CN113332358A - Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products - Google Patents

Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products Download PDF

Info

Publication number
CN113332358A
CN113332358A CN202110703296.3A CN202110703296A CN113332358A CN 113332358 A CN113332358 A CN 113332358A CN 202110703296 A CN202110703296 A CN 202110703296A CN 113332358 A CN113332358 A CN 113332358A
Authority
CN
China
Prior art keywords
preparation
cordycepin
compound
group
parts
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.)
Pending
Application number
CN202110703296.3A
Other languages
Chinese (zh)
Inventor
应汉杰
唐成伦
陈勇
温庆仕
刘庆国
赵南
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing Institute Of White Biotech Co ltd
Nanjing Life Original Health Technology Co ltd
Nanjing Tech University
Original Assignee
Nanjing Institute Of White Biotech Co ltd
Nanjing Life Original Health Technology Co ltd
Nanjing Tech University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Nanjing Institute Of White Biotech Co ltd, Nanjing Life Original Health Technology Co ltd, Nanjing Tech University filed Critical Nanjing Institute Of White Biotech Co ltd
Priority to CN202110703296.3A priority Critical patent/CN113332358A/en
Publication of CN113332358A publication Critical patent/CN113332358A/en
Priority to CN202210713732.XA priority patent/CN115837051B/en
Pending legal-status Critical Current

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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/066—Clavicipitaceae
    • A61K36/068—Cordyceps
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • 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
    • A61K36/13—Coniferophyta (gymnosperms)
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention discloses a compound cordycepin preparation, a preparation method thereof and application thereof in preparing a product for resisting small cell lung cancer; the compound cordycepin preparation comprises the following components in parts by weight: 20-500 parts of cordycepin, 5-100 parts of black nightshade extract and 1-20 parts of taxus chinensis extract. The compound cordycepin preparation provided by the invention can enhance the drug effect of treating small cell lung cancer and reduce the side effect.

