CN112438982A - Pharmaceutical composition and application thereof - Google Patents

Abstract

The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition and application thereof. The pharmaceutical composition consists of icaritin and madecassic acid. The invention also discloses application of the pharmaceutical composition in preparing a medicament for treating ulcerative colitis or bedsore. The pharmaceutical composition has the advantages of good curative effect, no side effect and high safety when being used for treating ulcerative colitis or bedsore, and has good development prospect and social and economic benefits.

Description

Pharmaceutical composition and application thereof

Technical Field

The invention belongs to the field of medicines, relates to a pharmaceutical composition and application thereof, and particularly relates to a composition containing icariin and madecassic acid and application thereof in preparing a medicine for treating ulcerative colitis or bedsore.

Background

The icariin belongs to flavonol compounds, is slightly present in epimedium medicinal materials, and has the following chemical structural formula:

icariin can be isolated from epimedium medicinal material (grandson, xu Ying, Wen bright light, etc., chemical components of epimedium koreanum, China journal of phytochemistry 1998, 8 (2): 122-125), or icariin can be isolated by enzymolysis (leaf spergualin, Liujia, Loujia, preparation of icariin derivatives and studies on estrogen-like action thereof, proceedings of Zhejiang university, 2005, 34 (2): 131-136).

There is a report that icaritin has the effect of resisting apoptosis of rat primary culture nerve cells caused by A beta peptide (Zhang Xiang, Wang Huan, Wang Zhi Qiang, etc., icaritin has the effect of resisting apoptosis of rat primary culture nerve cells caused by A beta peptide, Zhejiang university report 2007, 36 (3): 224-. Chinese patent CN101836976A discloses that icaritin has the function of resisting tumor angiogenesis. Chinese patent CN101428015A discloses that icaritin has the effect of resisting endotoxemia. Chinese patent CN101284000A discloses that icariin has the function of preventing and treating obesity or fatty liver. Chinese patent CN1869204A discloses the use of icariin in inducing stem cell in vitro directional differentiation. Chinese patent CN1194701C discloses the application of icariin or demethylicariin in the preparation of estrogen receptor modulators.

Madecassic acid is an important pentacyclic triterpenic acid compound in centella asiatica of Umbelliferae, and has the following chemical structural formula:

recent studies have shown that asiatic acid and madecassic acid have certain effects in resisting oxidation and cancer. Chinese patent CN201110040181.7 discloses that madecassic acid has obvious inhibitory effect on mammary gland hyperplasia of experimental rats. Chinese patent CN200910067429.1 discloses the use of asiatic acid and madecassic acid in the preparation of drugs for alpha-glucosidase inhibitors.

The content of aglycone such as madecassic acid in centella asiatica is much lower than that of madecassic acid glycoside, the content of saponin in centella asiatica is generally 1.8-5%, and the content ratio of sapogenin to saponin is generally 1: 2.5. chinese patent CN201610728601.3 discloses a method for preparing madecassic acid by hydrolyzing madecassoside. The method can rapidly break glycosidic bond at normal temperature and normal pressure, has mild hydrolysis process and thorough hydrolysis, and does not generate configuration change of madecassic acid.

Ulcerative colitis, also known as chronic nonspecific ulcerative colitis, is mainly characterized by superficial diseases of the colon and the rectum, and diseases accompanied by the damage of multiple organs outside the intestine. The first is the diffuse inflammation change of the superficial mucosa, and the subsequent congestion, edema, hypertrophy and brittleness increase, small ulcer is produced, and then large ulcer is developed, and the advanced colon tissue hyperplasia causes the thickening and narrowing of the intestinal wall and the shortening of the intestinal canal. The disease course is long, the health and the life quality of patients are seriously influenced, and the probability of colorectal cancer is increased along with the prolongation of the disease course, so the disease course is listed as one of the modern refractory diseases by the world health organization. The disease is less common in our country than Europe and America, and the course of the disease is generally mild, but in recent years, the prevalence rate is gradually increased, and severe cases are often reported.

The scheme for treating ulcerative colitis at home and abroad is basically consistent, and the sulfasalazine salicylic acid preparation, prednisone or dexamethasone and other hormone preparations, an immunosuppressant azathioprine and the like are mainly used for clinical treatment, but the curative effect is poor and the great adverse reaction is caused. Therefore, people pay attention to research and develop the medicine for treating the ulcerative colitis for a long time, and the medicine has very important significance for relieving the pain of patients and improving the life quality of the patients.

