CN109045053B - Ginsenoside composition for treating leukopenia and application - Google Patents
Ginsenoside composition for treating leukopenia and application Download PDFInfo
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- CN109045053B CN109045053B CN201810707155.7A CN201810707155A CN109045053B CN 109045053 B CN109045053 B CN 109045053B CN 201810707155 A CN201810707155 A CN 201810707155A CN 109045053 B CN109045053 B CN 109045053B
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Abstract
The invention relates to a ginsenoside composition for treating leukopenia and application, wherein the composition comprises ginsenoside Rk1 and ginsenoside Rg5 in a mass ratio of (1: 3) to (2: 3). The in vitro granulocyte-macrophage hematopoietic progenitor cell colony culture and mouse experiments prove that the mixture consisting of the ginsenoside Rk1 and the ginsenoside Rg5 can obviously promote the proliferation of CFU-GM and has obvious effect of increasing the white blood cells of a leukopenia model mouse.
Description
Technical Field
The invention relates to the field of biochemical engineering, and in particular relates to a ginsenoside composition for treating leucopenia and application thereof.
Background
Leukocytes originate from Hematopoietic Stem Cells (HSCs) in the bone marrow, undergo committed progenitor cells, primitive and naive cells and then become mature leukocytes with various functions, and are then released regularly into the blood circulation. The differentiation and proliferation of leukocytes are positively regulated by Hematopoietic Growth Factors (HGFs), Colony Stimulating Factors (CSFs), certain cytokines, and the like. In addition, there is a class of inhibitory factors, such as granulostatin, lactoferrin and transforming growth factorEtc., which can directly inhibit the proliferation of leukocytes, and also can reduce peripheral leukocytes by limiting the release or action of CSF. Leukopenia (leukopenia) means that the absolute count of white blood cells in peripheral blood cells persists below 4.9X 109And L. Normally, the differentiation, maturation and release of hematopoietic cells in bone marrow are relatively constant with the senescence, destruction and elimination of blood cells in peripheral blood, and certain factors disrupt this balance, resulting in leukopenia. The causes of leukopenia are primary and secondary. It is generally considered to be associated withThe factors of transmission, immunity, physics, chemistry, medicine and the like have close relation, and especially the leucopenia caused by radiotherapy and chemotherapy of tumor patients is prominent.
The ginseng has the effects of preventing and treating diseases and prolonging life proved by ancient and modern pharmacology and clinical research. The "Shennong Ben Cao Jing" in the east Han period and the "Ben Cao gang mu" in Li Shizhen, a famous medical specialist in the Ming dynasty both have a detailed and very definite record on the efficacy of Ginseng radix. Modern pharmacology and clinical practice further prove the pharmacological action of ginseng. The rare ginsenoside has stronger free radical scavenging, antioxidant and anticancer activities than common ginsenoside. Research shows that rare ginsenoside is a substance which is present or absent in trace amount in ginseng, but is more and more concerned because the rare ginsenoside is easier to be absorbed and utilized in vivo and has more remarkable pharmacological activity.
Disclosure of Invention
The invention aims to provide a ginsenoside composition for treating leukopenia and application thereof, wherein the composition contains ginsenoside Rk1 and ginsenoside Rg5, and can effectively increase the level of white blood cells.
The technical scheme adopted by the invention is as follows:
a ginsenoside composition for treating leukopenia, which is characterized in that:
the composition comprises ginsenoside Rk1 and ginsenoside Rg5 in a mass ratio of (1: 3) - (2: 3).
The purity of the ginsenoside Rk1 and ginsenoside Rg5 is more than 95 percent.
The application of the ginsenoside composition for treating leucopenia is characterized in that:
the composition is used as an effective component of a medicament for treating leukopenia.
The medicine containing the composition contains medically acceptable pharmaceutic adjuvants.
The medicine containing the composition is in oral dosage forms, including tablets, powders, capsules, granules, sugar-coated agents, pills, liquids and syrups; or injectable formulations, including suspensions, liposomes, and solutions; or topical dosage forms, including ointment, solid, suspension, spirit, powder, paste, aerosol, film coating, lotion and emulsion.
The composition can increase the action concentration of mouse leucocyte in vivo to 200 mg/kg.
The invention has the following advantages:
the composition provided by the invention consists of ginsenoside Rk1 and ginsenoside Rg5, and the mixture consisting of ginsenoside Rk1 and ginsenoside Rg5 can obviously promote the proliferation of CFU-GM and has an obvious effect of increasing white blood cells of a leukopenia model mouse through in vitro granulocyte-macrophage lineage hematopoietic progenitor cell colony culture and mouse experiments.
