CN101612179B - Traditional Chinese medicine composition for treating hepatitis and liver cancer - Google Patents

Traditional Chinese medicine composition for treating hepatitis and liver cancer Download PDF

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CN101612179B
CN101612179B CN2009100870687A CN200910087068A CN101612179B CN 101612179 B CN101612179 B CN 101612179B CN 2009100870687 A CN2009100870687 A CN 2009100870687A CN 200910087068 A CN200910087068 A CN 200910087068A CN 101612179 B CN101612179 B CN 101612179B
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quercetin
metabolism
radix
class material
chinese medicine
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CN101612179A (en
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赵瑞芝
刘少军
袁东
陈有军
刘丽娟
赵莹
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No2 Clinico-Medicine College Guangzhou Univ Of Traditional Chinese Medicine
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No2 Clinico-Medicine College Guangzhou Univ Of Traditional Chinese Medicine
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Abstract

The invention discloses a traditional Chinese medicine composition for treating hepatitis and liver cancer, comprising the following raw material medicines according to parts by weight: 1 to 120 parts of rhein or rhubarb class substances capable of being metabolized into the rhein in vivo, 1 to 50 parts of quercetin or quercetinic acid glucoside class substances capable of metabolized into the quercetinic acid in vivo and 3 to 60 parts of vinegar radix bupleuri, wherein the rhein is a market-sold product artificially synthesized or naturally extracted, and the purity is more than or equal to 80%. The composition can be prepared into various traditional Chinese medicine preparation medicines which can suppress the multiplication of liver cancer cells and promote the death of the liver cancer cells; an animal experiment validates that compared with the original anticancer medicine, the medicine can greatly enhance the concentration of the medicine in the liver and prolong the detention time of the medicine.

