Lotus freeze-dried buccal sugar and preparation method thereof

Abstract

The invention provides a hundred-lotus freeze-dried buccal sugar and a preparation method thereof, and belongs to the field of pharmaceutical preparations, the hundred-lotus freeze-dried buccal sugar is composed of a hundred-lotus extract and other matrixes, the effective component hundred-lotus extract accounts for 20%-90% of the total solid weight of the preparation, a skeleton support material accounts for 1%-60% of the total solid weight of the preparation, and a freeze-drying protective additive accounts for 0%-5% of the total solid weight of the preparation. The preparation method of the hundred-lotus freeze-dried buccal sugar comprises the steps of solution or suspension preparation, pre-freezing, sublimation drying, desorption drying, packaging and the like. The traditional Chinese medicine compound food preparation is few in variety of auxiliary materials, convenient in preparation process, high in disintegration speed and good in permeable membrane absorption, and can provide a traditional Chinese medicine compound food preparation which is rapid in absorption, good in taste and convenient to take, takes a traditional Chinese medicine theory as a core, is rich in trace elements and is homologous in medicine and food for people lack of trace elements.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical preparations, and particularly to a baihe freeze-dried lozenge and its preparation method and application. Background Art

[0002] The baihe freeze-dried lozenge is a traditional Chinese medicine compound food preparation for oral administration with "medicine and food homology", which treats various diseases caused by the lack of trace elements in the human body. The baihe freeze-dried lozenge selects lotus leaf, galangal, chrysanthemum, lily, and black date as the main prescriptions. The lotus leaf, galangal, chrysanthemum, lily, and black date are respectively combined with the five colors, five directions, four natures and five flavors. According to the five-color theory: green enters the liver and can regulate the liver; red enters the heart and can nourish the heart blood and please the mind; yellow enters the spleen and can tonify the spleen and stomach; white enters the lung and can tonify the lung qi; black enters the kidney and can nourish the kidney essence. The main production areas of the five-flavor traditional Chinese medicines correspond to the five directions (east, south, middle, west, north); the five-flavor traditional Chinese medicines basically conform to the four natures (cold, heat, warm, cool) and the five flavors (sour, bitter, sweet, pungent, salty). "Plain Questions·Chapter on the Formation of the Five Viscera" states: "The heart desires bitterness, the lung desires pungency, the liver desires sourness, the spleen desires sweetness, and the kidney desires saltiness." It nourishes the five viscera, regulates the disharmony of the visceral functions, maintains the balance of trace elements in the body, and keeps the body healthy. Also, using the concept of wholeness, the five-flavor traditional Chinese medicines respectively correspond to the rhizome, scale leaf, flower, fruit / seed, representing the complete plant body, symbolizing the complete human body, and coordinating the trace elements in the human body to be in a good state of dynamic balance.

[0003] Trace elements refer to elements with a content of no more than one ten-thousandth in the human body. Although the content is extremely small, they play a very important role in the normal metabolism and functions of the body. Iron participates in many functions such as the transportation and storage of oxygen, electron transfer, maintenance of hematopoiesis, and immunity; copper is an important catalyst in the human body and participates in the composition of many enzymes such as ceruloplasmin, cytochrome C oxidase, and superoxide dismutase. Copper participates in the hematopoiesis process. Copper can maintain the normal structure of hair, and copper is also a conductor of bioelectric current in the human body; zinc is closely related to the development of the body and is known as the "spark of life" and the "source of wisdom". Zinc participates in the composition of more than 200 enzymes in the human body, and most of the participation forms are as the active centers of metalloenzymes, which are closely related to the synthesis and decomposition of biological components such as lipids, carbohydrates, proteins, and nucleic acids in the body and the normal development of the body; manganese is known as the "longevity element" and can protect the body from the invasion of reactive oxygen species (ROS), making people live long. Manganese promotes bone development, and manganese is related to reproduction; selenium is known as the "king of anti-cancer" and the "star nutrient", and selenium has a great effect on antioxidant, and can be used as a free radical scavenger and anti-cancer agent, and can show high activity. Selenium can effectively control T2DM; Cr3+ is closely related to the regulation of blood glucose metabolism and can affect the utilization of amino acids and the synthesis of cholesterol and nucleic acids.

