CN103800342B - Composition with reduced toxicity of cucurbitacin and medical application thereof - Google Patents
Composition with reduced toxicity of cucurbitacin and medical application thereof Download PDFInfo
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- CN103800342B CN103800342B CN201210456230.XA CN201210456230A CN103800342B CN 103800342 B CN103800342 B CN 103800342B CN 201210456230 A CN201210456230 A CN 201210456230A CN 103800342 B CN103800342 B CN 103800342B
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Abstract
The invention discloses a composition with reduced toxicity of cucurbitacin and medical application thereof. The composition comprises cucurbitacin and at least one of coenzyme Q10 and taurine. In case that the composition comprises cucurbitacin and coenzyme Q10, the weight ratio of cucurbitacin to coenzyme Q10 is 1:(0.1-100,000); in case that the composition comprises cucurbitacin and taurine, the weight ratio of cucurbitacin to taurine is 1:(1-10,000); in case that the composition comprises cucurbitacin, coenzyme Q10 and taurine, the weight ratio of cucurbitacin to coenzyme Q10 to taurine is 1:(0.1-100,000):(0.1-100,000). The composition can be clinically used for treating chronic hepatitis, and can also be used for preventing and treating cancer.
Description
Technical field
The invention belongs to pharmaceutical technology field, a kind of compositionss reducing cucurbitacin toxicity and its medical usage are disclosed.
Background technology
Cucurbitacine（Cucurbitacins）Composition is the highly oxidized tetracyclic triterpenes of a class extracting from plant
Compound, has been found that kind more than 40 so far.Ancient Times in China just adopts Chinese medicine muskmelon pedicel, treats jaundice, and the emetic, eliminating the phlegm of energy, is used for
Sputum dyspepsia, Pedicellus Melo once recorded by legendary god of farming's book on Chinese herbal medicine, and to eliminate water wet, eliminates diseases due to noxious agents produced by various parasites, under making inducing vomiting, rushing down, for treating serious water
Heresy, four limbs edema, cough and asthma, and eat poisonous substance by mistake, it is stopped at gastral cavilty not yet absorber it can be seen that cucurbitacine medicine is at me
State, the history cured the sickness to save the patient long.This constituents majority is present in cucurbitaceous plant, partly exists in other plants.
At present, the cucurbitacin that China's approval produces is Cucurbitacine again, is Chinese medicine muskmelon pedicel (another name：Pedicellus Melo) extract, mainly contain
The compositions such as Cucurbitacin B, E, in existing extract, Cucurbitacin B content is more than 60%, and its quality standard records to be issued in portion of China
In standard.There are the multiple biological activities such as antitumor, anti-chemocarcinogenesiss, liver protection, enhance immunity.
In vitro tests shows that CuBE has very strong cell toxicant to KB cell (KB) and human cervical carcinoma cell (HeLa)
Effect, its median effective dose (ED50) is 0.005～0.01 μ g/mL, and liver, the cerebral tumor and malignant melanoma are also had
Stronger inhibitory action.Some scholar's research CuBE find to during the sensitivity of human mouth scale cancer (Tca8113, BcaCD885),
CuBE has stronger lethal effect to human mouth squamous cell carcinoma.Zoopery shows CuBE（0.5 mg/kg, ip）To sarcoma 180
There is good therapeutic effect with Ehrlich ascites carcinoma, have obvious inhibitory action to murine sarcoma 37 and murine hepatocarcinoma cell, and right
Rat Walkler cancer and Mouse With Lewis Lung Cancer have good therapeutic effect.CuBE is made nanoparticle by Yang Kai etc. in recent years, and treatment is little
The oral cancer Cervical Lymph Node Metastasis animal model that Mus cervical carcinomal U14 is set up, achieves good anticancer effect.Clinical test results
Show that CuBE is used for treating hepatocarcinoma, preferable to the curative effect of early stage, mid-term hepatocarcinoma, simple type total effective rate is 80 %, obvious effective rate 66
%；Atherosclerotic type total effective rate 65 %, obvious effective rate 28 %.Anti- chemical carcinogenesis test result indicate that, benzopyrene is in cellular metabolism
In can produce carcinogen, and the CuBE of low dose can to significantly inhibit benzene be 9 than the metabolite of pyrene, 10- glycol-B (a) P and
The generation of 9- hydroxyl-B (a) P, thus suppressing the formation of ultimate carcinogenss matter, plays anti-chemical carcinogenesis.
