Summary of the invention
For solving above-mentioned problems of the prior art, the invention provides one and treating psoriatic medicine and preparation method thereof.
Specifically, the invention provides:
(1) one is used for the treatment of psoriatic medicine, and wherein, this medicine is made up of 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) medicine Gen Ju (1), wherein, the weight portion of described crude drug is respectively: Bulgaria inquinans 10 parts, Radix Angelicae Sinensis 10 parts, Cortex Dictamni 10 parts, 6 parts, Radix Glycyrrhizae.
(3) one is used for the treatment of psoriatic medicine, and wherein, this medicine is made up of 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) medicine Gen Ju (3), wherein, the weight portion of described crude drug is respectively: Bulgaria inquinans 10 parts, Radix Angelicae Sinensis 10 parts, Cortex Dictamni 10 parts, 6 parts, Radix Glycyrrhizae, Radix Salviae Miltiorrhizae 10 parts.
(5) a kind of extracting method according to the medicine in (1)-(4) described in any one, it comprises:
By described crude drug coarse pulverization, successively with alcohol reflux 2-4 time of 3-7 times of weight, each extraction time is 1-3 hour, filters, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, thus obtains extract.
(6) extracting method Gen Ju (5), it comprises: by described crude drug coarse pulverization, uses the alcohol reflux 3 times of 5 times of weight successively, 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) a kind of extract obtained according to (5) or the extracting method described in (6).
(8) extract Gen Ju (7) for the preparation for the treatment of psoriatic medicament in purposes.
(9) a kind of preparation method of the capsule according to the medicine in (1)-(4) described in any one, it comprises:
A) by described crude drug coarse pulverization, successively with the alcohol reflux 3 times of 3-7 times of weight, each extraction time is 1-3 hour, filters, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, thus obtains extract;
B) get the extract that step a) obtains to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, pours into capsule, obtains capsule.
(10) capsule that obtains of a kind of preparation method Gen Ju (9).
Medicine of the present invention compared with prior art has the following advantages and good effect:
Medicine of the present invention has antipruritic, calm, blood circulation promoting and blood stasis dispelling, reduction blood viscosity, improves microcirculation, heat clearing and damp drying, removing toxic substances, antibacterial effect, it has certain photodynamics can increase therapeutic effect, and medicine of the present invention has the psoriatic effect of significant treatment especially.
Detailed description of the invention
Below by way of the description of detailed description of the invention, the invention will be further described, but this is not limitation of the present invention, those skilled in the art are according to basic thought of the present invention, various amendment or improvement can be made, but only otherwise depart from basic thought of the present invention, all within the scope of the present invention.
The present inventor be 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 psoriatic effect for the treatment of useful especially, 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 Bulgaria inquinans section fungus Bulgaria inquinans Bulgaria inquinans (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 attach most importance to lip.Therefore locality is " snoot mushroom " or " arch mouth mushroom " also known as Bulgaria inquinans.
The main chemical compositions of Bulgaria inquinans is ergosterol, oxalic acid, galactitol and benzofluoranthrene quinones etc.Bulgaria inquinans has 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, photodynamic effect (photosensitivity reaction) is there is after patient takes, affected part can be rubescent and have the reaction of similar inflammation after sunlight irradiates, 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 does not have 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 volatile oil composition and polysaccharide composition mainly, such as 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-dodecanoic-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, antibacterial effect.
Cortex Dictamni has heat clearing and damp drying, dispelling wind for relieving itching, the effect of removing toxic substances, its chemical composition is dictamine (dictamnine) mainly, .beta.-fagarine (skimmianine), .gamma.-fagarine (g-fagarine), front .beta.-fagarine (preskimmianine), different speckle boils forest-grass alkali (isomaculosindine), 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 antibacterial, antifungal, antipyretic, the effect that increases cardiac muscular tension.
Radix Glycyrrhizae has the effect of heat-clearing and toxic substances removing, its chemical composition 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 antibacterial, antiinflammatory, antiallergic action, removing toxic substances, and have the effect of adrenocortical hormone sample.
Pharmaceutical composition of the present invention have followed the theory of traditional Chinese medical science monarch, have followed the theory of instruction of Chinese Medicine theory application in TCM, Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae four Chinese medicine are according to monarch prescription, wherein, Bulgaria inquinans is monarch drug, when being classified as ministerial drug, Cortex Dictamni is adjuvant drug, Radix Glycyrrhizae is for making medicine.
From the angle of modern Chinese medicine chemistry, four Chinese medicine chemical constituent of the present invention is definite, Bulgaria inquinans mainly containing ergosterol, oxalic acid, galactitol and benzofluoranthrene quinones composition, Radix Angelicae Sinensis mainly containing volatile oil composition and polysaccharide composition, Cortex Dictamni mainly containing alkaloids composition, Radix Glycyrrhizae mainly containing 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 show 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, antibacterial 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 that is antibacterial, removing toxic substances.Four work, the effect of heat-clearing and toxic substances removing, promoting blood circulation to remove obstruction in the collateral, antipruritic, calm, antibacterial, removing toxic substances, having can the alleviating and reverses psoriasis pathology and change of highly significant, and has and treats psoriatic effect especially significantly.
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.Have and improve microcirculation, promote the reparation of tissue and regeneration, suppress the effect of the fibroblast of hyperplasia.In the present invention, further, Radix Salviae Miltiorrhizae can be ministerial drug with Radix Angelicae Sinensis altogether, plays and reduces psoriatic's blood viscosity further, improve microcirculatory effect.
