CN117503829A - Traditional Chinese medicine cellulose granule for relaxing bowel and preparation method and application thereof - Google Patents
Traditional Chinese medicine cellulose granule for relaxing bowel and preparation method and application thereof Download PDFInfo
- Publication number
- CN117503829A CN117503829A CN202311509067.3A CN202311509067A CN117503829A CN 117503829 A CN117503829 A CN 117503829A CN 202311509067 A CN202311509067 A CN 202311509067A CN 117503829 A CN117503829 A CN 117503829A
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- cellulose
- chinese medicine
- traditional chinese
- constipation
- wheat
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/717—Celluloses
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- A—HUMAN NECESSITIES
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A61K36/18—Magnoliophyta (angiosperms)
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- A—HUMAN NECESSITIES
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a traditional Chinese medicine cellulose granule for relaxing bowel and a preparation method and application thereof, wherein the traditional Chinese medicine cellulose granule is prepared from the following raw materials in parts by weight: 1 to 8 parts of wheat cellulose, 1 to 10 parts of xylooligosaccharide, 1 to 10 parts of angelica, 1 to 10 parts of cistanche deserticola, and 1 to 5 parts of isomaltulose alcohol. The invention combines the dialectical treatment of the deficiency constipation by the traditional Chinese medicine, selects medicinal materials which can be used for improving the constipation and carries out compatibility; meanwhile, the synergistic effect between the insoluble dietary fiber wheat cellulose and the soluble dietary fiber xylooligosaccharide is remarkable in constipation, and the synergistic effect is achieved, so that the symptom of deficiency constipation can be greatly improved; the obtained product is simple, convenient, low in cost and effective, and simultaneously, the bitter taste of oral administration of traditional Chinese medicine is avoided.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and in particular relates to traditional Chinese medicine cellulose granules for relaxing bowel and a preparation method and application thereof.
Background
Functional constipation refers to constipation caused by abnormality such as primary, persistent, organic and biochemical abnormality, and dysfunction of colon, rectum and anus, and is a clinically common and frequently occurring disease. The change of life style and diet structure gradually increases the incidence of constipation, especially for old and parturient women, and the incidence of constipation in China gradually increases. Constipation is characterized by too long a residence time of stool in the large intestine, i.e., by too long a residence time of food residues in the intestinal lumen. Too little, too hard, too difficult to expel are the three major symptoms of constipation.
The harm of constipation is gradual, and the harm of long-term intractable constipation to human body is not neglected. Constipation affects appetite and intestinal nutrient absorption of patients, and symptoms such as abdominal distention, abdominal pain, nausea, emesis, inappetence, etc., and even malignant tumor of intestinal tract (such as colon cancer), hepatic encephalopathy, cardiovascular disease and cerebrovascular disease, etc. can be induced. Constipation and some anorectal diseases are closely related, such as hemorrhoids, anal fissure, etc. Therefore, early prevention and rational treatment of constipation will greatly alleviate the serious consequences and social burden associated with constipation.
The traditional Chinese medicine has thousands of years history in treating constipation, and the traditional Chinese medicine is used for guiding the medication by using the whole view and dialectical treatment theory, so that the traditional Chinese medicine can achieve definite curative effect, can obviously improve constipation and reduce recurrence. Chronic constipation is frequently found in middle-aged and elderly people, women and other weak people, and in theory of traditional Chinese medicine, the people are easy to cause constipation due to deficiency of qi and blood and no body fluid moistening in intestinal tracts, namely deficiency constipation, namely syndrome of deficiency and deficiency of qi and blood and syndrome of body fluid and dryness in the intestines of traditional Chinese medicine. For the treatment of constipation of middle-aged and elderly people, the Chinese medicine has definite curative effect, has the characteristics of wide medicine selection surface, flexible formula, small toxic and side effects and the like, and has incomparable advantages of chemical synthetic medicines. As in patent document CN105641335A, CN106806470a, a traditional Chinese medicine composition for relaxing bowel to change constipation is provided, and in patent document CN107183705A, a functional food containing various extracts for relaxing bowel to improve constipation is provided.
Modern medicine mainly uses laxatives, intestinal motility promoting medicines, enemas and suppositories for treatment, can relieve symptoms but cure symptoms but not root cause, and has certain side effects. The principle of treating the head in the consensus of chronic constipation experts in China (2019) is as follows: the dietary fiber and water are added, the lifestyle adjustment such as exercise is increased, and the method is a basic treatment for treating chronic constipation. The dietary fibers comprise soluble dietary fibers and insoluble dietary fibers; bulk laxatives (wheat bran, etc.) are strongly recommended. The gas after the soluble dietary fiber is fermented by intestinal microorganisms can promote intestinal peristalsis, so that the discharge speed of the excrement is increased. The insoluble dietary fiber has strong water absorption and swelling properties, is not easy to be digested by enzymes and is not easy to be glycolyzed by microorganisms in intestinal tracts, so that more solid food residues can be formed, the quality and the volume of the excrement are increased, and the excrement is soft and easy to discharge.
