CN103800341B - The combination medicine of anti-curing oncoma - Google Patents
The combination medicine of anti-curing oncoma Download PDFInfo
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- CN103800341B CN103800341B CN201210455705.3A CN201210455705A CN103800341B CN 103800341 B CN103800341 B CN 103800341B CN 201210455705 A CN201210455705 A CN 201210455705A CN 103800341 B CN103800341 B CN 103800341B
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Abstract
The present invention is the combination medicine of a kind of anti-curing oncoma, has the effect reducing chemotherapy and radiation side effect.The described combination medicine for anti-curing oncoma is made up of with at least one in coenzyme Q10, taurine cucurbitacin；Cucurbitacin is 1:0.1 10000 with the weight ratio of coenzyme Q10.Cucurbitacin is 1:0.1 10000 with the weight ratio of taurine.When medicine is made up of cucurbitacin, coenzyme Q10 and taurine, the weight ratio of cucurbitacin, coenzyme Q10 and taurine is 1:0.1 10000:0.1 10000.And propose dosage.Jointly or the dosage forms such as tablet, capsule, granule, powder, patch, ointment, suspensoid, syrup, controlled release agent, nanoparticle or Emulsion can be respectively prepared with pharmaceutically acceptable carrier.Can be clinically used for chronic hepatitis treatment it can also be used to the prevention of cancer and treatment.
Description
Technical field
The invention belongs to pharmaceutical technology field, relate to the combination medicine of anti-curing oncoma, particularly relate to containing cucurbitacin
The combination medicine for anti-curing oncoma.
Background technology
In recent years, cancer has exceeded cardiovascular and cerebrovascular disease becomes the number one killer threatening human health.According to world health group
Knitting statistical data to show, there are about more than 700 ten thousand people in the whole world dies from cancer, in the most every 8 deaths in the whole world the most every year
1 people is just had to die from cancer.This tissue expects the year two thousand thirty global annual number of cancer deaths may be on the basis of now
Be doubled, reach 17,000,000.Therefore, seek effectively to prevent and treat tumorigenesis, shift and the strategy that recurs is extremely urgent.
Chemotherapy is as existing more than the 60 year history of conventional means of clinical anticancer.Although chemotherapy is in cure diseases, improve
Resection Rate and survival rate, improve life quality aspect and played bigger effect, but its problem existed also is not allowed suddenly
Depending on.Most of chemotherapeutics lack preferable selectivity, cause " being non-unclear ", " failing to differentiate between the enemy and ourselves ", at killing tumor cell
Meanwhile, also killed human normal cell (as medulla hematopoietic system suppression, liver cell infringement, irreversible and accumulative
Cardiac toxicity etc.), cause patient body function to be made patient be difficult to stand by infringement in various degree, force give the normal course for the treatment of
To interrupt, greatly reduce the curative effect of medicine；Additionally, chemotherapeutics exists and easily produces drug resistance also to make it apply certain
Limitation.
Therefore, how while keeping and improving antitumor drug curative effect, reduce its treatment cost, extension is suitable for people
Group, reduction toxicity, raising compliance are the emphasis that antitumor drug is researched and developed with toleration etc..
Cucurbitacine composition is the highly oxidized tetracyclic triterpenoid of class extracted from plant, has been found that so far
Kind more than 40.This constituents majority is present in cucurbitaceous plant, at Cruciferae, Scrophulariaceae, Begoniaceae, Elaeocarpaceae, four numbers
The higher plants such as Ochnaceae and some macro fungis are also found.At present, the cucurbitacin that China's approval produces is again Cucurbitacine,
For Chinese medicine muskmelon pedicel (another name: Pedicellus Melo) extract, the mainly composition Han Cucurbitacin B, E etc., in existing extract, Cucurbitacin B contains
Amount is more than 60%, and its quality standard records in China's ministry standard.
