CN113384667B - Pharmaceutical composition for preventing and treating liver injury and/or liver cancer and preparation method and application thereof - Google Patents
Pharmaceutical composition for preventing and treating liver injury and/or liver cancer and preparation method and application thereof Download PDFInfo
- Publication number
- CN113384667B CN113384667B CN202110827474.3A CN202110827474A CN113384667B CN 113384667 B CN113384667 B CN 113384667B CN 202110827474 A CN202110827474 A CN 202110827474A CN 113384667 B CN113384667 B CN 113384667B
- Authority
- CN
- China
- Prior art keywords
- parts
- pharmaceutical composition
- radix
- liver
- liver cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/233—Bupleurum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/58—Reptiles
- A61K35/586—Turtles; Tortoises, e.g. terrapins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/284—Atractylodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
- A61K36/634—Forsythia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/74—Rubiaceae (Madder family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
- A61K36/8998—Hordeum (barley)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Abstract
The invention provides a pharmaceutical composition for preventing and treating liver injury and/or liver cancer, which is prepared from the following raw material medicines: 200-300 parts of radix bupleuri, 150-250 parts of radix scutellariae, 200-300 parts of radix astragali, 50-150 parts of liquorice, 200-300 parts of fructus forsythiae, 100-200 parts of rhizoma atractylodis macrocephalae, 200-300 parts of radix paeoniae alba, 20-120 parts of madder, 20-120 parts of malt, 50-150 parts of cuttlebone, 20-120 parts of turtle shell, 20-120 parts of endothelium corneum gigeriae galli, 10-110 parts of cinnamon, 1-10 parts of borneol and 1-10 parts of menthol. The pharmaceutical composition has low toxicity, can effectively prevent and treat liver injury, protect liver function, and inhibit proliferation, invasion and migration of liver cancer cells, and has good clinical application prospect.
Description
Technical Field
The invention belongs to the field of biological medicines, and particularly relates to a pharmaceutical composition for preventing and treating liver injury and/or liver cancer, and a preparation method and application thereof.
Background
Liver damage is caused by the destruction and toxic effects of metabolites in the body on hepatocytes, and is an acute or chronic liver organ disease based on metabolic disorders of the liver. Liver injury is a common clinical disease harmful to human health, 140 million chronic liver disease patients exist in the world every year, China is a high-incidence liver disease country, about 1 hundred million hepatitis B virus carriers exist, and 2000 million chronic hepatitis patients exist.
The causative factors of liver damage are mainly of two types: 1. liver inflammation caused by infection with pathogenic microorganisms such as viruses, such as hepatitis A, hepatitis B, and the like. 2. Chemical liver injury, i.e., liver injury caused by chemical hepatotoxic substances, includes steatosis, lipid peroxidation, cholestasis, etc. The liver, which is an important detoxification organ of the human body, has a dual blood supply of hepatic artery and hepatic vein, and chemicals can enter the liver through the portal vein of the gastrointestinal tract or systemic circulation to be transformed, so that the liver is easily damaged by toxic substances among the chemicals. Alcohol, environmental chemical poisons, etc. can cause damage to the liver. Liver failure and hepatic encephalopathy caused by serious liver injury have high morbidity and mortality, and greatly threaten the health of human beings.
Primary liver cancer (HCC) is the sixth most common tumor worldwide, the third leading cause of cancer-related mortality, with a 5-year Overall Survival (OS) of only 10% -15%, with HBV infection, alcohol, aspergillus flavus, overweight and diabetes as their major causes. The easy recurrence after radical operation of patients with early primary liver cancer and the lack of effective antitumor drugs in patients with middle and late stages are important reasons for poor prognosis of patients. Therefore, there is an urgent need to find a therapeutic means for preventing tumor recurrence and prolonging survival time.
No matter the liver injury or the liver cancer is treated, the chemical medicament has great side effect in treatment, and can generate medicament resistance after long-term use to cause medicament residue; in recent years, the clinical application of the traditional Chinese medicinal materials and preparations thereof in the aspect of treating liver diseases in China is increasing day by day, and the unique advantages of low toxic and side effects and the like are shown. However, some of the traditional herbs have been found to have potential hepatotoxicity, or the therapeutic effect is still not ideal.
Therefore, the method further develops a new medicine which has low toxicity and excellent effect of preventing and treating liver injury and liver cancer, and has important significance and value.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for regulating qi activity, regulating liver and stomach, tonifying spleen and promoting diuresis.
The invention provides a pharmaceutical composition for preventing and treating liver injury and/or liver cancer, which is prepared from the following raw material medicines:
200-300 parts of radix bupleuri, 150-250 parts of radix scutellariae, 200-300 parts of radix astragali, 50-150 parts of liquorice, 200-300 parts of fructus forsythiae, 100-200 parts of rhizoma atractylodis macrocephalae, 200-300 parts of radix paeoniae alba, 20-120 parts of madder, 20-120 parts of malt, 50-150 parts of cuttlebone, 20-120 parts of turtle shell, 20-120 parts of endothelium corneum gigeriae galli, 10-110 parts of cinnamon, 1-10 parts of borneol and 1-10 parts of menthol.
