A kind of aralia leaf formula granule and preparation method thereof

Abstract

The present invention provides a larvae leaf formula granule and a preparation method thereof, and belongs to the technical field of formula granules. The preparation method of the larvae leaf formula granule comprises the following steps: a. mixing the larvae leaf decoction pieces with water and hydroxypropyl-β-cyclodextrin, heating and extracting after soaking, and separating the extract and the residue; b. adding water to the residue and continuing to heat and extract, and separating the extract and the residue; c. combining the extracts in step a and step b for concentration to obtain a clear paste; d. mixing the clear paste with dextrin or silicon dioxide, and then spray drying and dry granulating in sequence to obtain the larvae leaf formula granule. The preparation method of the present invention improves the transfer rate and stability of kaempferol-3-O-gentiobioside in the larvae leaf formula granule, ensures the quality of the larvae leaf formula granule, and ensures the safety and effectiveness of clinical medication.

Description

Technical Field

[0001] The invention relates to the technical field of formula particles, and in particular to a larix ternata leaf formula particle and a preparation method thereof. Background Art

[0002] Chinese medicine granules are made from single Chinese medicine slices through water extraction, concentration, drying and granulation. After the clinical prescription of traditional Chinese medicine, they are taken by patients. Longli leaf is a traditional medicine in the south. It has the effect of moistening the lungs and relieving coughs. It has a good effect on dry coughs, sore throat and aphonia.

[0003] Sauropus spatulifolius Beille is the dried leaf of the Euphorbiaceae plant Sauropus spatulifolius Beille. It is sweet, light, and flat in nature. It enters the lung and stomach meridians and has the effects of moistening the lungs, relieving cough, and relieving constipation. It is used for dry cough, sore throat, aphonia, and constipation. Sauropus spatulifolius Beille mainly contains a variety of biologically active ingredients such as monoterpenes, sesquiterpenes, coumarins, and flavonoid glycosides. Among them, the flavonoid glycoside component kaempferol-3-O-gentiobioside has anti-inflammatory, antitussive, antispasmodic, and anti-ulcer effects, and is the main active ingredient of Sauropus spatulifolius Beille.

[0004] The existing production technology of galangal leaf formula granules mainly adopts the extraction method of static decoction twice, and the static decoction has the problems of high decoction temperature and long decoction time. The effective ingredient of galangal leaf, kaempferol-3-O-gentiobioside, is thermally unstable and has poor water solubility. It is degraded by the influence of long-term high temperature during water extraction, decoction, concentration, atomization drying, granulation and drying, resulting in low transfer rate and content deviation from the technical requirements of standard decoctions, affecting the safety and effectiveness of clinical medication. Therefore, developing a new preparation method to improve the transfer rate and stability of kaempferol-3-O-gentiobioside in galangal leaf formula granules can effectively promote its clinical application effect, ensure the quality and efficacy of the drug, and meet the needs of the development of modern Chinese medicine. Summary of the invention

[0005] The object of the present invention is to provide a method for preparing galangal leaf formula granules, which can improve the content of kaempferol-3-O-gentiobioside and ensure the quality of the galangal leaf formula granules.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing granules of galangal leaves, comprising the following steps:

[0008] a. Mix the Longru leaf pieces with water and hydroxypropyl-β-cyclodextrin, soak and heat to extract, and separate the extract and the residue;

[0009] b. Add water to the residue and continue heating and extracting, and separating the extract and the residue;

[0010] c. combining the extracts in step a and step b and concentrating them to obtain a clear paste;

[0011] d. The clear paste is mixed with dextrin or silicon dioxide, and then spray-dried and dry-granulated to obtain the larkspur leaf formula granules.

[0012] Preferably, the Longtan Leaf pieces in step a are pieces obtained by selecting medicinal materials.

[0013] Preferably, the amount of water added in step a is 13 to 17 times the weight of the Longtou Leaf slices, and the amount of hydroxypropyl-β-cyclodextrin added is 3 to 5% of the weight of the Longtou Leaf slices.

