CN1307987C - New usage of alkannin - Google Patents
New usage of alkannin Download PDFInfo
- Publication number
- CN1307987C CN1307987C CNB2005100870388A CN200510087038A CN1307987C CN 1307987 C CN1307987 C CN 1307987C CN B2005100870388 A CNB2005100870388 A CN B2005100870388A CN 200510087038 A CN200510087038 A CN 200510087038A CN 1307987 C CN1307987 C CN 1307987C
- Authority
- CN
- China
- Prior art keywords
- suppository
- present
- group
- alkannin
- prostatitis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention discloses a new function of alkannin. The inventor of the present invention verifies through experiments that alkannin has the effect of prostatitis treatment and can be used for preparing medicines for treating prostatitis. More specifically, the present invention discloses a suppository for treating prostatitis, which is basically composed of alkannin and suppository matrixes; the alkannin accounts for 0.5 to 1.5% of the suppository by weight, and the rest are the suppository matrixes; the suppository matrixes are composed of 50 to 70 wt% of semisynthetic fatty glyceride, 10 to 30 wt% of liquid paraffin and 15 to 25 wt% of vaseline. The inventor of the present invention creatively discovers that the alkannin, as the extract of the Chinese medicine arnebia root, has the activity for treating prostatitis. The medicine using the alkannin as main components has the functions of antisepsis, inflammation resistance, heat elimination and diuresis promotion, and has the advantages of obvious effect on treating prostatitis, small toxicity and wide application prospects.
Description
Technical field
The present invention relates to the new purposes of shikonin.
Background technology
Radix Arnebiae (Radix Lithospermi) nature and flavor bitter cold has the merit of removing heat from blood and promoting blood circulation, heat-clearing and toxic substances removing." Bencao Jingshu " carries Radix Arnebiae (Radix Lithospermi) can " damp eliminating diarrhea of heat type key ", speech again: " bitter cold is sliding, so sharp nine orifices and tonneau water channel are also "; Just record, is controlled the urine soldier and is drenched for loosing with Radix Arnebiae (Radix Lithospermi) one or two in supplement to Thousand Golden Prescriptions; Control stranguria with blood with Radix Arnebiae (Radix Lithospermi) in " Standards of Diagnosis and Treatment "; " Zhenglei Bencao " also puts down in writing Radix Arnebiae (Radix Lithospermi) master trusted subordinate pathogen, five types of jaundice, invigorating the spleen and replenishing QI, sharp nine orifices, waterway.
In China, lithospermum euchromum Royle Arnebia euchroma (Royle) Johnst., Radix Arnebiae (Radix Lithospermi) (Lithospermumerythrorhizon sieb.et Zucc.) or arnebia guttata Bunge several Radix Arnebiae (Radix Lithospermi)s such as (Arnebia guttata Bunge) are distributed more widely.Shikonin can extract from the dry root of Radix Arnebiae (Radix Lithospermi) and obtain, and molecular formula is C
16H
16O
5, molecular weight 288, its structural formula is suc as formula shown in the I.Shikonin is the purple powder, and the special little hardship of distinguishing the flavor of is not drawn moistly, and fusing point is 148～149 ℃ (Chinese herbal medicine information centers of State Pharmaceutical Administration station, active ingredient of autonomic drug handbook, 1986,956 pages).
In the prior art, mostly field of medicaments is to be called Oleum Radix Arnebiae (Oleum Radix Lithospermi) by oil-soluble Gronwell naphthaquinone composition in the Radix Arnebiae (Radix Lithospermi) if being used.Oleum Radix Arnebiae (Oleum Radix Lithospermi) has the merit of heat clearing away, detumescence, pain relieving, antiinflammatory.Employing Radix Arnebiae (Radix Lithospermi)s such as Zhang Xing town are coated with outward and traditional Chinese medical science combined treatment is burnt (Zhang Xing town, Wang Xiuping. the combination of Chinese and Western medicine is with the 285 routine clinical observations of Oleum Radix Arnebiae (Oleum Radix Lithospermi) exterior coating treatment burn and scald. combination of Chinese and Western medicine magazine, 1986; 6 (11): 695); Employing such as Chen Xiaoqiu Oleum Radix Arnebiae (Oleum Radix Lithospermi) sliver treatment osteomyelitis (Chen Xiaoqiu etc. it is wonderful that the Oleum Radix Arnebiae (Oleum Radix Lithospermi) Orthopeadic Surgery is used. Chinese medicine information, 1994; 2:43); Yang Baoya, Zhou Qingmei etc. with Oleum Radix Arnebiae (Oleum Radix Lithospermi) treat cervical erosion (Oleum Radix Arnebiae (Oleum Radix Lithospermi) treatment cervical erosion clinical observation on the therapeutic effect. combination of Chinese and Western medicine magazine, 1986; 6 (4): 237); Reports such as Gao Xiuyun are used (Gao Xiuyun etc., 3 of Oleum Radix Arnebiae (Oleum Radix Lithospermi) externals, Chinese medicine information, 1995 such as the Oleum Radix Arnebiae (Oleum Radix Lithospermi) external curing is burnt, wound; 2:21); Radix Arnebiae (Radix Lithospermi) Ointment in Treatment diseases of oral mucosa is adopted in the middle respectful political affairs in village etc., effective percentage 89.7% (the respectful political affairs in middle village etc., tooth circle prospect .57 (7): 1351,1981).
Summary of the invention
The new purposes that the purpose of this invention is to provide shikonin.
The inventor confirms that by experiment shikonin has the prostatitic effect of treatment, can be used for the prostatitic medicine of preparation treatment.The said shikonin of the present invention had both comprised Shikonin, comprised shikonin again.
When needing, in said medicine, can also add one or more pharmaceutically acceptable carriers.Described carrier comprises diluent, filler, binding agent, wetting agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc., can also add flavouring agent, sweeting agent etc. in case of necessity.
The dosage form of this medicine can be diversified, can be multiple dosage forms such as suppository, tablet, capsule, but mainly is preferred with suppository, and various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
When medicine of the present invention was suppository, it was made up of shikonin and suppository base substantially, and generally speaking, described shikonin accounts for the 0.5-1.5% of described suppository weight, and surplus is a suppository base; Described suppository base is by the semi-synthetic fatty acid glyceride of 50-70% weight, and the vaseline of the liquid paraffin of 10-30% weight and 15-25% weight is formed.
Wherein, shikonin preferably accounts for 1% of suppository weight, and suppository base preferably by the semi-synthetic fatty acid glyceride of 70% weight, form by the vaseline of the liquid paraffin of 10% weight and 20% weight.
Suppository adopts anus topical administration mode, with cleaning around the anus, then thromboembolism is gone into the anus deep and gets final product before the medication, and its every suppository is 0.9g generally speaking, one time one, one day twice was a course of treatment with one month.
The present inventor has creatively found the extract shikonin as the Chinese medicine Radix Arnebiae (Radix Lithospermi), has the prostatitic activity of treatment, with be the medicine of main component, antibiotic, antiinflammatory, analgesic, diuresis are arranged, it is obvious to treat prostatitic effect, and toxicity is little, has broad application prospects.
Description of drawings
Fig. 1 is the extraction process flow chart of shikonin;
Fig. 2 is the thin layer identification chromatography figure of shikonin;
Fig. 3 is preparation technology's flow chart of suppository of the present invention;
Fig. 4 is the thin layer identification chromatography figure of suppository of the present invention.
