Method for preparing preparation for treating habitual diarrhea from traditional Chinese medicine pomelo fruit and application
阅读说明：本技术 中药材柚果制备治疗习惯性腹泻制剂的方法及应用 (Method for preparing preparation for treating habitual diarrhea from traditional Chinese medicine pomelo fruit and application ) 是由 古练权 于 2021-02-04 设计创作，主要内容包括：本发明公开了一种中药材柚果制备治疗习惯性腹泻制剂的方法及应用。柚果是中药材新品种(广东省中药材标准,2011年版),为梅州柚的幼果经干燥加工制得。本发明属于中药科学技术领域。本发明发现,柚果及其制剂能有效治疗非感染性(功能性)习惯性腹泻病症,开发了柚果及其制剂新的治疗病症用途。治疗习惯性腹泻的药用有效成分为柚果及以柚果为原料制备的药用制剂。柚果制剂的制备方法是将柚果粉碎,获得柚果全粉,再与药用辅料混合,制备成片剂、胶囊剂、滴丸剂及缓释剂等。本发明对柚果及其制剂进行了相关实验,证明了对习惯性腹泻治疗的有效性,使用安全。(The invention discloses a method for preparing a preparation for treating habitual diarrhea by using a traditional Chinese medicine pomelo fruit and application thereof. The pomelo fruit is a new variety of Chinese medicinal materials (standard of Chinese medicinal materials in Guangdong province, 2011 edition), and is prepared by drying young fruits of Citrus paradisi. The invention belongs to the technical field of traditional Chinese medicine science. The invention discovers that the pomelo fruit and the preparation thereof can effectively treat the non-infectious (functional) habitual diarrhea, and develops the new purpose of treating the diseases of the pomelo fruit and the preparation thereof. The medicinal effective component for treating habitual diarrhea is pomelo fruit and medicinal preparation prepared from pomelo fruit as raw material. The preparation method of fructus Citri Grandis comprises pulverizing fructus Citri Grandis to obtain powder, mixing with medicinal adjuvants, and making into tablet, capsule, dripping pill, sustained release preparation, etc. The invention carries out relevant experiments on the pomelo fruit and the preparation thereof, proves the effectiveness of treatment on the habitual diarrhea and has safe use.)
1. The application of Chinese medicinal material pomelo fruit in preparing medicine for treating habitual diarrhea is disclosed.
2. A pomelo fruit preparation for treating habitual diarrhea is characterized in that the pomelo fruit preparation is prepared by taking a traditional Chinese medicine pomelo fruit as a raw material, taking whole pomelo fruit powder obtained by crushing as an intermediate, and mixing with pharmaceutical auxiliary materials.
3. The pomelo fruit preparation for treating habitual diarrhea according to claim 2, wherein the pomelo fruit preparation is in the form of tablets, capsules, dripping pills or sustained-release preparations.
4. The preparation method of the pomelo fruit preparation for treating habitual diarrhea of claim 2 or 3, wherein the whole pomelo fruit powder obtained by crushing pomelo fruit is mixed with various pharmaceutical excipients and prepared into tablets, capsules, dripping pills, sustained-release agents and the like.
Technical Field
The invention relates to the technical field of traditional Chinese medicine science, in particular to a method for preparing a preparation for treating habitual diarrhea from a traditional Chinese medicine pomelo fruit and application of the preparation.
Background
The pomelo fruit, i.e. young fruit of Citrus paradisi (harvested at diameter of 3-7 cm), is prepared by drying and processing. Is a novel high-quality traditional Chinese medicine material with characteristics of Meizhou origin, namely 'traditional Chinese medicine material standard in Guangdong province, 2011 edition'.
