CN1559451A - Medicine compound having synergistic action - Google Patents
Medicine compound having synergistic action Download PDFInfo
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- CN1559451A CN1559451A CNA2004100043910A CN200410004391A CN1559451A CN 1559451 A CN1559451 A CN 1559451A CN A2004100043910 A CNA2004100043910 A CN A2004100043910A CN 200410004391 A CN200410004391 A CN 200410004391A CN 1559451 A CN1559451 A CN 1559451A
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
A synergistic composite medicine contains two Chinese-medicinal materials: nakeflower beautyberry leaf and medicina fatheadtree wood.
Description
Technical field
The present invention relates to comprise the pharmaceutical composition of Callicarpa nudiflora, specifically relate to strengthen the pharmaceutical composition of Callicarpa nudiflora beneficial effect.
Background technology
Callicarpa nudiflora (Callicarpa Nudiflora) is the leaf of Verenaceae plant Callicarpa nudiflora, contains flavonoid glycoside, comprehensive tannic acid, resinene, phenols, polysaccharide, hydroxy compounds and magnesium, calcium iron salt etc.Callicarpa nudiflora can suppress capillary permeability, to early stage inflammation ooze out, swelling has tangible anti-inflammatory response effect; Simultaneously can obviously shorten, clotting time, haemostatic effect is remarkable; Various bacteria can also be suppressed, the generation of secondary infection can be prevented; Also have function for protecting liver and reducing enzyme activity, the liver injury that HFRS is caused has prevention and therapeutical effect (Wang Zhenhua etc., Guangdong pharmacy, 1998,5; 5-9; Fu Jian etc., University Of Hainan's journal natural science edition, 2002,20 (2): 154-157).
The medicinal history of Callicarpa nudiflora is long, has good DEVELOPMENT PROSPECT.Regrettably, very limited to Callicarpa nudiflora chemical constituent and active further investigation thereof both at home and abroad at present (referring to Ren Fengzhi etc., research and development of natural products, 2001,13 (1): 33-34).Sun Shuchen has disclosed in CN1155437A and has comprised natural collagen protein and Callicarpa nudiflora extract compositions, and said composition is to have hemostasis, wound healing, antibacterial infection and detoxifcation to treat the effect of skin ulcer; Zhang Linwen etc. disclose the KANGGONGYAN PIAN that comprises Folium Callicarpae Formosanae, Herba Leonuri and the Radix Linderae in CN1092983A.
In the prior art, the general independent use of Callicarpa nudiflora, this has limited its extensive use clinically to a great extent, especially in the practice of handling some complex diseases (for example burn), its advantage be difficult to be effectively played.For example, studies show that Callicarpa nudiflora can effectively be treated by inflammation caused by bacterial infection, but the effectiveness of inflammation that non-bacterial infection is caused and/or compound inflammation is not obvious relatively.Though someone had once inquired into the pharmacological action (Xie Bin etc. of Callicarpa nudiflora on cellular level, ACAD J GCP, 1995,11 (3): 141-145), but up to now, nobody provides the foundation of science to the combined effect of Callicarpa nudiflora and other active component.
Therefore, those skilled in the art are readily appreciated that, also wish to develop urgently such Compositional type pharmaceutical composition; It can work in coordination with main effects such as the eliminating inflammation and expelling toxin that strengthens Callicarpa nudiflora, astringing to arrest bleeding pointedly, it is effective simultaneously can pair cell to infect inflammation or compound complicated inflammation that the inflammation, the especially non-bacterial infection that cause cause, and can shorten the course of disease, reduce the incidence rate of complication, and use conveniently, have no adverse reaction, be worthy of popularization.
Summary of the invention
We have carried out deep research to the Callicarpa nudiflora and the mechanism of action thereof, particularly by screening and prescription to given activity composition with antiinflammatory action, address the above problem effectively, and the present invention has promptly been finished in further research on this basis.
Through a large amount of experiment screenings, the inventor is surprised to find, and Lignum et Radix Naucleae can significantly strengthen the beneficial effect of Callicarpa nudiflora, and the compound artifact that comprises Lignum et Radix Naucleae and Callicarpa nudiflora simultaneously has significant treatment advantage than present commercially available prod.Lignum et Radix Naucleae (Nauclea officinalis) genus rubia section plant, its branch, bark etc. have medical value, contain flavonoid glycoside, phenols.Usually, Lignum et Radix Naucleae also is independent application, cures mainly fever caused by exogenous pathogens, acute jaundice, stomachache, acute tonsillitis and pharyngolaryngitis etc.In addition, its stem separator (being mainly alkaloid) has certain bacteriostasis (Chen Mengjing etc., Botany Gazette, 1984,26 (3): 281-282).(University Of Hainan's journal natural science edition such as Fu Jian, 2002,20 (1): 54-56) described the antiinflammatory action of Lignum et Radix Naucleae extractum sheet, it is the anti-inflammatory drug of a kind of " too many levels effect " that the author points out Lignum et Radix Naucleae, but does not hint or clearly instruct the beneficial effect of Lignum et Radix Naucleae and any other active component coupling.So far do not see as yet that the someone sets forth Lignum et Radix Naucleae and Callicarpa nudiflora use in conjunction effect clinically.
