Dropping pills of Ganlu Shengmai and preparation process

Abstract

The present application relates to the technical field of traditional Chinese medicine, and specifically discloses a kind of Ganlu Shengmai drop pills and preparation process thereof, and the Ganlu Shengmai drop pills are composed of the following raw medicinal materials by weight: Fructus Choerospondi 0.8-1.5 parts, Fructus Amomi Rotundus 0.3-0.6 parts, Fructus Lycii 0.3-0.6 parts, Radix Paeoniae Rubra 0.3-0.6 parts, Rhododendron simsii 0.2-0.5 parts, Cinnamomum cassia 0.2-0.5 parts, Herba Epimedii 0.1-0.4 parts, Ephedra 0.1-0.4 parts, Poria cocos 0.1-0.4 parts, Red Ginseng 0.1-0.3 parts, Herba Avellanae 0.05-0.2 parts, Herba Linderae 0.03-0.1 parts, Polygonatum 0.1-0.4 parts. The preparation process of the Ganlu Shengmai drop pills includes the following steps: (a) extracting volatile oil; (b) encapsulating volatile oil; (c) extracting non-volatile components; (d) concentrating and drying; (e) preparing drop pills; (f) coating: the drop pills obtained in step (e) are coated with 10%-20% Opadry II alcohol-soluble coating solution. The present application can be targeted at the characteristics of Mongolian medicine compound, and take into account the preparation technology of active ingredient retention, patient compliance, dosage form modernization and quality controllability.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and more specifically to a Ganlu Shengmai Dripping Pill and its preparation process. Background Technology

[0002] Bradyarrhythmia is a common cardiovascular disease characterized by low heart rate and reduced cardiac output. Clinically, it is often accompanied by symptoms such as palpitations, fatigue, dizziness, and even syncope, seriously threatening patients' lives and health. In Mongolian medicine, this type of disease is often classified under "Badagan type palpitation syndrome," and its pathogenesis is considered closely related to factors such as insufficient heart yang, deficiency of qi and blood, and invasion of cold pathogens. Currently, Western medicine treatment mainly relies on artificial pacemakers or medications. However, pacemaker implantation is an invasive procedure, expensive and carries surgical risks, while chemical drugs easily cause various adverse reactions such as dry mouth, facial flushing, and ventricular arrhythmias, which are poorly tolerated by patients.

[0003] Mongolian medicine possesses a unique theoretical system and rich practical experience in treating cardiovascular diseases, particularly demonstrating advantages in overall regulation and safety. However, traditional Mongolian medicine preparations have significant shortcomings in clinical application: First, traditional dosage forms are typically large in volume and require large doses, and most have a bitter taste, especially those rich in volatile oils which can produce a strong unpleasant odor, leading to poor patient compliance; second, volatile oils, as key active ingredients in many Mongolian medicine formulas, are chemically unstable and easily volatilize, oxidize, and deteriorate during traditional preparation and storage, resulting in the loss of effective components and seriously affecting the stability and reproducibility of therapeutic effects. While existing technologies offer some improved dosage forms, such as capsules or tablets, simple whole-powder granulation or extract drying and tableting still cannot fundamentally solve the problems of volatile oil loss and odor masking for Mongolian medicine compound formulas containing volatile components. Some studies have attempted to encapsulate volatile oils before adding them to the formulation, but these often lack integrated process optimization across the entire process from raw material pretreatment, extraction, molding to post-coating. This leads to improper coordination between stages, resulting in unsatisfactory final product quality stability, dissolution behavior, and clinical efficacy. Summary of the Invention

[0004] In view of this, the present invention provides a Ganlu Shengmai dripping pill and its preparation process, which is a formulation technology that takes into account the characteristics of Mongolian medicine compound prescriptions, while taking into account the preservation of active ingredients, patient compliance, dosage form modernization and quality control.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A type of Ganlu Shengmai Dripping Pill is composed of the following raw materials in parts by weight: jujube 0.8-1.5 parts, long pepper 0.3-0.6 parts, wolfberry 0.3-0.6 parts, red peony root 0.3-0.6 parts, four o'clock flower 0.2-0.5 parts, cinnamon 0.2-0.5 parts, epimedium 0.1-0.4 parts, ephedra 0.1-0.4 parts, poria cocos 0.1-0.4 parts, red ginseng 0.1-0.3 parts, asafoetida 0.05-0.2 parts, asarum 0.03-0.1 parts, and polygonatum odoratum 0.1-0.4 parts.