Description

Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products
Technical Field
The invention belongs to the technical field of natural medicines, and particularly relates to a compound cordycepin preparation, a preparation method thereof and application thereof in preparation of a small cell lung cancer resistant product.
Background
Small cell lung cancer accounts for about 15% -20% of bronchiogenic lung cancer, and when small cell lung cancer is diagnosed, patients with tumors in the limited stage account for about 30%, and the rest are in the extensive stage (when tumors spread out of the supraclavicular zone, the extensive stage). Compared with other types of lung cancer, the small cell lung cancer has better chemotherapy and radiotherapy curative effects. However, small cell lung cancer is often difficult to cure because the tumor is likely to spread widely when the small cell lung cancer is diagnosed.
Cordycepin is also called as cordyceps sinensis, cordycepin and cordycepin, and is also called as 3' -deoxyadenosine, and is the first nucleoside antibiotic separated from fungi. It has antibacterial, antiinflammatory, antiviral, antitumor and immunoregulatory pharmacological activities; cordycepin is a non-mutagenic and nontoxic compound, and has potential antiproliferative and anti-migratory effects on small cell lung cancer cells.
The taxol is a natural secondary metabolite separated and purified from the bark of a gymnosperm yew, and has good anti-tumor effect through clinical verification, and particularly has special effects on lung cancer, ovarian cancer, uterine cancer, breast cancer and the like with high cancer incidence. Paclitaxel is the most popular anticancer drug in the international market in recent years, and is considered to be one of the most effective anticancer drugs in human for the next 20 years. Paclitaxel, however, has strong side effects including allergic reactions, neurotoxicity, cardiovascular reactions, intestinal reactions, liver poisoning and local inflammatory reactions.
The steroid saponin and steroid alkaloid can influence and reduce the expression of protein on the tumor cell membrane, such as reducing the content of sialic acid, inhibiting ATPase activity, and down-regulating the expression of N-acetyltransferase, thereby reducing the fluidity of the tumor cell membrane, inhibiting the metabolic growth of tumor cells, reducing the energy metabolism in the cancer cells, preventing the growth of the cancer cells, and inhibiting the proliferation thereof. Meanwhile, the steroid saponin and the steroid alkaloid can activate a signal path of cancer cell apoptosis and promote cancer cell apoptosis. But it also has some side effects such as slight poisoning, or itching of oral mucosa and throat, and after several hours, it can be completely relieved by self-metabolism, and the patient with serious poisoning may have epigastric pain, nausea, emesis, diarrhea, etc. If the patient gets worse, the patient may be dehydrated due to vomiting and diarrhea, increase in body temperature and pupil enlargement, photophobia, tinnitus, convulsion of limbs, dyspnea, blood pressure drop, shock, or even death, so the patient should be treated in hospital as early as possible.
Therefore, the invention provides a compound cordycepin preparation, a preparation method thereof and application thereof in preparing a product for resisting small cell lung cancer.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to solve the technical problem of providing a compound cordycepin preparation aiming at the defects of the prior art.
The technical problem to be solved by the invention is to provide a preparation method of the compound cordycepin preparation.
The invention further aims to solve the technical problem of providing the application of the compound cordycepin preparation.
In order to solve the first technical problem, the invention discloses a compound cordycepin preparation, which comprises the following components in parts by weight:
20-500 parts of cordycepin
5-100 parts of black nightshade extract
1-20 parts of a taxus chinensis extract.
Preferably, the compound cordycepin preparation comprises the following components in parts by weight:
50-100 parts of cordycepin
25-50 parts of black nightshade extract
2-5 parts of a taxus chinensis extract.
Further preferably, the compound cordycepin preparation comprises the following components in parts by weight:
75 parts of cordycepin
Solanum nigrum extract 22 parts
3 parts of a Chinese yew extract.
Still preferably, the compound cordycepin preparation comprises the following components in parts by weight:
cordycepin 75g
Solanum nigrum extract 22g
Taxus chinensis extract 3 g.
Wherein the cordycepin is extracted from wild Cordyceps militaris and/or artificially cultured Cordyceps militaris.
Wherein the purity of the cordycepin is more than 50%.
Wherein the rest components of cordycepin are polysaccharide compounds or other impurities; preferably, the rest components of the cordycepin are mainly polysaccharide compounds; further preferably, the rest of the cordycepin is polysaccharide compound.
