Traditional Chinese medicine preparation, alkaline preparation, phospholipid-based drug-loaded preparation and preparation method

Abstract

The invention relates to a traditional Chinese medicine preparation, an alkaline preparation, a phospholipid-based drug-loaded preparation and a preparation method. The traditional Chinese medicine preparation comprises 3-5 parts of anoectochilus formosanus, 3-5 parts of prepared rehmannia root, 10-15 parts of Korean ginseng, 1-3 parts of angelica keiskei, 5-10 parts of wine-prepared fructus corni, 5-10 parts of rose, 7-12 parts of lucid ganoderma, 3-5 parts of poria cocos, 3-5 parts of rhizoma alismatis, 7-10 parts of dendrobe, 70-100 parts of sodium hydroxide and 5-15 parts of egg white. The invention discloses a traditional Chinese medicine preparation based on phospholipid complex drug loading. The traditional Chinese medicine preparation is prepared from the following raw materials in parts by weight through a phospholipid complex drug loading technology: 3-5 parts of anoectochilus formosanus, 3-5 parts of prepared rehmannia root, 10-15 parts of Korean ginseng, 1-3 parts of angelica keiskei, 5-10 parts of wine-prepared fructus corni and 70-100 parts of sodium hydroxide. The phospholipid complex is formed by traditional Chinese medicine extract and phospholipid according to the mass ratio of (0.5-2): 1, and the particle size of the complex is 100-500 nm. The osmotic pressure of the traditional Chinese medicine preparation is 280-310 mOsm / L, and the pH value is 4.5-10.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, and specifically relates to a traditional Chinese medicine preparation, a traditional Chinese medicine preparation based on phospholipid complex loading, an alkaline preparation for regulating the body's acid-base balance, and a preparation method thereof. Background Technology

[0002] Data shows that many diseases caused by unhealthy lifestyles in modern society are due to an acidic body constitution, such as: sub-health, joint and muscle problems, skin problems, digestive and immune system problems, endocrine and metabolic disorders, male impotence, female hormonal imbalance, cardiovascular diseases, and serious diseases such as cancer, diabetes, and hypertension.

[0003] Current Western medicine, in treating chronic diseases (such as diabetes and hypertension) and cancer, still neglects the role of the body's acid-base balance, treats symptoms but not the root cause, suffers from drug resistance, toxic side effects, and cancer metastasis and recurrence. It also ignores where the disease comes from and focuses on how to treat it once it occurs.

[0004] Most chronic diseases treated with Western medicine rely solely on hormone therapy, which only controls symptoms and cannot cure the underlying condition. Examples include chronic respiratory inflammation (such as pharyngitis, COPD, pulmonary bullae, and asthma); traditional Chinese medicine preparations often fail to penetrate the respiratory mucosal barrier, resulting in low bioavailability; and nebulized solutions are highly irritating and can easily trigger airway spasms. Hormone nebulization only suppresses the inflammatory response and cannot regulate the pathogenesis of "spleen and kidney yang deficiency." Current technologies using enzymatic hydrolysis have low conversion rates of active ingredients (≤35.2 mg / g flavonoids) and high nebulization residues (>12%). Summary of the Invention

[0005] The purpose of this invention is to provide a method for administering an alkaline solution into the human body to regulate acid-base balance and achieve therapeutic effects. The method involves inhalation administration: the drug is nebulized in the pharynx and rapidly absorbed into the bloodstream through the rich capillaries of the lungs, resulting in rapid onset of action and synergistic treatment of inflammation throughout the respiratory tract (nose, pharynx, and lungs). It also overcomes the permeability barriers of drug components and reduces the irritation of the nebulized solution to the airways. This invention relates to a traditional Chinese medicine nebulization preparation and its preparation method for treating inflammation throughout the respiratory tract.