[0014] Preferably, the soaking time in step a is 30 to 60 minutes; the temperature during the heating extraction is 85 to 100° C. and the time is 1.0 to 1.5 hours.

[0015] Preferably, the amount of water added in step b is 10 to 14 times the weight of the medicinal residue, and the temperature during the heating extraction is 80 to 100° C. and the time is 0.5 to 1.0 h.

[0016] Preferably, the concentration temperature in step c is 50-70° C., and the relative density of the clear paste is 1.01-1.05.

[0017] Preferably, the amount of dextrin or silicon dioxide added in step d is 0.5-1.5% of the weight of the medicinal piece.

[0018] Preferably, in the step d, the inlet air temperature of the spray drying is 165-180°C, the outlet air temperature is 85-105°C, and the atomizing disk frequency is 25-35 Hz.

[0019] Preferably, the parameters of the dry granulation in step d are: a feeding speed of 35 to 60 r / min, a pressing wheel speed of 5 to 28 r / min, a main pressure of 10 to 50 bar for granulation, and a granulation screen mesh of 14 to 16 meshes.

[0020] The present invention also provides the aralia leaf formula granules prepared by the preparation method of the aralia leaf formula granules.

[0021] The preparation method of the galangal leaf formula granules provided by the present invention improves the solubility of kaempferol-3-O-gentiobioside in water and the stability of the heating process by adopting hydroxypropyl-β-cyclodextrin to assist in extraction, optimizes the feeding specification, extraction time and water addition amount, improves the extraction transfer rate of kaempferol-3-O-gentiobioside, which is an effective ingredient of the galangal leaf formula granules, and ensures the quality stability of the galangal leaf formula granules. DETAILED DESCRIPTION

[0022] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0023] Example 1

[0024] A preparation method of aralia leaf formula granules:

[0025] a. After selecting and removing impurities from the medicinal material of Longtan Leaf, and cleaning, obtain Longtan Leaf decoction pieces; put the Longtan Leaf decoction pieces into an extractor, add 15 times the weight of water, soak for 30 minutes, extract for 60 minutes at 100° C., filter and separate the extract and the medicinal residue; dynamic circulation extraction is adopted during heating extraction;

[0026] b. Take the residue from step a, add 12 times the weight of water, extract at 100° C. for 40 min, filter and separate the extract and the residue; dynamic circulation extraction is used during heating extraction;

[0027] c. Combine the extracts in step a and step b, cool to below 65°C, let stand for 6-8h, take the supernatant and concentrate under reduced pressure at 65°C to obtain a clear paste;

[0028] d. Add 1% dextrin in the amount of the decoction piece to the clear paste, stir evenly, and then spray dry (inlet air temperature 175°C, outlet air temperature 90-95°C, atomizing disk frequency 25Hz) to obtain a dry powder; the dry powder is evenly mixed with 0.5% maltodextrin by weight, and dry granulated (feeding speed 50r / min, pressure wheel speed 15r / min, main pressure 30bar for granulation, whole granulation screen mesh number 16 mesh) to obtain the longtan leaf formula granules.

[0029] Example 2

[0030] A preparation method of aralia leaf formula granules:

[0031] a. After removing impurities and cleaning the Longtou Leaf medicinal material, the Longtou Leaf medicinal material is cut into 5-10 mm wide threads to obtain Longtou Leaf medicinal pieces; the Longtou Leaf medicinal pieces are put into an extractor, 15 times the weight of the medicinal pieces of water and 4% weight of hydroxypropyl-β-cyclodextrin are added, the above-mentioned part is dissolved in water before the addition of hydroxypropyl-β-cyclodextrin to prepare a solution, soaked for 30 minutes, extracted at 100° C. for 60 minutes, and filtered to separate the extract and the medicinal residue; dynamic circulation extraction is adopted during heating extraction;

[0032] b. Take the residue from step a, add 12 times the weight of water, extract at 100° C. for 40 min, filter and separate the extract and the residue; dynamic circulation extraction is used during heating extraction;

[0033] c. Combine the extracts in step a and step b, cool to below 65°C, let stand for 6-8h, take the supernatant and concentrate under reduced pressure at 65°C to obtain a clear paste;

[0034] d. Add 1% dextrin in the amount of the decoction piece to the clear paste, stir evenly, and then spray dry (inlet air temperature 175°C, outlet air temperature 90-95°C, atomizing disk frequency 25Hz) to obtain a dry powder; the dry powder is evenly mixed with 0.5% maltodextrin by weight, and dry granulated (feeding speed 50r / min, pressure wheel speed 15r / min, main pressure 30bar for granulation, whole granulation screen mesh number 16 mesh) to obtain the longtan leaf formula granules.