The specific embodiment
The extraction of embodiment 1, shikonin and the preparation of suppository
One, the extraction of shikonin and evaluation
The process chart of extraction shikonin specifically can carry out according to following process: take by weighing Radix Arnebiae (Radix Lithospermi) 100g (branch, Beijing Tongrentang Changchun, alkannin content are 2.096%) as shown in Figure 1 from Radix Arnebiae (Radix Lithospermi), add petroleum ether 800ml, merceration 24 hours adds 0.25mol/L sodium hydroxide 800ml extraction 1 time, divides and gets the alkali liquor layer, placed 24 hours, add 0.5mol/L sulphuric acid 1600ml, the precipitation sucking filtration is washed to neutrality, place 90 ℃ of dryings, promptly get content and be about 90% shikonin.
Get above-mentioned sample, add ethanol and make the solution that every 1ml contains 1mg, as need testing solution.Other gets the Shikonin reference substance, adds ethanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 4 μ l of above-mentioned two kinds of solution, putting respectively on same silica gel g thin-layer plate, is developing solvent with toluene-ethyl acetate-formic acid (5: 1: 0.1), launches, take out, dry, its result as shown in Figure 2,1 is the Shikonin reference substance among the figure, 2 is the gained shikonin, 3 negative contrasts.As seen from the figure, resulting shikonin sample with the corresponding position of reference substance on, show identical aubergine speckle, show that what adopt said method to extract to obtain is shikonin.
Two, the preparation of suppository of the present invention
With shikonin is the prostatitic drug suppository of treatment of main ingredient, and its preparation technology specifically can operate according to following process as shown in Figure 3: take by weighing the shikonin 9.0g that obtains that extracts, place mortar to grind, cross 80 mesh sieves.Getting semi-synthetic fatty acid glyceride 630g, liquid paraffin 90g, vaseline 180g places water-bath (60 ℃) to go up heat fused, medicated powder is spread in the molten matrix, fully stir evenly, impouring while stirring scribbles in the bolt mould of releasing agent (liquid paraffin), to slightly overflowing till the die orifice.Take out the cooling back, can be made into 1000 suppositorys of the present invention.
Get 1 of the invention described above suppository, place centrifuge tube, add ethanol 10ml, 50 ℃ of heating in water bath dissolvings, natural cooling, centrifugal, filter, put in the 10ml measuring bottle, add ethanol dilution to scale.Other gets the Shikonin reference substance, adds ethanol and makes the solution that every 1ml contains 0.5mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2000), draw each 4 μ l of above-mentioned two kinds of solution, putting respectively on same silica gel g thin-layer plate, is developing solvent with toluene-ethyl acetate-formic acid (5: 1: 0.1), launches, take out, dry, the result as shown in Figure 4,1 is the Shikonin reference substance among the figure, 2 are suppository of the present invention, 3 negative contrasts.This suppository with the corresponding position of reference substance chromatograph, show identical aubergine speckle.
The pharmacodynamic experiment of embodiment 2, suppository of the present invention
One, experiment material
1, medicine
Suppository of the present invention: embodiment 1 described preparation, 0.9g/ piece (containing shikonin 9mg/ piece suppository).According to the trial test result, set mice dosage and be 0.48,0.24,0.12g/Kg, contain that shikonin is respectively 4.8,2.4,1.2mg/Kg (is equivalent to mice LD approximately
501/160,1/320,1/640); Rat dosage is 0.32,0.16,0.08g/Kg, contains that shikonin is respectively 3.2,1.6,0.8mg/Kg.Being mixed with suitable concentration with substrate 37 ℃ of water-baths before the experiment uses for experiment;
Bolt: 2g/ piece of prostatitis peace defended the accurate word Z-056 of medicine number, produced product batch number by Lizhu Chinese Medicine Factory: 020522, and be mixed with suitable concentration with warm water at 37 ℃ before the experiment and use for experiment;
Indometacin bolt (indomethacin bolt): the 0.1g/ grain, the accurate word H42021462 of traditional Chinese medicines, Dongxin Pharmaceutical Co., Ltd., Hubei Prov.'s product, product batch number: 030601, it is standby to be mixed with suitable concentration with substrate before the test;
Acetaminophen bolt: 0.15g/ piece, the accurate word H44024867 of traditional Chinese medicines, Jingxiutang's product, product batch number: 030107, it is standby to be mixed with suitable concentration with substrate before the test;
FUSAIMI PIAN, the 20mg/ sheet, the accurate word H12020163 of traditional Chinese medicines, Tianjin Lisheng Pharmaceutical Co., Ltd.'s product, product batch number: 0303004, it is standby to be mixed with suitable concentration with normal saline before the test;
XIAOZHILING ZHUSHEYE, 10ml/ props up, Chinese Jian-Yisheng Pharmaceutical Co., Ltd., Jilin product, product batch number: 011027;
The QIANLIEKANG relieving capsule, the accurate word B200020078 of traditional Chinese medicines, Zhenlai, Jilin Province Yin Nuoke pharmaceutcal corporation, Ltd product, lot number: 20041005;
Carrageenin, Shenyang Pharmacy College provides, lot number: 020215;
Yeast soaks powder, Beijing extensive and profound in meaning star biotechnology responsibility company limited, lot number: 011004.
2, laboratory animal
The Wistar rat, body weight 140-160g, 180-200g, 280-320g is male, and institute for drug control, Jilin Province animal housing provides, quality certification numbering: 10-1009.
Kunming mouse, 18-22g, 25-28g, male, institute of Biological Products animal housing in Changchun provides, quality certification numbering: 10-1001.
3, experimental strain
International standard strain: staphylococcus aureus ATCC25925, escherichia coli ATCC25922.
The common strain of clinical separation: golden yellow staphylococcus 15 strains, people's intestinal dust is wished bacterium 17 strains, klebsiella pneumoniae 18 strains, Pseudomonas aeruginosa 14 strains, common variable bacillus 9 strains, Diplococcus gonorrhoeae 6 strains, 8 strains of beta hemolysis streptococcus, Streptococcus mutans 6 strains.
Two, the antiinflammatory action of suppository of the present invention
1, the influence of rat paw edema due to the on Carrageenan
But the concrete grammar reference literature of this experiment (Li Yikui, middle pharmacological experimental methodology [M], Shanghai science skill publishing house, 1991:353 312289-292) carries out.
50 of rats, body weight 120-140g, male, be divided into 5 groups, 10 every group, by the rectally of dosage shown in the table 1 (irrigation stomach device enters rectum 1.5cm), fasting 12h before the administration, 0.2ml/ only, matched group is given equal volume substrate, fills in anus with spongy embolus at once after the administration and fixes (sponge ball parcel polyethylene film, put into anal with the tweezers clamping), take out behind the 4h, once a day, be total to 7d, 1h after the last administration, injection 1% carrageenin 0.1ml/ only causes inflammation under the aponeurosis (aponeuroses) of the right back sufficient sole of the foot of rat bottom, and measurement causes before the inflammation and causes inflammation back 1,2,3,4, the right back sufficient sole of the foot thickness of 5h, thus the sufficient sole of the foot difference in scorching front and back is as the swelling degree.The results are shown in Table 1.
The influence of rat paw edema due to table 1 on Carrageenan (x ± s, n=10)
| Group | Dosage (g/Kg) | Cause scorching back swelling degree (cm) | ||||
| 1h | 2h | 3h | 4h | 5h | ||
| Matched group indometacin bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.01 0.32 0.16 0.08 | 0.41±0.19 0.25±0.12 * 0.34±0.20 0.31±0.21 0.35±0.36 | 0.68±0.19 0.27±0.18 *** 0.51±0.14 * 0.50±0.14 * 0.54±0.20 | 1.02±0.13 0.34±0.17 *** 0.79±0.15 ** 0.84±0.15 * 0.87±0.18 * | 0.93±0.15 0.32±0.17 *** 0.77±0.16 * 0.83±0.22 0.81±0.28 | 0.90±0.13 0.34±0.18 *** 0.89±0.19 0.84±0.24 0.74±0.29 |
Annotate: compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001
By table 1 as seen, each group of suppository of the present invention causing the effect in 2-4 hour of scorching back obviously, relatively has the significance difference opposite sex with matched group respectively.
