WO2021185292A1 - 黄耆医药组合物在用于制备增强癌症治疗药物中的用途 - Google Patents

黄耆医药组合物在用于制备增强癌症治疗药物中的用途 Download PDF

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WO2021185292A1
WO2021185292A1 PCT/CN2021/081377 CN2021081377W WO2021185292A1 WO 2021185292 A1 WO2021185292 A1 WO 2021185292A1 CN 2021081377 W CN2021081377 W CN 2021081377W WO 2021185292 A1 WO2021185292 A1 WO 2021185292A1
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cancer
mannose
astragalus
drug
extract
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French (fr)
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李伊伶
郑建新
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怀特生技新药股份有限公司
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Priority to US17/912,799 priority Critical patent/US20230172957A1/en
Priority to KR1020227032322A priority patent/KR20220142510A/ko
Priority to EP21771258.7A priority patent/EP4122480A4/en
Publication of WO2021185292A1 publication Critical patent/WO2021185292A1/zh

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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • 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
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • 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
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising refined Astragalus polysaccharides (hereinafter referred to as: r-APS) and mannose combined with chemotherapy drugs to enhance the chemotherapy drugs for different cancer tumor cells The ability to poison cancer cells.
  • r-APS refined Astragalus polysaccharides
  • Astragalus (also known as Astragalus) is Mongolian Astragalus or Astragalus membranaceus.
  • Astragalus Astragalus refers to Astragalus membranaceus Bge.var.mongholicus (Bge.) Hsiao or Astragalus membranaceus (Bge.var.mongholicus (Bge.) Hsiao) or Astragalus membranaceus.
  • Huangqi is used to treat chronic nephritis, proteinuria, myositis, anti-hypertension, coronary heart disease, cerebral infarction, peptic ulcer (duodenal and gastric ulcer), kidney disease and diabetes.
  • astragalus extracts that can be used to treat tumors.
  • astragalus include monosaccharides, polysaccharides, flavonoids, amino acids, and trace elements.
  • polysaccharides are the most content, and it has been proven that polysaccharides have medical effects on the treatment of diseases, especially cancer-related diseases.
  • Tumor US Patent No. 5,268,467; Tang, W. Hemm, I. and Bertram, B. "The Latest Development of Anti-tumor Agents in Traditional Chinese Medicine", Part II, high molecular weight compounds.
  • Mannose can enhance the effect of chemotherapy for cancer patients without harming their overall health.
  • Mannose is a six-carbon sugar that exists in trace amounts in human blood. It is known that its supply path is not absorbed from food, but is mainly metabolized by glucose.
  • Chemotherapy drugs can be used effectively in the initial stage of treatment. When the patient takes the initial treatment, tumor growth can be effectively inhibited, but after a period of time, the tumor will grow again. But as the treatment time gets longer, the drugs begin to fail, and this phenomenon is called drug resistance in medicine. Drug resistance not only causes cancer to recur, but also makes patients face the desperate situation of no medicine available. To reduce the side effects of chemotherapy drugs and the resistance of cancer is an important issue in the treatment of cancer.
  • the pharmaceutical composition of Astragalus root extract and mannose of the present invention for patients with chemotherapeutic drug resistance, only needs to use the equivalent dose of chemotherapeutics, but the effect of allowing chemotherapeutics to reduce the survival rate of cancer cells The increase is at least 16%, so that even if the patient develops drug resistance, it can still effectively enhance the therapeutic effect of chemotherapeutic drugs.
  • the present invention provides a use of astragalus astragalus medicinal composition in the preparation of a medicine for enhancing the effect of cancer chemotherapeutics in inhibiting the survival rate of cancer cells, wherein the medicinal astragalus medicinal composition comprises astragalus extract and mannose.
  • the cancer chemotherapy drug is a chemotherapy target drug
  • the chemotherapy target drug is a chemotherapy target drug for a corresponding cancer type.
  • the cancer comprises colorectal cancer, ovarian cancer or lung cancer.
  • the chemotherapeutic target drug for the corresponding cancer species includes Regorafenib, Olaparib or Tarceva.
  • the effective dose ratio of the astragalus extract and the mannose in the pharmaceutical composition is 1.5-4.5:5.5-8.5, and the astragalus extract and the mannose composition
  • the concentration range is 0 ⁇ 10mg/mL.
  • the pharmaceutical composition may be a lozenge, pill, granule, powder, capsule or liquid.
  • astragalus medicinal composition in the preparation of a medicament for enhancing the cancer chemotherapeutic drugs for the treatment of drug-resistant cancers and inhibiting the survival rate of cancer cells, characterized in that the astragalus medicinal composition Contains astragalus extract and mannose.
  • the cancer is solid tumor cancer, wherein the solid tumor cancer includes colorectal cancer, ovarian cancer, and lung cancer.
  • astragalus medicinal composition in the preparation of a medicine that enhances the effect of cancer chemotherapeutics in inhibiting tumor cell proliferation, wherein the medical composition comprises astragalus medicinal extract and mannose.
  • the tumor cell is a drug resistant tumor cell.
  • tumor cells include colorectal cancer, ovarian cancer, and lung cancer.
  • Figure 1A shows the results of Huangqi extract (r-APS) on lung cancer resistant cell lines (HCC827GR cells).
  • Figure 1B shows the results of astragalus extract (r-APS) and a pharmaceutical composition with mannose on lung cancer resistant cell lines (HCC827GR cells).
  • Figure 1C shows the results of lung cancer chemotherapy drug Iressa on lung cancer resistant cell lines (HCC827GR cells).
  • FIG. 1A Astragalus extract results on lung cancer resistant cell lines (H1975 cells).
  • Figure 2B shows the results of a pharmaceutical composition of Astragalus extract (r-APS) and mannose on lung cancer resistant cell lines (H1975 cells).
  • Figure 2C shows the results of the lung cancer chemotherapy drug Tarceva on lung cancer resistant cell lines (H1975 cells).