Guiding test shows that the coupling of Callicarpa nudiflora and Lignum et Radix Naucleae shows synergism, significantly is better than and uses this two kinds of effectiveness that the single medicine is produced separately.Simultaneously, the inventor also is surprised to find, the two different proportioning (for example 1: 10-10: 1) and the relation between the effect be non-linear.For example, be that drug effect does not always show stronger situation along with the increase of Callicarpa nudiflora content in the scope of main effect (for example bacteriostasis) at the expection Callicarpa nudiflora; Similarly, the expection Lignum et Radix Naucleae be the inhibitory action of mice ear (for example to) in the scope of main effect, drug effect does not always strengthen along with the increase of Lignum et Radix Naucleae content yet, infers that this may exist multi-target effect relevant with the two.Especially it should be noted that in all guiding pharmacological evaluation and all found above-mentioned phenomenon that this obviously is different from instruction (for example, Chen Yuxiang etc., Hunan Medical University's journal, 1995,20 (5): 431-433) of prior art.Through further investigation, determined that further the part by weight of Callicarpa nudiflora and Lignum et Radix Naucleae is 1 among the present invention: 10-10: 1, be preferably 1: 5-5: 1, more preferably 1: 1.
Therefore, an object of the present invention is to provide Callicarpa nudiflora and the Lignum et Radix Naucleae coupling application in prevention or treatment inflammation, hemorrhage and/or viral hepatitis relevant disease.The present invention property created ground first proposes to unite and gives Callicarpa nudiflora and the above-mentioned disease that causes owing to many complicated reasons can be treated and/or control to Lignum et Radix Naucleae effectively, provide a kind of new therapeutic scheme as the substituting of prior art, this therapy will be that the doctor highly approves and puts forth effort and recommends.Described disease includes but not limited to the known kinds of Diseases that can treat or prevent of Callicarpa nudiflora, and for example described disease comprises: cold, fever, laryngopharynx swelling and pain, pharyngolaryngitis, external auditory meatus or skin furuncle and phyma, conjunctivitis, upper respiratory tract infection, acute and chronic tonsillitis, urinary system infection, hemorrhage (for example nose, respiratory tract, digestive tract or genitourinary system are hemorrhage), acute and chronic rhinitis, hemorrhoid, stomachache, acute jaundice, viral hepatitis or burn and scald.Described disease also comprises the inflammation that bacterial infection and/or non-bacterial infection cause, for example various gynecological inflammations: mastitis, cervicitis, vaginitis (comprising general vaginitis, candidal vaginitis, trichomonal vaginitis), enteritis, bacillary dysentery, urinary tract infection, cholecystitis, ulcer of the lower limb, tinea pedis infection, skin eczema, suppurative skin ulcer.Described unite comprise the order use the preparation that comprises Callicarpa nudiflora, Lignum et Radix Naucleae respectively, also comprise and use the pharmaceutical preparation that contains Callicarpa nudiflora and Lignum et Radix Naucleae simultaneously.
On the other hand, the invention provides a kind of pharmaceutical composition, comprise the Callicarpa nudiflora for the treatment of effective dose and Lignum et Radix Naucleae as active component, wherein the content of active component is about 1-85% weight, is preferably 20-65% weight.In context, described Callicarpa nudiflora comprises the former powder or the extract of Callicarpa nudiflora, wherein extract comprises water and/or alcohol extract, also can be the effective site extracted of other specific solvent (petroleum ether, ether, chloroform, ethyl acetate, n-butyl alcohol) or comprise that the combination of wherein single or several active component of flavonoid glycoside, phenols, tannin (for example appoints wind sesame etc., research and development of natural products, 2001,13 (1): 33-34; Ren Fengzhi etc., Chinese Pharmaceutical Journal, 2001,36 (7): 445-447; Wang Zhenhua etc., the Guangdong pharmacy, 1998,3:5-9); Described Lignum et Radix Naucleae is meant Lignum et Radix Naucleae extract, comprise water and/or alcohol extract, also can be the effective site extracted of other specific solvent (petroleum ether, ether, chloroform, ethyl acetate, n-butyl alcohol) or the combination that comprises flavonoid glycoside, phenols, alkaloidal single or several active component (Chen Meng cyanines etc. for example, Botany Gazette, 1984,26 (3): 281-282; Lin Mao etc., Acta Pharmaceutica Sinica, 1985,20 (12): 902-905).For example, consider, can adopt following extraction process from industrialization and economic aspect:
(1) Callicarpa nudiflora extracts: get Callicarpa nudiflora, crushed after being dried becomes the Callicarpa nudiflora coarse powder, with the purified water extraction of 3 times of amounts 3 times, and merge extractive liquid,, filter, be condensed into thick paste, add 95% ethanol of 4 times of amounts, fully stir, the washing back filters, discard ethanol mother solution (recovery ethanol), the vacuum drying precipitate, it is standby to cross 80 mesh sieves after pulverizing.