Wherein, the content of steroid compounds in the black nightshade extract is more than 50 percent.
Wherein the steroid compound is steroid saponin and/or steroid alkaloid.
Wherein the other components of the Solanum nigrum extract are polysaccharide compounds or other impurities; preferably, the remaining components of the black nightshade extract are mainly polysaccharide compounds; further preferably, the remaining components of the black nightshade extract are polysaccharide compounds.
Wherein the Taxus chinensis extract is extracted from natural wild and/or artificially cultured Taxus chinensis.
Wherein the content of paclitaxel in the Taxus chinensis extract is more than 50%.
Wherein the rest components of the Taxus chinensis extract are polysaccharide compounds or other impurities; preferably, the rest components of the taxus chinensis extract are mainly polysaccharide compounds; further preferably, the rest components of the taxus chinensis extract are polysaccharide compounds.
Wherein, the three components supplement each other and act together; specifically, the cordycepin is an RNA synthesis inhibitor, can selectively inhibit RNA synthesis, further influences protein synthesis, and has an anti-tumor effect, and the cordyceps has an effect of inducing tumor cell apoptosis; the steroid compounds in the black nightshade extract can reduce the membrane fluidity and the membrane protein level of tumor cells, and can also regulate a signal transduction pathway to promote apoptosis; the taxol in the taxus chinensis extract can promote the polymerization of the periscope protein heterodimer into microtubules, is combined on the microtubules to promote the stability of the microtubules and inhibit the dynamic change of the microtubules, so that the formation of a spinning body is interfered, chromosomes cannot be separated, and the mitosis is arrested in the metaphase.
The compound cordycepin preparation is in the dosage form of any one of powder, capsules, pills, granules, tablets and oral liquid.
In order to solve the second technical problem, the invention discloses a preparation method of the compound cordycepin preparation.
The preparation method comprises the steps of weighing the components according to the formula, mixing, dissolving in water, and preparing the liquid composition preparation.
The preparation method comprises the steps of weighing the components according to the formula, mixing, adding auxiliary materials required by preparation forming, and preparing the medicinal preparation by a conventional method.
In order to solve the third technical problem, the invention discloses an application of the compound cordycepin preparation in preparing a product for resisting small cell lung cancer.
Wherein the product is any one of functional food, medicine and health product additive.
Wherein, the product can be taken alone as functional food, and can also be used as medicine and health care product.
In the invention, the purity and the content are both mass percent.
Has the advantages that: compared with the prior art, the invention has the following advantages:
(1) compared with the traditional Chinese medicine composition for resisting small cell lung cancer, the compound cordycepin preparation provided by the invention is easier to be absorbed by human bodies, and the reason is that all the extracts are anticancer active ingredients of the medicine, and the balance is saccharides with small molecular weight, the weight average molecular weight is generally below 800, and the compound cordycepin preparation can be directly absorbed by the human bodies without metabolism.
(2) The three extracts provided by the invention are strictly screened, the three used medicinal components supplement each other, and the identification and synthesis of gene codes in the synthesis process of cancer cells have an inhibiting effect, so that the proliferation of small cell cancers is inhibited.
(3) The compound cordycepin preparation provided by the invention has obvious effects on the treatment of early cancer and the adjuvant therapy in the later chemotherapy process.
(4) The compound cordycepin preparation provided by the invention can enhance the drug effect of treating small cell lung cancer and reduce the side effect.
Drawings
The foregoing and/or other advantages of the invention will become further apparent from the following detailed description of the invention when taken in conjunction with the accompanying drawings.
FIG. 1 shows the tumor volume changes in mice at various stages in various examples (high dose group).
Fig. 2 is an image of a solid tumor in each example (high dose group); wherein, A is example 4, B is example 2, C is example 5, D is example 3, and E is blank control.
Detailed Description
The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
In the following examples, the purity of cordycepin is 95.5%, the content of polysaccharide compound is 4.5%, and the cordycepin is mainly oligosaccharide with weight average molecular weight of 720-180.
