CN1903276A - Medicinal composition for treating hepatitis B - Google Patents
Medicinal composition for treating hepatitis B Download PDFInfo
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- CN1903276A CN1903276A CNA200610111306XA CN200610111306A CN1903276A CN 1903276 A CN1903276 A CN 1903276A CN A200610111306X A CNA200610111306X A CN A200610111306XA CN 200610111306 A CN200610111306 A CN 200610111306A CN 1903276 A CN1903276 A CN 1903276A
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Abstract
A Chinese medicine for treating hepatitis B is prepared from 9 Chinese-medicinal materials including American ginseng, red sage root, oldenlandia, bear gall, etc. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of hepatitis B, specifically relate to a kind of pharmaceutical composition for the treatment of hepatitis B.
Background technology
Hepatitis B is the very strong infectious disease of a kind of viral infection, and the infectious rate of hepatitis B, mortality rate occupy first of 25 kinds of Category B notifiable diseases of China.Someone estimates that China has 1.3 hundred million people to carry hepatitis B virus, wherein has 80% people to need treatment, and that dies from hepatitis B and complication thereof, complication every year has more than 2,000,000 people, therefore says hepatitis B serious harm human health.The treatment of hepatitis B is an a great problem in the world today, so far the ideal medicine of neither one, lamivudine, the interferon of generally acknowledging all is a kind of single targeting control medicine at present, not only the medicine high price is expensive, and toxic and side effects is big, the course of treatment is long, take for a long time and can make virus variation, the drug withdrawal knock-on aggravates disease.
Summary of the invention
The purpose of this invention is to provide a kind of with supplementing QI and nourishing YIN, blood-activating and qi-promoting, eliminating damp-heat, treat the pharmaceutical composition of the treating both the principal and secondary aspects of a disease of acute and chronic hepatitis B, said preparation of compositions method and the purposes that is used to prepare drop pill, capsule, tablet, granule and the oral liquid for the treatment of hepatitis B.Wherein utilize Radix Panacis Quinquefolii it is cold in nature, bitter but slightly sweet taste, be longer than boosting qi and nourishing yin, relieve inflammation or internal heat and promote the production of body fluid, rectify and set upright the effect of gas.Experimental results show that Radix Panacis Quinquefolii saponin Rb
1Can suppress virus, protection infection cell, Radix Panacis Quinquefolii saponin R
oAcute and chronic inflammation all there is remarkable inhibitory action.Radix Panacis Quinquefolii saponin R
dPromote that the anabolic effect of serum albumin matter is the strongest.Utilize Radix Salviae Miltiorrhizae bitter in the mouth, cold nature, merit is arrogated to oneself current blood vessels, blood circulation promoting and blood stasis dispelling, but the effect of heat clearing and blood cooling again; Moreover also utilize flat, the fragrant catharsis of Radix Bupleuri bitter in the mouth, but depressed liver-energy dispersing and QI regulating, the effect of orderly and clearly mechanism of qi.It is capable also to utilize Radix Salviae Miltiorrhizae to close the handsome blood of Radix Panacis Quinquefolii gas, the effect of the meaning of useful qi and blood circulation promotion; Utilize the capable then blood of Radix Salviae Miltiorrhizae and Radix Bupleuri gas capable, the effect of promoting flow of QI and blood is arranged.These monarch-minister drugs match, and make gas because of saving the state, and mechanism of qi a surname is smooth, and the venation tonneau is in order to clearing away the dampness and heat.Rhizoma Polygoni Cuspidati, Herba Hedyotidis Diffusae as adjuvant drug have heat-clearing and toxic substances removing, the effect of blood stasis dispelling dehumidifying.
Monarch, minister in the pharmaceutical composition provided by the invention, help, make and match, the pharmaceutical composition that a large amount of evidence applications that the applicant did are awaited the reply had both met the Chinese medicine traditional theory, embodied the Chinese medicine unique distinction for the treatment of both the principal and secondary aspects of a disease, met the modern medicine and pharmacology theory again.To viral hepatitis, utilize the active component anti-hepatitis virus of Radix Salviae Miltiorrhizae, Rhizoma Polygoni Cuspidati, Herba Hedyotidis Diffusae, Radix Isatidis, Fel Ursi.Utilize Radix Panacis Quinquefolii mediator body immunity function, with Radix Bupleuri, Fructus Schisandrae Chinensis protection hepatocyte.Utilize Radix Salviae Miltiorrhizae, Radix Bupleuri, egg oil anti-hepatic fibrosis, thereby reach the purpose of the acute and chronic hepatitis B of Comprehensive Treatment.
A large amount of evidence pharmaceutical compositions provided by the invention are compositions usefuls that cure difficult and complicated cases disease.
The purpose of this invention is to provide a kind of compositions for the treatment of hepatitis B, said compositions comprises following compositions by weight:
6～26 parts of 14～34 parts of Radix Bupleuri of 10～30 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
2～10 parts of 2～12 parts of Radix Isatidis of 4～24 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.6～1.4 part of 0.6～1.4 part of egg oil of 6～16 parts of Fel Ursis of Herba Hedyotidis Diffusae.