2, the influence of xylol induced mice ear swelling
But the concrete grammar reference literature of this experiment (Li Yikui, middle pharmacological experimental methodology [M], Shanghai science skill publishing house, 1991:353 312289-292) carries out.
50 of mices, body weight 25-28g, male, be divided into 5 groups, every group 10, press the rectally of dosage shown in the table 2, fasting 12h before the administration, 0.05ml/ only, matched group is given equal volume substrate, fills in anus with spongy embolus at once after the administration and fixes, and takes out behind the 4h, once a day, be total to 7d, 1h after the last administration, the two sides is coated with dimethylbenzene 0.05ml before and after the ear of every Mus left side, mice is put to death in the cervical vertebra dislocation behind the 4h, cut ears,, lay auricle and weigh with 9mm diameter card punch, calculate every group of mice swelling degree (left auricle weight-auris dextra sheet is heavy), and swelling rate ((left auricle weight-auris dextra sheet is heavy)/auris dextra sheet is heavy).The results are shown in 2 tables.
The influence of table 2 xylol induced mice ear swelling (x ± s, n=10)
| Group | Dosage (g/Kg) | Swelling degree (mg) | The swelling rate |
| Matched group | 12.3±2.1 | 0.81±0.19 |
| Indometacin bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.01 0.48 0.24 0.12 | 6.1±3.2 *** 8.6±2.6 ** 9.0±2.2 ** 9.4±2.7 * | 0.41±0.20 *** 0.56±0.18 ** 0.61±0.19 * 0.60±0.23 * |
Annotate: compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001
By table 2 as seen, each administration group xylol induced mice ear thickness of suppository of the present invention and swelling rate have obvious inhibitory action, and relatively there were significant differences with matched group.
3, to the bullate influence of rat granuloma
But the concrete grammar reference literature of this experiment (Li Yikui, middle pharmacological experimental methodology [M], Shanghai science skill publishing house, 1991:353 312289-292) carries out.
50 of rats, body weight 140-160g, male, use etherization, at aseptic condition hypogastric region otch, with two sterilization cotton balls (each heavy 10mg, through autoclaving, each cotton balls adds ampicillin 1mg/0.1ml again, 50 ℃ of stove-dryings) to implant rat both sides axillary fossa respectively subcutaneous, postoperative began by the grouping of dosage shown in the table 3 rectally the same day, and fasting 12h before the administration, 0.2ml/ are only, matched group is given equal volume substrate, at once fill in anus with spongy embolus after the administration and fix, take out behind the 4h, once a day, be total to 7d, cervical vertebra dislocation in the 8th day is put to death, and takes out cotton balls, 60 ℃ of baking 12h, weigh, deduct the raw cotton ball weight, be granuloma weight, and calculate suppression ratio.The results are shown in Table 3.
The bullate influence of table 3 pair rat granuloma (x ± s, n=10)
| Group | Dosage (g/Kg) | Cotton balls granulation weight (mg) | Suppression ratio (%) |
| Matched group indometacin bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.01 0.32 0.16 0.08 | 96.7±24.0 63.5±15.8 ** 67.4±13.5 ** 70.0±18.9 * 73.0±17.2 * | 34.3 30.3 27.6 24.5 |
Annotate: compare with matched group
*P＜0.05,
*P＜0.01
By table 3 as seen, each dosage group of suppository of the present invention all has obvious inhibitory action to rat granuloma is swollen, relatively has significant difference with matched group.
Two, suppository analgesic activity of the present invention
Dichlorodiphenyl Acetate causes the influence of mouse writhing reaction times, but the concrete grammar reference literature of this experiment (Li Yikui, middle pharmacological experimental methodology [M], Shanghai science skill publishing house, 1991:353 312289-292) carries out.
50 of mices, body weight 20-22g, male, divide equally 5 groups at random, press the rectally respectively of dosage shown in the table 4, fasting 12h before the administration, 0.05ml/ only, matched group is given equal volume substrate, fills in anus with spongy embolus at once after the administration and fixes, take out behind the 4h, once a day, continuous 7 days, 1h after the last administration, every Mus lumbar injection 0.7% glacial acetic acid 0.1ml/10g, the writhing response number of times behind the record injection algogen in the 5-15min.The results are shown in Table 4.
Table 4 Dichlorodiphenyl Acetate cause the mouse writhing reaction times influence (x ± s, n=10)
| Group | Dosage (g/Kg) | Turn round the body number of times (inferior/10min) | Suppression ratio (%) |
| Matched group indometacin bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.01 0.48 0.24 0.12 | 37.0±7.9 12.5±5.8*** 29.5±7.4* 30.2±7.8 33.8±7.6 | 66.2 20.3 18.4 8.6 |
Annotate: compare P＜0.05 with matched group,
* *P＜0.001
By table 4 as seen, suppository 0.48g/Kg of the present invention group Dichlorodiphenyl Acetate causes the mouse writhing reaction, and obvious inhibitory action, suppression ratio are arranged is 20.3%, relatively has the significance difference opposite sex with matched group.
Three, to the influence of rat fever due to the yeast
But the concrete grammar reference literature of this experiment (Li Yikui, middle pharmacological experimental methodology [M], Shanghai science skill publishing house, 1991:353 312289-292) carries out.
Rat body weight 150-180g; male; choose continuous survey body temperature on the three, change 50 of rats being no more than 0.3 ℃, divide equally 5 groups at random; fasting 14h before the experiment; suppository is put 37 ℃ of water-baths melt, rectum gives acetyl-amino phenol bolt 0.03g/Kg respectively, suppository 0.32,0.16 of the present invention, 0.08g/Kg; 0.2ml/ only, matched group is given with volume substrate.At once in rat back subcutaneous injection 25% dry yeast suspension 10ml/kg, 3h is administered once after the pyrogenicity after the administration, then in 4,6,8,10h respectively surveys body temperature once, the results are shown in Table 5.
The influence of rat fever due to the table 5. pair yeast (x ± s, n=10)
| Group | Dosage (g/Kg) | Body temperature before the pyrogenicity (℃) | Different time body temperature variation after the pyrogenicity (℃) | |||
| 4 | 6 | 8 | 10 | |||
| Matched group | 37.1±0.3 | 1.65±0.46 | 2.22±0.33 | 1.89.0±0.34 | 1.23±0.46 | |
| To acetyl-amino phenol bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.03 0.32 0.16 0.08 | 37.0±0.4 37.1±0.4 37.1±0.4 37.0±0.4 | 0.64±0.44 *** 0.76±0.44 *** 0.87±0.62** 1.14±0.52* | 0.89±0.54 *** 1.13±0.43 *** 1.32±0.49** 1.64±0.53** | 0.97±0.82 ** 1.00±0.37 *** 1.19±0.72* 1.31±0.36** | 0.78±0.74 0.73±0.45 * 0.86±0.39 1.10±0.70 |
Annotate: compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with matched group
By table 5 as seen, the high, medium and low dosage group of suppository of the present invention raises to rat temperature due to the yeast the obvious suppression effect.