According to the traditional Chinese medicine, the pomelo fruit has the functions of relieving epigastric distention, promoting qi circulation, invigorating stomach and promoting digestion. Can be used for treating dyspepsia, alcoholic intoxication, abdominal psychroalgia, emesis, and diarrhea. The main effective component of the Meizhou pomelo is naringin (the content is more than or equal to 20 percent), and other components are mainly different flavonoid compounds and polysaccharide, so the Meizhou pomelo has good medicinal properties.
Habitual diarrhea is a common functional gastrointestinal disorder. Office people, white-collar people, especially middle-aged and old people are most susceptible to the disease. The disease is repeated diarrhea, so that the patient is nervous, bellyache, urgent defecation, frequent defecation and the like, but the disease is not cured for a long time without pathogenic viruses or bacteria in laboratory examination. Belongs to a functional disease with high incidence in modern people, and the patients account for more than 1/3 of the special clinic of gastrointestinal tract. At present, no specific medicine aiming at the disease exists clinically.
By deeply understanding the pharmacology of the traditional Chinese medicines of the pummelo fruit in Meizhou and combining the characteristic analysis of the active substances of the pummelo fruit, the pummelo fruit has the functions of 'widening middle energizer and promoting qi circulation, invigorating stomach and promoting digestion, abdominal psychroalgia, nausea and vomiting and diarrhea', can regulate and relieve adverse symptoms generated by gastrointestinal tract disorder, and has great development potential and value in the aspect of treating non-infectious (functional) habitual diarrhea and other gastrointestinal tract diseases.
Through a large amount of research, many traditional Chinese medicines contain flavonoid glycoside active ingredients. The traditional Chinese medicine composition has no obvious killing effect on bacteria, viruses and pathological cells, but can correct the disordered state of the organism through action mechanisms such as special regulation (including immune regulation), balance (deficiency and accumulation, cold and heat, dispersion and accumulation) and the like, so as to achieve the effects of strengthening the body resistance and consolidating the constitution, namely, the traditional Chinese medicine composition has a diversity regulation function on the gastrointestinal tract of the organism.
Naringin, the main medicinal component in pomelo fruit of Meizhou, belongs to flavanone glycoside. Other main components comprise narirutin (dihydroflavonoid glycoside), rhoifolin (flavonoid glycoside), naringenin (naringenin) and the like, theoretically have good oxidation resistance, and harmful gas generated in gastrointestinal tracts is reduced.
Naringin belongs to flavanone compound and is very unstable in property; under the condition of aqueous solution, the catalyst is easy to be oxidized into complex oxidation products. In addition, naringin is easily dissolved in water, and the active ingredients of naringin and other flavonoid ingredients of the extract of the pomelo fruit obtained by the water extraction method are greatly lost, and the ingredients become very complex, so that the drug effect is directly reduced, and the unknown side effect is increased.
Disclosure of Invention
The first purpose of the invention is to provide a method for preparing a preparation for treating habitual diarrhea from a traditional Chinese medicine pomelo fruit.
The second purpose of the invention is to provide an application of a traditional Chinese medicine pomelo fruit in preparing a preparation for treating habitual diarrhea.
The first purpose of the invention is realized by the following technical scheme:
a pomelo fruit preparation for treating habitual diarrhea is prepared by taking pomelo fruits as raw materials, taking pomelo fruit powder obtained by crushing as an intermediate, and mixing with pharmaceutical auxiliary materials to prepare the pomelo fruit preparation.
Preferably, the dosage forms of the pomelo fruit preparation are tablets, capsules, dripping pills and sustained release preparations.
Preferably, the whole powder of the pomelo fruit obtained by crushing the pomelo fruit is mixed with various pharmaceutical excipients and prepared into tablets, capsules, dripping pills, sustained-release agents and the like.
The inventor establishes a high-quality and genuine resource base of the Meizhou pomelo medicinal materials. Through comprehensive material basic research and identification of pomelo fruit resources from different sources, the resource with the best quality and stable property is selected as a raw material source for preparing pomelo fruit medicinal materials and preparations thereof. Develops a whole anhydrous pomelo fruit powder preparation process. Provides raw materials with high quality, high stability and high drug property for preparing the pomelo fruit preparation.
