Formula and preparation process of pearl, radix salviae miltiorrhizae and fructus gardeniae granules

Abstract

The invention relates to a formula and a preparation process of pearl, salvia miltiorrhiza and fructus gardeniae granules. The formula comprises nacre mother of pearl, oyster, vinegar-processed bupleurum chinense, mint, angelica sinensis, albizia flower, parched white peony root, salvia miltiorrhiza, platycladi seed, tuber fleeceflower stem, red date, cortex moutan and raw fructus gardeniae. The traditional Chinese medicine formula follows ancient but not muddy, realizes dialectical treatment, adopts medicines, has the effects of calming the liver, suppressing yang, soothing the liver, clearing heat and tranquilizing by nourishing the heart on the basis of the traditional effects of soothing the liver, clearing heat and tranquilizing the mind, follows the compatibility principle of monarch, minister, assistant and guide, realizes the effects of calming the liver, suppressing yang, soothing the liver, clearing heat, nourishing the heart and tranquilizing the mind, and complements each other. The process flow of the formula is standardized, and the quality processes of pretreatment, cleaning, first decoction, twice extraction of medicine residues, distillation for extraction of volatile oil, beta-cyclodextrin inclusion, concentration, drying, granulation, subpackaging and the like are controllable. The systematized and standardized extraction process is scientific and reasonable, effective components are extracted and retained to the maximum extent, the quality meets the standards of Pharmacopoeia (2025 edition) of the People's Republic of China, and the homogeneity and identity of finished products are high.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine granule manufacturing technology, specifically relating to a formula and manufacturing process of Pearl Danzhi Granules. Background Technology

[0002] The existing raw materials for Pearl Gardenia Granules are of mixed varieties, and the different growing environments and processing methods of the medicinal materials may lead to differences in the content of their active ingredients. If the active ingredients of the raw materials are not strictly controlled during the production process, the content of active ingredients in the finished product may be low or unstable, affecting the efficacy of the drug.

[0003] In terms of technology Excessive viscosity of the extract makes granulation difficult: During the production of pearl granules, the extract itself acts as a binder. When the extract is too viscous, it easily adsorbs the excipients and clumps together, resulting in "lumps" on the sieve during granulation and making the granules prone to mottled appearance. Inconsistent particle size: In the wet granulation process, if the soft material is not stirred evenly, the ethanol content of the wetting agent is too high, or the sieve is not properly selected, the resulting particles may be too coarse or too fine, have too much powder at the beginning, or have a low yield of particles in one pass, which will affect the quality and stability of the product. Uneven particle color: Insufficient mixing of extract and excipients, high moisture content of excipients, incomplete cleaning of equipment and containers, and inconsistent particle drying temperature may all cause uneven particle color or the presence of discolored spots or mottling, affecting the appearance quality of the product. Poor solubility: If the precipitant is not used in accordance with the process standard during the extraction of refined extract, or if the precipitation time is insufficient or no precipitation is carried out, the extract may contain a large amount of insoluble and ineffective components such as starch and protein. Alternatively, if the separation method after refining is inappropriate, the extract may contain a large number of impurity particles, which may result in the solubility of the particles not meeting the requirements. Non-standard production processes: Some companies may have problems with their production processes, such as not strictly controlling parameters such as extraction temperature and time, and not following standard operating procedures in concentration and drying, which affect the extraction and retention of the active ingredients in the product, and thus affect the product quality. Summary of the Invention

[0004] The purpose of this invention is to solve the above-mentioned problems. This application proposes a formula and manufacturing process for Pearl Danzhi Granules, in which the proportions of medicinal materials are clearly defined, conforming to the principle of monarch, minister, assistant and guide in the formulation, and the medicinal materials are treated in a targeted manner to improve the utilization rate of the ingredients and ensure the efficacy of soothing the liver and relieving depression.