Bedsore refers to pressure ulcer and pressure sore. It is the damage and necrosis caused by the loss of normal function of skin due to blood circulation disorder and tissue nutrition deficiency caused by long-term compression of local tissues of the body. High incidence in elderly, spinal cord injury, severe and bedridden patients. Once it occurs, it not only can bring pain to the patient, aggravate the disease condition and prolong the recovery time of the disease, but also can endanger the life due to secondary infection. The complication rate of bedsore infection can reach 50% under the hospitalization condition.

Bedsores are often difficult to cure due to prolonged course of disease, which brings great difficulty to clinical treatment and nursing. Meanwhile, due to the occurrence of bedsore, the economic burden of a patient is increased, and the life quality is seriously reduced. Therefore, finding a method for quickly and effectively curing the bedsore is an important subject to which the clinician and the nursing staff are urgently required to research. At present, clinical treatment of bedsore is mostly limited to local dressing change treatment in western medicine, and the effect is poor. The simple local dressing change treatment is not enough for healing of the bedsore wound surface, especially for patients with severe bedsore, the blood circulation of the local wound surface tissue is promoted, the anti-infection capability of the local tissue is enhanced, and the enhancement of the healing capability of the tissue is the root for quickly healing the bedsore.

In view of the limitation of the traditional Chinese and western medicine for treating the bedsore, the research and development of the safe and effective medicine for treating the bedsore is significant.

Tissue damage and necrosis are accompanied in the onset process of ulcerative colitis and bedsore.

Through search, no pharmaceutical composition taking icariin and madecassic acid as active ingredients exists at present. No report related to the medical application of a pharmaceutical composition taking icariin and madecassic acid as active ingredients exists in the prior art.

Disclosure of Invention

One of the purposes of the invention is to provide a safe and effective pharmaceutical composition, which takes icariin and madecassic acid as main active ingredients.

The weight ratio of the icariin to the madecassic acid in the pharmaceutical composition is preferably 1: 0.01-30.

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 needs.

The inventor considers the requirement of convenient medication for patients and the characteristic that two medicaments are convenient for taking in one time compared with the two medicaments taken in a plurality of times, and prepares the medicinal composition into solid medicinal preparations, such as tablets, capsules, granules, pills, dropping 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 the solid pharmaceutical preparation, has the advantages of convenient carrying and use and simple and easy administration route, and is easy to be accepted by patients.

In addition, the pharmaceutical composition can also be prepared into external preparations such as ointment and the like, so that the pharmaceutical composition is convenient for patients to use.

The invention also aims to provide the medical application of the pharmaceutical composition, namely the application of the pharmaceutical composition in preparing a medicament for treating colitis or bedsore.

The colitis may be caused by one or more of genetic, infectious, autoimmune, psychiatric factors, and the like.

Preferably, the colitis is one of specific colitis and nonspecific colitis.

Further preferably, the specific colitis is one of infectious colitis, ischemic colitis and pseudomembranous colitis; the non-specific colitis is ulcerative colitis.

More preferably, the colitis is ulcerative colitis.

The inventor aims at the development of treatment medicines for a long time, and unexpectedly finds that the combined application of icariin and madecassic acid has a remarkable repairing effect on tissue damage and necrosis, has a good treatment effect on the treatment of ulcerative colitis or bedsore, especially ulcerative colitis, and has a remarkable synergistic treatment effect when the two medicines are combined.

Example 1 of the invention shows that the composition of icariin and madecassic acid has obvious therapeutic effect on rats with ulcerative colitis, can obviously improve general morphological and pathological changes of intestinal mucosa and protect intestinal mucosa barriers, and the effect of the composition of the invention on improving general morphological and pathological changes of intestinal mucosa is obviously superior to that of icariin single drug and that of madecassic acid single drug.

Example 2 of the invention shows that the composition of icariin and madecassic acid has obvious therapeutic effect on bedsore rats and can significantly increase the wound healing rate.

The effect of the pharmaceutical composition for treating ulcerative colitis is not only obviously superior to the effect of two drugs when the two drugs are used independently, but also superior to the addition of the two effects; the two medicines are combined for use, so that the respective dosage can be obviously reduced, and adverse reactions are reduced; meanwhile, clinical medication selection of patients with ulcerative colitis or bedsore is increased, and the method has good clinical application prospect.

