CN108309985B - Anticancer medicine composition - Google Patents
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- CN108309985B CN108309985B CN201810145877.8A CN201810145877A CN108309985B CN 108309985 B CN108309985 B CN 108309985B CN 201810145877 A CN201810145877 A CN 201810145877A CN 108309985 B CN108309985 B CN 108309985B
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- hydroxycamptothecin
- ethyl
- ball milling
- pharmaceutical composition
- sodium glycyrrhetinate
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- 230000001093 anti-cancer Effects 0.000 title abstract description 22
- 239000003814 drug Substances 0.000 title description 19
- 239000000203 mixture Substances 0.000 title description 11
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims abstract description 52
- 238000000498 ball milling Methods 0.000 claims abstract description 28
- MOCOXAJEZKHXSF-IHMBCTQLSA-M sodium;(2s,4as,6ar,6as,6br,8ar,10s,12as,14br)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1h-picene-2-carboxylate Chemical compound [Na+].C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C([O-])=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MOCOXAJEZKHXSF-IHMBCTQLSA-M 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 238000005303 weighing Methods 0.000 claims abstract description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- 229910000831 Steel Inorganic materials 0.000 claims description 6
- 239000010959 steel Substances 0.000 claims description 6
- 238000000227 grinding Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 5
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 description 13
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 8
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical class Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 229960003720 enoxolone Drugs 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical class C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 description 2
- 102000004308 Carboxylic Ester Hydrolases Human genes 0.000 description 2
- 108090000863 Carboxylic Ester Hydrolases Proteins 0.000 description 2
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 2
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 2
- 229960004949 glycyrrhizic acid Drugs 0.000 description 2
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 2
- 239000001685 glycyrrhizic acid Substances 0.000 description 2
- 235000019410 glycyrrhizin Nutrition 0.000 description 2
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008063 pharmaceutical solvent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an anticancer pharmaceutical composition, which is characterized by consisting of 7-ethyl-10-hydroxycamptothecin and sodium glycyrrhetinate, and is prepared by the following method: (1) preparing raw materials: weighing 7-ethyl-10-hydroxycamptothecin and sodium glycyrrhetinate in dark place; (2) ball milling by a roller: performing roller ball milling on the 7-ethyl-10-hydroxycamptothecin and the sodium glycyrrhetinate at the ball milling rotation speed of 10-30rpm at the temperature of 20-30 ℃ for 12-36 h. The anti-cancer pharmaceutical composition disclosed by the invention is simple in preparation process, free of environmental pollution, suitable for large-scale production, and capable of remarkably improving the solubility of 7-ethyl-10-hydroxycamptothecin and has a good anti-cancer effect.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to an anticancer pharmaceutical composition.
Background
7-Ethyl-10-hydroxycamptothecin (7-ethyl-10-hydroxycamptothecin, SN-38) is a bioactive metabolite of irinotecan hydrochloride (CPT-11). CPT-11 is an inactive prodrug that is converted in vivo by Carboxylesterases (CES) in plasma, small intestinal mucosa and liver to the active metabolite SN-38, which was approved by the FDA in 2000 as a first-line therapeutic for advanced colon cancer. However, in practice, the antitumor activity of SN-38 is 1000 times that of CPT-11, and only a small fraction of CPT-11 is converted to SN-38 after intravenous or oral administration of CPT-11, and varies greatly from patient to patient. Whereas SN-38, an active metabolite of CPT-11 used directly, is limited mainly by its solubility, SN-38 is hardly soluble in water (1-3. mu.g/ml) and insoluble in most pharmaceutical solvents and oils, and thus is difficult to directly prepare into liquid formulations.
At present, the prior art mainly achieves the aim of increasing the solubility of SN-38 by encapsulating in a drug carrier or chemically modifying the drug carrier.
Chinese patent CN201480018947.3 filed by zonio pharmaceutical products limited provides a liposome composition in which a sparingly soluble drug such as SN-38 is encapsulated in a liposome by remote or active loading, thereby ensuring delivery of the sparingly soluble drug in the body while prolonging the drug residence time.
Chinese patent CN201010288427.8 applied by qianshun pionshen drug research limited company provides a method for solubilizing camptothecin compounds, which comprises dissolving camptothecin compounds in an alkaline aqueous solution to obtain camptothecin solution, dissolving water-soluble cyclodextrin derivatives in the alkaline aqueous solution, mixing the two solutions, and finally obtaining a cyclodextrin inclusion compound solution of camptothecin compounds, thereby successfully increasing the solubility of the compounds by more than 100 times.
Chinese patent CN201510181114.5 applied by Tianjin scientific university provides a novel water-soluble polyethylene glycol coupled hydroxycamptothecin derivative, which improves the solubility and anticancer activity by chemically modifying hydroxycamptothecin.
Although the prior art achieves the technical effect of increasing the solubility of SN-38, the processes are complex, and the utilization cost of SN-38 drugs is increased.