[0006] The first technical solution of the present invention is the aforementioned traditional Chinese medicine preparation, which is characterized by comprising the following components by weight: 3-5 parts of Anoectochilus roxburghii, 3-5 parts of Rehmannia glutinosa, 10-15 parts of Panax ginseng, 1-3 parts of Ashitaba, 5-10 parts of Cornus officinalis, 5-10 parts of Rosa rugosa, 7-12 parts of Ganoderma lucidum, 3-5 parts of Poria cocos, 3-5 parts of Alisma plantago-aquatica, 7-10 parts of Dendrobium nobile, 70-100 parts of sodium hydroxide, and 5-15 parts of animal egg white.

[0007] As a preferred option, it also includes 1-3 parts of Platycodon grandiflorus and 3-5 parts of Fritillaria thunbergii. Platycodon grandiflorus saponins promote drug deposition in the respiratory tract, while Fritillaria thunbergii alkaloids synergistically enhance the expectorant and anti-inflammatory effects.

[0008] The second technical solution of the present invention is a method for preparing the traditional Chinese medicine preparation, characterized by comprising the following steps:

[0009] (1) Fermentation treatment: The raw materials are beaten into powder, and 70 to 100 parts of sodium hydroxide and 5 to 15 parts of animal egg white are added according to the total weight of the raw materials. The mixture is then fermented in a sealed container for ≥3 days. The amount of animal egg white added is 20 to 30 parts of the total weight of the raw materials. The animal egg white provides protease to assist in the degradation of macromolecular components. Through microbial fermentation, macromolecular components are degraded into small molecule active fragments with a molecular weight ≤5kDa.

[0010] (2) Graded filtration: Add sodium hydroxide to the fermentation broth, let it stand, and then filter it sequentially through G1-G6 sand core funnels with progressively larger pore sizes of 16-30 μm; retain the active ingredients with a particle size ≤1.5 μm.

[0011] (3) Formulation compatibility: Add distilled water to the filtrate to adjust the pH to 4.5–14.0;

[0012] (4) Prepare traditional Chinese medicine formulations.

[0013] Preferably, the traditional Chinese medicine preparation is any dosage form as defined in pharmaceutics.

[0014] The Chinese medicine preparations mentioned are any dosage form as defined in pharmaceutics.

[0015] The fourth technical solution of the present invention is the traditional Chinese medicine preparation based on phospholipid complex loading, which is characterized in that it is prepared from the following raw materials in parts by weight using phospholipid complex loading technology:

[0016] 3-5 parts of Anoectochilus roxburghii, 3-5 parts of Rehmannia glutinosa, 10-15 parts of Panax ginseng, 1-3 parts of Ashitaba, 5-10 parts of Cornus officinalis, and 70-100 parts of sodium hydroxide.

[0017] The phospholipid complex is formed by combining traditional Chinese medicine extracts and phospholipids in a mass ratio of 0.5 to 2:1, and the particle size of the complex is 100 to 500 nm.

[0018] The traditional Chinese medicine preparation has an osmotic pressure of 280–310 mOsm / L and a pH value of 4.5–10.

[0019] Preferably, the phospholipid is hydrogenated soybean phospholipid with a phase transition temperature ≥50℃; it also includes a platycodon saponin-phospholipid complex.

[0020] The fifth technical solution of the present invention is a method for preparing the traditional Chinese medicine preparation based on phospholipid complex loading, characterized by the following steps:

[0021] (1) Supercritical CO2 extraction: Extracting active ingredients at a pressure of 25-35 MPa and a temperature of 40-50℃;

[0022] (2) Formation of phospholipid complex: The extract, soybean phospholipid, and sodium hydroxide were reacted in a mass ratio of 1:1:8 for 2 hours;

[0023] (3) Nanoparticle processing: The nanoparticle suspension with an average particle size of 200 nm was obtained by circulating it three times at 150 MPa using a microfluidic homogenizer.

[0024] (4) Isotonic adjustment: Distilled water is added to adjust the osmotic pressure to 290±5mOsm / L to obtain the traditional Chinese medicine preparation.

