Summary of the invention
For solving above-mentioned problems of the prior art, the invention provides a kind of psoriatic medicine and preparation method thereof for the treatment of.
Particularly, the invention provides:
(1) a psoriatic medicine, wherein, this medicine is made by the crude drug of following weight portion: Bulgaria inquinans 6-10 part, Radix Angelicae Sinensis 6-12 part, Cortex Dictamni 6-15 part, Radix Glycyrrhizae 3-9 part.
(2) according to the medicine (1) described, wherein, the weight portion of described crude drug is respectively: 10 parts of Bulgaria inquinanss, 10 parts of Radix Angelicae Sinensis, 10 parts of Cortex Dictamni, 6 parts, Radix Glycyrrhizae.
(3) a psoriatic medicine, wherein, this medicine is made by the crude drug of following weight portion: Bulgaria inquinans 6-10 part, Radix Angelicae Sinensis 6-12 part, Cortex Dictamni 6-15 part, Radix Glycyrrhizae 3-9 part, Radix Salviae Miltiorrhizae 9-15 part.
(4) according to the medicine (3) described, wherein, the weight portion of described crude drug is respectively: 10 parts of Bulgaria inquinanss, 10 parts of Radix Angelicae Sinensis, 10 parts of Cortex Dictamni, 6 parts, Radix Glycyrrhizae, 10 parts of Radix Salviae Miltiorrhizaes.
(5) extracting method for the medicine in (1)-(4) described in any one, it comprises:
By described crude drug coarse pulverization, with the alcohol reflux of 3-7 times of weight 2-4 time, each extraction time is 1-3 hour successively, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, thus obtain extract.
(6) extracting method according to (5), it comprises: by described crude drug coarse pulverization, use successively the alcohol reflux 3 times of 5 times of weight, time is respectively 2 hours, 1.5 hours, 1.5 hours, filters merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, thus obtain described extract.
(7) extract that the described extracting method in a kind of basis (5) or (6) obtains.
(8) extract described in basis (7) is in the purposes for the preparation of in the psoriatic medicament for the treatment of.
(9) preparation method for the capsule of the medicine in (1)-(4) described in any one, it comprises:
A), by described crude drug coarse pulverization, with the alcohol reflux of 3-7 times of weight 3 times, each extraction time is 1-3 hour successively, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, thus obtain extract;
B) get the extract that step a) obtains and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, pours into capsule, obtains capsule.
(10) capsule that the described preparation method of a kind of basis (9) obtains.
Medicine of the present invention compared with prior art has the following advantages and good effect:
That medicine of the present invention has is antipruritic, calm, blood circulation promoting and blood stasis dispelling, reduction blood viscosity, improve microcirculation, heat clearing and damp drying, removing toxic substances, antibiotic effect, it has certain photodynamics can increase therapeutic effect, and medicine of the present invention has the psoriatic effect of significant treatment especially.
The specific embodiment
Below the invention will be further described for the description by the specific embodiment, but this is not limitation of the present invention, those skilled in the art are according to basic thought of the present invention, can make various modifications or improvement, but only otherwise depart from basic thought of the present invention, all within the scope of the present invention.
The inventor have been surprisingly found that by a large amount of research, and the combination medicine form of Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae can provide the useful especially psoriatic effect for the treatment of, and its effect is better than any one-component.
The drug action mechanism of Combined effects of the present invention is:
Bulgaria inquinans is the dry sporophore of the fungus Bulgaria inquinans Bulgaria inquinans of Bulgaria inquinans section (Pers.) Fr., summer and autumn gather, dry, Forest in Changbai Mountain Forest Region, the place of production, after common local resident's continuous several times or once excessive edible glue gyro, through exposure in sunshine, the body exposure positions such as face occur red and swollen, especially with lip, attach most importance to.Therefore locality claims that again Bulgaria inquinans is " snoot mushroom " or " arch mouth mushroom ".