Drawings
FIG. 1 shows the effect of the combination of ginsenoside Rk1 and Rg5 (1: 3) on CFU-GM colonies.
FIG. 2 shows the effect of the combination of ginsenoside Rk1 and Rg5 (2: 3) on CFU-GM colonies.
FIG. 3 shows the effect of the combination of ginsenoside Rk1 and Rg5 (3: 7) on CFU-GM colonies.
FIG. 4 shows that the combination of ginsenoside Rk1 and Rg5 (1: 3) has effect of increasing leukocyte.
FIG. 5 shows that the combination of ginsenoside Rk1 and Rg5 (2: 3) has effect of increasing leukocyte.
FIG. 6 shows that the combination of ginsenoside Rk1 and Rg5 (3: 7) has effect of increasing leukocyte.
Detailed Description
The present invention will be described in detail with reference to specific embodiments.
The invention relates to a ginsenoside composition for treating leukopenia, which comprises ginsenoside Rk1 and ginsenoside Rg5, wherein the mass ratio of the ginsenoside Rk1 to the ginsenoside Rg5 is (1: 3) - (2: 3). The purity of the ginsenoside Rk1 and ginsenoside Rg5 is more than 95 percent. The composition can be used as an effective component of a medicine for treating leukopenia, and the medicine containing the composition contains a medically acceptable pharmaceutic adjuvant.
The medicine containing the composition is in oral dosage forms, including tablets, powders, capsules, granules, sugar-coated agents, pills, liquids and syrups; or injectable formulations, including suspensions, liposomes, and solutions; or topical dosage forms, including ointment, solid, suspension, spirit, powder, paste, aerosol, film coating, lotion and emulsion. For example, the oral dosage form can be prepared into capsules, wherein the ginsenoside Rk1 and ginsenoside Rg5 are mixed in a ratio of 1:3, mixing the materials in proportion, granulating by using 70-75% of ethanol, drying and filling to obtain the compound feed additive, wherein the content of active ingredients is 100%; the tablet can be prepared by mixing ginsenoside Rk1 and ginsenoside Rg5 in a ratio of 1:3, mixing the raw materials in proportion, adding magnesium stearate, stachyose and povidone auxiliary materials, and tabletting to form the tablet, wherein the content of the effective components can reach 80-95%; the injection can be prepared into fat emulsion by mixing ginsenoside Rk1 and ginsenoside Rg5 at a ratio of 1:3, adding castor oil, homogenizing by a high-speed homogenizer, uniformly dispersing the monomers, and sterilizing the mixture to obtain the injection, wherein the content of active ingredients can reach 10-30 mg/mL.
The composition can increase the action concentration of mouse leucocyte in vivo to 200 mg/kg.
EXAMPLE 1 preparation of a ginsenoside composition for the treatment of leukopenia
Preparing ginsenoside compositions with total saponin concentrations of 500 mug/mL, 250 mug/mL, 125 mug/mL and 62.5 mug/mL according to the following table:
the ginsenoside with the proportion is mixed to prepare a mixture according to the proportion in the table 1, two ginsenoside monomers with the same concentration are used as a reference to act on colony culture of the granulocyte-macrophage hematopoietic progenitor cells, and the experimental result is shown in the attached figure 1. The result shows that by using the agar in vitro culture method, the ginsenoside mixture can obviously promote the proliferation of CFU-GM when the concentration is higher than 125 mg/mL, and has significant difference compared with ginsenoside Rk1 and ginsenoside Rg5 monomers.
EXAMPLE 2 preparation of a ginsenoside composition for the treatment of leukopenia
Preparing ginsenoside compositions with total saponin concentrations of 500 mug/mL, 250 mug/mL, 125 mug/mL and 62.5 mug/mL according to the following table:
the ginsenosides in the above proportions are mixed to prepare a mixture according to the proportion in table 2, and two ginsenosides monomers with the same concentration are used as a control to act on colony culture of granulocyte-macrophage hematopoietic progenitor cells, and the experimental result is shown in figure 2. The result shows that by using the agar in vitro culture method, the ginsenoside mixture can obviously promote the proliferation of CFU-GM when the concentration is higher than 125 mg/mL, and has significant difference compared with ginsenoside Rk1 and ginsenoside Rg5 monomers.