A further object of the present invention provides a kind of preferred therapeutic hepatitis B pharmaceutical composition, and said compositions comprises following compositions by weight:
11～21 parts of 19～29 parts of Radix Bupleuri of 15～25 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
4～8 parts of 6～8 parts of Radix Isatidis of 9～19 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.8～1.2 part of 0.8～1.2 part of egg oil of 15～25 parts of Fel Ursis of Herba Hedyotidis Diffusae.
The 3rd purpose of the present invention provides a kind of hepatitis B pharmaceutical composition of more preferably treating, and said compositions comprises following compositions by weight:
11～18 parts of 19～28 parts of Radix Bupleuri of 17～25 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
4～8 parts of 6～8 parts of Radix Isatidis of 11～19 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.8～1.2 part of 0.8～1.2 part of egg oil of 15～25 parts of Fel Ursis of Herba Hedyotidis Diffusae.
The 4th purpose of the present invention provides a kind of most preferred treatment hepatitis B pharmaceutical composition, and said compositions comprises following compositions by weight:
11～21 parts of 19～29 parts of Radix Bupleuri of 15～20 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
4～6 parts of 6～8 parts of Radix Isatidis of 9～19 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.8～1.2 part of 1.0～1.2 parts of egg oil of 15～18 parts of Fel Ursis of Herba Hedyotidis Diffusae.
The 5th purpose of the present invention is to utilize aforementioned pharmaceutical compositions to make such as drop pill, tablet, capsule, granule and oral liquid.
The present invention also provides a kind of method for preparing said pharmaceutical composition, and except that Radix Panacis Quinquefolii, Radix Salviae Miltiorrhizae and Radix Bupleuri adopted following method processing, other composition was all handled by universal method.The Radix Panacis Quinquefolii alcohol reflux filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin, ethanol elution, the eluent decompression recycling ethanol concentrates, is lyophilized into fine powder; Radix Salviae Miltiorrhizae, each 1.5 hours, is collected decompression filtrate recycling ethanol and is concentrated into fluid extract, is lyophilized into fine powder at 45-65 ℃ of following reduced-pressure backflow with ethanol; Radix Bupleuri alkaline ethanol reduced-pressure backflow, get filtrate decompression recycling ethanol below 60 ℃ after 4 ℃ of cold room cold preservation, get the precipitation cold drying become fine powder.
In the pharmaceutical composition preferred for preparation method of the present invention, Radix Panacis Quinquefolii, Radix Salviae Miltiorrhizae and Radix Bupleuri are handled as follows: Radix Panacis Quinquefolii is with 65-85% alcohol reflux 3 times, each 1-2 hour, filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used the 40-60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.Radix Salviae Miltiorrhizae, was collected filtrate in each 1.5 hours and is concentrated into fluid extract at 50-70 ℃ of following decompression recycling ethanol is lyophilized into fine powder under-40-60 ℃ 45-65 ℃ of following reduced-pressure backflow 3 times with ethanol.Radix Bupleuri 75-85 ℃ of following reduced-pressure backflow 3 times, each 1-2 hour, is got filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder with the 70-80% alkaline ethanol.
Rhizoma Polygoni Cuspidati, Herba Hedyotidis Diffusae, Radix Isatidis and Fructus Schisandrae Chinensis adopt universal method to extract.Universal method in this description is an alcohol extracting-water precipitating.
Embodiment 1
The porphyrize Fel Ursi powder (has except the explanation for 0.6 part in addition, said part is weight portion in the present patent application), 30 parts of usefulness of Radix Panacis Quinquefolii, 70% alcohol reflux 3 times, each 2 hours, filter extracting solution, decompression recycling ethanol D101 macroporous resin to the fluid extract is used 60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.14 parts of Radix Salviae Miltiorrhizaes, were collected filtrate in each 1.5 hours and are concentrated into fluid extract at 70 ℃ of following decompression recycling ethanols and are lyophilized into fine powder at-50 ℃ 50 ℃ of following reduced-pressure backflows 3 times with ethanol.80 ℃ of alkaline ethanols of 6 parts of usefulness of Radix Bupleuri are 80 ℃ of following reduced-pressure backflows 3 times, each 1.5 hours, get filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder.Go sarcocarp to carry out alcohol extraction to 4 parts of Fructus Schisandrae Chinensis, reclaim the ethanol condensed cream.2 parts of Rhizoma Polygoni Cuspidati, 6 parts of Herba Hedyotidis Diffusaes and Radix Isatidis carry out alcohol extraction for 2 parts, and drying under reduced pressure becomes fine powder.With the above-mentioned fine powder of gained, extractum and 0.6 part of mixing of egg oil, stir evenly the back in the thawing polyethylene glycol 6000 of adding equivalent and make the 40mg/ ball with the drop pill machine.