Domestic cucurbitacin is mainly used in chronic hepatitis and primary liver cancer, and be grown up each 0.1～0.3 mg, 3 times on the 1st
, dosage must not arbitrarily strengthen, and maximum dose is 0.6 mg/ time.The cucurbitacin pharmacological action of foreign literature report mainly has: cell in vitro
Poison and antitumor, improve immunity, anti-hepatitis, environment resistant chemical carcinogen, affect cell and ask that signal transduction, stimulating gastrointestinal are transported
Move, strengthen capillary permeability, improve microcirculation etc..
Coenzyme Q compounds is extensive in distributed in nature, is present in many animals, plant and microorganism, the most sends out
Existing coenzyme Q kind includes that CoQ1 is to CoQ1 3.Most in human body is coenzyme Q10, nineteen fifty-seven, Britain Morton professor from
Suffer from isolated coenzyme Q10 in the rat liver of hypovitaminosis A, and referred to as ubiquinone.
The quinoid structure of coenzyme Q10 and the iso-amylene structure of side chain, determine its critical function in organism.It is
Important hydrogen carrier in respiratory chain, is biological cell energy forming element；It also has antioxidation and controls intracellular oxygen
The function of flowing；It is cellular metabolism activator and nonspecific immunity strengthening agent；It can be that cells survival is required food conversion
Energy, make cell keep optimum state, protect biofilm structure integrity；Improve organic immunity.At medicinal aspect:
It is currently used primarily in the adjuvant drug of cardiovascular disease, acute, chronic hepatitis and cancer, to acquired immune deficiency syndrome (AIDS), diabetes, Parkinson's disease etc.
Neurodegenerative diseases and mitochondrial disease have and significantly assist treatment.
Taurine, also known as 2-aminoethyl sulfonic acid, is separated by Calculus Bovis the earliest, therefore gains the name.It is a kind of nonprotein
Aminoacid, is not involved in the biosynthesis of vivo protein matter, but closely related with the metabolism of cystine, cysteine.Its physiology
Function is extensive, mainly has promotion infant brain tissue and intelligent development, raising nerve conduction and visual function, suppression platelet to coagulate
Collection, reduce blood fat, keep human normal blood pressure, prevent arteriosclerosis, arrhythmia, reduction blood cholesterol level, control
Treat heart failure, affect the absorption of lipid, improve endocrinosity, enhancing human body specificity and non-specific immunity, no
Depend on increase the hypoglycemic activity of insulin, suppress cataractous to develop, improves remember function, calmness, ease pain, disappear
The effects such as inflammation.
Summary of the invention
It is an object of the invention to provide a kind of combination medicine for anti-curing oncoma and medical usage thereof.
A kind of combination medicine for anti-curing oncoma provided by the present invention is by cucurbitacin and coenzyme Q10 and/or cattle sulphur
Acid composition.
When a kind of combination medicine for anti-curing oncoma provided by the present invention is made up of with coenzyme Q10 cucurbitacin,
Cucurbitacin is 1:0.1-1000 with the weight ratio of coenzyme Q10, and as preferably, cucurbitacin is 1:1-with the weight ratio of coenzyme Q10
1000, as it is further preferred that the weight ratio of cucurbitacin and coenzyme Q10 is 1:5-100.
When a kind of combination medicine for anti-curing oncoma provided by the present invention is made up of with taurine cucurbitacin, calabash
Lu Su is 1:0.1-1000 with the weight ratio of taurine, and as preferably, cucurbitacin is 1:1-1000 with the weight ratio of taurine,
As it is further preferred that the weight ratio of cucurbitacin and taurine is 1:5-100.
When a kind of combination medicine for anti-curing oncoma provided by the present invention is by cucurbitacin, coenzyme Q10 and taurine
During composition, the weight ratio of cucurbitacin, coenzyme Q10 and taurine is 1:0.1-1000:0.1-1000, as preferably, cucurbitacin,
The weight ratio of coenzyme Q10 and taurine is 1:1-1000: 1-1000, as it is further preferred that cucurbitacin, coenzyme Q10 and cattle
The weight ratio of sulfonic acid is 1:5-100: 5-100.