Four, to the influence of water load rat urine amount
50 of rats, body weight 170-200g, male, divide equally 5 groups, in metabolic cage, adapt to 1 day in advance, water 18h is can't help in fasting before the experiment.Gently depress abdomen during the experiment beginning, drain surplus urine, the furosemide 0.01g/Kg of positive drug group (because of not choosing the positive drug that is fit to rectally, and selecting oral formulations for use) ig normal saline preparation, 5.0ml/100g, other respectively organizes ig normal saline 5.0ml/100g body weight, suppository rectally 0.2ml/ of the present invention, dosage is as shown in table 6, fills in anus with spongy embolus at once after the administration and fixes, and at once rat is put into metabolic cage, collect record 2h and 5h amount of urine respectively.The results are shown in Table 6.
The influence of table 6. pair water load rat urine (x ± s, n=10)
| Group | Dosage (g/Kg) | Voided volume/(ml/100g body weight) | |
| 2h | 5h | ||
| Matched group furosemide suppository of the present invention suppository of the present invention suppository of the present invention | 0.01 0.32 0.16 0.08 | 1.17±0.28 2.36±0.41 *** 1.67±0.28 ** 1.59±0.34 ** 1.51±0.33 * | 0.62±0.13 1.05±0.13 *** 0.82±0.13 ** 0.79±0.14 ** 0.77±0.12 * |
Annotate; Compare with matched group
*P＜0.05
*P＜0.01
* *P＜0.001
By table 6 as seen, each dosage group of suppository of the present invention all has obvious facilitation to water load rat urine amount, relatively has significant diversity with matched group.
But five, the concrete grammar reference literature (Zhang Yaqiang that influences this experiment of rat nonbacterial prostatitis, the Liu You a tree, used in making timber for boats, Yu Linghui etc. Chinese medicine prostate soup is to the influence [J] of experimental prostatitis pathological model. combination of Chinese and Western medicine magazine, 1991, (8): 480-481.; Lei Jiushi, Guo Zihua, Zhu Xiaoming etc. anticusp is clearly to the influence [J] of the scorching model pathological change of rat prostate. Hunan College of Traditional Chinese Medicine's journal, 1998,48 (2): 22-23.) carry out.
60 of rats, body weight 280-320g, male.Press literature method, etherization, the aseptic operation operation, the about 2-3cm of animal median incision of lower abdomen, through abdominal cavity, bladder and both sides seminal vesicle are proposed, exposure invests the prostate notopodium of seminal vesicle inboard, and except that 10 injections of matched group 0.2ml sterile saline, all the other equal bilaterals are injected 25% XIAOZHILING ZHUSHEYE 0.2ml respectively, send multiple abdominal cavity immediately, sew up.After moulding the 3rd day, begin the rectally that divides into groups, 0.2ml/ only, fasting be can't help water 12 hours before the administration, matched group is given equal volume substrate, fills in anus with spongy embolus at once after the administration and fixes, and takes out behind the 4h, once a day, continuous 30 days, 24h after the last administration weighed in, and put to death rat.Win prostate, carry out anatomic observation, take by weighing the prostate weight in wet base, calculate the prostate index, and fix with 10% formalin solution, carry out histological observation, estimate by the semi-quantitative assessment standard, the result carries out Ridit and analyzes.The results are shown in Table 7, table 8.
The table 7. pair exponential influence of rat nonbacterial prostatitis prostate (x ± s, n=10)
| Group | Dosage (g/Kg) | Prostate weight in wet base (g) | Prostate index (g/100g body weight) |
| Matched group model group prostatitis peace bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.18 0.32 0.16 0.08 | 1.393±0.129 1.717±0.179 ΔΔΔ 1.540±0.188 * 1.483±0.248 * 1.518±0.155 * 1.558±0.146 *Δ | 0.398±0.040 0.553±0.074 ΔΔΔ 0.440±0.061 ** 0.420±0.067 *** 0.439±0.052 *** 0.451±0.080 ** |
Annotate: compare with matched group
ΔP＜0.05
Δ Δ ΔP＜0.001
Compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with model group
By table 7 as seen, the prostate index of each dosage group of suppository of the present invention and prostatitis peace bolt group prostatitis model that xiaozhiling injection is caused all has the inhibitory action of highly significant.
Anatomic observation: control rats prostate gland tissue softness, light red, glossy, flexible, there is not adhesion with surrounding tissue.Model group prostate body of gland obviously increases, and is heavier with the surrounding tissue adhesion, visible kermesinus in portion of tissue surface or canescence tuberosity.Prostatitis peace bolt group body of gland moderate increases, and with surrounding tissue adhesion is arranged, poor flexibility, and the portion of tissue surface is dark red, and its degree obviously alleviates than model group.Suppository high dose group body of gland of the present invention swelling alleviates with the surrounding tissue adhesion lighter, and body of gland is soft and the surface is glossy.In the suppository of the present invention, the swelling of low dose group body of gland, elasticity and adhesion degree reduce with dosage and increase the weight of.
Histopathology is observed: control rats prostate lumen of gland is not of uniform size, the glandular epithelium surface forms a lot of pleats, make lumen of gland very irregular, the acinus epithelium mostly be the monolayer column or cube, be false multiple layer individually, the secretions that visible a large amount of dark powder dye in the lumen of gland, the formation prostatic concretions that has is normal histology's structure; Pathological changes in various degree appears in other each group except that matched group, cell infiltration such as the lymphocyte of visible varying number, mononuclear cell in the matter between prostate; Even because cell infiltration, the fibrous connective tissue hypertrophy makes the obvious broadening of a matter.Grade scale is as follows:
No tangible pathological change is "-" in the section;
The pathological change scope accounts for below 1/4 of the full visual field, is "+";
Pathological change is obvious, and scope accounts for more than the 1/4-1/2 in the full visual field, is " ++ ";
The pathological change degree is serious, and scope accounts for more than 1/2 of the full visual field, for " +++".
Suppository of the present invention and prostatitis peace bolt have significant improvement effect to the histogenetic cell infiltration of rat prostate, fibrous connective tissue hypertrophy, the minimizing of glandular secretion thing, the results are shown in Table 8.
The influence that table 8 pair nonbacterial prostatitis rat histopathology changes
| Group | Dosage (g/Kg) | n | The pathological change degree | |||
| - | + | ++ | +++ | |||
| Control group model group Prostant suppository of the present invention suppository of the present invention suppository of the present invention | 0.18 0.32 0.16 0.08 | 10 10 10 10 10 10 | 9 0 5 7 6 5 | 1 4 5 3 4 5 | 0 5 0 0 0 0 | 0 1 ΔΔΔ 0 ** 0 *** 0 ** 0 ** |
Annotate: compare with matched group
Δ Δ ΔP＜0.001
Compare with model group
*P＜0.01
* *P＜0.001
As seen, each administration group of suppository of the present invention and prostatitis peace bolt group and model group compare, and, proliferation of fibrous tissue bad to cell infiltration, glandular secretion that the prostata tissue of injecting the xiaozhiling injection rat takes place all has improvement in various degree.
Six, to the influence of rat bacterial prostatitis
60 of rats, body weight 280-320g, male, divide equally 6 groups, every group 10, press the rectally of dosage shown in the table 8,0.2ml/ is only, method is the same, every day 1 time, continuous 7 days, pressed literature method on 4th, etherization, aseptic operation operation, the about 2-3cm of animal median incision of lower abdomen, through abdominal cavity proposes bladder and both sides seminal vesicle, exposure invests the prostate notopodium of seminal vesicle inboard, and except that 0.2ml/ sterile saline of matched group injection, all the other all inject 1.4 * 10
7Individual/ml escherichia coli (clinical separation strain), 0.2ml/ only send multiple abdominal cavity immediately, sews up.Put to death animal behind the 48h, open the abdominal cavity, win prostate, get 10 μ l massage of prostate liquid,, count leukocyte count in microscopically with 20 times of leukocyte diluted.Other gets 10 μ l and counts the lecithin number in microscopically.Put electronic balance simultaneously and claim weight in wet base, calculate the prostate index, and fix with 10% formalin solution, carry out histological observation, estimate by the semi-quantitative assessment standard, the result carries out the Ridit analysis, the results are shown in Table 9, table 10, table 11.
