CN106727481B - Application of chlorogenic acid in preparation of appetite-enhancing drugs or health care products - Google Patents
Application of chlorogenic acid in preparation of appetite-enhancing drugs or health care products Download PDFInfo
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- CN106727481B CN106727481B CN201611130322.3A CN201611130322A CN106727481B CN 106727481 B CN106727481 B CN 106727481B CN 201611130322 A CN201611130322 A CN 201611130322A CN 106727481 B CN106727481 B CN 106727481B
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- chlorogenic acid
- preparation
- appetite
- anorexia
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- 239000006041 probiotic Substances 0.000 description 1
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- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 235000018770 reduced food intake Nutrition 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
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- 229960000553 somatostatin Drugs 0.000 description 1
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- 230000004580 weight loss Effects 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses application of chlorogenic acid in preparation of appetite-enhancing medicines or health-care products. The drug effect experiment shows that the chlorogenic acid can greatly improve the food intake of anorexia rats and increase the weight of the anorexia rats, and the effect is equivalent to that of a commercially available drug Jiangzhong stomach strengthening digestion promoting tablet, which shows that the chlorogenic acid has obvious appetite enhancing effect, can be used for treating anorexia and has wide clinical application prospect.
Description
Technical Field
The invention relates to application of chlorogenic acid in preparation of appetite-enhancing medicines or health-care products, and belongs to the field of medicines.
Background
Normal people generally have good appetite, which is one of important signs for judging the health of the human body. Thus, appetite abnormalities often indicate that the human body is in a pathological state. Anorexia is the most common abnormal appetite symptom in clinic, usually caused by disease influence, improper feeding or obvious reduction of food intake or food intake caused by emotional factors, and has obvious harm to human health: the light people have the problems of reduced food intake, weight loss, sallow complexion, serious patients with malnutrition, low immunity, metabolism, endocrine disturbance and the like, and even can have cachexia and body failure caused by extremely lack of nutrition, thus endangering life.
Anorexia is a common disease in children, and is frequently found in children aged 1-6 years. Anorexia patients have long-term anorexia or anorexia, and can be eating inappetence, even refusal to eat, malnutrition, anemia, rickets and hypoimmunity, recurrent respiratory tract infection, and different degrees of influence on growth and development, nutritional status and intelligence development of children.
Therefore, it is important to develop a medicament or health-care product with the effect of enhancing appetite, especially a medicament or health-care product with the effect of treating anorexia.
Disclosure of Invention
The invention aims to provide application of chlorogenic acid in preparation of appetite-enhancing medicines or health-care products.
The invention provides application of chlorogenic acid in preparation of medicines or health products for enhancing appetite.
Further, the medicine or the health care product has the efficacy of treating and/or preventing anorexia.
Further, the medicine or the health care product has the efficacy of treating and/or preventing infantile anorexia.
Further, the medicine or the health care product has the function of regulating the ghrelin-appetite center.
Further, the medicine or health care product has the functions of improving the concentration of beta-EP, reducing the concentration of CCK-8, improving the expression level of VIP or reducing the expression level of SS.
Further, the medicine or the health care product has the functions of improving the beta-EP concentration in hypothalamus, antrum and blood plasma, reducing the CCK-8 concentration in hypothalamus and blood plasma, improving the VIP expression level in the fundus tissue and jejunum tissue and reducing the SS expression level in the fundus tissue and jejunum tissue.
Further, the medicine or the health care product has the efficacy of improving immunity.
Further, the medicine or health care product has the efficacy of improving spleen index, thymus index, serum IL-2 or IL-6.
Further, the medicine or health care product is a preparation prepared by taking effective amount of chlorogenic acid as an active ingredient and adding auxiliary materials or auxiliary ingredients acceptable in the medicine or health care product.
Further, the auxiliary components are other components with the effect of enhancing appetite, and can comprise Chinese medicinal components such as liquorice, dried orange peel, hawthorn, dark plum, digestive enzyme components and/or probiotic components and the like.
Furthermore, the single chlorogenic acid form or the compound effective pharmaceutical ingredient consisting of chlorogenic acid and pharmaceutical ingredients with similar effects is added with auxiliary materials acceptable in pharmacy or health care products, and the corresponding oral preparation form of the medicament is obtained through corresponding preparation methods or processes.
Further, the above acceptable excipients may include, for example, excipients or auxiliary ingredients acceptable and used in tablets, granules, powders, capsules, suspensions, solutions, buccal agents, pellets, granules or pills.
Further, the preparation is an oral preparation.
Further, the preparation is tablets, granules, powder, capsules, suspension, solution, pills, buccal agents, pellets or medicinal granules.