The main chemical compositions of Bulgaria inquinans is ergosterol, oxalic acid, galactitol and benzofluoranthrene quinones etc.Bulgaria inquinans has the effect of heat-clearing and toxic substances removing, promoting blood circulation to remove obstruction in the collateral, the psoriatic pharmacological action of Bulgaria inquinans extract for treating is very special, be different from traditional Chinese medicine, after taking, patient there is photodynamic effect (photosensitivity reaction), can be rubescent after solar radiation and have a reaction of similar inflammation in affected part, within after drug withdrawal 1-2 days, disappear, this process has benefit very to psoriatic recovery from illness.This photodynamic effect is similar to the photochemotherapy (PUVA) in western medicine, and there is no the common toxic and side effects of photochemotherapy.
Radix Angelicae Sinensis has the effect of enriching blood and invigorating blood circulation, and its chemical composition is mainly volatile oil composition and polysaccharide composition, for example butylidenephthalide (Butylidene phthalide), nopinene (β-Pinene), australene, camphene (Camphene), to P-cymene (p-Cymene), β-phellandrene (β-Phellandrene), myrcene (Myrcene), alloocimene (Allo-ocimene), 6-normal-butyl-cycloheptadiene-Isosorbide-5-Nitrae (6-n-butyl-cycloheptadiene-1,4), 2-methyl-dodecane-5-ketone (2-Methyl-dodecane-5-one), 1-Phenylethanone. (Acetophenone), β-bisabolence (β-Bisabolene), different Rhizoma Acori Graminei alkene (Isoacroraene), acoradiene (Acoradiene), cuparene (Chamigrene), α-himachalene (α-Cedrene), ligustilide (Ligustilide), normal-butyl Si Qingization Fu lactone (n-Butyl-tetrahydrophthalide), Zheng butylphthalide (n-Butyl-phthalide), Zheng Ding Xi Fu lactone (n-Buty-lidene phthalide), n-dodecane alcohol (Dodecanol), bergapton (Bergapten) etc.There is blood vessel dilating, promote humoral immunization, antibiotic effect.
Cortex Dictamni has heat clearing and damp drying, dispelling wind for relieving itching, the effect of removing toxic substances, its chemical composition is mainly dictamine (dictamnine), .beta.-fagarine (skimmianine), .gamma.-fagarine (g-fagarine), front .beta.-fagarine (preskimmianine), the different speckle forest-grass alkali (isomaculosindine) that boils, limonin (limonin, dictamnolactone), obacunone (obakunone), fraxinellon (fraxinellone), and sitosterol, acidic materials and Saponin etc. Herb is still containing 7-geranyloxycoumarin (aurapten), Bergapten (bergapten). aerial parts is also containing psoralen (psoralen), xanthotoxin (xanthotoxin) and volatile oil, root bark is still containing campesterol (campesterol).There is antibiotic, antifungal, analgesic, the effect that increases cardiac muscular tension.
Radix Glycyrrhizae has the effect of heat-clearing and toxic substances removing, its chemical composition is mainly glycyrrhizic acid, liquiritin etc., such as: glycyrrhizin, enoxolone, liquiritin, isoliquiritin, neoliquriitin, neoisoliquiritin, glycyrrhizin, isoliquiritigenin and licoricidin (+)-Licoricidin., glycyrol, isoglycyrol, 7-methylcoumarin essence, umbelliferone etc.There is the effect of antibiotic, antiinflammatory, antiallergic action, removing toxic substances, and have the effect of adrenocortical hormone sample.
Pharmaceutical composition of the present invention has been followed the theory of traditional Chinese medical science monarch, followed the theory of instruction of Chinese Medicine theory Chinese medicine application, Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae four Chinese medicine are according to monarch prescription, wherein, Bulgaria inquinans be monarch drug, when being classified as ministerial drug, Cortex Dictamni is that adjuvant drug, Radix Glycyrrhizae are for making medicine.