The influence of table 9. pair rat bacterial prostatitis (x ± s, n=10)
| Group | Dosage (g/Kg) | Lecithin (10 9/L) | Leukocyte (10 9/L) |
| Matched group model group prostatitis peace bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.18 0.32 0.16 0.08 | 3.96±1.20 1.96±0.87 ΔΔΔ 2.87±0.92 *Δ 3.04±0.73 ** 2.96±0.91 * 2.63±0.71 ΔΔ | 0.74±0.34 1.54±0.42 ΔΔΔ 1.08±0.53 * 0.91±0.65 * 1.04±0.47 * 1.18±0.45 Δ |
Annotate: compare Δ P＜0.05 Δ Δ P＜0.01 Δ Δ Δ P＜0.001 with matched group
Compare with model group
*P＜0.05
*P＜0.01
* *P＜0.001
By table 9 as seen, suppository 0.32 of the present invention, 0.16g/Kg group and prostatitis peace bolt 0.18g/Kg organize the content that can increase lecithin in the prostate with prostatitis model group comparison due to the escherichia coli, reduce leukocyte count.
The table 10. pair exponential influence of rat bacterial prostatitis prostate (x ± s, n=10)
| Group | Dosage (g/Kg) | Prostate heavy (g) | Prostate index (g/100g body weight) |
| The matched group model group | 0.820±0.133 1.073±0.125 ΔΔΔ | 0.250±0.044 0.330±0.034 ΔΔΔ |
| Prostatitis peace bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.18 0.32 0.16 0.08 | 0.876±0.119 ** 0.953±0.120 *Δ 0.966±0.169 Δ 0.978±0.142 Δ | 0.282±0.061 * 0.290±0.042 * 0.293±0.055 0.302±0.045 Δ |
Annotate: compare Δ P＜0.05 Δ Δ Δ P＜0.001 with matched group
Compare with model group
*P＜0.05
*P＜0.01
* *P＜0.001
By table 10 as seen, increase has obvious inhibitory action to suppository high dose group of the present invention and prostatitis peace bolt group to bacterial prostatitis model body of gland.
Histopathology is observed: the rat prostate lumen of gland is not of uniform size, the glandular epithelium surface forms a lot of pleats, make lumen of gland very irregular, the acinus epithelium mostly be the monolayer column or cube, be false multiple layer individually, the secretions that visible a large amount of dark powder dye in the lumen of gland, the formation prostatic concretions that has is normal histology's structure; Except that the normal control group, other is respectively organized, and matter has neutrophilic leukocyte, the mononuclear cell of varying number between prostate and number capsule, and a spot of lymphocytic infiltration, even visible a small amount of pus cell in the prostate seminal vesicle lumen have the visible chronic inflammatory granulation tissue in place to form.The minimizing in various degree of lumen of gland secretions is pale red dyeing, no secretions in the lumen of gland that has.Judge that the branch standard is the same, the results are shown in Table 11.
The influence that table 11. pair bacterial prostatitis rat histopathology changes
| Group | Dosage (g/Kg) | n | The pathological change degree | |||
| - | + | ++ | +++ | |||
| Matched group model group prostatitis peace bolt suppository of the present invention suppository of the present invention suppository of the present invention | 0.18 0.32 0.16 0.08 | 10 10 10 10 10 10 | 9 0 3 3 2 1 | 1 0 3 4 4 1 | 0 1 0 0 0 0 | 0 9 ΔΔΔ 4 *ΔΔ 3 **ΔΔ 4 *ΔΔ 8 *ΔΔΔ |
Annotate: compare with model group
*P＜0.05
*P＜0.01
Compare with matched group
The Δ ΔP＜0.05
Δ Δ ΔP＜0.001
As seen, each dosage group of suppository of the present invention and prostatitis peace bolt group and model group relatively can obviously alleviate the prostatic lesion degree.
Seven, to the influence of other rat prostate models
1, the influence of nonbacterial prostatitis due to the on Carrageenan
Get rat 70 (250-300g) and be divided into 7 groups at random, be respectively blank group (A group), model control group (B group), the QIANLIEKANG 1.6g/kg (C group) that relaxes, suppository of the present invention (ig) 30mg/kg, 15mg/kg group (D, E group), suppository of the present invention (ip) 5mg/kg, 2.5mg/kg group (F, G group).C, D, E treated animal ig administration, A, B organize to consubstantiality hydrops (20ml/Kg); F, G organize ip administration (5ml/kg).Animal successive administration 8 days, pressed in 1 hour after the last administration literature method (Dai Sulin, etc. Chinese patent medicine, 1990; 12 (8): 27), animal is cut the abdominal cavity with etherization open under the aseptic condition, injects sterilization 1% carrageenin 0.1ml (A group injection physiological saline solution) by seminal vesicle in prostate, sews up.In operation sacrificed by decapitation rat after 24 hours, get and cause scorching prostate 50mg and add in 200ul leukocyte diluent and the 200ul normal saline, abundant mixing, mirror is record leukocyte count and the little body density of Lecithin down, and gets prostate and do the pathology inspection.The results are shown in Table 12.
The prostatitic influence of the non-antibacterial of rat due to the table 12 pair intersection dish glue (n=10, X ± S)
| Group | Number of animals (n) | Leukocyte (individual/mg) | Lecithin (individual/mg) |
| A B C D E F G | 10 10 10 10 10 10 10 | 32.0±14.1 174.2±52.1 ### 96.4±41.5 ** 89.2±41.6 *** 97.2±51.2 ** 68.6±46.7 *** 86.6±56.6 ** | 256.2±88.4 89.5±55.3 ### 172.4±70.1 ** 193.0±82.1 ** 160.1±67.9 * 197.0±86.4 ** 170.2±68.9 ** |
Annotate: compare with the blank group
#P＜0.05
##P＜0.01
###P＜0.001
Compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with model control group
The result shows that model control group and normal control group compare, leukocyte showed increased in the prostate, and the Lecithin corpusculum obviously reduces, and a large amount of leukocyte infiltrations appear in model control group, and the blank group does not have leukocyte infiltration; With the model matched group relatively, QIANLIEKANG is relaxed and each group of suppository of the present invention all can obviously reduce leukocyte count, increases the little body density of Lecithin, and there were significant differences.
Pathologic finding finds that QIANLIEKANG is relaxed and each group of suppository of the present invention, the apparent in view minimizing of cellular infiltration and model control group.
2, to the influence of rat bacterial prostatitis due to the escherichia coli
Get 70 of 250-300g rats, be divided at random 7 groups the same, the continuous gastric infusion of animal 8 days.After the administration in the 5th day 1 hour, press literature method (Dai Sulin, etc. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 1991; 16 (9): 562) with 0.1ml escherichia coli (1.4 * 10
7/ ml) cause inflammation (method is the same), cause scorching 72 hours after disconnected marrow put to death rat, the aseptic respectively prostate 50mg that gets adds in 200ul leukocyte diluent and the 200ul normal saline, microscopy, record leukocyte count and the little body density of Lecithin are got prostate simultaneously and are done the pathology inspection, the results are shown in Table 13.