Specifically, the invention provides one and treat psoriatic medicine, this medicine by comprise Bulgaria inquinans, Radix Angelicae Sinensis, Cortex Dictamni, Radix Glycyrrhizae crude drug make, 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, preferably include Bulgaria inquinans 10 parts, Radix Angelicae Sinensis 10 parts, Cortex Dictamni 10 parts, 6 parts, Radix Glycyrrhizae further.
Further preferably, prepare the crude drug that medicine of the present invention adopts, according to the ratio of the weight of crude drug, containing 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 containing Bulgaria inquinans 10 parts, Radix Salviae Miltiorrhizae 10 parts, Radix Angelicae Sinensis 10 parts, Cortex Dictamni 10 parts, 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 medicine of the present invention through extraction process.
Can be obtained by methods such as the water extraction of routine, ethanol extraction, water extract-alcohol precipitations, preferably be extracted by following method and obtain:
Crude drug coarse pulverization, successively with alcohol reflux 2-4 time of 3-7 times of weight, each extraction time is 1-3 hour, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains getting thing.
Further preferred extracting method is: crude drug coarse pulverization, and use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, 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 delivery form of medicine of the present invention can be any conventional formulations such as tablet, capsule, granule, oral liquid, mixture, effervescent tablet, oral cavity disintegration tablet.Preferably capsule.
The preparation method of the capsule of medicine of the present invention is preferably:
A) crude drug coarse pulverization, use the alcohol reflux 3 times of 3-7 times amount successively, each extraction time is 1-3 hour, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions 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 embodiments are not to be construed as limiting the scope of the invention.
Embodiment 1
A) above-mentioned raw materials medicine coarse pulverization, use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, fill capsule.
Embodiment 2
A) above-mentioned raw materials medicine coarse pulverization, use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, fill capsule.
Embodiment 3
A) above-mentioned raw materials medicine coarse pulverization, use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, fill capsule.
Embodiment 4
A) above-mentioned raw materials medicine coarse pulverization, use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, fill capsule.
Embodiment 5
A) above-mentioned raw materials medicine coarse pulverization, use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, fill capsule.
Embodiment 6
A) above-mentioned raw materials medicine coarse pulverization, use the alcohol reflux 3 times of 5 times of weight successively, the time is 2 hours, 1.5 hours, 1.5 hours, and filter, merging filtrate, decompression recycling ethanol, concentrating under reduced pressure, obtains extract;
B) get said extracted thing to mix homogeneously by the weight ratio of 1:1:0.5 with starch, microcrystalline Cellulose, dry, pulverize under 60 DEG C of-70 DEG C of conditions is 80 order fine powders, fill capsule.
The beneficial effect of medicine of the present invention is verified further below by way of test example:
Test example 1: medicine of the present invention is on the impact of Animal Models of Psoriasis---medicine of the present invention is on the mitotic impact of mouse oestrogen phase vaginal epithelial cell
Experiment purpose: psoriatic pathological characters is cutaneous lesion epidermis cell hyper-proliferative and parakeratosis.The mouse vagina epithelial cell proliferation being in the estrogen phase enlivens, and is the common model 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 extracting with reference to the method described in embodiment 1 extract obtained, are mixed with debita spissitudo with distilled water before use.
Experimental technique: Kunming kind female mice 130, only, lumbar injection diethylstilbestrol 0.2mg/ only, every day 1 time, continuous 3 days, makes it be in the estrogen phase, within 4th, is divided into 13 groups at random 20-30g/, often organizes 10.Divide into groups by table 3, every day gastric infusion 1 time, continuous 3 days, 2 hours lumbar injection colchicine 2mg/kg after last administration, put to death mice after 4 hours and get vagina, 10% formalin is fixed, the conventional film-making of paraffin embedding, HE dyes, and count the mitosis number of 300 vagina epithelium basal cells under light microscopic, 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 mouse oestrogen phase vaginal epithelial cell (n=10)
Experiment conclusion: medicine of the present invention has obvious inhibitory action (P < 0.05, P < 0.01) to mouse oestrogen 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.Further, 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, thus medicine of the present invention has synergy.
Test example 2: the impact that the impact-of the present invention medicine of medicine of the present invention on Animal Models of Psoriasis generates mouse tail epidermal granular cell
Experiment purpose: psoriatic pathological characters is cutaneous lesion epidermis cell hyper-proliferative and parakeratosis.The keratinization of mouse tail epidermis is formed similar to mankind psoriatic, lacks granular cell, is the common model 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 extracting with reference to the method described in embodiment 1 extract obtained, are mixed with debita spissitudo with distilled water before use.
Experimental technique: Kunming mouse 130,20-30g/ only, is divided into 13 groups at random by table 4, often organizes 10, male and female half and half, every day gastric infusion 1 time, successive administration 20 days.Within after last administration 2 hours, put to death whole mice, get apart from Mus root of the tail portion 1.8cm place dorsal skin one rectangular, 10% formalin is fixed, and the conventional film-making of paraffin embedding, HE dyes, and counts the middle eyepiece micrometer scope of 10, scale 132 μm of endoparticle cell number 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: the generation of medicine of the present invention to mouse tail granular cell has obvious facilitation (P < 0.05, P < 0.01), and 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.Further, 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, thus medicine of the present invention has synergy.