CN112773806B - Medical application of pharmaceutical composition containing icariin and madecassic acid - Google Patents
Medical application of pharmaceutical composition containing icariin and madecassic acid Download PDFInfo
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- CN112773806B CN112773806B CN202011214089.3A CN202011214089A CN112773806B CN 112773806 B CN112773806 B CN 112773806B CN 202011214089 A CN202011214089 A CN 202011214089A CN 112773806 B CN112773806 B CN 112773806B
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- icariin
- pharmaceutical composition
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- psoriasis
- madecassic acid
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- TZJALUIVHRYQQB-XLRXWWTNSA-N icariin Chemical compound C1=CC(OC)=CC=C1C1=C(O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)C(=O)C2=C(O)C=C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-XLRXWWTNSA-N 0.000 title claims abstract description 56
- PRAUVHZJPXOEIF-AOLYGAPISA-N madecassic acid Chemical compound C1[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]2[C@H](O)C[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C PRAUVHZJPXOEIF-AOLYGAPISA-N 0.000 title claims abstract description 52
- TZJALUIVHRYQQB-XFDQAQKOSA-N Icariin Natural products O(C)c1ccc(C2=C(O[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)C(=O)c3c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O4)c(C/C=C(\C)/C)c3O2)cc1 TZJALUIVHRYQQB-XFDQAQKOSA-N 0.000 title claims abstract description 48
- TZJALUIVHRYQQB-UHFFFAOYSA-N icariine Natural products C1=CC(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(C)O2)O)C(=O)C2=C(O)C=C(OC3C(C(O)C(O)C(CO)O3)O)C(CC=C(C)C)=C2O1 TZJALUIVHRYQQB-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229940011656 madecassic acid Drugs 0.000 title claims abstract description 45
- BUWCHLVSSFQLPN-UHFFFAOYSA-N madecassic acid Natural products CC1CCC2(CCC3(C)C(=CCC4C5(C)CC(O)C(O)C(C)(C5CCC34C)C(=O)O)C2C1C)C(=O)OC6OC(COC7OC(CO)C(OC8OC(C)C(O)C(O)C8O)C(O)C7O)C(O)C(O)C6O BUWCHLVSSFQLPN-UHFFFAOYSA-N 0.000 title claims abstract description 45
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- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 7
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
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- JXSVIVRDWWRQRT-UYDOISQJSA-N asiatic acid Chemical compound C1[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C JXSVIVRDWWRQRT-UYDOISQJSA-N 0.000 description 4
- 229940011658 asiatic acid Drugs 0.000 description 4
- LBGFKBYMNRAMFC-PYSQTNCISA-N asiatic acid Natural products C[C@@H]1CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]5CC[C@@]34C)[C@]2(C)[C@H]1C)C(=O)O LBGFKBYMNRAMFC-PYSQTNCISA-N 0.000 description 4
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
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- BNMGUJRJUUDLHW-HCZMHFOYSA-N Madecassoside Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)OC[C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(C[C@@H](O)[C@H]4[C@](C)(CO)[C@@H](O)[C@H](O)C[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O BNMGUJRJUUDLHW-HCZMHFOYSA-N 0.000 description 2
- BNMGUJRJUUDLHW-HLUHVYOBSA-N Madecassoside Natural products C[C@@H]1CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]5[C@H](O)C[C@@]34C)[C@@H]2[C@H]1C)C(=O)O[C@@H]6O[C@H](CO[C@@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@H](C)[C@H](O)[C@@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@@H](O)[C@H](O)[C@H]6O BNMGUJRJUUDLHW-HLUHVYOBSA-N 0.000 description 2
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 description 1
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- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
Abstract
The invention belongs to the field of medicines, and particularly relates to a medical application of a pharmaceutical composition. The pharmaceutical composition consists of icariin and madecassic acid. The invention also discloses application of the pharmaceutical composition in preparing medicines for treating psoriasis. The effect of the pharmaceutical composition for treating psoriasis is obviously better than the effect of the two medicines when the two medicines are independently used and is better than the addition of the effects of the two medicines; the combined use of the two medicaments can obviously reduce the respective dosage and reduce adverse reactions; meanwhile, the clinical medication selection of psoriasis patients is increased, and the method has good clinical application prospect.