In the following examples, the reference literature for the extraction process of solanine in the solanum nigrum extract (the extraction method of solanine in potatoes) mainly contains solanine, wherein the content of the solanine is 83.8%, the content of the carbohydrate is 16.2%, and the oligosaccharide mainly contains oligosaccharide with the weight-average molecular weight of 720-180.
In the following examples, the taxus extract contains 82.3% of paclitaxel and 17.7% of polysaccharide compounds, and mainly comprises oligosaccharides with weight average molecular weight of 720-180.
The experimental mice used in the invention are purchased from the experimental animal center of Nanjing agriculture university, the Lewis lung cancer cell strain is purchased from the experimental animal center of Nanjing agriculture university, and the mouse CD4 monoclonal antibody and the CD8 monoclonal antibody are purchased from Saimer Feishell science and technology (China) Limited company; TNF-alpha, IL-2, IL-7ELISA kits, Abcam, UK.
The invention adopts a gas-yin deficiency type Lewis lung cancer mouse model, and a preparation method thereof is carried out according to a reference document (attenuation and synergy effects of modified Guilu Erxian glue soup on the chemotherapy of a gas-yin deficiency Lewis tumor-bearing mouse, traditional Chinese medicinal materials 2014,37(8): 1434-1437).
The animal breeding environment of the invention is as follows: SPF level, room temperature of 20.0-22.5 ℃, relative humidity of 54.4-68.4% RH, breeding in group cages with 10 animals per cage.
The invention carries out detection through the following indexes:
1. general observations of mice: general conditions such as stool and hair color of each group of mice were observed daily after administration.
2. The weight loss rate was (day 1 weight-day 22 weight)/day 1 weight × 100%.
3. Organ index and tumor inhibition rate calculation: on day 22, mice were sacrificed by cervical dislocation and tumor, spleen and thymus tissues were isolated.
Spleen and thymus indices and tumor inhibition rates were calculated according to the following formulas.
Spleen index equals spleen mass/body mass x 100%;
thymus index is thymus mass/body mass x 100%;
tumor inhibition rate (average tumor mass in normal control group-average tumor mass in experimental group)/average tumor mass in normal control group
×100％。
Example 1
(1) Preparing compound cordycepin preparation
According to the mass of cordycepin, the taxus chinensis extract and the black nightshade extract being 50 mg: 900 mg: 50mg of each composition was weighed, mixed and dissolved in 1L of physiological salt water.
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results of the experiment are shown in tables 1-3:
TABLE 1
Group of Weight loss Rate (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 7 Stool sample Light and slight Of moderate degree
Middle dose group 10 Is soft and soft Light and slight Light and slight
Low dose group 14 Is normal Is normal Is normal
TABLE 2
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 0.98±0.36 72.5％
Middle dose group 1.56±0.41 56.2％
Low dose group 2.43±0.45 31.7％
TABLE 3
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.23±0.02 0.74±0.07
Middle dose group 0.33±0.05 0.56±0.09
Low dose group 0.37±0.02 0.42±0.06
Example 2
(1) Preparing compound cordycepin preparation
According to the mass of the cordycepin, the taxus chinensis extract and the black nightshade extract being 900 mg: 50 mg: 50mg of each composition was weighed, mixed and dissolved in 1L of physiological salt water.
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results of the experiments are shown in tables 4-6:
TABLE 4
Group of Under the weight of the bodyPercent reduction (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 5 Is normal Is normal Of moderate degree
Middle dose group 8 Is normal Is normal Is normal
Low dose group 10 Is normal Is normal Is normal
TABLE 5
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 0.93±0.27 74.9％
Middle dose group 1.36±0.34 61.8％
Low dose group 2.63±0.45 26.1％
TABLE 6
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.21±0.02 0.72±0.06
Middle dose group 0.32±0.05 0.57±0.06
Low dose group 0.37±0.02 0.39±0.07
Example 3
(1) Preparing compound cordycepin preparation
According to the formula of cordycepin: the Chinese yew extract: the mass of the black nightshade extract is 50 mg: 50 mg: 900mg of each composition was weighed, mixed and dissolved in 1L of physiological salt water.
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results of the experiment are shown in tables 7 to 9:
TABLE 7
Group of Weight loss Rate (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 8 Stool sample Of moderate degree Of moderate degree
Middle dose group 12 Is soft and soft Light and slight Light and slight
Low dose group 15 Is normal Is normal Is normal
TABLE 8
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 1.32±0.36 62.9％
Middle dose group 1.68±0.41 52.8％
Low dose group 2.98±0.45 16.3％
TABLE 9
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.23±0.02 0.74±0.07
Middle dose group 0.33±0.05 0.56±0.09
Low dose group 0.36±0.02 0.42±0.06
Example 4