Description

A kind of Chinese medicine composition for the treatment of hepatitis and hepatocarcinoma
Technical field
The present invention relates to a kind of Chinese medicine composition for the treatment of hepatitis and hepatocarcinoma.
Background technology
Hepatitis B is Chinese disease occurred frequently, among the crowd about 20% suffer from hepatitis B, about 5% finally can develop into hepatocarcinoma, China's 500,000 liver cancer patients of having an appointment every year, serious threat human health.The general at present operative treatment of advocating; but the patient of the less than 15% of only having an appointment in all liver cancer patients meets operation to be accused of; Drug therapy is still the means of indispensable prolongation patient life; yet because liver is the internal metabolism organ; have abundant drug metabolism enzyme and protectiveness efflux pump; medicine is difficult to enter liver and the performance drug effect is stayed in storage, so the result of Drug therapy is very undesirable.
Summary of the invention
The purpose of this invention is to provide a kind of Chinese medicine composition for the treatment of hepatitis and hepatocarcinoma.
For achieving the above object, technical scheme of the present invention provides a kind of Chinese medicine composition for the treatment of hepatitis and hepatocarcinoma, comprises following bulk drugs:
But metabolism is the Radix Et Rhizoma Rhei class material of chrysophanic acid in chrysophanic acid or the body: 1~120,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 1~50,
Radix Bupleuri (processed with vinegar): 3~60,
Wherein said chrysophanic acid is the commercially available prod of synthetic or natural extract, purity 〉=80%.
Chinese medicine composition of the present invention, when direct employing chrysophanic acid was used as medicine, optimum ratio was:
Chrysophanic acid: 10~60,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 10~40,
Radix Bupleuri (processed with vinegar): 3~60.
Wherein most preferably proportioning is:
Chrysophanic acid: 10~50,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 20~40,
Radix Bupleuri (processed with vinegar): 6~24.
Chinese medicine composition of the present invention, but metabolism is that the Radix Et Rhizoma Rhei class material of chrysophanic acid such as Radix Et Rhizoma Rhei, Radix Et Rhizoma Rhei are feared quinone, Radix Et Rhizoma Rhei extract or diacerein etc. when being used as medicine in selecting body for use, and optimum ratio is:
But metabolism is the Radix Et Rhizoma Rhei class material of chrysophanic acid in the body: 20~120,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 10~40,
Radix Bupleuri (processed with vinegar): 3~60.
Wherein most preferably proportioning is:
Radix Et Rhizoma Rhei: 20~100,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 20~40,
Radix Bupleuri (processed with vinegar): 5~30.
Or
Radix Et Rhizoma Rhei is feared quinone: 25~80,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 20~40,
Radix Bupleuri (processed with vinegar): 15~30.
Above-mentioned Chinese crude drug all has commercially available.
Chrysophanic acid chemistry 1.8-dihydroxy by name-3-carboxyl is feared quinone, the material that internal metabolism is mainly chrysophanic acid has Radix Et Rhizoma Rhei, rhubarb free to fear quinone (rhubarb free is feared quinone and comprised emodin, chrysophanic acid, physcione, chrysophanol, aloe-emodin etc., commercially available have the crude extract Radix Et Rhizoma Rhei to fear quinone), rhababerone extract, diacerein etc.
Quercetin chemistry is by name 3,3 ', 4 ', 5, the 7-pentahydroxyflavone, the quercetin glycoside class material that Dai Xieke produces Quercetin among the present invention has rutin, hyperin etc.
Radix Bupleuri is the root of herbaceous plant Radix Bupleuri [Radix Bupleuri (B μ ple μ r μ m chinese DC) and Radix Bupeuri Scorzonerfolii. (B μ ple μ r μ m scorzonerifoli μ m Willd)].Be usually used in treating influenza, fever, malaria, hepatitis, jaundice, nephritis, pneumonopathy, cancer, bitter taste and menoxenia etc.Radix Bupleuri (processed with vinegar) is to spray with rice vinegar after Radix Bupleuri dries cutting, and is vexed, with the little stir-fry of the slow fire person of being used as medicine.
Chinese medicine composition of the present invention can be prepared into the various pharmaceutical preparatioies of treatment hepatitis and hepatocarcinoma, as tablet or capsule or pill etc., preparation method can be: Radix Bupleuri (processed with vinegar) is with water extraction, simmer down to extractum or after being ground into fine powder or being ground into coarse powder, adding ethanol extraction and concentrate, but but metabolism is the quercetin glycoside class material of Quercetin in Radix Et Rhizoma Rhei class material, Quercetin or the body that the interior metabolism of adding chrysophanic acid body is a chrysophanic acid, adds adjuvant or filler and fluidizer and is prepared into tablet or capsule or pill.
The present invention adopts anticarcinogen, antimetabolite, inhibition efflux pump medicine to form the pharmaceutical preparation of treatment hepatitis and hepatocarcinoma, by back two kinds of compositions delay drug metabolism and prolong its in liver retention time and strengthen its absorption, thereby heighten the effect of a treatment.That crude drug chrysophanic acid among the present invention has is antibiotic, antiinflammatory, antiviral effect, but inducing leukemia cell, nasopharyngeal carcinoma cell, apoptosis of tumor cells such as hepatoma carcinoma cell, cervical cancer cell.Chrysophanic acid can suppress the growth of tumor cell by inhibition tumor cell energy acquisition or Sugar intake, is one of potential drug of treatment hepatocarcinoma, and main metabolic is a chrysophanic acid glucal anhydride in the chrysophanic acid body, and drug effect reduces; Quercetin is a flavone compound, has the effect of stronger inhibition drug metabolism enzyme, can delay the metabolism of chrysophanic acid, thereby improves its curative effect; Radix Bupleuri (processed with vinegar) is the Radix Bupleuri processed product, glutathione level in the liver can raise, reduce the liver collagen content, promote that thereby liver cell proliferation has hepatoprotective effect, thereby the scalable INF-γ factor has antiinflammatory action, Radix Bupleuri also has anti-fibroid and becomes, antioxidation, antitumor, enhance immunity, antiviral, analgesic, antiulcer, multiple pharmacologically actives such as immunomodulating and anti-hypercholesterolemiccompounds effect, modern medicine its treatment liver cirrhosis commonly used, hepatic lesions such as hepatic fibrosis, the main Liver Channel of returning after the Radix Bupleuri vinegar system, be the Liver Channel guiding drug, can strengthen the distribution of chrysophanic acid in liver, prolong its action time in liver, thereby strengthen its curative effect.