[0025] Preferably, step (2) involves adding sodium hydroxide as an acid-base balance regulator.

[0026] Preferably, the traditional Chinese medicine preparation is any dosage form as defined in pharmaceutics.

[0027] The sixth technical solution of the present invention is a method for preparing the traditional Chinese medicine preparation, characterized by the following steps:

[0028] (1) Use 70-100 parts of high-purity liquid alkali, add 10-20 parts of animal egg white and 3-5 parts of Ganoderma lucidum, and let stand for several days; the high-purity liquid alkali is composed of high-purity sodium hydroxide diluted with distilled water.

[0029] (2) Fermentation: Utilizing animal egg whites, a protein carrier, and microbial fermentation to transform macromolecular components and enhance permeability;

[0030] (3) Filtration: G1-G6 sand core funnel, pore size 16-30μm, removes impurities and retains small molecule active ingredients; the molecular weight of the preparation is <500Da to be qualified;

[0031] (4) Bottle the filtered medicine to obtain the injectable medicine;

[0032] (5) The pH value of the injection solution is adjusted to between 4.5 and 10 with distilled water, and the adjusted injection solution is used with glucose solution.

[0033] Preferably, the traditional Chinese medicine preparation is any dosage form as defined in pharmaceutics.

[0034] The seventh technical solution of the present invention is a method for preparing the alkaline preparation for regulating the body's acid-base balance, characterized by the following steps:

[0035] (1) Use 70-90 parts of high-purity liquid alkali and add 10-20 parts of animal egg white. The high-purity liquid alkali is composed of high-purity sodium hydroxide and distilled water. Let it stand for several days.

[0036] (2) Fermentation: Animal egg whites, which are protein carriers, are fermented with microorganisms to transform macromolecular components and enhance permeability;

[0037] (3) Filtration: G1-G6 sand core funnels with a pore size of 16-30μm are used to remove impurities and retain small molecule active ingredients; the molecular weight of the preparation is <500Da to be considered qualified.

[0038] (4) Prepared as a liquid medicine.

[0039] Preferably, the liquid medicine is any dosage form as defined in pharmaceutics.

[0040] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0041] (1) The principal-assistant-adjuvant synergy of the present invention: warming and tonifying the spleen and kidney (Ashitaba / Korean ginseng) + clearing heat and detoxifying (Anoectochilus roxburghii) + resolving phlegm and promoting diuresis (Alisma plantago-aquatica / Poria cocos), treating both the symptoms and the root cause.

[0042] (2) Fermentation process of the present invention: fermentation of animal egg white + distilled water for ≥3 days. Microbial fermentation converts active ingredients into small molecules. Animal egg white acts as a protein carrier to enhance permeability, thereby solving the problem that large molecules are difficult to penetrate the mucous membrane.

[0043] (3) The multi-stage filtration of the present invention: G1-G6 sand core funnel 1.5~250μm staged filtration, accurately removes large particulate impurities, retains small molecule active ingredients ≤1.5μm, reduces irritation, and solves the problem of airway irritation caused by impurities and loss of effective ingredients.

[0044] (4) The nebulization adaptation of the present invention: when mixed with 5% to 10% glucose water, pH 5.5 to 10, the glucose adjusts the isotonic environment, and the pH buffer reduces the risk of airway spasm, so as to solve the problem of mucosal damage caused by osmotic pressure imbalance of the nebulizing solution.

[0045] (5) This invention is the first to combine a compound formula of "warming and tonifying the spleen and kidneys + clearing heat and detoxifying + resolving phlegm and promoting diuresis" with a process of duck egg white fermentation-multi-stage filtration-glucose isotonic adaptation; it breaks through the problem of the inability to simultaneously achieve good permeability and irritation in the atomization of traditional Chinese medicine. Process parameters: pH 5.5~10, particle size 16~30μm, suitable for industrial production.