The medicinal preparation which has better medicinal effect and pharmacokinetic property, more stable quality and more convenient use is prepared by taking the Chinese medicinal material pomelo fruit as a raw material through a scientific processing technology, and is an important direction for the scientific and technical development of the traditional Chinese medicine.
The second purpose of the invention is realized by applying the traditional Chinese medicine pomelo fruit in preparing the medicine for treating the habitual diarrhea.
The invention has the following advantages:
(1) the medicinal functions of the pomelo fruit recorded in the Guangdong province Chinese medicinal material standard (2011 edition) are basically described by the theory of traditional Chinese medicine, and do not relate to the case of treating specific diseases. The invention applies the pomelo fruit and the preparation thereof to the treatment of non-infectious (functional) habitual diarrhea, and discloses a new application of the pomelo fruit and the preparation thereof in the aspect of treating diseases.
(2) The invention takes the traditional Chinese medicine pomelo fruit as a raw material, obtains the pomelo fruit powder as an intermediate after direct crushing and refining, and mixes the pomelo fruit powder with various proper auxiliary materials to prepare different medicinal pomelo fruit preparations. The preparation process is simple, the active ingredients in the product can be completely retained, the product quality is controllable, the use is convenient, and the product can be suitable for people with different requirements.
(3) The invention carries out relevant experiments on the pomelo fruit and the preparation thereof, and proves the effectiveness and the safety of the treatment of the habitual diarrhea.
Drawings
Fig. 1 is a liquid chromatogram of the whole grapefruit powder prepared in example 1 of the present invention.
In figure 1, A is naringin reference substance, B is pomelo fruit powder, and C is blank solvent.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below. The drawings are only for purposes of illustration and are not intended to be limiting, and are merely schematic and non-limiting. For those skilled in the art to which the invention pertains, several simple deductions or substitutions can be made without departing from the spirit of the invention, and all shall be considered as belonging to the protection scope of the invention.
The parts, percentages and parts in the examples are by mass unless otherwise specified.
Example 1 preparation of Whole grapefruit powder
Selecting well-preserved and dried Meizhou pomelo, slicing, crushing and screening by a 80-mesh sieve; removing impurities to obtain off-white powder, namely the shaddock fruit full powder.
Through liquid chromatography detection, the naringin content in the whole powder of pomelo fruit is 22.83%, as shown in figure 1, A is naringin reference substance, B is whole powder of pomelo fruit, and C is blank solvent.
The instrument comprises the following steps: shimadzu LC20AB high performance liquid chromatograph.
A chromatographic column: agilent eclipse XDB-C18, 4.6X 250mm, 5 μm.
Chromatographic conditions are as follows: the mobile phase is methanol-acetic acid-water (35:4:61, volume ratio), the flow rate is 0.8mL/min, and the detection wavelength is 283 nm.
EXAMPLE 2 preparation of pomelo fruit tablets
80 parts of the shaddock fruit powder prepared in the example 1, 10 parts of crospovidone (PVPP), 4 parts of microcrystalline cellulose (MCC), 4 parts of sodium carboxymethylcellulose (CMC-Na) and 2 parts of vitamin C are uniformly mixed, sprayed and moistened by ethanol with the volume fraction of 95% and tableted. The specification is 0.3 g/tablet, and each tablet contains more than or equal to 50mg of naringin as an effective component.
EXAMPLE 3 preparation of pomelo fruit capsules
80 parts of the pomelo fruit powder prepared in the example 1, 10 parts of crospovidone (PVPP), 4 parts of microcrystalline cellulose (MCC), 4 parts of sodium carboxymethylcellulose (CMC-Na) and 2 parts of vitamin C are uniformly mixed and then encapsulated. The specification is 0.3 g/grain, and each grain contains more than or equal to 50mg of active ingredient naringin.