The specific embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is described in further detail.Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1:
Radix Bupleuri (processed with vinegar) 24 grams are with water extraction, simmer down to extractum, (rutin 40 restrains or hyperin 50 grams, adds adjuvant such as starch, microcrystalline Cellulose, lactose or other filler and is prepared into capsule or is pressed into tablet for adding chrysophanic acid 10 grams (purity 〉=80%) (Radix Et Rhizoma Rhei 20 grams or Radix Et Rhizoma Rhei are feared quinone 25 grams), Quercetin 40 grams.
Embodiment 2:
Radix Bupleuri (processed with vinegar) 3 grams are ground into fine powder, add chrysophanic acid 50 grams (purity 〉=80%) (Radix Et Rhizoma Rhei 60 grams or Radix Et Rhizoma Rhei are feared quinone 70 grams), Quercetin 20 grams (rutin 30 or hyperin 40 grams), add adjuvant such as starch, microcrystalline Cellulose, lactose or other filler and fluidizer and be prepared into tablet or capsule or pill.
Embodiment 3:
Radix Bupleuri (processed with vinegar) 60 grams are ground into coarse powder, adding ethanol extraction concentrates, add chrysophanic acid 60 grams (Radix Et Rhizoma Rhei 100 grams or Radix Et Rhizoma Rhei are feared quinone 80 grams), Quercetin 10 grams (rutin 15 or hyperin 20 grams), add various filleies such as adjuvant such as starch, microcrystalline Cellulose, hydroxypropyl emthylcellulose, lactose and fluidizer and be prepared into various dosage forms.
Test example 1: antitumor action
This product cell experiment has significant apoptosis-promoting effect to hepatoma carcinoma cell.With well-grown rat hepatoma cell with 2 * 10 5/ mL concentration is inoculated in one 96 orifice plate, and every hole 150 μ L place 37 ℃, 5%CO 2Cultivate 24h in the incubator, after treating that cell is adherent fully, the Chinese medicine composition that adds the embodiment of the present application 1, making chrysophanic acid dosage is 2 μ g/mL, matched group adds the culture medium equivalent of distilled water diluting, after 24h was cultivated in dosing, 37 ℃, 5%CO were continued after adding 5mg/ml MTT (tetramethyl azo azoles salt) solution 20 μ L in every hole 2Cultivate 4h in the incubator.Then abandon waste liquid, add DMSO (dimethyl sulfoxide) solution 150 μ L, fully behind the mixing, measure each hole absorbance (A value), measure wavelength 550nm, reference wavelength 620nm with microplate reader.Result such as following table:
Table 1MTT method is measured short hepatoma cell apoptosis effect (9 cell mean)
Figure G2009100870687D00041
As seen from the above table, Chinese medicine composition provided by the invention has the effect of significant promotion hepatoma cell apoptosis.
Test example 2: the present invention is to normal hepatocellular effect
With well-grown rat hepatocytes with 2 * 10 5/ mL concentration is inoculated in one 96 orifice plate, and every hole 150 μ L place 37 ℃, 5%CO 2Cultivate 24h in the incubator, after treating that cell is adherent fully, the Chinese medicine composition that adds the embodiment of the present application 3, making chrysophanic acid dosage is 2 μ g/mL, matched group adds the culture medium equivalent of distilled water diluting, after 24h was cultivated in dosing, 37 ℃, 5%CO were continued after adding 5mg/ml MTT (tetramethyl azo azoles salt) solution 20 μ L in every hole 2Cultivate 4h in the incubator.Then abandon waste liquid, add DMSO (dimethyl sulfoxide) solution 150 μ L, fully behind the mixing, measure each hole absorbance (A value), measure wavelength 550nm, reference wavelength 620nm with microplate reader.The results are shown in Table 2.
Table 2MTT measures this prescription to normal rat hepatocytes effect (9 cell mean)
Figure G2009100870687D00051
As seen from the above table, Chinese medicine composition provided by the invention is nontoxic to the rat normal liver cell.
Test example 3: the present invention strengthens the effect that distributes in the chrysophanic acid liver
108 of rats were raised after 7 days, were divided into 2 groups at random, and the administration group gives Chinese medicine composition of the present invention (embodiment 2), makes chrysophanic acid dosage 80mg/kg, Radix Bupleuri (processed with vinegar) 300mg/kg, and wherein mice dosage reduction formula is: Db=Da * (Rb/Ra) * (Wa/Wb) 1/3Be that Radix Bupleuri (processed with vinegar) people consumption is 3 grams, then the dosage of rat is 300 milligrams of per kilograms, Ra=100, Wa=60kg, Wb=0.2kg, Rb=90, Da=3g/60kg; Matched group gives the chrysophanic acid with administration group moderate, respectively at 15min, and 0.5,1,2,3, heart blood sampling in 4,6,8 hours, put to death rat, core, liver, spleen, lung, kidney, dry blood with filter paper, reject fatty tissue, serum 0.5mL is with ethyl acetate extraction twice, combining extraction liquid, nitrogen dries up, and residue adds the 0.2mL dissolve with methanol, as test liquid.The tissue sample precision is weighed, and adds normal saline according to 1: 10 ratio, and homogenate is got homogenate 0.5mL and handled with blood sample.With high effective liquid chromatography for measuring chrysophanic acid concentration wherein, content in the computation organization, and area under the time graph.The results are shown in following table:
Table 3 respectively organizes area under the pharmaceutical concentration-time curve to account for the percentage ratio of area summation
Figure G2009100870687D00061
Can draw from table, compare with the chrysophanic acid group, the interior targeting efficient relatively of compound recipe group chrysophanic acid liver is 3.51 times of chrysophanic acid group, can greatly improve curative effect of medication.Medicine of the present invention can significantly increase drug distribution in the rats'liver, reduces other tissue distribution.
As can be seen from the above embodiments, medicine of the present invention can suppress hepatoma cell proliferation, impels its apoptosis, and animal experiment confirms that this medicine compares with former cancer therapy drug, can significantly improve concentration in its liver, prolongs its holdup time.
The above only is a preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the technology of the present invention principle; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims (10)