At present, a plurality of products for improving constipation are available in the market, but a plurality of Chinese patent medicines in the market have some problems, and the plurality of Chinese patent medicines contain anthraquinone (rheum officinale, aloe, senna leaf and polygonum multiflorum) irritant components. The laxatives have quick effect and good laxative effect, mainly act through the intestinal internus plexus, are easy to damage the intestinal internus plexus after long-term administration, reduce the reactivity of colon to intestinal content stimulation, have weak colonic exercise function and even lose the function of self defecation, namely the laxative colon, so that the long-term administration of the stimulating laxative is not required, and only short-term or intermittent administration is recommended.
The traditional Chinese medicine composition components and the dietary fiber are combined mutually, so that the traditional Chinese medicine composition can exert a larger curative effect on functional constipation, and has the advantages of less side effect, small drug dependence and obvious long-term curative effect. At present, the products are few in the market, so the products have great market potential.
In view of the above, it is desirable to provide a traditional Chinese medicine cellulose granule for relaxing bowel.
Disclosure of Invention
Aiming at the technical problems, the invention aims to provide traditional Chinese medicine cellulose granules for relaxing bowel, a preparation method and application thereof, which comprehensively treat constipation and improve curative effect; the obtained product is simple, convenient, low in cost and effective, and simultaneously, the bitter taste of a large amount of oral traditional Chinese medicines is avoided.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
in a first aspect, the invention provides traditional Chinese medicine cellulose granules for relaxing bowel, which are prepared from the following raw materials in parts by weight:
according to the technical scheme, the wheat cellulose is insoluble dietary fiber, and the volumetric purgative agent expands after absorbing water in the intestines, so that the stool volume is increased, the intestinal volume is expanded, the intestinal peristalsis is stimulated, the stool reflex is caused, constipation is relieved, the wheat cellulose almost contains no phytic acid, the defect that the traditional cellulose contains phytic acid and immunogenicity is overcome, intestinal inflammation is avoided, and the safety is better.
Xylo-oligosaccharide: is soluble dietary fiber, and is a functional polymeric sugar formed by combining 2-7 xylose molecules with beta-1, 4 glycosidic bonds. Compared with oligosaccharide substances such as soybean oligosaccharide, fructooligosaccharide, isomaltooligosaccharide and the like, the preparation method has the unique advantage that the preparation method can selectively promote the proliferation activity of intestinal bifidobacteria, and the bifidus factor function of the preparation method is 10-20 times that of other polymeric saccharides. The xylooligosaccharide can selectively promote the proliferation activity of bifidobacteria in the intestinal tract, relieve constipation, improve the environment in the intestinal tract and protect the intestinal tract.
Chinese angelica root: replenishing blood, promoting blood circulation, loosening bowel to relieve constipation, and relieving constipation due to blood deficiency.
Cistanche deserticola: nourish kidney yang, moisten intestines and relieve constipation, and relieve constipation due to deficiency of the kidney.
Isomalt: compared with sucrose or white granulated sugar, isomaltulose has the characteristics of relatively low sweetness, low caries, low calorie, no influence on blood sugar and the like.
In the technical scheme, unlike the prior art that most of traditional Chinese medicine compositions are used for treating constipation, the traditional Chinese medicine composition is prepared into granules so as to be convenient for oral administration; in terms of components, the Chinese medicinal composition has only 4 active components, is simple in component, and has good effects of relaxing bowel and preventing constipation by compounding the active components with insoluble dietary fibers, soluble dietary fibers and traditional Chinese medicinal components and a synergistic effect, and the raw materials are common and have very remarkable effects.
As a further preferable mode of the technical scheme, the traditional Chinese medicine cellulose granule is prepared from the following raw materials in parts by weight:
as a further preferable mode of the technical scheme, the traditional Chinese medicine cellulose granule is prepared from the following raw materials in parts by weight:
in a second aspect, the invention provides a preparation method of the traditional Chinese medicine cellulose granules, which comprises the following steps:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 9-12 times of water for 2-3 times, each time for 1-3 hours, filtering after the decoction is completed to obtain filtrate for later use;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure to obtain thick paste; adding a first part of wheat cellulose, uniformly stirring, drying under reduced pressure, and finally crushing and sieving to obtain extract powder for later use;
(4) Uniformly mixing the isomaltulose alcohol sieved in the step (1), the second part of wheat cellulose, the xylooligosaccharide and the extract powder obtained in the step (3), and then granulating, drying, finishing and packaging to obtain the traditional Chinese medicine cellulose granules.
In the technical scheme, firstly, the active ingredients in the angelica and the cistanche are fully extracted by water extraction; and a part of wheat fiber is added into the thick paste and then is dried under reduced pressure, so that the prepared product is loose and easy to crush, the drying time is reduced, and the product is ensured to have no burnt smell brought by common drying and spray drying.
As a further preferable mode of the above technical scheme, in the step (1), the isomalt is crushed and then sieved by a 80-mesh sieve.
As a further preferable mode of the above technical scheme, in the step (2), 200 mesh filtration is performed after the completion of the decoction.
