Intestinal trefoil factor oral preparation and application thereof

Abstract

The invention relates to the technical field of biological medicine, and discloses an intestinal trefoil factor oral preparation which is composed of intestinal trefoil factors, traditional Chinese medicine extracts and auxiliary materials. The traditional Chinese medicine extract is prepared from the following components in parts by mass: 12 to 18 parts of honeysuckle flower extract, 20 to 25 parts of radix paeoniae alba extract, 5 to 8 parts of fructus aurantii immaturus extract, 5 to 8 parts of radix aucklandiae extract, 10 to 15 parts of radix codonopsis extract, 4 to 6 parts of fructus arctii extract, 4 to 6 parts of liquorice root extract and 4 to 6 parts of rhizoma coptidis extract; the intestine three-leaf factor is 40-50 parts by mass. The oral preparation prepared by the invention is composed of an intestinal trefoil factor, a traditional Chinese medicine extract and auxiliary materials, the traditional Chinese medicine extract comprises a honeysuckle extract, a white peony root extract, an immature bitter orange extract, a radix aucklandiae extract, a codonopsis pilosula extract, a burdock extract, a licorice extract and a coptis chinensis extract, and inflammatory cells on colonic mucosa can be reduced; the continuity of epithelial cells is recovered, the inflammatory response is relieved, and the effect of treating and preventing gastrointestinal diseases is remarkable.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to an oral intestinal trefoil factor preparation and application thereof. Background Art

[0002] Intestinal trefoil factor (TFF3) is the most studied member of the trefoil factor family. It is mainly distributed in the intestine and has the functions of protecting the gastrointestinal mucosa and repairing the epithelium. Its mechanisms of action include: interaction with mucin, migration, anti-apoptosis, angiogenesis, immunomodulation, and interaction with its receptors.

[0003] A Chinese patent discloses an oral preparation of intestinal trefoil factor and its clinical application (Announcement No. CN1275645C). This patented technology can rapidly promote the proliferation of gastrointestinal epithelial cells, stabilize the gastrointestinal mucus layer, does not interfere with sugar metabolism and promotes gluconeogenesis, and has no side effects of promoting the expression of bacterial resistance genes and promoting tumor cell growth. However, its effect in treating and preventing gastrointestinal diseases is not good. Summary of the invention

[0004] The object of the present invention is to provide an oral preparation of intestinal trefoil factor and its application to solve the problems raised in the above background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] An oral preparation of intestinal trefoil factor, comprising intestinal trefoil factor, Chinese herbal medicine extracts and auxiliary materials. The Chinese herbal medicine extracts are composed of the following by weight: 12 to 18 parts of honeysuckle extract, 20 to 25 parts of white peony extract, 5 to 8 parts of immature bitter orange extract, 5 to 8 parts of costusroot extract, 10 to 15 parts of codonopsis pilosula extract, 4 to 6 parts of arctium extract, 4 to 6 parts of liquorice extract and 4 to 6 parts of coptis chinensis extract; the intestinal trefoil factor is 40 to 50 parts by weight.

[0007] As a further solution of the present invention: the auxiliary materials are composed of the following by mass: 10 to 15 parts of stabilizer, 15 to 20 parts of filler, 3 to 5 parts of surfactant and 5 to 8 parts of colorant.

[0008] As a further solution of the present invention: the stabilizer is one or more of polysaccharides, amino acids, liposomes and high molecular polymers. The polysaccharides may be sucrose, glucose, and fructose, and the high molecular polymers may be polyvinyl alcohol and polyethylene glycol. The stabilizer can effectively prevent the degradation or inactivation of intestinal trefoil factor.

[0009] As a further solution of the present invention: the filler is one or more of lactose, starch, cellulose, mannitol and sorbitol, and the filler can make the intestinal trefoil factor be evenly dispersed in the oral preparation.

[0010] As a further solution of the present invention: the surfactant is one or more of Tween, poloxamer and polysorbate, and the intestinal trefoil factor can be rapidly absorbed by body fluids through the surfactant.