The for example drop pill that the pharmaceutical composition that provides by present embodiment makes has carried out anti-hepatitis virus and the liver protecting and ALT lowering test, and test explanation pharmaceutical composition provided by the invention has anti-hepatitis virus and the liver protecting and ALT lowering effect.
---the anti-hepatitis virus test
Obtained drop pill treatment of infection (calling anti-hepatitis virus test 1 in the following text) effect to DHB in the duck body is as follows 1.:
One age in days Beijing duck intravenous injection DHB begins after 7 days to duck oral hepatitis B drop pill, and 3 dosage groups are respectively 1.0,0.5,0.25g/kg, and 1 day 2 times, Bid * 10; The positive drug lamivudine, oral administration 50mg, every day 2 times, Bid * 10.Experiment shows, the heavy dose of group of hepatitis B drop pill 1.0g/kg is oral nontoxic.By OD value pairing statistical analysis before and after the administration, three batches of experiments, except that first, administration shows repeatably statistical significance difference, administration group different time suppression ratio and infection matched group, statistical analysis is respectively with the horizontal suppression ratio of the clear DHBV-DNA of matched group comparison Sanguis Anas domestica at 2～3 batches: 16.15% (P＜0.01 22.28%, in groups, or P＜0.05), positive control drug 3TC suppression ratio 38.8%.Show that the hepatitis B drop pill has therapeutic effect in the 1.0g/kg group to duck hepatitis B virus infection.
In the 2.2.1.5 cell culture to the inhibitory action of hepatitis B virus (calling anti-hepatitis virus test 2 in the following text)
The toxicity that 8 days hepatitis B drop pill and positive drug lamivudine pair cell in the infectious human liver cell 2.2.1.5 of hepatitis B virus cell line is cultivated are cultivated in dosing has been observed in this test respectively, to the inhibitory action of HBV-DNA in HBsAg and HeAg secretion and cells and supernatant and the cell, the result:
(1) in the 2.2.1.5 cell culture to the secretion inhibition of HBsAg and HBeAg (calling anti-hepatitis virus test 2 in the following text).
The nontoxic Cmax of hepatitis B drop pill by the present embodiment preparation of compositions is 300 μ g/ml, is 30.03 ± 14.48% to HBsAg secretion suppression ratio; To HbeAg secretion suppression ratio is 30.38 ± 15.04%.Lamivudine maximal non-toxic concentration 800 μ g/ml do not have obvious inhibitory action to the secretion of HbsAg and HbeAg.
To sum up: the infection to DHB in the duck body of the hepatitis B drop pill of present embodiment preparation of compositions has therapeutic effect: to HBAg and HbeAg secretion suppression ratio 30.14% and 30.38%, contrast medicine lamivudine (3TC) does not have obvious effect to HBAg and HbeAg secretion suppression ratio in the 2.2.1.5 cell culture;
---the liver protecting and ALT lowering test
1, carbon tetrachloride is caused the prevention and the therapeutical effect (calling the liver protecting and ALT lowering test 1 in the following text) of chmice acute hepatic injury.
Preventive effect, mice use respectively the hepatitis B drop pill little (5.4g crude drug/kg), in (7.2 crude drug g/kg), big (three dosage gastric infusions of 9.6g crude drug/kg).1h lumbar injection 0.12%CCL after administration in the 6th day is respectively organized in administration
4Peanut oil solution 0.1ml/10g, 16h gets eyeball blood and surveys Serum ALT, AST after the modeling.The execution animal is got liver and weighs, and calculates the liver coefficient.The result: large, medium and small dosage group and model group relatively ALT, AST value all obviously reduce (P＜0.01, or P＜0.05).Model and model group compare, and the liver coefficient does not have significant change (P＜0.05).
Therapeutical effect, the equal gastric infusion of each medicine group of 1h, 12h and 23h is 1 time after the same modeling, wins eyeball behind the 24h and gets blood, surveys Serum ALT, AST.The result: each administration group and model group relatively ALT, AST all obviously reduce (P＜0.01 or P＜0.05).
2, D-Gal is caused the prevention and the therapeutical effect preventive effect (calling the liver protecting and ALT lowering test 2 in the following text) of mouse liver injury.Mice is used hepatitis B drop pill three each dosage group (dosage is the same) gastric infusions respectively.Administration is organized respectively in the 6th day that equal lumbar injection dosage is the D-GlaN0.1ml/10g of 1200mg/kg, and 1h wins eyeball and gets blood after the administration in the 7th day, surveys Serum ALT, AST; Get liver and weigh, calculate the liver coefficient.The result: in, heavy dose of group and model group relatively, ALT, AST average obviously reduce (P＜0.05 or P＜0.01).