Further, each preparation unit of the medicine or the health care product contains 30-500 mg of chlorogenic acid.
The invention provides application of chlorogenic acid in preparation of medicines or health products for enhancing appetite. The drug effect experiment shows that the chlorogenic acid can greatly improve the food intake of anorexia rats and increase the weight of the anorexia rats, and the effect is equivalent to that of a commercially available drug Jiangzhong stomach strengthening digestion promoting tablet, which shows that the chlorogenic acid has obvious appetite enhancing effect, can be used for treating anorexia and has wide clinical application prospect.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Detailed Description
The materials and equipment used in the embodiments of the present invention are all known products and are obtained by purchasing commercially available products.
Example 1 animal experiments with chlorogenic acid to enhance appetite
1. Animal model building
According to the situation that fat and protein in the diet of children 2-6 years old in China reach higher level and the intake of calcium, iron, riboflavin and the like is lower, the special feed for modeling has high crude protein and crude fat content and low contents of various minerals and various vitamins, particularly low contents of calcium, iron and riboflavin, and the model causes are the same as the main causes of infantile anorexia. In addition, the animals can eat food freely in the experiment, and the situation is very similar to the clinical situation.
50 healthy SD rats with the mass of 60+/-10 g and male and female half of the healthy SD rats are selected 1 week after weaning. After 50 rats were acclimatized for 1 week, they were divided into 5 groups of 10 according to the digital random table method. Group A: blank control group. Group B: model control group. Group C: chlorogenic acid high dose group, simply referred to as high dose group. Group D: chlorogenic acid small dose group, short small dose group. E positive control group.
All animals were fed under the same conditions (room temperature 20-24 ℃ C., relative humidity 50%). Group A was fed with conventional feed (i.e., normal adult feed M02 for rats and mice), and the remaining 4 groups were fed with special feed. The special feed is prepared by mixing fish floss, milk powder, corn flour, soybean powder, white sugar, fresh egg and fresh fat meat at a ratio of 1:1:1:2:1:1.8:2, kneading into biscuit shape, air drying, and refrigerating at 4deg.C. All animals were kept in single cages and fed water ad libitum for 4 weeks. The food intake and the body mass are recorded every day, so that the average food intake of the molding rats is reduced by 20% -30% or the body mass is lower than that of the control group by 10% -15%, and the molding is successful after the molding is maintained for 4 days, and the stomach filling of each group is started after the molding is successful. The A group and the B group are filled with equal volume of distilled water every day, the C group and the D group are filled with 2mL of chlorogenic acid water solution with corresponding dosage, and the E group is filled with 2mL of tablet suspension for strengthening stomach and promoting digestion every day. Each group of rats was gavaged 1 time a day, followed by 16d of gavage.
2. Specimen collection
Observing the feed intake and the weight of animals every day, collecting blood from eyeballs of all the animals in the same time period after the test is finished, storing the animals in two groups, adding aprotinin 20ul/ml into each tube before one group of blood collection, injecting the blood into a heparin tube after the orbit blood collection, fully shaking uniformly, standing, separating plasma by centrifugation at 4000r/min for 10min at low temperature, and storing the plasma at-70 ℃ to be tested. Another group of eyesockets are taken and injected into a heparin tube for shaking uniformly, standing, and then centrifuging at a low temperature of 4000r/min for 10min to separate to obtain serum which is stored at-70 ℃ to be measured; rapidly breaking the head of a rat after taking blood, taking out the whole brain and stomach, boiling in boiling physiological saline for 5min, separating hypothalamus, scraping gastric sinus mucosa, respectively weighing by an analytical balance, adding 1ml of 1mol/L glacial acetic acid into a glass homogenizing tube, fully homogenizing, pouring into a plastic test tube, standing at room temperature for 100min, adding 1ml of NaOH, centrifuging at 4000r/min for 10min at low temperature, and taking supernatant to be measured at-70 ℃ for preservation. Meanwhile, the spleen and thymus are planed and taken, and jejunum section tissues are taken.
4. Detection method
Determination of spleen index and thymus index: the weights of spleen and thymus were weighed by an electronic balance and calculated as mg/g body weight, respectively. Serum IL-2, IL-6 assay: the detection is carried out by adopting a put-free method respectively (the specific method is operated according to the instruction of the kit). Determination of CCK-8, beta-EP: the measurement was performed by radioimmunoassay (specific method was performed by loading the sample according to radioimmunocartridge instructions, using an automated 16-probe r counter for a few seconds standard curve from America and printing the results). Measurement of fundus tissue, jejunum segment VIP, SS: the area is 1.5cm multiplied by 1cm, and the sample is fixed, embedded and sliced, covered with polylysine and subjected to HE dyeing and then to be measured; after the stomach tissue sections are stained with VIP and SS primary antibodies respectively by immunohistochemical method, the expression levels of the substances in each group are compared by using average optical density values due to the expression levels of VIP and SS.