[0005] The formula for Pearl Gardenia Granules includes mother-of-pearl, oyster shell, vinegar-processed Bupleurum chinense, peppermint, angelica sinensis, Albizia julibrissin flower, stir-fried white peony root, salvia miltiorrhiza, Platycladus orientalis seed, Polygonum multiflorum stem, red dates, peony bark, and raw gardenia fruit. Its manufacturing process includes: S1. Pre-processing of medicinal materials Mother-of-pearl and oyster shells are magnetically separated to remove metallic impurities, washed with water to remove dust, and then crushed to 20-30 mesh using a crusher. Pit the red dates manually; Raw gardenia fruit is processed using a crusher; The ingredients, including Albizia julibrissin flowers, stir-fried white peony root, Salvia miltiorrhiza, Platycladus orientalis seed, Polygonum multiflorum stem, and Paeonia suffruticosa root bark, are soaked and treated. S2. Volatile oil extraction Vinegar-processed Bupleurum chinense, Angelica sinensis, and Mentha haplocalyx were extracted separately by distillation. During distillation, 6 times the amount of purified water was added to each herb, and the extraction was carried out for 2 hours. The distillate was collected and allowed to stand for separation. The volatile oil was then separated from the volatile oil. β - Cyclodextrin encapsulation yields volatile oil inclusion compounds for later use; the distilled residue is combined with other medicinal materials for conventional decoction; S3. Simmering 3.1 Soak the raw materials for 1 hour before decoction, and decoct them in two batches. For the first decoction, add 10 times the amount of purified water as the total amount of medicinal materials and decoct for 1 hour. Then, press out the residue. 3.2 For the second decoction, add 8 times the amount of water as the total amount of medicinal materials, and decoct the dregs from the first decoction again for 45 minutes. Combine the two decoctions. S4. Concentration and spray drying 4.1 The mixture was concentrated under reduced pressure at 65±5℃ for 4 hours to obtain a thick paste with a relative density of 1.28 to 1.32; 4.2 The thick paste is dried to become a powder, resulting in a dry paste powder; S5. Granulation and Packaging 5.1 Mixing and granulation: The dry powder, volatile oil inclusion complex and excipients are mixed in a mixer and then wet-granulated using a granulator to obtain whole granules; 5.2 The whole grains are screened through a 16-mesh sieve; 5.3 The granules were dried in a fluidized bed at 60℃ for 30 min, and then screened using a 14-mesh sieve, with a particle yield ≥95%; 5.4 Packaging: Packed with aluminum-plastic composite film, with a specification of 6±0.15g / bag.

[0006] Furthermore, a steam distillation apparatus is selected for the extraction of volatile oils.

[0007] Furthermore: The decoction is carried out using an inverted conical extraction tank, and the water level is monitored in real time using a water level gauge. The temperature is controlled by a gradient. After the first decoction boils, the temperature is adjusted to a gentle boil of 95~98℃, and the second decoction is carried out at 100℃.

[0008] Furthermore: the excipients in step S5 are dextrin and steviol glycosides.

[0009] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention's formula follows ancient practices without being bound by them. It differentiates syndromes and treats accordingly, prescribing and using medicines accordingly. Based on the traditional methods of soothing the liver and clearing heat, calming the mind and relieving anxiety, it first proposes the effects of "calming the liver and suppressing yang, soothing the liver and clearing heat, nourishing the heart and calming the mind." It combines "calming the liver" and "soothing the liver," emphasizes "suppressing yang" and "clearing heat," and nourishes the heart in order to calm the mind. The proportions of medicinal herbs in the formula conform to the theories of traditional Chinese medicine, demonstrating precise drug use. Mother-of-pearl and oyster shell are the principal herbs, used to calm the liver and subdue yang, accounting for 20.51% of the formula. Vinegar-processed Bupleurum chinense, peppermint, Angelica sinensis, Albizia julibrissin, stir-fried Paeonia lactiflora, Paeonia suffruticosa, and raw Gardenia jasminoides are the assistant herbs, used to soothe the liver and clear heat, accounting for 43.59% of the formula. Among them, Paeonia suffruticosa and raw Gardenia jasminoides account for 10.26% of the formula. Salvia miltiorrhiza, Platycladus orientalis seed, and Polygonum multiflorum are the adjuvant herbs, used to nourish the heart and calm the mind, accounting for 25.64% of the formula. A small dose of jujube is used to nourish blood, calm the mind, strengthen the spleen and replenish qi, and harmonize the other herbs, accounting for 10.26% of the formula. Following the principle of principal, assistant, adjuvant, and adjuvant herbs, each herb plays its role in calming the liver, subduing yang, soothing the liver, clearing heat, nourishing the heart, and calming the mind, complementing each other.