A kind of combination medicine for anti-curing oncoma provided by the present invention, wherein cucurbitacin include cucurbitacin A, B, C,
D, E, I, Q, S, double hydrogen cucurbitacin A, B, C, D, E, I, Q, S and isocucurbitacin A, B, C, D, E, I, Q, S, various cucurbitacins are corresponding
More than the one or two kinds of in glucoside material.
The medical usage of a kind of combination medicine for anti-curing oncoma provided by the present invention, described swollen for preventing and treating
The combination medicine of tumor jointly with pharmaceutically acceptable carrier or can be respectively prepared tablet, capsule, granule, dissipate
Agent, patch, ointment, suspensoid, syrup, oral liquid, patch, aerosol, suppository, nasal drop or injection, and accordingly
Controlled release agent；Clathrate, liposome, microsphere, nanoparticle or Emulsion can also be made, for cavity/canal drug administration, external, oral,
Injection.
The medical usage of a kind of combination medicine for anti-curing oncoma provided by the present invention, it is characterised in that described
The amount of each component in the combination medicine of anti-curing oncoma, with Mouse oral dosage calculate: cucurbitacin is as 0.001-
15 mg/kg, as preferably, cucurbitacin is 0.01-10 mg/kg, as it is further preferred that cucurbitacin is 0.1-5 mg/kg；Coenzyme
Q10 is 1-15 000 mg/kg, and as preferably, coenzyme Q10 is 5-10000 mg/kg, as it is further preferred that coenzyme Q10 is 50-1
000 mg/kg；Taurine is 1-2000 mg/kg, and as preferably, taurine is 10-1000mg/kg, as it is further preferred that cattle sulphur
Acid is 50-1000 mg/kg, point 1 time-4 times administrations.
The medical usage of a kind of combination medicine for anti-curing oncoma provided by the present invention, it is characterised in that described
The amount of each component in the combination medicine of anti-curing oncoma, with health adult's Rapid Dose Calculation: cucurbitacin is as 0.01-10mg/
D, as preferably, cucurbitacin is 0.1-8mg/kg, as it is further preferred that cucurbitacin is 0.3-3mg/kg；Coenzyme Q10 is 1-3000
Mg/d, as preferably, coenzyme Q10 is 10-2000 mg/kg, as it is further preferred that coenzyme Q10 is 30-1500 mg/kg；Taurine
For 1-3000 mg/d, as preferably, taurine is 10-2000 mg/kg, as it is further preferred that taurine is 50-1500 mg/
kg；Divide 1 time-4 times and be administered.
Should be appreciated that a kind of use for the combination medicine of anti-curing oncoma of the present invention includes following two side
Formula:
One is that a kind of combination medicine for anti-curing oncoma of the present invention is respectively prepared single preparation, two kinds
The dosage form of preparation can be identical, it is also possible to different, can use successively in use, it is also possible to take simultaneously.When being administered successively,
Before when giving n component, n-1 kind (n=3) component should also not lose its useful effect in vivo.
Two is that a kind of combination medicine for anti-curing oncoma of the present invention is made single compound preparation, uses
Time take simultaneously.
The invention have the advantage that the present invention has preferable curative effect for the treatment of tumor, it may also be used for the prevention of tumor, can
Treatment for chronic hepatitis.Keeping and improving while antitumor drug curative effect, reduce treatment cost, extend applicable
Crowd, toxicity is little, improve compliance and toleration.
Curative effect is preferable, does not has chemotherapy and radiocurable toxic and side effects.
Detailed description of the invention
For the understanding present invention more removed, the technical scheme under this invention be given below in conjunction with inventor is completed
The present invention is described in further detail for embodiment.
The following is the embodiment that the present inventor provides, the invention is not limited in these embodiments, the present invention is done
Any pro forma accommodation and/or change fall within scope.