5. Statistical treatment
All data are expressed by mean ± standard deviation, SPSS13.0 statistical software is used for processing, and multi-factor variance analysis is used among all index groups according to variance homogeneity.
6. Test results and statistical analysis
6.1 Effect on general cases in anorexia rats
6.1.1 comparison of the variation of the feed intake of the test animals of each group
Table 1 results of comparison of the changes in food intake of the test animals
Note that: the food intake unit is g; * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
The animal feed intake of each group is not significantly different from the test day 1, and the animal feed intake of four molding groups is reduced by 20% -30% on average by 8 days compared with the blank control group (group A), and the molding is successful after 4 days; starting from day 16, the ingestion of rats in group C, D, which were fed with chlorogenic acid in large and small doses, was significantly increased compared to the model control (group B), and there was no significant difference from the blank control group (a) after day 24; in addition, the change amplitude of the feeding amount of the rats in the large and small chlorogenic acid gastric lavage groups (C, D groups) is not significantly different from that of the positive drug control group E.
6.1.2 comparison of body weight changes in animals of each group
Table 2 comparison of the weight change of animals in each group
Note that: the weight unit is g; * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
The animal weights of all groups are not significantly different from day 1 to day 8, and compared with a blank control group, the animal weights of four molding groups are lower than 10% -15% of the control group and last for 4 days, so that molding is successful; the weight of the chlorogenic acid lavage C, D group rats is significantly increased compared with the model control group B from the beginning of the lavage on the 12 th day, and is not significantly different from the blank control group after the 24 th day, and the weight-increasing effect is equivalent to that of the positive drug control group E.
The results show that the chlorogenic acid can greatly improve the food intake of anorexia rats and increase the weight of the anorexia rats, and the effect is equivalent to that of a commercially available medicine Jiangzhong stomach strengthening digestion promoting tablet, which shows that the chlorogenic acid has obvious appetite enhancing effect and can be used for treating anorexia.
6.2 modulation of ghrelin-appetite center
Hypothalamus is a central hub regulating diet and energy balance, wherein a plurality of key areas regulating feeding behaviors are distributed, such as hypothalamus outer area (LH), hypothalamus inner side (VMH), arcus nucleus (ARC), paraventricular nucleus (PVN) and the like, and various nerve nuclei in the hypothalamus can generate a series of appetite regulating factors to promote or inhibit appetite, and the nerve nuclei cooperate and interact to form a complex 'appetite regulating net'. One of the main causes of anorexia is that the ingestion of food ingredients is unreasonable, which results in disturbance of ghrelin secretion, and then acts on the appetite center, and the ingestion behavior is affected, namely, disturbance of ghrelin-appetite center is an important link of anorexia occurrence and development. The purpose of this experiment was to investigate the effect of chlorogenic acid on ghrelin levels in anorexia model rats.
6.2.1 Effect of chlorogenic acid on beta-endorphin (beta-EP), octapeptide cholecystokinin (CCK-8) levels
Beta-endorphin (beta-EP) is an endogenous opioid peptide, can be synthesized and secreted in brain tissues and gastrointestinal tracts, and has the effect of promoting appetite; while the octapeptide cholecystokinin (CCK-8) has an appetite suppressing effect, and the octapeptide cholecystokinin and the octapeptide are a pair of mutually antagonistic substances in hypothalamic feeding regulation and play an important role in physiological regulation and pathological feeding reduction.
TABLE 3 Effect of chlorogenic acid on CCK-8 concentration
Note that: * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
The results of the CCK-8 level measurements in hypothalamus and plasma of rats in each experimental group are shown in Table 3. The test result shows that after the modeling is successful, the concentration of the hypothalamus and the plasma CCK-8 of the animal is increased compared with that of a blank control group, and the concentration of the hypothalamus and the plasma CCK-8 of the rats in a chlorogenic acid large-dose group and a chlorogenic acid small-dose group is reduced compared with that of a model control group and is equivalent to that of the blank control group.