(1) Preparing compound cordycepin preparation
According to the mass of the cordycepin, the taxus chinensis extract and the black nightshade extract being 750 mg: 30 mg: 220mg of each composition was weighed, mixed and dissolved in 1L of physiological salt water.
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results of the experiments are shown in tables 10-12:
watch 10
Group of Weight loss Rate (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 3 Is normal Is normal Is normal
Middle dose group 6 Is normal Is normal Is normal
Low dose group 10 Is normal Is normal Is normal
TABLE 11
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 0.62±0.36 82.5％
Middle dose group 1.26±0.41 64.6％
Low dose group 2.04±0.45 42.7％
TABLE 12
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.24±0.02 0.69±0.07
Middle dose group 0.35±0.05 0.47±0.09
Low dose group 0.36±0.02 0.45±0.06
Example 5
(1) Preparing compound cordycepin preparation
According to the technical scheme, the weight of cordycepin, the taxus chinensis extract and the black nightshade extract is 500 mg: 250 mg: 250mg of each composition was weighed, mixed and dissolved in 1L of physiological saline.
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results of the experiments are shown in tables 13-15:
watch 13
Group of Weight loss Rate (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 4 Is normal Is normal Is normal
Middle dose group 6 Is normal Is normal Is normal
Low dose group 10 Is normal Is normal Is normal
TABLE 14
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 1.08±0.36 69.7％
Middle dose group 1.46±0.41 60.0％
Low dose group 2.33±0.37 34.6％
Watch 15
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.23±0.02 0.64±0.06
Middle dose group 0.33±0.05 0.52±0.07
Low dose group 0.37±0.02 0.43±0.06
Example 6
(1) Preparing compound cordycepin preparation
According to the mass of the cordycepin, the taxus chinensis extract and the black nightshade extract as 250 mg: 500 mg: 250mg of each composition was weighed, mixed and dissolved in 1L of physiological saline.
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results of the experiment are shown in tables 16 to 18:
TABLE 16
Group of Weight loss (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 6 Is soft and soft Hematochezia Of moderate degree
Middle dose group 10 Is soft and soft Light and slight Light and slight
Low dose group 12 Is normal Is normal Is normal
TABLE 17
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 1.25±0.36 64.9％
Middle dose group 1.76±0.41 50.6％
Low dose group 2.54±0.45 28.7％
Watch 18
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.28±0.3 0.69±0.07
Middle dose group 0.33±0.06 0.51±0.03
Low dose group 0.31±0.07 0.39±0.04
Example 7
(1) Preparing compound cordycepin preparation
According to the mass of the cordycepin, the taxus chinensis extract and the black nightshade extract as 250 mg: 250 mg: 500mg of each composition was weighed, mixed and dissolved in 1L of physiological salt water. .
(2) 4 groups of mice were set for the gavage experiment. Each group of mice had 5 mice each. The high dose group, the medium dose group, the low dose group and the blank control group were used separately. The dose of the high dose group mice was 80mg/kg, the dose of the medium dose group mice was 50mg/kg, and the dose of the low dose group mice was 20 mg/kg. The blank control group was an equal volume of saline. It is administered 2 times daily. For 22 days. The detection method is as described above.
The results are shown in tables 19-21:
watch 19
Group of Weight loss (%) Hardness of feces Hematochezia/occult blood Hair removal
Blank control group 23 Is normal Is normal Is normal
High dose group 7 Is soft and soft Light and slight Light and slight
Middle dose group 9 Light and slight Is normal Is normal
Low dose group 13 Is normal Is normal Is normal
Watch 20
Group of Tumor mass/g Tumor inhibition rate/%)
Blank control group 3.56±0.45 -
High dose group 1.28±0.36 64.0％
Middle dose group 1.86±0.41 47.8％
Low dose group 2.63±0.45 26.1％
TABLE 21
Group of Index of thymus Spleen index
Blank control group 0.42±0.04 0.84±0.08
High dose group 0.25±0.02 0.74±0.07
Middle dose group 0.34±0.05 0.56±0.09
Low dose group 0.36±0.02 0.42±0.06
From examples 1-7, it can be seen that when the contents of Taxus chinensis and Solanum nigrum are high, the feces of the mice tested with the high content of Taxus chinensis and Solanum nigrum extracts are soft, bloody stool and unhairing. The weight loss was also high due to the toxic effect of the high doses of extracts of taxus and solanum nigrum on the mice. Resulting in inappetence, complication of depilation and hematochezia, loose and soft feces and other adverse reactions. In the embodiment with high cordycepin content, the appearance characteristics of the mice are all normal, and the tumor suppression rate is also high. The tumor volume change and tumors of the mice in the high dose group and the blank control group of each example are shown in fig. 1 and 2, and it can be seen that the formulation of the ratio of example 4 exhibits the best effect. The thymus index and spleen index of the mice in each group of examples were not very different.