[0046] ⑹ This invention is the first to combine Korean ginseng for warming and strengthening the body with Anoectochilus roxburghii and Alisma plantago-aquatica for clearing heat and detoxifying. LC-MS has confirmed that it can simultaneously reduce IL-6 and TNF-α and increase sIgA. Detailed Implementation

[0047] The present invention will be further described in detail below with reference to embodiments:

[0048] Example 1:

[0049] 1. Preparation and functional testing of traditional Chinese medicine preparations:

[0050] (1) Ratio: 3 parts of Anoectochilus roxburghii, 5 parts of Rehmannia glutinosa, 10 parts of Panax ginseng, 3 parts of Ashitaba, 5 parts of Cornus officinalis, 5 parts of Rosa rugosa, 7 parts of Ganoderma lucidum, 3 parts of Poria cocos, 3 parts of Alisma plantago-aquatica, 7 parts of Dendrobium nobile, 100 parts of sodium hydroxide, and 15 parts of ostrich egg white.

[0051] (2) Fermentation: The raw materials are beaten into powder, and 100 parts of sodium hydroxide and 15 parts of ostrich egg white are added according to the total weight of the raw materials. The mixture is then sealed and fermented for 4 days. The amount of ostrich egg white added is 20 parts of the total weight of the raw materials. The ostrich egg white provides protease to help degrade macromolecular components. Through microbial fermentation, macromolecular components are degraded into small molecule active fragments with a molecular weight ≤5kDa. HPLC detection shows that flavonoid glycosides are converted into aglycones.

[0052] (3) Filtration: Add sodium hydroxide to the fermentation broth, let it stand, and then filter it sequentially through G1-G6 sand core funnels with a pore size of 30μm; the pore size of the G1-G6 sand core funnels gradually increases from 16-30μm, retaining the active ingredients with a particle size of 1μm.

[0053] (4) For compatibility with traditional Chinese medicine preparations: Add distilled water to the filtrate to adjust the pH to 7;

[0054] (5) The preparation of traditional Chinese medicine for intravenous injection requires the use of glucose solution after adjustment.

[0055] Example 2:

[0056] 1. Preparation of Traditional Chinese Medicine Preparations:

[0057] (1) Preparation of the medicine: The traditional Chinese medicine preparation based on phospholipid complex loading is prepared from the following raw materials in parts by weight using phospholipid complex loading technology: 3 parts of Anoectochilus roxburghii, 5 parts of Rehmannia glutinosa, 15 parts of Panax ginseng, 3 parts of Ashitaba, 5 parts of Cornus officinalis, and 100 parts of sodium hydroxide; the phospholipid complex is formed by the traditional Chinese medicine extract and phospholipids in a mass ratio of 0.5 to 2:1, and the particle size of the complex is 300 nm; the osmotic pressure of the traditional Chinese medicine preparation is 300 mOsm / L, and the pH value is 9.

[0058] (2) Supercritical CO2 extraction: Extract the active ingredients at 32MPa / 45℃ for 2 hours;

[0059] 2. Preparation of phospholipid complex:

[0060] (1) Extract: Hydrogenated soybean lecithin = 1:1 mass ratio;

[0061] (2) Add 100 parts of sodium hydroxide and stir at 60°C to form a complex, which can be used as a regulator of acid-base balance.

[0062] 3. Nanoparticle processing: The mixture was circulated three times at 150 MPa using a microfluidic homogenizer to obtain a nano-suspension with an average particle size of 200 nm.

[0063] (5) Prepare a traditional Chinese medicine atomized preparation; the pH of the preparation is adjusted to 9 with distilled water, and the adjusted preparation needs to be used with glucose water.

[0064] Example 3:

[0065] The preparation method of traditional Chinese medicine preparations includes the following steps:

[0066] (1) Use 80 parts of high-purity liquid alkali, add 15 parts of duck egg white and 4 parts of Ganoderma lucidum, and let stand for several days. The high-purity liquid alkali is composed of high-purity sodium hydroxide diluted with distilled water.