(2) Lignum et Radix Naucleae is extracted: get Lignum et Radix Naucleae and clean, section is extracted 3 times with 95% soak with ethanol of 3 times of amounts, merges ethanol extract, steams ethanol, adds an amount of purified water dissolving and filtration.With ADS-17 resin absorption filtrate, wash the back with 70% ethanol elution with an amount of purification.Concentrate eluant, vacuum drying, it is standby to cross 80 mesh sieves after pulverizing.
Preferably, pharmaceutical composition of the present invention can be made dosage form oral, intravenously administrable, for example granule, tablet, capsule, drop pill, pilule or injection.Advantageously, in order to adapt to the treatment demand, also can be made into dosage form, for example suppository, aerosol or Foradil Aerolizer formoterol fumarate for percutaneous or mucosa delivery.In addition, also pharmaceutical composition of the present invention can be added in binder or the gauze for direct external.
The active component that is suitable for the above-mentioned dosage form of the present invention can be solid, powder or granule, liquid form.Particularly advantageously; can adopt equipment such as microjet granulator, jet mill; with microcrystalline Cellulose, PVP, CMC or PEG etc. is dispersant; Callicarpa nudiflora, Lignum et Radix Naucleae are made micron dimension (1-75 μ m particle diameter), sub-micrometer scale (100-500nm particle diameter) or thinner ultra-fine grain; with its curative effect of further raising; reduce dosage (for example, being about the 20-80% of conventional powder consumption, preferred 35-60%).
The specific embodiment
The pharmacodynamics test example
Material
MedicineCallicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet of the present invention; The Callicarpa nudiflora sheet, specification 0.38g/ sheet, first pharmaceutcal corporation, Ltd in Hainan; The Lignum et Radix Naucleae sheet, specification 0.5g/ sheet, Hainan Pharmaceutical Factory Co., Ltd.; Aspirin tablet, Jiaozuo City chemical pharmaceutical factory.Each medicine is in facing with preceding with the purified water dissolved dilution.
AnimalKunming mouse and SD rat provide by medical faunae center, Hubei Province; Japan large rabbit is provided by experimental animal center, Hainan Province.The quality certification number: mice 19-082, rat 19-083, rabbit 30-003.
1. to the influence of mice capillary permeability
90 of mices, male and female half and half, body weight 18-22g is divided into 8 groups at random: (1) matched group (giving the isometric(al) distilled water); (2) aspirin group 0.2g/kg; (3)-(9) group gives the compound recipe Callicarpa nudiflora Lignum et Radix Naucleae sheet 2.0g/kg of Lignum et Radix Naucleae sheet, Callicarpa nudiflora sheet and different proportionings respectively.Each organizes PO administration every day 1 time, for three days on end, the blue normal saline solution 10mL/kg of the ivens of each Mus intravenous injection 0.1% of 30min after the last administration, every gives 0.6% glacial acetic acid (HAC) normal saline 0.2mL immediately, taking off cervical vertebra behind the 15min puts to death, every mice is washed abdominal cavity and sucking-off cleaning mixture for several times with the 6mL normal saline, adds normal saline after the merging to 10mL, and centrifuged supernatant is surveyed its optical density (OD) value in 722 spectrophotometers (590nm).