Therapeutical effect, each administration group of 1h, 12h and 23h is irritated stomach 0.2vml/10g administration 1 time after the same modeling, wins eyeball behind the 24h and gets blood survey ALT, AST, and each administration group and model group compare, and ALT, AST value be obviously decline (P＜0.05 or P＜0.01) all
3, carbon tetrachloride is caused the prevention and the therapeutical effect (calling the liver protecting and ALT lowering test 3 in the following text) of rat chronic hepatic injury
(1) the Wistar rat is irritated the large, medium and small dosage of stomach (the same) respectively, every day 1 time, gavages 24 days continuously.After the perfusion 3 days, normal group subcutaneous injection Oleum Arachidis hypogaeae semen, all the other respectively organize subcutaneous injection 25%CCL
4Oleum Arachidis hypogaeae semen 2ml/kg, 2 times weekly, in totally 3 weeks, 1h gets blood and surveys Serum ALT, AST, TP and ALB after the last administration, and the execution animal is got liver and does pathological examination, and surveys hydroxyl proline and glycogen initial value.Result: can obviously reduce CCL
4(the pathological examination result shows can alleviate CCL for P＜0.05 or P＜0.01, the hepatic glycogen and the A/G value (P＜0.05) that raise and reduce in the rising of the ALP that hepatic injury causes, AST (P＜0.05) and hydroxyl proline value
4The hepatic injury that causes.Prompting, the hepatitis B drop pill is to CCL
4Cause the rat chronic hepatic injury certain prevention protective effect (calling the liver protecting and ALT lowering test 4-1 in the following text) is arranged.
(2) Wistar rat skin lower injection 25%CCL
4Oleum Arachidis hypogaeae semen 2ml/kg 2 times weekly, causes the chronic hepatic injury model.The hepatitis B drop pill that stomaches are given large, medium and small dosage (the same) is irritated in 2 week backs, and every day 1 time, totally 4 weeks, administration is modeling 2 times weekly simultaneously.1h gets blood and surveys ALT, AST, TP and ALB after the last administration, and the execution animal is got liver and does histopathologic examination, and surveys hydroxyl proline and glycogen initial value.The result: in, heavy dose of and model group comparison, can obviously reduce CCL
4The ALP that hepatic injury causes, AST (P＜0.05), the rising of hydroxyl proline and liver coefficient value (P＜0.05), the hepatic glycogen and the A/G value (P＜0.05) that raise and reduce; Prompting is to CCL
4Cause the rat chronic hepatic injury certain therapeutical effect is arranged; The result of histopathologic examination is in the demonstration, heavy dose of animal liver pathological changes obviously is lighter than model group, shows certain therapeutical effect (calling the liver protecting and ALT lowering test 4-2 in the following text).
4. the influence of normal mouse humoral immune function (calling the liver protecting and ALT lowering test 4 in the following text)
The large, medium and small dosage of hepatitis B drop pill (the same) gastric infusion mice, every day 1 time, continuous 8 days.Respectively organize mouse peritoneal injection chicken red blood cell (CRBC) suspension 0.2ml every day, continuous 7 days, in last 24 hours, win eyeball and get blood, carry out external hemolytic reaction, survey top hemolysin content.The result: each dosage group thymus coefficient of hepatitis B drop pill and spleen index variation are little, in, heavy dose of group hemolysin growing amount obviously rises, relatively there were significant differences (P＜0.05 or P＜0.01) in normal group.Prompting, the hepatitis B drop pill has certain potentiation to the humoral immunization of normal mouse.Thymus, spleen histology performance are compared indifference, no abnormality seen pathological changes with normal group.
5, to the influence of macrophage phagocytosis of mice (calling the liver protecting and ALT lowering test 5 in the following text)
The large, medium and small dosage of hepatitis B drop pill (the same) gastric infusion mice, every day 1 time, continuous 7 days, 1h after the last administration carried out carbon and cleans up experiment, calculated phagocytic index.Get Mouse Liver simultaneously and spleen is weighed, and calculate organ coefficient.Among the result, heavy dose of and normal group comparison phagocytic index obviously rise (P＜0.05); Liver coefficient and spleen coefficient and normal group are not seen difference.Prompting, the hepatitis B drop pill has certain enhancing to non-specific immunity and does usefulness.Kupffer cell increases to some extent in liver, the spleen histological examination, sinus hepaticus, and cell endocytic is bitten a large amount of black particles, no significant difference (P＜0.05) between each group.Reach bone-marrow-derived lymphocyte hypertrophy in the red pulp in the dosage splenic nodule big or middle, visible karyokinesis phase, megalokaryocyte is dispersed in the spleen edge red pulp.As seen big or middle dosage has certain immunization to mice.