As a further preferable mode of the technical scheme, in the step (3), the specific operation of the reduced pressure concentration is as follows: concentrating under reduced pressure to a relative density of 1.20-1.30 under the conditions of minus 0.06-minus 0.10MPa and a temperature of less than or equal to 70 ℃; the technological parameters of the reduced pressure drying are as follows: -0.06 to-0.10 MPa, 50-70 ℃.
As a further preferable aspect of the above technical solution, in the step (3), the amount of the first part of wheat cellulose is 20 to 30% of the total amount of the wheat cellulose.
As a further preferred option of the above technical solution, in step (4), the granulation uses 85% ethanol as a wetting agent, and the granulation is 14 mesh; the whole grain is 12 mesh.
In a third aspect, the invention also provides application of the traditional Chinese medicine cellulose granules in preparation of medicaments for treating deficiency constipation.
The old people are mainly constipation caused by blood deficiency and yang deficiency, and the constipation caused by blood deficiency and fluid deficiency is caused by the same source of fluid and blood, the intestines are not nourished, and the intestines cannot be moistened due to the blood deficiency and the fluid and blood deficiency, so that the intestines are blood deficiency and intestine dryness; blood is a carrier of qi, and deficiency of blood inevitably leads to qi deficiency, and qi deficiency promotes debilitation and aggravates constipation symptoms. Senile constipation is particularly closely related to kidneys, and the temporary symptoms are based on the theory of ' kidney is stomach ', wherein kidney yin is sufficient to moisten large intestine, so that the stool is smooth, and fire of the gate is sufficient to evaporate body fluid, so that the large intestine is forceful in conduction, wherein the waste dregs of the large intestine are the functional basis and external manifestations of ' kidney is induced to two yin ', so that the temporary symptoms are based on treating kidney, warming kidney and tonifying essence due to yang qi deficiency, nourishing yin and tonifying kidney due to yin fluid deficiency, and the so-called ' kidney governs five fluids, so that the stool is normal due to body fluid. Cistanche is taken to nourish kidney yang, moisten intestines to relieve constipation, and angelica sinensis is used for enriching blood and activating blood, so that the cistanche is suitable for constipation caused by blood deficiency and essence deficiency. Therefore, cistanche and angelica are compounded on the basis of wheat cellulose and xylooligosaccharide, so that the symptoms of people suffering from deficiency constipation can be greatly improved. Therefore, other use forms such as the components provided by the invention, other components or auxiliary materials are added, and the like are all possible, and fall within the scope of the invention which is expected to be protected.
Compared with the prior art, the invention has the following beneficial effects:
1. the traditional Chinese medicine cellulose granule combines the dialectical treatment of the deficiency constipation in the traditional Chinese medicine, selects medicinal materials which can be used for improving the constipation to be compatible, and simultaneously has obvious synergistic effect on the constipation due to the synergistic effect of the insoluble dietary fiber wheat cellulose and the soluble dietary fiber xylooligosaccharide, can greatly improve the deficiency constipation symptom, and has simple and clear components and good efficacy.
2. The traditional Chinese medicine cellulose granule provided by the invention has good brewing taste, thoroughly changes the coarse feeling of wheat bran fiber after being brewed, has less mechanical stimulation to gastrointestinal tract, improves the experience of consumers, and avoids the bitter taste of a large amount of orally taken traditional Chinese medicines.
3. According to the preparation method of the traditional Chinese medicine cellulose granule, part of wheat fiber is added into the traditional Chinese medicine thick paste after extraction and concentration, and then the traditional Chinese medicine thick paste is dried under reduced pressure, so that the prepared product is loose and easy to crush, the drying time is greatly reduced, and the method is rapid and efficient; meanwhile, the quality of the product is ensured, and burnt smell brought out by common drying and spray drying treatment processes is avoided.
4. According to the traditional Chinese medicine cellulose granule provided by the invention, insoluble dietary fiber wheat fiber is specifically selected, so that the weight and volume of the excrement are greatly increased, the excrement is softened, the hardness of the excrement is normalized, the intestinal transit time is shortened, and the excrement is discharged more smoothly; compared with other insoluble dietary fibers, the wheat fiber has high water holding capacity and high swelling power, the dietary fiber content is extremely high (95 percent), the wheat fiber almost does not contain phytic acid, the defect that the traditional cellulose contains phytic acid and immunogenicity is overcome, intestinal inflammation is prevented from being induced, and the safety is better.
5. The traditional Chinese medicine cellulose granule provided by the invention not only can improve beta diversity of intestinal flora, but also can solve intestinal flora disorder caused by constipation, and remodel intestinal flora steady state to relieve constipation.
In a word, the invention surrounds the synergistic effect of the preferable active substances for relaxing bowel and treating constipation, thereby ensuring good curative effect; meanwhile, the preparation method is optimized, the prepared granules are convenient to take, part of wheat fibers are added in the preparation process, the treatment of spray drying and other processes is avoided, the quality of products is ensured, and the large-scale production is easy.
Drawings
FIG. 1 is an analysis of intestinal flora α diversity, wherein (A) Good's coverage index, (B) Chao1 index, (C) Shannon index, (D) Simpson index; in the figure, compared with the control group: * P < 0.001; comparison to model set: the # P is less than 0.05, # P is less than 0.01, # P is less than 0.001.