Further, the traditional Chinese medicine is prepared from the following raw material medicines:
250-300 parts of radix bupleuri, 180-230 parts of radix scutellariae, 200-250 parts of radix astragali, 50-100 parts of liquorice, 200-250 parts of fructus forsythiae, 100-150 parts of rhizoma atractylodis macrocephalae, 200-250 parts of radix paeoniae alba, 20-50 parts of madder, 20-50 parts of malt, 50-100 parts of cuttlebone, 20-50 parts of turtle shell, 20-50 parts of endothelium corneum gigeriae galli, 10-50 parts of cinnamon, 1-5 parts of borneol and 1-5 parts of menthol.
Furthermore, the traditional Chinese medicine is prepared from the following raw material medicines:
266.7 parts of bupleurum, 200 parts of scutellaria, 222.2 parts of astragalus, 66.7 parts of liquorice, 222.2 parts of forsythia, 133.3 parts of bighead atractylodes rhizome, 222.2 parts of white peony root, 22.2 parts of madder, 44.4 parts of malt, 88.9 parts of cuttlebone, 44.4 parts of turtle shell, 44.4 parts of chicken's gizzard-membrane, 22.2 parts of cinnamon, 2.2 parts of borneol and 2.2 parts of menthol.
Furthermore, the radix scutellariae is wine radix scutellariae, the liquorice is honey-fried licorice root, the bighead atractylodes rhizome is bran-fried bighead atractylodes rhizome, and the turtle shell is vinegar turtle shell.
Furthermore, the pharmaceutical composition is a preparation prepared by taking crude drug powder of the raw material medicines, water or organic solvent extract as active ingredients and adding or not adding pharmaceutically acceptable auxiliary materials.
Further, the above preparation is an oral preparation.
Furthermore, the oral preparation is pills, powder, capsules, decoction and granules; preferably a pill; more preferably, each 1g of the pill is equivalent to 1.5-1.7 g of the raw material medicine.
The invention also provides a preparation method of the pill, which comprises the following steps:
(1) weighing fructus forsythiae, rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, carapax Trionycis, endothelium corneum Gigeriae Galli, cortex Cinnamomi, Borneolum Syntheticum, and Mentholum in proportion, mixing, and pulverizing into fine powder;
(2) weighing bupleuri radix, Scutellariae radix, radix astragali and Glycyrrhrizae radix at a certain proportion, soaking in water, decocting, filtering, and concentrating the filtrate into soft extract;
(3) and (3) uniformly mixing the fine powder obtained in the step (1) and the thick paste obtained in the step (2), and making pills.
The invention also provides application of the pharmaceutical composition in preparing a medicament for preventing and treating liver injury and liver cancer.
Furthermore, the medicine for preventing and treating liver injury is a medicine for protecting liver cells and improving liver functions; the medicine for preventing and treating liver cancer is a medicine for inhibiting proliferation of liver cancer cells, promoting apoptosis of liver cancer cells and inhibiting invasion and migration of liver cancer cells.
The experimental result shows that the pharmaceutical composition has low toxicity, can effectively prevent and treat liver injury, and inhibit proliferation, invasion and migration of liver cancer cells, and has very good clinical application prospect when being used as a medicament for protecting and treating liver cancer.
In the formula of the invention, radix bupleuri soothes liver and regulates qi, and radix scutellariae clears pathogenic heat, the radix bupleuri and the radix scutellariae are compatible, and are in the meaning of minor radix bupleuri, and regulate Shaoyang pivot machine, and are monarch drugs together; the endothelium corneum gigeriae galli is good for removing blood stasis and reducing stomach qi, the malt is good for promoting qi circulation and helping digestion, and is good for dispersing liver qi, the compatibility of the two medicines can promote liver qi to rise, stomach qi is smooth and descending, and spleen qi is healthy and strong, and the two medicines are ministerial medicines; radix astragali and rhizoma atractylodis macrocephalae have the effects of strengthening spleen qi, caring acquired constitution, consolidating innate constitution of cortex cinnamomi to inhibit transverse indulgence of liver wood, promoting blood circulation and stimulating menstrual flow, activating blood circulation and dissolving stasis of madder, dredging blood vessels of cuttlebone, softening hardness and dissipating stagnation of turtle shell, clearing heat and dissipating stagnation of fructus forsythiae, moistening liver and protecting liver body by radix paeoniae alba, which are used as adjuvant drugs; licorice root, radix Glycyrrhizae and licorice root, radix Glycyrrhizae Praeparata are used as guiding drugs, which act as liver-soothing drugs and harmonize the effects of the other drugs in the recipe, and borneol and menthol are used as fragrant and smoothing liver collaterals. The compatibility of the medicines can ensure that qi movement is smooth, liver and stomach are harmonized, spleen qi is healthy, damp-heat is cleared, and mass is eliminated automatically.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 shows the results of HE staining of mouse liver lobes.
FIG. 2 is a graph of the effect of a pharmaceutical composition of the present invention on cell proliferative activity; note: a is HepG2 cell, the low, medium and high dose are 7.5, 15, 30mg/ml respectively; SMMC-7721 cells, the low, medium and high doses are 4.5, 9 and 18mg/ml respectively.