Description
Technical Field
The invention belongs to the field of medicines, relates to a medical application of a pharmaceutical composition, and in particular relates to an application of a composition containing icariin and madecassic acid in preparing a medicament for treating psoriasis.
Background
Icariin belongs to flavonols compounds, and a small amount of icariin exists in the epimedium herb, and the chemical structural formula of the icariin is as follows:
the icariin can be separated from herba Epimedii (Sun Pengyue, xu Ying, wen, etc., chemical components of Korean herba Epimedii, J.Chem.Chem.Chem. 1998,8 (2): 122-125), or can be obtained by subjecting icariin to enzymolysis and separation (She Haichong, liu Jian, loropetali, preparation of icariin derivatives, and estrogen-like effect research, university of Zhejiang, 2005, 34 (2): 131-136).
The effect of icariin on primary cultured nerve cell apoptosis of mice caused by Abeta peptide is reported in literature (Zhang Xiangna, wang Huanhuan, wang Zhijiang, etc.), and the effect of icariin on primary cultured nerve cell apoptosis of mice caused by Abeta peptide is reported in Zhejiang university journal, 2007, 36 (3): 224-226). Chinese patent CN101836976a discloses that icariin has an anti-tumor angiogenesis effect. Chinese patent CN101428015a discloses that icariin has an anti-endotoxemia effect. Chinese patent CN101284000a discloses that icariin has the effect of preventing and treating obesity or fatty liver. Chinese patent CN1869204a discloses the use of icariin in inducing stem cells to differentiate in vitro. Chinese patent CN1194701C discloses that icariin or noricariin has application in preparing estrogen receptor modulators.
Madecassic acid is an important pentacyclic triterpenic acid compound in centella asiatica of Umbelliferae, and has the chemical structural formula as follows:
recent researches show that asiatic acid and madecassic acid have a certain effect on antioxidation, anticancer and other aspects. Chinese patent CN201110040181.7 discloses that madecassic acid has a remarkable inhibitory effect on mammary gland hyperplasia in experimental mice. Chinese patent CN200910067429.1 discloses the use of asiatic acid and madecassic acid in the preparation of a medicament for the inhibition of α -glucosidase.
The content of aglycones such as madecassic acid in centella asiatica is much lower than that of madecassoside, generally the content of saponins in centella asiatica is 1.8-5%, whereas the ratio of sapogenin to saponins is generally 1:2.5. chinese patent CN201610728601.3 discloses a process for the preparation of madecassic acid by hydrolysis of madecassoside. The method can rapidly break off the glycosidic bond at normal temperature and normal pressure, has mild hydrolysis process and thorough hydrolysis, and can not generate the configuration change of madecassic acid.
Psoriasis is a common chronic recurrent inflammatory skin disease. The disease has a relatively long course and cannot be completely cured at present. As an erythema scaly skin disease, it often causes a damage to the appearance of the patient and severely affects the quality of life and even physical and mental health of the patient. The joints and a plurality of internal organs of a patient are possibly damaged in the later period of disease, and the life and the health of the patient are greatly threatened.