FIG. 2 shows an analysis of intestinal flora beta diversity, wherein (A) is based on the PCoA profile of Weighted Unifrac and (B) is based on the NMDS analysis of ASV.
FIG. 3 is a graph of different taxonomic level of flora composition analysis, wherein (A) the relative abundance of species at the phylum level, (B) the relative abundance of major species at the phylum level, and (C, D, E) the relative abundance of species at the genus level; in the figure, compared with the control group: * P <0.05, < P < 0.001; comparison to model set: the # P is less than 0.05, # P is less than 0.01, # P is less than 0.001.
Detailed Description
The following description of the embodiments of the present invention will clearly and fully describe the technical aspects of the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, are intended to fall within the scope of the present invention.
The medicinal materials in the invention are purchased through market approaches unless specified otherwise. Wherein, the wheat cellulose is purchased from Guangzhou Mantid biotechnology Co., ltd, and has the specification of WF600-30; xylo-oligosaccharide is purchased from Henan Jianju practice Co., ltd, and has a specification of 95%.
Example 1
A traditional Chinese medicine cellulose granule for relaxing bowel is prepared from the following raw materials in parts by weight:
in this embodiment, a preparation method of the above traditional Chinese medicine cellulose granule is also provided, including the following steps:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving the crushed isomaltulose alcohol with a sieve of 80 meshes for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 10 times of water for 3 times and 2 hr each time, filtering with 200 mesh sieve to obtain filtrate;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure (-0.06-0.10 MPa, less than or equal to 70 ℃) until the relative density is 1.20-1.30 (60+/-5 ℃), thus obtaining thick paste; then adding a first part of wheat cellulose (25% of the total amount), uniformly stirring, drying under reduced pressure (-0.06-0.10 MPa,60 ℃), and finally crushing and sieving with a 80-mesh sieve to obtain extract powder for later use;
(4) Uniformly mixing the isomaltulose alcohol sieved in the step (1), the second part of wheat cellulose, the xylooligosaccharide and the extract powder obtained in the step (3), then using 85% ethanol (the dosage is about 20% of the total amount of the mixture) as a wetting agent to prepare soft materials, granulating by using 14 meshes, and drying at 60+/-5 ℃ until the water content of the granules is controlled below 5%, and finishing the granules by using 12 meshes to obtain dry granules; finally, 6 g/bag of the obtained dry granules are packaged by a composite film, and the traditional Chinese medicine cellulose granule product is obtained.
Example 2
A traditional Chinese medicine cellulose granule for relaxing bowel is prepared from the following raw materials in parts by weight:
in this embodiment, a preparation method of the above traditional Chinese medicine cellulose granule is also provided, including the following steps:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving the crushed isomaltulose alcohol with a sieve of 80 meshes for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 11 times of water for 3 times and 2.5 hr each time, filtering with 200 mesh sieve to obtain filtrate;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure (-0.06-0.10 MPa, less than or equal to 70 ℃) until the relative density is 1.20-1.30 (60+/-5 ℃), thus obtaining thick paste; then adding a first part of wheat cellulose (25% of the total amount), uniformly stirring, drying under reduced pressure (-0.06-0.10 MPa,60 ℃), and finally crushing and sieving with a 80-mesh sieve to obtain extract powder for later use;
(4) Uniformly mixing the isomaltulose alcohol sieved in the step (1), the second part of wheat cellulose, the xylooligosaccharide and the extract powder obtained in the step (3), then using 85% ethanol (the dosage is about 20% of the total amount of the mixture) as a wetting agent to prepare soft materials, granulating by using 14 meshes, and drying at 60+/-5 ℃ until the water content of the granules is controlled below 5%, and finishing the granules by using 12 meshes to obtain dry granules; finally, 6 g/bag of the obtained dry granules are packaged by a composite film, and the traditional Chinese medicine cellulose granule product is obtained.
Example 3
A traditional Chinese medicine cellulose granule for relaxing bowel is prepared from the following raw materials in parts by weight:
in this embodiment, a preparation method of the above traditional Chinese medicine cellulose granule is also provided, including the following steps:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving the crushed isomaltulose alcohol with a sieve of 80 meshes for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 9 times of water for 3 times, each time for 1.5 hr, and filtering with 200 mesh sieve to obtain filtrate;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure (-0.06-0.10 MPa, less than or equal to 70 ℃) until the relative density is 1.20-1.30 (60+/-5 ℃), thus obtaining thick paste; then adding a first part of wheat cellulose (25% of the total amount), uniformly stirring, drying under reduced pressure (-0.06-0.10 MPa,60 ℃), and finally crushing and sieving with a 80-mesh sieve to obtain extract powder for later use;
(4) Uniformly mixing the isomaltulose alcohol sieved in the step (1), the second part of wheat cellulose, the xylooligosaccharide and the extract powder obtained in the step (3), then using 85% ethanol (the dosage is about 20% of the total amount of the mixture) as a wetting agent to prepare soft materials, granulating by using 14 meshes, and drying at 60+/-5 ℃ until the water content of the granules is controlled below 5%, and finishing the granules by using 12 meshes to obtain dry granules; finally, 6 g/bag of the obtained dry granules are packaged by a composite film, and the traditional Chinese medicine cellulose granule product is obtained.