[0011] As a further solution of the present invention: the colorant is one or more of a sweetener, a flavor, and a pigment. The sweetener may be sucrose or aspartame. The colorant may improve the taste of the oral preparation.

[0012] As a further embodiment of the present invention: the preparation is one of tablets, dispersible tablets, enteric-coated tablets, sustained-release tablets, capsules, granules, suspensions, oral solutions and syrups.

[0013] As a further solution of the present invention: the preparation method of the Chinese medicine extract is as follows:

[0014] S11, wash honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root respectively, dry them, and cut them into small pieces of 2-5 mm;

[0015] S12, soaking the cut honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root in water for 18 to 24 hours respectively, filtering out various Chinese medicine residues and soaking liquid;

[0016] S13, adding 15 to 18 times the weight of ethanol solution to each Chinese medicine filter residue, heating in a water bath at 60 to 70° C. and reflux extraction 3 to 4 times, each time for 2 to 3 hours, to obtain various Chinese medicine extracts;

[0017] S14, combining the various Chinese medicine soaking solutions in step S12 and the various Chinese medicine extract solutions in step S13, respectively, evaporating and concentrating them under reduced pressure, and drying them to obtain honeysuckle extract, white peony extract, immature bitter orange extract, costusroot extract, codonopsis pilosula extract, arctium lappa extract, liquorice extract and coptis chinensis extract respectively;

[0018] S15. Take 12 to 18 parts of honeysuckle extract, 20 to 25 parts of white peony root extract, 5 to 8 parts of immature bitter orange extract, 5 to 8 parts of costusroot extract, 10 to 15 parts of codonopsis pilosula extract, 4 to 6 parts of burdock fruit extract, 4 to 6 parts of liquorice extract and 4 to 6 parts of coptis root extract, and mix them to obtain a traditional Chinese medicine extract.

[0019] The invention also discloses an oral preparation of intestinal trefoil factor for treating and / or preventing gastrointestinal diseases.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The oral preparation prepared by the present invention is composed of intestinal trefoil factor, Chinese medicine extracts and auxiliary materials, wherein the Chinese medicine extracts include honeysuckle extract, white peony extract, immature bitter orange extract, costusroot extract, codonopsis extract, burdock fruit extract, licorice extract and coptis root extract. The oral preparation can reduce inflammatory cells on the colon mucosa, restore epithelial cell continuity, alleviate inflammatory response, and has a significant effect on the treatment and prevention of gastrointestinal diseases. DETAILED DESCRIPTION

[0022] Example 1

[0023] In an embodiment of the present invention, an oral granule of intestinal trefoil factor for treating and / or preventing gastrointestinal diseases is composed of intestinal trefoil factor, Chinese medicine extracts and excipients, wherein the Chinese medicine extracts are composed as follows in parts by mass: 12 parts of honeysuckle extract, 20 parts of white peony extract, 5 parts of immature bitter orange extract, 5 parts of costus root extract, 10 parts of codonopsis pilosula extract, 4 parts of burdock fruit extract, 4 parts of licorice extract and 4 parts of coptis root extract; the intestinal trefoil factor is 40 parts in parts by mass; and the excipients are composed as follows in parts by mass: 10 to 15 parts of sucrose, 15 parts of starch, 3 parts of tween and 5 parts of aspartame.

[0024] Wherein, the preparation method of Chinese medicine extract is as follows:

[0025] S11, wash honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root respectively, dry them, and cut them into 2 mm small sections;

[0026] S12, soaking the cut honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root in water for 18 hours, filtering out various Chinese medicine residues and soaking liquid;

[0027] S13, adding 15 times the weight of ethanol solution to each Chinese medicine filter residue, heating in a water bath at 60° C. and reflux extraction 4 times, each time for 3 hours, to obtain various Chinese medicine extracts;

[0028] S14, combining the various Chinese medicine soaking solutions in step S12 and the various Chinese medicine extract solutions in step S13, respectively, evaporating and concentrating them under reduced pressure, and drying them to obtain various Chinese medicine extracts;

[0029] S15. Take 12 parts of honeysuckle extract, 20 parts of white peony extract, 5 parts of immature bitter orange extract, 5 parts of costus root extract, 10 parts of codonopsis pilosula extract, 4 parts of arctium fruit extract, 4 parts of liquorice extract and 4 parts of coptis root extract, and mix them to obtain a traditional Chinese medicine extract.