[0067] (2) Fermentation: Utilizing duck egg white, a protein carrier, and microbial fermentation to transform macromolecular components and enhance permeability;

[0068] (3) Filtration: G1-G6 sand core funnel, pore size 20μm, removes impurities and retains small molecule active ingredients; the molecular weight of the preparation is <500Da to be qualified.

[0069] (4) After filtration, it is prepared into an injectable drug solution;

[0070] (5) The pH of the preparation is adjusted to 4.5 with distilled water, and the adjusted preparation needs to be used with glucose water.

[0071] Example 4:

[0072] The method for preparing the alkaline preparation for regulating the body's acid-base balance involves adding 20 parts of egg white to 100 parts of high-purity liquid alkali and letting it stand for several days.

[0073] (2) Fermentation: Egg white, a protein carrier, is fermented with microorganisms to transform macromolecular components and enhance permeability. The high-purity liquid alkali is made by diluting high-purity sodium hydroxide with distilled water.

[0074] (3) Filtration: G1-G6 sand core funnels with a pore size of 16-30μm remove impurities and retain small molecule active ingredients; the molecular weight of the preparation is <500Da to be qualified.

[0075] (4) Prepare as an injectable drug solution;

[0076] (5) If the pH of the preparation is adjusted to 7 by distilled water, the adjusted preparation needs to be used with glucose solution.

[0077] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made within the scope of the claims of the present invention should be covered by the claims of the present invention.

Claims

1. A traditional Chinese medicine preparation, characterized in that, The ingredients are composed of the following components by weight: 3-5 parts of Anoectochilus roxburghii, 3-5 parts of Rehmannia glutinosa, 10-15 parts of Panax ginseng, 1-3 parts of Ashitaba, 5-10 parts of Cornus officinalis, 5-10 parts of Rosa rugosa, 7-12 parts of Ganoderma lucidum, 3-5 parts of Poria cocos, 3-5 parts of Alisma plantago-aquatica, 7-10 parts of Dendrobium nobile, 70-100 parts of sodium hydroxide, and 5-15 parts of animal egg white.

2. The traditional Chinese medicine preparation according to claim 1, characterized in that, It also includes 1-3 parts of Platycodon grandiflorus and 3-5 parts of Fritillaria thunbergii. Platycodon grandiflorus saponins promote drug deposition in the respiratory tract, while Fritillaria thunbergii alkaloids synergistically enhance the expectorant and anti-inflammatory effects.

3. A method for preparing a traditional Chinese medicine preparation according to claim 1, characterized in that, Includes the following steps: (1) Fermentation treatment: The raw materials are beaten into powder, and 70 to 100 parts of sodium hydroxide and 5 to 15 parts of animal egg white are added according to the total weight of the raw materials. The mixture is then fermented in a sealed container for ≥3 days. The amount of animal egg white added is 20 to 30 parts of the total weight of the raw materials. The animal egg white provides protease to assist in the degradation of macromolecular components. Through microbial fermentation, macromolecular components are degraded into small molecule active fragments with a molecular weight ≤5kDa. (2) Graded filtration: Add sodium hydroxide to the fermentation broth, let it stand, and then filter it sequentially through G1-G6 sand core funnels with progressively larger pore sizes of 16-30 μm; retain the active ingredients with a particle size ≤1.5 μm. (3) Formulation compatibility: Add distilled water to the filtrate to adjust the pH to 4.5–14.0; (4) Prepare traditional Chinese medicine formulations.

4. The traditional Chinese medicine preparation according to any one of claims 1 to 3, characterized in that... The Chinese medicine preparations mentioned are any dosage form as defined in pharmaceutics.