[0004] Trace element deficiencies can lead to various complex and serious diseases in the human body. Iron deficiency can cause anemia, hypoxia, depression, decreased immune function and many other pathological conditions; copper deficiency can lead to microcytic hypochromic anemia, as well as pathological phenomena such as dull hair and hair depigmentation; zinc deficiency can lead to various risks. For example, spontaneous abortion, premature birth or post-term pregnancy toxemia, etc. Zinc deficiency can cause a variety of diseases, such as gonadal dysplasia, dwarfism, degeneration of lymphoid organs, insensitivity to smell and taste, and lack of appetite. Children are prone to depression, nervous system disorders, and may lead to epilepsy; manganese deficiency can cause dwarfism, decreased brain function, anemia, decreased sperm quality and other symptoms. Selenium deficiency can have an adverse effect on the function of the cardiovascular system and may be the direct cause of myocardial infarction. Selenium deficiency in the daily diet can lead to the occurrence of diseases caused by decreased body immunity. Selenium deficiency can lead to the development of depression, exacerbation of anxiety and aggravation of Alzheimer's disease; chromium deficiency can cause disorders in fat metabolism, resulting in hyperlipidemia, and induce arteriosclerosis and coronary heart disease. Chromium deficiency can lead to inhibition of protein synthesis and stagnation of growth and development. In China, Keshan disease is not only related to low selenium content, but also closely related to low chromium content.

[0005] The dosage form of Baihe Lyophilized Dissolving Candy is a lyophilized orally disintegrating tablet. The prescription composition of the lyophilized orally disintegrating tablet is the main drug and other matrices, and it is prepared by freeze-drying technology. The process includes the preparation of drug solution or suspension, pre-freezing, sublimation drying, desorption drying and packaging and other steps. The preparation process is fast, the process is simple, and it does not need to be taken with water. After directly putting it into the mouth or under the tongue, the lyophilized tablet will quickly dissolve when it comes into contact with oral saliva, disperse in the saliva, is quickly absorbed orally, and the active ingredient of the drug can enter the human circulation through the oral mucosa, with the characteristics of convenient carrying and taking and simple operation. Summary of the Invention

[0006] The Baihe Lyophilized Dissolving Candy mentioned in the present invention refers to a lyophilized orally fast-dissolving tablet prepared from the extracts of five traditional Chinese medicines, namely chrysanthemum, lotus leaf, lily, galangal and black date (hereinafter referred to as "Baihe extract") as raw materials during the preparation process.

[0007] The purpose of the present invention is to provide a trace element orally disintegrating tablet with rapid onset and convenient taking, which is made by vacuum freeze-drying technology, and does not require any auxiliary form for taking during the taking process, and is convenient for people lacking trace elements to use.

[0008] The present invention provides a Baihe Lyophilized Dissolving Candy. This orally disintegrating tablet is made of an effective dose of drug and other matrices. The effective ingredient, Baihe extract, accounts for 20% - 90% of the total solids weight of the preparation, the skeleton support material accounts for 1% - 60% of the total solids weight of the preparation, and the lyoprotectant accounts for 0% - 5% of the total solids weight of the preparation.

[0009] The present invention provides a Baihe freeze-dried lozenge. In the effective ingredient Baihe extract, the proportion of each medicinal material slice is as follows: chrysanthemum: 10% - 35%, lotus leaf 20% - 50%, lily 10% - 35%, galangal 10% - 35%, black date 10% - 35%.

[0010] The present invention provides a Baihe freeze-dried lozenge. The extraction process of the effective ingredient Baihe extract has two forms: adding acetic acid and not adding acetic acid, and the pH range is 3 - 7.

[0011] The present invention provides a Baihe freeze-dried lozenge. The skeleton support material consists of a single auxiliary material or multiple auxiliary materials, and the skeleton support material includes a binder and a skeleton agent.

[0012] The present invention provides a Baihe freeze-dried lozenge. The skeleton support material composed of a single auxiliary material has high viscosity, good space support performance and film-forming performance, and can be a water-soluble material, including but not limited to polymers, polysaccharides, sugar alcohols, sugars or amino acids.

[0013] The present invention provides a Baihe freeze-dried lozenge. The skeleton support material can be used as a freeze-drying protectant and a wetting agent.

[0014] The present invention provides a Baihe freeze-dried lozenge. The skeleton agent is selected from one or more of mannitol, xylitol, sorbitol, maltitol, lactitol, erythritol, dextrin, dextran, pullulan, lactose, trehalose, polyvinyl alcohol, glycine.

[0015] The present invention provides a Baihe freeze-dried lozenge. The binder includes but not limited to proteins, plant gums, amino acids, polypeptides, polysaccharides, polymers.

[0016] The present invention provides a Baihe freeze-dried lozenge. The binder is selected from one or more of gelatin, hydrolyzed gelatin, water-soluble polypeptide, guar gum, arabic gum, agar, dextran, pullulan, polyvinyl alcohol.

[0017] The present invention provides a Baihe freeze-dried lozenge. The Baihe freeze-dried lozenge also contains a flavoring agent and flavors of different tastes; wherein the flavoring agent is selected from one or more of AMP (adenosine monophosphate), ATP (adenosine triphosphate), neotame, sucrose, sodium cyclamate, acesulfame potassium, aspartame, sodium saccharin, protein sugar, steviol, tartaric acid, malic acid and lactic acid; the flavor is selected from one or more of mint essence, sweet orange essence, vanilla essence, strawberry essence, apple essence, chocolate essence, lemon essence and pineapple essence.