Psoriasis is classified according to its clinical characteristics, and is mainly classified into the type of common, joint, pustule and erythroderma, whereas more than 90% of psoriasis belongs to the type of common. Psoriasis vulgaris is mostly present in the parts of scalp knee, elbow, trunk, limbs and the like, and has the characteristic of symmetrical distribution, wherein basic skin lesions mainly comprise plaques of red pimples, silvery white scales are attached to the surfaces of the basic skin lesions, and punctiform bleeding occurs when the basic skin lesions are scraped off. Facial skin lesions are drip-like invasive erythema and rash; scalp skin damage occurs in a remarkable bundle shape; skin lesions in the areas with multiple friction such as armpits and breasts are manifested as symptoms of scaling reduction, exudation and erosion. The skin damage condition of the joint psoriasis is similar to that of the psoriasis vulgaris, but the skin damage is usually carried out before the joint symptoms appear, and the joint symptoms also can appear simultaneously. Any joint may be affected and the incidence of joint deformity increased. The clinical manifestations of erythrodermic psoriasis are usually that the whole body skin is flushed with swelling, a great deal of bran-like scales appear at the skin lesions, and further, the occurrence of systemic symptoms such as fever is likely to occur. Pustular psoriasis: classified as either localized or generalized. (1) The skin lesions of the limited pustular psoriasis are limited to palms and foot soles, are symmetrically distributed, and are small pustules based on erythema. (2) The generalized pustular psoriasis is frequently and acutely onset, and yellow-white superficial aseptic small pustules with different sizes are rapidly formed on normal skin with or without skin lesions of the psoriasis vulgaris, are densely distributed, can be fused, quickly reach the whole body, and can have general symptoms such as chills, high fever and the like. Some cases have fever, headache, arthralgia and superficial lymphadenectasis.
Psoriasis is a common disease of dermatology, the mild cases are mainly treated by external medicines, and the severe cases can be treated by whole body according to the condition. The new skin is not damaged, and the external medicine is the first choice. The oral medicine can be prepared from methotrexate, tretinoin, glucocorticoid, antibiotics, etc. Psoriasis has longer disease course, is easy to relapse and seriously damages the physical and mental health of patients.
Through searching, no report of using the combination of icariin and madecassic acid for treating psoriasis exists at present.
Disclosure of Invention
The invention aims to provide medical application of a pharmaceutical composition, which takes icariin and madecassic acid as main active ingredients, in particular to application of the pharmaceutical composition in preparing a medicament for treating psoriasis.
Preferably, the psoriasis is selected from psoriasis vulgaris, psoriasis arthrosis, psoriasis rubra, psoriasis pustulosa.
The inventor aims at developing therapeutic drugs for a long time, and on the basis of earlier research, the inventor unexpectedly discovers that the combined application of icariin and madecassic acid has a good therapeutic effect on psoriasis in the research, and the combined application of the two drugs shows remarkable synergistic therapeutic effect.
The embodiment 1 of the invention shows that the composition of the icariin and the madecassic acid has obvious treatment effect on mice with psoriasis, can obviously improve the histomorphology change of a psoriasis model, improve the infiltration number of skin inflammatory cells and the longitudinal epidermis area value, and has obvious treatment effect on the psoriasis.
The embodiment 2 of the invention shows that the composition of the icariin and the madecassic acid has obvious treatment effect on the mice with psoriasis and can relieve the symptoms of the psoriasis.
The effect of the pharmaceutical composition for treating psoriasis is obviously better than the effect of the two medicines when the two medicines are independently used and is better than the addition of the effects of the two medicines; the combined use of the two medicaments can obviously reduce the respective dosage and reduce adverse reactions; meanwhile, the clinical medication selection of psoriasis patients is increased, and the method has good clinical application prospect.
The asiatic acid in the pharmaceutical composition is asiatic acid, or a salt or a complex thereof.
The weight ratio of icariin to madecassic acid in the pharmaceutical composition of the invention is preferably 1:0.01-30.
The pharmaceutical composition also comprises a pharmaceutically acceptable carrier or auxiliary material.
The invention also provides a pharmaceutical preparation containing the pharmaceutical composition, and the pharmaceutical composition can be prepared into a proper and clinically acceptable pharmaceutical preparation according to the requirement.
Preferably, the clinically acceptable dosage form is an oral preparation, an injection preparation or an external preparation.
Preferably, the oral formulation is one or more of a tablet, capsule or microemulsion formulation thereof.
The inventor considers the requirement of convenient administration of patients and the characteristic that two medicines are taken at one time, compared with the two medicines taken in a divided way, the medicine composition of the invention is prepared into solid medicine preparations such as tablets, capsules, granules, pills, dripping pills and the like according to the properties of the active ingredients of madecassic acid and icariin. Wherein the tablet comprises common tablet, coated tablet, sugar coated tablet, film coated tablet, enteric coated tablet, effervescent tablet, chewable tablet, multilayer tablet, disintegrating tablet, dispersible tablet, sublingual tablet, buccal tablet, sustained release tablet, etc. The invention adopts solid pharmaceutical preparation, has the advantages of convenient carrying and use, simple and feasible administration route, and is easy to be accepted by patients.