TABLE 4 influence of chlorogenic acid on beta-EP concentration
Note that: * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
The results of the beta-EP level measurements for each group of rats are shown in Table 4. The test result shows that compared with the blank control group, the hypothalamic beta-EP concentration of the rat in the model control group has no significant difference, and the beta-EP concentration in the antrum and the blood plasma is significantly reduced. The concentration of beta-EP in chlorogenic acid in the hypothalamus, antrum and plasma was increased in the large dose group, the small dose group, and the plasma, respectively, as compared to the model group. And the concentration of beta-EP in hypothalamus and antrum is significantly higher than that in the blank control group.
6.2.2 effects of chlorogenic acid on the level of Vasoactive Intestinal Peptide (VIP), somatostatin (SS)
The physiological function of VIP is to stimulate secretion of pancreatic juice and intestinal juice, protect intestinal mucosa and regulate gastrointestinal absorption. SS can widely inhibit gastrointestinal motility, including gastric emptying, gastric segmental motility, and the like. Expression levels of VIP and SS in rats of each experimental group are shown in tables 5 and 6.
TABLE 5 optical density values of chlorogenic acid for VIP and SS in gastric fundus tissue of rats of each group
Note that: * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
TABLE 6 optical density values of chlorogenic acid for VIP and SS in jejunal tissues of rats of each group
Note that: * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
Compared with a blank control group, the VIP in the stomach fundus tissue and the jejunum section tissue of a model group is obviously reduced, the SS is obviously increased, and compared with the model control group, the VIP expression level in the stomach fundus tissue of the chlorogenic acid administration group of the invention is obviously increased, the SS expression level is greatly reduced, and the significant difference exists; the VIP expression level in the jejunum tissues of the rats is also obviously improved, and is even obviously higher than that of a blank control group. The SS in the rat jejunum tissue is significantly reduced, is equivalent to the expression level of the blank control group.
The results show that the chlorogenic acid has remarkable regulation and control effects on CCK-8 and beta-EP, VIP, SS and can play a good role in treating anorexia.
6.3 modulation of immune function in anorexia rats
Anorexia of patients suffering from anorexia is often caused by hypoimmunity and increased morbidity due to insufficient protein-heat energy. The aim of this experiment was to investigate the effect of chlorogenic acid on the regulation of immune function in anorexia model rats.
TABLE 7 comparison of spleen index and thymus index for animals of each group
Note that: * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
As can be seen from table 7, the model control group had significantly lower spleen index and thymus index compared to the blank control group. The large and small doses of chlorogenic acid can obviously improve the spleen index and thymus index of rats, and are obviously higher than that of a model control group, and compared with a blank control group, the large and small doses of chlorogenic acid can obviously increase the spleen index and thymus index, which indicates that the chlorogenic acid can increase the weight of immune organs under pathological conditions and normal conditions.
TABLE 8 comparison of serum IL-2 and IL-6 levels for groups of animals
Note that: * P was less than 0.05 compared to model control group, # was less than 0.05 compared to blank control group
As can be seen from Table 8, the chlorogenic acid large and small dose groups can significantly increase the serum IL-2 and IL-6 content of the model rats, and are significantly higher than that of the model control group. There was no significant difference compared to the blank control.
In summary, the invention provides the application of chlorogenic acid in preparing medicines or health products for enhancing appetite. The drug effect experiment shows that the chlorogenic acid can greatly improve the food intake of anorexia rats and increase the weight of the anorexia rats, and the effect is equivalent to that of a commercially available drug Jiangzhong stomach strengthening digestion promoting tablet, which shows that the chlorogenic acid has obvious appetite enhancing effect, can be used for treating anorexia and has wide clinical application prospect.
The foregoing description of the preferred embodiments of the present invention is not intended to be limiting, but rather, the invention is to be construed as limited to the appended claims.
Claims (7)
1. Use of chlorogenic acid in preparing medicine for treating and/or preventing infantile anorexia.
2. The use according to claim 1, characterized in that: the medicine has the effect of regulating the ghrelin-appetite center.
3. Use according to claim 1 or 2, characterized in that: the medicine has the functions of increasing the concentration of beta-EP, reducing the concentration of CCK-8, increasing the expression level of VIP or reducing the expression level of SS.
4. The use according to claim 1, characterized in that: the medicine is a preparation prepared by taking effective amount of chlorogenic acid as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
5. The use according to claim 4, characterized in that: the preparation is an oral preparation.
6. The use according to claim 5, characterized in that: the preparation is tablet, granule, powder, capsule, suspension, solution, buccal preparation, pill, granule or pill.
7. The use according to claim 1, characterized in that: the medicine contains 30-500 mg chlorogenic acid in each preparation unit.
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| PCT/CN2017/115150 WO2018103729A1 (en) | 2016-12-09 | 2017-12-08 | Use of chlorogenic acid in preparation of drugs or health-care products for stimulating appetite |
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