FIG. 3 shows the effect of the pharmaceutical composition of the present invention on the proliferation of liver cancer cells; note: the low, medium and high doses of HepG2 cells are 7.5, 15 and 30mg/ml respectively; the low, medium and high doses of SMMC-7721 cells are 4.5, 9 and 18mg/ml respectively.
FIG. 4 is a graph showing the effect of the pharmaceutical composition of the present invention on the healing capacity of liver cancer cell scratch; note: the effect of different concentrations (low, medium and high doses are respectively 7.5, 15 and 30mg/ml) of the pharmaceutical composition of the invention in HepG2 cells on the healing of the scratch, and the percentage of the healing area of the scratch of HepG2 cells; c, the effect of different concentrations (4.5, 9 and 18mg/ml for low, medium and high doses respectively) of the pharmaceutical composition on the healing of the scratch in the SMMC-7721 cells, and D, the percentage of the healing area of the scratch of the SMMC-7721 cells.
FIG. 5 shows the effect of the pharmaceutical composition of the present invention on the invasive potential of hepatoma cells (crystal violet staining); note: the low, medium and high doses of HepG2 cells are 7.5, 15 and 30mg/ml respectively; the low, medium and high doses of SMMC-7721 cells are 4.5, 9 and 18mg/ml respectively.
FIG. 6 shows the effect of the pharmaceutical composition of the present invention on the migration ability of hepatoma cells (crystal violet staining); note: the low, medium and high doses of HepG2 cells are 7.5, 15 and 30mg/ml respectively; the low, medium and high doses of SMMC-7721 cells are 4.5, 9 and 18mg/ml respectively.
Detailed Description
The production of license numbers provided by the laboratory animal center of the academy of traditional Chinese medicine of Sichuan province: SCXK 2018-19. The mice are housed in an SPF barrier system of the animal center of the academy of traditional Chinese medicine and sciences of Sichuan province, the indoor temperature is 20-22 ℃, the relative humidity is about 50%, the illumination is 12h bright, and the illumination is 12h dark. The environment use license number is SYXK (Chuan) 2018-. Free drinking water and full-nutrition granulated feed are provided by the experimental animal center of the academy of traditional Chinese medicine and pharmacology of Sichuan province.
Statistical analysis: all data are expressed as mean ± standard deviation (x ± s). The measurement data is analyzed by variance, and the difference between groups is tested by Student T.
The starting materials and equipment used in the invention are, unless otherwise stated, known products obtained by purchasing commercially available products.
Example 1 preparation of a pharmaceutical composition of the invention
[ prescription ]
[ PREPARATION METHOD ] mixing fructus forsythiae, bran-fried rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, vinegar-processed carapax Trionycis, and endothelium corneum Gigeriae Galli, pulverizing into fine powder, sterilizing under heating, and drying; pulverizing cortex Cinnamomi into fine powder, adding ethanol, sealing, keeping the temperature, and drying; mixing the above two fine powders with Borneolum Syntheticum and Mentholum, and pulverizing. Adding 8 times of water into the radix bupleuri, the wine radix scutellariae, the radix astragali and the radix glycyrrhizae preparata, soaking for 1 hour, decocting for three times, each time for 0.5 hour, filtering decoction, combining filtrates, concentrating into thick paste, mixing with the fine powder, making into pills, drying (60 ℃), selecting the pills, and subpackaging to obtain the traditional Chinese medicine.
[ PROPERTIES ] the product is a tan water-bindered pill; slightly fragrant smell and cool taste.
[ Specification ] 1g of the product is equivalent to 1.604g of the raw medicinal material.
Example 2 preparation of a pharmaceutical composition of the invention
[ prescription ]
[ PREPARATION METHOD ] mixing fructus forsythiae, bran-fried rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, vinegar-processed carapax Trionycis, and endothelium corneum Gigeriae Galli, pulverizing into fine powder, sterilizing under heating, and drying; pulverizing cortex Cinnamomi into fine powder, adding ethanol, sealing, keeping the temperature, and drying; mixing the above two fine powders with Borneolum Syntheticum and Mentholum, and pulverizing. Adding 8 times of water into the radix bupleuri, the wine radix scutellariae, the radix astragali and the radix glycyrrhizae preparata, soaking for 1 hour, decocting for three times, each time for 0.5 hour, filtering decoction, combining filtrates, concentrating into thick paste, mixing with the fine powder, making into pills, drying (60 ℃), selecting the pills, and subpackaging to obtain the traditional Chinese medicine.
[ PROPERTIES ] the product is a tan water-bindered pill; slightly fragrant smell and cool taste.
[ Specification ] 1g of the product is equivalent to 1.5g of the raw medicinal material.
Example 3 preparation of a pharmaceutical composition of the invention
[ prescription ]
[ PREPARATION METHOD ] mixing fructus forsythiae, bran-fried rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, vinegar-processed carapax Trionycis, and endothelium corneum Gigeriae Galli, pulverizing into fine powder, sterilizing under heating, and drying; pulverizing cortex Cinnamomi into fine powder, adding ethanol, sealing, keeping the temperature, and drying; mixing the above two fine powders with Borneolum Syntheticum and Mentholum, and pulverizing. Adding 8 times of water into the radix bupleuri, the wine radix scutellariae, the radix astragali and the radix glycyrrhizae preparata, soaking for 1 hour, decocting for three times, each time for 0.5 hour, filtering decoction, combining filtrates, concentrating into thick paste, mixing with the fine powder, making into pills, drying (60 ℃), selecting the pills, and subpackaging to obtain the traditional Chinese medicine.
