CN101224226B - Novel clinical uses of big nilgiri nettle - Google Patents
Novel clinical uses of big nilgiri nettle Download PDFInfo
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- CN101224226B CN101224226B CN200710201631XA CN200710201631A CN101224226B CN 101224226 B CN101224226 B CN 101224226B CN 200710201631X A CN200710201631X A CN 200710201631XA CN 200710201631 A CN200710201631 A CN 200710201631A CN 101224226 B CN101224226 B CN 101224226B
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Abstract
The invention discloses a new clinical use of scorpion grass, which more particularly relates to the application of the scorpion grass in drugs for treating liver damage, nephritis, benign prostatic hypertrophy, tumor and blood clots diseases. The invention uses the scorpion grass as raw material to produce extract of scorpion grass by extraction according to conventional technology; then accessory material is added, so as to prepare conventional oral dosage or non-oral dosage formulas suitable for clinical use. The invention can be applied to treating liver damage, nephritis, benign prostatic hypertrophy, tumor and blood clots diseases and other cardiovascular diseases.
Description
Technical field
The present invention relates to the novel clinical use of Herba Girardiniae Palmatae, the particularly application of Herba Girardiniae Palmatae extract in cardiovascular disease medicines such as preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism belongs to technical field of medicaments.
Background technology
Herba Girardiniae Palmatae Girardinia diversifolia (Link) Friis is the dry herb of Urticaceae Sedum spectabile Boreau platymiscium Herba Girardiniae Palmatae Girardinia diversifolia (Link) Friis, stem is tall and big 2 meters, tool 5 ribs, the fine hair of giving birth to seta and thin rough hair or stretching, multi-branched.The leaf alternate, blade profile width egg shape, oblateness or pentagon, the leaf of stem is bigger, and the leaf on the branch is less, length and wide equal 8～25cm, feel relieved shape or closely cut shape of base portion, tool (3-) 5-7 drastic crack sheet is rare, do not split, there are irregular tooth or heavy tooth in the edge, dredge to give birth to seta and strigose above, look unfamiliar down strigose or short bristle and on arteries and veins, dredge and give birth to seta, base is given birth to 3 in arteries and veins; Petiole long 3～15cm, fleece is with on the stem; Stipule is big, and oval shape is avette, long 10～30mm, and the outside is dredged and is given birth to thin strigose.Herba Girardiniae Palmatae, cool in nature, bitter in the mouth, suffering, poisonous.Have and eliminate the phlegm, dampness removing, the antidotal effect is used in the subregion of Guizhou Miao ethnic group, is used for cough with copious phlegm, edema.Sore is controlled in external.Consumption is 10～50g, and suitable amount used externally is fried in shallow oil washing.Herba Girardiniae Palmatae is used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, has had not yet to see report.
Summary of the invention
The objective of the invention is to, the novel clinical use of Herba Girardiniae Palmatae is provided.Be the application of Herba Girardiniae Palmatae in preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism medicine.With Herba Girardiniae Palmatae is that the pharmaceutical preparation that raw material is made has significant therapeutical effect to cardiovascular disease such as hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism.
Technical scheme of the present invention.The novel clinical use of Herba Girardiniae Palmatae is that Herba Girardiniae Palmatae is used in preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and the vessel embolism medicine.
In the novel clinical use of above-mentioned Herba Girardiniae Palmatae, the Herba Girardiniae Palmatae extract is applied to prepare the medicine of treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, can adopt any dosage form that allows clinically.Can be medicinal preparation for oral administration, as powder, tablet, granule, capsule, microcapsule, pill, drop pill, soft capsule, oral liquid, syrup, dispersible tablet, spray or aerosol etc.; Also can be non-medicinal preparation for oral administration, as suppository, injection (comprising intravenous injection, intramuscular injection), ointment, inhalant, gel etc.
In the novel clinical use of aforementioned Herba Girardiniae Palmatae, Herba Girardiniae Palmatae is used for preparation treatment hepatic injury, nephritis, prostate hyperplasia, the medicine of tumor and vessel embolism, be to be raw material with the Herba Girardiniae Palmatae, technology obtains the Herba Girardiniae Palmatae total extract through extraction routinely, and then add corresponding adjuvant, be prepared into any oral or non-peroral dosage form that is suitable for using clinically, as powder, tablet, granule, capsule, microcapsule, pill, drop pill, soft capsule, oral liquid, syrup, dispersible tablet, spray or aerosol, suppository, injection (comprises intravenous injection, intramuscular injection), ointment, inhalant, gel etc.Used adjuvant comprises excipient substances such as conventional solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant, lubricant, wetting agent, thickening agent, solubilizing agent, substrate.
In the novel clinical use of aforementioned Herba Girardiniae Palmatae, Herba Girardiniae Palmatae is used to prepare the medicine of treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, can also forms compound medicine with one or more the medicine in diaphoretic medicine, antipyretic, purgatives medicine, medicine for rheumatism, damp-resolving medicinal, damp-clearing drug, digestants, hemorrhage, drugs for dispelling internal cold, QI regulating medicine, stasis-resolving hemostatic, drug for invigorating blood circulation and eliminating stasis, expectorants, antitussives and anti-asthmatics medicine, sedative, medicine for calming liver and calming endopathic wind, awaking drug, the qi-restoratives medicine.