EXAMPLE 4 preparation of pomelo fruit drops
20 parts of polyethylene glycol-4000 (PED-4000), 20 parts of polyethylene glycol-6000 (PED-6000) and 8 parts of glycerol are uniformly mixed, and the mixture is heated to 80-90 ℃ to be in a molten state. Mixing 50 parts of pomelo fruit powder and 2 parts of vitamin C, spraying and wetting with 95% ethanol by volume fraction, uniformly mixing with PEG molten liquid under stirring, and making into dripping pills. The specification is 3-4 mm/pill, and each gram of the dripping pill contains more than or equal to 100mg of naringin as an effective component.
EXAMPLE 5 preparation of Slow Release agent for grapefruit fruit
Taking 50 parts of pomelo fruit powder, 10 parts of sodium carboxymethylcellulose (CMC-Na), 26 parts of hydroxypropyl methylcellulose (HPMC K100M), 10 parts of microcrystalline cellulose (MCC) and 2 parts of magnesium stearate. 2 parts of vitamin C, uniformly mixing, spraying and wetting by using ethanol with the volume fraction of 95%, tabletting and drying. The specification is 0.3 g/tablet, and each tablet contains more than or equal to 30mg of naringin as an effective component.
High lactose diarrhea animal model test pomelo fruit powder for treating habitual diarrhea symptom
(1) Animal model of high lactose diarrhea
Lactase is deficient in the human digestive system and lactose is not digested and absorbed in the small intestine. Lactose enters large intestine, and is fermented to produce a large amount of acidic substances and gases (carbon dioxide, sulfur-containing gas and the like), which cause symptoms such as abdominal pain, abdominal distension, diarrhea, borborborygmus and the like, and is called lactose intolerance. This symptom is similar to the clinically common symptom of habitual diarrhea. The rats also have lactose intolerance, so a pathological model of the diarrhea of the rats can be established by a high-lactose feeding method for research. This test model is currently the method used to evaluate the efficacy of drug therapy (functional or non-infectious) of habitual diarrhea. The present example references a method reported and modified according to the experimental objectives.
(2) Test method and evaluation content
The test method comprises the following steps:
30 wistar adult rats were randomly divided into a blank control group (10), a high lactose group (10) and a high lactose/pomelo fruit treatment group. The control group was fed with normal standard; the high lactose group was fed with 60 wt lactose; the feeding conditions of the high lactose/pomelo treated group were the same as those of the high lactose group, and administration of the whole pomelo powder was started on day 3 of the trial (the whole pomelo powder was orally administered to each rat 3 times a day, 10 mg/rat each time). The test time is 15 days.
Evaluation content: and observing the change condition of the body weight, the water content of the excrement and the anus state. From test day 1, each day will be detected, observed and recorded.
(3) Test conditions and results
The change of body weight: the total body weight of the control group steadily increased over the 15 day period, with nearly 23% weight gain. The total body weight in the high lactose group decreased slowly by 5% within 5 days of the start of the experiment. Body weight slowly rose later until the end of the test, increasing nearly 7% of body weight. The high lactose/pomelo treated group slowly declined by 4% within 5 days of the start of the trial, after which the body weight steadily rose, increasing nearly 16% by the end of the trial.
Water content of feces: the water content of the feces discharged from the control group remained stable throughout the 15 day test period. The water content of feces from the high lactose group increased by approximately 130% compared to the control group (compared to the control group) within 5 days of the start of the test, and thereafter stabilized substantially high until the end of the test. The water content of feces from the high lactose/pomelo treated group increased by 85% within 5 days of the start of the test, and then decreased steadily until the end of the test, returning substantially to the control group level.