[0006] Preferably, the above-mentioned Ganlu Shengmai Dripping Pill is composed of the following raw materials in parts by weight: 1.14 parts of jujube, 0.46 parts of long pepper, 0.46 parts of wolfberry, 0.46 parts of red peony root, 0.34 parts of four o'clock flower, 0.34 parts of cinnamon, 0.23 parts of epimedium, 0.23 parts of ephedra, 0.23 parts of poria cocos, 0.21 parts of red ginseng, 0.11 parts of asafoetida, 0.07 parts of asarum, and 0.23 parts of polygonatum odoratum.

[0007] A preparation process for Ganlu Shengmai Dripping Pills includes the following steps: (a) Extraction of volatile oil: Take cinnamon, asafoetida and asarum, crush them and soak them in 6-10 times the amount of water for 0.5-2 hours, distill for 4-6 hours, collect the distillate, refrigerate for 12 hours, and separate the volatile oil layer; (b) Encapsulation of volatile oil: The volatile oil obtained in step (a) is encapsulated with β-cyclodextrin, wherein the mass-volume ratio of β-cyclodextrin to volatile oil is 4:1 - 8:1 (g:ml), the mass ratio of β-cyclodextrin to water is 1:8 - 1:15, the encapsulation temperature is 40-60℃, the encapsulation is ultrasonically performed for 1.0-2.0 hours, the mixture is refrigerated for 24 hours, filtered, dried at 40℃, and pulverized for later use; (c) Extraction of non-volatile components: Mix the residue after distillation in step (a) with the remaining raw materials, extract with 60%-80% ethanol 1-2 times, each time with 6-10 times the amount of ethanol for 0.5-1.5 hours, combine the extracts, filter, and recover the ethanol under reduced pressure to obtain the extract; (d) Concentration and drying: The extract obtained in step (c) is concentrated to a thick paste with a relative density of 1.05-1.20 at 60°C, and then spray-dried at an inlet air temperature of 110-135°C and an outlet air temperature of 80-100°C to obtain a mixed extract. The β-cyclodextrin inclusion complex obtained in step (b) is then added. (e) Preparation of drop pellets: The mixture obtained in step (d) is mixed with an aqueous matrix PEG6000, melted at 60-75℃, and then dropped into a liquid paraffin condenser with a viscosity of 10-25 mPa·s to form a pellet. The surface paraffin is removed to obtain drop pellets with a weight of 40-60 mg per pellet. (f) Coating: The pellets obtained in step (e) are coated with a 10%-20% Opadry II alcohol-soluble coating solution. The coating conditions are: material temperature 35-45℃, atomization pressure 0.15-0.20 MPa, and intensified drying at 35℃ after coating to increase the weight gain of the coating by 1.5%-4.0%, resulting in coated pellets with a surface roughness Ra≤0.8μm and a disintegration time ≤20 minutes.

[0008] Preferably, in the above-mentioned preparation process of Ganlu Shengmai Dripping Pill, the volatile oil extraction in step (a) is carried out by steam distillation, with the amount of water added being 8 times that of the medicinal material, the soaking time being 1 hour, and the distillation time being 5 hours.

[0009] Preferably, in the above-mentioned preparation process of Ganlu Shengmai Dripping Pills, in the β-cyclodextrin inclusion process in step (b), the mass ratio of β-cyclodextrin to water is 1:10.

[0010] Preferably, in the above-mentioned preparation process of Ganlu Shengmai Dripping Pills, the ethanol extraction in step (c) is carried out by reflux extraction with 75% ethanol for 90 minutes, followed by secondary extraction with 55% ethanol for 90 minutes, and finally extraction with water for 60 minutes.

[0011] Preferably, in the above-mentioned preparation process of Ganlu Shengmai Dripping Pills, the coating solution in step (f) uses HPMC as the base material and ethanol as the solvent.