In the novel clinical use of aforementioned Herba Girardiniae Palmatae, Herba Girardiniae Palmatae is used for preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism medicine, described diaphoretic medicine is Ramulus Cinnamomi, Herba Asari, Rhizoma Zingiberis Recens, Herba Menthae, Radix Puerariae or Rhizoma Cimicifugae; Described antipyretic is Radix Scutellariae, Rhizoma Coptidis, Cortex Phellodendri, Herba Taraxaci or Herba Houttuyniae, described purgatives medicine is Radix Et Rhizoma Rhei, Folium Sennae or Fructus Crotonis, described medicine for rheumatism is Radix Angelicae Pubescentis, Radix Aconiti or Radix Tripterygii Wilfordii, described damp-resolving medicinal is Rhizoma Atractylodis or Cortex Magnoliae Officinalis, described damp-clearing drug is Poria, Polyporus, Rhizoma Alismatis or Semen Coicis, described digestants is Fructus Crataegi or Fructus Hordei Germinatus, and described hemorrhage is Radix Notoginseng, Pollen Typhae, Radix Rubiae or Pseudobulbus Bletillae (Rhizoma Bletillae), and described drugs for dispelling internal cold is Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis, Cortex Cinnamomi, Fructus Evodiae, Pericarpium Zanthoxyli or Flos Caryophylli; Described QI regulating medicine is Pericarpium Citri Reticulatae, Pericarpium Citri Reticulatae Viride, the Radix Aucklandiae, Rhizoma Cyperi, Fructus Toosendan or the Radix Linderae; Described stasis-resolving hemostatic is Radix Notoginseng, Pollen Typhae or Radix Rubiae; Described drug for invigorating blood circulation and eliminating stasis is Rhizoma Chuanxiong, Rhizoma Corydalis, Radix Curcumae, Rhizoma Curcumae Longae, Olibanum, Myrrha, Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae, Flos Carthami, Semen Persicae, Herba Leonuri, Radix Ilicis Pubescentis, Rhizoma Curcumae, Hirudo, Sanguis Draxonis or Semen Strychni; Described expectorants, antitussives and anti-asthmatics medicine is the Rhizoma Pinelliae, Rhizoma Arisaematis, Radix Platycodi (Radix Platycodonis), Bulbus Fritillariae Cirrhosae, Flos Daturae; Sedative is Semen Ziziphi Spinosae or Ganoderma; Medicine for calming liver and calming endopathic wind is Rhizoma Gastrodiae, Ramulus Uncariae Cum Uncis, Cornu Saigae Tataricae, Scorpio, Bombyx Batryticatus, Pheretima or Calculus Bovis; Described awaking drug is Moschus, Borneolum Syntheticum or Styrax; Described qi-restoratives medicine is Radix Ginseng, Radix Panacis Quinquefolii, Radix Codonopsis, the Radix Astragali, the Rhizoma Atractylodis Macrocephalae, Rhizoma Dioscoreae, Radix Glycyrrhizae or Radix Et Caulis Acanthopanacis Senticosi.
The present invention uses the medicine of Herba Girardiniae Palmatae preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, and its curative effect of medication can show by the influence of Herba Girardiniae Palmatae extract to experimental animal models such as hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism.
Below be experimental example of the present invention:
Experimental example 1: the Herba Girardiniae Palmatae extract is to the influence to the impatient liver damage of rat experiment
1. experiment material
1.1 material: the carbon dioxide supercritical fluid extraction thing of Herba Girardiniae Palmatae is the taupe powder.People's consumption is 0.5～12g (extract)/10～120g crude drug/60kg.
1.2 laboratory animal: healthy male SD rat, the ICR mice, the cleaning level, body weight is 180～220g, Guiyang Medical College experimental animal center, quality certification SCXK (Guizhou Province) 2002-2001.Animal is raised with test full-valence pellet feed (Guiyang Medical College experimental animal center provides), freely drinks water 22 ± 2 ℃ of room temperatures.
2. method
2.1 Herba Girardiniae Palmatae is induced the influence of acute liver damage model to D-Gal: 50 of SD rats, body weight is 180～220g, be divided into 5 groups at random, that is: normal control group (giving the isometric(al) distilled water), model group (giving the isometric(al) distilled water), drug component are three dosage group: 2.5g/kg, 5g/kg, 10g/kg, and the administration volume is 10ml/kg; After each organized continuous gastric infusion 5d, except that the normal control group, all the other respectively organized lumbar injection D-Gal 800mg/kg after the last administration, and behind the 11h, each group is irritated stomach and given medicine 1 time, behind the 1h, gets blood through the ball rear vein beard, analyzes AST, ALT.