[ PROPERTIES ] the product is a tan water-bindered pill; slightly fragrant smell and cool taste.
[ Specification ] 1g of the product is equivalent to 1.7g of the raw medicinal material.
Example 4 preparation of a pharmaceutical composition of the invention
[ prescription ]
[ PREPARATION METHOD ] mixing fructus forsythiae, bran-fried rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, vinegar-processed carapax Trionycis, and endothelium corneum Gigeriae Galli, pulverizing into fine powder, sterilizing under heating, and drying; pulverizing cortex Cinnamomi into fine powder, adding ethanol, sealing, keeping the temperature, and drying; mixing the above two fine powders with Borneolum Syntheticum and Mentholum, and pulverizing. Adding 8 times of water into the radix bupleuri, the wine radix scutellariae, the radix astragali and the radix glycyrrhizae preparata, soaking for 1 hour, decocting for three times, each time for 0.5 hour, filtering decoction, combining filtrates, concentrating into thick paste, mixing with the fine powder, making into pills, drying (60 ℃), selecting the pills, and subpackaging to obtain the traditional Chinese medicine.
[ PROPERTIES ] the product is a tan water-bindered pill; slightly fragrant smell and cool taste.
[ Specification ] 1g of the product is equivalent to 1.6g of the raw medicinal material.
Example 5 preparation of a pharmaceutical composition of the invention
[ prescription ]
[ PREPARATION METHOD ] mixing fructus forsythiae, bran-fried rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, vinegar-processed carapax Trionycis, and endothelium corneum Gigeriae Galli, pulverizing into fine powder, sterilizing under heating, and drying; pulverizing cortex Cinnamomi into fine powder, adding ethanol, sealing, keeping the temperature, and drying; mixing the above two fine powders with Borneolum Syntheticum and Mentholum, and pulverizing. Adding 8 times of water into the radix bupleuri, the wine radix scutellariae, the radix astragali and the radix glycyrrhizae preparata, soaking for 1 hour, decocting for three times, each time for 0.5 hour, filtering decoction, combining filtrates, concentrating into thick paste, mixing with the fine powder, making into pills, drying (60 ℃), selecting the pills, and subpackaging to obtain the traditional Chinese medicine.
[ PROPERTIES ] the product is a tan water-bindered pill; slightly fragrant smell and cool taste.
[ Specification ] 1g of the product is equivalent to 1.65g of the raw medicinal material.
The beneficial effects of the present invention are demonstrated by the following experimental examples.
Experimental example 1 toxicity study of pharmaceutical composition of the present invention
1. Experimental methods
The results of preliminary experiments show that the pharmaceutical composition of the invention has weak acute toxicity, so the maximum dosage test is carried out on the pharmaceutical composition.
After adaptive feeding for 1d, 40 SPF-level Kunming mice with the body mass of 18-22g are divided into two groups, namely a control group and an administration group, wherein each group comprises 20 mice with each half of male and female. After the mice are fasted for 14 hours without water inhibition, the mice are intragastrically administered once at the maximum concentration (0.864g crude drug/ml) and the maximum administration volume (0.4ml/10g) so that the administration dose reaches 34.55g crude drug/kg, and the mice are intragastrically administered with 0.5% CMC-Na solution in the same way as the control group. The toxic manifestations and death of the animals in 14d after administration were observed and recorded, and the body mass was weighed before and at 7d and 14d after administration. At the end of the experiment, mice were sacrificed by dislocation, and the heart, liver, spleen, lung, and kidney were weighed as the organ mass, and the organ index was calculated.
Organ index is organ mass (mg)/mouse mass (g) × 10g
2. Results of the experiment
As can be seen from Table 1, when the drug prepared in example 1 was administered to mice by gavage, no death or abnormality in behavior, excretion, secretion, etc. was observed in the mice. The body mass of the group to which the drug was administered was not statistically different from that of the control group.
TABLE 1 Effect of maximum tolerated dose of the pharmaceutical compositions of the invention on mouse body mass (x. + -. s)
The mice are sacrificed at the end of the test, and the main organs of all groups of mice are examined by dissection and naked eyes to find no macroscopic abnormality; as can be seen from Table 2, the example 1 drug had no significant effect on the organ index of mice, and had no statistical difference compared with the control group. Example 1 median lethal dose (LD50) >34.55g of crude drug/kg.
TABLE 2 Effect of the pharmaceutical compositions of the present invention on the visceral indices of mice (x. + -. s)
In the above results, the median lethal dose (LD50) >34.55g of crude drug/kg of the pharmaceutical composition of the present invention indicates that the drug of the present invention has low toxicity.