In summary, the present invention develops an anticancer pharmaceutical composition containing 7-ethyl-10-hydroxycamptothecin, which is prepared by ball milling 7-ethyl-10-hydroxycamptothecin with sodium glycyrrhetinate as adjuvant. The ball milling method in mechanochemistry is to make hard balls strongly impact, grind and stir raw materials by the rotation or vibration of a ball mill, so that the reaction activation energy can be obviously reduced, crystal grains can be refined, and the powder activity can be enhanced.
Disclosure of Invention
The invention aims to provide an anticancer medicine composition. The anti-cancer pharmaceutical composition disclosed by the invention is simple in preparation process, free of environmental pollution, suitable for large-scale production, and capable of remarkably improving the solubility of 7-ethyl-10-hydroxycamptothecin and has a good anti-cancer effect.
In order to achieve the purpose, the invention adopts the following technical scheme:
an anticancer pharmaceutical composition, which consists of 7-ethyl-10-hydroxycamptothecin and glycyrrhetinic acid sodium, and is prepared by the following method:
(1) preparing raw materials: weighing 7-ethyl-10-hydroxycamptothecin and sodium glycyrrhetinate in dark place;
(2) ball milling by a roller: performing roller ball milling on the 7-ethyl-10-hydroxycamptothecin and the sodium glycyrrhetinate at the ball milling rotation speed of 10-30rpm at the temperature of 20-30 ℃ for 12-36 h.
Further, the mass ratio of the 7-ethyl-10-hydroxycamptothecin to the sodium glycyrrhetinate is 1: 80-120.
Further, the roller ball milling conditions were: 20 small steel balls with the diameter of 4mm, 8mm and 12mm are respectively adopted, and the raw materials and the small steel balls are all put into a roller for ball milling.
Further, the ball milling speed is 20rpm, the temperature is 25 ℃, and the ball milling time is 24 hours.
Further, the grinding ball is prepared from the following raw materials in a mass ratio of 7-ethyl-10-hydroxycamptothecin: sodium glycyrrhetinate 1: 100.
Glycyrrhizic acid is the most important active ingredient in licorice. Glycyrrhizic acid and its series products have the functions of inhibiting the growth of sarcoma and cancer cell and raising immunity of human body. According to the invention, sodium glycyrrhetinate and 7-ethyl-10-hydroxycamptothecin are mixed, and an intermolecular interaction force exists between the sodium glycyrrhetinate and the 7-ethyl-10-hydroxycamptothecin, so that the water solubility of the 7-ethyl-10-hydroxycamptothecin can be promoted, the sodium glycyrrhetinate and the 7-ethyl-10-hydroxycamptothecin can play a synergistic effect, and the anticancer effect is improved.
The invention has the following technical characteristics:
1) according to the invention, sodium glycyrrhetinate and 7-ethyl-10-hydroxycamptothecin are scientifically compatible, and intermolecular force exists between the sodium glycyrrhetinate and the 7-ethyl-10-hydroxycamptothecin, so that the solubility of the 7-ethyl-10-hydroxycamptothecin in water is promoted, and the anticancer effect is increased.
2) The invention adopts a ball milling method to treat the 7-ethyl-10-hydroxycamptothecin, the ball milling process is simple, the environment is not polluted, the invention is suitable for large-scale production, and the solubility of the 7-ethyl-10-hydroxycamptothecin in water is increased from 1-3 mu g/ml to 0.212mg/ml, and the solubility is obviously improved.
3) The ball milling process of the invention not only obviously increases the water solubility of the 7-ethyl-10-hydroxycamptothecin, but also enhances the activity of the medicine, and has synergistic effect on the anticancer effect of the 7-ethyl-10-hydroxycamptothecin.
Detailed Description
The following specific examples are further illustrative of the methods and techniques provided by the present invention and should not be construed as limiting the invention thereto.
Preparation of anticancer pharmaceutical composition and comparative example:
1. preparation of anticancer pharmaceutical composition:
(1) preparing raw materials: weighing 100mg of 7-ethyl-10-hydroxycamptothecin and 10g of sodium glycyrrhetinate in a dark place;
(2) ball milling by a roller: preparing 20 steel balls with the diameter of 4mm, 8mm and 12mm respectively, putting the raw materials and the steel balls into a roller, uniformly stirring, sealing and screwing, setting the rotating speed at 20rpm and the temperature at 25 ℃, and rotating for 24 hours.
2. Comparative example 7-preparation of a common mixture of ethyl-10-hydroxycamptothecin pure drug and sodium glycyrrhetinate:
100mg of 7-ethyl-10-hydroxycamptothecin and 10g of sodium glycyrrhetinate are stirred and mixed uniformly by a stirrer, the rotation speed is set to be 20rpm, and the stirring is carried out for 24 hours.
(II) determination of solubility of anticancer drug composition
The high performance liquid chromatography is adopted to test the solubility of the anticancer medicine composition, and the chromatographic conditions are as follows: selecting a C18 chromatographic column; an ultraviolet detector; the mobile phase is methanol-0.2% formic acid water (0.8: 0.2); the flow rate is 1.0 ml/min; the column temperature is 30 ℃; the sample amount is 20 mul; the detection wavelength was 372 nm.