2.2 Herba Girardiniae Palmatae is to CCl
4The influence of inducing mouse liver injury model: 50 of ICR healthy male mices are divided into 5 groups at random, normal control group (giving the isometric(al) distilled water), model group (giving the isometric(al) distilled water), drug component are three dosage group: 4g/kg, 8g/kg, 16g/kg, and the administration volume is 20ml/kg; After each organizes continuous gastric infusion 5d, 1h after administration, all the other are respectively organized lumbar injection and contain 0.5%CCl except that the normal control group
4Olive oil 10ml/kg, 16h respectively organizes administration again 1 time after the modeling, mice ball rear vein beard is got blood behind the 1h, 1500 commentaries on classics/min, separation of serum is analyzed ALT, AST vigor by the commercial reagent box.
2.3 Herba Girardiniae Palmatae is to the protective effect of mice alcoholic liver injury: mice is divided into 5 groups at random: blank group (giving the isometric(al) distilled water), model group (giving the isometric(al) distilled water), drug component are three dosage group: 4g/kg, 8g/kg, 16g/kg, and the administration volume is 20ml/kg; Each organizes continuous gastric infusion 30d.60min after the last administration, all the other are respectively organized per os and irritate stomach ethanol 50% analytically pure ethanol 12ml/kg (4.8g/kg) for 1 time except that the blank group.The blank group gives distilled water, gets blood behind the fasting 12h and carries out biochemical analysis, puts to death animal, gets liver and makes 10% liver homogenate with normal saline, detects the content of MDA, GSH, TG in the hepatic tissue.
2.4 data analysis and statistical method: all data represent that with x ± s statistical analysis adopts the student-T check.
3. result
3.1 the Herba Girardiniae Palmatae extract is to the influence of rat acute hepatic injury due to the D aminogalactose: behind the model group lumbar injection D-Gal, AST, ALT significantly increase in the blood, and the continuous gastric infusion 5d of Herba Girardiniae Palmatae significantly reduces AST in the blood, ALT.The results are shown in Table 1.
Table 1 Sedum spectabile Boreau extract to D-Gal hepatic injury rat blood serum ALT and the active influence of AST (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01
3.2 the Herba Girardiniae Palmatae extract is to CCl
4Hepatic injury mice serum ALT and AST active influence: injected in mice CCl
4Back 16h, Serum ALT, AST vigor significantly raise.Compare with model group, the Herba Girardiniae Palmatae extract can significantly suppress the rising of ALT, AST vigor, shows that Herba Girardiniae Palmatae can obviously improve CCl
4The induced mice acute liver damage.The results are shown in Table 2.
Table 2 Herba Girardiniae Palmatae extract is to CCl
4The active influence of hepatic injury mice serum ALT and AST (x ± s, n=10)
| Group | Dosage (the g crude drug/kg) | AST(U/L) | ALT(U/L) |
| Matched group | 45.6±13.5 | 188.7±28.6 | |
| Model group | 108.6±43.7 ## | 298.3±65.3 ## | |
| Herba Girardiniae Palmatae | 16 | 48.6±15.8** | 206.3±50.7** |
| 8 | 60.25±20.6* | 235.6±60.3* | |
| 4 | 80.9±40.7 | 272.5±62.3 |
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
3.3 Herba Girardiniae Palmatae is to the protective effect of mice alcoholic liver injury: malonaldehyde, triacylglycerol in the ethanol liver injury model group murine liver tissue all are higher than the blank group, and difference has significance meaning (P＜0.01); Reduced glutathion in the ethanol liver injury model group murine liver tissue is lower than the blank group, and difference has significance meaning (P＜0.01), and the modelling success is described.Reduced glutathion is higher than ethanol liver injury model group in the 16g/kg Herba Girardiniae Palmatae group murine liver tissue, and difference has significance meaning (P＜0.05); Malonaldehyde, triacylglycerol in the 16g/kg Herba Girardiniae Palmatae group murine liver tissue are lower than ethanol liver injury model group, and difference has significance meaning (P＜0.05), the results are shown in Table 3.
Table 3 Herba Girardiniae Palmatae extract to the influence of alcoholic liver injury murine liver tissue MDA, GSH, TG (x ± s, n=10)
| Group | Dosage (the g crude drug/kg) | MDA (mmol/g) | GSH (mmol/g) | TG (mg/g) |
| The blank group | 87.0±18.7 | 6.6±0.9 | 2.81±0.92 | |
| Model group | 160.3±29.6 ## | 3.1±0.7 ## | 11.38±4.21 ## | |
| Herba Girardiniae Palmatae | 16 | 98.3±35.6** | 5.6±1.3* | 5.53±1.38* |
| 8 | 136.7±38.6 | 4.5±1.9 | 6.98±2.97 | |
| 4 | 160.5±42.7 | 5.6±1.2 | 8.12±3.96 |
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
Experimental example 2: the Herba Girardiniae Palmatae extract is to the influence of rat experiment nephritis
1. experiment material
1.1 material:
The carbon dioxide supercritical fluid extraction thing of Herba Girardiniae Palmatae, people's consumption are 0.5～12g (extract)/10～120g crude drug/60kg.