  • Figure 3A shows the results of astragalus extract combined with the lung cancer chemotherapy drug Tarceva on lung cancer resistant cells (H1975 cells).
  • Figure 3B shows the results of a pharmaceutical composition of astragalus extract (r-APS) and mannose combined with a lung cancer chemotherapeutic drug Tarceva on lung cancer resistant cell lines (H1975 cells).
  • FIG 4A shows the results of 60-70% chemotherapy inhibition by colorectal cancer cell lines (HCT116 cells).
  • Figure 4B shows the result of 48 hours of culture of colorectal cancer cell line (HCT116 cells) after adding Huangqi extract (r-APS).
  • Fig. 4C shows the result of 48 hours of culture of colorectal cancer cell line (HCT116 cells) after adding a pharmaceutical composition of astragalus extract (r-APS) and mannose (mannose).
  • Figure 4D shows the colorectal cancer cell line (HCT116 cells) added with astragalus extract (r-APS) combined with the colorectal cancer chemotherapy drug Regorafenib, the result of culturing for 48 hours.
  • FIG 4E shows the results of colorectal cancer cell lines (HCT116 cells) added with astragalus extract (r-APS) and mannose (mannose) pharmaceutical composition combined with colorectal cancer chemotherapy drug Regorafenib (Regorafenib) for 48 hours.
  • Figure 5A shows the results of 60-70% chemotherapy inhibition by ovarian cancer cell lines (OVCAR3 cells).
  • Figure 5B shows the result of 48 hours of culture of ovarian cancer cell lines (OVCAR cells) after adding Huangqi extract (r-APS).
  • Figure 5C shows the results of 48 hours of culture of ovarian cancer cell lines (OVCAR cells) after adding astragalus extract (r-APS) and mannose pharmaceutical composition.
  • Figure 5D shows the results of ovarian cancer cell lines (OVCAR cells) added with Huangqi extract (r-APS) combined with colorectal cancer chemotherapy drugs to make cancer cells (Olaparib) cultured for 48 hours.
  • Figure 5E shows the results of ovarian cancer cell lines (OVCAR cells) added with a pharmaceutical composition of astragalus extract (r-APS) and mannose combined with a colorectal cancer chemotherapy drug Olaparib after 48 hours of culture.
  • OVCAR cells ovarian cancer cell lines
  • r-APS astragalus extract
  • r-APS refers to Astragalus root extract
  • mannose refers to mannose
  • the enhancement of the effect of the chemotherapeutic drugs according to the present invention can increase the therapeutic effect by at least 16%.
  • the chemotherapeutic drugs of the present invention include chemotherapeutic target drugs, and the chemotherapeutic target drugs are chemotherapeutic target drugs for corresponding cancer types.
  • the present invention provides a pharmaceutical composition for improving the effect of chemotherapeutics in the treatment of cancer, which is composed of astragalus extract and mannose, wherein the weight ratio of the astragalus extract and mannose in the pharmaceutical composition is 1.5 to 4.5: 5.5 ⁇ 8.5.
  • the effective concentration of Astragalus extract is 0-10 mg/mL
  • the effective concentration of mannose is 0-10 mg/mL
  • the effective concentration of Astragalus root extract is 3 mg/mL
  • the effective concentration of mannose is 7 mg/mL.
  • the present invention also provides a pharmaceutical composition for improving or maintaining the therapeutic effect of chemotherapeutic drugs on drug-resistant cancer, which is composed of astragalus extract and mannose, wherein the astragalus extract and mannose in the pharmaceutical composition
  • the weight ratio is 1.5 ⁇ 4.5:5.5 ⁇ 8.5.
  • the effective concentration of Astragalus extract is 0-10 mg/mL
  • the effective concentration of mannose is 0-10 mg/mL
  • the effective concentration of Astragalus root extract is 3 mg/mL
  • the effective concentration of mannose is 7 mg/mL.
  • the present invention also provides a pharmaceutical composition for the treatment and inhibition of tumor cell proliferation, which is composed of astragalus extract and mannose, wherein the weight ratio of the astragalus extract and mannose in the pharmaceutical composition is 1.5-4.5: 5.5 ⁇ 8.5.
  • the effective concentration of Astragalus extract is 0-10 mg/mL
  • the effective concentration of mannose is 0-10 mg/mL
  • the effective concentration of Astragalus root extract is 3 mg/mL
  • the effective concentration of mannose is 7 mg/mL.
  • step (2) Heating the solution A formed in step (1) at a temperature, the heating temperature is 80-100°C, and the time is 2-4 hours;
  • step (3) Collect and concentrate the solution of step (2) to obtain extract A;
  • step (3) Put the extract A of step (3) in the container B, add 30-50% ethanol, stir and let stand for precipitation, then collect the supernatant and concentrate to obtain the concentrate A;
  • step (4) Add 75%-95% ethanol to the concentrated solution A obtained at the end of step (4), and after stirring, let it settle and collect the precipitate A;
  • step (5) The precipitate A of step (5) is dehydrated and filtered with suction, and then dissolved and alcohol-precipitated, and finally centrifuged, and the precipitate is centrifuged to obtain product A.
  • the components of product A include astragalus extract ( r- APS).
  • Test group 1 Different concentrations of Huangqi extract (r-APS) were 0.25mg/ml, 0.5mg/ml, 1mg/ml, 2mg/ml, 4mg/ml, respectively.
  • Test 2 groups different concentrations (Astragalus root extract: 30% mannose: 70%) Astragalus root extract and the pharmaceutical composition of mannose (r-APS+mannose) are 0.625mg/ml, 1.25mg/ml, 2.5mg/ml, 5mg/ml, 10mg/ml.
  • Test 3 groups Iressa (Iressa, suitable for HCC827GR cell line) or Desothea (Tarceva, suitable for H1975 cell line).