[0010] Specialized processing of medicinal materials enhances the utilization rate of components. Crushing mother-of-pearl and oyster shells increases the surface area, promoting the dissolution of water-soluble components such as calcium salts. Crushing raw gardenia before decoction increases the contact area, facilitating the extraction of components such as geniposide. Vinegar extraction of volatile oils from Bupleurum chinense, peppermint, and Angelica sinensis avoids the loss of volatile components during prolonged decoction. While ensuring the material basis of the medicinal materials, it also highlights the effects of calming the liver and suppressing yang, soothing the liver and clearing heat, and nourishing the heart and calming the mind.

[0011] The excipients are few in number and have clear functions, with no redundant components. Dextrin is used as a forming agent to improve the flowability of the dry powder and ensure the granulation rate. Stevia is used as a flavoring agent to mask the bitter taste of the medicinal materials and improve patient medication compliance.

[0012] The process flow is standardized, and the parameters have been optimized to balance efficiency and quality stability. The pretreatment and extraction processes are meticulous, laying the foundation for subsequent intrinsic quality. The extraction process is scientifically optimized, resulting in a high transfer rate of effective components. The concentration and drying processes are controllable, ensuring good product quality stability. The particle quality is controllable during the mixing and granulation process. The standardized and strict packaging process ensures high consistency of the finished product. Attached Figure Description

[0013] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only for more clearly illustrating the technical solutions in the embodiments of the present invention or the prior art. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0014] Figure 1 This is a flowchart illustrating the overall process of this invention. Figure 2This is a flowchart of the grouping and processing of medicinal materials according to the present invention; Figure 3 This is a flowchart of the volatile oil extraction process of the present invention; Figure 4 This is a flowchart of the mixing and granulation process in the present invention; Figure 5 This is a diagram showing the composition percentage of the dry paste of the present invention. Detailed Implementation

[0015] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below with reference to specific embodiments. However, the embodiments are only for illustration and are not intended to limit the present invention.

[0016] Pearl Danzhi Granules are derived from two classic formulas, "Jia Yi Gui Zang Tang" and "Dan Zhi Xiao Yao San," forming the unique formula of "Pearl Danzhi Granules." Jia Yi Gui Zang Tang comes from Volume 2 of "Yi Chun Sheng Yi" and was created by Fei Boxiong, a physician in the Qing Dynasty. The prescription consists of: pearl powder 8 qian, dragon teeth 2 qian, bupleurum 1 qian (vinegar-fried), mint 1 qian, rehmannia 6 qian, angelica 2 qian, white peony 1.5 qian (wine-fried), salvia miltiorrhiza 2 qian, cypress seed 2 qian, night-blooming jasmine 2 qian, agarwood 0.5 qian, jujube 10 pieces, and night-blooming jasmine 4 qian (sliced). The original formula of Dan Zhi Xiao Yao San comes from Xue Ji, a physician in the Ming Dynasty. In Volume 2 of Xue Ji's "Internal Medicine Summary," the prescription consists of: bupleurum 1 liang, angelica 1 liang, white peony 1 liang, atractylodes macrocephala 1 liang, poria cocos 1 liang, prepared licorice 0.5 liang, peony bark 1 qian, gardenia 1 qian, 3 slices of roasted ginger, and a little mint.