Bovine serum albumin (BSA) (Sino-American Biotec)
Staphyloentero-toxin (SEB) (Academy of Military Sciences of PLA)
Freund's complete adjuvant and Freund (Bio Basic)
1.2 laboratory animal: healthy SD rat, cleaning level, Guiyang Medical College experimental animal center, quality certification SCXK (Guizhou Province) 2002-2001.After animal via normal diet adaptability fed for 1 week, select for use urine erythrocyte, urine protein qualitative results negative patient to enter experiment.Animal is raised with test full-valence pellet feed (Guiyang Medical College experimental animal center provides), freely drinks water 22 ± 2 ℃ of room temperatures.
2. method
2.1 the Herba Girardiniae Palmatae extract is to the preventive and therapeutic effect of rat mesangial proliferative nephritis: 80 of SD rats, select 10 at random as the normal control group, other rats are irritated stomach 1 time (about 1ml/100g body weight) from experiment 1d next day of being made into aqueous solution with BSA 20mg, to the experiment end.Injected complete Freund's complete adjuvant 0.2ml (containing BSA 2mg) through subcutaneous branch in the 1st day of experiment, the 8th day injection incomplete Freund 0.2ml (containing BSA 2mg), test the 8th, 15d tail vein injection SEB (0.4mg/kg) each 1 time, wherein 30, irritate the Herba Girardiniae Palmatae that stomach gives various dose on the same day with model copy.Collect urine weekly and make routine examination RBC, WBC, (qualitative: 1+) prompting animal model success urine protein to occur, continue to irritate stomach BSA to 14 weekend, rat is divided into model group, Herba Girardiniae Palmatae extract 2.5,5.0,10g (crude drug)/dosage groups such as kg more at random.Irritate stomach every day 1 time, model group gives isometric distilled water, and each organizes the administration volume is 10ml/kg, puts to death animal to the 18th weekend.The urine of metabolic cage collection rat 24H at 0,2,6,10,14 and 18 weekend, Urine sediments analyzer is made conventional microscopy and is analyzed RBC, WBC and urine protein.The ball rear vein beard is got blood, and separation of serum is analyzed creatinine, blood urea nitrogen, total protein, albumin and ALT.
2.2 the Herba Girardiniae Palmatae extract is to the influence of rat Heymann nephritis model: get 150～200g left and right sides rat, the male and female dual-purpose is put to death the back and is taken out kidney insertion conduit, after washing repeatedly with normal saline, get renal cortex 5g and be ground into homogenate, be mixed into 10ml with Freund's complete adjuvant, add normal saline 20ml, give male rat ip of the same race, two weeks 1 time, each 1.5～2ml, totally 8 times, until albuminuria occurring.40 of the male SD rats of model will be formed, divide equally is 4 groups, be model control group, Herba Girardiniae Palmatae extract 2.5,5.0,10g (crude drug)/dosage groups such as kg, and get 10 of normal male rats and be made as the normal control group, the administration volume is 10ml/kg, every day 1 time, normal control group and model control group give the isometric(al) distilled water.Successive administration 30d, and before rat injection kidney homogenate Freund's complete adjuvant suspension, before the administration and after the administration, Cr, Bun and the Uricprotein of mensuration rabbit.
2.3 data analysis and statistical method: all data represent that with x ± s statistical analysis adopts the student-T check.
3. result
3.1 Herba Girardiniae Palmatae is to the preventive and therapeutic effect of rat mesangial proliferative nephritis
3.1.1 the influence to urine protein: urine examination RBC, WBC are all negative before the rat experiment, from the visible RBC0 of experiment the 2nd week modeling group～3/HP, but unstable result.In 6 weeks of experiment to the, albuminuria in various degree appears in the modeling group, the qualitative 1+ that reaches of the 11st week, and 24h urine protein quantitation and normal control group significant difference during the 14th, 18 weekends, and increase the weight of gradually.High dose group in the prevention group, preventive and therapeutic effect is obvious, and 14 all urine protein and model group significantly reduce; Urine protein significantly reduces after 4 weeks of treatment group treatment, with comparing difference before the treatment significance is arranged also.The results are shown in Table 4.
Table 4 Herba Girardiniae Palmatae extract to the influence of rat mesangial proliferative nephritis urine protein (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
3.1.2 the influence to rat serum Cr, Bun, TP, Alb, ALT: at 18 weekends, model group Cr, Bun and ALT significantly increase, and ALB and TP obviously reduce, and each index and normal control group relatively have significant difference (P＜0.05, P＜0.01); No matter the administration group prevents still treatment group, the Herba Girardiniae Palmatae extract obviously reduces blood Cr, Bun, ALT, rising blood TP, Alb, has significance (P＜0.05sP＜0.01) with the model group comparing difference, prevention administration group with treat between the administration group not between significant difference (P＞0.05), but the prevention group is more obvious than the effect trend of treatment group on the numerical value.The results are shown in Table 5.