  • test group 1, test group 2 and test group 3 to the lung cancer cell lines of HCC827GR or H1975, respectively, and test the cell survival of the lung cancer cell lines of HCC827GR or H1975 after 24 hours, 48 hours and 72 hours of each group.
  • the results are shown in Figure 1A-1C and Figure 2A-2C.
  • the HCC827GR cell line is a cell line resistant to the chemotherapeutic drug Iressa for treating lung cancer.
  • test group 2 (astragalus extract) and test group 3 (a pharmaceutical composition of astragalus extract and mannose) ) has a better anti-lung cancer effect (as shown in Figure 1A-1C).
  • test group 3 (a pharmaceutical composition of Astragalus extract and mannose) has the best anti-cancer effect (such as Shown in Figures 2A-2C).
  • Example 2 The effect of a pharmaceutical composition of astragalus extract and mannose combined with anticancer drugs on drug-resistant lung cancer cells
  • Test group 1 Different concentrations of Huangqi extract (r-APS) were 0.25mg/ml, 0.5mg/ml, 1mg/ml, 2mg/ml, 4mg/ml, respectively.
  • Test group 2 The pharmaceutical composition (r-APS+mannose) of different concentrations (astragalus extract: 30% mannose: 70%) of astragalus extract and mannose (r-APS+mannose) is 0.625mg/ml, 1.25mg/ml, 2.5mg/ml, 5mg/ml, 10mg/ml.
  • Each test group was used in combination with Tarceva (concentrations of 1.25 ⁇ M, 2.5 ⁇ M, 5 ⁇ M) and added to the H1975 lung cancer cell line. Each group was used for 24 hours, 48 hours and 72 hours, and H1975 was measured. Cell survival rate of the lung cancer cell line.
  • the H1975 cell line is a cell resistant to the chemotherapeutic drug Tarceva.
  • test group 1 (astragalus extract) and test group 2 (a pharmaceutical composition of astragalus extract and mannose combined with chemotherapeutic drugs Tarceva has the best anti-cancer effect (as shown in Figure 3A-3B), namely test group 1 (astragalus extract) and test group 2 (a pharmaceutical composition of astragalus extract and mannose) combined with chemotherapy
  • the drug Tarceva has the best therapeutic effect in reversing the resistance of anti-lung cancer drugs.
  • Example 3 The effect of the pharmaceutical composition of the present invention on colorectal cancer
  • toxin dose test (choose the dose of chemotherapeutics to inhibit the cell growth and the remaining 60 to 70% of the ability to carry out the follow-up test)
  • test concentrations of Astragalus extract were 0, 2, and 4mg/ml, and the concentrations of Astragalus extract and the pharmaceutical composition of mannose (r-APS+mannose) were tested. It is 0, 5, 10mg/ml.
  • the cytotoxicity of individual cells selected by the dose of chemotherapeutic drugs is between 35-40% of the dose.
  • the cell viability was tested at 48 and 72 hours after the addition.
  • astragalus extract or a pharmaceutical composition of astragalus extract and mannose (r-APS+mannose) and a chemotherapeutic drug were administered for 48 hours.
  • astragalus extract r-APS
  • astragalus extract r-APS
  • astragalus+mannose The pharmaceutical composition of the extract and mannose (r-APS+mannose) was selected as the tested dose of 4 toxins, and the cell survival rate was measured by MTS 48 hours later.
  • Test results of toxin dose As shown in Table 1, when the chemotherapy drug Regorafenib is 0.01mM, it can kill cancer cells to 60%, to simulate the situation of cancer patients after taking chemotherapy drugs, and then proceed to follow-up
  • r-APS astragalus extract
  • r-APS+mannose a pharmaceutical composition of astragalus extract and mannose
  • colorectal cancer cells (HCT116 cells) were cultured for 48 hours after adding astragalus extract (r-APS).
  • the results showed that the use of astragalus extract (r-APS) alone slightly promoted the cancer cells. Therefore, it is shown that the use of astragalus extract (r-APS) alone has no significant toxic effect (as shown in Figure 4B).
  • colorectal cancer cancer cells (HCT116 cells) were incubated with the chemotherapy drug Regorafenib (0.01mM) and astragalus extract (r-APS) for 48 hours.
  • the results showed that the astragalus extract was at an effective concentration. 2mg/mL promotes the growth of cancer cells, while at 4mg/mL it slightly inhibits the growth of cancer cells. Therefore, it shows that the astragalus extract (r-APS) has no significant toxic effect when combined with chemotherapeutics (Figure 4D). Shown).
  • HCT116 cells Colorectal cancer cancer cells (HCT116 cells) added chemotherapy drugs Regorafenib (0.01mM) and Huangqi extract (r-APS) cell survival rate (%) cultured for 48 hours
  • HCT116 was cultured for 48 hours after adding the chemotherapeutic drug Regorafenib (0.01mM), astragalus extract and mannose to the pharmaceutical composition (r-APS+mannose).
  • the results showed that the astragalus extract
  • the effective dose of the pharmaceutical composition (r-APS+mannose) is 10 mg/mL
  • the combination of chemotherapy drugs can effectively reduce the survival rate of cancer cells. Therefore, it is shown that the astragalus extract and the mannose pharmaceutical composition (r -APS+mannose) combined with chemotherapeutics have a significant toxic effect (as shown in Figure 4E).
  • HCT116 cells Colorectal cancer cancer cells (HCT116 cells) added chemotherapy drug Regorafenib (0.01mM), astragalus extract and mannose pharmaceutical composition (r-APS+mannose) cultured for 48 hours cell survival rate (%)
  • Example 4 The effect of the pharmaceutical composition of the present invention on ovarian cancer
  • Toxicide dose test Choose the dose of chemotherapeutic drug to inhibit the cell growth and the remaining 60-70% of the ability to carry out the follow-up test).
  • test concentrations of test drugs among which the test concentrations of Astragalus root extract (r-APS) are 0, 2, and 4mg/ml, respectively.