The influence that table 1 medicine increases the HAC induced mice abdominal cavity blood capillary general character (x ± s)
| Group | Dosage (g/kg) | Number of animals (only) | The OD value |
| Matched group | ????- | ????10 | ?0.196±0.08 |
| Aspirin | ????0.2 | ????10 | ?0.106±0.08 a |
| The Callicarpa nudiflora sheet | ????2.0 | ????10 | ?0.125±0.08 a |
| The Lignum et Radix Naucleae sheet | ????2.0 | ????10 | ?0.104±0.08 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 1) | ????2.0 | ????10 | ?0.076±0.08 a，b，c |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (2: 1) | ????2.0 | ????10 | ?0.098±0.08 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 2) | ????2.0 | ????10 | ?0.092±0.08 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (4: 1) | ????2.0 | ????10 | ?0.107±0.08 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 4) | ????2.0 | ????10 | ?0.1±0.08 a |
A: compare p＜0.05 with matched group; B: compare p＜0.05 with Callicarpa nudiflora sheet group; C: compare p＜0.05 with the gallbladder groups of strands
2. the influence of xylol induced mice ear swelling
Mice group and administration are with experiment 1,1h after the last administration, with dimethylbenzene 0.05mL/ only drip to mouse right ear, left ear compares, and puts to death animal behind the 15min, card punch with diameter 6mm downcuts ears with the position, be to weigh on the rigorous analysis balance of 1mg at sensibility reciprocal,, count out and respectively organize the swelling degree with heavy poor of left and right sides auricle, obtain inhibitory rate of intumesce (%), and the comparable group differences.
Table 2 medicine is to the influence (n=10) of mice ear (X ± S)
| Group | Dosage (g/kg) | Swelling degree (mg) | Press down swollen rate (%) |
| Matched group | ????- | ????8.9±1.8 | |
| Aspirin | ????0.2 | ????3.1±1.2 a | ????65 |
| The Callicarpa nudiflora sheet | ????2.0 | ????4.2±1.6 a | ????53 |
| The Lignum et Radix Naucleae sheet | ????2.0 | ????3.8±1.0 a | ????57 |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 1) | ????2.0 | ????2.3±1.5 a，b，c | ????74 |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (2: 1) | ????2.0 | ????2.9±1.3 a | ????67 |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 2) | ????2.0 | ????2.9±1.0 a | ????67 |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (4: 1) | ????2.0 | ????3.0±0.9 a | ????66 |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 4) | ????2.0 | ????3.2±1.0 a | ????64 |
A: compare p＜0.05 with matched group; B: compare p＜0.05 with Callicarpa nudiflora sheet group; C: compare p＜0.05 with the gallbladder groups of strands
3. to the bullate influence of rat paw due to the Ovum Gallus domesticus album
Body weight is 80 of the rats of 150-180g, and male and female half and half are divided 8 groups: (1) matched group (giving the isometric(al) distilled water) at random; (2) aspirin group 0.15g/kg; (3)-(8) group gives the compound recipe Callicarpa nudiflora Lignum et Radix Naucleae sheet 2.0g/kg of Lignum et Radix Naucleae sheet, Callicarpa nudiflora sheet and different proportionings respectively.Each organizes PO administration every day 1 time, and for three days on end, 1h respectively organizes fresh albumen 0.05mL/ so that inflammation of injection 100% under the right back sufficient lift after the last administration; Different time caused the following change in volume in scorching sufficient sole of the foot joint before and after measurement caused inflammation, and consequently scorching forebody-afterbody product moment value is the swelling degree, and compares between organizing.
Table 3 medicine is to the influence (n=10) of rat paw edema due to the Ovum Gallus domesticus album (X ± S)
| Group | Cause scorching back swelling rate (%) | |||
| ????1h | ????2h | ????4h | ????6h | |
| Matched group | 71.2±11.7 | 60.±13.2 | 45.6±12.3 | 36.7±9.8 |
| Aspirin | 55.1±13.7 a | 38.7±17.2 a | 21.8±10.8 a | 11.5±18.2 a |
| The Callicarpa nudiflora sheet | 65.2±18.2 | 50.1±15.0 a | 38.9±10.4 | 21.6±11.3 a |
| The Lignum et Radix Naucleae sheet | 60.5±15.2 | 47.7±10.8 a | 35.3±18.2 a | 17.6±12.7 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 1) | 48.2±9.8 a，c | 30.7±10.5 a，b，c | 20.9±14.6 a，b，c | 9.2±10.8 a，c |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (2: 1) | 53.7±15.2 a | 36.1±11.4 a | 25.7±12.0 a | 12.8±9.1 a，b |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 2) | 57.2±14.1 a | 39.8±8.6 a | 29.3±11.8 a | 15.2±14.0 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (4: 1) | 59.4±16.3 a | 42.3±9.1 a | 33.6±9.5 a | 17.2±11.9 a |
| Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet (1: 4) | 58.1±15.8 a | 44.9±12.8 a | 30.8±13.7 a | 18.9±17.3 a |
A: compare p＜0.05 with matched group; B: compare p＜0.05 with Callicarpa nudiflora sheet group; C: compare p＜0.05 with the gallbladder groups of strands
The result of experiment 1-3 shows that after Callicarpa nudiflora sheet and Lignum et Radix Naucleae sheet were made compound recipe by 1: 1 proportioning, its antiinflammatory action was significantly strengthened, and compares with Lignum et Radix Naucleae sheet and Callicarpa nudiflora sheet to have significant difference.Other four kinds of proportionings to a certain degree can strengthen its antiinflammatory action, but compare there was no significant difference with Lignum et Radix Naucleae sheet, Callicarpa nudiflora sheet.