And (3) anus state observation: the anus of the control group rat is kept in a normal state all the time during the 15-day test period, and abnormal red swelling and effusion are not generated. The anus of the rats in the high lactose group showed red swelling from day 3 of the test and did not regress. By day 10 of the experiment, 50% of the rats developed a red, swollen, darkened anus and fluid accumulation. The rats in the high lactose/pomelo treated group all developed symptoms of redness and swelling to varying degrees within 5 days of the start of the test. The red swelling subsided slowly thereafter, and by day 10 of the test, the red swelling subsided substantially.
The test results show that the pomelo fruit whole powder can effectively relieve the symptoms of diarrhea induced by high lactose.
Example of treatment of patients with habitual diarrhea (volunteers)
Volunteers were retired persons (patients) with typical habitual diarrhea symptoms. Before taking the medicine, the number of diarrhea times of most patients is more than 2.5 times per day. The test period was 30 days.
Test drugs: pomelo fruit/tablet/capsule/dripping pill/sustained release preparation, the specification refers to the preparation of the second to the fifth embodiment.
The test method comprises the following steps: the volunteers participated in the test without changing the original life style and eating habits. The number of diarrhea and symptoms were recorded every day from 5 days before the trial. The pomelo fruit slices are taken orally 3 times a day (once in the morning, at noon and at night), 3 tablets each time. After the test is finished, a statistical profile is required to be provided, and the content comprises the average times of defecating every day and the subjective feeling of the disease.
Characteristic case 1
Sex: for male
Age: 62
Symptoms are: habitual diarrhea has a 5-year history, with an average of 3.0 diarrhea per day.
The medication condition is as follows: the tablet is taken orally three times every day (once in the morning, in the middle of the morning and once in the evening), and the original life style and dietary habits are not changed.
And (3) test results: from day 3, the number of diarrhea per day began to decrease, and the degree of diarrhea was reduced, and the fecal status began to be normal; from day 10, normal defecation was changed to 1.8 times per day.
Subjective feeling: the food has strong irritation, and greasy food or wine can be repeatedly eaten and recovered to normal in the next day; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Second case of characteristic
Sex: woman
Age: 65
Symptoms are: habitual diarrhea has a 6-year history, with an average of 3.5 diarrhea per day.
The medication condition is as follows: the pomelo fruit capsule is orally taken three times (once in the morning, in the middle of the morning and at night) every day, and the original life style and dietary habits are not changed.
And (3) test results: from the third day, the diarrhea frequency per day begins to decrease, the diarrhea degree is reduced, and the excrement condition begins to be normal; from the tenth day, normal defecation was changed to 1.5 times per day.
Subjective feeling: the food has strong irritation, and greasy food or wine can be repeatedly eaten and recovered to normal in the next day; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Third case of disease
Sex: for male
Age: 73
Symptoms are: habitual diarrhea has a history of 8 years, with an average of 3.3 diarrhea per day.
The medication condition is as follows: the pomelo fruit dripping pill is orally taken three times (once in the morning, in the middle of the morning and at night) every day, and the original life style and dietary habits are not changed.
And (3) test results: from day 4 onwards, the number of diarrhea per day began to decrease, and the degree of diarrhea decreased; from day 6, fecal status began to be normal; from day 10, it became normal defecation 1.5 times per day, with occasional mild diarrhea (about once in 4 days); from day 20, normal defecation was changed to 1.2 times per day.
Subjective feeling: no discomfort or side effect caused by taking the medicine is generated in the whole process.
Four characteristic cases
Sex: for male
Age: 61
Symptoms are: habitual diarrhea has a 4-year history, with an average of 2.5 diarrhea per day.
The medication condition is as follows: the pomelo fruit granule is orally taken three times (once in the morning, in the middle of the morning and at night) every day, and the original life style and dietary habits are not changed.
And (3) test results: from day 2 onwards, the number of diarrhea per day began to decrease, and the degree of diarrhea decreased; from day 7, normal defecation was changed to 1.2 times per day.
Subjective feeling: no discomfort or side effect caused by taking the medicine is generated in the whole process.