  • Astragalus root extract and mannose pharmaceutical composition (r-APS+mannose) are tested. The concentrations are 0, 5, and 10 mg/ml, respectively.
  • the cytotoxicity of individual cells selected by the dose of chemotherapeutic drugs is between 35-40% of the dose.
  • the results of the toxin dose test are shown in Table 6.
  • the chemotherapeutic drug can kill cancer cells to 60% when Olaparib is 0.7M, to simulate the situation of cancer patients after taking chemotherapy drugs, and perform subsequent yellowing.
  • the ovarian cancer cell lines were cultured for 48 hours after adding the medicine composition of Astragalus extract and mannose (r-APS+mannose).
  • the results showed that the medicine combination of Astragalus extract and mannose was used.
  • the compound (r-APS+mannose) can promote the growth of cancer cells, so it is shown that the use of astragalus extract and the mannose pharmaceutical composition (r-APS+mannose) alone has no significant toxic effect (as shown in Figure 5C).
  • ovarian cancer cell lines (OVCAR cells) were cultured for 48 hours after adding Olaparib (0.7M), astragalus extract and mannose pharmaceutical composition (r-APS+mannose), and the results showed
  • Olaparib 0.7M
  • astragalus extract and mannose pharmaceutical composition (r-APS+mannose)
  • chemotherapy drugs can effectively inhibit the survival rate of ovarian cancer cell lines (OVCAR cells), so astragalus extract and mannose pharmaceutical composition (r -APS+mannose) combined with chemotherapeutic drugs have a significant toxic effect (as shown in Figure 5E).
  • the combination of Astragalus extract and the mannose pharmaceutical composition (r-APS+mannose) of the present invention can reduce the survival rate of cancer cells by at least 16%. Therefore, it can effectively enhance the chemotherapy drugs to reduce cancer cells. Survival rate, in addition, it can effectively inhibit the proliferation of tumor cells. Compared with the general use of astragalus extract (r-APS), it can achieve a stronger chemotherapeutic effect, and it can maintain or enhance even drug-resistant cancers. The therapeutic effect of chemotherapy drugs.

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Abstract

一种黄芪医药组合物在用于制备增强癌症治疗药物中的应用，其包含黄芪萃取物和甘露糖，该医药组合物可有效增强化疗药物的效果，降低癌细胞的存活率，针对具有抗药性的癌症亦有相同的效果，也可抑制肿瘤细胞的生长。

Description

黄耆医药组合物在用于制备增强癌症治疗药物中的用途 【技术领域】
本发明提供一种医药组合物为黄耆(黄芪)萃取物(refined Astragalus polysaccharides，以下简称：r-APS)和甘露糖(mannose)合并加入化疗药物后，对于不同癌症肿瘤细胞，增强其化疗药物的毒杀癌细胞的能力。
【先前技术】
黄耆(又称黄芪)为蒙古黄耆或膜荚黄耆，特定言之，黄耆是指膜荚黄耆蒙古亚种(Astragalus membranaceus Bge.var.mongholicus(Bge.)Hsiao)或膜荚黄耆亚种(A.membranaceus(Fisch.)Bge.)的干根部。根据传统药学的记载，黄耆用于治疗慢性肾炎、蛋白尿、肌炎、抗高血压、冠状动脉心脏病、脑梗塞、消化性溃疡(十二指肠与胃溃疡)、肾病与糖尿病。此外，有数种黄耆萃取物可用于治疗肿瘤。有些研究显示，治疗肿瘤的机转系透过调节免疫反应(Lau,B.H.S.,Ruckle,H.C.Botolazzo,T.与Lui,P.D.的“中医草药抑制老鼠肾细胞癌生长”。