[0017] The raw materials of the Pearl Gardenia Granules of this invention include mother-of-pearl, oyster shell, vinegar-processed Bupleurum chinense, peppermint, angelica sinensis, Albizia julibrissin flower, stir-fried white peony root, salvia miltiorrhiza, Platycladus orientalis seed, Polygonum multiflorum stem, red dates, peony bark, and raw gardenia. Its formula follows ancient practices but is not bound by them. It is based on syndrome differentiation and treatment, and the prescription and medication are based on traditional methods of soothing the liver and clearing heat, calming the mind and relieving anxiety. It first proposes the effects of "calming the liver and suppressing yang, soothing the liver and clearing heat, nourishing the heart and calming the mind". "Calming the liver" and "soothing the liver" are combined, "suppressing yang" and "clearing heat" are emphasized, and nourishing the heart is intended to calm the mind.

[0018] This example demonstrates the production of 1000 bags. The raw material concentration process uses a rotary evaporator. A small spray dryer was used for the drying process of volatile oil inclusion compounds; The raw materials used for 1000 bags of Pearl Danzhi Granules are: 1.845kg mother-of-pearl, 1.845kg oyster shell, 0.9225kg vinegar-processed Bupleurum chinense, 0.9225kg peppermint, 0.9225kg Angelica sinensis, 1.845kg Albizia julibrissin flower, 1.3835kg stir-fried white peony root, 0.9225kg Salvia miltiorrhiza, 1.845kg Platycladus orientalis seed, 1.845kg Polygonum multiflorum stem, 1.845kg jujube, 0.9225kg Paeonia suffruticosa root bark, and 0.9225kg raw Gardenia jasminoides.

[0019] Its production process includes, for example: Figures 1-5 As shown, it includes the following steps: S1. Pre-processing of medicinal materials Mineral and shell medicine: 1.845 kg of mother-of-pearl and 1.845 kg of oysters were magnetically separated to remove metal impurities, washed with water to remove dust, and then crushed in a crusher; The red dates are pitted manually, with the pit weight ≤ 3%. Raw gardenia fruit is processed using a crusher (particle size ≤ 3mm); Flower, leaf and stem medicinal materials (total 11.298kg): Albizia flower, stir-fried white peony root, Salvia miltiorrhiza, Platycladus orientalis seed, Polygonum multiflorum stem, and Paeonia suffruticosa bark are soaked in a soaking tank for treatment; S2. Volatile oil extraction 0.9225 kg of vinegar-processed Bupleurum chinense, 0.9225 kg of Angelica sinensis, and 0.9225 kg of Mentha haplocalyx were extracted separately by distillation. During distillation, 16.6 kg of purified water (6 times the amount of the medicinal materials) was added. Distillation was carried out for 2 hours at a temperature of 100–105℃. The distillate was collected and allowed to stand for separation. The distillation rate was 1.5 ± 0.5 ml / min, and the separation time was ≥30 min. The volatile oil was separated, yielding 10.4–15.5 g of volatile oil product. The volatile oil and... β - 0.48 kg of volatile oil inclusion complex was obtained by cyclodextrin inclusion and used for later use. The volatile oil extraction rate is shown in Table 1. Table 1 medicinal herbs Feed quantity (kg) Theoretical oil content (%) Estimated extraction rate (%) Oil quantity (g) Mint 0.9225 0.8～1.2 75% 6.9～10.4 Angelica sinensis 0.9225 0.4～0.6 65% 2.4～3.6 Vinegar-processed Bupleurum 0.9225 0.2～0.3 60% 1.1～1.7 total 2.7675 10.4～15.7 The total extraction rate of volatile oils was 0.038%–0.057% (as a percentage of the total medicinal material). The distilled residue is combined with other medicinal materials for conventional decoction. S3. Simmering 3.1 Soak the raw materials for 1 hour before decoction. Decoction is done in two batches. For the first decoction, add 10 times the amount of purified water (about 180L) of the total amount of medicinal materials and decoct for 1 hour. Press out the residue. 3.2 For the second decoction, add 8 times the total amount of purified water (about 144L) of the medicinal materials, and decoct the dregs after the first decoction for another 45 minutes. Combine the two decoctions. The decoction is performed using an inverted conical extraction tank. During the decoction process, the water level gauge is used for real-time monitoring. The temperature is controlled by gradient. After the first decoction reaches boiling point, the temperature is adjusted to a gentle boil of 95-98℃. The second decoction is performed at 100℃. S4. Concentration and Drying 4.1 The mixture was concentrated under reduced pressure at 65±5℃ for 4 hours to obtain a thick paste with a relative density of 1.28 to 1.32; 4.2 The thick paste was dried using a spray dryer to obtain a powder. The parameter settings for the spray dryer are shown in Table 2. Table 2 parameter Setting value Inlet air temperature 180±5℃ Air outlet temperature 85±5℃ Dry powder moisture ≤50% S5. Granulation and Packaging 5.1 Mixing and granulation: The dry powder, volatile oil inclusion complex and excipients are mixed in a mixer and then wet-granulated using a granulator to obtain whole granules; 5.2 The whole grains are screened through a 16-mesh sieve; 5.3 The granules were dried in a fluidized bed at 60℃ for 30 min, and then screened using a 14-mesh sieve, with a particle yield ≥95%; 5.4 Packaging: Aluminum-plastic composite film is used for packaging, with a specification of 6±0.15g / bag and a production speed of 40~50 bags / minute.