Preferably, the injection preparation is one or more of injection liquid or injection microemulsion thereof.
Preferably, the external preparation is one or more of powder, ointment, gel, cream, spray or patch, and the external preparation is administrated by skin.
The pharmaceutical composition of the invention can be used for treating psoriasis clinically. In the medical application, the medicine composition of the icariin and the madecassic acid can be prepared into a proper medicine preparation according to the condition of animals and the application position so as to be convenient for application, and the application time and the application times of the medicine composition for treating psoriasis need to be determined according to the specific diagnosis result of the condition, which are within the technical range of the person skilled in the art. For example, it will be apparent to one of ordinary skill in the art that a treatment regimen for psoriasis in mice is applied to humans and that the effective dose of all drugs to humans can be scaled by the effective dose of the drug to mice.
Compared with the prior art, the pharmaceutical composition has the following outstanding advantages in the aspect of treating psoriasis:
(1) Compared with singly-administered icariin or madecassic acid, the pharmaceutical composition containing the icariin and the madecassic acid has better treatment effect on psoriasis models, and the two pharmaceutical active ingredients show good synergistic effect in the aspect of treating psoriasis.
(2) The pharmaceutical composition contains the madecassic acid and the icariin, and the combined use of the madecassic acid and the icariin has a synergistic effect, and simultaneously can obviously reduce the dosage of the madecassic acid and the icariin, thereby obviously reducing the toxic and side effects of patients when the patients take the pharmaceutical composition and reducing the occurrence of adverse reactions.
(3) The pharmaceutical composition treats psoriasis in a fixed combination mode, is more convenient to take compared with the simultaneous taking of single drugs, improves the compliance and compliance of patients, and enhances the treatment effect on diseases to a certain extent.
Detailed Description
The present invention will be further described below by way of specific embodiments, but the scope of application of the present invention is not limited to the following examples. Substitutions and/or combinations of features of the present invention within the spirit, scope, and/or content of the present invention will be apparent to those skilled in the art and are included in the present invention.
Example 1 Effect of composition on imiquimod-induced psoriasis-like lesions in mice
1. Animal modeling, grouping and administration
1.1 modeling and grouping
BABL/c mice were dehaired on their backs and were approximately 2cm by 1.5cm in area, with gentle movements to avoid skin damage. 70 mice were randomly divided into 7 groups according to a random number table method, 10 mice per group were housed in separate cages, and were fed daily with sterilized water and normal mouse feed.
Randomly selecting one group as a normal control group, and smearing distilled water on the back hairless area about 0.5mL per day; the rest 6 groups of back hairless areas are coated with 5% imiquimod cream, 60mg/d (3 mg/d of effective drug) and continuously for 6d, and the back of the mice is provided with more stable erythema scale skin lesions, so that the model preparation is judged to be successful.
60 mice with successful modeling are divided into a model control group, an icariin group, a madecassic acid group, a composition A group, a composition B group and a composition C group, wherein 10 mice are respectively selected from each group.
After the model is successfully prepared, different drug treatments are respectively given according to groups.
1.2 administration
Icariin group: 1mg/kg icariin;
madecassic acid group: 20mg/kg madecassic acid;
composition a group: 10mg/kg icariin+2 mg/kg madecassic acid;
composition B group: 1mg/kg icariin+20 mg/kg madecassic acid;
composition C group: 10mg/kg icariin+1 mg/kg madecassic acid;
each test drug was suspended with 0.5% sodium carboxymethylcellulose and administered 1 time a day for 2 weeks. The normal control and model control were given equal volumes of 0.5% sodium carboxymethyl cellulose 1 time a day.
In the administration process, except for a normal control group, the back hairless areas of other groups of mice are coated with 5% imiquimod cream (60 mg/d) every other day so as to reduce the skin damage of model mice and naturally relieve the interference to the experiment.