近年来，已分析出黄耆的成分包括单糖、多糖、黄酮、氨基酸、与微量元素，其中以多糖的含量为最多，且已证实多糖对治疗疾病具有医疗效果，尤指与癌症有关的疾病，如：肿瘤(美国专利案No.5,268,467；Tang,W.Hemm,I.与Bertram,B.的“中医草药学的抗肿瘤剂最新发展”，第II部份，高分子量化合物。
恶性肿瘤为了让肿瘤快速生长，会比正常健康组织消耗更多葡萄糖，仅透过饮食很难控制体内的葡萄糖含量。英国比特森癌症研究所(Cancer  Research UK Beatson Institute)表示：“肿瘤需要大量葡萄糖才能生长，因此限制肿瘤可使用的葡萄糖量能减缓癌症发展。但问题是正常组织也需要葡萄糖，所以我们不能将葡萄糖彻底移除。在研究中发现，一定剂量的甘露糖可阻断够多葡萄糖，以减缓小鼠肿瘤生长，但却不至于影响正常组织。这还是早期研究，但未来若能找出完美平衡，甘露糖便能增强癌症患者的化疗效果，却不会损害他们的整体健康”。而甘露糖为一种六碳糖、微量存在于人类血液中，已知其供应路径并非自食物吸收而来，而主要是经葡萄糖代谢而来。
虽然标靶药物和精准医学的技术日趋成熟，但在癌症治疗上依然面临抗药性的难题，若是使用高剂量或是长期使用化疗标靶药物，经常会使癌细胞获得抗药性，由此在宿主中存活和持续生长，最终会导致化疗药物无效的癌症治疗。化疗药物在治疗初期能有效用，当患者初期服用后，肿瘤生长能被有效抑制，但经过一段时间后，肿瘤会再度生长。但随着治疗时间愈久，药物开始失效，医学上称此现象为抗药性。抗药性不仅会使癌症复发，还使病患面临无药可用的绝境，为降低化疗药物副作用及癌症的抗药性是治疗癌症时的重要课题。
因此，目前迫切需要开发一种有效、安全和耐抗药性的医药组合物。
【发明内容】
为解决上述问题，我们研究后发现黄耆萃取物再加上甘露糖的医药组合物，用于正在进行化疗的患者，可比单独使用黄耆萃取物或是单独使用甘露糖，使其仅需使用与原先相当剂量的化疗药物，但可让化疗药物降低癌细胞存活率的效果提升，因此可以有效的增强化疗药物的治疗效果。
本发明的黄耆萃取物再加上甘露糖的医药组合物，对于有着化疗药物抗药性的患者，使其仅需使用与原先相当剂量的化疗药物，但让化疗药物降低癌细胞存活率的效果提升至少16％，因此使患者即使在产生抗药性的情况下，仍 能有效的增强化疗药物的治疗效果。
本发明提供一种黄耆(黄芪)医药组合物在制备增强癌症化疗药物可抑制癌细胞存活率效果的药物的用途，其中所述黄耆医药组合物包含黄耆萃取物和甘露糖。
在本发明之一些的实施例中，其中所述癌症化疗药物为一化疗标靶药物，该化疗标靶药物为一针对相对应癌种的化疗标靶药物。
在本发明之一些的实施例中，其中所述癌症包含大肠癌、卵巢癌或肺癌。
在本发明之一些的实施例中，其中所述针对相对应癌种的化疗标靶药物包含癌瑞格(Regorafenib)、令癌莎(Olaparib)或得舒缓(Tarceva)。
在本发明之一些的实施例中，其中所述医药组合物中的黄耆萃取物和所述甘露糖的有效剂量比例为1.5～4.5:5.5～8.5，且黄耆萃取物和甘露糖组合物的浓度范围为0～10mg/mL。
在本发明一些实施例中，其中该医药组合物可为锭剂、丸剂、粒剂、粉末、胶囊或液体剂。
在本发明另一的实施例中提供一种黄耆医药组合物在制备增强治疗抗药性癌症的癌症化疗药物的抑制癌细胞存活率的药物中的用途，其特征是，所述黄耆医药组合物包含黄耆萃取物和甘露糖。
在本发明之一的实施例中，所述癌症为固态肿瘤癌，其中所述固态肿瘤癌包含大肠癌、卵巢癌、肺癌。
在本发明另一的实施例中提供一种黄耆医药组合物在制备增强癌症化疗药物可抑制肿瘤细胞增生效果的药物的用途，其中所述医药组合物包含黄耆萃取物和甘露糖。
在本发明之一的实施例中，其中所述肿瘤细胞为具有抗药性的肿瘤细胞。
在本发明之一的实施例中，其中所述肿瘤细胞包含大肠癌、卵巢癌、肺 癌。
为达到上述及其它目的，以下对本发明一或多个具体实施例进行说明。
本发明的其它特征或优点以实施例及请求项详细描述。
【附图说明】
图1A显示黄耆萃取物(r-APS)对肺癌耐药细胞株(HCC827GR cells)的结果。
图1B显示黄耆萃取物(r-APS)和与甘露糖(mannose)的医药组合物对肺癌耐药细胞株(HCC827GR cells)的结果。
图1C显示肺癌化疗药物艾瑞莎(Iressa)对肺癌耐药细胞株(HCC827GR cells)的结果。
图2A黄耆萃取物(r-APS)对肺癌耐药细胞株(H1975 cells)的结果。
图2B显示黄耆萃取物(r-APS)和甘露糖(mannose)的医药组合物对肺癌耐药细胞株(H1975 cells)的结果。
图2C显示肺癌化疗药物得舒缓(Tarceva)对肺癌耐药细胞株(H1975 cells)的结果。
图3A显示黄耆萃取物合并肺癌化疗药物得舒缓(Tarceva)对肺癌耐药细胞(H1975 cells)的结果。
图3B显示黄耆萃取物(r-APS)和甘露糖(mannose)的医药组合物合并肺癌化疗药物得舒缓(Tarceva)对肺癌耐药细胞株(H1975 cells)的结果。
图4A显示大肠癌细胞株(HCT116 cells)挑选60～70％化疗抑制结果。
图4B显示大肠癌细胞株(HCT116 cells)加入黄耆萃取物(r-APS)后培养48小时的结果。
图4C显示大肠癌细胞株(HCT116 cells)加入黄耆萃取物(r-APS)和甘露糖 (mannose)的医药组合物后培养48小时的结果。
图4D显示大肠癌细胞株(HCT116 cells)加入黄耆萃取物(r-APS)合并大肠癌化疗药物癌瑞格(Regorafenib)后培养48小时的结果。
图4E显示大肠癌细胞株(HCT116 cells)加入黄耆萃取物(r-APS)和甘露糖(mannose)医药组合物合并大肠癌化疗药物癌瑞格(Regorafenib)后培养48小时的结果。
图5A显示卵巢癌细胞株(OVCAR3 cells)挑选60～70％化疗抑制结果。
图5B显示卵巢癌细胞株(OVCAR cells)加入黄耆萃取物(r-APS)后培养48小时的结果。