EXAMPLE 3 preparation of a ginsenoside composition for the treatment of leukopenia
Preparing ginsenoside compositions with total saponin concentrations of 500 mug/mL, 250 mug/mL, 125 mug/mL and 62.5 mug/mL according to the following table:
the ginsenosides in the above proportions are mixed to prepare a mixture according to the proportion in table 3, and two ginsenosides monomers with the same concentration are used as a control to act on colony culture of granulocyte-macrophage hematopoietic progenitor cells, and the experimental result is shown in figure 3. The result shows that by using the agar in vitro culture method, the ginsenoside mixture can obviously promote the proliferation of CFU-GM when the concentration is higher than 125 mg/mL, and has significant difference compared with ginsenoside Rk1 and ginsenoside Rg5 monomers.
EXAMPLE 4 preparation of a ginsenoside composition for the treatment of leukopenia
A ginsenoside composition with a total saponin content of 200 mg/kg was administered to mice in a leukopenia model by intraperitoneal injection as follows:
the mixture of the above saponins and two saponin monomers of the same dosage were used as controls for intraperitoneal administration to mice according to the formulation in table 4. The experimental results are shown in figure 4. The result shows that when the saponin mixture is injected and administered at 200 mg/kg, the leucocyte can be effectively increased, the saponin composition has better effect than a single saponin monomer, the effect is better than that of a positive control drug, and the effect is more stable than that of the positive control drug rhG-CSF.
EXAMPLE 5 preparation of a ginsenoside composition for the treatment of leukopenia
A ginsenoside composition with a total saponin content of 200 mg/kg was administered to mice in a leukopenia model by intraperitoneal injection as follows:
the mixture of the above saponins and two saponin monomers of the same dosage were used as controls for intraperitoneal administration to mice according to the formulation in table 5. The experimental results are shown in figure 5. The result shows that when the saponin mixture is injected and administered at 200 mg/kg, the leucocyte can be effectively increased, the saponin composition has better effect than a single saponin monomer, the effect is better than that of a positive control drug, and the effect is more stable than that of the positive control drug rhG-CSF.
EXAMPLE 6 preparation of a ginsenoside composition for the treatment of leukopenia
A ginsenoside composition with a total saponin content of 200 mg/kg was administered to mice in a leukopenia model by intraperitoneal injection as follows:
the mixture of the above saponins and two saponin monomers of the same dosage were used as controls for intraperitoneal administration to mice according to the formulation in table 6. The experimental results are shown in figure 6. The result shows that when the saponin mixture is injected and administered at 200 mg/kg, the leucocyte can be effectively increased, the saponin composition has better effect than a single saponin monomer, the effect is better than that of a positive control drug, and the effect is more stable than that of the positive control drug rhG-CSF.
Further experiments show that compared with two monomers, the ginsenoside Rk1 and ginsenoside Rg5 composition can more effectively promote the proliferation of hematopoietic progenitor cells, promote the recovery of the hematopoietic function of an organism, regulate a bone marrow hematopoietic microenvironment, promote the secretion of granulocyte-macrophage colony stimulating factor (GM-CSF) and Stem Cell Factor (SCF) by bone marrow stromal cells, have a better promotion effect on the proliferation of the bone marrow cells and improve the hematopoietic function of the organism.
The invention is not limited to the examples, and any equivalent changes to the technical solution of the invention by a person skilled in the art after reading the description of the invention are covered by the claims of the invention.
Claims (5)
1. The application of the ginsenoside composition in preparing the medicine for treating leukopenia is characterized in that:
the ginsenoside composition comprises ginsenoside Rk1 and ginsenoside Rg5, and the mass ratio of the ginsenoside Rk1 to the ginsenoside Rg5 is (1: 3) - (2: 3).
2. The use of a ginsenoside composition of claim 1 in the preparation of a medicament for treating leukopenia, wherein:
the purity of the ginsenoside Rk1 and ginsenoside Rg5 is more than 95 percent.
3. The use of a ginsenoside composition of claim 2 in the preparation of a medicament for treating leukopenia, wherein:
the medicine containing the composition contains medically acceptable pharmaceutic adjuvants.
4. Use of a ginsenoside composition of claim 3 in the preparation of a medicament for treating leukopenia, wherein:
the medicine containing the composition is in oral dosage forms, including tablets, powders, capsules, granules, sugar-coated agents, pills, liquids and syrups; or injectable formulations, including suspensions, liposomes, and solutions; or topical dosage forms, including ointment, solid, suspension, spirit, powder, paste, aerosol, film coating, lotion and emulsion.
5. The use of a ginsenoside composition of claim 4 in the preparation of a medicament for treating leukopenia, wherein:
the composition can increase the action concentration of mouse leucocyte in vivo to 200 mg/kg.
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