2. Experimental method and data processing
2.1 sample collection of laboratory animals
Mice were sacrificed by cervical dislocation after the end of the experiment. Skin tissue biopsies were taken from back skin lesions, fixed in 10% formaldehyde solution for paraffin section preparation and HE staining.
2.2 observations of the area and severity of erythema and scaling lesions in mice of each group
The vital signs of the mice are carefully observed during the treatment process, and the changes of erythema scales at the skin lesions are observed at the same time every day.
2.3HE section staining method for detecting histological changes of skin
Tissue HE staining sections of the skin lesions of the mice were prepared, and the inflammatory cell infiltration number and the change of the epidermis thickness were observed. Each section was observed under microscope x 200 x and the inflammatory cell infiltration number (number/HP) was counted after magnification using image processing software; meanwhile, image processing software is adopted, the basal membrane belt is used as a boundary, the longitudinal epidermis area is marked and converted into a numerical value, and the larger the numerical value is, the thicker the skin damage thickness is.
2.4 data statistics and analysis
Data toThis shows that analysis of variance was performed using SPSS17.0 software.
3. Results and discussion
3.1 observations of the area and severity of erythema and scaling lesions in mice of each group
After 2 weeks of treatment, the skin on the back of the normal control group was normal and had hair growth.
Compared with the normal control group, the back skin loss of the model control group has obvious erythema and scale, obviously thickened skin and similar skin loss of psoriasis patients.
The symptoms of each treatment group are improved compared with the model control group, wherein the erythema scale reduction of each group of the composition is obvious. The reduction in erythema scale was more pronounced in the group a and group B compositions compared to the group C compositions.
3.2 skin histological changes of groups of mice after 2 weeks of treatment
HE staining shows that compared with the normal control group, the model control group has obviously thickened skin damage epidermis acantha cell layer, excessive keratinization and insufficient keratinization of the horny layer, and the dermal papilla blood vessel expansion tortuosity, and obvious infiltration of dermal layer and subcutaneous tissue inflammatory cells, and has similar skin damage histological appearance to psoriasis patients.
Compared with the model control group, the other drug treatment groups have obviously reduced skin loss thickness, smoother epidermis layer and obviously reduced inflammatory cell infiltration, wherein the skin loss thickness of each group of the composition is obviously reduced, and the inflammatory cells of the group A and the group B are most obviously reduced. The inflammatory cell infiltration numbers and longitudinal epidermal area values of each group are shown in Table 1.
TABLE 1 skin lesion inflammatory cell infiltration number and longitudinal epidermal area value of mice of each group
In comparison with the model control group, # P<0.05， ## P<0.01; compared with the icariin group, & P<0.05， && P<0.01; in contrast to the madecassic acid group, ★ P<0.05， ★★ P<0.01; in contrast to the group C of the composition, ＊ P<0.05， ＊＊ P<0.01。
the icariin and the madecassic acid are combined, and compared with single medicine, the medicine has obvious synergistic effect and obvious treatment effect on psoriasis. This has great significance in clinical application.
Example 2 Effect of external composition on imiquimod-induced psoriasis-like skin lesions in mice
1. Animal modeling, grouping and administration
1.1 modeling and grouping
BABL/c mice were shaved at the ears and were approximately 2cm by 1.5cm in area, and the movements were gentle to avoid damaging the skin. 70 mice were randomly divided into 7 groups according to a random number table method, 10 mice per group were housed in separate cages, and were fed daily with sterilized water and normal mouse feed.
Randomly selecting one group as a normal control group, and smearing distilled water on the hairless area of the ear at a daily time of about 0.5mL; the remaining 6 groups were serially 7d, once daily ear-applied 250mg:12.5mg imiquimod cream, and imiquimod-induced psoriasis mice models were prepared. Each administration group simultaneously and continuously smears different concentrations of medicines on the ear skin of the mouse in the modeling process. 60 mice with successful modeling are divided into a model control group, an icariin group, a madecassic acid group, a composition A group, a composition B group and a composition C group, wherein 10 mice are respectively selected from each group.
After erythema scales appear locally in each group of mouse models, materials are obtained.