Compared with the prior art, the pharmaceutical composition has the following outstanding advantages in the aspect of treating ulcerative colitis or bedsore:

(1) compared with the single administration of the icariin or the madecassic acid, the pharmaceutical composition containing the icariin and the madecassic acid has better treatment effect on ulcerative colitis or bedsore models, and the two pharmaceutical active ingredients show good synergistic effect in the aspect of treating the ulcerative colitis or the bedsore.

(2) The pharmaceutical composition contains madecassic acid and icariin, and the combined use of the madecassic acid and the icariin has a synergistic effect and can obviously reduce the use amount of the madecassic acid and the icariin, thereby obviously reducing the toxic and side effects of patients during medication and reducing the occurrence of adverse reactions.

(3) The pharmaceutical composition of the invention treats ulcerative colitis or bedsore in a fixed combination mode, is more convenient to take compared with taking single medicine simultaneously, improves the compliance and compliance of patients, and enhances the treatment effect on diseases to a certain extent.

The pharmaceutical composition can be clinically used for treating ulcerative colitis or bedsore. In the above medical application, the icariin and madecassic acid pharmaceutical composition can be prepared into a suitable pharmaceutical preparation for convenient administration according to the condition of an animal and the administration site, and the administration time and the administration frequency of the pharmaceutical composition for treating ulcerative colitis or bedsore according to the specific diagnosis result of the condition are within the technical scope mastered by the skilled in the art. For example, it will be apparent to those skilled in the art that the therapeutic regimen for ulcerative colitis or decubitus ulcers in rats or mice is applied to humans and that the effective dose of all drugs to humans can be converted to the effective dose of the drug to rats or mice.

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. Alterations and/or combinations of features of the invention will be apparent to those skilled in the art from the disclosure, spirit and/or scope of the invention, and are intended to be encompassed by the invention.

It should be noted that in the following animal test examples, the inventor only lists the therapeutic effect of the composition of the present invention on ulcerative colitis and decubitus rats, and for other types of colitis mentioned in the present invention, the inventor also performs related animal experimental studies, and the results of the studies show that the composition of the present invention can achieve the same or similar therapeutic effect on other types of colitis, and the following test examples are not intended to limit the present invention.

EXAMPLE 1 intervention of the composition on the intestinal mucosal immune barrier in rats with ulcerative colitis

1. Animal modeling, grouping and administration

1.1 Molding

Rats were randomly divided into 7 groups of 10 rats each, each group consisting of a blank control group, a model control group, icariin group, madecassic acid group, composition a group, composition B group, and composition C group.

Taking SPF-grade SD rats with half male and female parts and weight of 150-170 g, and molding according to a classical 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) method. The rats are fasted for 24 hours before model building, 4mL/kg of 10% chloral hydrate are subjected to intraperitoneal injection to anesthetize the rats, polyethylene hoses with the diameter of 0.4mm, which are lubricated by paraffin oil, are inserted into the rectum, the depth is about 8cm, 5% TNBS50mg/kg + 50% ethanol 0.25mL is slowly injected, then the tail of the rats is lifted and inverted for 60s, the liquid medicine is fully remained in the colorectal cavity, a normal group is subjected to enema with physiological saline with the same volume, water is freely drunk after waking, and after the model building group is subjected to TNBS enema for model building for 1 time, the model is continuously evaluated from the aspects of body mass change, stool properties, hematochezia conditions, visceral sensitivity, colon pathology and the like for 1 week. 2 patients are randomly drawn for dissection after 7 days of model building, and a colon pathology shows a series of changes such as congestion, edema, inflammatory cell infiltration, crypt abscess, goblet cell reduction, gland destruction and small ulcer formation, which indicates that the model building is successful.

1.2 grouping

60 successfully molded rats were divided into 10 groups, each group consisting of a model control group, icariin group, madecassic acid group, composition A group, composition B group and composition C group.

10 normal rats were taken as a blank control group.

1.3 administration of drugs

1.3.1 dosage of test drug

Icariin group: 1mg/kg icariin;

madecassic acid group: 30mg/kg madecassic acid;

composition group A: 10mg/kg icariin +3mg/kg madecassic acid;

composition B group: 1mg/kg of icaritin +30mg/kg of madecassic acid;

composition group C: 10mg/kg icariin +1mg/kg madecassic acid;

1.3.2 administration

From 7 days after molding, each test drug was suspended with 0.5% sodium carboxymethylcellulose 1 time a day; the normal group and the model group were given equal volume of 0.5% sodium carboxymethylcellulose 1 time per day; the administration is continued for 7 days.