The angle of modern Chinese medicine chemistry, four Chinese medicine chemical constituent of the present invention is definite, Bulgaria inquinans mainly contains that ergosterol, oxalic acid, galactitol and benzofluoranthrene quinones composition, Radix Angelicae Sinensis mainly contain volatile oil composition and polysaccharide composition, Cortex Dictamni mainly contains alkaloids composition, Radix Glycyrrhizae and mainly contains glycyrrhizic acid constituents, crude drug effective ingredient after extracting is concentrated, and drug effect is obvious.
Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae therapeutic alliance psoriasis have shown the effect of significant Synergistic, and curative effect is better than any one-component.Wherein, Bulgaria inquinans can play heat-clearing and toxic substances removing, promoting blood circulation to remove obstruction in the collateral, antipruritic, calm effect as monarch drug, it has certain photodynamics can increase therapeutic effect, Radix Angelicae Sinensis as ministerial drug have enrich blood invigorate blood circulation, blood vessel dilating, antibiotic effect, Cortex Dictamni has the effect of heat clearing and damp drying, dispelling wind for relieving itching, removing toxic substances as adjuvant drug, Radix Glycyrrhizae, as making medicine, has effect antibiotic, removing toxic substances.Four common onsets, the effect of heat-clearing and toxic substances removing, promoting blood circulation to remove obstruction in the collateral, antipruritic, calm, antibiotic, removing toxic substances, have can highly significant alleviate and reverse psoriasis pathology and change, have and treat especially significantly psoriatic effect.
In addition, the present invention, on the basis of above-mentioned four medicines, can increase Radix Salviae Miltiorrhizae again.Radix Salviae Miltiorrhizae has the effect of blood circulation promoting and blood stasis dispelling, its chemical composition is mainly: diterpene Quinone Pigments, TANSHINONES (tanshinone) I, II A, II B, cryptotanshinone (cryptotanshinone), iso tanshinone (isotanshinones) I, II, different cryptotanshinone (1socryptotanshinone), miltirone (miltirone), Methyl tanshinoate (methyl tanshinonate), hydroxytanshinone ⅡA Hydroxytanshinone IIA. (hydroxytanshinone), dihydrotanshinone Ⅰ (dihydrotanshinone I), neotanshinone A, second, third, methylene tanshinquinone (methylenetanshinquinone) and carnosol (salviol).Another report closes ferruginal (ferruginol), Δ l-miltirone (Δ l-dehydromiltirone), Δ l-tanshinone IIA (Δ l-dehydrotanshinone IIA), danshenxinkun fourth (danshenxinkun D) and 1,2-dihydro Radix Salviae Miltiorrhizae quinone etc.There is the effect that improves microcirculation, the reparation that promotes tissue and regeneration, suppresses the fibroblast of hyperplasia.In the present invention, further, Radix Salviae Miltiorrhizae can be ministerial drug with Radix Angelicae Sinensis altogether, plays further reduction psoriatic blood viscosity, improves microcirculatory effect.
Particularly, the invention provides a kind of psoriatic medicine for the treatment of, this medicine is made by the crude drug that comprises Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae, also can comprise pharmaceutically acceptable pharmaceutic adjuvant.
Prepare the crude drug that medicine of the present invention adopts, according to the ratio of the weight of crude drug, comprise Bulgaria inquinans 6-10 part, Radix Angelicae Sinensis 6-12 part, Cortex Dictamni 6-15 part, Radix Glycyrrhizae 3-9 part.
Prepare the crude drug that medicine of the present invention adopts, according to the ratio of the weight of crude drug, further preferably include 10 parts of Bulgaria inquinanss, 10 parts of Radix Angelicae Sinensis, 10 parts of Cortex Dictamni, 6 parts, Radix Glycyrrhizae.
Further preferably, prepare the crude drug that medicine of the present invention adopts, according to the ratio of the weight of crude drug, contain Bulgaria inquinans 6-10 part, Radix Salviae Miltiorrhizae 9-15 part, Radix Angelicae Sinensis 6-12 part, Cortex Dictamni 6-15 part, Radix Glycyrrhizae 3-9 part.More preferably contain 10 parts of Bulgaria inquinanss, 10 parts of Radix Salviae Miltiorrhizaes, 10 parts of Radix Angelicae Sinensis, 10 parts of Cortex Dictamni, 6 parts, Radix Glycyrrhizae.