Embodiment 2
1.4 parts of porphyrize Fel Ursi powders, 10 parts of usefulness of Radix Panacis Quinquefolii, 85% alcohol reflux 3 times each 1 hour, filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used 40% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.34 parts of Radix Salviae Miltiorrhizaes, each 1.5 hours, are collected filtrate and are concentrated into fluid extract at 70 ℃ of following decompression recycling ethanols and are lyophilized into fine powder at-50 ℃ 60 ℃ of following reduced-pressure backflows 3 times with ethanol.26 parts of usefulness 70% alkaline ethanols of Radix Bupleuri are 80 ℃ of following reduced-pressure backflows 3 times, each 1 hour, get filtrate at 50 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder.Fructus Schisandrae Chinensis goes sarcocarp to be crushed to coarse powder for 24 parts, and alcohol extraction is reclaimed alcohol and is condensed into extractum.12 parts of Rhizoma Polygoni Cuspidati, 16 parts of Herba Hedyotidis Diffusaes and Radix Isatidis are carried out alcohol extraction for 10 parts, reclaim the ethanol cream that contracts, drying under reduced pressure becomes fine powder.With the above-mentioned fine powder cream of gained and 1.4 parts of mixings of egg oil, stir evenly the back in the thawing polyethylene glycol 6000 of adding equivalent and make the 40mg/ ball with the drop pill machine.
The for example drop pill that the pharmaceutical composition that provides by present embodiment makes has carried out anti-hepatitis virus and the liver protecting and ALT lowering test, and test explanation pharmaceutical composition provided by the invention has anti-hepatitis virus and the liver protecting and ALT lowering effect.
Anti-hepatitis virus that for example drop pill that the pharmaceutical composition that provides by present embodiment makes carries out test 1 shows at 2～3 batches and is respectively with the horizontal suppression ratio of the clear DHBV-DNA of matched group comparison Sanguis Anas domestica: 10.15% (P＜0.01 23.28%,, or P＜0.05=, positive control drug 3TC suppression ratio 24.8%.Show that the hepatitis B drop pill has therapeutic effect in the 1.0g/kg group to duck hepatitis B virus infection.
Anti-hepatitis virus that for example drop pill that the pharmaceutical composition that provides by present embodiment makes carries out test 2 shows, is 310 μ g/ml by the nontoxic Cmax of hepatitis B drop pill of present embodiment preparation of compositions, is 30.03 ± 14.48% to HBsAg secretion suppression ratio; To HbeAg secretion suppression ratio is 30.38 ± 15.04%.Lamivudine maximal non-toxic concentration 800 μ g/ml do not have obvious inhibitory action to the secretion of HbsAg and HbeAg.
The above-mentioned the liver protecting and ALT lowering test of being undertaken by for example hepatitis B drop pill of present embodiment preparation of compositions shows the effect with said the liver protecting and ALT lowering test 1-5.
Embodiment 3
1.0 parts of porphyrize Fel Ursi powders, 13 parts of usefulness of Radix Panacis Quinquefolii, 70% alcohol reflux 3 times each 2 hours, filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used 60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.16 parts of Radix Salviae Miltiorrhizaes, were collected filtrate in each 1.5 hours and are concentrated into fluid extract at 70 ℃ of following decompression recycling ethanols and are lyophilized into fine powder at-50 ℃ 50 ℃ of following reduced-pressure backflows 3 times with ethanol.10 parts of usefulness 80% alkaline ethanols of Radix Bupleuri are 80 ℃ of following reduced-pressure backflows 3 times, each 1.5 hours, get filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder.Fructus Schisandrae Chinensis goes sarcocarp to be crushed to coarse powder for 10 parts, and alcohol extraction is reclaimed alcohol and is condensed into extractum.8 parts of 6 parts of alcohol extraction Rhizoma Polygoni Cuspidati, 10 parts of Herba Hedyotidis Diffusaes and Radix Isatidis reclaim the ethanol cream that contracts, and drying under reduced pressure becomes fine powder.With the above-mentioned fine powder cream of gained and 1.0 parts of mixings of egg oil, stir evenly the back in the thawing polyethylene glycol 6000 of adding equivalent and make the 40mg/ ball with the drop pill machine.
To make the anti-hepatitis virus test 1 and 2 that drop pill carries out by the present embodiment compositions.Anti-hepatitis virus test 1 shows: be respectively with the horizontal suppression ratio of the clear DHBV-DNA of matched group comparison Sanguis Anas domestica at 2～3 batches: 10.15% (P＜0.01, or P＜0.05=, positive control drug 3TC suppression ratio 26.8% 25.28%.Show that the hepatitis B drop pill has therapeutic effect in the 1.0g/kg group to duck hepatitis B virus infection.
To make the anti-hepatitis virus test 2 that drop pill carries out by the present embodiment compositions shows: the nontoxic Cmax of hepatitis B drop pill by the present embodiment preparation of compositions is 290 μ g/ml, is 35.03 ± 14.48% to HBsAg secretion suppression ratio; To HbeAg secretion suppression ratio is 34.38 ± 15.04%.Lamivudine maximal non-toxic concentration 800 μ g/ml do not have obvious inhibitory action to the secretion of HbsAg and HbeAg.