In the present invention, if not refering in particular to, described cucurbitacin includes cucurbitacin A, B, C, D, E, I, Q, S, double hydrogen cucurbitacin A,
B, C, D, E, I, Q, S and isocucurbitacin A, B, C, D, E, I, Q, S, one in the glucoside material that various cucurbitacins are corresponding or
Two or more.All of equipment and raw material etc. are all commercially available or the industry is conventional.
Embodiment 1: Cucurbitacin B (CuB) combines the research of anti-S180 function of tumor with coenzyme Q10 (Q10)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, S180 tumor is inoculated in right fore oxter, treats that tumor mass grows into greatly
In 50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuB:B (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: CuB Emulsion, B+Q multiple emulsion
Matched group: normal saline group
Experimental group: CuB group, CuB+Q10 group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: CuB group, the tumour inhibiting rate of CuB+Q10 group are respectively 48.6%, 56.8%.
Compared with CuB group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows obvious toxic and side effects.
Embodiment 2: Cucurbitacin B (CuB) combines the research of anti-S180 function of tumor with taurine (T)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, S180 tumor is inoculated in right fore oxter, treats that tumor mass grows into greatly
In 50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuB:5 mg/kg
T:300 mg/kg
Administering mode: CuB Emulsion, CuB+T multiple emulsion
Matched group: normal saline group
Experimental group: CuB Emulsion group, CuB+T multiple emulsion group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: the tumour inhibiting rate of CuB Emulsion group and CuB+T multiple emulsion group is respectively 48.6% and 54.5%.
Compared with CuB Emulsion group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows significantly poison secondary
Effect.
Embodiment 3: Cucurbitacin B (CuB) combines the research of anti-H22 function of tumor with coenzyme Q10 (Q10)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, H22 tumor is inoculated in right fore oxter, treats that tumor mass grows into and is more than
50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuB:B (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: CuB Emulsion, B+Q multiple emulsion
Matched group: normal saline group
Experimental group: CuB group, CuB+Q10 group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: CuB group, the tumour inhibiting rate of CuB+Q10 group are respectively 43.5%, 53.6%.
Compared with CuB group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows obvious toxic and side effects.
Embodiment 4: Cucurbitacin B (CuB) combines the research of anti-H22 function of tumor with taurine (T)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, H22 tumor is inoculated in right fore oxter, treats that tumor mass grows into and is more than
50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuB:5 mg/kg
T:300 mg/kg
Administering mode: CuB Emulsion, CuB+T multiple emulsion
Matched group: normal saline group
Experimental group: CuB Emulsion group, CuB+T multiple emulsion group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: the tumour inhibiting rate of CuB Emulsion group and CuB+T multiple emulsion group is respectively 43.5% and 55.2%.
Compared with CuB Emulsion group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows significantly poison secondary
Effect.
Embodiment 5: cucurbatacin E (CuE) combines the research of anti-S180 function of tumor with coenzyme Q10 (Q10)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, S180 tumor is inoculated in right fore oxter, treats that tumor mass grows into greatly
In 50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuE:E (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: CuE Emulsion, E+Q multiple emulsion
Matched group: normal saline group
Experimental group: CuE group, CuE+Q10 group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: CuE group, the tumour inhibiting rate of CuE+Q10 group are respectively 44.5%, 53.6%.
Compared with CuE group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows obvious toxic and side effects.
Embodiment 6: cucurbatacin E (CuE) combines the research of anti-S180 function of tumor with taurine (T)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, S180 tumor is inoculated in right fore oxter, treats that tumor mass grows into greatly
In 50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuE:5 mg/kg
T:300 mg/kg
Administering mode: CuE Emulsion, CuE+T multiple emulsion
Matched group: normal saline group
Experimental group: CuE Emulsion group, CuE+T multiple emulsion group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: the tumour inhibiting rate of CuE Emulsion group and CuE+T multiple emulsion group is respectively 44.5% and 54.1%.