In order to reach more concentrated pharmacological action and better drug effect, preferably crude drug Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae are made to medicine of the present invention through extraction process.
Can be obtained by methods such as conventional water extraction, ethanol extraction, water extract-alcohol precipitations, preferably by following method, extract and obtain:
Crude drug coarse pulverization, with the alcohol reflux of 3-7 times of weight 2-4 time, each extraction time is 1-3 hour successively, filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains getting thing.
Further preferred extracting method is: crude drug coarse pulverization, use successively the alcohol reflux 3 times of 5 times of weight, and the time is 2 hours, 1.5 hours, 1.5 hours, filters, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract.
Medicine preferred oral of the present invention administration, is also applicable to other administering mode, as parenteral, sublingual administration or oral transmucosal administration etc.
The oral administration form of medicine of the present invention can be any conventional formulation forms such as tablet, capsule, granule, oral liquid, mixture, effervescent tablet, oral cavity disintegration tablet.Capsule preferably.
The preparation method of the capsule of medicine of the present invention is preferably:
A) crude drug coarse pulverization, the alcohol reflux of doubly measuring with 3-7 successively 3 times, each extraction time is 1-3 hour, filters, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, pours into capsule, obtains capsule.
Mode by the following examples further explains and describes content of the present invention, but these embodiment are not to be construed as limiting the scope of the invention.
Embodiment 1
A) above-mentioned raw materials medicine coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, and the time is 2 hours, 1.5 hours, 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, fill capsule.
Embodiment 2
A) above-mentioned raw materials medicine coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, and the time is 2 hours, 1.5 hours, 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, fill capsule.
Embodiment 3
A) above-mentioned raw materials medicine coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, and the time is 2 hours, 1.5 hours, 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, fill capsule.
Embodiment 4
A) above-mentioned raw materials medicine coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, and the time is 2 hours, 1.5 hours, 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, fill capsule.
Embodiment 5
A) above-mentioned raw materials medicine coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, and the time is 2 hours, 1.5 hours, 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, fill capsule.
Embodiment 6
A) above-mentioned raw materials medicine coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, and the time is 2 hours, 1.5 hours, 1.5 hours, filter, and merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing and mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, under 60 ℃ of-70 ℃ of conditions, dry, pulverize is 80 order fine powders, fill capsule.
Below by test example, further verify the beneficial effect of medicine of the present invention:
Test example 1: the impact of medicine of the present invention on Animal Models of Psoriasis---medicine of the present invention is on the mitotic impact of mice estrogen phase vaginal epithelial cell
Experiment purpose: psoriatic pathological characters is skin lesion position epidermis cell hyper-proliferative and parakeratosis.Mouse vagina epithelial cell proliferation in the estrogen phase is active, is the common model of evaluating curing psoriasis medicine.
Experimental agents: medicine group of the present invention is drug extract extract powder of the present invention, is mixed with debita spissitudo before use with distilled water; Blank group is distilled water; Positive control drug group is Etretinate granule (Radix Sophorae Flavescentis, Radix Glycyrrhizae, Cortex Dictamni, Radix Saposhnikoviae, Rhizoma Smilacis Glabrae, Periostracum Cicadae, Cortex Phellodendri, Radix Rehmanniae, Flos Lonicerae, Radix Paeoniae Rubra, Fructus Forsythiae, Radix Angelicae Sinensis); Bulgaria inquinans extract group, Radix Angelicae Sinensis extract group, Radix Salviae Miltiorrhizae extract group, Cortex Dictamni extract group, Radix Glycyrrhizae extract group, for extract the extract obtaining with reference to the method described in embodiment 1, are mixed with debita spissitudo with distilled water before use.