[0012] As can be seen from the above technical solution, compared with the prior art, this invention discloses a Ganlu Shengmai Dripping Pill and its preparation process, which preserves the efficacy of the entire formula to the greatest extent, especially ensuring the stability and bioavailability of the volatile oil components. Firstly, by optimizing the steam distillation parameters, the heat-sensitive volatile oil components in cinnamon, asarum, and asafoetida are extracted efficiently and directionally, avoiding potential losses and decomposition when decocted with other ingredients. This invention uses β-cyclodextrin for inclusion complexation, encapsulating the volatile oil molecules within the cyclodextrin cavity. This not only greatly reduces volatilization and oxidation losses during preparation and storage but also effectively masks unpleasant odors, improves the patient's medication experience, and increases treatment compliance. Simultaneously, the inclusion complexation technology forms a molecular-level dispersion system, which helps improve the solubility and dissolution rate of the volatile oil in vivo, thereby enhancing its bioavailability.

[0013] This invention involves mixing the extract obtained after alcohol extraction and water precipitation with an encapsulated volatile oil powder, and preparing droplets using a water-soluble matrix such as PEG6000. The droplets form a solid dispersion in the hydrophilic matrix, resulting in high drug dispersion. Upon entering the gastrointestinal tract, the drug rapidly dissolves and releases, exhibiting rapid onset of action, meeting the requirements for rapid drug efficacy in arrhythmia diseases. Through systematic optimization of the matrix ratio, condensation conditions, and other molding processes, the resulting droplets exhibit good sphericity, moderate hardness, minimal weight variation, and stable and controllable quality.

[0014] Based on the drop pills, this invention further introduces the Opadry II alcohol-soluble coating system. This coating layer not only further isolates the product from external factors (moisture, light) and enhances product stability, but also makes the pill surface smoother and easier to take. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0016] Figure 1 The attached figure is a flowchart of the preparation process of Ganlu Shengmai Dripping Pills according to the present invention. Detailed Implementation

[0017] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0018] Example 1:

[0019] A type of Ganlu Shengmai Dripping Pill is composed of the following raw materials in parts by weight: jujube 0.8-1.5 parts, long pepper 0.3-0.6 parts, wolfberry 0.3-0.6 parts, red peony root 0.3-0.6 parts, four o'clock flower 0.2-0.5 parts, cinnamon 0.2-0.5 parts, epimedium 0.1-0.4 parts, ephedra 0.1-0.4 parts, poria cocos 0.1-0.4 parts, red ginseng 0.1-0.3 parts, asafoetida 0.05-0.2 parts, asarum 0.03-0.1 parts, and polygonatum odoratum 0.1-0.4 parts.

[0020] Example 2:

[0021] A type of Ganlu Shengmai Dripping Pill is composed of the following raw materials in parts by weight: 1.14 parts of jujube, 0.46 parts of long pepper, 0.46 parts of wolfberry, 0.46 parts of red peony root, 0.34 parts of four o'clock flower, 0.34 parts of cinnamon, 0.23 parts of epimedium, 0.23 parts of ephedra, 0.23 parts of poria cocos, 0.21 parts of red ginseng, 0.11 parts of asafoetida, 0.07 parts of asarum, and 0.23 parts of polygonatum odoratum.

[0022] Example 3:

[0023] A preparation process for Ganlu Shengmai Dripping Pills includes the following steps: (a) Extraction of volatile oil: Take cinnamon, asafoetida and asarum, crush them and soak them in 6-10 times the amount of water for 0.5-2 hours, distill for 4-6 hours, collect the distillate, refrigerate for 12 hours, and separate the volatile oil layer; (b) Encapsulation of volatile oil: The volatile oil obtained in step (a) is encapsulated with β-cyclodextrin, wherein the mass-volume ratio of β-cyclodextrin to volatile oil is 4:1 - 8:1 (g:ml), the mass ratio of β-cyclodextrin to water is 1:8 - 1:15, the encapsulation temperature is 40-60℃, the encapsulation is ultrasonically performed for 1.0-2.0 hours, the mixture is refrigerated for 24 hours, filtered, dried at 40℃, and pulverized for later use; (c) Extraction of non-volatile components: Mix the residue after distillation in step (a) with the remaining raw materials, extract with 60%-80% ethanol 1-2 times, each time with 6-10 times the amount of ethanol for 0.5-1.5 hours, combine the extracts, filter, and recover the ethanol under reduced pressure to obtain the extract; (d) Concentration and drying: The extract obtained in step (c) is concentrated to a thick paste with a relative density of 1.05-1.20 at 60°C, and then spray-dried at an inlet air temperature of 110-135°C and an outlet air temperature of 80-100°C to obtain a mixed extract. The β-cyclodextrin inclusion complex obtained in step (b) is then added. (e) Preparation of drop pellets: The mixture obtained in step (d) is mixed with an aqueous matrix PEG6000, melted at 60-75℃, and then dropped into a liquid paraffin condenser with a viscosity of 10-25 mPa·s to form a pellet. The surface paraffin is removed to obtain drop pellets with a weight of 40-60 mg per pellet. (f) Coating: The pellets obtained in step (e) are coated with a 10%-20% Opadry II alcohol-soluble coating solution. The coating conditions are: material temperature 35-45℃, atomization pressure 0.15-0.20 MPa, and intensified drying at 35℃ after coating to increase the weight gain of the coating by 1.5%-4.0%, resulting in coated pellets with a surface roughness Ra≤0.8μm and a disintegration time ≤20 minutes.