Comparative example 1
The formulation and preparation method were substantially the same as in example 1, except that wheat cellulose was replaced with oat cellulose.
Comparative example 2
The formulation and preparation method were substantially the same as in example 1, except that the xylooligosaccharide was replaced with fructooligosaccharide.
Comparative example 3
The formulation and preparation method are basically the same as in example 1, except that cistanche is replaced with cassia seed.
Comparative example 4
A traditional Chinese medicine cellulose granule for relaxing bowel is prepared from the following raw materials in parts by weight:
in this comparative example, there is also provided a method for preparing the above-mentioned Chinese medicinal cellulose granule, comprising the steps of:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving the crushed isomaltulose alcohol with a sieve of 80 meshes for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 10 times of water for 3 times and 2 hr each time, filtering with 200 mesh sieve to obtain filtrate;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure (-0.06-0.10 MPa, less than or equal to 70 ℃) to obtain a concentrated solution with the relative density of 1.05-1.10 (measured at 60+/-2 ℃), adding isomaltitol with the medicinal material content of 100%, stirring and dissolving uniformly, performing spray drying (the air inlet temperature is 170-180 ℃, the air outlet temperature is 90-95 ℃, the liquid inlet speed is 16-24 rpm, and the atomization frequency is 45 Hz), and sieving the spray dried powder with a 80-mesh sieve for later use;
(4) Uniformly mixing the wheat cellulose, the xylooligosaccharide and the spray-dried powder sieved in the step (3) in a wet granulator, then preparing a soft material by using 85% ethanol (the dosage is about 20% of the total amount), granulating by using 14 meshes, and drying at 60+/-5 ℃ until the water content of the granules is controlled below 5%, and finishing the granules by using 12 meshes to obtain dry granules; finally, 6 g/bag of the obtained dry granules are packaged by a composite film, and the traditional Chinese medicine cellulose granule product is obtained.
The part of the traditional Chinese medicine cellulose granule product prepared in comparative example 4 has a certain burnt smell.
Comparative example 5
A traditional Chinese medicine cellulose granule for relaxing bowel is prepared from the following raw materials in parts by weight:
in this comparative example, there is also provided a method for preparing the above-mentioned Chinese medicinal cellulose granule, comprising the steps of:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving the crushed isomaltulose alcohol with a sieve of 80 meshes for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 10 times of water for 3 times and 2 hr each time, filtering with 200 mesh sieve to obtain filtrate;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure (-0.06-0.10 MPa, less than or equal to 70 ℃) until the relative density is 1.20-1.30 (60+/-5 ℃), thus obtaining thick paste; stirring, drying under reduced pressure (-0.06-0.10 MPa,60 deg.C), pulverizing, and sieving with 80 mesh sieve to obtain extract powder;
(4) Uniformly mixing the isomaltulose alcohol, the wheat cellulose, the xylooligosaccharide obtained in the step (1) and the extract powder obtained in the step (3), then using 85% ethanol (the dosage is about 20% of the total amount of the mixture) as a wetting agent to prepare a soft material, granulating through 14 meshes, drying at 60+/-5 ℃ until the water content of the granules is controlled below 5%, and finishing the granules through 12 meshes to obtain dry granules; finally, 6 g/bag of the obtained dry granules are packaged by a composite film, and the traditional Chinese medicine cellulose granule product is obtained.
The step (3) of the comparative example 5, in which no wheat cellulose was added during the drying under reduced pressure, was difficult to dry the thick paste, and it took more than 48 hours to dry, and the dried product was hard and difficult to pulverize, resulting in a hard texture of the final product; in the step (3) of the embodiment 1, part of wheat cellulose is added in the decompression drying process, and the decompression drying only needs 5-6 hours, so that the drying time is greatly reduced, the preparation is more rapid and efficient, and the method is suitable for industrial production.
Test example 1: animal test
In the test example, a mouse constipation model is established by loperamide hydrochloride, and the effect of the product on constipation of a constipation mouse is evaluated.
1.1 test materials and methods
Preparing loperamide hydrochloride suspension: the loperamide hydrochloride capsule with the concentration of 0.03 percent contains 2mg of loperamide hydrochloride per capsule, and is taken according to the practical dosage and prepared at present.
Preparing ink: accurately weighing 100g of gum arabic, adding 800mL of water, boiling until the solution is transparent, weighing 50g of activated carbon (powder) and adding into the solution, boiling for three times, cooling the solution, adding water to 1000mL, keeping the volume at 4 ℃ in a refrigerator, and shaking uniformly before use.
Sample grouping: in the small intestine exercise animal experiment and the defecation function animal experiment, the product of example 1 was set as formula 1, the product of comparative example 1 was set as formula 2, the product of comparative example 2 was set as formula 3, and the product of comparative example 3 was set as formula 4. In the intestinal flora 16S rRNA sequencing experiment, the product of the example 1 is used as a test group, and is divided into a formula high-dose group and a formula low-dose group according to different dosing amounts.