Experimental technique: 130 of Kunming kind female mices, 20-30g/, lumbar injection diethylstilbestrol 0.2mg/, every day 1 time, continuous 3 days, make it in the estrogen phase, within 4th, be divided at random 13 groups, 10 every group.Press table 3 grouping, every day, gastric infusion was 1 time, continuous 3 days, after last administration, 2 hours lumbar injection colchicine 2mg/kg, put to death mice after 4 hours and get vagina, and 10% formalin is fixed, the conventional film-making of paraffin embedding, HE dyes, and counts the mitosis number of 300 vagina epithelium basal cells under light microscopic, and its percentage rate is mitotic index.
Experimental result is in Table 1.
Table 1: medicine of the present invention is on the mitotic impact of mice estrogen phase vaginal epithelial cell (n=10)
Experiment conclusion: medicine of the present invention has obvious inhibitory action (P < 0.05, P < 0.01) to mice estrogen phase vaginal epithelial cell mitosis.Wherein, the pharmacological action of the middle and high dosage group of medicine of the present invention is obviously better than positive control drug Etretinate granule.And the pharmacological action of medicine group of the present invention is obviously better than single Radix Salviae Miltiorrhizae extract group, Bulgaria inquinans extract group, Radix Angelicae Sinensis extract group, Cortex Dictamni extract group and Radix Glycyrrhizae extract group, thereby medicine of the present invention has synergy.
Test example 2: the impact that medicine of the present invention generates mouse tail epidermal granular cell the impact of Animal Models of Psoriasis-medicine of the present invention
Experiment purpose: psoriatic pathological characters is skin lesion position epidermis cell hyper-proliferative and parakeratosis.The keratinization of mouse tail epidermis forms similar to mankind psoriatic, lacks granular cell, is the common model of evaluating curing psoriasis medicine.
Experimental agents: medicine group of the present invention is drug extract extract powder of the present invention, is mixed with debita spissitudo before use with distilled water; Blank group is distilled water; Positive control drug group is Etretinate granule (Radix Sophorae Flavescentis, Radix Glycyrrhizae, Cortex Dictamni, Radix Saposhnikoviae, Rhizoma Smilacis Glabrae, Periostracum Cicadae, Cortex Phellodendri, Radix Rehmanniae, Flos Lonicerae, Radix Paeoniae Rubra, Fructus Forsythiae, Radix Angelicae Sinensis); Bulgaria inquinans extract group, Radix Angelicae Sinensis extract group, Radix Salviae Miltiorrhizae extract group, Cortex Dictamni extract group, Radix Glycyrrhizae extract group, for extract the extract obtaining with reference to the method described in embodiment 1, are mixed with debita spissitudo with distilled water before use.
Experimental technique: 130 of Kunming mouses, 20-30g/ only, is divided into 13 groups at random by table 4, and 10 every group, male and female half and half, every day, gastric infusion was 1 time, successive administration 20 days.Within after last administration 2 hours, put to death whole mices, get apart from the Mus root of the tail 1.8cm of portion place dorsal skin one rectangularly, 10% formalin is fixed, the conventional film-making of paraffin embedding, and HE dyeing, counts 10 middle eyepiece micrometer scope 132 μ m endoparticle cell number of scale under light microscopic.
Experimental result is in Table 2.
Table 2: the impact that medicine of the present invention generates mouse tail epidermal granular cell
Experiment conclusion: medicine of the present invention has obvious facilitation (P < 0.05, P < 0.01) to the generation of mouse tail granular cell, granular cell showed increased, Keratoderma layer obviously thickens.Wherein, the pharmacological action of the middle and high dosage group of medicine of the present invention is obviously better than positive control drug Etretinate granule.And the pharmacological action of medicine group of the present invention is obviously better than single Radix Salviae Miltiorrhizae extract group, Bulgaria inquinans extract group, Radix Angelicae Sinensis extract group, Cortex Dictamni extract group and Radix Glycyrrhizae extract group, thereby medicine of the present invention has synergy.