Compared with CuE Emulsion group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows significantly poison secondary
Effect.
Embodiment 7: cucurbitacin I (CuI) combines the research of anti-H22 function of tumor with coenzyme Q10 (Q10)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, H22 tumor is inoculated in right fore oxter, treats that tumor mass grows into and is more than
50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuI:I (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: CuI Emulsion, B+Q multiple emulsion
Matched group: normal saline group
Experimental group: CuI group, CuI+Q10 group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: CuI group, the tumour inhibiting rate of CuI+Q10 group are respectively 42.9%, 51.8%.
Compared with CuI group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows obvious toxic and side effects.
Embodiment 8: cucurbitacin D (CuD) combines the research of anti-H22 function of tumor with taurine (T)
Experimental program:
Taking Kun Ming mice, body weight 18～22 grams, male, H22 tumor is inoculated in right fore oxter, treats that tumor mass grows into and is more than
50 mm2Time, it is randomly divided into 3 groups, often group 10, each group gastric infusion respectively, scheme is as follows:
Dosage: CuD:5 mg/kg
T:300 mg/kg
Administering mode: CuD Emulsion, CuD+T multiple emulsion
Matched group: normal saline group
Experimental group: CuD Emulsion group, CuD+T multiple emulsion group
Successive administration 14 days, in being administered latter 24 hours for the last time, puts to death animal, takes tumor and weigh, calculate tumour inhibiting rate.
Result: the tumour inhibiting rate of CuD Emulsion group and CuD+T multiple emulsion group is respectively 45.7% and 56.4%.
Compared with CuD Emulsion group, administering drug combinations group tumour inhibiting rate is higher, and mice is in good condition, does not shows significantly poison secondary
Effect.
Embodiment 9: Cucurbitacin B (CuB) is studied with coenzyme Q10 Bio-prevention S180 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate S180 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuB:B (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: B+Q multiple emulsion
Matched group: normal saline group
Experimental group: B+Q group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 14.0cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of B+Q multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.0cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, Cucurbitacin B (CuB) and coenzyme Q10 administering drug combinations, can substantially suppress generation and the growth of S180 tumor.
Embodiment 10: Cucurbitacin B (CuB) is studied with taurine (T) Bio-prevention S180 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate S180 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuB:B (5 mg/kg)
Taurine: T(300 mg/kg)
Administering mode: B+T multiple emulsion
Matched group: normal saline group
Experimental group: B+T group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 14.0cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of B+T multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.0cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, Cucurbitacin B (CuB) and taurine administering drug combinations, can substantially suppress generation and the growth of S180 tumor.
Embodiment 11: Cucurbitacin B (CuB) is studied with coenzyme Q10 Bio-prevention H22 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate H22 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuB:B (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: B+Q multiple emulsion
Matched group: normal saline group
Experimental group: B+Q group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 12.5cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of B+Q multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.5cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, Cucurbitacin B (CuB) and coenzyme Q10 administering drug combinations, can substantially suppress generation and the growth of H22 tumor.
Embodiment 12: Cucurbitacin B (CuB) is studied with taurine (T) Bio-prevention H22 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate H22 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuB:B (5 mg/kg)
Taurine: T(300 mg/kg)
Administering mode: B+T multiple emulsion
Matched group: normal saline group
Experimental group: B+T group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 12.5cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of B+T multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.0cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, Cucurbitacin B (CuB) and taurine administering drug combinations, can substantially suppress generation and the growth of H22 tumor.
Embodiment 13: cucurbatacin E (CuE) is studied with coenzyme Q10 Bio-prevention S180 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate S180 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuE:E (5mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: E+Q multiple emulsion
Matched group: normal saline group
Experimental group: E+Q group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 12.0cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of E+Q multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.0cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, cucurbatacin E (CuE) and coenzyme Q10 administering drug combinations, can substantially suppress generation and the growth of S180 tumor.