The above-mentioned the liver protecting and ALT lowering test of being undertaken by for example hepatitis B drop pill of present embodiment preparation of compositions shows the effect with said the liver protecting and ALT lowering test 1-5.
Embodiment 4
0.9 part of porphyrize Fel Ursi powder, 15 parts of usefulness of Radix Panacis Quinquefolii, 70% alcohol reflux 3 times each 2 hours, filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used 60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.18 parts of Radix Salviae Miltiorrhizaes, were collected filtrate in each 1.5 hours and are concentrated into fluid extract at 70 ℃ of following decompression recycling ethanols and are lyophilized into fine powder at-50 ℃ 50 ℃ of following reduced-pressure backflows 3 times with ethanol.15 parts of usefulness 80% alkaline ethanols of Radix Bupleuri are 80 ℃ of following reduced-pressure backflows 3 times, each 1.5 hours, get filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder.Fructus Schisandrae Chinensis goes sarcocarp to be crushed to coarse powder for 17 parts, and pure and strong one-tenth extractum is reclaimed in alcohol extraction.8 parts of Rhizoma Polygoni Cuspidati, 13 parts of Herba Hedyotidis Diffusaes and Radix Isatidis are carried out alcohol extraction for 5 parts, reclaim the ethanol cream that contracts, drying under reduced pressure becomes fine powder.With the above-mentioned fine powder of gained, extractum and 1.0 parts of mixings of egg oil, stir evenly the back in the thawing polyethylene glycol 6000 of adding equivalent and make the 40mg/ ball with the drop pill machine.
To make the anti-hepatitis virus test 1 and 2 that drop pill carries out by the present embodiment compositions.Anti-hepatitis virus test 1 shows: be respectively with the horizontal suppression ratio of the clear DHBV-DNA of matched group comparison Sanguis Anas domestica at 2～3 batches: 10.15% (P＜0.01, or P＜0.05) 26.28%,, positive control drug 3TC suppression ratio 25.8%.Show that the hepatitis B drop pill has therapeutic effect in the 1.0g/kg group to duck hepatitis B virus infection.
To make the anti-hepatitis virus test 2 that drop pill carries out by the present embodiment compositions shows: the nontoxic Cmax of hepatitis B drop pill by the present embodiment preparation of compositions is 280 μ g/ml, is 38.03 ± 14.48% to HBsAg secretion suppression ratio; To HbeAg secretion suppression ratio is 36.38 ± 15.04%.Lamivudine maximal non-toxic concentration 800 μ g/ml do not have obvious inhibitory action to the secretion of HbsAg and HbeAg.
The above-mentioned the liver protecting and ALT lowering test of being undertaken by for example hepatitis B drop pill of present embodiment preparation of compositions shows the effect with said the liver protecting and ALT lowering test 1-5.
Embodiment 5
1.4 parts of porphyrize Fel Ursi powders, 17 parts of usefulness of Radix Panacis Quinquefolii, 70% alcohol reflux 3 times each 2 hours, filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used 60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.34 parts of Radix Salviae Miltiorrhizaes, were collected filtrate in each 1.5 hours and are concentrated into fluid extract at 70 ℃ of following decompression recycling ethanols and are lyophilized into fine powder at-50 ℃ 50 ℃ of following reduced-pressure backflows 3 times with ethanol.26 parts of usefulness 80% alkaline ethanols of Radix Bupleuri are 80 ℃ of following reduced-pressure backflows 3 times, each 1.5 hours, get filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder.Fructus Schisandrae Chinensis goes sarcocarp to be crushed to coarse powder for 23 parts, and alcohol extraction is reclaimed alcohol and is condensed into extractum.8 parts of Rhizoma Polygoni Cuspidati, 13 parts of Herba Hedyotidis Diffusaes and Radix Isatidis are carried out alcohol extraction for 5 parts, reclaim the ethanol cream that contracts, drying under reduced pressure becomes fine powder.With the above-mentioned fine powder of gained, extractum and 1.0 parts of mixings of egg oil, stir evenly the back in the thawing polyethylene glycol 6000 of adding equivalent and make the 40mg/ ball with the drop pill machine.
To make the anti-hepatitis virus test 1 and 2 that drop pill carries out by the present embodiment compositions.Anti-hepatitis virus test 1 shows: be respectively with the horizontal suppression ratio of the clear DHBV-DNA of matched group comparison Sanguis Anas domestica at 2～3 batches: 20.15% (P＜0.01, or P＜0.05) 30.28%,, positive control drug 3TC suppression ratio 38.8%.Show that the hepatitis B drop pill has therapeutic effect in the 1.0g/kg group to duck hepatitis B virus infection.
To make the anti-hepatitis virus test 2 that drop pill carries out by the present embodiment compositions shows: the nontoxic Cmax of hepatitis B drop pill by the present embodiment preparation of compositions is 310 μ g/ml, is 40.03 ± 14.48% to HBsAg secretion suppression ratio; To HbeAg secretion suppression ratio is 40.38 ± 15.04%.Lamivudine maximal non-toxic concentration 800 μ g/ml do not have obvious inhibitory action to the secretion of HbsAg and HbeAg.