The prostatitic influence of rat antibacterial due to the table 2 pair intersection dish glue (n=10, X ± S)
| Group | Number of animals (n) | Leukocyte (individual/mg) | Lecithin (individual/mg) |
| A B C D E F G | 10 10 10 10 10 10 10 | 22.0±10.2 37.2±9.1 ## 26.4±6.5 ** 24.2±6.6 ** 26.2±7.2 ** 24.6±6.7 ** 25.6±6.6 ** | 301.2±73.2 185.5±57.3 ## 285.3±75.8 ** 256.2±71.4 * 231.0±83.1 271.4±87.5 * 247.2±96.6 |
Annotate: compare with the blank group
#P＜0.05
##P＜0.01
###P＜0.001
Compare * P＜0.05 * * P＜0.01 * * * P＜0.001 with model control group
The result shows, QIANLIEKANG is relaxed and each group of suppository of the present invention, rat bacterial prostatitis due to the escherichia coli there is obvious inhibitory action, suppository ig30mg/kg group of the present invention and ip5mg/kg group all can obviously reduce leukocyte count, increase the little body density of Lecithin, significant difference is relatively arranged with model control group.
The above results shows, rat non-bacterial and bacterial prostatitis have the obvious suppression effect due to shikonin on Carrageenan, the escherichia coli, can obviously improve lecithin density, obviously reduce the prostate leukocyte count, have good curing prostatitis activity.
Eight, antibacterial experiment
1, antibacterial tests in the body
But the concrete grammar reference literature of this experiment (Li Yikui, middle pharmacological experimental methodology [M], Shanghai science skill publishing house, 1991:353 312289-292) carries out.
200 of mices, body weight 20-22g, male, divide equally 10 groups at random, 20 every group, press the rectally of dosage shown in the table 12 2 minor tick 6h, 1h after the administration for the first time, the staphylococcus aureus (ATCC25925), escherichia coli (ATCC25922) the bacterium liquid that trial test have been recorded minimum lethal dose (100%MLD) infect each Mus with minimum lethal dose (100%MLD), and lumbar injection 0.5ml/ is only, observe dead rate of animal and time-to-live in 5 days, the results are shown in Table 14.
Antibacterial experiment in table 14. body (x ± s, n=20)
| Group | Dosage (g/kg) | Staphylococcus aureus | Escherichia coli |
| Mortality rate (%) time-to-live (my god) | Mortality rate (%) time-to-live (my god) | ||||
| Matched group | 0 | 1.2±0.4 | 0 | 1.2±0.4 | |
| Prostatitis peace bolt | 0.26 | 85 | 1.8±1.4 | 50 | 2.4±1.8 * |
| Suppository of the present invention | 0.48 | 85 | 1.8±1.4 | 70 | 2.1±1.7 * |
| Suppository of the present invention | 0.24 | 90 | 1.6±1.2 | 90 | 1.6±1.2 |
| Suppository of the present invention | 0.12 | 90 | 1.5±1.2 | 90 | 1.6±1.2 |
Annotate: compare with matched group
*P＜0.05
By table 14 as seen, suppository high dose group of the present invention and prostatitis peace bolt group can prolong the life span that infects escherichia coli, escherichia coli is had certain inhibitory action in vivo, but staphylococcus aureus life span and mortality rate are not had obvious influence.
2, in-vitro antibacterial experiment
Culture medium: blood agar culture-medium is used to cultivate beta hemolytic streptococcus; Chocolate agar medium is used to cultivate Diplococcus gonorrhoeae and Streptococcus mutans; The ordinary nutrient agar culture medium is used to cultivate other antibacterials.
Medicine under aseptic condition, is ground to form powdery, after a small amount of cosolvent dissolving, adopt sterile distilled water to make solution, this solution is mixed by doubling dilution with culture medium, make the drug level in the culture medium be respectively 64,32,16,8,4,2,1,0.5mg/ml.With well-grown antibacterial in the solid medium, with the antibacterial eluting, proofread and correct bacterial concentration with physiological saline solution, make its turbidity that is equivalent to 0.5 Maxwell pipe, 1: 100 times of redilution is standby.Get with inoculating loop that the bacterium liquid to be checked of corrected concentrations is inoculated in media surface, put 37 ℃ of incubators, (Diplococcus gonorrhoeae, beta hemolytic streptococcus and Streptococcus mutans and Streptococcus mutans were put CO in 18-24 hour
2Incubator 24-48 hour) observed result.MIC to the examination bacterial strain sees Table 15.
Table 15 suppository agent of the present invention is to the MIC measurement result of examination bacterial strain
| Antibacterial | The strain number | Medicine | MIC(mg/ml) | MIC 50 | MIC 90 |
| Staphylococcus aureus (ATCC25925) escherichia coli (ATCC25922) staphylococcus aureus | 1 1 15 | Peace bolt suppository of the present invention prostatitis peace bolt suppository of the present invention prostatitis, suppository of the present invention prostatitis peace bolt | 8 8 8 16 1-16 1-64 | 4 8 | 8 32 |
| EHEC pseudomonas aeruginosa pneumonia klebsiella proteus vulgaris NEISSERIA GONORRHOEAE beta hemolytic streptococcus streptococcus mutans | 17 14 18 9 6 8 6 | Suppository Prostant of the present invention suppository Prostant of the present invention suppository Prostant of the present invention suppository Prostant of the present invention suppository Prostant of the present invention suppository Prostant of the present invention suppository Prostant of the present invention | 0.5-32 1-64 16-64 16-64 8-64 32-64 32-64 32-64 8-32 4-32 16-32 16-32 ＞32 ＞32 | 32 64 32 16 16 64 64 64 8 8 32 32 ＞32 ＞32 | 32 ＞64 64 32 64 ＞64 64 64 ＞32 ＞32 ＞32 ＞32 ＞32 ＞32 |
By table 15 as seen, suppository agent of the present invention has different inhibitory action to staphylococcus aureus (ATCC25925), escherichia coli (ATCC25922), staphylococcus aureus, escherichia coli, Pseudomonas aeruginosa, Klebsiella Pneumoniae, proteus vulgaris, Diplococcus gonorrhoeae and beta hemolytic streptococcus, especially to staphylococcus aureus, the inhibition effect of escherichia coli and Klebsiella Pneumoniae is more obvious.
Can find that by as above experiment the high, medium and low dosage rectally of suppository of the present invention can suppress obviously that dimethylbenzene induced mice ear swelling, carrageenin cause rat paw edema and rat granuloma is swollen.Suppository high dose group of the present invention can obviously reduce acetic acid induced mice writhing response number of times; The high, medium and low dosage group of suppository of the present invention all can obviously reduce the rising of rat temperature due to the yeast; Each dosage group of suppository of the present invention all has obvious facilitation to water load rat urine amount.Each dosage group of suppository of the present invention has obvious inhibitory action to the scorching model of rat prostate due to the xiaozhiling injection, can reduce the prostate index, alleviates lesion degree; Compare with rat bacterial prostatitis disease model group, each dosage group of suppository of the present invention can increase lecithin content in the prostate, reduces leukocyte count, reduces the prostate index, alleviates the prostatic lesion degree; Antibacterial experiment can obviously prolong the life span of ehec infection mice in the body; External can have different inhibitory action to staphylococcus aureus (ATCC25925), escherichia coli (ATCC25922), staphylococcus aureus, escherichia coli, Pseudomonas aeruginosa, Klebsiella Pneumoniae, proteus vulgaris, Diplococcus gonorrhoeae and beta hemolytic streptococcus.
Above-mentioned experimental result shows that suppository of the present invention of the present invention has antibiotic, antiinflammatory, and analgesic, diuresis can improve animal prostatitis model lesion degree, is clinical heat-clearing and toxic substances removing, the inducing diuresis for treating stranguria syndrome of being used for, the pharmacological basis of treatment acute and chronic prostatitis.