[0018] The present invention provides a Baihe freeze-dried lozenge. The freeze-drying protectant is selected from one or more of trehalose, lactose, mannitol, pullulan, water-soluble polypeptide, gelatin, glycine.

[0019] The present invention provides a dried and freeze-dried lozenge containing lotus and lily, and is further characterized in that: the solvent includes one or several of purified water, ethanol, and tert-butanol, wherein the organic solvent accounts for 0 to 40% of the total amount of the solvent.

[0020] The present invention provides a method for preparing a dried and freeze-dried lozenge containing lotus and lily, and the steps are as follows: (I) Preparation of a solution or suspension: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh a quantitative proportion of the five Chinese herbal medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date into a multi-functional extraction tank; ② Add a quantitative multiple of acetic acid or purified water (pH = 3 to 7) and decoct, and reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (lotus and lily extract) with a relative density of 1.15 to 1.25 (60 °C); (2) Preparation of a solution or suspension of the dried and freeze-dried lozenge containing lotus and lily: ① Weigh the prescribed amount of lotus and lily extract and place it in container ①, and add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, and add 1 / 3 of water to fully dissolve them; ③ Transfer the liquid material in container ① to container ②, mix evenly, then transfer it to an emulsifier, rinse the container with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the uniformly mixed medicinal liquid to a degassing bottle, and under normal temperature magnetic stirring, evacuate to remove air until there are no bubbles; ⑤ Filter the above-mentioned liquid material through a 60-mesh sieve from the discharge port, and use a pipette or other suitable perfusion equipment to inject the medicinal liquid into the blister; (II) Pre-freezing: Place the medicinal liquid in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the medicinal liquid into a solid state; (III) The freeze-drying curve is shown in the following table: Table 1 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% to 40%, and inkjet print the production date and batch number.

[0021] The present invention provides a dried and freeze-dried lozenge containing lotus and lily. This orally disintegrating tablet is prepared by vacuum freeze-drying technology, and the method is simple and easy to implement. The preparation method of this dried and freeze-dried lozenge containing lotus and lily includes the preparation of a solution or suspension, pre-freezing, sublimation drying, analytical drying, and packaging, and can provide an orally disintegrating tablet rich in trace elements with rapid absorption, good taste, and convenient administration for people lacking trace elements. Specific embodiments

[0022] The following examples are for better illustrating the present invention and shall not be used to limit the protection scope of the present invention.