Table 5 Herba Girardiniae Palmatae extract to the influence of rat mesangial proliferative nephritis blood parameters (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
3.2 the influence of Herba Girardiniae Palmatae extract rat Heymann nephritis model: as can be known by experimental result, model group is behind model copy 30d, and the content of Cr and Bun significantly increases in urine protein, the blood, compares with the normal control group, significant difference (P＜0.05, P＜0.01); And after giving Herba Girardiniae Palmatae extract 30d continuously, significantly reduce the content of Cr, Bun in the amount of 24h urine protein and the blood, with model group relatively, significant difference (P＜0.05, P＜0.01).The results are shown in Table 6, table 7.
Table 6 Herba Girardiniae Palmatae extract to the influence of rat Heymann nephritis urine protein content (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
Table 7 Herba Girardiniae Palmatae extract to the influence of rat Heymann nephritis Cr and Bun (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
Experimental example 3 Herba Girardiniae Palmatae extracts are to the influence of experimental prostate hyperplasia model
1. experiment material
1.1 material: the carbon dioxide supercritical fluid extraction thing of Herba Girardiniae Palmatae, people's consumption are 0.5～12g (extract)/10～120g crude drug/60kg.
1.2 laboratory animal: healthy SD rat, ICR mice, cleaning level, Guiyang Medical College experimental animal center, quality certification SCXK (Guizhou Province) 2002-2001.After animal via normal diet adaptability fed for 1 week, select for use urine erythrocyte, urine protein qualitative results negative patient to enter experiment.Animal is raised with test full-valence pellet feed (Guiyang Medical College experimental animal center provides), freely drinks water 22 ± 2 ℃ of room temperatures.
2. method
2.1 the Herba Girardiniae Palmatae extract influences the rat prostate model of hyperplasia: cause rat prostate hypertrophy method by Testosterone Propionate, i.e. excision rat bilateral testes, after 1 week, every rat sc Testosterone Propionate 0.5mg/d in continuous 4 weeks, carries out drug treating simultaneously.Rat is divided 5 groups, 10 every group.Sham-operated control group: the overall process of excision rat bilateral testes that undergos surgery, but do not excise testis, the solvent of subcutaneous injection Testosterone Propionate is grabbed olive oil; Model of hyperplasia group: operation back the 2nd week beginning sc Testosterone Propionate 0.5mg/d, continuous 4 weeks; 2.5,5,10g crude drug/kg 3 dosage groups of Herba Girardiniae Palmatae extract:, in the time of the sc Testosterone Propionate, ig gives the Herba Girardiniae Palmatae extract respectively, and 1 time/day, continuous 4 weeks.Behind last administration 24h, put to death animal, cut open and get each leaf of prostate, measure prostate volume, each leaf weight in wet base.
2.2 the Herba Girardiniae Palmatae extract influences the mice prostatic hyperplasia model: the healthy male mice of body weight 20～25g, be divided into normal control group, model group, Herba Girardiniae Palmatae extract 16,8,3 dosage groups of 4g crude drug/kg at random, each organizes gastric infusion, the administration volume is 20ml/kg, and normal control group and model group are irritated stomach and given isometric distilled water.Except that the normal control group, 40min subcutaneous injection Testosterone Propionate 5mg/kg after all the other each treated animal administrations, continuous drug administration by injection 7d, each group is put to death 2～3 of animals at random after 7 days, cut open and get prostate and claim weight in wet base, calculate prostate index=weight of prostate/Mus heavy (mg/g), the success of results suggest model copy.Since 8d, irritate stomach and give drug treating, continue subcutaneous injection simultaneously and give Testosterone Propionate 5mg/kg, continuous 3 weeks.
2.3 data analysis and statistical method: all data represent that with x ± s statistical analysis adopts the student-T check.
3. result
3.1 the Herba Girardiniae Palmatae extract is to the outgrowth influence of rat prostate: excision testis, continuous subcutaneous injection Testosterone Propionate are after 4 weeks, and the model group prostate volume increases, and each leaf weight in wet base of prostate is obviously greater than Sham-operated control group, significant difference, (P＜0.01).Herba Girardiniae Palmatae extract 10,5g crude drug/kg dosage group significantly reduce the increase (P＜0.05, P＜0.01) of prostate volume and Ge Ye weight.The results are shown in Table 8.
Table 8 Herba Girardiniae Palmatae extract to the outgrowth influence of rat prostate (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01
3.2 the Herba Girardiniae Palmatae extract is to the influence of mice prostatic hyperplasia: with the normal control group relatively, model group prostate weight in wet base, weight in wet base index all increase (P＜0.01).Herba Girardiniae Palmatae extract 10,5g crude drug/kg dosage group significantly reduce prostate weight in wet base and weight in wet base index (P＜0.05, P＜0.01).The results are shown in Table 9.
Table 9 Herba Girardiniae Palmatae extract to the influence of mice prostatic hyperplasia (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01
Experimental example 4 Herba Girardiniae Palmatae extracts are to the influence of mouse experiment tumor model
1. experiment material
1.1 material: the carbon dioxide supercritical fluid extraction thing of Herba Girardiniae Palmatae, people's consumption are 0.5～12g (extract)/10～120g crude drug/60kg.