The acute toxicity test of embodiment 3, shikonin
Medicine: embodiment 1 gained shikonin; Under 37 ℃ of water-baths, be mixed with desired concn for rectally before the experiment, or be mixed with desired concn for irritating stomach and drug administration by injection with 1%CMC and injection solvent with substrate.
Animal: ages in Kunming kind white mice 6 week, body weight 19-21g, male and female half and half, available from animal housing of Changchun Biological Products Institute, the mice quality certification number: 10-1001.The Wistar rat, body weight 120-130g, male and female half and half, available from institute for drug control, Jilin Province animal housing, the rat quality certification number: 10-1009.
One, rectally LD
50Mensuration
Choose 60 of healthy mices,, male and female half and half, according to the trial test result, be divided into 6 groups at random, dosage sees Table 16.Mice fasting (can't help water) 16 hours, rectally 0.05ml/20g, irrigation stomach device enter rectum 1.5cm, give to use behind the medicine spongy embolus (sponge ball parcel polyethylene film, clamp put into anal with tweezers) fixing immediately, and take out 4 little backs.Observe in 7 days, mice outward appearance behavioral activity, the mental status, diet, defecation and color thereof, fur, the colour of skin, breathing, nose, ear, eye, oral cavity have or not abnormal secretion thing, situations such as body weight change and death.The results are shown in Table 16.
Table 16. shikonin mice rectally LD
50Measure
| Group | Dosage (mg/kg) | Logarithm metering (X) | Number of animals (only) | Dead animal number (only) | Mortality rate (%) | LD 50And confidence limit |
| 1 2 3 4 5 6 | 1200.0 968.0 768.0 614.4 491.5 393.2 | 3.0791 2.9823 2.8854 2.7884 2.6915 2.5946 | 10 10 10 10 10 10 | 10 8 4 2 1 0 | 100 80 40 20 10 0 | LD 50=763.6 95% crediblely are limited to 650.4～896.4 |
After administration, bradypnoea before animal performance peace and quiet, few moving, perpendicular hair, the death, feces is black, nose, eye, the no abnormal secretions in oral cavity.Death appears in animal after 6 hours, and the death time mainly concentrates between the 8-30h.Dead mice is dissected the equal Non Apparent Abnormality of main organs such as the perusal heart, liver, spleen, lung, kidney and changes, and does histopathologic examination and does not see obvious pathological change.Put to death the residue animal after 7 days, dissect the perusal heart, liver, spleen, lung, all no abnormal variation of kidney, obvious pathological change is not seen by histopathologic examination.Statistics dead mouse number calculates LD with the Bliss method
50Value and 95% fiducial limit, mice rectally LD
50Be 763.6mg/kg, the 95% credible 650.4～896.4mg/kg that is limited to.
Get 50 of healthy rats, male and female half and half, five equilibrium is 5 groups at random, fasting 16h before the experiment, rectally, 0.2ml/120g, dosage sees Table 2, and irrigation stomach device enters rectum 1.5cm, gives to fill in anus with spongy embolus immediately behind the medicine and fix, and take out 4 little backs.Observe in 7 days, rat outward appearance behavioral activity, the mental status, diet, defecation and color thereof, fur, the colour of skin, breathing, nose, ear, eye, oral cavity have or not abnormal secretion thing, situations such as body weight change and death.
The results are shown in Table 17.
Table 17 Radix Arnebiae extract rat rectally LD
50Measure
| Group | Dosage (mg/kg) | Log10 dose (X) | Number of animals (only) | Dead animal number (only) | Mortality rate (%) |
| 1 2 3 4 5 | 820.0 656.0 524.8 419.8 335.9 | 2.9138 2.8169 2.7200 2.6231 2.5262 | 10 10 10 10 10 | 5 5 4 2 1 | 50 50 40 20 10 |
Toxic reaction appears in animal behind the administration 20min, mainly shows as animal activity minimizing, lethargy, a quilt hair vegetables pine, dyspnea, and feces is black, nose, eye, the no abnormal secretions in oral cavity, and the death time is between 6-26h.The high mortality of animal is 50%, fails to measure rat LD
50Value.
Two, oral administration LD
50Measure
Choose 60 of healthy mices, male and female half and half, be divided into 6 groups at random, fasting 16h before the experiment, according to the trial test result, to irritate stomach respectively and give the various dose shikonin, volume is 40ml/Kg, observe that mice outward appearance behavioral activity, the mental status, diet, defecation and color thereof, fur, the colour of skin, breathing, nose, ear, eye, oral cavity have or not abnormal secretion thing, situations such as body weight change and death in 7 days.The results are shown in Table 18.
Table 18. shikonin mouse stomach administration LD
50Measure
| Group | Dosage (g/kg) | Logarithm metering (X) | Number of animals (only) | Dead animal number (only) | Mortality rate (%) | LD 50And confidence limit |
| 1 2 3 4 5 6 | 8.000 6.400 5.120 4.096 3.277 2.621 | 0.9031 0.8062 0.7093 0.6128 0.5159 0.4183 | 10 10 10 10 10 10 | 7 5 3 2 1 0 | 70 50 30 20 10 0 | LD 50=6.319 95% crediblely are limited to 4.791～8.334 |
Bradypnoea, administration are urinated after 30 minutes and are that purple, feces are black before animal performance peace and quiet after administration, few moving, perpendicular hair, the death, and animal has death after 10 hours, and the death time mainly concentrated between 12-30 hour.Dead animal is dissected the perusal heart, liver, spleen, lung, all no abnormal variation of kidney, does histopathologic examination and does not see obvious pathological change.Put to death the residue animal after 7 days, dissect the perusal heart, liver, spleen, lung, all no abnormal variation of kidney, do histopathologic examination and do not see obvious pathological change.Statistics animal dead number calculates LD with the Bliss method
50Value and 95% fiducial limit, mouse stomach administration LD
50Be 6.319g/kg, the 95% credible 4.791～8.334g/kg that is limited to.
Three, drug administration by injection LD
50Measure
Choose 50 of healthy mices, male and female half and half, be divided into 5 groups at random, according to the trial test result, lumbar injection gives the various dose Radix Arnebiae extract respectively, volume is 5ml/Kg, observes that mice outward appearance behavioral activity, the mental status, diet, defecation and color thereof, fur, the colour of skin, breathing, nose, ear, eye, oral cavity have or not abnormal secretion thing, situations such as body weight change and death in 7 days.The results are shown in Table 19.
Table 19 Radix Arnebiae extract mouse peritoneal drug administration by injection LD
50Measure
| Group | Dosage (mg/kg) | Log10 dose (X) | Number of animals (only) | Dead animal number (only) | Mortality rate (%) | LD 50And confidence limit |
| 1 2 3 4 5 | 20.00 16.00 12.80 10.24 8.192 | 1.3010 1.2041 1.1072 1.0103 0.9134 | 10 10 10 10 10 | 10 9 8 1 0 | 100 90 80 10 0 | LD 50=12.06 95% crediblely are limited to 10.48～13.89 |
Toxic reaction occurs behind administration 10min, mainly show as animal activity minimizing, lethargy, a quilt hair vegetables pine, dyspnea, animal has death behind the 5h, and the death time mainly concentrates between the 8-24h.Dead animal is dissected the perusal heart, liver, spleen, lung, all no abnormal variation of kidney.Put to death the residue animal after 7 days, dissect the perusal heart, liver, spleen, lung, all no abnormal variation of kidney.Statistics animal dead number calculates LD with the Bliss method
50Value and 95% fiducial limit, mouse peritoneal drug administration by injection LD
50Be 12.06mg/kg, the 95% credible 10.48～13.89mg/kg that is limited to.
