CN101041061A - Anti-hepatitis B virus medicine agent and its preparing process - Google Patents
Anti-hepatitis B virus medicine agent and its preparing process Download PDFInfo
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Abstract
The invention provides a drug composite for resisting hepatitis B, formed by 0.001-0.01 deals of ascidiology polypeptide Ser-Ser-Leu-Ser-Lys-Ala-Ala, and 5-8 deals of phyllanthol extractive, with high hepatitis B resistance activity, to be used to prepare the hepatitis B drug.
Description
Technical field
The present invention relates to the antiviral drugs field, be specifically related to a kind of pharmaceutical composition of anti-hepatitis B virus.
Background technology
Hepatitis B is one of national healthy disease of serious harm.At present, the Western medicine that catches for hepatitis B virus (HBV) mainly is biological species medicines such as nucleotide medicine such as lamivudine and interferon, these medicines all exist side effect big, be easy to generate shortcomings such as drug resistance and treatment back knock-on.
Cacumen Securinegae Suffruticosae Phyllanthus urinaria L. is the herb of Euphorbiaceae Euphorbiaceae Leafflower phyllanthus, record the earliest in " the SHENGCAO property of medicine is wanted fully ", effect with calming liver and clearing heat, promoting diuresis to remove toxic substance is used for the treatment of enteritis, dysentery, urinary tract infection, nameless gall etc.Phyllanthus plant has more than 600 kind approximately in the whole world, there are 6 subgenus, 7 groups, 33 kinds, 4 mutation in China, and phyllanthus plant can be draft, shrub or arbor, is distributed widely in the torrid zone, subtropical zone and temperate zone.India scholar Thyagarajan report can make 59% patient's hepatitis B surface antigen (HBsAg) turn out cloudy with Phyllanthusamarus (Phyllanthus amarus) treatment hepatitis B virus carriers; Wang Rongguo (Cacumen Securinegae Suffruticosae anti-hepatitis virus research overview, Chinese medicine research, 2001,17 (1): 58-60) also done the research of Cacumen Securinegae Suffruticosae anti-hepatitis virus related fields, proved that it has the effect that suppresses hepatitis B virus duplication; (phyllanthus for treating chronic viral hepatitis B progress, Xinjiang Chinese medicine, 2004,22 (2): 58-60) described the obtained progress in phyllanthus for treating chronic viral hepatitis B aspect such as Luo Dehui; State knows that office disclosed an application for a patent for invention and " utilized phyllanthus for treating chronic inflammatory and fibrotic processes " (notification number is: CN1364085) disclose a kind of Cacumen Securinegae Suffruticosae extract, this extract has prevention and treatment hepatic fibrosis and keeps the effect of reductive glutathione level on August 14th, 2002; State knows that office on October 11st, 1999 disclosed one " pharmaceutical composition that is used for the treatment of hepatitis B that comprises the extract of Cacumen Securinegae Suffruticosae in the Usu and/or Cacumen Securinegae Suffruticosae " (application number CN1234741), and said composition has the effect of treatment hepatitis B.
Phyllanthusamarus shows that through the clinical application research result it has the hepatitis B virus duplication of inhibition, improves curative effects such as liver function and anti-hepatic fibrosis.Cacumen Securinegae Suffruticosae is higher to the HBeAg negative conversion rate, but not high to the HBsAg negative conversion rate.From the clinical practice situation, the liver health has the short cloudy effect of changeing of index of duplicating to the male patient of chronic viral hepatitis B HBeAg, HBV-DNA, can reflect its antiviral effect, and not high to the HBsAg negative conversion rate.
Ascidean (Ascidia) is the urochordata of Urochordata (Uronordata) guiding principle, the Hu Wenjun master of No.1 Military Medical Univ. thesis " research of wrinkle tumor ascidean anti-hepatitis virus effective ingredient " discloses two kinds of polypeptide of separating and has had anti-hepatitis B activity from wrinkle tumor ascidean, the aminoacid sequence of this two peptide species is respectively Lys-Gly-Lys-Ile-Glu-His and Ser-Ser-Leu-Ser-Lys-Ala-Ala, these two kinds of Acidian polypeptides are higher to the HBsAg negative conversion rate, but to the HBeAg action effect a little less than, and effect such as the liver protecting and ALT lowering remains further research.