Experimental example 2, pharmaceutical composition of the present invention and Effect on liver injury in mice
1. Experimental method
66 male Kunming mice with the body weight of 18-22g and the SPF grade are adaptively fed for 1 d. Control, model, bicyclol (100mg/kg), example 1 (12g crude drug/kg, 6g crude drug/kg, 3g crude drug/kg) were randomized by body weight for 6 groups, and the groups were gavaged at 0.2ml/10g and an equal volume of 0.5% CMC-Na solution once a day for ten consecutive days. After three days of continuous administration, 0.1ml/10g of dimethyl nitrosamine (DMN) solution (10mg/kg) is injected intraperitoneally to induce liver injury, and an equal volume of normal saline is injected intraperitoneally to the control group once every other day for three consecutive days. After the last administration, fasting for 14h without water prohibition, taking blood from carotid artery, and biochemically detecting ALT, AST, ALP, TP, ALB, TBIL, DBIL and TBA liver function indexes in serum; weighing the liver by wet weight, and calculating organ indexes; fixing 10% formaldehyde in liver lobe, and performing pathological analysis after HE staining.
After the experiment, the liver is taken, fully fixed by 10% formalin, dehydrated by gradient alcohol, embedded by paraffin, prepared into a pathological section of 3-5 mu m, and the histological structure of the liver is observed under an optical microscope.
The specimens were grouped and counted as follows:
histopathological scoring: the histological scoring standard of liver injury, the content of reference documents and the actual situation of the experiment are combined to draw up 'vacuole formation of liver cells' and 'necrosis of liver cells' as observation indexes. The lesion extent was analyzed semi-quantitatively: grade 1, mild; grade 2, mild; grade 3, medium; grade 4, severe; grade 5, severe.
And (3) counting pathological changes: semi-quantitative scoring is carried out on the pathological changes of each liver specimen according to a histopathological scoring standard, and after the scores of each specimen are accumulated, two-sample analysis of grade data is carried out between a model control group and a blank control group and among all administration groups by using a rank sum test. All tests were two-sided, α ═ 0.05, and all statistical analyses were performed under SPSS for Windows 20.0 software.
2. Results of the experiment
As shown in Table 3, the doses of the pharmaceutical composition of example 1 did not significantly affect the body mass and liver index of DMN-induced liver injury mice, and the difference was not statistically different from that of the model group, indicating that the pharmaceutical composition of the present invention has no significant hepatotoxicity.
TABLE 3 influence of the pharmaceutical composition of the present invention on the physical quality and liver of DMN-induced liver injury mice
Compared to the model group, P <0.05 × P < 0.01 × P < 0.001 (same below).
As shown in Table 4, compared with the model group, the liver function index of the mouse with liver injury caused by DMN (dimethyl formamide) is found to remarkably reduce the ALT index by each dose of the pharmaceutical composition, and the AST index is remarkably reduced by 12g of crude drug/kg and 6g of crude drug/kg of the drug in example 1; example 1 drug 12g protoplasm/kg significantly reduced the TBIL and TBA indicators with statistical differences. The above results illustrate that: the pharmaceutical composition can improve the liver function of a liver-damaged mouse.
TABLE 4 Effect of the pharmaceutical composition of the present invention on liver function of DMN-induced liver injury mice
As can be seen from FIG. 1, the pharmaceutical composition of the present invention can significantly reduce the vacuolation of liver cells and reduce the necrosis of liver cells. From observations of the histological structure of the liver:
(1) blank control group: in 10 specimens, the hepatic lobules of all specimens have clear structures, the shapes of the hepatic cells are not abnormal, and the interstitium does not have hyperplasia and inflammatory cell infiltration.
(2) Model control group: in 12 specimens in total, hepatocellular necrosis (grade 2, grade 3, and 7 cases) and formation of vacuoles in hepatocytes (grade 1, grade 3, grade 4, and grade 5, and 2 cases) were observed. Showed mild to mild hepatocellular necrosis and mild to severe intrahepatocellular vacuolization, with severe lesions and statistically significant differences compared to the blank control group (P < 0.05).
(3) Bicyclol 100mg/kg group: in all 12 specimens, hepatocellular necrosis (8 specimens, grade 1, 4 specimens, grade 2) and formation of vacuoles in hepatocytes (3 specimens, grade 1, 5 specimens, grade 3, 4 specimens, grade 4) were observed. Showing mild to mild hepatocellular necrosis and mild to severe intrahepatocellular vacuolization, the lesions were less severe and the differences were statistically significant (P <0.05) compared to the model control group.
(4) Example 1 drug 3g protoplasm/kg group: in total, 10 specimens were observed, with hepatocellular necrosis in 9 specimens (5 specimens at grade 1, 3 specimens at grade 2, and 1 specimen at grade 4), and vacuolation in hepatocytes in 10 specimens (1 specimen at grade 1, 6 specimens at grade 2, 1 specimen at grade 3, and 2 specimens at grade 4). Shows slight to severe hepatocyte necrosis and slight to severe vacuolation in hepatocytes, and the severity of the lesions is reduced compared with the model control group, and the difference is statistically significant (P < 0.05).