Research display CuB is abroad had to have the active anticancer more higher than positive control drug amycin, and to people's colon, breast
The cancerous cell of gland, liver and central nervous system all shows growth inhibition effect the strongest.There is researcher from Cucurbita
Extract CuB, D, E and I monomer in andreana fruit, and have rated these compounds respectively to people's colon（HCT-116）, breast
Gland（MCF-7）, lung（NCI-H460）And central nervous system（CNS）（SF-268）The inhibitory action of growth of cancer cells, by result
Understand, CuB all shows the growth stronger than similar compound to the cancerous cell of people's colon, mammary gland, liver and central nervous system
Inhibitory action.It can be seen that the active anticancer of CuB is worth further and studying and applies.
Although extensively, its toxicity is also larger, and after taking cucurbitacin, some cases can cause for the pharmacological action of cucurbitacin
The gastrointestinal reactions such as abdominal discomfort, nausea, laxativeness, minority case may occur in which of short duration xerostomia, giddy.During heavy dose of use,
Severe anemia, frequently vomit leaf and diarrhoea can be caused, in addition breathing, circulatory failure and dead.
Therefore, how while keeping and improve cucurbitacin curative effect, reduce its treatment cost, the applicable crowd of extension, subtract
Little toxicity, raising compliance and toleration etc. are the emphasis of cucurbitacine medicament research and development.
Coenzyme Q compounds in distributed in nature extensively, are present in many animals, plant and microorganism, send out at present
Existing coenzyme Q kind includes CoQ1 to CoQ1 3.Most in human body is coenzyme Q10, nineteen fifty-seven, Britain Morton professor from
Obtain coenzyme Q10 with separating in the rat liver of hypovitaminosis A, and be referred to as ubiquinone.
The iso-amylene structure of the quinoid structure of coenzyme Q10 and side chain, determines 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 required for cells survival 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 significant auxiliary treatment.
Taurine, also known as 2-aminoethyl sulfonic acid, is separated by Calculus Boviss earliest, therefore gains the name.It is a kind of nonprotein
Aminoacid, is not involved in the biosynthesiss of vivo protein, but closely related with the metabolism of cystine, cysteine.Its physiology
Function extensively, mainly has promotion infant brain tissue and intelligent development, improves nerve conduction and visual function, suppresses platelet to coagulate
Collection, reduction blood fat, keep human normal blood pressure, prevent arteriosclerosis, arrhythmia, reduce blood cholesterol level, control
Treat heart failure, the absorption of impact lipid, improve endocrinosity, strengthen human body specificity and non-specific immunity, no
Depend on increase the hypoglycemic activity of insulin, suppression is cataractous develops, improve the function of remembering, calmness, ease pain, disappear
Inflammation etc. acts on.
At present although there being document report, Sodium Acetate Trihydrate, glucose, vitamin C cause to B, E mixture minimum lethal dose
Dead mouse has obvious protective function, and that is, Sodium Acetate Trihydrate, glucose, vitamin C can reduce the poison pair of cucurbitacin to a certain extent
Effect, but not yet have and cucurbitacin is used in combination with coenzyme Q10 and/or taurine, reduce and use while cucurbitacin toxic and side effects
In the prevention of cancer and/or the auxiliary treatment for the treatment of and chronic persistent hepatitises.
Content of the invention：
Based on above-mentioned, it is proposed that the purpose of the present invention, that is, provide a kind of compositionss reducing cucurbitacin toxicity and its doctor
Medicinal way.
A kind of compositionss reducing cucurbitacin toxicity provided by the present invention are by cucurbitacin and coenzyme Q10 and/or cattle sulphur
Acid composition.