Example 8
Formula a: the mass of cordycepin, the taxus chinensis extract and the black nightshade extract is respectively 750 mg: 30 mg: 220mg (same as example 4);
and (b) formula: 1000g of cordycepin.
And (c) formula: the mass of the taxus chinensis extract and the weight of the black nightshade extract are respectively 120 mg: 880 mg.
And (3) formula d: the mass of cordycepin and Chinese yew extract is 961 mg: 39 mg.
And (e) formula: the mass of cordycepin and black nightshade extract is 773 mg: 227 mg.
And (f) formula: the mass of cordycepin, the taxus chinensis extract and the black nightshade extract is respectively 750 mg: 92 mg: 152 mg.
The dose is the middle dose group.
The experimental procedure was as in example 4. The results are shown in tables 22 to 24.
TABLE 22
Group of Weight loss (%) Hardness of feces Hematochezia/occult blood Hair removal
Formulation a 6 Is normal Is normal Is normal
Formulation b 6 Is normal Is normal Is normal
Formulation c
10 Light and slight Light and slight Light and slight
Formulation d
10 Light and slight Is normal Is normal
Formulation e 11 Is normal Light and slight Light and slight
Formulation f 9 Is normal Is normal Is normal
TABLE 23
Group of Tumor mass/g Tumor inhibition rate/%)
Formulation a 1.26±0.41 64.6％
Formulation b 1.78±0.49 50％
Formulation c 1.66±0.44 53.3％
Formulation d 1.75±0.36 50.8％
Formulation e 1.69±0.41 52.5％
Formulation f 1.57±0.45 55.9％
Watch 24
Group of Index of thymus Spleen index
Formulation a 0.35±0.05 0.47±0.09
Formulation b 0.37±0.02 0.74±0.07
Formulation c 0.41±0.05 0.56±0.09
Formulation d 0.47±0.04 0.75±0.08
Formulation e 0.35±0.05 0.69±0.07
Formulation f 0.34±0.05 0.48±0.06
Example 9: toxicity test
(1) Acute toxicity test
The experimental method comprises the following steps: the 6 experimental groups and 1 control group are respectively corresponding to compound cordycepin preparations (cordycepin 750 mg: Taxus chinensis extract 30 mg: Solanum nigrum extract 220 mg)/weight of mice of 15g/kg, 12g/kg, 9g/kg, 6g/kg, 3g/kg and 0 k/kg. Dissolving in normal saline to obtain gastric lavage liquid. Gavage experiments were performed on 10 mice per group. The stomach was gavaged twice for 24h, and the animals were fasted overnight before gavage, and had free access to water. Normal diet was given after gavage and observed for 14 days, and toxicant characteristics and mortality were recorded.
Experimental phenomena: a single feeding of 15g/kg of the compound cordycepin preparation can cause the death rate of the mice to be 20 percent, and the rest groups have no death. Mice in a group corresponding to 15g/kg of the compound cordycepin preparation have the conditions of watery stool and inappetence. The rest mice all defecate normally, and the liveness and feeding condition were higher than those of the control group.
The experimental results are as follows: the Minimum Lethal Dose (MLD) of the compound cordycepin preparation for a mouse oral single dose is 15g/kg (equivalent to 2.38g/kg of human equivalent dose), and the maximum drug tolerance (MID) >12g/kg (equivalent to 2.14g/kg of human dose). The LD50 of the compound cordycepin preparation is more than 15g/kg and is far higher than 2000mg/kg specified by OECD acute correlation principle. Therefore, the compound cordycepin preparation has the risk of serious acute poisoning.
(2) Chronic toxicity test
The experimental method comprises the following steps: the compound cordycepin preparation is continuously administered to mice for three months, and the toxicity reaction and the severity degree of the toxicity reaction, the main toxic target organs and the damage condition of the mice are observed.
A high-dose group (80mg/kg, 20 times of the quasi-clinical dose), a medium-dose group (40mg/kg, 10 times of the quasi-clinical dose), a low-dose group (20mg/kg, 5 times of the quasi-clinical dose) and a control group (normal saline) of the compound cordycepin preparation are arranged. The administration is carried out by intragastric administration once a day for 13 weeks.
The experimental results are as follows: during the administration period, no significant abnormalities were observed in the appearance, behavior, stool behavior, and food intake of the mice. The long-term administration of cordycepin has no influence on the weight of the patient. The blood index of the mouse has no obvious change, the AST in the serum of the rat can be obviously reduced due to the high and medium dose of the compound cordycepin preparation, and the AST in the serum is normal because the ASY value is lower than that of the liver function of the mouse, so that the toxic action on the liver and kidney functions of the mouse can be avoided.
The invention provides a compound cordycepin preparation, a preparation method thereof, and an application concept and a method thereof in preparing a small cell lung cancer resistant product, and a method and a way for realizing the technical scheme are many. All the components not specified in the present embodiment can be realized by the prior art.