1.2 test methods
1.2.1 small intestine motion animal experiments
Healthy male SPF-class Kunming mice are 36, 5-6 weeks old, 30-35 g in mass, and after 5 days of adaptive rearing, they are randomly divided into 6 groups of 6. Respectively negative control group, model group, formula 1 group, formula 2 group, formula 3 group and formula 4 group.
The daily gastric lavage dosage of the formula 1, the formula 2, the formula 3 and the formula 4 is 1.2g/kg BW, the control group and the model group are filled with equal volume of distilled water daily, after continuous gastric lavage for 7 days, each group of mice is fasted without water forbidden for 16 hours, and then the model group, the formula 1, the formula 2, the formula 3 and the formula 4 are filled with 3mg/kg BW of loperamide hydrochloride suspension. The control group was perfused with equal volumes of distilled water. After 0.5 hours, groups 1, 2, 3, and 4 were each given ink at the corresponding test drug dose, and the control and model groups were filled with equal volumes of ink. After 25 minutes, the pylorus was cut to the ileocecal region, the length of the intestinal canal was measured as the "total length of small intestine (cm)", and the front from pylorus to ink was measured as the "advanced length of small intestine (cm)". The small intestine thrust rate was calculated as follows: small intestine propulsion (%) = (small intestine propulsion length/small intestine total length) ×100% of the total length of the small intestine
1.2.2 animal experiments with bowel movement function
Healthy male SPF-class Kunming mice are 36, 5-6 weeks old, 30-35 g in mass, and after 5 days of adaptive rearing, they are randomly divided into 6 groups of 6. Respectively negative control group, model group, formula 1 group, formula 2 group, formula 3 group and formula 4 group.
The daily gastric lavage dosage of the formula 1, the formula 2, the formula 3 and the formula 4 is 1.2g/kg BW, the control group and the model group are filled with equal volume of distilled water daily, after continuous gastric lavage for 7 days, each group of mice is fasted without water forbidden for 16 hours, and then the model group, the formula 1, the formula 2, the formula 3 and the formula 4 are filled with loperamide hydrochloride suspension of 6mg/kg BW. The control group was perfused with equal volumes of distilled water. After 0.5 hours, groups 1, 2, 3, and 4 were each given ink at the corresponding test drug dose, and the control and model groups were filled with equal volumes of ink. Single cage feeding, normal drinking water and feeding. And (4) starting timing when the ink filling is finished, recording the time of the mice to discharge the first black stool, collecting the excrement of each group of mice within 5 hours, and recording the total amount and total weight of the discharged black stools.
1.3.3 intestinal flora 16S rRNA sequencing
Healthy male SPF-class Kunming mice are 24, 5-6 weeks old, 30-35 g in mass, and after 5 days of adaptive rearing, they are randomly divided into 4 groups of 6. The control group, the model group, the formula high dose group (3.6 g/kg BW) and the formula low dose group (0.6 g/kg BW) were respectively given. Except for the control group, the other groups were perfused with loperamide hydrochloride at 10mg/kg BW for 14 days to establish a mouse constipation model. On day 8, the high and low dose groups were filled with each dose of the test drug daily, the control group and the model group were given equal volumes of distilled water, and after 7 days of continuous gastric feeding, each group was fasted without water withdrawal for 16 hours, the cecal contents were taken, and the samples were sequenced.
1.3 test results
Data were processed by SPSS27.0 software, data expressed as (x+ -s), and comparisons between groups used one-way anova. P <0.05 indicates that the difference is statistically significant, and the test results are as follows:
1.3.1 Effect on constipation mouse intestinal motility function
The intestinal pushing function was recorded after administration of the corresponding drug for each test group, and the results are shown in table 1. Compared with a control group, the small intestine propulsion rate of the model group is obviously reduced, which indicates that the modeling of the mice is successful; compared with a model group, the medicine group of the formula group can enhance the small intestine propulsion function after drying, and improve the small intestine ink propulsion distance and the ink propulsion rate; compared with different formula groups, the effect of the formula 1 group is obviously better than that of the formula 2-4 groups, and compared with a comparative example, the product of the embodiment of the invention can better promote the small intestine peristalsis of constipation mice.
Table 1: influence on the intestinal motility function of constipation micen＝6)
| Group of | Ink Propulsion (%) |
| Control group | 84±16 |
| Model group | 49±15*** |
| Formulation 1 group | 70±13 ## |
| Formulation 2 group | 61±11 # |
| Formulation 3 group | 63±15 # |
| Formulation 4 group | 66±12 ## |
Note that: p < 0.001 compared to control group; compared with the model group, #P <0.05, #P < 0.01.