[0020] This invention has key quality control points throughout the production process. The control procedures and testing items are shown in Table 3 below. Table 3 Process Testing items Standard range Volatile oil extraction Oil yield ≥0.04% (total medicinal materials) Mineral medicine decoction Total calcium ions ≥1.2mg / ml Combined decoction Paeonol ≥0.35mg / ml Spray drying Moisture ≤5.0% Finished product Gardenoside content ≥1.0mg / bag Microbial limits Total number of aerobic bacteria ≤1000 CFU / g The material balance sheet is shown in Table 4. Table 4 materials Input (kg) Output (kg) Utilization rate (%) Total medicinal materials 17.9885 Dry powder 4.30 23.91 Volatile oil inclusion complex 0.48 2.67 dextrin 1.60 1.60 100 Steviosides 0.05 0.05 100 Total finished products 6.00 100 The composition of the finished product is calculated as shown in Table 5 below, based on the average value of the pilot test. Table 5 Finished product type Percentage (%) Weight of a single bag (g) Source Explanation Extract dry paste 71.7% 4.30 Water extract concentrate (containing mineral ions, etc.) volatile oil 0.8% 0.048 Inclusion volatile oil (-cyclodextrin carrier) auxiliary materials 27.5% 1.65 Dextrin + Flavoring Agent The quality balance verification, using 1000 bags as an example, is shown in Table 6. Table 6 materials Input amount (kg) Output (kg) Utilization Total amount of medicinal materials 17.9885 Amount of ointment obtained 4.30 23.9% volatile oil 0.048 0.27% auxiliary materials 1.65 1.65 100% Final product 6.00 1. The content of paeonol in each batch is tested (≥0.45mg / bag). 2. The bulk density of the particles should be controlled between 0.65 and 0.75 g / cm³. 3. Finished product moisture content ≤ 6% (loss on drying method) Three batches of this product were manufactured using this process, and the data is shown in Table 7 below. Table 7 batch Ointment yield (%) Volatile oil yield (%) Finished product qualification rate 250801 23.7 0.041 98.3% 250802 24.2 0.049 99.1% 250803 22.9 0.053 97.8% Based on the traditional methods of soothing the liver and clearing heat, calming the mind and relieving anxiety, the formula of this invention is the first to propose the effects of "calming the liver and suppressing yang, soothing the liver and clearing heat, nourishing the heart and calming the mind". It combines "calming the liver" and "soothing the liver", emphasizes "suppressing yang" and "clearing heat", and nourishes the heart in order to calm the mind.