[0023] Example 1: This example provides a 5 mg specification of Baihe Lyophilized Lozenge Sugar and its preparation method: Table 2 Prescription Composition Ingredient Content (mg) Function Lotus Extract 5.00 Drug Active Ingredient Pullulan Polysaccharide 0.80 Binder Neotame 0.50 Flavoring Agent Purified Water 393.70 Solvent The preparation steps of the lyophilized orally disintegrating tablets are as follows: (1) Preparation of solution or suspension: (1) Preparation of extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh five traditional Chinese medicine decoction pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae in a ratio of 10:10:3:3:3 and place them in a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe Lyophilized Lozenge Sugar solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in Container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in Container ②, add 1 / 3 of water to fully dissolve them; ③ Transfer the liquid material in Container ① to Container ②, mix evenly, then transfer it to an emulsifier, rinse Container 3 times or more with the remaining water, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above liquid material through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister; (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (3) The freeze-drying curve is shown in the following table: Table 3 Freeze-drying Curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0024] Example 2: This example provides a 5 mg specification of Baihe Lyophilized Lozenge Sugar and its preparation method: Table 4 Prescription Composition Ingredient Content (mg) Function Lotus Extract 5.00 Drug Active Ingredient Pullulan Polysaccharide 0.80 Binder Neotame 0.50 Flavoring Agent Purified Water 393.70 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of the solution or suspension: (1) Preparation of the extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh the five traditional Chinese medicine pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae in a ratio of 1:1:1:1:1 and place them in a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of the Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly, then transfer it to an emulsifier, rinse the container with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister; (II) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 5 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0025] Example 3: This example provides a 5 mg specification of Baihe freeze-dried lozenge and its preparation method: Table 6 Prescription composition Ingredient Content (mg) Function Lotus Extract 5.00 Drug Active Ingredient Pullulan Polysaccharide 0.80 Binder Neotame 0.50 Flavoring Agent Purified Water 393.70 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of the solution or suspension: (1) Preparation of the extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh the five traditional Chinese medicine pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae in a ratio of 1:4:1:1:1 and place them in a multi-functional extraction tank; ② Add 5 times the amount of acetic acid or purified water (pH = 3 - 7), decoct, and reflux extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear extract (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried soluble tablets or suspensions: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of the water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of the water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix well, then transfer it to an emulsifying machine. Rinse container ① with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifying machine as well; ④ Transfer the well-mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate to remove air until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blisters; (II) Pre-freezing: Place the liquid medicine in the blisters in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 7 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum foil composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0026] Example 4: This example provides a 5 mg specification of Baihe freeze-dried soluble tablets and its preparation method: Table 8 Prescription composition Ingredient Content (mg) Function Lotus Extract 5.00 Drug Active Ingredient Pullulan Polysaccharide 1.50 Binder Neotame 0.50 Flavoring Agent Purified Water 393.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of the solution or suspension: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh the five Chinese herbal medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date in a ratio of 10:10:3:3:3 and place them in a multi-functional extraction tank; ② Add 5 times the amount of acetic acid or purified water (pH = 3 - 7), decoct, and reflux extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear extract (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried soluble tablets or suspensions: ① Weigh the prescribed amount of lotus extract and place it in container ①. Add 1 / 3 of water to dissolve it. ② Weigh pullulan polysaccharide and neotame and place them in container ②. Add 1 / 3 of water to fully dissolve them. ③ Transfer the liquid in container ① to container ②, mix evenly, then transfer it to an emulsifier. Rinse the container with the remaining water for more than 3 times and transfer the rinsing liquid to the emulsifier together. ④ Transfer the evenly mixed liquid medicine to a degassing bottle. Under normal temperature and magnetic stirring, evacuate to remove air until there are no bubbles. ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister. (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state. (3) The freeze-drying curve is shown in the following table: Table 9 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0027] Example 5: This example provides a 5 mg specification lotus freeze-dried lozenge and its preparation method: Table 10 Prescription composition Ingredient Content (mg) Function Lotus Extract 5.00 Drug Active Ingredient Pullulan Polysaccharide 1.50 Binder Neotame 0.50 Flavoring Agent Purified Water 393.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (1) Preparation of solution or suspension: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh the five Chinese herbal medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date in a ratio of 1:1:1:1:1 and place them in a multi-functional extraction tank. ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct. Reflux and extract at 100 °C for 2 hours. ③ Under reduced pressure, concentrate the filtrate to a clear paste (lotus extract) with a relative density of 1.15 - 1.25 (60 °C). (2) Preparation of lotus freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of lotus extract and place it in container ①. Add 1 / 3 of water to dissolve it. ② Weigh pullulan polysaccharide and neotame and place them in container ②. Add 1 / 3 of water to fully dissolve them. ③ Transfer the liquid in container ① to container ②, mix evenly, then transfer it to an emulsifier. Rinse the container with the remaining water for more than 3 times and transfer the rinsing liquid to the emulsifier together. ④ Transfer the well - mixed liquid medicine into a degassing bottle, and under magnetic stirring at room temperature, evacuate to remove air until no bubbles are present. ⑤ Filter the above - mentioned liquid material through a 60 - mesh sieve from the discharging port, and inject the liquid medicine into the blister using a pipette or other suitable filling equipment. (2) Pre - freezing: Place the liquid medicine in the blister in an environment of - 40°C to - 80°C and pre - freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state. (3) The freeze - drying curve is shown in the following table: Table 11 Freeze - drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminum - paper composite film in an environment with a relative humidity of 5% - 40%, and ink - jet print the production date and batch number.