1.3.2 Effect on constipation mouse defecation function
The effect on the bowel movement function of constipation mice was recorded after administration of the corresponding drugs for each test group, and the results are shown in Table 2. Compared with a control group, the time for discharging first black stool of the model group is obviously prolonged, and the quantity and quality of black stool discharged in 5 hours are obviously reduced, which indicates that the model building of the mice is successful; after the treatment of each formula drug group, the first granule of black stool discharged in the formula 1 group is obviously shortened, the quantity and weight of black stools discharged in 5 hours are obviously increased, and the intestinal power and the defecation function of the constipation mice can be promoted to different degrees by other formulas; compared with different formula groups, the effect of the formula 1 group is obviously better than that of the formula 2-4 groups, and compared with the comparative example, the product of the embodiment of the invention can better promote the intestinal power and defecation function of constipation mice.
Table 2: influence on the defecation parameters of the constipation micen＝6)
| Group of | Discharge first granule black stool time (min) | Number of black stools (grains) in 5h | Quality of black stool (g) in 5h |
| Control group | 95.21±35.88 | 19.55±4.35 | 0.60±0.15 |
| Model group | 188.75±48.87*** | 8.01±5.21* | 0.25±0.10* |
| Formulation 1 group | 120.60±25.35 ## | 19.95±4.98 # | 0.65±0.25 # |
| Formulation 2 group | 141.50±21.05 # | 16.31±7.05 # | 0.45±0.43 |
| Formulation 3 group | 133.47±27.56 # | 17.18±6.67 # | 0.54±0.16 # |
| Formulation 4 group | 128.52±31.57 # | 18.22±6.25 # | 0.58±0.13 # |
Note that: p < 0.001 compared to control group; compared with the model group, #P <0.05, #P < 0.01.
1.3.3 effects on constipation mice intestinal flora
The Good' S Coverage index was used to evaluate the sequencing depth of the 16S rRNA test samples, and the control group, model group and formulation high and low dose group were all above 0.99, indicating that the sequencing depth covered substantially all species, the data volume was reasonable, and the intestinal microbiota composition could be truly reflected (fig. 1A). The Chao1 index evaluates the abundance of the flora and the Shannon and Simpson indices evaluate the diversity and uniformity of the flora. The α diversity results showed no significant differences between the Chao1 index groups (FIG. 1B); the Shannon and Simpson indices were both significantly reduced (P < 0.001 ) in the model group compared to the control group, and significantly increased (P <0.05, P < 0.01) in the formula high dose group compared to the model group, and more significantly increased (P < 0.001 ) in the formula low dose group (fig. 1C, D). The results show that the species richness among the groups is not obviously different, but the intestinal flora diversity and uniformity of the constipation mice are reduced, obvious callback exists after the intervention of the high-low dose group of the formula, and the effect of the low-dose group is more obvious.
Principal coordinate analysis and non-metric multidimensional scaling analysis were used to assess similarity between microflora, i.e. intestinal flora β diversity. The PCoA cluster plot results show (fig. 2A) that the model group showed a clear distinction in microbial diversity from the control group, whereas the mice after dosing with the formulated drug had microbial diversity closer to the control group than the model group, where the formulated low dose group appeared to overlap mostly with the control group. In the NMDS analysis results (fig. 2B), stress=0.13, there was no overlap between the model group and the control group and the high-low dose treatment group sample points, indicating a significant difference in intestinal flora species composition between the groups. In summary, the product of example 1 of the present invention can improve β diversity of intestinal flora, and has better effect in low dose group.
1.3.4 modulation of the relative abundance of intestinal flora
At the portal level (fig. 3A, B), there was a difference in the composition of the intestinal flora of each group. Compared with a control group, the abundance of Bactoidota (bacteroides) and Firmics (Firmicutes) in the samples of the model group is obviously reduced, and the abundance of Verrucomictobiota (verrucomicron) is obviously increased; formula low dose group intervention can significantly reduce Verrucomicrobiota abundance, raise Bacteroidota and Firmicutes abundance, but the differences are not statistically significant. On the genus level (fig. 3C, D, E), akkermansia (Akkermansia muciniphila) was significantly up-regulated in the model group compared to the control group, whereas bacterioides (Bacteroides) and Alistipes (amycolatopsis) were in a reduced trend. The level of Akkermansia was significantly reduced in both the high and low dose formulation groups compared to the model group, while the relative abundance of bacterioides and alititle was significantly increased. In summary, constipation causes a disturbance of the intestinal flora of mice, and the product intervention in example 1 of the present invention can remodel the intestinal flora homeostasis of mice to relieve constipation.
Test example 2: human body test
The test example refers to the consensus of chronic constipation specialists in China, which is edited in 2019, and Chinese medicine science (9 th edition), proposes the Chinese medicine diagnosis principle of deficiency constipation, and evaluates the medicine effect of the product on the constipation relieving of the deficiency constipation crowd.
2.1 inclusion criteria
Main symptoms are as follows: 1. difficult defecation; 2. hard and dry feces or similar to sheep feces; 3. the defecation is laborious; 4. no more than three times per week of autonomous complete bowel movements; 5. the defecation time interval is more than 3 days.