1.2 laboratory animal: healthy Kunming mouse, cleaning level, body weight 18～22g provides by the Guiyang Medical College Experimental Animal Center, the animal quality certification number: SCXK (Guizhou Province) 2002-0001.Animal is raised with test full-valence pellet feed (Guiyang Medical College experimental animal center provides), freely drinks water 22 ± 2 ℃ of room temperatures.
1.1.3 tumor cell line:
Rat liver cancer H
22: the Huaxi Medical Univ institute of oncology;
Mice S
180Sarcoma: cell research institute of the Shanghai Chinese Academy of Sciences;
Above tumor strain low temperature is frozen, and going down to posterity according to a conventional method after recovery during test is used for test.
2. method
2.1 the Herba Girardiniae Palmatae extract is to mice H
22The influence of experimental animal models tumor model: get H
22Tumor cell line is made cell suspension with culture fluid, the cell suspension of getting a little adds 0.4% trypan blue dye liquor of equivalent, microscopically blood cell counting plate living cell counting is moved into suspension in the 25ml culture bottle behind the counting, is diluted to 1 * 10 in proportion with the culture fluid that contains 10% calf serum
7/ ml.Culture bottle is put into 37 ℃ of temperature, relative humidity 100% contains 5%CO again
2, the incubator of 95% air is cultivated.Change liquid once for every day the cell in the culture bottle, 2～3d goes down to posterity once, goes down to posterity 4 times, and medium centrifugal is got spissated tumor cell, and it is 1 * 10 that redilution becomes concentration
7Behind the cell of/ml, be inoculated in the mouse peritoneal with asepsis injector, 0.2ml/ only.The tumor pearl is gone down to posterity after 4 times in animal body, the animal of selecting 8 days abdominal paries of inoculation obviously to expand, and the cervical vertebra dislocation is fixed on the stencil plate, the sterile working, suction ascites is mixed the ascites of 6 animals.Drip the ascites mixed liquor on microscope slide, push jack carries out the cell divide numeration, oncocyte number＞95% under the Wright's staining, mirror.Ascites is diluted to 1 * 10 with aseptic PBS liquid
7Individual/ml, the right oxter inoculation of every Mus 0.2ml cell.Random packet behind the 24h, that is: normal control group (isometric(al) distilled water), model group (isometric(al) distilled water), Herba Girardiniae Palmatae extract 2.5,5.0,10g (crude drug)/dosage groups such as kg; Every group 10.Every day, gastric infusion was 1 time, successive administration 7d.1h ball rear vein beard is got blood after the last administration, puts to death mice, weighs and peels off the subcutaneous tumors piece, claims tumor heavy, calculates tumour inhibiting rate.Experiment repeats three batches, and the homology thing of not moving is adopted in the every batch of experiment.
2.2 the Herba Girardiniae Palmatae extract is to mice S
180The influence of sarcoma experimental animal models tumor model: get S
180Tumor cell line is made cell suspension with culture fluid, the cell suspension of getting a little adds 0.4% trypan blue dye liquor of equivalent, microscopically blood cell counting plate living cell counting is moved into suspension in the 25ml culture bottle behind the counting, is diluted to 1 * 10 in proportion with the culture fluid that contains 10% calf serum
7/ ml.Culture bottle is put into 37 ℃ of temperature, relative humidity 100% contains 5%CO again
2, the incubator of 95% air is cultivated.Change liquid once for every day the cell in the culture bottle, 2～3d goes down to posterity once, goes down to posterity 4 times, and medium centrifugal is got spissated tumor cell, and it is 1 * 10 that redilution becomes concentration
7Behind the cell of/ml, be inoculated in the mouse peritoneal with asepsis injector, 0.2ml/ only.The tumor pearl is gone down to posterity after 4 times in animal body, the animal of selecting 8 days abdominal paries of inoculation obviously to expand, and the cervical vertebra dislocation is fixed on the stencil plate, the sterile working, suction ascites is mixed the ascites of 6 animals.Drip the ascites mixed liquor on microscope slide, push jack carries out the cell divide numeration, oncocyte number＞95% under the Wright's staining, mirror.Ascites is diluted to 1 * 10 with aseptic PBS liquid
7Individual/ml, the right oxter inoculation of every Mus 0.2ml cell.Random packet behind the 24h, that is: normal control group (isometric(al) distilled water), model group (isometric(al) distilled water), Herba Girardiniae Palmatae extract 2.5,5.0,10g (crude drug)/dosage groups such as kg; Every group 10.Every day, gastric infusion was 1 time, successive administration 7d.1h ball rear vein beard is got blood after the last administration, puts to death mice, weighs and peels off the subcutaneous tumors piece, claims tumor heavy, calculates tumour inhibiting rate.Experiment repeats three batches, and the homology thing of not moving is adopted in the every batch of experiment.
2.3 data analysis and statistical method: all data represent that with x ± s statistical analysis adopts the student-T check.
Rate of change calculates: tumour inhibiting rate (%)=(model group administration group)/model group * 100%
3. result
3.1 the Herba Girardiniae Palmatae extract is to mice H
22The influence of experimental animal models tumor model: the results suggest of three batches of tests, Herba Girardiniae Palmatae extract high dose tumour inhibiting rate all is higher than 30%, and the Herba Girardiniae Palmatae extract suppresses H significantly
22The tumor growth effect with model group comparing difference remarkable (p＜0.01), and is certain dose-effect relationship, three batches of experimental result basically identicals.The results are shown in Table 10.