When a kind of compositionss reducing cucurbitacin toxicity provided by the present invention are made up of with coenzyme Q10 cucurbitacin,
The weight of cucurbitacin and coenzyme Q10 is than for 1:0.1-100000, preferably, the weight of cucurbitacin and coenzyme Q10 is than for 1:
1-10000, as it is further preferred that the weight of cucurbitacin and coenzyme Q10 is than for 1: 5-1000.
When a kind of compositionss reducing cucurbitacin toxicity provided by the present invention are made up of with taurine cucurbitacin, calabash
Element and the weight of taurine ratio is for 1:0.1-100000, preferably, the weight of cucurbitacin and taurine is than for 1:1-10000,
As it is further preferred that the weight of cucurbitacin and taurine is than for 1: 5-1000.
When a kind of combination reducing cucurbitacin toxicity provided by the present invention is made up of cucurbitacin, coenzyme Q10 and taurine
When, the weight of cucurbitacin, coenzyme Q10 and taurine is than for 1:0.1-100000:0.1-100000, preferably, cucurbitacin,
The weight of coenzyme Q10 and taurine is than for 1: 1-10000 :1-10000, as it is further preferred that cucurbitacin, coenzyme Q10 and
The weight of taurine is than for 1: 5-1000 : 5-1000.
Provided by the present invention a kind of reduce cucurbitacin toxicity compositionss, 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, the corresponding sugar of various cucurbitacin
One of glycoside material or two or more.
A kind of medical usage of compositionss reducing cucurbitacin toxicity provided by the present invention is it is characterised in that described use
In reduce cucurbitacin toxicity combination can common with pharmaceutically acceptable carrier or be respectively prepared tablet, capsule,
Granule, powder, patch, ointment, suspensoid, syrup, oral liquid, patch, aerosol, suppository, nasal drop or injection,
And its corresponding controlled release agent；Clathrate, liposome, microsphere, nanoparticle or Emulsion can also be made, for cavity/canal drug administration, outward
With, oral, injection.
A kind of medical usage of compositionss reducing cucurbitacin toxicity provided by the present invention is it is characterised in that described
For reducing the amount of each component in the combination of cucurbitacin toxicity, calculated with Mouse oral dosage：Cucurbitacin is 0.0001-15
Mg/kg, preferably, cucurbitacin is 0.001-10 mg/kg, as it is further preferred that cucurbitacin is 0.01-5 mg/kg；Coenzyme
Q10 is 1-15 000 mg/kg, preferably, coenzyme Q10 is 5-10 000 mg/kg, as it is further preferred that coenzyme Q10 is 50-1
000 mg/kg；Taurine be 1-20 000 mg/kg, preferably, taurine be 10-10 000 mg/kg, as it is further preferred that
Taurine is 50-1000 mg/kg, point 1 time -4 times administrations.
A kind of medical usage of compositionss reducing cucurbitacin toxicity provided by the present invention is it is characterised in that described
For reducing the amount of each component in the combination of cucurbitacin toxicity, with health adult's Rapid Dose Calculation：Cucurbitacin is 0.01-10mg/d,
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, preferably, coenzyme Q10 is 10-2000 mg/kg, as it is further preferred that coenzyme Q10 is 30-1500 mg/kg；Taurine is
1-3000 mg/d, preferably, taurine is 10-2000 mg/kg, as it is further preferred that taurine is 50-1500 mg/kg；
Divide 1 time -4 times administrations.
A kind of medical usage of compositionss reducing cucurbitacin toxicity provided by the present invention is it is characterised in that be used for slow
The treatment of property hepatitis.
A kind of medical usage of compositionss reducing cucurbitacin toxicity provided by the present invention is it is characterised in that be used for swelling
The prevention of tumor.
A kind of medical usage of compositionss reducing cucurbitacin toxicity provided by the present invention is it is characterised in that be used for swelling
The treatment of tumor.
It should be appreciated that using of a kind of compositionss reducing cucurbitacin toxicity of the present invention includes following two modes：
One is that a kind of compositionss reducing cucurbitacin toxicity of the present invention are respectively prepared single preparation, two kinds of systems
The dosage form of agent can identical it is also possible to different, can be successively using it is also possible to take simultaneously when using.When being administered successively, give
Give n-1 kind before n group timesharing（n=3）Component should also not lose its useful effect in vivo.