[0035] Example 3

[0036] A preparation method of aralia leaf formula granules:

[0037] a. After selecting and removing impurities from the medicinal material of Longtou Leaf and cleaning, Longtou Leaf decoction pieces are obtained; the Longtou Leaf decoction pieces are put into an extractor, 15 times the weight of the decoction pieces of water and 4% weight of hydroxypropyl-β-cyclodextrin are added, the above-mentioned part is dissolved in water to prepare a solution before the addition of hydroxypropyl-β-cyclodextrin, soaked for 30 minutes, extracted at 100° C. for 60 minutes, and filtered to separate the extract and the medicinal residue; dynamic circulation extraction is adopted during heating extraction;

[0038] b. Take the residue from step a, add 12 times the weight of water, extract at 100° C. for 40 min, filter and separate the extract and the residue; dynamic circulation extraction is used during heating extraction;

[0039] c. Combine the extracts in step a and step b, cool to below 65°C, let stand for 6-8h, take the supernatant and concentrate under reduced pressure at 65°C to obtain a clear paste;

[0040] d. Add 1% dextrin in the amount of the decoction piece to the clear paste, stir evenly, and then spray dry (inlet air temperature 175°C, outlet air temperature 90-95°C, atomizing disk frequency 25Hz) to obtain a dry powder; the dry powder is evenly mixed with 0.5% maltodextrin by weight, and dry granulated (feeding speed 50r / min, pressure wheel speed 15r / min, main pressure 30bar for granulation, whole granulation screen mesh number 16 mesh) to obtain the longtan leaf formula granules.

[0041] Example 4

[0042] A preparation method of aralia leaf formula granules:

[0043] a. After selecting and removing impurities from the medicinal material of Longtou Leaf and cleaning, Longtou Leaf decoction pieces are obtained; the Longtou Leaf decoction pieces are put into an extractor, 15 times the weight of the decoction pieces of water and 4% weight of hydroxypropyl-β-cyclodextrin are added, the above-mentioned part is dissolved in water to prepare a solution before the addition of hydroxypropyl-β-cyclodextrin, soaked for 30 minutes, extracted at 100° C. for 60 minutes, and filtered to separate the extract and the medicinal residue; dynamic circulation extraction is adopted during heating extraction;

[0044] b. Take the residue from step a, add 12 times the weight of water, extract at 100° C. for 40 min, filter and separate the extract and the residue; dynamic circulation extraction is used during heating extraction;

[0045] c. Combine the extracts in step a and step b, cool to below 65°C, let stand for 6-8h, take the supernatant and concentrate under reduced pressure at 65°C to obtain a clear paste;

[0046] d. Add 1% silicon dioxide in the amount of the decoction piece to the clear paste, stir evenly, and then spray dry (inlet air temperature 175°C, outlet air temperature 90-95°C, atomizing disk frequency 25Hz) to obtain a dry powder; the dry powder is evenly mixed with 0.5% maltodextrin by weight, and dry granulated (feeding speed 50r / min, pressure wheel speed 15r / min, main pressure 30bar, granulation, whole granulation screen mesh number 16 mesh) to obtain the longtan leaf formula granules.