[0030] Example 2

[0031] In an embodiment of the present invention, an oral granule of intestinal trefoil factor for treating and / or preventing gastrointestinal diseases is composed of intestinal trefoil factor, Chinese medicine extracts and excipients, wherein the Chinese medicine extracts are composed as follows in parts by mass: 15 parts of honeysuckle extract, 22 parts of white peony extract, 6 parts of immature bitter orange extract, 6 parts of costus root extract, 12 parts of codonopsis pilosula extract, 5 parts of burdock fruit extract, 5 parts of licorice extract and 5 parts of coptis root extract; the intestinal trefoil factor is 45 parts in parts by mass; and the excipients are composed as follows in parts by mass: 12 parts of amino acids, 18 parts of fiber, 3 parts of poloxamer and 6 parts of flavors.

[0032] Wherein, the preparation method of Chinese medicine extract is as follows:

[0033] S11, wash honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root respectively, dry them, and cut them into 3 mm small sections;

[0034] S12, soaking the cut honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root in water for 21 hours, filtering out various Chinese medicine residues and soaking liquid;

[0035] S13, adding 16 times the weight of ethanol solution to each Chinese medicine filter residue, heating in a water bath at 65°C and reflux extraction 3 times, each time for 3 hours, to obtain various Chinese medicine extracts;

[0036] S14, combining the various Chinese medicine soaking solutions in step S12 and the various Chinese medicine extract solutions in step S13, respectively, evaporating and concentrating them under reduced pressure, and drying them to obtain honeysuckle extract, white peony extract, immature bitter orange extract, costusroot extract, codonopsis pilosula extract, arctium lappa extract, liquorice extract and coptis chinensis extract respectively;

[0037] S15. Take 15 parts of honeysuckle extract, 22 parts of white peony extract, 6 parts of immature bitter orange extract, 6 parts of costusroot extract, 12 parts of codonopsis pilosula extract, 5 parts of arctium fruit extract, 5 parts of liquorice extract and 5 parts of coptis chinensis extract, and mix them to obtain a traditional Chinese medicine extract.

[0038] Example 3

[0039] In an embodiment of the present invention, an oral granule of intestinal trefoil factor for treating and / or preventing gastrointestinal diseases is composed of intestinal trefoil factor, Chinese medicine extracts and excipients, wherein the Chinese medicine extracts are composed of the following by mass: 18 parts of honeysuckle extract, 25 parts of white peony extract, 8 parts of immature bitter orange extract, 8 parts of costusroot extract, 15 parts of codonopsis extract, 6 parts of arctium extract, 6 parts of liquorice extract and 6 parts of coptis extract;

[0040] Intestinal trefoil factor is 50 parts by mass;

[0041] The auxiliary materials are composed of 15 parts of polyvinyl alcohol, 20 parts of sorbitol, 5 parts of polysorbate and 8 parts of flavor.

[0042] Wherein, the preparation method of Chinese medicine extract is as follows:

[0043] S11, wash honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root respectively, dry them, and cut them into 5 mm small sections;

[0044] S12, soaking the cut honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root in water for 24 hours, filtering out various Chinese medicine residues and soaking liquid;

[0045] S13, adding 18 times the weight of ethanol solution to each Chinese medicine filter residue, heating in a water bath at 70°C and reflux extraction 4 times, each time for 2 hours, to obtain various Chinese medicine extracts;

[0046] S14, combining the various Chinese medicine soaking solutions in step S12 and the various Chinese medicine extract solutions in step S13, respectively, evaporating and concentrating them under reduced pressure, and drying them to obtain honeysuckle extract, white peony extract, immature bitter orange extract, costusroot extract, codonopsis pilosula extract, arctium lappa extract, liquorice extract and coptis chinensis extract respectively;

[0047] S15, take 18 parts of honeysuckle extract, 25 parts of white peony extract, 8 parts of immature bitter orange extract, 8 parts of costus root extract, 15 parts of codonopsis pilosula extract, 6 parts of arctium fruit extract, 6 parts of liquorice extract and 6 parts of coptis root extract, and mix them to obtain a traditional Chinese medicine extract.