Two is a kind of compositionss reducing cucurbitacin toxicity of the present invention to be made single compound preparation, during use
Take simultaneously.
It is an advantage of the invention that：Cucurbitacin is used in combination with coenzyme Q10 and/or taurine, is reducing the secondary work of cucurbitacin poison
With while can be used for the prevention of cancer and/or the auxiliary treatment for the treatment of and chronic persistent hepatitises.
Brief description
The average weight variation tendency of mice after Fig. 1 B+Q1 group and B+Q2 group and matched group administration；
The average weight variation tendency of mice after Fig. 2 B+T1 group, B+T2 group and B+T3 group and matched group administration；
The average weight variation tendency of mice after Fig. 3 B+Q+T1 group, B+Q+T2 group and B+Q+T3 group and comparison administration；
Fig. 4 B+Q+T1, B+Q+T2 and B+Q+T3 group administration after and matched group administration after each group CuB " apparent median lethal
Amount " compares B cucurbitacin, Q coenzyme Q10, T taurine.
Specific embodiment
For the understanding present invention of more removing, completed below in conjunction with the technical scheme under this invention that inventor is given
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 flexible and/or change falls within the scope of the present invention.
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 of corresponding glucoside material of various cucurbitacin or
Two or more.All of equipment and raw material etc. be all commercially available or the industry commonly use.Embodiment 1：Cucurbitacin, coenzyme
The preparation of Q10 capsule
Prescription is as follows：
Cucurbitacin 100mg
Coenzyme Q10 50g
F68 50g
Microcrystalline Cellulose 400g
1000
Technique：
Weigh each component by prescription, after fully mixing, No. 1 capsule of fill 1000.
Embodiment 2：Cucurbitacin, the preparation of coenzyme Q10 tablet
Prescription is as follows：
Cucurbitacin 100mg
Coenzyme Q10 50g
Lactose 100g
Starch 110g
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 3：Cucurbitacin, the preparation of taurine capsule
Prescription is as follows：
Cucurbitacin 100mg
Taurine 50g
F68 50g
Microcrystalline Cellulose 400g
1000
Technique：
Weigh each component by prescription, after fully mixing, No. 1 capsule of fill 1000.
Embodiment 4：Cucurbitacin, the preparation of taurine tablet
Prescription is as follows：
Cucurbitacin 100mg
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 5：Cucurbitacin, coenzyme Q10, the preparation of taurine capsule
Prescription is as follows：
Cucurbitacin 100mg
Coenzyme Q10 50g
Taurine 50g
F68 50g
Microcrystalline Cellulose 350g
1000
Technique：
Weigh each component by prescription, after fully mixing, No. 1 capsule of fill 1000.
Embodiment 6：Cucurbitacin, coenzyme Q10, the preparation of taurine tablet
Prescription is as follows：
Cucurbitacin 100mg
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 becoming, spray granulation.Add PVP 10 g, magnesium stearate 10 g, after mix homogeneously, be pressed into 1000.
Embodiment 7：Cucurbitacin, the preparation of coenzyme Q10 multiple emulsion
Prescription is as follows：
Cucurbitacin 15mg
Coenzyme Q10 150mg
SPC 300mg
RH40 600mg
MCT 3000mg
Glycerol 300mg
Distillation appropriate amount of water
30mL
Technique：Weigh recipe quantity cucurbitacin, coenzyme Q10, MCT, SPC, RH40 composition oil phase；Weigh recipe quantity glycerol,
Form aqueous phase in distilled water, be 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, prepared colostrum.By colostrum with microjet instrument 14000
Psi, after homogenizing 5 times, with distilled water diluting its to 30 ml, cross 0.22 μm of microporous filter membrane, be sub-packed in cillin bottle, inflated with nitrogen,
Jump a queue, plus aluminium lid sealing, 100 DEG C of flowing steam sterilization 30 min, cold water spray makes emulsion be rapidly decreased to room temperature, gets product.