1.2 administration
The different drug treatments were given separately by group:
icariin group: icariin 10 ug/time;
madecassic acid group: madecassic acid 2 mg/time;
composition a group: icariin 100 ug/time + 200 ug/time madecassic acid;
composition B group: icariin 10 ug/time +2 mg/time madecassic acid;
composition C group: icariin 100 ug/time + madecassic acid 100 ug/time;
each test drug was dissolved in diethylene glycol monoethyl ether and administered 1 time a day for 2 weeks. The normal control group and the model control group were given equal volumes of diethylene glycol monoethyl ether 1 time a day.
2. Experimental method and data processing
Psoriasis-like mouse model external treatment comparative analysis: the mice were observed for gross changes, comparing the levels of erythema and scaling. And (3) dehydrating the collected mouse skin loss gradient alcohol, performing HE (high-speed) staining after the xylene is transparent, measuring the thickness of mouse ear epidermis by using a vernier caliper, and comparing the infiltration degree of inflammatory cells.
3. Results and discussion
3.1 group of mice symptom comparison
The mice were continuously and externally applied with imiquimod cream 7d for psoriasis modeling, and the skin of the ears was observed to find that the ears of the mice became red, enlarged, scales were attached to the surfaces, and the vasodilation was obvious. In the modeling process, the skin of the mouse is simultaneously and continuously coated with various groups of medicines with different concentrations, the phenotype of the mouse is observed after 7d, and compared with a model control group, the erythema scale of the mouse is obviously reduced after the medicines of various groups are coated with the skin of the mouse, and the thickness of the epidermis is obviously reduced.
3.2 comparison of ear edge epidermis thickness of mice of each group
By measuring the ear edge thickness, each treatment group is improved compared with the ear edge thickness of a model control group, wherein the improvement of the ear edge thickness of each group of the composition is obvious. The ear edge thickness was more pronounced for the composition a and composition B groups compared to the composition C group. See table 2.
TABLE 2 ear margin thickness variation for mice of each group
| Group of | n | Ear margin thickness (mm) |
| Normal control group | 10 | 0.22±0.027 ## |
| Model control group | 10 | 0.69±0.071 |
| Icariin group | 10 | 0.53±0.064 # |
| Madecassic acid group | 10 | 0.49±0.051 # |
| Composition A group | 10 | 0.35±0.037 ##&&★★＊ |
| Composition group B | 10 | 0.31±0.032 ##&&★★＊ |
| Composition C group | 10 | 0.42±0.056 ##&★ |
In comparison with the model control group, # P<0.05， ## P<0.01; compared with the icariin group, & P<0.05， && P<0.01；
in contrast to the madecassic acid group, ★ P<0.05， ★★ P<0.01; in contrast to the group C of the composition, ＊ P<0.05， ＊＊ P<0.01。
3.3 comparison of skin histopathological examination of mice in groups
Skin histopathological examination of the ear was performed and HE staining showed: compared with the blank control group, the model control group mice have the defects of incomplete keratinization, excessive keratinization, obvious thickening of epidermis acantha layer, expansion of dermis superficial blood vessel and inflammatory cell infiltration, and each treatment group obviously relieves the symptoms of psoriasis and obviously reduces the quantity of dermis infiltration lymphocytes. Wherein the reduction of the skin damage thickness of each group of the composition is more obvious, and the reduction of inflammatory cells of the group A and the group B of the composition is most obvious.
The results indicate that the topical icariin, the madecassic acid and the composition groups can directly act on keratinocytes to relieve psoriasis symptoms, and the treatment effect of each composition group is obviously enhanced, so that the composition has better psoriasis treatment effect.
Example 3 preparation of tablets
Prescription: 10g of icariin, 2g of madecassic acid, 25g of microcrystalline cellulose, 20g of lactose and 1.5g of magnesium stearate.
Mixing the above materials and adjuvants, granulating by conventional wet method, drying, and tabletting.
Example 4 preparation of injection
Prescription: icariin 10g, madecassic acid 20g, sodium chloride 800g and water for injection in proper amount.