[0021] The process flow is standardized, and the parameters have been optimized to balance efficiency and quality stability. The entire extraction process is refined and reasonable, laying the foundation for the extraction of effective components. The scientifically optimized extraction process results in a high transfer rate of effective components. The concentration and drying processes are controllable, ensuring the stability of the finished product quality. The mixed granulation process ensures controllable particle quality, and the packaging process has strict standards, resulting in high consistency of the finished product.

[0022] All content not described in detail in this invention is prior art.

[0023] The above description is merely a preferred embodiment of the present invention and is not limited to the description in the specification and embodiments. Therefore, all equivalent changes or modifications made to the structure, features, and principles described in the claims of this invention should be included within the scope of this patent application.

Claims

1. Pearl Danzhi Granules, characterized in that: The formula includes mother-of-pearl, oyster shell, vinegar-processed Bupleurum chinense, peppermint, angelica sinensis, Albizia julibrissin flower, stir-fried white peony root, salvia miltiorrhiza, Platycladus orientalis seed, Polygonum multiflorum stem, red dates, peony bark, and raw gardenia fruit. Its production process includes: S1. Pre-processing of medicinal materials After removing impurities from mother-of-pearl and oysters, and washing them to remove dust, they are crushed to 20-30 mesh using a crusher. Pit the red dates manually; Raw gardenia fruit is processed using a crusher; Soak the following ingredients in cold purified water for 1 hour: Albizia julibrissin flowers, stir-fried white peony root, salvia miltiorrhiza, arborvitae seed, Polygonum multiflorum stem, and peony bark. S2. Volatile oil extraction Vinegar-processed Bupleurum chinense, Angelica sinensis, and Mentha haplocalyx were extracted separately by distillation. During distillation, 6 times the amount of purified water was added to each herb, and the extraction was carried out for 2 hours. The distillate was collected and allowed to stand for separation. The volatile oil was then separated from the volatile oil. β - Cyclodextrin encapsulation yields volatile oil inclusion compounds for later use; the distilled residue is combined with other medicinal materials for conventional decoction; S3. Simmering 3.1 Soak the raw materials for 1 hour before decoction, and decoct them in two batches. For the first decoction, add 10 times the amount of purified water as the total amount of medicinal materials and decoct for 1 hour. Then, press out the residue. 3.2 For the second decoction, add 8 times the total amount of purified water of the medicinal materials, and decoct the dregs after the first decoction for another 45 minutes. Combine the two decoctions. S4. Concentration and spray drying 4.1 The mixture was concentrated under reduced pressure at 65±5℃ for 4 hours to obtain a thick paste with a relative density of 1.28 to 1.32; 4.2 The thick paste is spray-dried to become a powder, resulting in a dry paste powder; S5. Granulation and Packaging 5.1 Mixing and granulation: The dry powder, volatile oil inclusion complex and excipients are mixed in a mixer and then wet-granulated using a granulator to obtain whole granules; 5.2 The whole grains are screened through a 16-mesh sieve; 5.3 The granules were dried in a fluidized bed at 60℃ for 30 min, and then screened using a 14-mesh sieve, with a particle yield ≥95%; 5.4 Packaging: Packed with aluminum-plastic composite film, with a specification of 6±0.15g / bag.

2. The manufacturing process of the pearl powder granules according to claim 1, characterized in that: Steam distillation equipment is selected for the extraction of volatile oils.

3. The manufacturing process of pearl powder granules according to claim 1, characterized in that: The decoction is performed using an inverted conical extraction tank. During the decoction process, the water level is monitored in real time using a gauge. The temperature is controlled by a gradient. After the first decoction reaches boiling point, the temperature is adjusted to a gentle boil of 95-98℃. The second decoction is performed at 100℃.

4. The manufacturing process of pearl powder granules according to claim 1, characterized in that: The excipients in step S5 are dextrin and steviol glycosides.

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