(5) Example 1 drug 6g protoplasm/kg group: in total, 11 specimens were observed for hepatocellular necrosis (6 specimens at grade 1, 3 specimens at grade 2, and 2 specimens at grade 3) and formation of vacuoles in hepatocytes (3 specimens at grade 1, 2 specimens at grade 2, 4 specimens at grade 3, 1 specimen at grade 4, and 1 specimen at grade 5). Shows slight to moderate hepatocyte necrosis and slight to severe vacuolation in hepatocytes, and the severity of the lesions is reduced compared with the model control group, and the difference is statistically significant (P < 0.05).
(6) Example 1 drug 12g protoplasm/kg group: in total, 9 specimens were examined, with 5 specimens showing hepatocyte necrosis (grade 2, grade 1, grade 3, grade 2) and 8 specimens showing vacuolization in hepatocytes (grade 1, grade 2, grade 3, grade 4). Showing mild to mild hepatocellular necrosis and mild to severe intrahepatocellular vacuolization, the lesions were less severe and the differences were statistically significant (P <0.05) compared to the model control group.
The specific data are shown in Table 5.
TABLE 5 histological grading results of the specimens of each group
*: the difference is statistically significant (P)<0.05)。
Therefore, as can be seen from the results of case analysis after HE staining and histopathological detection, the pharmaceutical composition of the invention can protect liver cells, reduce hepatocyte necrosis, reduce vacuole formation in liver cells, and has the effect of preventing and treating liver injury.
Test example 3 Effect of the pharmaceutical composition of the present invention on various liver cancer cell lines
1. Materials and methods
(1) Experimental Material
The drugs of example 1, human hepatoma cells HepG2 and SMMC-7721 were stored in the inventors' laboratory.
1.2 Experimental reagents
DMEM high-glucose medium (Gibco, usa), fetal bovine serum (PAN, germany), CCK8 kit (synneus chemical, japan), Martige matrigel (BD corporation, usa), Annexin-VFITC apoptosis detection kit (bi yunnan corporation, china).
(2) Experimental methods
2.1 extraction of drug Water
The drug of example 1 was pulverized into powder, 5g of the powder was taken, 8 times of ultrapure water was added, ultrasonic extraction was performed for 30min (power 250W, frequency 40kHz), cooled to room temperature, centrifuged at 12000rpm for 10min, the supernatant was collected, and filtered and sterilized with a 0.22um sterilizing filter.
2.2 drug concentration screening and cell viability assay
The liver cancer cells SMMC-7721 and HepG2 in logarithmic growth phase are respectively inoculated in a 96-well plate, and after 24 hours, the drugs of example 1 with different concentrations are added for intervention. According to the specification, CCK8 working solution is prepared according to the proportion of complete culture medium to CCK8 reagent which is 10 to 1, after the complete culture medium and the CCK8 reagent are fully mixed, 100 mu l of the working solution is added into each hole, the mixture is incubated for 1h at 37 ℃ in an incubator, and the absorbance value (A value) is detected by a microplate reader at 450 nm. Cell viability ═ 100% (a dosed-a blank)/(a control-a blank). The optimal drug concentration (HepG2 optimal drug concentration is 15mg/ml, SMMC-7721 optimal drug concentration is 9mg/ml) is screened out, and high-dose and low-dose groups are set according to 2 times and 1/2 times of the optimal drug concentration, and cell viability is detected for 24 hours, 48 hours and 72 hours respectively.
2.3 plate cloning experiments
Inoculating cells into a 6-well plate according to 3000-5000 cells/well, intervening with different drug concentrations after 24 hours, changing the liquid every 2-3 days, stopping cloning when macroscopic cloning occurs to the cells, washing with PBS once, fixing with methanol for 30min, staining with 0.1% crystal violet for 20min, and taking a picture for recording.
2.4 cell scratch test
Inoculating SMMC-7721 and HepG2 cells into a 12-hole plate, carrying out drug intervention for 24 hours when the cells grow to about 80%, carrying out linear scratch in the cells after the cells grow full, washing with PBS, replacing a serum-free culture medium, observing the healing conditions of the cells for 24 hours, 48 hours and 72 hours, and taking pictures for recording.
2.5 cell invasion assay
According to the specification of Matrigel, a proper amount of Matrigel is added into a Transwell chamber, placed into an incubator at 37 ℃ and 5% CO2 for incubation for 1 hour, solidified and taken out. Preparing a cell suspension of SMMC-7721 liver cancer cells subjected to drug dry prognosis with different drug concentrations by using a serum-free culture medium according to the proportion of 1 × 105 cells/ml, adding 600ul of a complete culture medium containing 20% fetal calf serum into a lower chamber, placing the lower chamber into an incubator at 37 ℃ and 5% CO2, taking out the cells after 24 hours, washing the cells with PBS, fixing the cells with methanol, dyeing the cells with crystal violet, observing the number of transmembrane cells under a microscope, and taking a picture for recording.
2.6 cell migration assay
The cell invasion experiment was performed as described above except that matrigel was not added to the upper chamber.
2.7 statistical methods
All data were analyzed using SPSS 22.0 software, fitting normally distributed metrology data to
The comparison among groups adopts a paired t test, and the difference is statistically significant when P is less than 0.05. P <0.05, P < 0.01, P < 0.0001.