2. Experimental methods and data processing

2.1 specimen Collection

After the last administration, fasting and water deprivation are carried out for 24 hours, 4.0mL/kg of 10% chloral hydrate is injected into an abdominal cavity to anaesthetize the rat, the rat is killed after the blood taking is finished, blood, colon tissues and the like are collected for index detection, and the rat is stored at the temperature of minus 20 ℃ for detection.

2.2 general morphological Observation of rat Colon

Colon 8 + -2 cm from anus, cut along the longitudinal axis, washed clean with saline, and scored for mucosal damage in colon by reference to Luketal criteria (Xu B, Liu X L, Dong W, et al. EGCG maintainans Th1/Th2 balance and tissues emulsion concentration induced by dextran sulfate sodium TLR4/MyD 88/NF-. kappa.B signaling pathway in rates [ J ]. J Gastroenterol Heapatol, 2017): 0 point, no inflammation and ulcer; 1 point, local congestion without ulcer; 2 points, hyperemia and thickening of the intestinal wall without ulceration; 3 minutes, 1 part of ulcer and inflammation, and the diameter is about 0-1 cm; ulcer and inflammation at 4 minutes, 2 or more than 2 places, the diameter is about 1-2 cm, but the intestinal canal and peripheral organs are not adhered; and 5, the ulcer extends over 2cm, the intestinal canal is thickened, the adhesion with surrounding organs is serious, and the general morphological damage of the colonic mucosa is evaluated.

2.3 Observation of pathological changes in rat Colon tissue

Fixing colon tissue with 4% paraformaldehyde, decalcifying, dehydrating, permeabilizing, embedding in paraffin, slicing to 4-5 μm, dewaxing the slice with xylene, hydrating with absolute ethanol, fixing with HE staining, observing histological change under microscope, and grading pathologically according to histological grade: 0 minute, the intestinal mucosa and the villus are complete, and the structure is completely normal; 1 point, mild submucosa and/or lamina propria separation; 2 min, moderate submucosa and/or lamina propria separation; submucosa and/or muscularis edema; 3 points, severe submucosa and/or lamina propria separation, submucosa and/or muscularis edema, local intestinal villus sloughing; 4 points, disappearance of intestinal villi and intestinal necrosis) (Hou Y, Lu X, Zhang Y. IRAK inhibition or protectants the intestinal track of the adjacent inflammatory substances by inhibiting the Toll-like receptor (TLR) affinity signalling pathway in rates [ J ] Med Sci monitor, 2018,24: 3366-.

2.4 data statistics and analysis

Data to

Shown, analysis of variance was performed using SPSS17.0 software.

3. Results and discussion

3.1 general Condition and disease Activity changes in rats

The rats in the blank control group had good spirit, glossy hair, normal activity, food intake and stool, and naturally increased physical quality. The rats in the model group showed depressed spirit, lusterless hair, decreased physical quality, decreased activity, mucus and bloody stool, and the general conditions of each administration group were obviously improved compared with the model group.

The rat colon mucosa of the model control group can be seen with obvious congestion and edema, and colon mucosa erosion with different degrees, and a plurality of small ulcers and pseudomembranes can be seen in the intestinal cavity.

Compared with a blank control group, the degree of intestinal mucosa injury of the rats in the model group is obviously increased (P < 0.01).

Compared with the model control group, the degree of intestinal mucosa injury score of each administration group is remarkably reduced (P <0.05, P < 0.01).

Compared with icariin groups, the scores of the damage degree of the colon mucous membrane of the composition A group, the composition B group and the composition C group are obviously reduced (P <0.05 and P < 0.01).

Compared with the madecassic acid group, the colonic mucosa injury degree scores of the composition A group, the composition B group and the composition C group are obviously reduced (P <0.05 and P < 0.01).

Compared with the composition C group, the grading of the damage degree of the colon mucous membrane of the composition A group and the composition B group is obviously reduced (P < 0.05).

The results are shown in Table 1.