4. in-vitro antibacterial effect
Test used clinical isolates strain and amount to 62 strains, be the clinical isolates strain of area, Changsha various big hospital.Every strain antibacterial is divided pure before experiment through agar plate, 37 ℃ of fresh cultured of spending the night are done and are used for experiment after the suitable dilution.Adopt the agar doubling dilution to measure minimum inhibitory concentration (MIC), the results are shown in Table 4.
The external MIC measurement result of the different proportioning Lignum et Radix Naucleae of table 4 Callicarpa nudiflora
| Test organisms | Trial drug | ??MIC 50??(g/ml) | MIC 90(g/ml) | MIC scope (g/ml) |
| Staphylococcus aureus n=20 | The nauclea officinalis sheet is a callicarpa nudiflora callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of callicarpa nudiflora nauclea officinalis sheet (1: 1) (2: 1) (1: 2) (4: 1) (1: 4) | ??0.05 ??0.0125 ??0.0063 ??0.0085 ? ??0.0125 ??0.025 ??0.0125 | ?0.2 ?0.025 ?0.0125 ?0.0106 ? ?0.025 ?0.05 ?0.025 | ??0.0125-0.8 ??0.0031-0.2 ??0.0016-0.1 ??0.0031-0.8 ? ??0.0063-0.2 ??0.0063-0.4 ??0.0125-0.4 |
| Staphylococcus epidermidis n=16 | The nauclea officinalis sheet is a callicarpa nudiflora callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of callicarpa nudiflora nauclea officinalis sheet (1: 1) (2: 1) (1: 2) (4: 1) (1: 4) | ??0.025 ??0.0125 ??0.0016 ??0.0063 ? ??0.0063 ??0.0125 ??0.0125 | ?0.05 ?0.025 ?0.0125 ?0.0125 ? ?0.0125 ?0.05 ?0.025 | ??0.0031-0.2 ??0.0063-0.4 ??0.0008-0.1 ??0.0031-0.05 ? ??0.0063-0.1 ??0.0016-0.2 ??0.0031-0.2 |
| Escherichia coli n=20 | The nauclea officinalis sheet is a callicarpa nudiflora callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of callicarpa nudiflora nauclea officinalis sheet (1: 1) (2: 1) (1: 2) (4: 1) (1: 4) | ??0.1 ??0.05 ??0.0063 ??0.0125 ? ??0.025 ??0.0125 ??0.025 | ?0.2 ?0.1 ?0.0125 ?0.025 ? ?0.05 ?0.05 ?0.1 | ??0.025-0.8 ??0.0063-1.6 ??0.0063-0.1 ??0.0063-0.2 ? ??0.0125-0.8 ??0.0063-0.4 ??0.0125-0.8 |
| Salmonella n=6 | The nauclea officinalis sheet is a callicarpa nudiflora callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of the callicarpa nudiflora nauclea officinalis sheet of callicarpa nudiflora nauclea officinalis sheet (1: 1) (2: 1) (1: 2) (4: 1) (1: 4) | ??0.2 ??0.05 ??0.0031 ??0.0063 ? ??0.025 ??0.0063 ??0.05 | ?0.4 ?0.1 ?0.0125 ?0.025 ? ?0.1 ?0.0125 ?0.1 | ??0.025-＞1.6 ??0.0063-0.8 ??0.0031-0.05 ??0.0031-0.1 ? ??0.0063-0.2 ??0.0016-0.05 ??0.0125-0.8 |
The result shows, for staphylococcus aureus, staphylococcus epidermidis and escherichia coli, the antibacterial action of Lignum et Radix Naucleae sheet a little less than, but antibacterial effect the best of 1: 1 prescription of itself and Callicarpa nudiflora, and the compound recipe sheet of 2: 1,4: 1,1: 2,1: 4 proportioning is similar to the effect of Callicarpa nudiflora sheet; For Salmonella, the Callicarpa nudiflora Lignum et Radix Naucleae compound recipe sheet antibacterial effect of 1: 1,2: 1,4: 1 proportionings is close, slightly is better than the compound recipe sheet of Lignum et Radix Naucleae sheet, Callicarpa nudiflora sheet and 1: 2,1: 4 proportioning, and the effect of Lignum et Radix Naucleae sheet is the most weak.