1. a Chinese medicine composition for the treatment of hepatitis and hepatocarcinoma is characterized in that, comprises following bulk drugs:
But metabolism is the Radix Et Rhizoma Rhei class material of chrysophanic acid in chrysophanic acid or the body: 10~120,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 10~50,
Radix Bupleuri (processed with vinegar): 3~60,
Wherein but metabolism is that the Radix Et Rhizoma Rhei class material of chrysophanic acid is Radix Et Rhizoma Rhei or Radix Et Rhizoma Rhei anthraquinone in the body; But metabolism is that the quercetin glycoside class material of Quercetin is rutin or hyperin in the body.
2. Chinese medicine composition according to claim 1 is characterized in that, comprises following bulk drugs:
Chrysophanic acid: 10~60,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 10~40,
Radix Bupleuri (processed with vinegar): 3~60.
3. Chinese medicine composition according to claim 1 is characterized in that, comprises following bulk drugs:
But metabolism is the Radix Et Rhizoma Rhei class material of chrysophanic acid in the body: 20~120,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 10~40,
Radix Bupleuri (processed with vinegar): 3~60.
4. Chinese medicine composition according to claim 2 is characterized in that, comprises following bulk drugs:
Chrysophanic acid: 10~50,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 20~40,
Radix Bupleuri (processed with vinegar): 6~24.
5. Chinese medicine composition according to claim 3 is characterized in that, comprises following bulk drugs:
Radix Et Rhizoma Rhei: 20~100,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 20~40,
Radix Bupleuri (processed with vinegar): 5~30.
6. Chinese medicine composition according to claim 3 is characterized in that, comprises following bulk drugs:
Radix Et Rhizoma Rhei anthraquinone: 25~80,
But metabolism is the quercetin glycoside class material of Quercetin in Quercetin or the body: 20~40,
Radix Bupleuri (processed with vinegar): 15~30.
7. according to the application of each described Chinese medicine composition of claim 1-6 in preparation treatment hepatitis and liver-cancer medicine preparation.
8. application according to claim 7 is characterized in that, described pharmaceutical preparation is tablet or capsule or pill.
9. the preparation method of pharmaceutical preparation according to claim 8, it is characterized in that, Radix Bupleuri (processed with vinegar) is with water extraction, simmer down to extractum, or be ground into fine powder, or after being ground into coarse powder, adding ethanol extraction and concentrate, but but metabolism is the quercetin glycoside class material of Quercetin in Radix Et Rhizoma Rhei class material, Quercetin or the body that the interior metabolism of adding chrysophanic acid or body is a chrysophanic acid, adds adjuvant and is prepared into tablet or capsule or pill.
10. preparation method according to claim 9 is characterized in that described adjuvant is selected from filler and fluidizer.
CN2009100870687A 2009-06-17 2009-06-17 Traditional Chinese medicine composition for treating hepatitis and liver cancer Expired - Fee Related CN101612179B (en)

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程书权,等.中草药活性成分治疗慢性肝病的现代研究.《国外医学中医中药分册》.2004,第26卷(第4期),209-213. *

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