Embodiment 8：Cucurbitacin, the preparation of taurine multiple emulsion
Prescription is as follows：
Cucurbitacin 9mg
Taurine 300mg
SPC 300mg
RH40 600mg
MCT 3000mg
Glycerol 300mg
Distillation appropriate amount of water
30mL
Technique：Weigh recipe quantity cucurbitacin, MCT, SPC, RH40 composition oil phase；Weigh recipe quantity glycerol, taurine, steaming
Form aqueous phase in distilled water, be 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, prepared colostrum.Colostrum is existed with microjet instrument
14000 psi, after homogenizing 5 times, with distilled water diluting its to 30 ml, cross 0.22 μm of microporous filter membrane, be sub-packed in cillin bottle, fill
Nitrogen, jumps a queue, plus aluminium lid sealing, 100 DEG C of flowing steam sterilization 30 min, and cold water spray makes emulsion be rapidly decreased to room temperature, obtains final product
Finished product.
Embodiment 9：Cucurbitacin, coenzyme Q10, the preparation of taurine multiple emulsion
Prescription is as follows：
Cucurbitacin 9mg
Coenzyme Q10 150mg
Taurine 300mg
SPC 300mg
RH40 600mg
MCT 3000mg
Glycerol 300mg
Distillation appropriate amount of water
30mL
Technique：Weigh recipe quantity cucurbitacin, coenzyme Q10, MCT, SPC, RH40 composition oil phase；Weigh recipe quantity glycerol,
Form aqueous phase in taurine, distilled water, be separately heated to 50 ~ 55 DEG C by biphase.After biphase middle material is completely dissolved, in magnetic force
Under conditions of stirring, aqueous phase is slowly added in oil phase, continues stirring 20 min, prepared colostrum.By colostrum microjet instrument
In 14000 psi, after homogenizing 5 times, with distilled water diluting its to 30 ml, cross 0.22 μm of microporous filter membrane, be sub-packed in cillin bottle,
Inflated with nitrogen, jumps a queue, plus aluminium lid sealing, 100 DEG C of flowing steam sterilization 30 min, and cold water spray makes emulsion be rapidly decreased to room temperature, that is,
Obtain finished product.
Prove beneficial effects of the present invention below by way of pharmacodynamicss embodiment further.
Embodiment 10：Coenzyme Q10（It is abbreviated as:Q）Toxicity reduction Effect study to Cucurbitacin B
Take Kun Ming mice, 18～22 grams of body weight, male, random packet, every group 10, each group dosage regimen is as follows：
Dosage：CuB:B(5 mg/kg)
Q10:Q1(50 mg/kg) Q2(100 mg/kg)
Administering mode：B+Q multiple emulsion
Matched group：1.B (5 mg/kg) group
Experimental group:2.B+Q1 group 3.B+Q2 group
Each mice daily according to 0.2ml/10g body weight gastric infusion 1 time, continuous 7 days.
Evaluation index：
1. it is administered mice reaction in latter 1 hour
2. the average weight variation tendency of mice during being administered
Experimental result：
1. it is administered mice reaction in latter 1 hour
CuB group show such as blepharoptosiss, close mesh, rapid breathing, as you were, tremble（Tremble）, temperature decline, gathering
Motionless, movement is slow, body is rolled up into the apparent toxicity such as hedgehog, disequilibrium, and continued 1 hour about.
B+Q1 group and B+Q2 group can show slight toxic and side effects when being administered latter 20 minutes, but recover normal quickly.
2. the average weight variation tendency of mice（Accompanying drawing 1）
Embodiment 11：(Tau is abbreviated as taurine:T) the toxicity reduction Effect study to Cucurbitacin B
Take Kun Ming mice, 18～22 grams of body weight, male, random packet, every group 10, each group dosage regimen is as follows：
Dosage：CuB:B(5 mg/kg)
Tau:T1(300 mg/kg) T2(600 mg/kg) T3(900 mg/kg)
Administering mode：B+T multiple emulsion
Matched group：1. B (5 mg/kg) group
Experimental group:2. B+T1 group 3. B+T2 group 4. B+T3 group
Each mice daily according to 0.2ml/10g body weight gastric infusion 1 time, continuous 7 days.