TABLE 1 Effect of the compositions of the invention on the score of the degree of injury of the intestinal mucosa in rats with ulcerative colitis

Note: compared with the blank control group, the composition of the composition,^￥P<0.05，^￥￥P<0.01; compared with the model control group,^#P<0.05，^##P<0.01; compared with the icariin group,^&P<0.05，^&&P<0.01; compared with the madecassic acid group,^★P<0.05，^★★P<0.01; compared with the composition C group,^＊P<0.05，^＊＊P<0.01。

the intestinal mucosa of the model control group is obviously congested and edematous, obvious ulcer formation can be seen, glands around the ulcer are defected and distributed disorderly, the intestinal wall is widely fibrillated, and the disease of the model control group is deepened to the submucosa and the muscular layer.

The congestion and edema of the intestinal mucosa and the submucosa of the rat in each administration group are reduced, the ulcer of the intestinal mucosa is changed in a healing way, and the newborn glands are accompanied around part of ulcer.

Compared with the blank control group, the pathology score of the model control group is obviously increased (P < 0.01).

Compared with the model control group, the intestinal mucosa pathological score of each administration group is significantly reduced (P <0.05, P < 0.01).

Compared with icariin groups, histopathological scores of the composition A group, the composition B group and the composition C group are obviously reduced (P <0.05 and P < 0.01).

Histopathological scores were significantly lower in the composition a, composition B, and composition C groups compared to the madecassic acid group (P <0.05, P < 0.01).

The histopathological scores of the composition A and composition B groups were significantly reduced compared to the composition C group (P < 0.05).

The results are shown in Table 2.

TABLE 2 Effect of the compositions of the invention on the Scoring of the pathology of the intestinal mucosa of rats with ulcerative colitis

Note: compared with the blank control group, the composition of the composition,^￥P<0.05，^￥￥P<0.01; compared with the model control group,^#P<0.05，^##P<0.01; compared with the icariin group,^&P<0.05，^&&P<0.01; compared with the madecassic acid group,^★P<0.05，^★★P<0.01; compared with the composition C group,^＊P<0.05，^＊＊P<0.01。

the combination of the icaritin and the madecassic acid has obvious synergistic effect compared with a single medicine, and has obvious treatment effect on the ulcerative colitis. This is of great significance in clinical application.

Example 2 Observation of therapeutic Effect of icaritin and madecassic acid composition on rat decubitus ulcer

1. Animal modeling, grouping and administration

1.1 Molding

Taking SPF SD rats with half male and female parts and weight of 150-170 g. After 1 week of adaptive feeding with a general feed, a rat pressure sore model was prepared by referring to the pressure sore model preparation method of Tsuji S et al (Shinsaku Tsuji MD, Shigeru Ichiaka MD, Naomi Sekiya MT, Takashi Nakatsuka MD. analysis of ischemia-perfusion in a microcirculation model of pressure emulsifiers [ J ]. Wound Repair and Regeneration, 2005, 13 (2)). The specific method comprises the following steps: after the abdominal cavity of the rat is anesthetized, the back is depilated and disinfected, a 3cm long full-layer transverse incision penetrating through the skin is made on the two sides of the waist and the back near the spinal column of the back of the rat, a magnetic sheet sterilized by high-pressure steam is placed in the skin incision and is sewn, and the diameter of the magnetic sheet is 13mm, and the thickness of the magnetic sheet is 2 mm. Animal postoperative d2, in vitro using a permanent magnet with a magnetic flux density of 1500 gauss on rat dorsal magnetic sheet implant area for 2h induced ischemia, and then removing the magnet to allow reperfusion of the skin in the area for 0.5h, which is a cycle of 5 cycles per day, repeated for 5 days. The total number of ischemia/reperfusion is 25, the total ischemia time is 50h, and the ulcer is judged by taking skin blackening, hardening and non-bleeding due to acupuncture as a standard, namely the bedsore model is considered to be successfully prepared. The magnetic sheets used by the model making of each rat are consistent in size so as to ensure that the areas of the initial pressure sores are consistent in size; in this experiment, after the molding was successful, the area of pressure sores on each rat was measured by copper sulfate paper, and statistical analysis showed no significant statistical significance, i.e., the initial area of pressure sores on each rat was substantially consistent.

1.2 grouping

Taking 60 successfully molded rats, randomly dividing the rats into 6 groups according to body weight, and each group comprises 10 rats, namely a model control group, an icariin group, a madecassic acid group, a composition A group, a composition B group and a composition C group.

From the day of the successful molding, the medicine is changed in groups every day, and the following medicines are respectively given to each group:

icariin group: 1% icaritin;

madecassic acid group: 0.1% madecassic acid;

composition group A: 2% icaritin + 0.02% madecassic acid;

composition B group: 1% icaritin + 0.1% madecassic acid;

composition group C: 0.2% icaritin + 0.1% madecassic acid.