Summary of the invention
The pharmaceutical composition that the purpose of this invention is to provide a kind of new anti-hepatitis virus.
The present invention realizes that the technical scheme of above-mentioned purpose is:
A kind of pharmaceutical composition of anti-hepatitis B virus, said composition is made up of following components in weight percentage:
0.001～0.01 part of Acidian polypeptide
5～8 parts of Cacumen Securinegae Suffruticosae alcohol extraction things
Wherein, the aminoacid sequence of Acidian polypeptide is Ser Ser Leu Ser Lys Ala Ala (SEQ NO.1), and Ser is a serine in the formula, and Leu is a leucine, and Lys is a lysine, and Ala is an alanine.
Cacumen Securinegae Suffruticosae of the present invention is Common Leafflower Herb Herba Phyllanthi Urinariae.
Preparation of drug combination method of the present invention is by proportioning Cacumen Securinegae Suffruticosae alcohol extraction thing and Acidian polypeptide mixing to be got final product.
The preparation method of described Cacumen Securinegae Suffruticosae alcohol extraction thing is (the Rhizoma Zingiberis Recens plan of known percolation, Sun Qi, Gao Xiuying. the Cacumen Securinegae Suffruticosae extraction process is inquired into. Chinese patent medicine .1999,21:1-2), be specially: Cacumen Securinegae Suffruticosae is broken into coarse powder, is that the 6-8 of medical material doubly measures by percolation with 55% ethanol extraction percolate, filters, decompression recycling ethanol and simmer down to 1: 1 get Cacumen Securinegae Suffruticosae alcohol extraction thing.
The preparation method of Acidian polypeptide of the present invention see state know the office 2006 invention disclosed patent application on July 19, " a kind of Acidian polypeptide and preparation method thereof " (publication number is: CN1803831), be specially: at first use and weight 2 weeks of 95% soak with ethanol ascidean such as ascidean, reclaim ethanol and obtain extractum, with the water dissolution of extractum with 2～3 times of volumes, use then and the isopyknic organic solvent extraction of water, the water intaking layer, use chromatography separate to purify at last, getting the inspection of thin layer chromatography ultraviolet light, to know Rf be 0.2～0.3 eluent.Wherein, described organic solvent be ethyl acetate, chloroform, dichloromethane, n-butyl alcohol, ether, petroleum ether, normal hexane, cyclohexane extraction wherein one or more; Described chromatography be macroporous resin chromatography, silica gel chromatography, SephadexLH-20 chromatography wherein one or more, chromatography of the present invention preferably uses macroporous resin chromatography, silica gel chromatography, Sephadex LH-20 chromatography successively; Described thin layer chromatography condition: developing solvent is a n-butyl alcohol: water: acetic acid is 4: 5: 1; Developer is 5% sulphuric acid ethanol liquid.
Pharmaceutical composition of the present invention can be used to prepare the preparation for the treatment of hepatitis B, and those skilled in the art can add the adjuvants such as agent and excipient of distinguishing the flavor of according to the requirement of different dosage form, is prepared into various dosage forms, preferably oral liquid.
Utilize the anti-hepatitis B virus oral liquid of drug regimen preparation of the present invention, contain the component of following weight proportion:
0.001～0.01 part of Acidian polypeptide, 5～8 parts of Cacumen Securinegae Suffruticosae alcohol extraction things, 2～3 parts of antiseptic, sweeting agent are an amount of, 800～1000 parts in water.
In the said components, sweeting agent can be a cyclamate or/and sucrose, and antiseptic can be that benzoic acid is or/and ethyl hydroxybenzoate.
Anti-hepatitis B virus oral liquid of the present invention also contains 20～50 parts of Herba Menthaes in this oral liquid.
Anti-hepatitis B pharmaceutical composition of the present invention has higher anti-hepatitis B activity, wherein said Cacumen Securinegae Suffruticosae alcohol extraction thing has the hepatitis B virus duplication of inhibition, improves curative effects such as liver function and anti-hepatic fibrosis, higher to the HBeAg negative conversion rate, but not high to the HBsAg negative conversion rate; Acidian polypeptide has the inhibition hepatitis B virus duplication, and is all higher to the HBsAg negative conversion rate, but to the HBeAg action effect a little less than; Behind the two compatibility, the secretion of inhibition HBeAg, HBsAg and the pharmacologically active that duplicates of hepatitis B virus DNA are all increased, simultaneously, effects such as anticancer in addition, antibiotic, anti-fibrinolytic and the liver protecting and ALT lowering.Pharmaceutical composition of the present invention can be used for preparing the medicine for the treatment of hepatitis B.
Below the effect that the present invention has will be described by experiment.
The aminoacid sequence of the Acidian polypeptide in the following experiment is Ser-Ser-Leu-Ser-Lys-Ala-Ala (SEQ NO.1)
1. external serology experiment
The preparation of test liquid A: get Acidian polypeptide (Guangdong Daya Gulf wrinkle tumor ascidean) 10mg, add normal saline to 1000mL, being made into concentration is 10 μ gmL
-1Test liquid.
The preparation of test liquid B: get Cacumen Securinegae Suffruticosae alcohol extraction thing (Shaanxi Province's Phyllanthusamarus) 5g, add normal saline to 1000mL, being made into concentration is 5mgmL
-1Test liquid.
The preparation of test liquid C: get Acidian polypeptide 10mg and Cacumen Securinegae Suffruticosae alcohol extraction thing 5g, add normal saline, be made into mixed solution to 1000mL.
Get A, B, C test liquid respectively with standby serum under 37 ℃ of conditions 1: 2 by volume the effect 8h, getting wherein small three positive seroreaction liquid then is ELISA and measures HBsAg, gets great three positive seroreaction liquid and be ELISA and measure HBeAg, pressing the negative contrast of reactant liquor of the same terms and normal saline effect simultaneously with normal human serum, is blank with the normal saline.Operational approach is undertaken by the test kit description, but incubation time extends to 60min.
The detection of HBsAg, HBeAg is adopted ELISA to measure box and is detected.Suppression ratio (%)=[(control wells P/N value-experimental port P/N value)/(control wells P/N value-blank well P/N value)] * 100%.
Table 1 test sample is to HBsAg in serum and the antigenic inhibitory action of HBeAg (n=5, X ± S)
| Group | Dosage mL | HBsAg | HBeAg | ||
| The A value | Suppression ratio % | The A value | Suppression ratio % | ||
| A | 0.05 | 0.77±0.26 | 61.15 | 0.62±0.11 | 45.31 |
| B | 0.05 | 1.40±0.25 | 27.06 | 0.47±0.06 c | 59.81 |
| C | 0.05 | 0.50±0.12 | 83.62 | 0.38±0.07 | 68.50 |
| Negative control group | 1.90±0.02 | 1.08±0.01 | |||
| The blank group | 0.02 | 0.05 | |||
Each experimental group compares P＜0.05 with corresponding negative control group.
Result: through external serology experimentation, each group of test liquid and corresponding negative control group are done the individual event variance analysis relatively, P＜0.05 in P＜0.05, the HBeAg group shows that test sample A, B, C all have certain inhibitory action to HBsAg in serum and HBeAg antigen in the HBsAg group; We can draw analytical table 1, and anti-HBV compositions C is better than its folk prescription A, B to HBsAg in serum and the antigenic inhibitory action of HBeAg, brings into play its drug synergism preferably from the pharmacological function of multiple spot position, has remedied the deficiency of its folk prescription.
2. external HepG2 2.2.15 cell suppresses hepatitis B virus (HBV) antigen secretion test
HepG2 2.2.15 cell (infecting internal medicine by Nanfang Hospital gives): be that (2 HBV heads are to the tail dimer with containing the HBV genome, with tail to tail direction series connection) the transfer vector plasmid transfection HepG 2 cell, screen through G418, clone energy HBsAg, the HBeAg and the Dane granule that obtain, can detect cell DNA and RNA, but not have cccDNA.
The preparation of test liquid A: get Acidian polypeptide (Guangdong Daya Gulf wrinkle tumor ascidean) 1mg, add the cell culture fluid to 1000mL, being made into concentration is 1 μ gmL
-1Test liquid.
The preparation of test liquid B: get Cacumen Securinegae Suffruticosae alcohol extraction thing (Shaanxi Province's Phyllanthusamarus) 0.5g, add the cell culture fluid to 1000mL, being made into concentration is 0.5mgmL
-1Test liquid.
The preparation of test liquid C: get Acidian polypeptide 1mg and Cacumen Securinegae Suffruticosae alcohol extraction thing 0.5g, add the cell culture fluid, be made into mixed solution to 1000mL.
To the 25cm culture bottle, every bottle adds DMEM culture fluid (containing 10% hyclone, 10000u/ml mycillin, 200 μ g/ml G418) 5ml, puts 37 ℃, 5%CO with the 2.2.15 cell inoculation
2In the constant incubator, went down to posterity every 3～4 days.
With 0.25% trypsin the 2.2.15 cell dissociation is dispersed into the individual cells suspension, by 3 * 10
4The cells/well branch is planted in 96 orifice plates, uses the pastille culture fluid instead after 2 days, and each concentration adds 4 holes.Test liquid A, B, C respectively with cytosis after 12 days, draw cell conditioned medium liquid, measure HBsAg, HBeAg titre with the ELISA method.Experiment with the cell that do not add any medicine as the cell matched group.Medicine group test data and cell matched group are contrasted, investigate its difference.
The ELISA method is surveyed HBsAg, HBeAg: every hole adds specimen 50 μ l to be measured, establishes feminine gender, each 2 hole of positive control, and establishes blank 1 hole.Every hole adds enzyme conjugates 50 μ l (except that blank), and fully shrouding behind the mixing is put 37 ℃ and hatched half an hour.By hand wash plate: discard the liquid hole in, drying after 5 seconds is left standstill in full each hole of cleaning mixture storage, pats dry after repeating 5 times.Every hole adds developer A liquid, each 50 μ l of B liquid successively, abundant mixing, and shrouding is put 37 ℃ and was hatched 15 minutes; Every hole adds stop buffer 50 μ l, mixing; Measure with microplate reader.Get wavelength 450nm, with blank well school zero, read each hole OD value then earlier, negative control OD value is lower than 0.05 as 0.05 calculating, is higher than 0.05 according to actual OD calculating.
Table 2 test sample is to 2.2.15 cell HBsAg and the antigenic suppression ratio of HBeAg (n=5, X ± S)
| Group | Dosage mL | HBsAg | HBeAg | ||
| OD±S | Suppression ratio % | OD±S | Suppression ratio % | ||
| A | 0.05 | 0.47±0.12 | 63.27 | 1.21±0.12 | 43.51 |
| B | 0.05 | 0.65±0.11 | 48.49 | 0.66±0.11 | 69.23 |
| C | 0.05 | 0.25±0.06 | 81.35 | 0.50±0.19 | 76.81 |
| The cell contrast | 1.24±0.05 | 2.12±0.04 | |||
| Blank | 0.02 | 0.01 | |||
Each group compares P＜0.05 with corresponding negative control group.
Result: through external 2.2.15 cell experiment research, each group of test sample and corresponding negative control group are done the individual event variance analysis relatively, P＜0.05 in P＜0.05, the HBeAg group shows that test sample A, B, C all have certain inhibitory action to HBsAg in the 2.2.15 cell and HBeAg antigen in the HBsAg group; We can draw analytical table 2, and anti-HBV compositions C is higher than its folk prescription A, B to the antigenic suppression ratio of HBsAg and HBeAg in the 2.2.15 cell, brings into play its drug synergism preferably from the pharmacological function of multiple spot position, has remedied the deficiency of its folk prescription.