[0028] Example 6: This example provides a 5 - mg - specification Baihe freeze - dried lozenge - like sugar and its preparation method: Table 12 Prescription composition Ingredient Content (mg) Function Lotus Extract 5.00 Drug Active Ingredient Pullulan Polysaccharide 1.50 Binder Neotame 0.50 Flavoring Agent Purified Water 393.00 Solvent The preparation steps of the freeze - dried orally disintegrating tablets are as follows: (1) Preparation of solution or suspension: (1) Preparation of extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh the five Chinese herbal medicine pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae in a ratio of 1:4:1:1:1 and place them in a multi - purpose extraction tank. ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100°C for 2 hours. ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60°C). (2) Preparation of Baihe freeze - dried lozenge - like sugar solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in Container ①, add 1 / 3 of water to dissolve it. ② Weigh pullulan polysaccharide and neotame and place them in Container ②, add 1 / 3 of water to dissolve them fully. ③ Transfer the liquid material in Container ① into Container ②, mix well and then transfer it into an emulsifier. Rinse Container 3 times or more with the remaining water, and transfer the rinsing liquid into the emulsifier together. ④ Transfer the well - mixed liquid medicine into a degassing bottle, and under magnetic stirring at room temperature, evacuate to remove air until no bubbles are present. ⑤ Filter the above - mentioned liquid material through a 60 - mesh sieve from the discharging port, and inject the liquid medicine into the blister using a pipette or other suitable filling equipment. (2) Pre - freezing: Place the liquid medicine in the blister in an environment of - 40°C to - 80°C and pre - freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state. (3) The freeze-drying curve is shown in the following table: Table 13 Freeze-drying Curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminized paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0029] Example 7: This example provides 30 mg specification Baihe Lyophilized Lozenge Candy and its preparation method: Table 14 Prescription Composition Ingredient Content (mg) Function Lotus Extract 30.00 Drug Active Ingredient Pullulan Polysaccharide 4.80 Binder Neotame 0.30 Flavoring Agent Purified Water 364.90 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (1) Preparation of the solution or suspension: (1) Preparation of extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh 10:10:3:3:3 of the five Chinese medicinal pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae into a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of the Baihe Lyophilized Lozenge Candy solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly, then transfer it to an emulsifying machine, rinse container 3 times or more with the remaining water, and transfer the rinsing liquid to the emulsifying machine together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister; (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C for pre-freezing for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (3) The freeze-drying curve is shown in the following table: Table 15 Freeze-drying Curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminized paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0030] Example 8: This embodiment provides a 15mg specification Baihe freeze-dried lozenge sugar and its preparation method: Table 16 Prescription composition Ingredient Content (mg) Function Lotus Extract 30.00 Drug Active Ingredient Pullulan Polysaccharide 4.80 Binder Neotame 3.00 Flavoring Agent Purified Water 364.90 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of solution or suspension: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh 1:1:1:1:1 of the five traditional Chinese medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date into a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried lozenge sugar solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly and then transfer it to an emulsifier, rinse container 3 times or more with the remaining water, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister; (II) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C for pre-freezing for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 17 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0031] Example 9: This embodiment provides a 15mg specification Baihe freeze-dried lozenge sugar and its preparation method: Table 18 Prescription composition Ingredient Content (mg) Function Lotus Extract 30.00 Drug Active Ingredient Pullulan Polysaccharide 4.80 Binder Neotame 3.00 Flavoring Agent Purified Water 364.90 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of solution or suspension: (1)Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh the five Chinese herbal medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date in a ratio of 1:4:1:1:1 and place them in a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (hundred lotus extract) with a relative density of 1.15 - 1.25 (60 °C); (2)Preparation of hundred lotus freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of hundred lotus extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly and then transfer it to an emulsifier, rinse the container with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and inject the liquid medicine into the blister using a pipette or other suitable filling equipment; (II)Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (III)The freeze-drying curve is shown in the following table: Table 19 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV)Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0032] Example 10: This example provides a 30 mg specification of hundred lotus freeze-dried lozenge and its preparation method: Table 20 Prescription composition Ingredient Content (mg) Function Lotus Extract 30.00 Drug Active Ingredient Pullulan 9.00 Binder Neotame 3.00 Flavoring Agent Purified Water 358.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I)Preparation of solution or suspension: (1)Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh the five Chinese herbal medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date in a ratio of 10:10:3:3:3 and place them in a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③Under reduced pressure, concentrate the filtrate to a clear paste (Bahe extract) with a relative density of 1.15 - 1.25 (60 °C); (2)Preparation of Bahe freeze-dried lozenge solution or suspension: ①Weigh the prescribed amount of Bahe extract and place it in Container ①, add 1 / 3 of the water to dissolve it; ②Weigh pullulan polysaccharide and neotame and place them in Container ②, add 1 / 3 of the water to dissolve them fully; ③Transfer the liquid in Container ① to Container ②, mix evenly and then transfer it to an emulsifier. Rinse Container 3 times or more with the remaining water and transfer the rinsing liquid to the emulsifier together; ④Transfer the evenly mixed liquid medicine to a degassing bottle, and under magnetic stirring at room temperature, evacuate to remove air until there are no bubbles; ⑤Filter the above liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blisters; (2)Pre-freezing: Place the liquid medicine in the blisters in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (3)The freeze-drying curve is shown in the following table: Table 21 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4)Packaging: Cover with an aluminized paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0033] Example 11: This example provides Bahe freeze-dried lozenges with a specification of 30 mg and its preparation method: Table 22 Prescription composition Ingredient Content (mg) Function Lotus Extract 30.00 Drug Active Ingredient Pullulan 9.00 Binder Neotame 3.00 Flavoring Agent Purified Water 358.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (1)Preparation of solution or suspension: (1)Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ①Weigh the five traditional Chinese medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date in a ratio of 1:1:1:1:1 and place them in a multi-functional extraction tank; ②Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 hours; ③Under reduced pressure, concentrate the filtrate to a clear paste (Bahe extract) with a relative density of 1.15 - 1.25 (60 °C); (2)Preparation of Bahe freeze-dried lozenge solution or suspension: ①Weigh the prescribed amount of Bahe extract and place it in Container ①, add 1 / 3 of the water to dissolve it; ②Weigh pullulan and neotame, place them in container ②, and add 1 / 3 of the water to dissolve them fully; ③Transfer the liquid medicine in container ① to container ②, mix evenly, then transfer it to an emulsifier. Rinse container 3 times or more with the remaining water, and transfer the rinsing liquid to the emulsifier together; ④Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and inject the liquid medicine into the blister using a pipette or other suitable filling equipment; (II) Pre-freezing: Place the liquid medicine in the blister in an environment of -40°C to -80°C and pre-freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 23 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0034] Example 12: This example provides a 30mg specification Baihe freeze-dried lozenge and its preparation method: Table 24 Prescription composition Ingredient Content (mg) Function Lotus Extract 30.00 Drug Active Ingredient Pullulan 9.00 Binder Neotame 3.00 Flavoring Agent Purified Water 358.