[0024] Example 4:

[0025] A preparation process for Ganlu Shengmai Dripping Pills includes the following steps: (a) Extraction of volatile oil: Take cinnamon, asafoetida and asarum, crush them and soak them in 6-10 times the amount of water for 0.5-2 hours, distill for 4-6 hours, collect the distillate, refrigerate for 12 hours, and separate the volatile oil layer; (b) Encapsulation of volatile oil: The volatile oil obtained in step (a) is encapsulated with β-cyclodextrin, wherein the mass-volume ratio of β-cyclodextrin to volatile oil is 4:1 - 8:1 (g:ml), the mass ratio of β-cyclodextrin to water is 1:8 - 1:15, the encapsulation temperature is 40-60℃, the encapsulation is ultrasonically performed for 1.0-2.0 hours, the mixture is refrigerated for 24 hours, filtered, dried at 40℃, and pulverized for later use; (c) Extraction of non-volatile components: Mix the residue after distillation in step (a) with the remaining raw materials, extract with 60%-80% ethanol 1-2 times, each time with 6-10 times the amount of ethanol for 0.5-1.5 hours, combine the extracts, filter, and recover the ethanol under reduced pressure to obtain the extract; (d) Concentration and drying: The extract obtained in step (c) is concentrated to a thick paste with a relative density of 1.05-1.20 at 60°C, and then spray-dried at an inlet air temperature of 110-135°C and an outlet air temperature of 80-100°C to obtain a mixed extract. The β-cyclodextrin inclusion complex obtained in step (b) is then added. (e) Preparation of drop pellets: The mixture obtained in step (d) is mixed with an aqueous matrix PEG6000, melted at 60-75℃, and then dropped into a liquid paraffin condenser with a viscosity of 10-25 mPa·s to form a pellet. The surface paraffin is removed to obtain drop pellets with a weight of 40-60 mg per pellet. (f) Coating: The pellets obtained in step (e) are coated with a 10%-20% Opadry II alcohol-soluble coating solution. The coating conditions are: material temperature 35-45℃, atomization pressure 0.15-0.20 MPa, and intensified drying at 35℃ after coating to increase the weight gain of the coating by 1.5%-4.0%, resulting in coated pellets with a surface roughness Ra≤0.8μm and a disintegration time ≤20 minutes.

[0026] The volatile oil extraction in step (a) is carried out by steam distillation, with the amount of water added being 8 times that of the medicinal material, the soaking time being 1 hour, and the distillation time being 5 hours.

[0027] In the β-cyclodextrin inclusion process described in step (b), the mass ratio of β-cyclodextrin to water is 1:10.

[0028] The ethanol extraction in step (c) involves reflux extraction with 75% ethanol for 90 minutes, followed by a second extraction with 55% ethanol for 90 minutes, and finally extraction with water for 60 minutes.

[0029] The coating solution described in step (f) uses HPMC as the base material and ethanol as the solvent.

[0030] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since they correspond to the methods disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to the method section.