The above-mentioned the liver protecting and ALT lowering test of being undertaken by for example hepatitis B drop pill of present embodiment preparation of compositions shows the effect with said the liver protecting and ALT lowering test 1-5.
Embodiment 6
1.1 parts of porphyrize Fel Ursi powders, 19 parts of usefulness of Radix Panacis Quinquefolii, 70% alcohol reflux 3 times each 2 hours, filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used 60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.23 parts of Radix Salviae Miltiorrhizaes are 50 ℃ of following reduced-pressure backflows 3 times, collect filtrate in each 1.5 hours and are concentrated into fluid extract at 70 ℃ of following decompression recycling ethanols and are lyophilized into fine powder at-50 ℃.15 parts of usefulness 80% alkaline ethanols of Radix Bupleuri are 80 ℃ of following reduced-pressure backflows 3 times, each 1.5 hours, get filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder.Fructus Schisandrae Chinensis goes sarcocarp to be crushed to coarse powder for 18 parts, and pure and strong one-tenth extractum is reclaimed in alcohol extraction.5 parts of Rhizoma Polygoni Cuspidati, 10 parts of Herba Hedyotidis Diffusaes and Radix Isatidis are carried out alcohol extraction for 5 parts, reclaim the ethanol cream that contracts, drying under reduced pressure becomes fine powder.With the above-mentioned fine powder of gained, extractum and 0.9 part of mixing of egg oil, stir evenly the back in the thawing polyethylene glycol 6000 of adding equivalent and make the 40mg/ ball with the drop pill machine.
To make the anti-hepatitis virus test 1 and 2 that drop pill carries out by the present embodiment compositions.Anti-hepatitis virus test 1 shows: be respectively with the horizontal suppression ratio of the clear DHBV-DNA of matched group comparison Sanguis Anas domestica at 2～3 batches: 23.15% (P＜0.01, or P＜0.05) 32.28%,, positive control drug 3TC suppression ratio 38.8%.Show that the hepatitis B drop pill has therapeutic effect in the 1.0g/kg group to duck hepatitis B virus infection.
To make the anti-hepatitis virus test 2 that drop pill carries out by the present embodiment compositions shows: the nontoxic Cmax of hepatitis B drop pill by the present embodiment preparation of compositions is 310 μ g/ml, is 43.03 ± 14.48% to HBsAg secretion suppression ratio; To HbeAg secretion suppression ratio is 43.38 ± 15.04%.Lamivudine maximal non-toxic concentration 800 μ g/ml do not have obvious inhibitory action to the secretion of HbsAg and HbeAg.
The above-mentioned the liver protecting and ALT lowering test of being undertaken by for example hepatitis B drop pill of present embodiment preparation of compositions shows the effect with said the liver protecting and ALT lowering test 1-5.
The for example hepatitis B drop pill of preparation of pharmaceutical compositions provided by the invention and single targeting of prior art be the lamivudine of inside and outside anti-hepatitis virus ratio for example preferably, and surface antigen, the e antigen of hepatitis B is all had significant inhibitory effect.
After those skilled in the art of the present technique read the present patent application description; can carry out many variations; the for example replacement of component; change on the dosage form; these all are after those skilled in the art read the present patent application description; at its monarch, minister, help, make and need not under the inspiration of invention thought to pay that creative work can realize, all within the claim protection domain that application is awaited the reply.
Claims (9)
1. compositions for the treatment of hepatitis B is characterized in that said compositions comprises following compositions by weight:
6～26 parts of 14～34 parts of Radix Bupleuri of 10～30 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
2～10 parts of 2～12 parts of Radix Isatidis of 4～24 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.6～1.4 part of 0.6～1.4 part of egg oil of 6～16 parts of Fel Ursis of Herba Hedyotidis Diffusae.
2. according to the compositions of claim 1, it is characterized in that said compositions comprises following compositions by weight:
11～21 parts of 19～29 parts of Radix Bupleuri of 15～25 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
4～8 parts of 6～8 parts of Radix Isatidis of 9～19 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.8～1.2 part of 0.8～1.2 part of egg oil of 9～15 parts of Fel Ursis of Herba Hedyotidis Diffusae.
3. according to the compositions of claim 1 or 2, it is characterized in that said compositions comprises following compositions by weight:
11～14 parts of 19～28 parts of Radix Bupleuri of 17～25 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
4～8 parts of 6～8 parts of Radix Isatidis of 10～19 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.8～1.2 part of 0.8～1.2 part of egg oil of 10～14 parts of Fel Ursis of Herba Hedyotidis Diffusae.