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of solution or suspension: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ①Weigh the five traditional Chinese medicine pieces of chrysanthemum, lotus leaf, lily, galangal, and black date in a ratio of 1:4:1:1:1 and place them in a multi-functional extraction tank; ②Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100°C for 2 hours; ③Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60°C); (2) Preparation of Baihe freeze-dried lozenge solution or suspension: ①Weigh the prescribed amount of Baihe extract and place it in container ①, and add 1 / 3 of the water to dissolve it; ②Weigh pullulan and neotame, place them in container ②, and add 1 / 3 of the water to dissolve them fully; ③Transfer the liquid medicine in container ① to container ②, mix evenly, then transfer it to an emulsifier. Rinse container 3 times or more with the remaining water, and transfer the rinsing liquid to the emulsifier together; ④Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharging port, and inject the liquid medicine into the blister using a pipette or other suitable perfusion equipment; (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40°C to -80°C and pre-freeze it for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (3) The freeze-drying curve is shown in the following table: Table 25 Freeze-drying Curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0035] Example 13: This example provides 50mg specification Baihe freeze-dried lozenges and its preparation method: Table 26 Prescription Composition Ingredient Content (mg) Function Lotus Extract 50.00 Drug Active Ingredient Pullulan 8.00 Binder Neotame 5.00 Flavoring Agent Purified Water 337.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (1) Preparation of solution or suspension: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal, and black date: ① Weigh 10:10:3:3:3 of the five traditional Chinese medicine decoction pieces of chrysanthemum, lotus leaf, lily, galangal, and black date and place them in a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100°C for 2 hours; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to fully dissolve them; ③ Transfer the liquid medicine in container ① to container ②, mix evenly and then transfer it to an emulsifier, rinse the container with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharging port, and inject the liquid medicine into the blister using a pipette or other suitable perfusion equipment; (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40°C to -80°C and pre-freeze it for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (3) The freeze-drying curve is shown in the following table: Table 27 Freeze-drying Curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0036] Example 14: This example provides 50 mg specification Baihe freeze-dried lozenges and its preparation method: Table 28 Prescription composition Ingredient Content (mg) Function Lotus Extract 50.00 Drug Active Ingredient Pullulan 8.00 Binder Neotame 5.00 Flavoring Agent Purified Water 337.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of solution or suspension: (1) Preparation of extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh 1:1:1:1:1 of the five traditional Chinese medicine decoction pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae into a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly, then transfer it to an emulsifying machine, rinse the container with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifying machine together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister; (II) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 29 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0037] Example 15: This example provides 50 mg specification Baihe freeze-dried lozenges and its preparation method: Table 30 Prescription Composition Ingredient Content (mg) Function Lotus Extract 50.00 Drug Active Ingredient Pullulan 8.00 Binder Neotame 5.00 Flavoring Agent Purified Water 337.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of the solution or suspension: (1) Preparation of the extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh the five traditional Chinese medicine pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae in a ratio of 1:4:1:1:1 and put them into a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100 °C for 2 h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of the Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly and then transfer it to an emulsifying machine, rinse the container with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifying machine together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blister; (II) Pre-freezing: Place the liquid medicine in the blister in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 min to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 31 Freeze-drying Curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0038] Example 16: This example provides a 50 mg specification of Baihe freeze-dried lozenge and its preparation method: Table 32 Prescription Composition Ingredient Content (mg) Function Lotus Extract 50.00 Drug Active Ingredient Pullulan 15.00 Binder Neotame 5.00 Flavoring Agent Purified Water 330.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of the solution or suspension: (1) Preparation of the extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh 10:10:3:3:3 parts by weight of five Chinese herbal medicine pieces, namely chrysanthemum, lotus leaf, lily, galangal, and black date, and place them in a multi-functional extraction tank; ② Add 5 times the amount of acetic acid or purified water (pH = 3 - 7), decoct, and reflux extract at 100 °C for 2 hours; ③ Under reduced pressure, concentrate the filtrate to a clear extract (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of the water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of the water to fully dissolve them; ③ Transfer the liquid in container ① to container ②, mix evenly, then transfer it to an emulsifier. Rinse container ① with the remaining water more than 3 times, and transfer the rinsing liquid to the emulsifier as well; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and use a pipette or other suitable filling equipment to inject the liquid medicine into the blisters; (II) Pre-freezing: Place the liquid medicine in the blisters in an environment of -40 °C to -80 °C and pre-freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (III) The freeze-drying curve is shown in the following table: Table 33 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (IV) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0039] Example 17: This example provides a 50 mg specification of Baihe freeze-dried lozenge and its preparation method: Table 34 Prescription composition Ingredient Content (mg) Function Lotus Extract 50.00 Drug Active Ingredient Pullulan 15.00 Binder Neotame 5.00 Flavoring Agent Purified Water 330.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (I) Preparation of solution or suspension: (1) Preparation of chrysanthemum, lotus leaf, lily, galangal, and black date extract: ① Weigh 1:1:1:1:1 parts by weight of five Chinese herbal medicine pieces, namely chrysanthemum, lotus leaf, lily, galangal, and black date, and place them in a multi-functional extraction tank; ② Add 5 times the amount of acetic acid or purified water (pH = 3 - 7), decoct, and reflux extract at 100 °C for 2 hours; ③ Under reduced pressure, concentrate the filtrate to a clear extract (Baihe extract) with a relative density of 1.15 - 1.25 (60 °C); (2) Preparation of Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of the water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of the water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly and then transfer it to an emulsifier. Rinse container ① with the remaining water for more than 3 times, and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle, and under normal temperature magnetic stirring, evacuate and degas until there are no bubbles; ⑤ Filter the above-mentioned liquid medicine through a 60-mesh sieve from the discharge port, and inject the liquid medicine into the blister using a pipette or other suitable filling equipment; (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40°C to -80°C and pre-freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (3) The freeze-drying curve is shown in the following table: Table 35 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0040] Example 18: This example provides Baihe freeze-dried lozenge with a specification of 50 mg and its preparation method: Table 36 Prescription composition Ingredient Content (mg) Function Lotus Extract 50.00 Drug Active Ingredient Pullulan 15.00 Binder Neotame 5.00 Flavoring Agent Purified Water 330.00 Solvent The preparation steps of the freeze-dried orally disintegrating tablets are as follows: (1) Preparation of solution or suspension: (1) Preparation of extracts of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae: ① Weigh the five traditional Chinese medicine pieces of Flos Chrysanthemi, Folium Nelumbinis, Bulbus Lilii, Rhizoma Alpiniae Officinarum, and Fructus Jujubae in a ratio of 1:4:1:1:1 and place them in a multi-functional extraction tank; ② Add 5 times of acetic acid or purified water (pH = 3 - 7) and decoct, reflux and extract at 100°C for 2 hours; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15 - 1.25 (60°C); (2) Preparation of Baihe freeze-dried lozenge solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container ①, add 1 / 3 of the water to dissolve it; ② Weigh pullulan polysaccharide and neotame and place them in container ②, add 1 / 3 of the water to dissolve them fully; ③ Transfer the liquid in container ① to container ②, mix evenly and then transfer it to an emulsifier. Rinse the container with the remaining water more than 3 times and transfer the rinsing liquid to the emulsifier together; ④ Transfer the evenly mixed liquid medicine to a degassing bottle. Under magnetic stirring at room temperature, evacuate to remove air until there are no bubbles; ⑤ Filter the above-mentioned liquid through a 60-mesh sieve from the discharging port, and inject the liquid medicine into the blister using a pipette or other suitable filling equipment; (2) Pre-freezing: Place the liquid medicine in the blister in an environment of -40°C to -80°C and pre-freeze for 5 - 30 minutes to quickly freeze the liquid medicine into a solid state; (3) The freeze-drying curve is shown in the following table: Table 37 Freeze-drying curve Set Temperature Heating-up Time Duration Vacuum Control Shelf Pre-cooling to -35°C before Feeding —— —— —— -35℃ 10min 80min <200 μbar -25℃ 30min 60min <200 μbar -5℃ 60min 30min <200 μbar 25℃ 90min 90min <200 μbar (4) Packaging: Cover with an aluminum paper composite film in an environment with a relative humidity of 5% - 40%, and inkjet print the production date and batch number.