图5C显示卵巢癌细胞株(OVCAR cells)加入黄耆萃取物(r-APS)和甘露糖(mannose)医药组合物后培养48小时的结果。
图5D显示卵巢癌细胞株(OVCAR cells)加入黄耆萃取物(r-APS)合并大肠癌化疗药物令癌莎(Olaparib)后培养48小时的结果。
图5E显示卵巢癌细胞株(OVCAR cells)加入黄耆萃取物(r-APS)和甘露糖(mannose)的医药组合物合并大肠癌化疗药物令癌莎(Olaparib)后培养48小时的结果。
【具体实施方式】
本发明中所述的“r-APS”是指黄耆萃取物，“mannose”是指甘露糖。
本发明所述的增强化疗药物的效果，其增强为最少增加16％的治疗效果。
本发明所述的化疗药物包含化疗标靶药物，且化疗标靶药物为针对相对应癌症种类的化疗标靶药物。
本发明提供一种医药组合物用于提高化疗药物治疗癌症效果的用途，由黄耆萃取物和甘露糖所组成，其中所述医药组合物中黄耆萃取物和甘露糖的重 量比为1.5～4.5:5.5～8.5。本发明的医药组合物中黄耆萃取物有效浓度为0～10mg/mL，甘露糖有效浓度为0～10mg/mL。较佳地，黄耆萃取物有效浓度为3mg/mL，甘露糖有效浓度为7mg/mL。
本发明另提供一种医药组合物用于提高或维持化疗药物对于具有抗药性癌症的治疗效果的用途，由黄耆萃取物和甘露糖所组成，其中医药组合物中黄耆萃取物和甘露糖的重量比为1.5～4.5:5.5～8.5。本发明的医药组合物中黄耆萃取物有效浓度为0～10mg/mL，甘露糖有效浓度为0～10mg/mL。较佳地，黄耆萃取物有效浓度为3mg/mL，甘露糖有效浓度为7mg/mL。
本发明又提供一种医药组合物用于治疗抑制肿瘤细胞增生的用途，由黄耆萃取物和甘露糖所组成，其中医药组合物中黄耆萃取物和甘露糖的重量比为1.5～4.5:5.5～8.5。本发明的医药组合物中黄耆萃取物有效浓度为0～10mg/mL，甘露糖有效浓度为0～10mg/mL。较佳地，黄耆萃取物有效浓度为3mg/mL，甘露糖有效浓度为7mg/mL。
本发明黄耆萃取物的制作过程:
(1)取黄耆饮片置于一容器中，加入一纯水，形成一溶液A；
(2)以一温度加热步骤(1)形成的溶液A，该加热温度为80-100℃，该时间为2-4小时；
(3)收集并浓缩步骤(2)的溶液，获得萃取液A；
(4)将步骤(3)的萃取液A置于容器B中，加入30～50％乙醇，搅拌后静置沉淀，再收取上清液并浓缩，取得浓缩液A；
(5)将步骤(4)最后取得的浓缩液A加入75％～95％乙醇，搅拌后静置沉淀，收集沉淀物A；
(6)将步骤(5)的沉淀物A进行脱水及抽滤，再进行溶解及酒精醇沉，最后进行离心，而离心沉淀物，得产物A，该产物A的成分包含黄耆萃取物(r- APS)。
实施例一、黄耆萃取物和甘露糖对肺癌耐药细胞的影响
本实施例探讨黄耆萃取物和甘露糖对肺癌耐药细胞的影响，共有三组试验组，分别处理如下:
(1)试验组1：不同浓度的黄耆萃取物(r-APS)分别为0.25mg/ml、0.5mg/ml、1mg/ml、2mg/ml、4mg/ml。
(2)试验2组：不同浓度的(黄耆萃取物：甘露糖为30％：70％)黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)分别为0.625mg/ml、1.25mg/ml、2.5mg/ml、5mg/ml、10mg/ml。
(3)试验3组：艾瑞沙(Iressa，适用于HCC827GR细胞株)或得舒缓(Tarceva，适用于H1975细胞株)。
将测试组1、测试组2和测试组3分别加至HCC827GR或H1975的肺癌细胞株中，每组分别作用24小时、48小时和72小时后，再测试HCC827GR或H1975的肺癌细胞株的细胞存活率，其结果如图1A-1C、图2A-2C所示。
HCC827GR细胞株是对治疗肺癌化疗药物艾瑞沙(Iressa)具有耐药性的细胞株，结果显示测试组2(黄耆萃取物)和测试组3(黄耆萃取物与甘露糖的医药组合物)具有更好的抗肺癌作用(如图1A-1C所示)。
H1975细胞株是一种对治疗肺癌药物得舒缓(Tarceva)具有耐药性的细胞株，结果显示测试组3(黄耆萃取物和甘露糖之医药组合物)具有最佳的抗癌作用(如图2A-2C所示)。
实施例二、黄耆萃取物和甘露糖的医药组合物合并抗癌药物对肺癌耐药细胞的作用
本实施例探讨黄耆萃取物和甘露糖的医药组合物对肺癌耐药性细胞的影响，共有三组试验组，分别处理如下:
(1)试验组1：不同浓度的黄耆萃取物(r-APS)分别为0.25mg/ml、0.5mg/ml、1mg/ml、2mg/ml、4mg/ml。
(2)测试组2：不同浓度的(黄耆萃取物：甘露糖为30％：70％)黄耆萃取物和甘露糖之医药组合物(r-APS+mannose)分别为0.625mg/ml、1.25mg/ml、2.5mg/ml、5mg/ml、10mg/ml。
每组测试组与得舒缓(Tarceva)合并使用(浓度分别为1.25μM、2.5μM、5μM)并分别添加到H1975的肺癌细胞株中，每组分别作用24小时，48小时和72小时，测量H1975的肺癌细胞株的细胞存活率。
H1975细胞株是对化疗药物得舒缓(Tarceva)具有耐药性的细胞，结果显示测试组1(黄耆萃取物)和测试组2(黄耆萃取物与甘露糖的医药组合物合并化疗药物得舒缓(Tarceva)具有最佳的抗癌作用(如图3A-3B所示)，即试验组1(黄耆萃取物)和试验组2(黄耆萃取物与甘露糖的医药组合物)合并化疗药物得舒缓(Tarceva)具有逆转抗肺癌药物耐药性的最佳治疗效果。
实施例三、本发明医药组合物对于大肠癌的影响
实验方式:
首先，毒杀剂量测试(选择化疗药物剂量为抑制细胞生长剩下60～70％能力的剂量进行后续试验)
接种细胞于96孔盘后，培养24小时。
添加不同浓度的测试药物，其中黄耆萃取物(r-APS)测试浓度分别为0、2、4mg/ml，黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)测试浓度分别为0、5、10mg/ml。
化疗药物剂量挑选个别细胞的毒杀效果介于35-40％间剂量。
于添加后48、72小时测试细胞存活率。
黄耆萃取物(r-APS)与黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)化疗增效实验。
接种细胞于96孔盘，培养24小时。