Choose 50 of healthy rats, male and female half and half, be divided into 5 groups at random, according to the trial test result, lumbar injection gives the various dose Radix Arnebiae extract respectively, volume is 5ml/Kg, observes that mice outward appearance behavioral activity, the mental status, diet, defecation and color thereof, fur, the colour of skin, breathing, nose, ear, eye, oral cavity have or not abnormal secretion thing, situations such as body weight change and death in 7 days.The results are shown in Table 20.
Table 20 Radix Arnebiae extract rats by intraperitoneal injection administration LD
50Measure
| Group | Dosage (mg/kg) | Log10 dose (X) | Number of animals (only) | Dead animal number (only) | Mortality rate (%) | LD 50And confidence limit |
| 1 2 3 4 5 | 15.00 12.00 9.600 7.680 6.144 | 1.1761 1.0792 0.9823 0.8854 0.7884 | 10 10 10 10 10 | 10 8 6 1 0 | 100 80 60 10 0 | LD 50=9.635 95% crediblely are limited to 8.251～11.25 |
Toxic reaction occurs behind administration 10min, mainly show as animal activity minimizing, lethargy, a quilt hair vegetables pine, dyspnea, animal has death behind the 5h, and the death time mainly concentrates between the 8-24h.Dead animal is dissected the perusal heart, liver, spleen, lung, all no abnormal variation of kidney.Put to death the residue animal after 7 days, dissect the perusal heart, liver, spleen, lung, all no abnormal variation of kidney.Statistics animal dead number calculates LD with the Bliss method
50Value and 95% fiducial limit, rats by intraperitoneal injection administration LD
50Be 9.635mg/kg, the 95% credible 8.251～11.25mg/kg that is limited to.
Mice rectally Radix Arnebiae extract LD
50Be 763.6mg/kg, the 95% credible 650.4～896.4mg/kg that is limited to; Irritate stomach and give Radix Arnebiae extract LD
50Be 6.319g/kg, the 95% credible 4.791～8.334g/kg that is limited to; Mouse peritoneal drug administration by injection LD
50Be 12.06mg/kg, the 95% credible 10.48～13.89mg/kg that is limited to.Rat rectally and gastric infusion are not measured LD
50Value; Intraperitoneal injection LD
50Be 9.635mg/kg, the 95% credible 8.251～11.25mg/kg that is limited to.
In sum, shikonin has therapeutic activity to prostatitis, be that the suppository of main component has excellent curative to various prostatitis models.
Claims (4)
1, the application of shikonin in preparation treatment prostatitis medicine.
2, application according to claim 1 is characterized in that: described treatment prostatitis medicine is a suppository.
3, the prostatitic suppository of a kind of treatment is made up of shikonin and suppository base, and described shikonin accounts for the 0.5-1.5% of described suppository weight, and surplus is a suppository base; Described suppository base is by the semi-synthetic fatty acid glyceride of 50-70% weight, and the vaseline of the liquid paraffin of 10-30% weight and 15-25% weight is formed, and above-mentioned three percentage compositions are the percentage composition that accounts for the suppository base total amount.
4, the prostatitic suppository of treatment according to claim 3, it is characterized in that: described shikonin accounts for 1% of described suppository weight, described suppository base is by the semi-synthetic fatty acid glyceride of 70% weight, and the vaseline of the liquid paraffin of 10% weight and 20% weight is formed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100870388A CN1307987C (en) | 2005-07-25 | 2005-07-25 | New usage of alkannin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100870388A CN1307987C (en) | 2005-07-25 | 2005-07-25 | New usage of alkannin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1726904A CN1726904A (en) | 2006-02-01 |
| CN1307987C true CN1307987C (en) | 2007-04-04 |
Family
ID=35926543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100870388A Active CN1307987C (en) | 2005-07-25 | 2005-07-25 | New usage of alkannin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1307987C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102198130B (en) * | 2011-03-30 | 2012-08-29 | 中国人民解放军第二军医大学 | Use of shikonin as antifungal medicine synergist |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004073699A1 (en) * | 2003-02-21 | 2004-09-02 | Beijing Jbc Chinese Traditional Medicine Science And Technology Develop Co. Ltd. | Pharmaceuticals comprising shikonins as active constituent |
| CN1548036A (en) * | 2003-05-08 | 2004-11-24 | 北京金本草中药科技发展有限公司 | Medicine containing acarnine compound as active component |
-
2005
- 2005-07-25 CN CNB2005100870388A patent/CN1307987C/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004073699A1 (en) * | 2003-02-21 | 2004-09-02 | Beijing Jbc Chinese Traditional Medicine Science And Technology Develop Co. Ltd. | Pharmaceuticals comprising shikonins as active constituent |
| CN1548036A (en) * | 2003-05-08 | 2004-11-24 | 北京金本草中药科技发展有限公司 | Medicine containing acarnine compound as active component |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1726904A (en) | 2006-02-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1883492A (en) | Water solution of 20(R)-ginsenoside Rg3 pharmaceutical composition and preparation method thereof | |
| CN101040915A (en) | Method for preparing a Shuanhuanglian injection and the component detecting method | |
| CN1307987C (en) | New usage of alkannin | |
| CN1857362A (en) | Jingankang medicine preparation and its preparing process | |
| CN1872279A (en) | Composition of medication for treating ulcer in the oral cavity, and preparation method | |
| CN1772136A (en) | Medicine composition for treating soft tissue damage and osteoarthropathy and its prepn process | |
| CN1219130A (en) | Composition comprising a nitrone compound for use in treating ocular inflammation | |
| CN1608662A (en) | Medicine with antiphlogistic, analgetic, microbiostatic and diuretic effects | |
| CN1850202A (en) | Vagina external-use medicine composition and its preparing method and use | |
| CN1606979A (en) | Effect of scutellarein as antifebrile, analgesic, antiphlogistic, antibiotic and antiviral agent | |
| CN1562113A (en) | Medicine for treating chronic pelvic inflammation and its preparing method | |
| CN1709418A (en) | Katsumadai seed extract and its preparation | |
| CN1872326A (en) | Composition of external remedy for treating hemorrhoids, and preparation method | |
| CN1853655A (en) | Oral colon target preparation for treating colitis ulcerativa and its making method | |
| CN1739616A (en) | Skullcap root extract prepn for eye and its prepn process | |
| CN1239169C (en) | Externally applied medicinal composition for resisting inflammation and repressing and killing bacteria and preparing method | |
| CN1457772A (en) | Injection for curing acute lung injury and acute respirotary distress syndrome | |
| CN1220515C (en) | Medicine for treating throat disease | |
| CN1739507A (en) | Medicine composition for treating mixed infectious disease | |
| CN1261452C (en) | Sugar latticeing material CHB extracted from serum of turtle or/and tortoise, preparation process and application in pharmacy thereof | |
| CN1281218C (en) | Preparation method of clam meat extract and medicinal composition containing same and its application | |
| CN1259080C (en) | Bacteria and virus resisting and inflammation eliminating eye drop and its preparing process | |
| CN1720905A (en) | The application of beta-Asarone in pharmacy | |
| CN1931231A (en) | Chinese medicine gargle for treating periodontal disease and stomatocace | |
| CN1314388C (en) | Four component tumeric tablet and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP02 | Change in the address of a patent holder | ||
| CP02 | Change in the address of a patent holder |
Address after: Room 902, Ming Shang Building, 55 Suzhou Street, Haidian District, Beijing 100089 Patentee after: Lingruweiye Tech Co., Ltd., Beijing Address before: 100029 Beijing Chaoyang District Xiaoguanbeili 45 Century Jiayuan Building 29A Patentee before: Lingruweiye Tech Co., Ltd., Beijing |