[0041] Appearance evaluation: 20 evaluators, aged between 20 and 40, respectively take 5 pieces of Baihe freeze-dried lozenges prepared in Specific Example 1 - Specific Example 17 for appearance evaluation. The test results are shown in the following table: Table 38 Appearance evaluation 1

[0042] Table 39 Appearance evaluation 2 。

Claims

1. A Baihe freeze-dried sugar-containing orally disintegrating tablet, which is made of five Chinese medicinal extracts of chrysanthemum, lotus leaf, lily, galangal, black date (hereinafter referred to as "Baihe extract") and other matrix, with specifications ranging from 1mg to 50mg, with no limit on tablet weight, characterized by: The matrix of the preparation includes: skeleton support material accounting for 1% to 60% of the total solid weight of the preparation, freeze-dried protective agent accounting for 0% to 5% of the total solid weight of the preparation, and active ingredient Baihe extract accounting for 20% to 90% of the total solid weight of the preparation.

2. The freeze-dried sugar containing saccharide according to claim 1, characterized in that: The proportions of each medicinal material in Baihe extract are: chrysanthemum: 10%~35%, lotus leaf 20%~50%, lily 10%~35%, galangal 10%~35%, black dates 10%~35%. The extraction process has two forms: with and without acetic acid, and the pH range is 3~7.