3. Results
3.1 Effect of the pharmaceutical composition of the invention on human hepatoma cell proliferation and apoptosis
Compared with the control group, the effect of the drug of the invention for inhibiting the activity (figure 2, P < 0.01, P < 0.0001) and the proliferation capacity (figure 3) of the human liver cancer cells HepG2 and SMMC-7721 is stronger along with the increase of the action time and the drug concentration, and the difference has statistical significance. The pharmaceutical composition can inhibit the proliferation of the liver cancer cells and promote the apoptosis of the liver cancer cells.
3.2 Effect of the pharmaceutical composition of the invention on migration and invasion capabilities of human hepatoma cells
The pharmaceutical composition of the invention, with intervention at different drug concentrations, reduced the cell healing rate of HepG2 and SMMC-7721 (fig. 4), inhibited the invasion (fig. 5) and migration (fig. 6) of cells, and was dose-dependent, with higher drug concentrations, stronger effects, and statistical differences (P <0.05, P < 0.01, P < 0.0001). The pharmaceutical composition can inhibit the invasion and migration of the liver cancer cells.
In conclusion, the pharmaceutical composition for preventing and treating liver injury and inhibiting the activity of liver cancer cells provided by the invention has low toxicity, has a repairing effect on liver cells, can inhibit the progress of liver cancer cells, realizes the effects of protecting liver and resisting liver cancer, and has a good clinical application prospect.
Claims (10)
1. A pharmaceutical composition for preventing and treating liver injury and/or liver cancer is characterized by being prepared from the following raw material medicines:
200-300 parts of radix bupleuri, 150-250 parts of wine scutellaria baicalensis, 200-300 parts of astragalus membranaceus, 50-150 parts of honey-fried licorice root, 200-300 parts of fructus forsythiae, 100-200 parts of bran-fried bighead atractylodes rhizome, 200-300 parts of radix paeoniae alba, 20-120 parts of madder, 20-120 parts of malt, 50-150 parts of cuttlebone, 20-120 parts of vinegar turtle shell, 20-120 parts of endothelium corneum gigeriae galli, 10-110 parts of cinnamon, 1-10 parts of borneol and 1-10 parts of menthol.
2. The pharmaceutical composition of claim 1, which is prepared from the following raw material drugs:
250-300 parts of radix bupleuri, 180-230 parts of wine scutellaria baicalensis, 200-250 parts of astragalus membranaceus, 50-100 parts of honey-fried licorice root, 200-250 parts of fructus forsythiae, 100-150 parts of bran-fried bighead atractylodes rhizome, 200-250 parts of radix paeoniae alba, 20-50 parts of madder, 20-50 parts of malt, 50-100 parts of cuttlebone, 20-50 parts of vinegar turtle shell, 20-50 parts of endothelium corneum gigeriae galli, 10-50 parts of cinnamon, 1-5 parts of borneol and 1-5 parts of menthol.
3. The pharmaceutical composition of claim 2, which is prepared from the following raw materials:
266.7 parts of bupleurum, 200 parts of wine scutellaria, 222.2 parts of astragalus, 66.7 parts of honey-fried licorice root, 222.2 parts of forsythia, 133.3 parts of bran-fried atractylodes, 222.2 parts of white peony root, 22.2 parts of madder, 44.4 parts of malt, 88.9 parts of cuttlebone, 44.4 parts of vinegar turtle shell, 44.4 parts of chicken's gizzard-membrane, 22.2 parts of cinnamon, 2.2 parts of borneol and 2.2 parts of menthol.
4. The pharmaceutical composition according to any one of claims 1 to 3, which is a preparation prepared from crude drug powder of the raw drug materials, water or an organic solvent extract as an active ingredient, with or without pharmaceutically acceptable excipients.
5. The pharmaceutical composition of claim 4, wherein the formulation is an oral formulation.
6. The pharmaceutical composition of claim 5, wherein the oral formulation is a pill, powder, capsule, decoction, or granule.
7. The pharmaceutical composition of claim 6, wherein the oral formulation is a pill.
8. The pharmaceutical composition according to claim 7, wherein 1g of the pill is equivalent to 1.5-1.7 g of the bulk drug.
9. A process for preparing a pharmaceutical composition according to claim 7, comprising the steps of:
(1) weighing fructus forsythiae, rhizoma Atractylodis Macrocephalae, radix Paeoniae alba, radix Rubiae, fructus Hordei Germinatus, Endoconcha Sepiae, carapax Trionycis, endothelium corneum Gigeriae Galli, cortex Cinnamomi, Borneolum Syntheticum, and Mentholum in proportion, mixing, and pulverizing into fine powder;
(2) weighing bupleuri radix, Scutellariae radix, radix astragali and Glycyrrhrizae radix at a certain proportion, soaking in water, decocting, filtering, and concentrating the filtrate into soft extract;
(3) and (3) uniformly mixing the fine powder obtained in the step (1) and the thick paste obtained in the step (2), and making pills.