5. refrigeration function
Get 24 of rabbit, 24 ℃ of room temperatures, 2d surveys anus temperature 4 times every day before the experiment, selects body temperature to be no more than 0.3 ℃ animal for experiment usefulness 39.0-39.8 ℃ and body temperature fluctuation every day.After surveying the basal body temperature of animal morning experiment day, be divided into totally 3 groups of Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet 1.2g/kg, 0.6g/kg and matched groups (giving equal-volume 0.5% carboxymethylcellulose sodium solution) at random, every group 8, press the 10ml/kg gastric infusion respectively 1 time after pressing 0.5ml/kg auricular vein injection with the typhoid Vi polysaccharide vaccine, then every 1h survey anus temperature 1 time.
Table 5 medicine is to rabbit body temperature liter due to the rabbit typhoid Vi polysaccharide vaccine
High influence (n=8) (X ± S)
| Group | Body temperature value after vaccine inoculation and the administration | ||||
| ????1h | ????2h | ????3h | ????4h | ????5h | |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet (1.2g/kg) | 39.4±0.6 * | 39.5±0.7 * | 39.2±0.7 * | 392±0.6 * | 39.1±0.5 * |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet (0.6g/kg) | 39.8±0.5 * | 39.9±0.8 * | 39.7±0.6 * | 39.7±0.3 * | 39.4±0.6 * |
| 0.5% carboxymethylcellulose sodium solution | 40.8±0.5 | 40.9±0.6 | 41.2±0.7 | 41.0±0.5 | 41.0±0.6 |
Annotate: the t check, compare with matched group,
*P＜0.05
The result shows, Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet 1.2g/kg, 0.6g/kg and matched group fervescence be 3h arrival peak after giving vaccine inoculation all, administration group body temperature is respectively 39.2 ± 0.7 ℃ and 39.7 ± 0.6 ℃, matched group body temperature is 41.2 ± 0.7 ℃, shows that Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet has certain refrigeration function to the rabbit body temperature rising due to the typhoid Vi polysaccharide vaccine.
6. analgesic activity
Mice group and administration are with experiment 1, and to give concentration be 0.7%HAC normal saline 0.1ml lumbar injection to 30min after the last administration, observe in the 15min animal and turn round the body number of times, with matched group comparable group differences.
Table 6 Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet is turned round the mice due to the glacial acetic acid
The influence of body (n=10)
| Group | Dosage (g/kg) | Turn round body number of times (X ± S) | The P value * |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????1.2 | ????7.4±6.2 | ????＜0.01 |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????0.6 | ????8.2±6.4 | ????＜0.01 |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????0.3 | ????9.5±6.7 | ????＜0.05 |
| The aspirin sheet | ????0.2 | ????9.0±6.1 | ????＜0.01 |
| Contrast | ????17.0±6.7 |
Annotate:
*Compare with matched group
The result shows, Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet 1.2g/kg, 0.6g/kg and three dosage groups of 0.3g/kg all have the inhibitory action of highly significant to the mouse writhing due to the glacial acetic acid.
7. to the influence of mice non-specific immunity (phagocytic function)
Mice group and administration are with experiment 1, behind each treated animal administration 7d, after the tail vein is pressed the india ink of 0.1ml/10g injection 10%, get blood 20 μ l in 2min and 10min eye socket, be added to lysed erythrocyte in the 4ml distilled water, use 722 type spectrophotometers (600nm) and measure optical density (OD) value, with OD value and matched group comparable group differences.
The result shows that Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet 1.2g/kg, 0.6g/kg and three dosage groups of 0.3g/kg all can obviously strengthen the non-specific function of mice.
Table 7 Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet gulps down the mice reticuloendothelial system
Bite the influence (X ± S) of function
| Group | Dosage (g/kg) | 2min OD value | 10min OD value |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????1.2 | ????0.10±0.05 * | ????0.08±0.02 ** |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????0.6 | ????0.11±0.02 ** | ????0.11±0.02 * |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????0.3 | ????0.13±0.02 * | ????0.11±0.02 * |
| The aspirin sheet | ????0.2 | ????0.09±0.01 ** | ????0.10±0.01 ** |
| Contrast | ????0.15±0.03 | ????0.13±0.02 |
Annotate: the t check, compare with matched group,
*P＜0.05,
*P＜0.01
8. to the influence of mice delayed allergy (DTH)
Mice group and medication be experiment 1 together, successive administration 5d, and in administration 3d tail vein injection sheep red blood cell sensitization, administration 5d compares with volume normal saline injection right side sole with sheep red blood cell injection left side sole.Measure two sole thickness after 24 hours, with both difference and matched group comparable group differences.
Table 8 Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet is to mouse cell Immune Effects (n=10)
| Group | Dosage (g/kg) | Two sufficient sole of the foot thickness differences (cm, X ± S) | The P value * |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????1.2 | ????0.03±0.01 | ??＜0.01 |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????0.6 | ????0.03±0.02 | ??＜0.01 |
| Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet | ????0.3 | ????0.05±0.02 | ??＜0.05 |
| The aspirin sheet | ????0.2 | ????0.03±0.02 | ??＜0.01 |
| Reference substance | ????0.08±0.03 |
Annotate:
*Compare with matched group.