3. The freeze-dried sugar containing saccharide according to claim 1, characterized in that: The skeleton support material is composed of a single auxiliary material or a plurality of auxiliary materials; the skeleton support material composed of a plurality of auxiliary materials is characterized in that the skeleton support material is composed of an adhesive and a skeleton agent; the skeleton support material composed of a single auxiliary material is characterized in that it has viscosity and good spatial support performance and film-forming performance.

4. A skeleton support material for freeze-dried saccharide-containing Baihe as claimed in any one of claims 1 and 3, characterized in that: The skeleton material is a water-soluble material and can be used as a freeze-drying protective agent or a wetting agent; the skeleton agent includes but is not limited to polymers, polysaccharides, sugar alcohols, sugars or amino acids, and is selected from one or more of mannitol, xylitol, sorbitol, maltitol, lactitol, erythritol, dextrin, dextran, pullulan, lactose, trehalose, polyvinyl alcohol, and glycine; the adhesive includes but is not limited to protein, plant gum, amino acid, polypeptide, polysaccharide, polymer, and is selected from one or more of gelatin, hydrolyzed gelatin, water-soluble polypeptide, guar gum, gum arabic, agar, dextran, pullulan, and polyvinyl alcohol.

5. The freeze-dried sugar containing saccharide according to any one of claims 1 and 3, characterized in that: The freeze-dried orally disintegrating tablet may contain flavoring agents and flavors of different flavors, wherein the flavoring agent is selected from one or more of AMP (adenosine monophosphate), ATP (adenine nucleoside triphosphate), neotame, sucrose, sodium cyclamate, acesulfame potassium, aspartame, saccharin sodium, protein sugar, stevioside, tartaric acid, malic acid and lactic acid, and the flavor is selected from one or more of mint flavor, sweet orange flavor, vanilla flavor, strawberry flavor, apple flavor, chocolate flavor, lemon flavor and pineapple flavor.

6. The freeze-dried sugar containing saccharide according to claim 5, characterized in that: The freeze-drying protective agent is selected from one or more of trehalose, lactose, mannitol, pullulan, water-soluble polypeptide, gelatin and glycine.

7. The freeze-dried sugar containing saccharide according to claim 6, characterized in that: The solvent includes one or more of purified water, ethanol and tert-butyl alcohol, wherein the organic solvent accounts for 0 to 40% of the total solvent.

8. A method for preparing the freeze-dried sugar-containing Baihe according to claim 7, comprising the following steps:

1. Preparation of solutions or suspensions: (1) Preparation of extracts of chrysanthemum, lotus leaf, lily, galangal and black date: ① Weigh a quantitative proportion of five Chinese medicinal pieces of chrysanthemum, lotus leaf, lily, galangal and black jujube into a multi-functional extraction tank; ② Add quantitative acetic acid or pure water (pH=3-7) and boil, then reflux and extract at 100℃ for 2h; ③ Under reduced pressure, concentrate the filtrate to a clear paste (Baihe extract) with a relative density of 1.15-1.25 (60 ℃); (2) Preparation of freeze-dried sugar-containing solution or suspension: ① Weigh the prescribed amount of Baihe extract and place it in container 1, and add 1 / 3 of water to dissolve it; ② Weigh pullulan and neotame and place them in container 2, add 1 / 3 of water to fully dissolve them; ③ Transfer the liquid in container 1 to container 2, mix evenly, and then transfer to the emulsifier. Rinse the container with the remaining water for more than 3 times, and transfer the rinse liquid to the emulsifier; ④ Transfer the evenly mixed liquid medicine to the degassing device, and degas under vacuum under magnetic stirring at room temperature until there are no bubbles; ⑤ Filter the above liquid from the discharge port through a 60-mesh screen, and inject the liquid into the blister using a pipette or other suitable perfusion equipment; (ii) Pre-freezing: Place the blister Chinese medicine solution in a -40°C to -80°C environment for 5-30 minutes to quickly freeze the solution into a solid state; (III) Freeze-drying: Stage 1: Precooling the shelf before feeding, set temperature: -35℃; Stage 2: Place the blister containing the drug solution into the freeze dryer, set the temperature to -35°C, the heating time to 10 min, the holding time to 80 min, and evacuate the air. The vacuum control is <200 μbar. Stage 3: Raise the shelf temperature to -25°C, heating time 30 min, holding time 60 min, vacuum control: <200 μbar; Stage 4: Raise the shelf temperature to -5°C, heating time 60 min, holding time 30 min, vacuum control: <200 μbar; Stage 5: Raise the shelf temperature to 25°C, heating time 90 min, maintain time 90 min, vacuum control: <200 μbar; (IV) Packaging: Cover with aluminum paper composite film in an environment with a relative humidity of 5% to 40%, and print the production date and batch number with inkjet.

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