4. according to the compositions of claim 3, it is characterized in that said compositions comprises following compositions by weight:
12～13 parts of 19～27 parts of Radix Bupleuri of 15～20 parts of Radix Salviae Miltiorrhizaes of Radix Panacis Quinquefolii
4～6 parts of 6～8 parts of Radix Isatidis of 9～19 parts of Rhizoma Polygoni Cuspidati of Fructus Schisandrae Chinensis
0.8～1.2 part of 1.0～1.2 parts of egg oil of 13～14 parts of Fel Ursis of Herba Hedyotidis Diffusae.
5. utilize drop pill, capsule, tablet, granule and the oral liquid of treatment hepatitis B of the preparation of pharmaceutical compositions of above-mentioned arbitrary claim.
6. arbitrary preparation of drug combination method among the claim 1-4 is characterized in that, except that Radix Panacis Quinquefolii, Radix Salviae Miltiorrhizae and Radix Bupleuri adopted following method processing, other composition was all handled by universal method; The Radix Panacis Quinquefolii alcohol reflux filters extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin, ethanol elution, the eluent decompression recycling ethanol concentrates, is lyophilized into fine powder; Radix Salviae Miltiorrhizae, each 1.5 hours, is collected decompression filtrate recycling ethanol and is concentrated into fluid extract, is lyophilized into fine powder at 45-65 ℃ of following reduced-pressure backflow with ethanol; Radix Bupleuri alkaline ethanol reduced-pressure backflow, get filtrate decompression recycling ethanol below 60 ℃ after 4 ℃ of cold room cold preservation, get the precipitation cold drying become fine powder.
7. according to the preparation of drug combination method of claim 6, it is characterized in that, in the pharmaceutical composition preferred for preparation method of the present invention, Radix Panacis Quinquefolii, Radix Salviae Miltiorrhizae and Radix Bupleuri are handled as follows: Radix Panacis Quinquefolii 65-85% alcohol reflux 3 times, each 1-2 hour, filter extracting solution, decompression recycling ethanol D to the fluid extract
101Macroporous resin is used the 40-60% ethanol elution, the eluent decompression recycling ethanol be concentrated into relative density be behind the 1.31-1.33-50 ℃ be lyophilized into fine powder.Radix Salviae Miltiorrhizae, was collected filtrate in each 1.5 hours and is concentrated into fluid extract at 50-70 ℃ of following decompression recycling ethanol is lyophilized into fine powder under-40-60 ℃ 45-65 ℃ of following reduced-pressure backflow 3 times with ethanol.Radix Bupleuri 75-85 ℃ of following reduced-pressure backflow 3 times, each 1-2 hour, is got filtrate at 60 ℃ of following decompression recycling ethanols to 1: 1 (crude drug amount: water-soluble liquid measure) get the precipitation cold drying after 24 hours 4 ℃ of cold room cold preservations and become fine powder with the 70-80% alkaline ethanol.
8. arbitrary compositions is being used for preparing the purposes for the treatment of hepatitis B medicine among the claim 1-4.
Among the claim 1-4 arbitrary compositions function with cure mainly: the function with supplementing QI and nourishing YIN, blood circulation promoting and blood stasis dispelling, clearing away heat-damp and promoting diuresis, removing dampness detoxifcation; The disease, the disease that are used for deficiency of both QI and YIN, qi depression to blood stasis, hot and humid ecchymosis see that side of body rib dull pain, abdominal distention after meal, fatigue and weakness, inappetence, dry mouth and tougue, red tongue have the acute and chronic hepatitis B of ecchymosis, thin fur chest, stringy and thready pulse.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200610111306XA CN100482252C (en) | 2006-08-18 | 2006-08-18 | Medicinal composition for treating hepatitis B |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200610111306XA CN100482252C (en) | 2006-08-18 | 2006-08-18 | Medicinal composition for treating hepatitis B |
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| CN100482252C CN100482252C (en) | 2009-04-29 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102342995A (en) * | 2010-08-05 | 2012-02-08 | 于红雨 | Medicinal composition for treating liver cirrhosis and liver ascites and preparation method thereof |
| CN103977393A (en) * | 2014-05-21 | 2014-08-13 | 黄杰 | External targeted lead-in liquid |
| CN116350695A (en) * | 2023-05-16 | 2023-06-30 | 杨洪印 | New use of pharmaceutical composition for treating pulmonary nodules |
-
2006
- 2006-08-18 CN CNB200610111306XA patent/CN100482252C/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102342995A (en) * | 2010-08-05 | 2012-02-08 | 于红雨 | Medicinal composition for treating liver cirrhosis and liver ascites and preparation method thereof |
| CN103977393A (en) * | 2014-05-21 | 2014-08-13 | 黄杰 | External targeted lead-in liquid |
| CN116350695A (en) * | 2023-05-16 | 2023-06-30 | 杨洪印 | New use of pharmaceutical composition for treating pulmonary nodules |
| CN116350695B (en) * | 2023-05-16 | 2023-11-17 | 杨洪印 | New use of pharmaceutical composition for treating pulmonary nodules |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100482252C (en) | 2009-04-29 |
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