The above test drugs are dissolved in glycerol and applied to bedsore parts.

Model control group: the same volume of glycerol is applied to the bedsore part.

The wound sizes were recorded on days 6, 9, and 12 after molding, and the healing rates of the skin pressure sores of the rats in each group were calculated.

2. Experimental methods and data processing

2.1 wound healing Rate

Measuring the area of pressure sore of rat on 6 th, 9 th and 12 th days after molding, sticking transparent copper sulfate paperboard on the surface of pressure sore skin and using a pen because the wound surface is irregular healingPlotting pressure sore area (cm) on paper²) Carrying out statistics by using photoshop image processing software; the wound healing rate was calculated by the formula P ═ 1-a1/a0 × 100%, and the wound healing rate was evaluated. (P: rate of healing; A1: existing wound area; A0: original wound area.)

2.2 data statistics and analysis

Data to

Shown, analysis of variance was performed using SPSS17.0 software.

3. Results and discussion

3.1 wound healing Rate

Compared with the model control group, the wound healing rate of each administration group is obviously increased except for icariin group (P is less than 0.01).

Compared with icariin groups, the wound healing rate of the composition A group, the composition B group and the composition C group is obviously increased (P is less than 0.05, and P is less than 0.01).

Compared with the madecassic acid group, the wound healing rates of the composition A group, the composition B group and the composition C group are obviously increased (P <0.05 and P < 0.01).

Compared with the composition C group, the wound healing rate of the composition A group and the composition B group is obviously increased (P is less than 0.05).

The results are shown in Table 3.

TABLE 3 Effect of the composition of the present invention on the rate of healing of bedsores in rats

Note: compared with the model control group,^#P<0.05，^##P<0.01; compared with the icariin group,^&P<0.05，^&&P<0.01; compared with the madecassic acid group,^★P<0.05，^★★P<0.01; compared with the composition C group,^＊P<0.05，^＊＊P<0.01。

the combination of the icaritin and the madecassic acid has obvious synergistic effect compared with a single medicine, and has obvious treatment effect on bedsore.

EXAMPLE 3 preparation of tablets

The preparation process comprises mixing icariin, madecassic acid and adjuvants of microcrystalline cellulose and sodium carboxymethyl starch, adding appropriate amount of starch slurry to make soft mass, sieving with 16 mesh sieve, and granulating. Drying wet granules at 60 deg.C, sieving dry granules with 20 mesh sieve, grading, sieving to obtain fine powder, mixing with magnesium stearate, mixing with dry granules, and tabletting to obtain tablet of about 200 mg.

Example 4 icaritin injection

The preparation process comprises the following steps: mixing propylene glycol and ethanol, adding icariin and madecassic acid, stirring for dissolving, adding 0.9% sodium chloride solution, stirring, adding 0.5% needle activated carbon, stirring, and removing carbon.

EXAMPLE 5 preparation of capsules

The preparation process comprises mixing icariin, madecassic acid and adjuvants of microcrystalline cellulose and sodium carboxymethyl starch, adding appropriate amount of starch slurry to make soft mass, sieving with 16 mesh sieve, and granulating. Drying wet granules at 60 deg.C, sieving dry granules with 20 mesh sieve, grading, and making into capsule.

Claims (10)

1. A pharmaceutical composition contains icaritin and madecassic acid.

2. The pharmaceutical composition of claim 1, wherein: the weight ratio of the icariin to the madecassic acid in the pharmaceutical composition is 1: 0.01-30.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that: the pharmaceutical composition can be prepared into clinically acceptable dosage forms.

4. The pharmaceutical composition of claim 3, wherein: the dosage form is one or more of powder, injection, capsule, tablet, oral liquid or ointment.

5. Use of a pharmaceutical composition according to claims 1-4 for the preparation of a medicament for the prevention or treatment of colitis or bedsores.

6. The use of claim 5, wherein the colitis is caused by one or more of genetic, infection, autoimmune response, psychiatric factors, and the like.

7. The use of claim 5, wherein the colitis is one of specific colitis or non-specific colitis.

8. The use of claim 7, wherein the specific colitis is one of infectious colitis, ischemic colitis, pseudomembranous colitis.

9. The use of claim 7, wherein the non-specific colitis is ulcerative colitis.

10. The use of claim 5, wherein the colitis is ulcerative colitis.