[0047] Comparative Example

[0048] A preparation method of aralia leaf formula granules:

[0049] a. After removing impurities and cleaning the Longtou leaf medicinal material, the Longtou leaf medicinal material is cut into 5-10 mm wide threads to obtain Longtou leaf medicinal pieces; the Longtou leaf medicinal pieces are put into an extractor, 15 times the weight of water is added to the medicinal pieces, and the extract is extracted at 100° C. for 1 hour, and the extract and the medicinal residue are separated by filtration;

[0050] b. Take the residue from step a, add 12 times the weight of water, extract at 100° C. for 40 min, and filter and separate the extract and the residue;

[0051] c. Combine the extracts in step a and step b, cool to below 65°C, let stand for 6-8 hours, and concentrate the supernatant under reduced pressure at 65°C;

[0052] d. Add 1% dextrin in the amount of the decoction piece to the clear paste, stir evenly, and then spray dry (inlet air temperature 175°C, outlet air temperature 90-95°C, atomizing disk frequency 25Hz) to obtain a dry powder; the dry powder is evenly mixed with 0.5% maltodextrin by weight, and dry granulated (feeding speed 50r / min, pressure wheel speed 15r / min, main pressure 30bar for granulation, whole granulation screen mesh number 16 mesh) to obtain the longtan leaf formula granules.

[0053] The relative density of the clear paste in the above-mentioned Examples 1 to 5 and the comparative example is between 1.03 and 1.05.

[0054] Test Example 1

[0055] 1. Determination method of paste yield

[0056] Accurately measure 25 ml of the concentrated clear paste into a constant weight evaporating dish (M0), weigh the total mass of the evaporating dish and the drug solution M1, evaporate to dryness in a water bath, dry at 105°C for 3 h, quickly take out and place in a desiccator for 30 min, weigh the weight M closely, and calculate the paste rate.

[0057]

[0058] 2. Determination of kaempferol-3-O-gentiobioside content in decoction pieces

[0059] Determined according to the Chinese Pharmacopoeia High Performance Liquid Chromatography (General Chapter 0512).

[0060] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel is used as filler; methanol-0.4% phosphoric acid solution (48:52) is used as mobile phase; detection wavelength is 349nm. The theoretical plate number calculated based on the kaempferol-3-O-gentiobioside peak should be no less than 3000.

[0061] Preparation of reference solution: Take an appropriate amount of kaempferol-3-O-gentiobioside reference substance, accurately weigh it, and add 50% methanol to make a solution containing 55 μg per 1 ml.

[0062] Preparation of test solution: Take about 1 g of the powder of the product (passed through No. 2 sieve), accurately weigh it, place it in a stoppered conical flask, accurately add 25 ml of 50% methanol, stopper it, weigh it, ultrasonically treat it (power 250 W, frequency 33 kHz) for 40 minutes, cool it, weigh it again, make up the lost weight with 50% methanol, shake it well, filter it, and take the filtrate to obtain it.

[0063] Accurately pipette 10 μl of reference solution and test solution respectively, inject into liquid chromatograph, and measure to obtain the result.

[0064] 3. Determination method of kaempferol-3-O-gentiobioside content in formula granules

[0065] Determined by high performance liquid chromatography (General Rules 0512 of the Chinese Pharmacopoeia 2020 Edition).

[0066] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel as filler; methanol-0.4% phosphoric acid solution (43:57) as mobile phase; flow rate of 0.8 ml per minute; detection wavelength of 349 nm. The theoretical plate number calculated based on the kaempferol-3-O-gentiobioside peak should be no less than 3000.

[0067] Preparation of reference solution: Take an appropriate amount of kaempferol-3-O-gentiobioside reference substance, weigh it accurately, place it in a brown volumetric flask, and add methanol to make a solution containing 100 μg per 1 ml.

[0068] Preparation of test solution: Take an appropriate amount of the product, grind it into powder, take about 0.2g, weigh it accurately, put it in a stoppered conical flask, accurately add 25ml of 50% methanol, weigh it, ultrasonically treat it (power 250W, frequency 40kHz) for 60 minutes, cool it, weigh it again, make up the lost weight with 50% methanol, shake it well, filter it, and take the filtrate to obtain it.

[0069] Accurately pipette 5 μl of reference solution and test solution respectively, inject into liquid chromatograph, and measure to obtain the result.