The result shows that Lignum et Radix Naucleae extractum-Callicarpa nudiflora sheet 1.2g/kg, 0.6g/kg and three dosage groups of 0.3g/kg all can obviously improve cell immune function of human body.
Example of formulations
Embodiment 1 tablet
| Prescription 1 | Prescription 2 | ||
| Callicarpa nudiflora extract | 240mg | Callicarpa nudiflora extract | 80mg |
| Lignum et Radix Naucleae extract | 240mg | Lignum et Radix Naucleae extract | 80mg |
| Lactose | 20mg | Ethyl cellulose | 180mg |
| Magnesium stearate | 0.9mg | Microcrystalline Cellulose | 85mg |
| 60% ethanol | In right amount | Lactose | 15mg |
| Prescription 3 | Prescription 4 (dispersible tablets) | ||
| Callicarpa nudiflora extract | 120mg | Callicarpa nudiflora extract | 50mg |
| Lignum et Radix Naucleae extract | 120mg | Lignum et Radix Naucleae extract | 50mg |
| Microcrystalline Cellulose | 140.5mg | Cross-linked pvp | 40mg |
| Carboxymethyl starch sodium | 15mg | Microcrystalline Cellulose | 100mg |
| Micropowder silica gel | 1.5mg | Lactose | 180mg |
| Magnesium stearate | 3mg | Micropowder silica gel | 10mg |
| 95% ethanol | In right amount | ||
Exemplary process: get active component and lactose and place V-type blender mixing, add an amount of 60% alcohol granulation after sieving, 60 ℃ of dryings add magnesium stearate, abundant mixing, tabletting.The gained tablet is coating further.
Embodiment 2 injections
| Prescription 1 | Prescription 2 (infusion solutionses) |
| Callicarpa nudiflora extract 2g Lignum et Radix Naucleae extract 2g water for injection 1000ml | Callicarpa nudiflora extract 0.2g Lignum et Radix Naucleae extract 0.2g sodium chloride 8.0g water for injection 1000ml |
Exemplary process: get Lignum et Radix Naucleae extract and be added in the water for injection, regulate PH and be about 6.8-8.0, stir dissolving fully.Dissolve Callicarpa nudiflora extract with water for injection, add to then in the Lignum et Radix Naucleae extract solution.Add proper amount of active carbon, heat little boiling 30 minutes, carbon removal, fine straining, embedding, sterilization, promptly.
Embodiment 3 sprays
| Prescription |
| Callicarpa nudiflora extract 5.0g Lignum et Radix Naucleae extract 5.0g |
Exemplary process: get Callicarpa nudiflora extract 5.0g, it is an amount of to add purified water, and adjust pH 7.5-8.0 makes dissolving, gets Lignum et Radix Naucleae extract 5.0g, adds purified water and makes dissolving in right amount, merges above-mentioned two solution, adds purified water to 1000mL, mixing, fill.Specification: 60ml/ bottle.
Embodiment 4 suppositorys
| Prescription (1000) |
| Callicarpa nudiflora extract 50g Lignum et Radix Naucleae extract 50g polyethylene glycol 6000 400g polyethylene glycol 1500 700g |
Exemplary process: get 400g polyethylene glycol 6000,700g polyethylene glycol 1500, be heated to 65 ℃ and make fusing, stir evenly, as substrate, get Callicarpa nudiflora extract 50g, Lignum et Radix Naucleae extract 50g, it is an amount of to add water, grind to form thick paste, add in the substrate 65 ℃ of insulations under stirring, stir evenly, moulding, that is, and specification: 1.2g/ grain.
Embodiment 5 drop pills
| Prescription |
| Callicarpa nudiflora extract 50mg Lignum et Radix Naucleae extract 50mg polyethylene glycol 6000 200mg poloxamer 30mg stearic acid 70mg |
Process example: get the PEG6000 heating and melting, add Callicarpa nudiflora Lignum et Radix Naucleae extract, poloxamer and stearic acid, treat complete fusion after, stir and add Lignum et Radix Naucleae extract down.Mixture splashed in the liquid paraffin condensed fluid become ball.
Claims (11)
1, a kind of have a synergistic pharmaceutical composition, it is characterized in that comprise active component and an amount of pharmaceutical excipient, described active component is made up of Callicarpa nudiflora and Lignum et Radix Naucleae.