[0031] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A type of Ganlu Shengmai Droplet, characterized in that, It is composed of the following raw materials in parts by weight: jujube 0.8-1.5 parts, long pepper 0.3-0.6 parts, wolfberry 0.3-0.6 parts, red peony root 0.3-0.6 parts, four o'clock flower 0.2-0.5 parts, cinnamon 0.2-0.5 parts, epimedium 0.1-0.4 parts, ephedra 0.1-0.4 parts, poria cocos 0.1-0.4 parts, red ginseng 0.1-0.3 parts, asafoetida 0.05-0.2 parts, asarum 0.03-0.1 parts, and polygonatum odoratum 0.1-0.4 parts.

2. The Ganlu Shengmai Dripping Pill according to claim 1, characterized in that, The raw materials are composed of the following parts by weight: jujube 1.14 parts, long pepper 0.46 parts, wolfberry 0.46 parts, red peony root 0.46 parts, four o'clock flower 0.34 parts, cinnamon 0.34 parts, epimedium 0.23 parts, ephedra 0.23 parts, poria cocos 0.23 parts, red ginseng 0.21 parts, asafoetida 0.11 parts, asarum 0.07 parts, and polygonatum odoratum 0.23 parts.

3. A preparation process for Ganlu Shengmai Dripping Pills, characterized in that, Includes the following steps: (a) Extraction of volatile oil: Take cinnamon, asafoetida and asarum, crush them and soak them in 6-10 times the amount of water for 0.5-2 hours, distill for 4-6 hours, collect the distillate, refrigerate for 12 hours, and separate the volatile oil layer; (b) Encapsulation of volatile oil: The volatile oil obtained in step (a) is encapsulated with β-cyclodextrin, wherein the mass-volume ratio of β-cyclodextrin to volatile oil is 4:1 - 8:1 (g:ml), the mass ratio of β-cyclodextrin to water is 1:8 - 1:15, the encapsulation temperature is 40-60℃, the encapsulation is ultrasonically performed for 1.0-2.0 hours, the mixture is refrigerated for 24 hours, filtered, dried at 40℃, and pulverized for later use; (c) Extraction of non-volatile components: Mix the residue after distillation in step (a) with the remaining raw materials, extract with 60%-80% ethanol 1-2 times, each time with 6-10 times the amount of ethanol for 0.5-1.5 hours, combine the extracts, filter, and recover the ethanol under reduced pressure to obtain the extract; (d) Concentration and drying: The extract obtained in step (c) is concentrated to a thick paste with a relative density of 1.05-1.20 at 60°C, and then spray-dried at an inlet air temperature of 110-135°C and an outlet air temperature of 80-100°C to obtain a mixed extract. The β-cyclodextrin inclusion complex obtained in step (b) is then added. (e) Preparation of drop pellets: The mixture obtained in step (d) is mixed with an aqueous matrix PEG6000, melted at 60-75℃, and then dropped into a liquid paraffin condenser with a viscosity of 10-25 mPa·s to form a pellet. The surface paraffin is removed to obtain drop pellets with a weight of 40-60 mg per pellet. (f) Coating: The pellets obtained in step (e) are coated with a 10%-20% Opadry II alcohol-soluble coating solution. The coating conditions are: material temperature 35-45℃, atomization pressure 0.15-0.20 MPa, and intensified drying at 35℃ after coating to increase the weight gain of the coating by 1.5%-4.0%, resulting in coated pellets with a surface roughness Ra≤0.8μm and a disintegration time ≤20 minutes.

4. The preparation process of the Ganlu Shengmai Dripping Pill according to claim 3, characterized in that, The volatile oil extraction in step (a) is carried out by steam distillation, with the amount of water added being 8 times that of the medicinal material, the soaking time being 1 hour, and the distillation time being 5 hours.

5. The preparation process of the Ganlu Shengmai Dripping Pill according to claim 3, characterized in that, In the β-cyclodextrin inclusion process described in step (b), the mass ratio of β-cyclodextrin to water is 1:

10.

6. The preparation process of the Ganlu Shengmai Dripping Pill according to claim 3, characterized in that, The ethanol extraction in step (c) involves reflux extraction with 75% ethanol for 90 minutes, followed by a second extraction with 55% ethanol for 90 minutes, and finally extraction with water for 60 minutes.

7. The preparation process of the Ganlu Shengmai Dripping Pill according to claim 3, characterized in that, The coating solution described in step (f) uses HPMC as the base material and ethanol as the solvent.

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