Preparing 0.2% formic acid water and 500ml of chromatographic grade methanol respectively, and performing ultrasonic treatment for 20min for later use. A standard solution with a concentration gradient is prepared by using 7-ethyl-10-hydroxycamptothecin, an appropriate amount of the solution is put in a liquid phase small bottle and placed on a sample injector, and a standard curve is prepared by HPLC. Adding 7-ethyl-10-hydroxycamptothecin pure drug into a certain amount of water until the pure drug can not be dissolved, measuring peak area by HPLC, and calculating the solubility to be 1ug/ml according to a standard curve. Adding the pharmaceutical composition into a certain amount of water, ball-milling until the pharmaceutical composition cannot be dissolved, measuring the peak area by HPLC, and calculating the solubility of 7-ethyl-10-hydroxycamptothecin to be 0.212mg/ml according to a standard curve.
(III) comparison of anticancer Effect
Setting 7-ethyl-10-hydroxycamptothecin pure drug, 7-ethyl-10-hydroxycamptothecin pure drug and common glycyrrhetinic acid sodium mixture, setting three groups of contrast groups of the anti-cancer composition obtained by ball milling 7-ethyl-10-hydroxycamptothecin and glycyrrhetinic acid sodium, setting concentration gradients of 50 mug/ml, 100 mug/ml, 125 mug/ml, 150 mug/ml, 175 mug/ml and 200 mug/ml, adding the contrast groups into the same quantity of breast cancer tumor cells, and acting for 24 hours at 19.40 ℃. Cell viability was then determined separately by MTT.
Subculturing breast cancer cells (Bcap-37) in a culture bottle, and adding pancreatin into the culture bottle when the number of the cells is proper to enable the breast cancer cells to be uniform suspension. 200 mul of cell suspension and 10 mul of mtt solution are added into a 96-well plate, and three groups of drugs with different concentration gradients, namely 7-ethyl-10-hydroxycamptothecin pure drug (sample 1), 7-ethyl-10-hydroxycamptothecin pure drug and common mixture of glycyrrhetinic acid sodium (sample 2), and the anti-cancer composition (sample 3) obtained by ball milling of the 7-ethyl-10-hydroxycamptothecin and the glycyrrhetinic acid sodium of the invention, are respectively added.
The results of the experiment are shown in table 1:
TABLE 1
As can be seen from table 1:
(1) the sodium glycyrrhetinate has a synergistic effect on the anti-cancer effect of the 7-ethyl-10-hydroxycamptothecin, and can effectively reduce the survival rate of breast cancer cells, wherein the survival rate of the breast cancer cells is 61.53-89.07%.
(2) The ball milling process of the present invention also obviously enhances the activity of the medicine, when the concentration is increased to more than 150 mug/ml, the survival rate of the breast cancer cells is less than 50%, and when the concentration is increased to more than 175 mug/ml, the survival rate of the breast cancer cells is less than 12%.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core ideas. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.
Claims (3)
1. A pharmaceutical composition for resisting breast cancer, which is characterized by consisting of 7-ethyl-10-hydroxycamptothecin and sodium glycyrrhetinate, and is prepared by the following method:
(1) preparing raw materials: weighing 7-ethyl-10-hydroxycamptothecin and sodium glycyrrhetinate in dark place; the mass ratio of the 7-ethyl-10-hydroxycamptothecin to the sodium glycyrrhetinate is 1: 80-120;
(2) ball milling by a roller: carrying out roller ball milling on 7-ethyl-10-hydroxycamptothecin and sodium glycyrrhetinate, wherein the roller ball milling conditions are as follows: respectively adopting 20 small steel balls with the diameters of 4mm, 8mm and 12mm, and putting the raw materials and the small steel balls into a roller for ball milling; the ball milling speed is 10-30rpm, the temperature is 20-30 ℃, and the ball milling time is 12-36 h.
2. The pharmaceutical composition for resisting breast cancer according to claim 1, wherein the ball milling rotation speed is 20rpm, the temperature is 25 ℃, and the ball milling time is 24 h.
3. The pharmaceutical composition for resisting breast cancer according to claim 1, wherein the grinding ball is prepared from the following raw materials in a mass ratio of 7-ethyl-10-hydroxycamptothecin: sodium glycyrrhetinate 1: 100.
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| CN201810145877.8A CN108309985B (en) | 2018-02-12 | 2018-02-12 | Anticancer medicine composition |
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| CN201810145877.8A CN108309985B (en) | 2018-02-12 | 2018-02-12 | Anticancer medicine composition |
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| CN108309985B true CN108309985B (en) | 2021-05-04 |
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| CN104447777A (en) * | 2014-11-26 | 2015-03-25 | 浙江大学 | Capsicine-camptothecin anti-cancer drug conjugate and preparation method and application thereof |
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| 甘草次酸抗肿瘤作用机制的研究进展;康潇等;《中国中药杂志》;20111130;第36卷(第22期);3213-3216 * |
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