10. Use of the pharmaceutical composition of any one of claims 1 to 8 in the preparation of a medicament for the prevention and treatment of liver injury and/or liver cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110827474.3A CN113384667B (en) | 2021-07-21 | 2021-07-21 | Pharmaceutical composition for preventing and treating liver injury and/or liver cancer and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110827474.3A CN113384667B (en) | 2021-07-21 | 2021-07-21 | Pharmaceutical composition for preventing and treating liver injury and/or liver cancer and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113384667A CN113384667A (en) | 2021-09-14 |
| CN113384667B true CN113384667B (en) | 2022-05-24 |
Family
ID=77626695
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110827474.3A Active CN113384667B (en) | 2021-07-21 | 2021-07-21 | Pharmaceutical composition for preventing and treating liver injury and/or liver cancer and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113384667B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1907462A (en) * | 2006-08-07 | 2007-02-07 | 张庆存 | Traditional Chinese medicine composition for treating hepatitis and fatty liver |
| CN101332284A (en) * | 2008-07-30 | 2008-12-31 | 佛山德众药业有限公司 | Chinese traditional medicine composition for treating ulcerative colitis and its preparation method |
| CN110170015A (en) * | 2019-06-18 | 2019-08-27 | 河北中医学院 | A kind of Chinese medicine composition and its preparation method and application of protective agents hepatic injury |
| CN110237198A (en) * | 2019-07-17 | 2019-09-17 | 南京万厚中医医院有限责任公司 | A kind of Softing liver and contracting spleen Chinese medicine composition |
-
2021
- 2021-07-21 CN CN202110827474.3A patent/CN113384667B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1907462A (en) * | 2006-08-07 | 2007-02-07 | 张庆存 | Traditional Chinese medicine composition for treating hepatitis and fatty liver |
| CN101332284A (en) * | 2008-07-30 | 2008-12-31 | 佛山德众药业有限公司 | Chinese traditional medicine composition for treating ulcerative colitis and its preparation method |
| CN110170015A (en) * | 2019-06-18 | 2019-08-27 | 河北中医学院 | A kind of Chinese medicine composition and its preparation method and application of protective agents hepatic injury |
| CN110237198A (en) * | 2019-07-17 | 2019-09-17 | 南京万厚中医医院有限责任公司 | A kind of Softing liver and contracting spleen Chinese medicine composition |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113384667A (en) | 2021-09-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100548323C (en) | A kind of pharmaceutical composition of making by Herb Gynostemmae Pentaphylli, Radix Panacis Quinquefolii and the Radix Astragali | |
| CN102138966B (en) | Tibetan capillaris extract and preparation method, pharmaceutical composition and use thereof | |
| CN1872106A (en) | Application of wild basil circle leaves in treating disease of virulence cold | |
| WO2013071727A1 (en) | Anti-tumor traditional chinese medical composition | |
| CN105434648A (en) | Traditional Chinese medicine composition for treating acute mastitis and preparation method thereof | |
| CN101850032B (en) | Anti-tumor traditional Chinese medicine composition and preparation method and application thereof | |
| CN107551001B (en) | A Chinese medicinal composition for preventing and treating alcoholic hepatic injury and its preparation method | |
| CN108452009A (en) | A kind of application including Common Leafflower Herb, rainbow conk, Radix Salviae Miltiorrhizae and the Chinese medicine composition of Asian puccoon in the drug for preparing treatment liver cancer | |
| CN113384667B (en) | Pharmaceutical composition for preventing and treating liver injury and/or liver cancer and preparation method and application thereof | |
| CN101773490B (en) | Active part of Sambucus williamsii Hance for reducing risk of bone-related diseases of menopausal women and application thereof | |
| CN104435977B (en) | It is a kind of to be used to treat medicine of hepatic injury and preparation method thereof | |
| CN104547588B (en) | A kind of preparation method of stomach health drop pills | |
| CN101411779A (en) | Chinese medicine effective component composition for treating liver cancer and method for preparing the same | |
| CN108452008A (en) | A kind of application including Common Leafflower Herb, rainbow conk, Radix Salviae Miltiorrhizae and the Chinese medicine composition of Asian puccoon in preparing the drug for inhibiting recurrence of PHC | |
| CN102078409B (en) | Traditional Chinese medicine preparation for treating liver cancer | |
| CN102240328B (en) | Traditional Chinese medicine for treating cold and preparation method thereof | |
| CN104257955A (en) | Anti-hepatoma traditional Chinese medicine mixture containing arisaema amurense and production method of anti-hepatoma traditional Chinese medicine mixture | |
| CN1969937B (en) | Pharmaceutical composition for treating hepatitis | |
| CN101011543A (en) | Antineoplastic medicine composition | |
| CN103169844A (en) | Traditional Chinese medicine composition having anti-lung cancer and anti-liver cancer effects | |
| US20060177520A1 (en) | Compositions and methods for reducing cytotoxicity and inhibiting angiogenesis | |
| CN112717031B (en) | Pharmaceutical composition for treating Alzheimer's disease and preparation method thereof | |
| CN108126134B (en) | Traditional Chinese medicine compound composition for treating liver injury, preparation method and application thereof | |
| CN102552848B (en) | Ginger and kudzuvine root composition for reducing vomiting caused by cancer chemotherapy and improving chemotherapy effects, and preparation method for ginger and kudzuvine root composition | |
| CN114073721B (en) | Preparation and application of vinegar-soaked licorice tablets |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |