Summary of the invention: the preparation technology who the object of the present invention is to provide a kind of common arange daylily and Rumex crispus L containing liver-benefiting medicine of the novel form that can effectively treat hepatitis B, can be accepted by all patients again.
The present invention is achieved in that with following materials of weight proportions component and makes by following method for making:
Radix Rumicis 500-700g Hemerocallis fulva L. 150-250g Herba Senecionis Scandentis 140-220g
Fructus actinidiae chinensis 140-220g Rhizoma Smilacis Glabrae 140-220g Flos rosae multiflorae 80-160g
Herba Swertiae bimaculatae 80-160g Radix Pimpinellae Candolleanae 80-160g Fructus Schisandrae Sphenantherae 80-160g
Radix Salviae Miltiorrhizae 80-160g Radix Glycyrrhizae 20-60g
Method for making:
(1) with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae respectively with 80% alcohol reflux twice of medical material 5 times of amounts, 3 times of amounts, 1.5 hours time, 1.0 hours, filtration, merging filtrate is put coldly, under constantly stirring, slowly adds ethanol and transfers to and contain alcohol 80%, left standstill 24 hours, and got A liquid, medicinal residues are continued to employ;
(2) other eight flavors medical materials add above-mentioned medicinal residues, add the hot reflux of 5 times of amounts of medical material drinking water and extract 2.5 hours, filter merging filtrate, be concentrated into 1.10 ± 50 ℃ of relative densities, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, B liquid;
(3) merge A, the heavy supernatant of B liquid, be concentrated into relative density 1.35 ± 0.02,80 ℃ of drying under reduced pressure were also pulverized 100 mesh sieves, or be concentrated into relative density and be spray dried to fine powder for 1.10 ± 50 ℃, add adjuvant, granulate, oven dry with 75% ethanol, granulate, the conventional operation of process is directly or indirectly made any in capsule, granule, the tablet.
Described adjuvant is dextrin, protein sugar or starch, and the proportioning of crude drug processing fine powder and adjuvant is 5: 1-50.
Wherein capsule prepares like this: with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae respectively with twice of 80% alcohol reflux of medical material 5 times of amounts, 3 times of amounts, 1.5 hours time, 1.0 hour, filter merging filtrate, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get A liquid, medicinal residues are continued to employ; Other eight flavors medical materials add above-mentioned medicinal residues, add the hot reflux of 5 times of amounts of medical material drinking water and extract 2.5 hours, filter merging filtrate, be concentrated into 1.10 ± 50 ℃ of relative densities, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, B liquid; Merge A, the heavy supernatant of B liquid, be concentrated into relative density 1.35 ± 0.02,80 ℃ of drying under reduced pressure were also pulverized 100 mesh sieves, or were concentrated into relative density and are spray dried to fine powder for 1.10 ± 50 ℃, added starch by the total amount of making, granulate with 75% ethanol, oven dry, granulate, total mixing, fill, blister package promptly gets the Huang-Xuan-Yi-gan capsule.
Granule prepares like this: with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae respectively with twice of 80% alcohol reflux of medical material 5 times of amounts, 3 times of amounts, 1.5 hours time, 1.0 hour, filter merging filtrate, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get A liquid, medicinal residues are continued to employ; Other eight flavors medical materials add above-mentioned medicinal residues, add the hot reflux of 5 times of amounts of medical material drinking water and extract 2.5 hours, filter merging filtrate, be concentrated into 1.10 ± 50 ℃ of relative densities, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, B liquid; Merge A, B
Liquid sinks supernatant, is concentrated into relative density 1.35 ± 0.02, adds dextrin, protein sugar by the total amount of making, through granulating, and oven dry, granulate, total mixing, packing promptly gets the Huang-Xuan-Yi-gan granule.
Tablet prepares like this: with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae respectively with twice of 80% alcohol reflux of medical material 5 times of amounts, 3 times of amounts, 1.5 hours time, 1.0 hour, filter merging filtrate, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get A liquid, medicinal residues are continued to employ; Other eight flavors medical materials add above-mentioned medicinal residues, add the hot reflux of 5 times of amounts of medical material drinking water and extract 2.5 hours, filter merging filtrate, be concentrated into 1.10 ± 50 ℃ of relative densities, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, B liquid; Merge A, the heavy supernatant of B liquid, be concentrated into relative density 1.35 ± 0.02,80 ℃ of drying under reduced pressure were also pulverized 100 mesh sieves, or were concentrated into relative density and are spray dried to fine powder for 1.10 ± 50 ℃, by the starch of the amount of making adding always, dextrin, granulate oven dry, granulate with 75% ethanol, total mixing, tabletting, coating, packing promptly gets the Huang-Xuan-Yi-gan tablet.
Huang-Xuan-Yi-gan capsule, Huang-Xuan-Yi-gan granule and the Huang-Xuan-Yi-gan tablet that preparation technology of the present invention makes overcome the deficiency of original Huang-Xuan-Yi-gan powder, can be accepted by extensive patients, different patients' needs have been satisfied, make this national characters medicine can be widely used in hepatitis B patient, pharmaceutical preparations is through clinical verification, determined curative effect.
The Clinical results of Huang-Xuan-Yi-gan capsule, Huang-Xuan-Yi-gan granule and Huang-Xuan-Yi-gan tablet in treatment chronic viral hepatitis B:
One, the object of observation and grouping
1, the object of observation and grouping
Table 1 object of observation and grouping
The group example number sex age (year)
The men and women
Yellow tawny daylily hepatitis B capsule group 114 72 42 35.7 ± 8.98
Yellow tawny daylily hepatitis B groups of grains 117 68 49 38.3 ± 9.14
Yellow tawny daylily hepatitis B tablet group 111 70 41 35.4 ± 8.69
Matched group 58 36 22 36.2 ± 8.54
Table 1 analysis result shows, 4 groups of sexes, age differences not statistically significant have better comparability.
More than 4 groups of patients all do not accept treatments such as interferon, hepatitis B immune regulator.
2, the Therapeutic Method and the course of treatment
(1) yellow tawny daylily hepatitis B capsule group: oral yellow tawny daylily hepatitis B capsule, each 4, three times on the one.3 months is 1 course of treatment.
(2) yellow tawny daylily hepatitis B groups of grains: oral yellow tawny daylily hepatitis B granule, each 1 bag, three times on the one.3 months is 1 course of treatment.
(3) yellow tawny daylily hepatitis B tablet group: oral yellow tawny daylily hepatitis B tablet, each 4, three times on the one.3 months is 1 course of treatment.
(4) oleanolic acid tablet matched group: oral oleanolic acid tablet, each 40 milligrams, three times on the one.3 months is 1 course of treatment.
3, observation index
(1) clinical symptoms, sign: weak, poor appetite, jaundice, loose stool, liver enlargement, spleen enlargement, spider angioma, white and greasy fur, stringy and rolling pulse etc.
(2) laboratory liver function test: ALT, AST, bilirubin, albumin, A/G.
(3) the hepatitis virus mark is checked: HBsAg, anti--HBs, HBeAg, anti--HBe, anti--HBc (ELISA method).
Two, curative effect determinate standard (the clinical research guideline with reference to new Chinese medicine treatment viral hepatitis is formulated)
1, produce effects: transference cure, liver spleen recover normal or retraction, no tenderness and kowtowing bitterly, and liver function is normal again, and HBV DNA, HBsAg, HBeAg all turn out cloudy.More than every index be stabilized in more than 6 months.
2, effective: symptom obviously alleviates or disappears, and hepatosplenomegaly is stablized constant, does not have obvious tenderness and kowtows pain, and liver function test recovers normal or descends more than 50% than exceptional value before the treatment, and HBV DNA, HBsAg, HBeAg have 1 to turn out cloudy.More than every index be stabilized in more than 3 months.
3, do not reach above-mentioned standard person.
Three, therapeutic outcome
1, clinical efficacy contrast
The contrast of table 2 clinical efficacy
Group example number clinical efficacy total effective rate %
The produce effects enabledisable
N % N % N %
Yellow tawny daylily hepatitis B capsule group 114 42 36.84 45 39.47 27 23.68 76.32
Yellow tawny daylily hepatitis B groups of grains 117 40 34.19 47 40.17 30 25.64 74.36
Yellow tawny daylily hepatitis B tablet group 111 42 37.84 41 36.94 28 25.23 74.77
Matched group 58 14 24.14 18 31.03 26 44.83 55.17
(1) yellow tawny daylily hepatitis B capsule group and matched group relatively adopt the Wilcoxon check, Z=2.62, and P=0.01, two groups of curative effect differences have statistical significance.
(2) yellow tawny daylily hepatitis B groups of grains and matched group relatively adopt the Wilcoxon check, Z=2.29, and P=0.02, two groups of curative effect differences have statistical significance.
(3) yellow tawny daylily hepatitis B tablet group and matched group relatively adopt the Wilcoxon check, Z=2.53, and P=0.01, two groups of curative effect differences have statistical significance.
(4) three kinds of dosage form curative effects of yellow tawny daylily hepatitis B relatively adopt the Kruskal-Wallis check, H=0.25, P=0.88, three groups of curative effect difference not statistically significants.
Analysis result shows in the table, and four kinds of preparations all have clinical efficacy preferably, but the clinical efficacy of three kinds of dosage forms of yellow tawny daylily hepatitis B all is better than the oleanolic acid tablet matched group; Three kinds of dosage form curative effects of yellow tawny daylily hepatitis B difference not statistically significant, therapeutic equivalence.
2, change before and after the laboratory checking index treatment
Change before and after the treatment of table 3 laboratory liver function test index
P in the group of treatment back before the treatment of index group example number
The yellow tawny daylily hepatitis B capsule of ALT (IU/L) group 114 145.55 ± 65.72 65.32 ± 24.17
*<0.01
Yellow tawny daylily hepatitis B groups of grains 117 147.30 ± 53.76 63.98 ± 30.18
*<0.01
Yellow tawny daylily hepatitis B tablet group 111 140.27 ± 63.01 66.11 ± 26.17
*<0.01
Matched group 58 139.91 ± 59.87 85.47 ± 33.41<0.01
The yellow tawny daylily hepatitis B capsule of AST (IU/L) group 114 136.19 ± 42.16 55.74 ± 26.81
*<0.01
Yellow tawny daylily hepatitis B groups of grains 117 133.72 ± 42.10 54.91 ± 25.69
*<0.01
Yellow tawny daylily hepatitis B tablet group 111 143.52 ± 40.61 55.21 ± 24.99
*<0.01
Matched group 58 134.53 ± 37.66 65.60 ± 30.42<0.01
The yellow tawny daylily hepatitis B capsule of bilirubin group 114 76.43 ± 18.52 38.86 ± 12.59
*<0.01
(umol/L) yellow tawny daylily hepatitis B groups of grains 117 71.32 ± 20.71 39.12 ± 10.73
*<0.01
Yellow tawny daylily hepatitis B tablet group 111 73.77 ± 23.92 36.27 ± 18.72
*<0.01
Matched group 58 74.36 ± 22.65 45.72 ± 19.62<0.01
The yellow tawny daylily hepatitis B capsule of albumin group 114 18.43 ± 3.53 45.82 ± 5.82
*<0.01
(g/L) yellow tawny daylily hepatitis B groups of grains 117 19.01 ± 5.82 46.92 ± 5.51
*<0.01
Yellow tawny daylily hepatitis B tablet group 111 20.11 ± 4.32 43.55 ± 5.87
*<0.01
Matched group 58 20.37 ± 5.92 36.67 ± 4.79<0.01
The yellow tawny daylily hepatitis B capsule of A/G group 114 1.25 ± 0.15 1.58 ± 0.19
*<0.01
Yellow tawny daylily hepatitis B groups of grains 117 1.19 ± 0.98 1.53 ± 0.23
*<0.01
Yellow tawny daylily hepatitis B tablet group 111 1.28 ± 0.87 1.56 ± 0.45
*<0.01
Matched group 58 1.32 ± 0.72 1.47 ± 0.32<0.01
Annotate: compare with matched group, adopt t check in groups: △ P>0.05
*P<0.05
*P<0.01
Analysis result shows in the table, and abnormal liver function all obtains improvement in various degree behind four groups of patient treatments.But three kinds of dosage forms of yellow tawny daylily hepatitis B are better than the oleanolic acid tablet matched group to the improvement of abnormal liver function.
3, the hepatitis b virus marker check result relatively
Table 4 hepatitis b virus marker check result relatively
Positive routine number treatment back negative conversion rate (%) before the treatment of index group
Positive negative
The yellow tawny daylily hepatitis B capsule of anti--HBc group 65 55 10 15.38 △
Yellow tawny daylily hepatitis B groups of grains 69 59 10 14.49 △
Yellow tawny daylily hepatitis B tablet group 60 51 9 15.00 △
Matched group 32 28 4 12.50
The yellow tawny daylily hepatitis B capsule of HBeAg group 76 60 16 21.05 △
Yellow tawny daylily hepatitis B groups of grains 75 60 15 20.00 △
Yellow tawny daylily hepatitis B tablet group 71 58 13 18.31 △
Matched group 25 22 3 12.00
The yellow tawny daylily hepatitis B capsule of anti--HBe group 64 53 11 17.19 △
Yellow tawny daylily hepatitis B groups of grains 68 53 15 22.06 △
Yellow tawny daylily hepatitis B tablet group 56 48 8 14.29 △
Matched group 22 20 2 9.09
The yellow tawny daylily hepatitis B capsule of HBsAg group 53 43 10 18.87 △
Yellow tawny daylily hepatitis B groups of grains 61 50 11 18.03 △
Yellow tawny daylily hepatitis B tablet group 51 42 9 17.65 △
Matched group 28 25 3 10.71
The yellow tawny daylily hepatitis B capsule of anti--HBs group 57 48 9 15.78 △
Yellow tawny daylily hepatitis B groups of grains 67 55 12 17.91 △
Yellow tawny daylily hepatitis B tablet group 61 51 10 16.39 △
Matched group 23 19 4 17.39
Annotate: compare with matched group, adopt the x2 check: △ P>0.05
*P<0.05
*P<0.01
Analysis result shows in the table, all has part patient virus marker thing to turn out cloudy behind four groups of patient treatments, but virus marker thing negative conversion rate compares between four groups, the equal not statistically significant of difference.
4, clinical symptoms, sign curative effect
Behind four groups of chronic viral hepatitis B patient treatments, the clinical symptoms of its performance and sign are comprised that weak, poor appetite, jaundice, loose stool, liver enlargement, spleen enlargement, tongue pulse condition etc. all have improvement in various degree, the degree difference not statistically significant (P>0.05) of doing well,improving between yellow tawny daylily hepatitis B three preparations.
Model case:
Example one: Song Renkui, the man, 47 years old, because of weak, one week of poor appetite is admitted to hospital, the patient once suffered from hepatitis B, and to live the treatment of my institute surplus January, and clinical cure is left hospital, and is weak sometimes after leaving hospital, poor appetite and uncomfortable liver area, and, once intermittently took hepatoprotective and anti-hbv drug with more obvious after the fatigue, because of being afraid of the work that influences hospitalization once more not always, a nearly week comes because of the fatigue of working, add night shift self-induction above-mentioned symptom and increase the weight of and hospitalization, have a medical check-up: the slight jaundice of skin sclera, liver about 2cm under rib, the soft minute-pressure pain of matter, spleen just touch.Chemical examination: ALT150u, the total bilirubin/straight red matter 46/31umo/L of gallbladder, the serum HBV sign is checked, HBsAg+, HBc+.Being admitted to hospital, the Huang-Xuan-Yi-gan granule is given by chronic active hepatitis in the back and supporting treatment is treated, and about first quarter moon clinical symptoms disappears substantially, and liver obviously bounces back, and ALT reduces to 99.70u.Clinical symptoms after January, hepatosplenomegaly and ALT all recover normally, and the serum HBV sign is checked
The HBsAg positive, sundry item is turned out cloudy, and through hospitalization February, clinical cure is left hospital.
Example two: Wang Jiazhen, woman, 30 years old.Because of the weak poor appetite of discontinuity 2 years surplus, institute go to a doctor to me March calendar year 2001, this patient before 2 years once Hospital Attached to Guiyang Medical College be diagnosed as chronic hepatitis B, hospitalization is surplus February, disease takes a turn for the better and leaves hospital, the all chance work fatigues in back of leaving hospital are promptly felt and being short of physical strength, diet is not good, so fail to go to work carefully always, once lived Hospital Attached to Guiyang Medical College repeatedly, the Guizhou Province People ' s Hospital, Guiyang infectious hospital used interferon, transfer factor, Drug therapys such as Hepatitis B virus vaccine, symptom is alleviated sometimes, hepatitis B Mark Detection HBeAg, anti--sun when cloudy during HBc, most time is that great three positive changes, through taking the Huang-Xuan-Yi-gan capsule for treating three months, clinical basic disappearance can be adhered to operate as normal, HbsAg, anti--HBc, HBeAg all turns out cloudy.
Example three: Chen Zhonghe, man, 26 years old, the worker of business unit.Once be chronic hepatitis B after diagnosing in Affiliated Hospital of Guiyang College of Traditional Chinese Medicine before 3 years, the treatment in February of being in hospital, sb.'s illness took a favorable turn leaves hospital.Leaving hospital, fatigue is met in the back and work and study increase the weight of, and has repeatedly again.February the cause xanthochromia, body is soft weak, and increases the weight of day by day, satisfies at my institute's hospitalization.Show through looking into liver function: ALT:150IU/L, bilirubin 90.01umol/L, anti--HBs+, HBeAg+.Liver 2cm place under right rib can reach, and tenderness is arranged in the liver, and spleen is not laid one's hand on and (-).Give yellow tawny daylily hepatitis B tablet treatment, oral, each 4, three times on the one.Took continuously 3 months.After taking for 2 weeks, clinical symptoms and sign are obviously improved.Every symptom disappears substantially after March, and anti--HBs, HBeAg all turns out cloudy, and it is normal to look into every liver function index.
The specific embodiment:
Embodiment 1: take by weighing Radix Rumicis 654.75g, Hemerocallis fulva L. 231.75g, Herba Senecionis Scandentis 207g, Fructus actinidiae chinensis 207g, Rhizoma Smilacis Glabrae 207g, Flos rosae multiflorae 139.5g, Herba Swertiae bimaculatae 139.5g, Radix Pimpinellae Candolleanae 139.5g, Fructus Schisandrae Sphenantherae 139.5g, Radix Salviae Miltiorrhizae 139.5g, Radix Glycyrrhizae 45g makes 1000 seed lac wafers, with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae is used 5 times of amounts of medical material respectively, twice of 80% alcohol reflux of 3 times of amounts, time is 1.5 hours, 1.0 hour, filter, merging filtrate, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get A liquid, medicinal residues are continued to employ, other eight flavors medical materials add above-mentioned medicinal residues, adding the hot reflux of 5 times of amounts of medical material drinking water extracted 2.5 hours, filter, merging filtrate, be concentrated into relative density 1.10 ± (50 ℃), put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get B liquid, merge above-mentioned A, B liquid sinks supernatant, is concentrated into relative density 1.35 ± 0.02 (50 ℃), and 80 ℃ of drying under reduced pressure were also pulverized 100 mesh sieves, or be concentrated into relative density 1.10 ± (50 ℃) and be spray dried to fine powder, by the starch of the amount of making adding always, granulate oven dry with 75% ethanol, granulate, total mixing filled, and blister package promptly gets the Huang-Xuan-Yi-gan capsule.
Embodiment 2: take by weighing Radix Rumicis 523.8g, Hemerocallis fulva L. 185.4g, Herba Senecionis Scandentis 165.6g, Fructus actinidiae chinensis 165.6g, Rhizoma Smilacis Glabrae 165.6g, Flos rosae multiflorae 111.6g, Herba Swertiae bimaculatae 111.6g, Radix Pimpinellae Candolleanae 111.6g, Fructus Schisandrae Sphenantherae 111.6g, Radix Salviae Miltiorrhizae 111.6g, Radix Glycyrrhizae 36g makes 1000 gram granules, with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae is used 5 times of amounts of medical material respectively, twice of 80% alcohol reflux of 3 times of amounts, time is 1.5 hours, 1.0 hour, filter, merging filtrate, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get A liquid, medicinal residues are continued to employ, and other eight flavors medical materials add above-mentioned medicinal residues, add the hot reflux of 5 times of amounts of medical material drinking water and extract 2.5 hours, filter, merging filtrate is concentrated into relative density 1.10 ± (50 ℃), puts cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, B liquid, merge above-mentioned A, B liquid sinks supernatant, and is dense
Contract to relative density 1.35 ± 0.02 (50 ℃),,, dry through granulating by the dextrin of the amount of making adding always, protein sugar, granulate, total mixing packed and promptly got the Huang-Xuan-Yi-gan granule.
Embodiment 3: take by weighing Radix Rumicis 654.75g, Hemerocallis fulva L. 231.75g, Herba Senecionis Scandentis 207g, Fructus actinidiae chinensis 207g, Rhizoma Smilacis Glabrae 207g, Flos rosae multiflorae 139.5g, Herba Swertiae bimaculatae 139.5g, Radix Pimpinellae Candolleanae 139.5g, Fructus Schisandrae Sphenantherae 139.5g, Radix Salviae Miltiorrhizae 139.5g, Radix Glycyrrhizae 45g makes 1000 tablets of tablets, with Radix Rumicis, Fructus Schisandrae Sphenantherae, Radix Salviae Miltiorrhizae is used 5 times of amounts of medical material respectively, twice of 80% alcohol reflux of 3 times of amounts, time is 1.5 hours, 1.0 hour, filter, merging filtrate, put cold, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get A liquid, medicinal residues are continued to employ, other eight flavors medical materials add above-mentioned medicinal residues, adding the hot reflux of 5 times of amounts of medical material drinking water extracted 2.5 hours, filter, merging filtrate, be concentrated into relative density 1.10 ± (50 ℃), put coldly, under constantly stirring, slowly add ethanol and transfer to and contain alcohol 80%, left standstill 24 hours, get B liquid, merge above-mentioned A, B liquid sinks supernatant, is concentrated into relative density 1.35 ± 0.02 (50 ℃), 80 ℃ of drying under reduced pressure were also pulverized 100 mesh sieves, or be concentrated into relative density 1.10 ± (50 ℃) and be spray dried to fine powder, add starch by the total amount of making, dextrin is granulated with 75% ethanol, oven dry, granulate, total mixed, tabletting, coating, packing promptly gets the Huang-Xuan-Yi-gan tablet.