同时给予黄耆萃取物(r-APS)或黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)及化疗药物培养48小时，其中黄耆萃取物(r-APS)与黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)挑选剂量为测试的4个毒杀剂量，48小时后以MTS测量细胞存活率。
毒杀剂量测试结果:如表一所示，化疗药物癌瑞格(Regorafenib)在0.01mM时，可将癌细胞毒杀至60％，以模拟癌症患者服用化疗药物后的情况，而进行后续的黄耆萃取物(r-APS)与黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)化疗增效实验结果。(如图4A所示)
表一、不同浓度的化疗药物癌瑞格(Regorafenib)毒杀大肠癌癌细胞(HCT116 cells)后的细胞存活率(％)
Figure PCTCN2021081377-appb-000001
如表二所示，大肠癌癌细胞(HCT116 cells)加入黄耆萃取物(r-APS)后 培养48小时，结果显示单独使用黄耆萃取物(r-APS)反而还些微的促进癌细胞的生长，因此显示单独使用黄耆萃取物(r-APS)无显著毒杀效果(如图4B所示)。
表二、大肠癌癌细胞(HCT116 cells)加入不同浓度的黄耆萃取物(r-APS)后培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000002
如表三所示，HCT116加入黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)处理48小时候，结果显示使用黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)，反而还促进癌细胞的生长，因此显示使用黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)无显著毒杀效果(如图4C所示)。
表三、大肠癌癌细胞(HCT116 cells)加入不同浓度的黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)后培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000003
Figure PCTCN2021081377-appb-000004
如表四所示，大肠癌癌细胞(HCT116 cells)加入化疗药物癌瑞格(Regorafenib)(0.01mM)与黄耆萃取物(r-APS)培养48小时，结果显示黄耆萃取物在有效浓度2mg/mL时促进了癌细胞的生长，而在4mg/mL时有些微的抑制癌细胞的生长，因此显示黄耆萃取物(r-APS)合并化疗药物时无显著毒杀效果(如图4D所示)。
表四、大肠癌癌细胞(HCT116 cells)加入化疗药物癌瑞格(Regorafenib)(0.01mM)与黄耆萃取物(r-APS)培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000005
如表五所示，HCT116加入化疗药物癌瑞格(Regorafenib)(0.01mM)与黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)后培养48小时，结果显示在黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)有效剂量在10mg/mL时，合并化疗药物可以有效的降低癌细胞的存活率，因此显示黄耆萃取物和甘露糖医药组合物(r-APS+mannose)合并化疗药物具有显著毒杀效果(如图4E所示)。
表五、大肠癌癌细胞(HCT116 cells)加入化疗药物癌瑞格(Regorafenib)(0.01mM)与黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000006
本实验结果显示，本发明之黄耆萃取物与甘露糖之医药组合物合并化疗药物，对比仅使用药物可额外再降低16％大肠癌癌细胞的存活率，因此可以有效的增强化疗药物的治疗效果。
实施例四、本发明的医药组合物对于卵巢癌的影响
实验方式:
(1)毒杀剂量测试(选择化疗药物剂量为抑制细胞生长剩下60～70％能力的剂量进行后续试验)。
(2)接种细胞于96孔盘后，培养24小时。
(3)添加不同浓度的测试药物，其中黄耆萃取物(r-APS)测试浓度分别为0、2、4mg/ml，黄耆萃取物和甘露糖医药组合物(r-APS+mannose)测试浓度分别为0、5、10mg/ml。
(4)化疗药物剂量挑选个别细胞的毒杀效果介于35-40％间剂量。
(5)于添加后48、72小时测试细胞存活率。
(6)黄耆萃取物(r-APS)与黄耆萃取物和甘露糖医药组合物(r-APS+mannose)化疗增效实验。
(7)接种细胞于96孔盘，培养24小时。
(8)同时给予黄耆萃取物(r-APS)或黄耆萃取物和甘露糖医药组合物(r-APS+mannose)及化疗药物培养48小时，其中黄耆萃取物(r-APS)与黄耆萃取物和甘露糖医药组合物(r-APS+mannose)挑选剂量为测试的3个毒杀剂量，48小时候以MTS测量细胞存活率。
毒杀剂量测试结果如表六所示，化疗药物令癌莎(Olaparib)在0.7M时，可将癌细胞毒杀至60％，以模拟癌症患者服用化疗药物后的情况，而进行后续的黄耆萃取物(r-APS)与黄耆萃取物和甘露糖医药组合物(r-APS+mannose)化疗增效实验。(实验结果如图5A)
表六、不同浓度的化疗药物令癌莎(Olaparib)毒杀卵巢癌细胞株(OVCAR cells)的细胞存活率(％)
Figure PCTCN2021081377-appb-000007
Figure PCTCN2021081377-appb-000008
黄耆萃取物(r-APS)与黄耆萃取物和甘露糖之医药组合物(r-APS+mannose)化疗增效实验结果如下表七所示，卵巢癌细胞株(OVCAR cells)加入黄耆萃取物(r-APS)后培养48小时，结果显示单独使用黄耆萃取物(r-APS)反而还促进癌细胞的生长，因此显示单独使用黄耆萃取物(r-APS)无显著毒杀效果(如图5B所示)