Embodiment 14: cucurbitacin I (CuI) studies with taurine (T) Bio-prevention S180 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate S180 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuI:I (5 mg/kg)
Taurine: T(300 mg/kg)
Administering mode: I+T multiple emulsion
Matched group: normal saline group
Experimental group: I+T group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 13.0cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of I+T multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.0cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, cucurbitacin I (CuI) and taurine administering drug combinations, can substantially suppress generation and the growth of S180 tumor.
Embodiment 15: cucurbitacin D (CuD) studies with coenzyme Q10 Bio-prevention H22 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate H22 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuD:D (5 mg/kg)
Q10: Q ( 50 mg/kg)
Administering mode: D+Q multiple emulsion
Matched group: normal saline group
Experimental group: D+Q group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 13.5cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of D+Q multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.5cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, cucurbitacin D (CuD) and coenzyme Q10 administering drug combinations, can substantially suppress generation and the growth of H22 tumor.
Embodiment 16: cucurbitacin D (CuD) studies with taurine (T) Bio-prevention H22 function of tumor
Experimental program:
Take Kun Ming mice, body weight 12～16 grams, male, be randomly divided into 2 groups, often group 10, respectively organize respectively gavage to
Medicine, continuous 14 days, after in right fore oxter inoculate H22 tumor, the most normally raise, observed and recorded tumor situation of change.
Dosage regimen is as follows:
Dosage: CuD:D (5 mg/kg)
Taurine: T(300 mg/kg)
Administering mode: D+T multiple emulsion
Matched group: normal saline group
Experimental group: D+T group
Result: normal saline group tumor growth is rapid, connects after tumor 14 days, and mean tumor volume has reached 13.5cm2Left and right, place
Post mortem is observed, and find to have gathered on mouse liver speckle, it is seen that tumor large area spreads.Swelling of D+T multiple emulsion group
Tumor poor growth, mean tumor volume reaches 1.0cm2Time, tumor starts necrosis, when connecing after tumor 21 days, and complete tumor necrosis, 30 days
Left and right, " neoplasm necrosis tissue " comes off, presents " without hair " neoplastic skin, the tissue that similar wound is newborn after healing completely.
As can be seen here, cucurbitacin D (CuD) and taurine administering drug combinations, can substantially suppress generation and the growth of H22 tumor.
Embodiment 17: cucurbitacin, the preparation of coenzyme Q10 capsule
Prescription is as follows:
Cucurbitacin 100 mg
Coenzyme Q10 50g
F68 50g
Microcrystalline Cellulose 400g
1000
Technique:
Each component is weighed by prescription, fully after mixing, No. 1 capsule of fill 1000.
Embodiment 18: cucurbitacin, the preparation of coenzyme Q10 tablet
Prescription is as follows:
Cucurbitacin 100 mg
Coenzyme Q10 50g
Lactose 100g
Starch 110 g
PVP 10g
Magnesium stearate 10g
1000
Technique:
Weigh the cucurbitacin of recipe quantity, coenzyme Q10, lactose, after mix homogeneously, add 10% shallow lake that 110g starch is made
Slurry, spray granulation.It is pressed into 1000 after adding PVP 10g magnesium stearate 10g mix homogeneously.
Embodiment 19: cucurbitacin, the preparation of taurine capsule
Prescription is as follows:
Cucurbitacin 100 mg
Taurine 50g
F68 50g
Microcrystalline Cellulose 400g
1000
Technique:
Each component is weighed by prescription, fully after mixing, No. 1 capsule of fill 1000.
Embodiment 20: cucurbitacin, the preparation of taurine tablet
Prescription is as follows:
Cucurbitacin 100 mg
Taurine 50g
Lactose 100g
Starch 110g
PVP 20g
Pulvis Talci 20g
1000
Technique:
Weigh the cucurbitacin of recipe quantity, taurine, lactose, after mix homogeneously, add 10% shallow lake that 110 g starch are made
Slurry, spray granulation.It is pressed into 1000 after adding PVP 20 g magnesium stearate 20 g mix homogeneously.