[0048] In order to better illustrate the technical effects of the present invention, the following embodiments are described:

[0049] 8-week-old clean-grade SD rats weighing 180 g to 220 g were taken and adaptively raised in an environment with a temperature of 22°C to 24°C and a humidity of 50% to 60% for 1 week;

[0050] The mice were randomly divided into a normal control group, a model control group, a positive control group, an embodiment 1 group, an embodiment 2 group, and an embodiment 3 group, with 10 mice in each group;

[0051] Among them, except for the normal control group that drank distilled water, the other groups drank dextran sulfate sodium salt solution, and observed and recorded the weight and feces of the rats every day, and performed fecal occult blood test; when the following appeared: weight loss of more than 5%, loose stools, and blood in the stool, the rat colitis model was determined to be successful;

[0052] After the rat colitis model was successfully established, the rats in the positive control group were given 0.5 g / kg of sulfasalazine enteric-coated tablets, the rats in the Example 1 group, the Example 2 group and the Example 3 group were given 0.5 g / kg of the oral granules prepared in Example 1, Example 2 and Example 3 of the present invention, respectively, and the rats in the normal control group and the model control group were given an equal amount of physiological saline; after continuous administration for 6 weeks, the rats were killed;

[0053] 1. The body weight (unit: g) and colon length (unit: mm) of rats in each group were measured, and the colon mucosal tissue damage was scored. The scoring criteria were as follows: normal colon mucosa was 0 points; less than 1 / 3 of the colon mucosal damage was 0-1 points; less than 2 / 3 of the mucosal damage was 1-2 points; granulocyte infiltration with a small amount of damage was 2-3 points; a large amount of granulocyte infiltration in the damage and ulcer was 3-4 points; and recorded in Table 1 below;

[0054] Table 1 Colon mucosal analysis and evaluation table

[0055]

[0056] From Table 1 above, it can be concluded that: compared with the normal control group, the body weight and colon length of the rats in the model control group were significantly decreased, and there were a large number of granulocyte infiltrations at the colon mucosal damage and ulcers; compared with the model control group, the body weight and colon length of the rats in the positive control group, Example 1 group, Example 2 group and Example 3 group were increased to varying degrees, but the increase in the body weight and colon length of the rats in Example 1 group, Example 2 group and Example 3 group was more significant; and the colon mucosal damage of the rats in the positive control group was accompanied by a small amount of damaged granulocyte infiltration; while the colon mucosal damage of the rats in Example 1 group, Example 2 group and Example 3 group was relatively small, and it can be concluded that the intestinal trefoil factor oral preparation prepared by the present invention can reduce colon mucosal damage and make the mucosal layer tend to be complete.

[0057] 2. Take colon tissue of about 1 cm, cut it into pieces, add physiological saline, make 20% homogenate, centrifuge and separate, take the supernatant, detect and analyze the cytokine content, including myeloperoxidase (MPO, unit: ng / ml), tumor necrosis factor-α (TNF-α, unit: ng / ml) and interleukin-6 (IL-6, unit: ng / ml), and record it in the following Table 2;

[0058] Table 2 Cytokine content analysis table

[0059]

[0060]

[0061] It can be concluded from Table 2 above that compared with the normal control group, the myeloperoxidase, tumor necrosis factor-α and interleukin-6 in the colon mucosa of the rats in the model control group were significantly increased; compared with the model control group, the myeloperoxidase, tumor necrosis factor-α and interleukin-6 in the colon mucosa of the rats in the positive control group, Example 1 group, Example 2 group and Example 3 group were decreased to varying degrees, but the decrease in myeloperoxidase, tumor necrosis factor-α and interleukin-6 in the colon mucosa of the rats in Example 1 group, Example 2 group and Example 3 group was more significant. It can be concluded that the intestinal trefoil factor oral preparation prepared by the present invention can reduce inflammatory cells on the colon mucosa, restore epithelial cell continuity, alleviate inflammatory response, and has a significant effect on the treatment and prevention of gastrointestinal diseases.