3.HBV experiment in the body of transgenic mice
The HBV transgene mouse model: the HBV transgenic mice that the suitable HBV research that utilizes Guangzhou air hospital successfully to cultivate is used experimentizes.
Experiment grouping and medication: get 6 age in week 32 of HBV transgenic mices, male and female are not limit, and are divided into 4 groups at random, 8 every group, all raise in cages separately for every.1. blank group: feed with normal diet; 2. A Acidian polypeptide dosage group: dosage is 5mgkg
-1D
-13. B Cacumen Securinegae Suffruticosae alcohol extraction agent amount group: dosage is 300mgkg
-1D
-14. C compositions of the present invention (preparation example 1 described compositions) dosage group: dosage is 50mgkg
-1D
-1
Detection method: the experimental drug time was 12 weeks, and before medication, 4 weeks of medication, 8 weeks, 12 weeks are detected the serum HBV dna content with fluorescent PCR, and carried out the curative effect assessment.The results are shown in Table 3.
Serum HBV DNA titre situation of change before and after table 3 medication (n=8, X ± S)
| Group | Serum HBV DNA(copies/mL) | |||
| T0 | T4 | T8 | T12 | |
| A | 1.60E05± 2.54E04 | 3.52E04± 1.63E04 bf | 4.85E03± 8.12E02 bf | 2.34E03± 4.48E02 cf |
| B | 1.73E05± 4.69E04 | 8.39E04± 1.32E04 | 4.07E04± 1.63E04 bf | 2.19E04± 7.53E03 bf |
| C | 1.52E05± 4.21E04 | 8.63E03± 1.18E03 bf | 3.51E03± 2.47E02 cf | 1.12E03± 3.38E02 cf |
| The blank group | 1.35E05± 3.64E04 | 1.34E05± 3.20E04 | 1.53E05± 3.10E04 | 1.30E05± 2.43E04 |
Handle front and back for same group and relatively (promptly compare) with T0,
bP＜0.05,
cP＜0.01; Each treatment group and matched group compare,
fP＜0.01.
Result: HBV transgene mouse model experimentation in body, each group of experiment has all presented the phenomenon that serum HBV DNA titre reduces after treatment, the replication variance analysis shows, the A group is after treatment, from 12 weeks of the 4th week to the of administration, compare before its serum HBV DNA titre and the administration and remarkable decline occurred; B group from 12 weeks of the 8th week to the of administration, is compared before its serum HBV DNA titre and the administration and remarkable decline occurred after treatment; C group from 12 weeks of the 4th week to the of administration, is compared before its serum HBV DNA titre and the administration and remarkable decline occurred after treatment.It is more more obvious than the decline of its folk prescription A, B group serum HBV DNA titre that analytical table 3-1 can draw the C group, brings into play its drug synergism preferably from the pharmacological function of multiple spot position, remedied the deficiency of its folk prescription.
The specific embodiment
The aminoacid sequence of the Acidian polypeptide among the following embodiment is: Ser-Ser-Leu-Ser-Lys-Ala-Ala.
Preparation example:
Example 1
Prescription: Acidian polypeptide 1mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 8g.
Preparation method:
(1) Cacumen Securinegae Suffruticosae being broken into coarse powder, is 8 times of amounts of medical material by percolation with 55% ethanol extraction percolate, filters, and decompression recycling ethanol and simmer down to 1: 1 get Cacumen Securinegae Suffruticosae alcohol extraction thing.
(2) use and weight 2 weeks of 95% soak with ethanol ascidean such as ascidean, reclaim ethanol and obtain extractum, with the water dissolution of extractum with 2 times of volumes, use then and the water equal volume of ethyl acetate, water intaking layer uses macroporous resin chromatography to separate at last and purifies, and getting the inspection of thin layer chromatography ultraviolet light, to know Rf be 0.5～0.6 eluent, wave most solvent, get Acidian polypeptide.Described thin layer chromatography condition: developing solvent is a n-butyl alcohol: water: acetic acid is 4: 5: 1; Developer is 5% sulphuric acid ethanol liquid.
(3) get Acidian polypeptide 1mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 8g mixes, and gets final product.