[0070] 4. Calculation method of kaempferol-3-O-gentiobioside content transfer rate

[0071]

[0072] The specifications of the formula granules are: every 1g of formula granules is equivalent to 2.5g of medicinal pieces, and the specifications mentioned in the calculation formula are 2.5.

[0073] 5. Take the galangal leaf formula granules prepared in each embodiment and comparative example, measure the content of kaempferol-3-O-gentiobioside, and calculate the cream rate and transfer rate. The results are shown in Table 1:

[0074] Table 1 Comparison of the process of the embodiment and comparative example of the formula granule of the dragon tongue leaf

[0075]

[0076] It can be seen from the above table that compared with the comparative example, Example 1 does not shred the pretreatment, and the content transfer rate is significantly improved; compared with the comparative example, Example 2 adds hydroxypropyl β-cyclodextrin during the extraction process, and the transfer rate is significantly improved; it can be seen that both the methods of not shredding the pieces and adding hydroxypropyl-β-cyclodextrin can significantly improve the transfer rate of kaempferol-3-O-gentiobioside; Example 3 simultaneously adopts the method of selecting the pieces without cutting them, extracting and adding hydroxypropyl-β-cyclodextrin, and the transfer rate of kaempferol-3-O-gentiobioside is 3 times that of the comparative example; further changing the fluidity of the spray-dried paste powder, Example 4 uses silicon dioxide for spray drying, and the content transfer rate is slightly improved. It is considered that silicon dioxide improves the viscosity of the material, and the paste powder yield is high, which improves the content and transfer rate of kaempferol-3-O-gentiobioside.

[0077] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a granule of aralia leaf formula, characterized in that: The steps include: a. Mix the Longru leaf pieces with water and hydroxypropyl-β-cyclodextrin, soak and heat to extract, and separate the extract and the residue; b. Add water to the residue and continue heating and extracting, and separating the extract and the residue; c. combining the extracts in step a and step b and concentrating them to obtain a clear paste; d. The clear paste is mixed with dextrin or silicon dioxide, and then spray-dried and dry-granulated to obtain the granules of the herba spatholobi.

2. The method for preparing the larkspur leaf formula granules according to claim 1, characterized in that: The Longtan leaf decoction pieces in step a are decoction pieces obtained by cleaning the medicinal materials.

3. The method for preparing the larix galanga leaf formula granules according to claim 1, characterized in that: In the step a, the amount of water added is 13 to 17 times the weight of the Longtou leaf slices, and the amount of hydroxypropyl-β-cyclodextrin added is 3 to 5% of the weight of the Longtou leaf slices.

4. The method for preparing the larix galanga leaf formula granules according to claim 1, characterized in that: The soaking time in step a is 30 to 60 minutes; the temperature during the heating extraction is 85 to 100° C. and the time is 1.0 to 1.5 hours.

5. The method for preparing the larix galanga leaf formula granules according to claim 1, characterized in that: The amount of water added in step b is 10 to 14 times the weight of the medicinal residue, and the temperature during the heating extraction is 80 to 100° C. and the time is 0.5 to 1.0 h.

6. The method for preparing the larkspur leaf formula granules according to claim 1, characterized in that: The concentration temperature in step c is 50-70° C., and the relative density of the clear paste is 1.01-1.

05.

7. The method for preparing the larkspur leaf formula granules according to claim 1, characterized in that: In the step d, the amount of dextrin or silicon dioxide added is 0.5-1.5% of the weight of the medicinal piece.

8. The method for preparing the larix galanga leaf formula granules according to claim 1, characterized in that: In the step d, the inlet air temperature of the spray drying is 165-180° C., the outlet air temperature is 85-105° C., and the atomizing disk frequency is 25-35 Hz.

9. The method for preparing the larix galanga leaf formula granules according to claim 1, characterized in that: The parameters of the dry granulation in step d are: a feeding speed of 35 to 60 r / min, a pressing wheel speed of 5 to 28 r / min, a main pressure of 10 to 50 bar for granulation, and a granulation screen mesh of 14 to 16 meshes.

10. An Aralia dahurica leaf formula granule prepared by the method for preparing the Aralia dahurica leaf formula granule according to any one of claims 1 to 9.

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