterized in that: The steps include: Step 1: Decocting: decoct the silkworm excrement slices with purified water, filter, and obtain silkworm excrement decoction; Step 2, concentration: Concentrate the silkworm excrement decoction and cool it to 30-65°C; Step 3, enzymolysis: add 0.1%-0.2% of the compound enzyme to the silkworm excrement concentrate, keep the temperature at 30-65℃ for 1-3h, then heat to 95-100℃ to inactivate the enzyme for 15-20min, and collect the permeate after filtering through a 300-mesh filter; Step 4, standing and removing impurities: placing the silkworm excrement extract concentrate after enzymatic hydrolysis in an inverted conical container and standing for 5-10 hours, and then collecting the supernatant; Step 5, secondary concentration and drying: taking the supernatant and concentrating it to a solid content of 20-30%, adding auxiliary materials of 3-10% of the amount of silkworm excrement medicinal materials, and spray drying to obtain silkworm excrement dry paste powder; Step six, granulation: granulate the obtained silkworm excrement dry paste powder into granules to obtain the finished silkworm excrement traditional Chinese medicine formula granules.

2. The preparation method according to claim 1, characterized in that: In the step 1, a single-layer non-woven bag with a mesh size of 300-400 is used to encapsulate 1 / 2-1 / 3 of the volume of the silkworm excrement slices in the non-woven bag, and then 7-14 times the amount of purified water is added and boiled for 1-1.5 hours, 1-3 times of boiling, and the boiling temperature is 60-85° C., and then the silkworm excrement decoction is obtained after filtering through a double filter with a pore size of 100-200.

3. The preparation method according to claim 1, characterized in that: In the step 2, the decoction is concentrated to a solid content of 10-20%.

4. The preparation method according to claim 1, characterized in that: In the step 3, the type and mass ratio of the complex enzyme are neutral protease: cellulase: pectinase = 1:1:

1.

5. The preparation method according to claim 1, characterized in that: In the step 5, the auxiliary material is maltodextrin, and the spray drying parameters are the induced draft fan frequency of 30Hz-50Hz, the atomizer frequency of 30Hz-50Hz, the purge air temperature of 50℃-85℃, the conveying air temperature of 40℃-60℃, the inlet air temperature of 180℃-200℃, and the outlet air temperature of 100℃-120℃.

6. The preparation method according to claim 1, characterized in that: In the step six, the silkworm excrement Chinese medicine formula granules obtained have a paste yield of 11% to 20%.

7. A silkworm excrement Chinese medicine formula granule prepared by the preparation method according to any one of claims 1 to 6.

8. The silkworm excrement Chinese medicine formula granules according to claim 7, characterized in that: The obtained silkworm excrement formula granules are subjected to chromatographic detection. Five characteristic peaks should be present in the chromatogram, and the retention time should correspond to the five characteristic peaks in the chromatogram of the reference medicinal material. The peak corresponding to the protocatechuic acid reference peak is the S peak. The relative retention time of each characteristic peak and the S peak is calculated. The relative retention time of peak 1, peak 3, and peak 4 should be within the range of ±10% of the specified value, and the relative retention time of peak 5 should be within the range of ±15% of the specified value. The specified value is: 0.39 (peak 1), 1.12 (peak 3), 1.40 (peak 4), 2.23 (peak 5).

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