Embodiment 21: cucurbitacin, coenzyme Q10, the preparation of taurine capsule
Prescription is as follows:
Cucurbitacin 100 mg
Coenzyme Q10 50g
Taurine 50g
F68 50g
Microcrystalline Cellulose 350g
1000
Technique:
Each component is weighed by prescription, fully after mixing, No. 1 capsule of fill 1000.
Embodiment 22: cucurbitacin, coenzyme Q10, the preparation of taurine tablet
Prescription is as follows:
Cucurbitacin 100 mg
Coenzyme Q10 50g
Taurine 50g
Lactose 100g
Starch 110g
PVP 10g
Magnesium stearate 10g
1000
Technique:
Weigh the cucurbitacin of recipe quantity, coenzyme Q10, taurine, lactose, after mix homogeneously, add 110 g starch systems
10% starch slurry become, spray granulation.Add PVP 10 g, magnesium stearate 10 g, after mix homogeneously, be pressed into 1000.
Embodiment 23: cucurbitacin, the preparation of coenzyme Q10 multiple emulsion
Prescription is as follows:
Cucurbitacin 15 mg
Coenzyme Q10 150 mg
SPC 300 mg
RH40 600 mg
MCT 3000 mg
Glycerol 300 mg
Distilled water is appropriate
30 mL
Technique: weigh recipe quantity cucurbitacin, coenzyme Q10, MCT, SPC, RH40 form oil phase；Weigh recipe quantity glycerol,
Distilled water forms aqueous phase, is separately heated to 50 ~ 55 DEG C by biphase.After in oil phase, material is completely dissolved, in magnetic agitation
Under the conditions of, aqueous phase is slowly added in oil phase, continues stirring 20 min, prepare colostrum.By colostrum with microjet instrument 14000
Psi, after homogenizing 5 times, with distilled water diluting its to 30 ml, cross 0.22 μm microporous filter membrane, be sub-packed in cillin bottle, inflated with nitrogen,
Jumping a queue, add aluminium lid and seal, 100 DEG C of flowing steam sterilization 30 min, cold water spray makes emulsion be rapidly decreased to room temperature, gets product.
Embodiment 24: cucurbitacin, the preparation of taurine multiple emulsion
Prescription is as follows:
Cucurbitacin 9 mg
Taurine 300 mg
SPC 300 mg
RH40 600 mg
MCT 3000 mg
Glycerol 300 mg
Distilled water is appropriate
30 mL
Technique: weigh recipe quantity cucurbitacin, MCT, SPC, RH40 form oil phase；Weigh recipe quantity glycerol, taurine, steaming
Distilled water forms aqueous phase, is separately heated to 50 ~ 55 DEG C by biphase.After in oil phase, aqueous phase, material is completely dissolved, in magnetic agitation
Under conditions of, aqueous phase is slowly added in oil phase, continues stirring 20 min, prepare colostrum.Colostrum microjet instrument is existed
14000 psi, after homogenizing 5 times, with distilled water diluting its to 30 ml, cross 0.22 μm microporous filter membrane, be sub-packed in cillin bottle, fill
Nitrogen, jumps a queue, and adds aluminium lid and seals, 100 DEG C of flowing steam sterilization 30 min, and cold water spray makes emulsion be rapidly decreased to room temperature, to obtain final product
Finished product.