Claims (10)

1. The compound cordycepin preparation is characterized by comprising the following components in parts by weight:
20-500 parts of cordycepin
5-100 parts of black nightshade extract
1-20 parts of a taxus chinensis extract.
2. The compound cordycepin preparation according to claim 1, which is characterized by comprising the following components in parts by weight:
50-100 parts of cordycepin
25-50 parts of black nightshade extract
2-5 parts of a taxus chinensis extract.
3. The compound cordycepin preparation according to claim 1, which is characterized by comprising the following components in parts by weight:
75 parts of cordycepin
Solanum nigrum extract 22 parts
3 parts of a Chinese yew extract.
4. The compound cordycepin preparation according to claim 1, which is characterized by comprising the following components in parts by weight:
cordycepin 75g
Solanum nigrum extract 22g
Taxus chinensis extract 3 g.
5. The compound cordycepin preparation according to claim 1, wherein the purity of cordycepin is 50% or more.
6. The compound cordycepin preparation as claimed in claim 1, wherein the content of steroid compounds in the Solanum nigrum extract is more than 50%; wherein the steroid compound is steroid saponin and/or steroid alkaloid.
7. The compound cordycepin preparation as claimed in claim 1, wherein the Taxus chinensis extract contains paclitaxel 50% or more.
8. The compound cordycepin preparation according to claim 1, wherein the compound cordycepin preparation is in the form of any one of powder, capsules, pills, granules, tablets and oral liquid.
9. The use of the compound cordycepin preparation according to any one of claims 1 to 8 in the preparation of a product for treating small cell lung cancer.
10. The use according to claim 9, wherein the product is any one of functional foods, pharmaceuticals and nutraceuticals.
CN202110703296.3A 2021-06-24 2021-06-24 Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products Pending CN113332358A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN202110703296.3A CN113332358A (en) 2021-06-24 2021-06-24 Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products
CN202210713732.XA CN115837051B (en) 2021-06-24 2022-06-22 Composite cordycepin preparation, preparation method thereof and application thereof in preparation of small cell lung cancer resistant products