表七、卵巢癌细胞株(OVCAR cells)加入不同浓度的黄耆萃取物(r-APS)后培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000009
Figure PCTCN2021081377-appb-000010
如表八所示，卵巢癌细胞株(OVCAR cells)加入黄耆萃取物和甘露糖的医药组合物(r-APS+mannose)后培养48小时，结果显示使用黄耆萃取物和甘露糖医药组合物(r-APS+mannose)会促进癌细胞的生长，因此显示单独使用黄耆萃取物和甘露糖医药组合物(r-APS+mannose)无显著毒杀效果(如图5C所示)。
表八、卵巢癌细胞株(OVCAR cells)加入不同浓度的黄耆萃取物和甘露糖医药组合物(r-APS+mannose)后培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000011
如表九所示，卵巢癌细胞株(OVCAR cells)加入令癌莎(Olaparib)(0.7M)与黄耆萃取物(r-APS)后培养48小时，结果显示使用黄耆萃取物(r-APS)合并化疗药物令癌莎(Olaparib)可以有效的抑制卵巢癌细胞株(OVCAR cells)的存活率，因此黄耆萃取物(r-APS)合并化疗药物有显著毒杀效果(如图5D所示)。
表九、卵巢癌细胞株(OVCAR cells)加入令癌莎(Olaparib)(0.7M)与黄耆萃取物(r-APS)培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000012
如表十所示，卵巢癌细胞株(OVCAR cells)加入令癌莎(Olaparib)(0.7M)与黄耆萃取物和甘露糖医药组合物(r-APS+mannose)后培养48小时，结果显示使用黄耆萃取物和甘露糖医药组合物(r-APS+mannose)合并化疗药物可以有效的抑制卵巢癌细胞株(OVCAR cells)的存活率，因此黄耆萃取物和甘露糖医药组合物(r-APS+mannose)合并化疗药物有显著毒杀效果(如图5E所示)。
表十、卵巢癌细胞株(OVCAR cells)加入令癌莎(Olaparib)(0.7M)与黄耆萃取物和甘露糖之医药组合物(r-APS+mannose)培养48小时的细胞存活率(％)
Figure PCTCN2021081377-appb-000013
Figure PCTCN2021081377-appb-000014
本实验结果显示，本发明的黄耆萃取物与甘露糖医药组合物合并化疗药物，对比仅使用药物可额外再降低43％大肠癌癌细胞的存活率，因此可以有效的增强化疗药物的治疗效果。
综上所述，本发明黄耆萃取物和甘露糖医药组合物(r-APS+mannose)合并使用化疗药物，最少可以降低16％的癌细胞存活率，因此可以有效的增强化疗药物降低癌细胞存活率的能力，另外也能有效抑制肿瘤细胞的增生，比起一般只使用黄耆萃取物(r-APS)能达到更强的化疗效果，且即使是具有抗药性的癌症亦能维持或增强化疗药物的治疗效果。
本发明所揭露的所有特征应可以任何结合方式实现。本发明所揭露的每一特征应可以相同、均等或相似目的的取代物所取代。因此，除非有明确的指定，否则所揭露的每一个特征仅仅只是均等物或相似特征的一个种类的一实施例。

Claims (18)

  1. 一种黄耆医药组合物在制备增强癌症化疗药物的抑制癌细胞存活率的药物中的用途，其特征是，所述黄耆医药组合物包含黄耆萃取物和甘露糖。
  2. 如权利要求1所述的用途，其特征是，所述癌症化疗药物为化疗标靶药物，所述化疗标靶药物为针对相对应癌种的化疗标靶药物。
  3. 如权利要求1所述的用途，其特征是，所述癌症包含大肠癌、卵巢癌或肺癌。
  4. 如权利要求2所述的用途，其特征是，所述针对相对应癌种的化疗标靶药物包含癌瑞格(Regorafenib)、令癌莎(Olaparib)或得舒缓(Tarceva)。
  5. 如权利要求1所述的用途，其特征是，所述黄耆萃取物和所述甘露糖的有效剂量比例为1.5～4.5:5.5～8.5，且黄耆萃取物和甘露糖组合物的浓度范围为0～10mg/mL。
  6. 如权利要求1所述的用途，其特征是，所述医药组合物为锭剂、丸剂、粒剂、粉末、胶囊或液体剂。
  7. 一种黄耆医药组合物在制备增强治疗抗药性癌症的癌症化疗药物的抑制癌细胞存活率的药物中的用途，其特征是，所述黄耆医药组合物包含黄耆萃取物和甘露糖。
  8. 如权利要求7所述的用途，其特征是，所述癌症化疗药物为化疗标靶药物，所述化疗标靶药物为针对相对应癌种的化疗标靶药物。
  9. 如权利要求8所述的用途，其特征是，所述针对相对应癌种的化疗标靶药物包含癌瑞格(Regorafenib)、令癌莎(Olaparib)或得舒缓(Tarceva)。
  10. 如权利要求7所述的用途，其特征是，所述癌症为固态肿瘤癌。
  11. 如权利要求8所述的用途，其特征是，所述固态肿瘤癌包含大肠癌、卵巢癌或肺癌。
  12. 如权利要求7所述的用途，其特征是，所述黄耆萃取物和所述甘露糖的有效剂量比例为1.5～4.5:5.5～8.5，且黄耆萃取物和甘露糖组合物的浓度范围为0～10mg/mL。
  13. 一种黄耆医药组合物在制备增强癌症化疗药物的抑制肿瘤细胞增生效果的药物中的用途，其特征是，所述黄耆医药组合物包含黄耆萃取物和甘露糖。
  14. 如权利要求13所述用途，其特征是，所述肿瘤细胞为具有抗药性的肿瘤细胞。
  15. 如权利要求13所述的用途，其特征是，所述癌症化疗药物为化疗标靶药物，所述化疗标靶药物为针对相对应癌种的化疗标靶药物。
  16. 如权利要求15所述的用途，其特征是，所述针对相对应癌种的化疗标靶药物包含癌瑞格(Regorafenib)、令癌莎(Olaparib)或得舒缓(Tarceva)。
  17. 如权利要求13所述的用途，其特征是，所述肿瘤细胞包含大肠癌、卵巢癌或肺癌。
  18. 如权利要求13所述的用途，其特征是，所述黄耆萃取物和所述甘露糖的有效剂量比例为1.5～4.5:5.5～8.5，且黄耆萃取物和甘露糖组合物的浓度范围为0～10mg/mL。
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