Five characteristic cases
Sex: woman
Age: 58
Symptoms are: habitual diarrhea has a 4-year history, with an average of 3.2 diarrhea per day.
The medication condition is as follows: the slow-release preparation is orally taken three times (once in the morning, in the middle and at night) every day without changing the original life style and eating habits.
And (3) test results: from day 2 onwards, the degree of diarrhea was reduced; from day 3, the number of diarrhea was reduced and the stool morphology began to be normal; from day 15, normal defecation was changed to 1.5 times per day.
Subjective feeling: the food has strong irritation, and greasy food or wine can be repeatedly eaten and recovered to normal in the next day; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Six characteristic cases
Sex: for male
Age: 67
Symptoms are: habitual diarrhea has a 5-year history, with an average of 3.1 diarrhea per day.
The medication condition is as follows: the tablet is taken orally three times every day (once in the morning, in the middle of the morning and once in the evening), and the original life style and dietary habits are not changed.
And (3) test results: from day 3, the diarrhea degree is reduced, the diarrhea frequency is reduced, and the stool form begins to be normal; from day 15, normal defecation was changed to 1.2 times per day.
Subjective feeling: the repeated eating of food, greasy food or wine with strong irritation and the like does not occur; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Seven characteristic cases
Sex: for male
Age: 68
Symptoms are: habitual diarrhea has a 6-year history, with an average of 3.6 diarrhea per day.
The medication condition is as follows: the tablet is taken orally three times every day (once in the morning, in the middle of the morning and once in the evening), and the original life style and dietary habits are not changed.
And (3) test results: from day 3 onwards, the number of diarrhea per day began to decrease, and the degree of diarrhea decreased; from day 10, fecal status began to be normal; from day 20, normal defecation became 1.2 times daily, with occasional mild diarrhea (about once on day 3).
Subjective feeling: the food has strong irritation, and greasy food or wine can be repeatedly eaten and recovered to normal in the next day; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Eight characteristic cases
Sex: for male
Age: 74
Symptoms are: habitual diarrhea has a 9-year history, with an average of 2.8 diarrhea per day.
The medication condition is as follows: the slow-release preparation is orally taken three times (once in the morning, in the middle and at night) every day without changing the original life style and eating habits.
And (3) test results: from day 2 onwards, the number of diarrhea per day began to decrease, and the degree of diarrhea decreased; from day 5, fecal status began to be normal; from day 12, normal defecation was changed to 1.6 times per day.
Subjective feeling: strong stimulation to eat, and no repeated use of greasy food or alcohol; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Nine characteristic cases
Sex: woman
Age: 65
Symptoms are: habitual diarrhea has a 4-year history, with an average of 2.4 diarrhea per day.
The medication condition is as follows: the tablet is taken orally three times every day (once in the morning, in the middle of the morning and once in the evening), and the original life style and dietary habits are not changed.
And (3) test results: from day 3 onwards, the number of diarrhea per day began to decrease, and the degree of diarrhea decreased; from day 10, the diarrhea degree was significantly improved and the fecal status began to be normal; from day 20, normal defecation was changed to 1.5 times per day.
Subjective feeling: the food has strong irritation, is slightly repeated when people eat greasy food or drink wine, and is recovered to be normal the next day; no discomfort or side effect caused by taking the medicine is generated in the whole process.
Ten characteristic cases
Sex: woman
Age: 72
Symptoms are: habitual diarrhea has a history of 8 years, with an average of 3.5 diarrhea per day.
The medication condition is as follows: the tablet is taken orally three times every day (once in the morning, in the middle of the morning and once in the evening), and the original life style and dietary habits are not changed.
And (3) test results: from day 3 onwards, the number of diarrhea per day began to decrease, and the degree of diarrhea decreased; the diarrhea degree is obviously improved from the 10 th day; from day 20, fecal conditions began to defecate normally 1.8 times.
Subjective feeling: no discomfort or side effect caused by taking the medicine is generated in the whole process.