5. A traditional Chinese medicine preparation based on a phospholipid complex-loaded drug, characterized in that, Prepared from the following raw materials using phospholipid complex drug delivery technology: 3-5 parts of Anoectochilus roxburghii, 3-5 parts of Rehmannia glutinosa, 10-15 parts of Panax ginseng, 1-3 parts of Ashitaba, 5-10 parts of Cornus officinalis, and 70-100 parts of sodium hydroxide. The phospholipid complex is formed by combining traditional Chinese medicine extracts and phospholipids in a mass ratio of 0.5 to 2:1, and the particle size of the complex is 100 to 500 nm. The traditional Chinese medicine preparation has an osmotic pressure of 280–310 mOsm / L and a pH value of 4.5–10.

6. The traditional Chinese medicine preparation based on phospholipid complex loading according to claim 5, characterized in that, The phospholipid is hydrogenated soybean phospholipid with a phase transition temperature ≥50℃; it also includes a platycodon saponin-phospholipid complex.

7. A method for preparing a traditional Chinese medicine preparation based on a phospholipid complex-loaded drug as described in claim 5, characterized in that, Includes the following steps: (1) Supercritical CO2 extraction: Extracting active ingredients at a pressure of 25-35 MPa and a temperature of 40-50℃; (2) Formation of phospholipid complex: The extract, soybean phospholipid, and sodium hydroxide were reacted in a mass ratio of 1:1:8 for 2 hours; (3) Nanoparticle processing: The nanoparticle suspension with an average particle size of 200 nm was obtained by circulating it three times at 150 MPa using a microfluidic homogenizer. (4) Isotonic adjustment: Distilled water is added to adjust the osmotic pressure to 290±5mOsm / L to obtain the traditional Chinese medicine preparation.

8. The method for preparing a traditional Chinese medicine preparation based on a phospholipid complex-loaded drug according to claim 7, characterized in that, In step (2), sodium hydroxide is added as an acid-base balance regulator.

9. The traditional Chinese medicine preparation according to any one of claims 5 to 8, characterized in that... The Chinese medicine preparations mentioned are any dosage form as defined in pharmaceutics.

10. A method for preparing a traditional Chinese medicine preparation, characterized in that, Includes the following steps: (1) Use 70-100 parts of high-purity liquid alkali, add 10-20 parts of animal egg white and 3-5 parts of Ganoderma lucidum, and let stand for several days; the high-purity liquid alkali is composed of high-purity sodium hydroxide diluted with distilled water. (2) Fermentation: Utilizing animal egg whites, a protein carrier, and microbial fermentation to transform macromolecular components and enhance permeability; (3) Filtration: G1-G6 sand core funnel, pore size 16-30μm, removes impurities and retains small molecule active ingredients; the molecular weight of the preparation is <500Da to be qualified; (4) Bottle the filtered medicine to obtain the injectable medicine; (5) The pH value of the injection solution is adjusted to between 4.5 and 10 with distilled water, and the adjusted injection solution is used with glucose solution.

11. The method for preparing the traditional Chinese medicine preparation according to claim 10, characterized in that... The Chinese medicine preparations mentioned are any dosage form as defined in pharmaceutics.

12. A method for preparing an alkaline preparation for regulating the body's acid-base balance, characterized in that, Includes the following steps: (1) Use 70-90 parts of high-purity liquid alkali and add 10-20 parts of animal egg white. The high-purity liquid alkali is composed of high-purity sodium hydroxide and distilled water. Let it stand for several days. (2) Fermentation: Animal egg whites, which are protein carriers, are fermented with microorganisms to transform macromolecular components and enhance permeability; (3) Filtration: G1-G6 sand core funnels with a pore size of 16-30μm are used to remove impurities and retain small molecule active ingredients; the molecular weight of the preparation is <500Da to be considered qualified. (4) Prepared as a liquid medicine.

13. The method for preparing the alkaline preparation for regulating the body's acid-base balance according to claim 12, characterized in that... The liquid medicine refers to any dosage form as defined in pharmaceutics.