Evaluation index：
1. it is administered mice reaction in latter 1 hour
2. the average weight variation tendency of mice during being administered（Accompanying drawing 2）
Experimental result：
1. it is administered mice reaction in latter 1 hour
CuB group show such as blepharoptosiss, close mesh, rapid breathing, as you were, tremble（Tremble）, temperature decline, gathering
Motionless, movement is slow, body is rolled up into the apparent toxicity such as hedgehog, disequilibrium, and continued 1 hour about.
B+T1 group, B+T2 group and B+T3 group can show slight toxic and side effects when being administered latter 30 minutes, but recover quickly
Normally.
2. the average weight variation tendency of mice
Embodiment 12：Coenzyme Q10（It is abbreviated as:Q）, (Tau is abbreviated as taurine:T) the toxicity reduction effect to Cucurbitacin B is ground
Study carefully
Take Kun Ming mice, 18～22 grams of body weight, male, random packet, every group 10, each group dosage regimen is as follows：
Dosage：CuB:B(5 mg/kg)
Q10:Q(50 mg/kg)
Tau:T1(300 mg/kg) T2(600 mg/kg) T3(900 mg/kg)
Administering mode：B+Q+T multiple emulsion
Matched group：(1.B 5 mg/kg) group
Experimental group：2.B+Q+T1 group 3. B+Q+T2 group 4. B+Q+T3 group
Each mice daily according to 0.2ml/10g body weight gastric infusion 1 time, continuous 7 days.
Evaluation index：
1. it is administered mice reaction in latter 1 hour
2. the average weight variation tendency of mice during being administered（Accompanying drawing 3）
Experimental result：
1. it is administered mice reaction in latter 1 hour
CuB group show such as blepharoptosiss, close mesh, rapid breathing, as you were, tremble（Tremble）, temperature decline, gathering
Motionless, movement is slow, body is rolled up into the apparent toxicity such as hedgehog, disequilibrium, and continued 1 hour about.
B+Q+T1 group, B+Q+T2 group and B+Q+T3 group can show slight toxic and side effects when being administered latter 20 minutes, but very
Fast recovery is normal.
2. the average weight variation tendency of mice
Embodiment 13：The impact to Mouse oral cucurbitacin " apparent median lethal dose(LD 50) " of coenzyme Q10, taurine
Experimental program：
Take Kun Ming mice, 18～22 grams of body weight, male, random packet, every group 10, each group dosage regimen is as follows：
Initial dosages：CuB:B(5 mg/kg)、Q10: Q (50 mg/kg)
Tau:T1(300 mg/kg) T2(600 mg/kg) T3(900 mg/kg)
Administering mode：B+Q+T multiple emulsion
It is each that with CuB original measurement (5 mg/kg) beginning gastric infusion, often to 7 days, CuB increases the dosage of 2.5mg/kg,
Till dead mouse half.
Matched group：(1.B 5 mg/kg) group
Experimental group：2.B+Q+T1 group 3. B+Q+T2 group 4. B+Q+T3 group
Evaluation index：
1. it is administered mice reaction in latter 1 hour
2. the average weight variation tendency of mice during being administered
The apparent median lethal dose(LD 50) of 3.CuB
Experimental result：
1. it is administered mice reaction in latter 1 hour
CuB group shows such as blepharoptosiss, closes the apparent toxicity such as mesh, rapid breathing, and continues 1 hour left side
Right.
B+Q+T1, B+Q+T2 and B+Q+T3 group can show make secondary compared with the poison that CuB group substantially mitigates when being administered latter 20 minutes
With, and quickly（When 30 minutes）Recover normal.
2. the average weight variation tendency of mice
Increase the couple of days after dosage every time, each group average mice body weight all has different degrees of decline, but
During by the 7th or eight day, average mice body weight can recover normally to increase again, and general trend is to rise.See accompanying drawing 4.