2, pharmaceutical composition according to claim 1, described Callicarpa nudiflora comprises the former powder of Callicarpa nudiflora, water and/or alcohol extract or other specific solvent, petroleum ether, ether, chloroform, ethyl acetate, the effective site of n-butanol extraction or wherein single or several active component, comprise flavonoid glycoside, phenols, the combination of tannin, described Lignum et Radix Naucleae comprises Lignum et Radix Naucleae water and/or alcohol extract, other specific solvent, petroleum ether, ether, chloroform, ethyl acetate, single or several active component of the effective site of n-butanol extraction comprise flavonoid glycoside, phenols, alkaloidal combination.
3, according to the pharmaceutical composition of claim 2, wherein the content of active component is the 1-85% of composition weight.
4, according to the pharmaceutical composition of claim 2, wherein the content of active component is the 20-65% of composition weight.
5, according to the pharmaceutical composition of one of claim 1-4, wherein the part by weight of Callicarpa nudiflora and Lignum et Radix Naucleae is 1: 10-10: 1.
6, according to the pharmaceutical composition of claim 5, wherein the part by weight of Callicarpa nudiflora and Lignum et Radix Naucleae is 1: 5-5: 1.
7, according to the pharmaceutical composition of claim 6, wherein the part by weight of Callicarpa nudiflora and Lignum et Radix Naucleae is 1: 1.
8,, be the dosage form of oral administration, intravenously administrable, percutaneous or mucosa delivery according to the pharmaceutical composition of claim 1 or 2.
9, a kind of have synergistic pharmaceutical composition is used for preventing or treat the medicine of inflammation, hemorrhagic and/or viral hepatitis relevant disease in preparation a application, it is characterized in that, said pharmaceutical composition comprises active component and an amount of pharmaceutical excipient, and described active component is made up of Callicarpa nudiflora and Lignum et Radix Naucleae.
10, according to the application of claim 9, described disease comprises: cold, fever, laryngopharynx swelling and pain, pharyngolaryngitis, external auditory meatus or skin furuncle and phyma, conjunctivitis, upper respiratory tract infection, acute and chronic tonsillitis, urinary system infection, nose, respiratory tract, digestive tract or genitourinary system are hemorrhage, rhinitis, hemorrhoid, stomachache, acute jaundice, viral hepatitis or burn.
11, according to the application of claim 9 or 10, described disease further comprises the inflammation that bacterial infection and/or non-bacterial infection cause, described inflammation comprises mastitis, cervicitis, general vaginitis, candidal vaginitis, trichomonal vaginitis, enteritis, bacillary dysentery, urinary tract infection, cholecystitis, ulcer of the lower limb, tinea pedis infection, skin eczema, suppurative skin ulcer.
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| CNB2004100043910A CN1285360C (en) | 2004-02-17 | 2004-02-17 | Medicine compound having synergistic action |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100043910A CN1285360C (en) | 2004-02-17 | 2004-02-17 | Medicine compound having synergistic action |
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| CN1285360C CN1285360C (en) | 2006-11-22 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100390530C (en) * | 2005-05-31 | 2008-05-28 | 哈尔滨工业大学 | Image type online flaws detection equipment in line array for surface of strip steel, and detection method |
| CN104740171A (en) * | 2015-04-20 | 2015-07-01 | 海南黎药堂生物科技开发有限公司 | Traditional Chinese medicine composition, preparation as well as preparation method and use of traditional Chinese medicine composition |
| CN106389687A (en) * | 2016-11-07 | 2017-02-15 | 海南医学院 | Preparation method of Li medical callicarpa nudiflora scald ointment |
| CN106421476A (en) * | 2016-11-08 | 2017-02-22 | 周昌煜 | Burning medicine |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113171412A (en) * | 2021-05-20 | 2021-07-27 | 海南崇原药物开发有限公司 | Callicarpa nudiflora traditional Chinese medicine composition and preparation method thereof |
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2004
- 2004-02-17 CN CNB2004100043910A patent/CN1285360C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100390530C (en) * | 2005-05-31 | 2008-05-28 | 哈尔滨工业大学 | Image type online flaws detection equipment in line array for surface of strip steel, and detection method |
| CN104740171A (en) * | 2015-04-20 | 2015-07-01 | 海南黎药堂生物科技开发有限公司 | Traditional Chinese medicine composition, preparation as well as preparation method and use of traditional Chinese medicine composition |
| CN104740171B (en) * | 2015-04-20 | 2019-01-01 | 海南黎药堂生物科技开发有限公司 | A kind of Chinese medicine composition, preparation and preparation method, purposes |
| CN106389687A (en) * | 2016-11-07 | 2017-02-15 | 海南医学院 | Preparation method of Li medical callicarpa nudiflora scald ointment |
| CN106421476A (en) * | 2016-11-08 | 2017-02-22 | 周昌煜 | Burning medicine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1285360C (en) | 2006-11-22 |
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