[0062] What is described above is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. An oral preparation of intestinal trefoil factor, comprising intestinal trefoil factor, a Chinese herbal extract and excipients, characterized in that: The Chinese medicine extract is composed of the following parts by mass: 12 to 18 parts of honeysuckle extract, 20 to 25 parts of white peony extract, 5 to 8 parts of immature bitter orange extract, 5 to 8 parts of costus root extract, 10 to 15 parts of codonopsis pilosula extract, 4 to 6 parts of burdock fruit extract, 4 to 6 parts of liquorice extract and 4 to 6 parts of coptis root extract; the intestinal trefoil factor is 40 to 50 parts by mass.

2. An oral preparation of intestinal trefoil factor according to claim 1, characterized in that: The auxiliary materials are composed of the following parts by mass: 10 to 15 parts of stabilizer, 15 to 20 parts of filler, 3 to 5 parts of surfactant and 5 to 8 parts of colorant.

3. An oral preparation of intestinal trefoil factor according to claim 2, characterized in that: The stabilizer is one or more of polysaccharides, amino acids, liposomes and high molecular polymers. The polysaccharides may be sucrose, glucose, and fructose, and the high molecular polymers may be polyvinyl alcohol and polyethylene glycol. The stabilizer can effectively prevent the degradation or inactivation of intestinal trefoil factor.

4. The oral preparation of intestinal trefoil factor according to claim 2, characterized in that: The filler is one or more of lactose, starch, cellulose, mannitol and sorbitol. The filler can make the intestinal trefoil factor evenly dispersed in the oral preparation.

5. The oral preparation of intestinal trefoil factor according to claim 2, characterized in that: The surfactant is one or more of Tween, poloxamer and polysorbate. The surfactant can enable the intestinal trefoil factor to be rapidly absorbed by body fluid.

6. The oral preparation of intestinal trefoil factor according to claim 2, characterized in that: The colorant is one or more of a sweetener, a flavor, and a pigment. The sweetener may be sucrose or aspartame. The colorant can improve the taste of the oral preparation.

7. The oral preparation of intestinal trefoil factor according to claim 1, characterized in that: The preparation is one of tablets, dispersible tablets, enteric-coated tablets, sustained-release tablets, capsules, granules, suspensions, oral solutions and syrups.

8. The oral preparation of intestinal trefoil factor according to claim 1, characterized in that: The preparation method of the Chinese medicine extract is as follows: S11, wash honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root respectively, dry them, and cut them into small pieces of 2-5 mm; S12, soaking the cut honeysuckle, white peony root, immature bitter orange, costusroot, codonopsis pilosula, burdock fruit, liquorice and coptis root in water for 18 to 24 hours respectively, filtering out various Chinese medicine residues and soaking liquid; S13, adding 15 to 18 times the weight of ethanol solution to each Chinese medicine filter residue, heating in a water bath at 60 to 70° C. and reflux extraction 3 to 4 times, each time for 2 to 3 hours, to obtain various Chinese medicine extracts; S14, combining the various Chinese medicine soaking solutions in step S12 and the various Chinese medicine extract solutions in step S13, respectively, evaporating and concentrating them under reduced pressure, and drying them to obtain honeysuckle extract, white peony extract, immature bitter orange extract, costusroot extract, codonopsis pilosula extract, arctium lappa extract, liquorice extract and coptis chinensis extract respectively; S15. Take 12 to 18 parts of honeysuckle extract, 20 to 25 parts of white peony root extract, 5 to 8 parts of immature bitter orange extract, 5 to 8 parts of costusroot extract, 10 to 15 parts of codonopsis pilosula extract, 4 to 6 parts of burdock fruit extract, 4 to 6 parts of liquorice extract and 4 to 6 parts of coptis root extract, and mix them to obtain a traditional Chinese medicine extract.

9. The intestinal trefoil factor oral preparation according to any one of claims 1 to 8 is used for treating and / or preventing gastrointestinal diseases.

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