Example 2
Prescription: Acidian polypeptide 3mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 7g.
(1) Cacumen Securinegae Suffruticosae being broken into coarse powder, is 7 times of amounts of medical material by percolation with 55% ethanol extraction percolate, filters, and decompression recycling ethanol and simmer down to 1: 1 get Cacumen Securinegae Suffruticosae alcohol extraction thing.
(2) use and weight 2 weeks of 95% soak with ethanol ascidean such as ascidean, reclaim ethanol and obtain extractum, with the water dissolution of extractum with 3 times of volumes, use then and the isopyknic chloroform extraction of water, water intaking layer uses silica gel chromatography to separate at last and purifies, and getting the inspection of thin layer chromatography ultraviolet light, to know Rf be 0.5～0.6 eluent, wave most solvent, get Acidian polypeptide.Described thin layer chromatography condition: developing solvent is a n-butyl alcohol: water: acetic acid is 4: 5: 1; Developer is 5% sulphuric acid ethanol liquid.
(3) get Acidian polypeptide 3mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 7g mixes, and gets final product.
Example 3
Prescription: Acidian polypeptide 6mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 7g.
Preparation method:
(1) Cacumen Securinegae Suffruticosae being broken into coarse powder, is 6 times of amounts of medical material by percolation with 55% ethanol extraction percolate, filters, and decompression recycling ethanol and simmer down to 1: 1 get Cacumen Securinegae Suffruticosae alcohol extraction thing.
(2) use and weight 2 weeks of 95% soak with ethanol ascidean such as ascidean, reclaim ethanol and obtain extractum, with the water dissolution of extractum with 3 times of volumes, use then and the isopyknic n-butanol extraction of water, water intaking layer uses silica gel chromatography to separate purifications with the SephadexLH-20 chromatography at last successively, and getting the thin layer chromatography ultraviolet light, to examine knowledge Rf be 0.5～0.6 eluent, wave most solvent, get Acidian polypeptide.Described thin layer chromatography condition: developing solvent is a n-butyl alcohol: water: acetic acid is 4: 5: 1; Developer is 5% sulphuric acid ethanol liquid.
(3) get that Acidian polypeptide 6mg and Cacumen Securinegae Suffruticosae alcohol extraction thing 7g are mixed to get final product.
Example 4
Prescription: Acidian polypeptide 10mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 5g.
Preparation method:
(1) Cacumen Securinegae Suffruticosae being broken into coarse powder, is 8 times of amounts of medical material by percolation with 55% ethanol extraction percolate, filters, and decompression recycling ethanol and simmer down to 1: 1 get Cacumen Securinegae Suffruticosae alcohol extraction thing.
(2) use and weight 2 weeks of 95% soak with ethanol ascidean such as ascidean, reclaim ethanol and obtain extractum, with the water dissolution of extractum with 3 times of volumes, use then and the isopyknic n-hexane extraction of water, water intaking layer uses successively at last and uses macroporous resin chromatography, silica gel chromatography, Sephadex LH-20 chromatography to separate successively to purify, and getting the inspection of thin layer chromatography ultraviolet light, to know Rf be 0.5～0.6 eluent, wave most solvent, get Acidian polypeptide.Described thin layer chromatography condition: developing solvent is a n-butyl alcohol: water: acetic acid is 4: 5: 1; Developer is 5% sulphuric acid ethanol liquid.
(3) get that Acidian polypeptide 10mg and Cacumen Securinegae Suffruticosae alcohol extraction thing 5g are mixed to get final product.
Application examples
Example 5
The anti-hepatitis B virus oral liquid: Acidian polypeptide 10mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 8g, cyclamate 1g, sucrose 60g, Herba Menthae 40g, ethyl hydroxybenzoate 0.5g, sodium benzoate 2g, water adds to 1000g.
Preparation method: get the described compositions adding distil water dissolving of preparation example 1, add ethyl hydroxybenzoate, sodium benzoate solution again, add cyclamate, sucrose, Herba Menthae at last and stir and make dissolving, adding distil water is to full dose again, fill, and sterilization is promptly.