Embodiment 25: cucurbitacin, coenzyme Q10, the preparation of taurine multiple emulsion
Prescription is as follows:
Cucurbitacin 9 mg
Coenzyme Q10 150 mg
Taurine 300 mg
SPC 300 mg
RH40 600 mg
MCT 3000 mg
Glycerol 300 mg
Distilled water is appropriate
30 mL
Technique: weigh recipe quantity cucurbitacin, coenzyme Q10, MCT, SPC, RH40 form oil phase；Weigh recipe quantity glycerol,
Taurine, distilled water form aqueous phase, is separately heated to 50 ~ 55 DEG C by biphase.After biphase middle material is completely dissolved, at magnetic force
Under conditions of stirring, aqueous phase is slowly added in oil phase, continues stirring 20 min, prepare colostrum.Colostrum is used microjet instrument
At 14000 psi, after homogenizing 5 times, with distilled water diluting its to 30 ml, cross 0.22 μm microporous filter membrane, be sub-packed in cillin bottle,
Inflated with nitrogen, jumps a queue, and adds aluminium lid and seals, 100 DEG C of flowing steam sterilization 30 min, and cold water spray makes emulsion be rapidly decreased to room temperature, i.e.
Obtain finished product.
Beneficial effects of the present invention is proved further below by way of pharmacodynamics embodiment.
Use example below by way of clinical patients, further prove beneficial effects of the present invention.
Embodiment 26: primary hepatocarcinoma
Open xx, man, 43 years old, check in Affiliated Hospital of Xxx medical university in May, 2010 and be diagnosed as primary hepatocarcinoma, (CT
Inspection result shows: multiple occupy-place in liver, and left and right page is shown in multiple low echo occupy-place of differing in size, lobus dexter maximum occupy-place 4.7*
3.8cm, gollbladder dilation), take conventional chemotherapy medicine May, without positive effect, 10 the end of month in 2010 start to take cucurbitacin liquid simultaneously
(Shanghai Pharmaceutical Group company limited letter friendship pharmacy head factory produces for body capsule (production of Jin Hai pharmaceutical factory of Macao), coenzyme Q10 capsule
), to adhere to that taking March checks once, simultaneously it is noted that diet, carry out third time at local hospital after half a year and check, CT report is aobvious
Showing: liver is little, form is normal, and leaf low echo occupy-place in left and right reduces, wherein maximum 4.5*3.4cm, gollbladder dilation.By before
CT report contrast finds, being obviously reduced before right lobe of liver maximum occupy-place relatively, little occupy-place has reduced, the most always
Taking cucurbitacin liquid capsule and coenzyme Q10 capsule, up to the present, weight in patients too increases 8 jin, and the mental status is good,
Through returning to unit working.
Claims (4)
- The combination medicine of the most anti-curing oncoma, is prepared as cucurbitacin and coenzyme Q10 combining use for treat and prevent tumor Medicine, cucurbitacin is 1:0.1-10000 with the weight ratio of coenzyme Q10, and wherein cucurbitacin is cucurbitacin A, B, C, D, E, I, Q, S, More than the one or two kinds of in double hydrogen cucurbitacin A, B, C, D, E, I, Q, S and isocucurbitacin A, B, C, D, E, I, Q, S.
- 2. the combination medicine of the anti-curing oncoma described in claim 1, it is characterised in that: the combination medicine of described anti-curing oncoma Jointly or tablet, capsule, granule, powder, patch, ointment can be respectively prepared with pharmaceutically acceptable carrier Agent, suspensoid, syrup, oral liquid, patch, aerosol, suppository, nasal drop or injection, and corresponding controlled release agent；Also Clathrate, liposome, microsphere, nanoparticle or Emulsion can be made, for cavity/canal drug administration, external, oral, injection.
- The combination medicine of anti-curing oncoma the most as claimed in claim 1, it is characterised in that: described anti-curing oncoma combine use The amount of each component in medicine, calculates with Mouse oral dosage: cucurbitacin is 0.001-15 mg/kg, and coenzyme Q10 is 5-15 000 mg/kg, point 1 time-4 times administrations；With health adult's Rapid Dose Calculation: cucurbitacin is 0.1-10 mg/d, coenzyme Q10 is 10- 300 mg/d, point 1 time-4 times administrations.
- The combination medicine of anti-curing oncoma the most as claimed in claim 1, it is characterised in that: described medicine can be also used for system The medicine of standby treatment chronic hepatitis.
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