Table 10 Herba Girardiniae Palmatae extract to the inhibitory action of mice H22 (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
3.2 the Herba Girardiniae Palmatae extract is to mice S
180The influence of experimental animal models tumor model: the results suggest of three batches of tests, Herba Girardiniae Palmatae extract high dose tumour inhibiting rate all is higher than 30%, and the Herba Girardiniae Palmatae extract suppresses S significantly
180The tumor growth effect with model group comparing difference remarkable (p＜0.01), and is certain dose-effect relationship, three batches of experimental result basically identicals.The results are shown in Table 11.
Table 11 Herba Girardiniae Palmatae extract to the inhibitory action of mice H22 (x ± s, n=10)
Compare with the normal control group
##* * P＜0.01, * P＜0.05 are compared with model group in P＜0.01.
Experimental example 5 Herba Girardiniae Palmatae extracts are to the influence of vessel embolism animal model
1. experiment material
1.1 material: the carbon dioxide supercritical fluid extraction thing of Herba Girardiniae Palmatae, people's consumption are 0.5～12g (extract)/10～120g crude drug/60kg.
1.2 laboratory animal: healthy Kunming mouse, SD rat, cleaning level provides by the Guiyang Medical College Experimental Animal Center, the animal quality certification number: SCXK (Guizhou Province) 2002-0001.Animal is raised with test full-valence pellet feed (Guiyang Medical College experimental animal center provides), freely drinks water 22 ± 2 ℃ of room temperatures.
2. method
2.1 the Herba Girardiniae Palmatae extract is to the thrombotic influence of rat vein: rat is divided into 4 groups at random: i.e. Herba Girardiniae Palmatae 2.5,5 and 10g crude drug/kg3 dosage group and model group.10 of every group of rats, each administration group rat gavages corresponding medicine by the 1ml/100g body weight, and model group is irritated stomach with the equal-volume distilled water.Behind the successive administration 7 days, after the last administration 1 hour, with 10% chloral hydrate 0.4ml/100g intraperitoneal injection of anesthesia rat, dorsal position is fixed, open the abdominal cavity, separate postcava, and under postcava, wear a silk thread, in left renal vein and postcava infall ligation postcava, sew up stomach wall then, reopen the abdominal cavity after 4 hours, 2 centimeters are closed blood vessel with the hemostasis clamp below ligation, cut tube chamber open, take out embolus, inhale with filter paper and go to claim weight in wet base after the residual blood, again embolus is put into 70 ℃ of baking ovens, claim dry weight after 4 hours, calculate the thrombosis suppression ratio by following formula:
Thrombosis suppression ratio %=(model group thrombus weight-administration group thrombus weight)/model group thrombus weight * 100%
2.2 the Herba Girardiniae Palmatae extract is to the influence of rat platelet aggregation: rat is divided into 4 groups at random: i.e. Herba Girardiniae Palmatae 2.5,5 an and 10g crude drug/kg3 dosage group and blank group.The administration group is irritated stomach with the 1ml/100g body weight, the blank group gives isometric distilled water, successive administration 7 days, after the last administration 1 hour, 0.64% pentobarbital sodium 0.4ml/100g body weight intraperitoneal injection of anesthesia, abdominal aortic blood is then by 9: 1 (whole bloods: anticoagulant) put into 3.8% sodium citrate anticoagulant tube and 2%EDTA-Na respectively
2In the anticoagulant tube, 500 rev/mins are taken out upper strata platelet rich plasma (PRP) after centrifugal 5 minutes, the latter's PRP is centrifugal 5 minutes with 2000 rev/mins again, the precipitation platelet, the slurry of dehematizing inclines, after will precipitating platelet usefulness platelet cleaning mixture washed twice then, the improvement tyrode's solution that adds former blood plasma volume (contains KCl 195mg, MgCl in the 1000ml solution
26H
2O 212.5mg, NaCl 8g, CaCl
2144mg, Tris 1.2g, glucose 1g, bovine serum albumin 2.5g, pH7.4).Light transmittance with PPP or improvement tyrode's solution is 100%, 200 μ LPRP or 37 ℃ of incubations of platelet suspension are added ADP (final concentration 4 μ mol/L), thrombin (final concentration 125U/L) and arachidonic acid (final concentration 0.8mmol/L) respectively after 5 minutes, trace 5 minutes curve of platelet aggregation then, with maximum agglutination rate, 1 minute aggregation rate and depolymerization rate is observation index, and platelet aggregation inhibition rate calculates by following formula.
3. result
3.1 the Herba Girardiniae Palmatae extract is to the thrombotic influence of rat vein: after rat gave Herba Girardiniae Palmatae extract 2.5,5 and 10g crude drug/kg in continuous 7 days, its wet weight of thrombus is compared with model group with dry weight and is the dose dependent reduction, the thrombosis suppression ratio is respectively 30.4%, 44.9%, 50.7% and 34.2%, 47.4%, 52.6%.The result shows that the bolt curing capsule of dispelling has the obvious suppression effect to rat vein thrombosis, and certain dose-effect relationship is arranged.The results are shown in Table 12.