Dissolving sodium chloride with injectable water under stirring, adding icariin and madecassic acid respectively, dissolving completely, adding injectable water to total amount, filtering to clarify, packaging, and sterilizing.
Example 5 preparation of capsules
Prescription: 10g of icariin, 2g of madecassic acid, 30g of starch, 10g of microcrystalline cellulose, a proper amount of 2% hydroxypropyl cellulose (HPMC) aqueous solution and 0.5g of magnesium stearate.
Uniformly mixing icariin, madecassic acid, starch and microcrystalline cellulose, adding 2% HPMC water solution, and stirring to obtain soft material. Granulating, oven drying, adding magnesium stearate, grading, mixing, and making into capsule.
EXAMPLE 6 preparation of ointments
Prescription: 0.15g of icariin, 0.25g,PEG400 5.45g,PEG3350 4.00g g of madecassic acid and 0.30g of hexadecanol.
Heating and dissolving icariin, madecassic acid, hexadecanol, PEG400 and PEG3350 in water bath, stirring, and mixing uniformly until condensing.
Claims (9)
1. The use of a pharmaceutical composition containing icariin and madecassic acid in the preparation of a medicament for the treatment of psoriasis, characterized in that: the weight ratio of the icariin to the madecassic acid in the pharmaceutical composition is 1:0.1-20.
2. The use according to claim 1, characterized in that: the medicine is used for treating psoriasis vulgaris, joint type psoriasis, erythrodermic type psoriasis and pustular type psoriasis.
3. Use according to claim 1 or 2, characterized in that: the pharmaceutical composition also comprises a pharmaceutically acceptable carrier or auxiliary material.
4. Use according to claim 1 or 2, characterized in that: the madecassic acid in the pharmaceutical composition is madecassic acid or a salt thereof.
5. Use according to claim 1 or 2, characterized in that: the pharmaceutical composition can be prepared into clinically acceptable dosage forms.
6. Use according to claim 5, characterized in that: the clinically acceptable dosage forms are oral preparations, injection preparations or external preparations.
7. The use according to claim 6, wherein the oral formulation is one or more of a tablet, capsule or microemulsion formulation thereof.
8. The use according to claim 6, wherein the injectable formulation is one or more of an injectable solution or an injectable microemulsion thereof.
9. The use according to claim 6, wherein the external preparation is one or more of powder, ointment, gel, cream, spray or patch, and the external preparation is administered by skin.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000050667A (en) * | 1999-01-13 | 2000-08-05 | 최덕규 | Compositions for whitening and curing skin diseases |
| CN1774257A (en) * | 2002-12-10 | 2006-05-17 | 拜尔消费者保健股份公司 | Method for preparing a centella asiatica extracts rich in madecassoside and in terminoloside |
| KR100821683B1 (en) * | 2006-11-01 | 2008-04-15 | 우석대학교 산학협력단 | A composition containing icariside ii for preventing and treating diseases associated with abnormal angiogenesis |
| WO2009089365A2 (en) * | 2008-01-11 | 2009-07-16 | Shanghai Institute Of Pharmaceutical Industry (Sipi) | Therapeutic formulations based on asiatic acid and selected salts thereof |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000050667A (en) * | 1999-01-13 | 2000-08-05 | 최덕규 | Compositions for whitening and curing skin diseases |
| CN1774257A (en) * | 2002-12-10 | 2006-05-17 | 拜尔消费者保健股份公司 | Method for preparing a centella asiatica extracts rich in madecassoside and in terminoloside |
| KR100821683B1 (en) * | 2006-11-01 | 2008-04-15 | 우석대학교 산학협력단 | A composition containing icariside ii for preventing and treating diseases associated with abnormal angiogenesis |
| WO2009089365A2 (en) * | 2008-01-11 | 2009-07-16 | Shanghai Institute Of Pharmaceutical Industry (Sipi) | Therapeutic formulations based on asiatic acid and selected salts thereof |
| CN101969942A (en) * | 2008-01-11 | 2011-02-09 | 上海医药工业研究院 | Therapeutic formulations based on asiatic acid and selected salts thereof |
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