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110703296.3A CN113332358A (en) 2021-06-24 2021-06-24 Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products

Publications (1)

Publication Number Publication Date
CN113332358A true CN113332358A (en) 2021-09-03

Family

ID=77478163

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202110703296.3A Pending CN113332358A (en) 2021-06-24 2021-06-24 Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products
CN202210713732.XA Active CN115837051B (en) 2021-06-24 2022-06-22 Composite cordycepin preparation, preparation method thereof and application thereof in preparation of small cell lung cancer resistant products

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202210713732.XA Active CN115837051B (en) 2021-06-24 2022-06-22 Composite cordycepin preparation, preparation method thereof and application thereof in preparation of small cell lung cancer resistant products

Country Status (1)

Country Link
CN (2) CN113332358A (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111067995A (en) * 2020-01-08 2020-04-28 林丽珠 Pharmaceutical composition and application thereof in preparing medicine for treating lung cancer

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
师林等: "加味龟鹿二仙胶汤对气阴两虚 Lewis荷瘤小鼠化疗的减毒增效作用", 《中药材》 *
李明慧等: "龙葵甾体类生物碱对S180及Lewis肺癌移植瘤小鼠的影响", 《中国天然药物》 *
李秀丽等: "肺复康对Lewis肺癌模型小鼠肿瘤及细胞周期的影响", 《山东中医药大学学报》 *
高飞等: "虫草素对Lewis小鼠肿瘤生长转移及VEGF、MVD表达的影响", 《第十五届中国科协年会第26分会场：政产学研协同创新与民生科技产业发展研讨会》 *

Also Published As

Publication number Publication date
CN115837051B (en) 2023-10-24
CN115837051A (en) 2023-03-24

Similar Documents

Publication Publication Date Title
Tewari et al. Withania somnifera (L.) Dunal: Phytochemistry, structure-activity relationship, and anticancer potential
US9700572B2 (en) Anti-cancer agent
Chan et al. Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms
US10905725B2 (en) Compositions and methods for enhancing cancer chemotherapy
AU2021246790B2 (en) Anti-tumor composition containing rare ginsenosides Rk2, CK, and PPT
US20160151435A1 (en) Pharmaceutical composition adjuvant to chemotherapy drugs and applications thereof
Wang et al. Diversity of potentially exploitable pharmacological activities of the highly prized edible medicinal fungus Antrodia camphorata
CN108815218B (en) Pharmaceutical composition and use thereof
WO2015192758A1 (en) Anti-tumor pharmaceutical application of pentacyclic triterpene saponin compounds of szechuan melandium root
CN105287611A (en) Application of ginsenoside Rh2 to inhibition of Treg cells
CN111467358B (en) Pharmaceutical composition containing ginsenoside Rh3, PPD and Rh2
CN111956776B (en) A Chinese medicinal composition for resisting cancer, stopping emesis, reducing toxicity and enhancing efficacy, and its preparation method
CN107551001B (en) A Chinese medicinal composition for preventing and treating alcoholic hepatic injury and its preparation method
US20130164382A1 (en) Ejaculum of animals as medicinal material and uses thereof in medicaments for treatment of diseases such as tumors, depression, etc
CN101143148B (en) Application of paris saponin I and its derivatives
CN101229175A (en) Medical applications of couple protopanoxadiol derivatives and compound body thereof
CN113332358A (en) Compound cordycepin preparation, preparation method thereof and application of compound cordycepin preparation in preparation of small cell lung cancer resistant products
CN1939311B (en) Ginseng sapogenin aglycone derivative biological preparation and its usage
Kolesárová et al. The effect of apricot seeds on microscopic structure of rabbit liver.
CN109731019B (en) A composition with chemotherapy synergistic effect comprises components, preparation and application
TW202206090A (en) Astragalus pharmaceutical composition enhances the use of cancer treatment
CN109045052B (en) Pharmaceutical formulation for treating colon cancer and application
CN109867657B (en) Dihydroxydibenzo [ b, f ] [1,5] dioxacin ring compound, preparation method, pharmaceutical composition and application thereof
CN111467367B (en) Plant monomer composition for inhibiting tumor cell growth and preparation method and application thereof
CN108159201A (en) A kind of product for adjusting Hyperlipemia population intestinal flora and preparation method and application

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
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20210903

WD01 Invention patent application deemed withdrawn after publication