Example 6
The anti-hepatitis B virus oral liquid: Acidian polypeptide 7mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 6g, sucrose 70g, ethyl hydroxybenzoate 1g, water adds to 1000g.
Preparation method: get preparation example 2 described compositions adding distil water dissolvings, add the ethyl hydroxybenzoate stirring and dissolving again, add the sucrose stirring at last and make dissolving, adding distil water is to full dose again, and fill is sterilized promptly.
Example 7
The anti-hepatitis B virus oral liquid: Acidian polypeptide 5mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 5g, cyclamate 1.5g, Herba Menthae 30g, sodium benzoate 2.5g water adds to 1000g.
Preparation method: get the described compositions adding distil waters dissolving of preparation example 3, add sodium benzoate solution again, add cyclamate at last, Herba Menthae stirs and makes dissolving, adding distil water is to full dose again, fill, and sterilization is promptly.
Example 8
The anti-hepatitis B virus oral liquid: Acidian polypeptide 1mg, Cacumen Securinegae Suffruticosae alcohol extraction thing 5g, cyclamate 1.2g, sucrose 90g, Herba Menthae 25g, ethyl hydroxybenzoate 1g, water adds to 1000g.
Preparation method: get the described compositions adding distil waters dissolving of preparation example 4, add ethyl hydroxybenzoate again, add cyclamate, sucrose, Herba Menthae at last and stir and make dissolving, adding distil water is to full dose again, fill, and sterilization is promptly.
SEQUENCE LISTING
＜110〉Nanfang Medical Univ
＜120〉pharmaceutical composition of a kind of anti-hepatitis B virus and preparation method thereof
<160>1
<170>PatentIn version 3.3
<210>1
<211>7
<212>PRT
<213>Ascidia
<400>1
Ser Ser Leu Ser Lys Ala Ala
1 5
Claims (4)
1, a kind of pharmaceutical composition of anti-hepatitis B virus, said composition is made up of following components in weight percentage:
0.001～0.01 part of Acidian polypeptide
5～8 parts of Cacumen Securinegae Suffruticosae alcohol extraction things
Wherein, the aminoacid sequence of described Acidian polypeptide is Ser Ser Leu Ser Lys Ala Ala (SEQ NO.1), and Ser is a serine in the formula, and Leu is a leucine, and Lys is a lysine, and Ala is an alanine.
2, the application of the described hepatitis B virus resisting medicine compositions of claim 1 in preparation treatment hepatitis B medicament.
3, application according to claim 2, wherein said medicine are the anti-hepatitis B virus oral liquids that contains the component of following weight proportion:
0.001～0.01 part of Acidian polypeptide, 5～8 parts of Cacumen Securinegae Suffruticosae alcohol extraction things, 2～3 parts of antiseptic, sweeting agent are an amount of, 800～1000 parts in water.
In the said components, sweeting agent is a cyclamate or/and sucrose, and antiseptic is that benzoic acid is or/and ethyl hydroxybenzoate.
4, anti-hepatitis B virus oral liquid according to claim 3 also contains 20～50 parts of Herba Menthaes in this oral liquid.
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| CNB2007100277870A CN100528221C (en) | 2007-04-29 | 2007-04-29 | Anti-hepatitis B virus medicine agent and its preparing process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100277870A CN100528221C (en) | 2007-04-29 | 2007-04-29 | Anti-hepatitis B virus medicine agent and its preparing process |
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| Publication Number | Publication Date |
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| CN101041061A true CN101041061A (en) | 2007-09-26 |
| CN100528221C CN100528221C (en) | 2009-08-19 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103980348A (en) * | 2014-05-26 | 2014-08-13 | 重庆市科学技术研究院 | Oligopeptide for diagnosing and treating hepatitis B and application of oligopeptide |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103980348A (en) * | 2014-05-26 | 2014-08-13 | 重庆市科学技术研究院 | Oligopeptide for diagnosing and treating hepatitis B and application of oligopeptide |
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| Publication number | Publication date |
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| CN100528221C (en) | 2009-08-19 |
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