Secondary symptoms: 1. hard before and soft after defecation, but difficult defecation, sweating and shortness of breath due to effort, hypodynamia after defecation and pale complexion and mental fatigue; 2. dry stool, lusterless complexion, pale lips, palpitation and shortness of breath; 3. dry stool like sheep feces, emaciation, dizziness and tinnitus, soreness of the waist and knees, hectic fever and night sweat; 4. dry or soft stool, difficult discharge, clear and long urine, pale complexion and cold limbs.
Tongue appearance: a red tongue with little or cracked coating, a yellow coating and a thready and rapid pulse.
Is suitable for at least two main symptoms, at least 1 secondary symptoms, namely the patients suffering from deficiency constipation.
2.2 clinical efficacy assessment criteria
The traditional Chinese medicine clinical disease diagnosis curative effect standard is referred to, and is divided into four grades of clinical cure, obvious effect, effective and ineffective, and the evaluation indexes mainly comprise:
clinical recovery: normal defecation is achieved in one month, the stool is soft, and no discomfort is caused once a day.
The effect is shown: the symptoms of difficult defecation in one month are improved, the defecation is smoother, the stool is soft, and the defecation can be performed at least once every other day.
The method is effective: the symptoms of difficult defecation in one month are improved, the defecation is basically smooth, but the occasional defecation time is slightly long, and the defecation is generally performed spontaneously at least once within 3 days, so that the hardness and dryness of the defecation are improved.
Invalidation: spontaneous defecation is still difficult, defecation interval is longer than three days, and symptoms are not obviously improved compared with those before treatment.
2.3 research methods
Case grouping: 30 subjects with constipation were screened for inclusion criteria as described above.
Treatment protocol: the granules were prepared using the method of example 1 of the present invention, 1 bag at a time, 2 bags a day.
2.4 results of the study
After one month of treatment is finished, 30 subjects in the treatment group are recorded for constipation, and the clinical curative effect evaluation is counted and graded to be the number of subjects with clinical recovery, obvious effect, effective and ineffective. The results are shown in Table 3 below.
TABLE 3 results of human efficacy tests
| Group of | The number of people | Healing of the wound | Has obvious effect | Effective and effective | Invalidation of |
| Treatment group | 30 | 6 | 14 | 9 | 1 |
As can be seen from Table 3, the patients after the administration treatment are evaluated as 6 patients with clinical recovery, 14 patients with obvious effect, 9 patients with effective effect and 1 patient with ineffective effect according to the clinical curative effect evaluation standard, the total effective number of the treatment is 29 patients, and the total effective rate is 96.7%.
The applicant states that the technical solution of the present invention is illustrated by the above embodiments, but the present invention is not limited to the above embodiments, i.e. it does not mean that the present invention must be implemented by the above embodiments. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of individual raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
Claims (10)
1. A traditional Chinese medicine cellulose granule for relaxing bowel is characterized by being prepared from the following raw materials in parts by weight:
2. the traditional Chinese medicine cellulose granule for relaxing bowel according to claim 1 is characterized by being prepared from the following raw materials in parts by weight:
3. the traditional Chinese medicine cellulose granule for relaxing bowel according to claim 1 is characterized by being prepared from the following raw materials in parts by weight:
4. a method for preparing the traditional Chinese medicine cellulose granules according to any one of claims 1 to 3, which is characterized by comprising the following steps:
(1) Weighing wheat cellulose, xylooligosaccharide, chinese angelica, cistanche and isomaltulose alcohol according to the amount, crushing the isomaltulose alcohol, and sieving for standby;
(2) Decocting radix Angelicae sinensis and herba cistanches with 9-12 times of water for 2-3 times, each time for 1-3 hours, filtering after the decoction is completed to obtain filtrate for later use;
(3) Concentrating the filtrate obtained in the step (2) under reduced pressure to obtain thick paste; adding a first part of wheat cellulose, uniformly stirring, drying under reduced pressure, and finally crushing and sieving to obtain extract powder for later use;
(4) Uniformly mixing the isomaltulose alcohol sieved in the step (1), the second part of wheat cellulose, the xylooligosaccharide and the extract powder obtained in the step (3), and then granulating, drying, finishing and packaging to obtain the traditional Chinese medicine cellulose granules.
5. The process according to claim 4, wherein in the step (1), isomalt is crushed and then sieved with an 80-mesh sieve.
6. The method according to claim 4, wherein in the step (2), 200 mesh filtration is performed after the completion of the decoction.
7. The method according to claim 4, wherein in the step (3), the specific operation of concentrating under reduced pressure is: concentrating under reduced pressure to a relative density of 1.20-1.30 under the conditions of minus 0.06-minus 0.10MPa and a temperature of less than or equal to 70 ℃; the technological parameters of the reduced pressure drying are as follows: -0.06 to-0.10 MPa, 50-70 ℃.
8. The process according to claim 4, wherein in step (3), the amount of the first portion of the wheat cellulose is 20 to 30% of the total amount of the wheat cellulose.
9. The process according to claim 4, wherein in step (4), the granulation is performed using 85% ethanol as a wetting agent, and 14 mesh granulation is performed; the whole grain is 12 mesh.
10. The use of the traditional Chinese medicine cellulose granules according to any one of claims 1 to 3 in the preparation of a medicament for treating deficiency constipation.
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