Table 12 dispel the bolt curing capsule to the thrombotic influence of rat vein (x ± s, n=10)
Compare * * P＜0.01 with model group.
3.2 the Herba Girardiniae Palmatae extract is to the influence of rat platelet aggregation: see Table 13,14,15.As shown in Table 13, compare with the blank group, Herba Girardiniae Palmatae extract three dosage groups can obviously suppress the inductive platelet maximum agglutination rate of ADP (P＜0.05, P＜0.01), and 3 maximum suppression ratio of assembling of dosage group rat platelet are respectively 13.8%, 16.7% and 24.0%; The 10g/kg group also can obviously suppress 1 minute aggregation rate (P＜0.05) of platelet.The Herba Girardiniae Palmatae extract that gives 5g/kg and 10g/kg dosage is the obvious depolymerization rate of platelet increasing (P＜0.05) also.As shown in Table 14, the Herba Girardiniae Palmatae extract is to the rat platelet aggregation of thrombin induction, though the dose-dependent inhibition effect is also arranged, only the 10g/kg group can suppress platelet maximum agglutination rate (P＜0.01) by significance, and its suppression ratio is 35.3%.As shown in Table 15,10g/kg Herba Girardiniae Palmatae extract has the obvious suppression effect to the rat platelet maximum agglutination rate of arachidonic acid-induction.
Table 13 Herba Girardiniae Palmatae extract A DP induce rat platelet aggregation influence (x ± s, n=10)
Compare * P＜0.05 with the blank group, * * P＜0.01.
Table 14 Herba Girardiniae Palmatae extract to the influence of thrombin induction rat platelet aggregation (x ± s, n=10)
Compare * P＜0.05 with the blank group, * * P＜0.01.
Table 15 Herba Girardiniae Palmatae extract to the influence of arachidonic acid-induction rat platelet aggregation (x ± s, n=10)
Compare * P＜0.05 with the blank group, * * P＜0.01.
The specific embodiment
The novel clinical use of Herba Girardiniae Palmatae is meant the application of Herba Girardiniae Palmatae in preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism medicine.
Embodiment 1: capsule
Get Herba Girardiniae Palmatae 600～1200g, preparation technology makes fine powder or granule routinely, mixing, 1000 of No. 0 capsules of packing into.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each 1-4 grain, 1-4 time on the one.
Embodiment 2: injection
Get Herba Girardiniae Palmatae 600～1200g, preparation technology makes 1000 of injections routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each one, intramuscular injection, 1-4 time on the one.
Embodiment 3: oral cavity disintegration tablet
Get Herba Girardiniae Palmatae 1200g, preparation technology makes 1000 of oral cavity disintegration tablets routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each 1-4 sheet, 1-4 time on the one.
Embodiment 4: the compound granular agent
Get Herba Girardiniae Palmatae 1500g, Ramulus Cinnamomi 320g, preparation technology makes 200 bags routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, every bag 5 gram, each 0.53 bag, 1-4 time on the one.
Embodiment 5: compound tablet
Get Herba Girardiniae Palmatae 1300g, Herba Menthae 150g, preparation technology makes 1000 in tablet routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each 1-4 sheet, 1-4 time on the one.
Embodiment 6: compound dripping pill
Get Herba Girardiniae Palmatae 400g, Borneolum Syntheticum 20g, preparation technology makes 1000 of drop pill routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each 1-8 grain, 1-4 time on the one.
Embodiment 7: compound capsules
Get Herba Girardiniae Palmatae 1500g, Radix Astragali 800g, preparation technology makes 1000 of soft capsules routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each 1-6 grain, 1-4 time on the one.
Embodiment 8: the compound recipe oral cavity disintegration tablet
Get Herba Girardiniae Palmatae 1500g, Radix Salviae Miltiorrhizae 600g, Rhizoma Corydalis 600g, preparation technology makes 1000 of oral cavity disintegration tablets routinely.Be used for the treatment of hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism, each 1-6 sheet, 1-4 time on the one.
Claims (3)
1. the application of Herba Girardiniae Palmatae in preparation treatment hepatic injury, nephritis, prostate hyperplasia, tumor and vessel embolism medicine.
2. application according to claim 1, it is characterized in that: be raw material with the Herba Girardiniae Palmatae, technology obtains the Herba Girardiniae Palmatae total extract through extraction routinely, and then adds corresponding adjuvant, is prepared into any oral or non-peroral dosage form that is suitable for using clinically.
3. application according to claim 2 is characterized in that: described oral or non-peroral dosage form is powder, tablet, granule, capsule, microcapsule, pill, oral liquid, syrup, spray or aerosol, suppository, intravenous injection, intramuscular dose, inhalant; Used adjuvant comprises conventional solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant, wetting agent, thickening agent, solubilizing agent, substrate.
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