The apparent median lethal dose(LD 50) of 3.CuB compares sees accompanying drawing 4.
Claims (6)
1. a kind of reduce cucurbitacin toxicity compositionss it is characterised in that being made up of cucurbitacin and coenzyme Q10 or taurine, or
It is made up of cucurbitacin, coenzyme Q10 and taurine, when being made up of cucurbitacin and coenzyme Q10, the weight of cucurbitacin and coenzyme Q10
Ratio 1:0.1-100000；When being made up of cucurbitacin and taurine, the weight of cucurbitacin and taurine ratio is for 1: 1-10000；By calabash
When Lu Su, coenzyme Q10 and taurine composition, the weight of cucurbitacin, coenzyme Q10 and taurine ratio is for 1:0.1-100000:
0.1-100000, wherein cucurbitacin include cucurbitacin A, B, C, E, Q；Double hydrogen cucurbitacin A, B, C, E, Q and isocucurbitacin A, B, C,
E、Q；One of corresponding glucoside material of various cucurbitacin or two or more.
2. the compositionss reducing cucurbitacin toxicity as claimed in claim 1 reduce answering in the medicine of cucurbitacin toxicity in preparation
With it is characterised in that described compositionss jointly or can be respectively prepared tablet, capsule with pharmaceutically acceptable carrier
Agent, granule, powder, patch, ointment, suspensoid, syrup, oral liquid, patch, aerosol, suppository, nasal drop or injection
Agent, and its corresponding controlled release agent；Or make clathrate, liposome, microsphere, nanoparticle or Emulsion, for cavity/canal drug administration, outward
With, oral, injection.
3. application as claimed in claim 2 is it is characterised in that each component in the compositionss of described reduction cucurbitacin toxicity
Amount, is calculated with Mouse oral dosage：Cucurbitacin is 0.001-15 mg/kg, and coenzyme Q10 is 5-15 000 mg/kg, cattle
Sulfonic acid is 5-20 000 mg/kg, point 1 time -4 times administrations；With health adult's Rapid Dose Calculation：Cucurbitacin is 0.1-10 mg/d, auxiliary
Enzyme Q10 is 10-300 mg/d, and taurine is 10-1 000 mg/d, point 1 time -4 times administrations.
4. application as claimed in claim 2 is it is characterised in that the compositionss of described reduction cucurbitacin toxicity are controlled for preparation
Treat the medicine of chronic hepatitiss.
5. application as claimed in claim 2 is it is characterised in that the compositionss of described reduction cucurbitacin toxicity are controlled for preparation
Treat the medicine of cancer.
6. application as claimed in claim 2 is it is characterised in that the compositionss of described reduction cucurbitacin toxicity are used for preparing cancer
The medicine of disease prevention.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210456230.XA CN103800342B (en) | 2012-11-14 | 2012-11-14 | Composition with reduced toxicity of cucurbitacin and medical application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210456230.XA CN103800342B (en) | 2012-11-14 | 2012-11-14 | Composition with reduced toxicity of cucurbitacin and medical application thereof |
Publications (2)
| Publication Number | Publication Date |
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| CN103800342A CN103800342A (en) | 2014-05-21 |
| CN103800342B true CN103800342B (en) | 2017-02-08 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1528282A (en) * | 2003-09-29 | 2004-09-15 | 济南开发区保法药物研究所 | Use of tauring for preparine medicine enhancing leucocyte function |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1528282A (en) * | 2003-09-29 | 2004-09-15 | 济南开发区保法药物研究所 | Use of tauring for preparine medicine enhancing leucocyte function |
Non-Patent Citations (3)
| Title |
|---|
| 葫芦素B 和阿霉素联合应用在体内外对肝癌细胞H22 的生长抑制作用;杨姣 等;《实用药物与临床》;20120515(第5期);257-259 * |
| 葫芦素的研究概况;么焕开 等;《齐鲁药事》;20051231;第24卷(第12期);737-739 * |
| 辅酶Q10预防阿霉素心脏毒性效果的临床研究;王晓明;《国际儿科学杂志》;19821231(第3期);163 * |
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